GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

DEFF Research Database (Denmark)

Pharoah, Paul D P; Tsai, Ya-Yu; Ramus, Susan J

2013-01-01

Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24...

A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations

Science.gov (United States)

Bossini-Castillo, Lara; Martin, Jose-Ezequiel; Broen, Jasper; Gorlova, Olga; Simeón, Carmen P.; Beretta, Lorenzo; Vonk, Madelon C.; Luis Callejas, Jose; Castellví, Ivan; Carreira, Patricia; José García-Hernández, Francisco; Fernández Castro, Mónica; Coenen, Marieke J.H.; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg H.W.; Koeleman, Bobby P.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Palm, Øyvind; Hesselstrand, Roger; Nordin, Annika; Airó, Paolo; Lunardi, Claudio; Scorza, Raffaella; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Tan, Filemon K.; Arnett, Frank C.; Agarwal, Sandeep K.; Assassi, Shervin; Fonseca, Carmen; Mayes, Maureen D.; Radstake, Timothy R.D.J.; Martin, Javier

2012-01-01

A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [PMH= 1.92 × 10−5 odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (PMH= 4.84 × 10−3 OR = 1.12). The second follow-up phase confirmed this finding (Pχ2 = 2.82 × 10−4 OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (PMH= 2.82 × 10−9 OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis. PMID:22076442

Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk.

Science.gov (United States)

Kar, Siddhartha P; Tyrer, Jonathan P; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S; Cramer, Daniel; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas F; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus K; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Paul, James; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kjaer, Susanne K; Kelemen, Linda E; Kellar, Melissa; Kelley, Joseph; Kiemeney, Lambertus A; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Iain A; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Narod, Steven A; Nedergaard, Lotte; Ness, Roberta B; Nevanlinna, Heli; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schildkraut, Joellen M; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Sucheston-Campbell, Lara E; Tangen, Ingvild L; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S; van Altena, Anne M; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A; Monteiro, Alvaro N A; Freedman, Matthew L; Gayther, Simon A; Pharoah, Paul D P

2015-10-01

Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. ©2015 American Association for Cancer Research.

Comment on 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' by Lam et al.

Science.gov (United States)

Hill, W David

2018-04-01

Intelligence and educational attainment are strongly genetically correlated. This relationship can be exploited by Multi-Trait Analysis of GWAS (MTAG) to add power to Genome-wide Association Studies (GWAS) of intelligence. MTAG allows the user to meta-analyze GWASs of different phenotypes, based on their genetic correlations, to identify association's specific to the trait of choice. An MTAG analysis using GWAS data sets on intelligence and education was conducted by Lam et al. (2017). Lam et al. (2017) reported 70 loci that they described as 'trait specific' to intelligence. This article examines whether the analysis conducted by Lam et al. (2017) has resulted in genetic information about a phenotype that is more similar to education than intelligence.

Improved Use of Small Reference Panels for Conditional and Joint Analysis with GWAS Summary Statistics.

Science.gov (United States)

Deng, Yangqing; Pan, Wei

2018-06-01

Due to issues of practicality and confidentiality of genomic data sharing on a large scale, typically only meta- or mega-analyzed genome-wide association study (GWAS) summary data, not individual-level data, are publicly available. Reanalyses of such GWAS summary data for a wide range of applications have become more and more common and useful, which often require the use of an external reference panel with individual-level genotypic data to infer linkage disequilibrium (LD) among genetic variants. However, with a small sample size in only hundreds, as for the most popular 1000 Genomes Project European sample, estimation errors for LD are not negligible, leading to often dramatically increased numbers of false positives in subsequent analyses of GWAS summary data. To alleviate the problem in the context of association testing for a group of SNPs, we propose an alternative estimator of the covariance matrix with an idea similar to multiple imputation. We use numerical examples based on both simulated and real data to demonstrate the severe problem with the use of the 1000 Genomes Project reference panels, and the improved performance of our new approach. Copyright © 2018 by the Genetics Society of America.

GenToS: Use of Orthologous Gene Information to Prioritize Signals from Human GWAS.

Directory of Open Access Journals (Sweden)

Anselm S Hoppmann

Full Text Available Genome-wide association studies (GWAS evaluate associations between genetic variants and a trait or disease of interest free of prior biological hypotheses. GWAS require stringent correction for multiple testing, with genome-wide significance typically defined as association p-value <5*10-8. This study presents a new tool that uses external information about genes to prioritize SNP associations (GenToS. For a given list of candidate genes, GenToS calculates an appropriate statistical significance threshold and then searches for trait-associated variants in summary statistics from human GWAS. It thereby allows for identifying trait-associated genetic variants that do not meet genome-wide significance. The program additionally tests for enrichment of significant candidate gene associations in the human GWAS data compared to the number expected by chance. As proof of principle, this report used external information from a comprehensive resource of genetically manipulated and systematically phenotyped mice. Based on selected murine phenotypes for which human GWAS data for corresponding traits were publicly available, several candidate gene input lists were derived. Using GenToS for the investigation of candidate genes underlying murine skeletal phenotypes in data from a large human discovery GWAS meta-analysis of bone mineral density resulted in the identification of significantly associated variants in 29 genes. Index variants in 28 of these loci were subsequently replicated in an independent GWAS replication step, highlighting that they are true positive associations. One signal, COL11A1, has not been discovered through GWAS so far and represents a novel human candidate gene for altered bone mineral density. The number of observed genes that contained significant SNP associations in human GWAS based on murine candidate gene input lists was much greater than the number expected by chance across several complex human traits (enrichment p-value as

Genome-wide prediction models that incorporate de novo GWAS are a powerful new tool for tropical rice improvement

Science.gov (United States)

Spindel, J E; Begum, H; Akdemir, D; Collard, B; Redoña, E; Jannink, J-L; McCouch, S

2016-01-01

To address the multiple challenges to food security posed by global climate change, population growth and rising incomes, plant breeders are developing new crop varieties that can enhance both agricultural productivity and environmental sustainability. Current breeding practices, however, are unable to keep pace with demand. Genomic selection (GS) is a new technique that helps accelerate the rate of genetic gain in breeding by using whole-genome data to predict the breeding value of offspring. Here, we describe a new GS model that combines RR-BLUP with markers fit as fixed effects selected from the results of a genome-wide-association study (GWAS) on the RR-BLUP training data. We term this model GS + de novo GWAS. In a breeding population of tropical rice, GS + de novo GWAS outperformed six other models for a variety of traits and in multiple environments. On the basis of these results, we propose an extended, two-part breeding design that can be used to efficiently integrate novel variation into elite breeding populations, thus expanding genetic diversity and enhancing the potential for sustainable productivity gains. PMID:26860200

Evaluation of European Schizophrenia GWAS Loci in Asian Populations via Comprehensive Meta-Analyses.

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Xiao, Xiao; Luo, Xiong-Jian; Chang, Hong; Liu, Zichao; Li, Ming

2017-08-01

Schizophrenia is a severe and highly heritable neuropsychiatric disorder. Recent genetic analyses including genome-wide association studies (GWAS) have implicated multiple genome-wide significant variants for schizophrenia among European populations. However, many of these risk variants were not largely validated in other populations of different ancestry such as Asians. To validate whether these European GWAS significant loci are associated with schizophrenia in Asian populations, we conducted a systematic literature search and meta-analyses on 19 single nucleotide polymorphisms (SNPs) in Asian populations by combining all available case-control and family-based samples, including up to 30,000 individuals. We employed classical fixed (or random) effects inverse variance weighted methods to calculate summary odds ratios (ORs) and 95 % confidence intervals (CIs). Among the 19 GWAS loci, we replicated the risk associations of nine markers (e.g., SNPs at VRK2, ITIH3/4, NDST3, NOTCH4) surpassing significance level (two-tailed P Asian replication samples and initial European GWAS findings, and the successful replications of these GWAS loci in a different ethnic group provide stronger evidence for their clinical associations with schizophrenia. Further studies, focusing on the molecular mechanisms of these GWAS significant loci, will become increasingly important for understanding of the pathogenesis to schizophrenia.

Methods for meta-analysis of multiple traits using GWAS summary statistics.

Science.gov (United States)

Ray, Debashree; Boehnke, Michael

2018-03-01

Genome-wide association studies (GWAS) for complex diseases have focused primarily on single-trait analyses for disease status and disease-related quantitative traits. For example, GWAS on risk factors for coronary artery disease analyze genetic associations of plasma lipids such as total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides (TGs) separately. However, traits are often correlated and a joint analysis may yield increased statistical power for association over multiple univariate analyses. Recently several multivariate methods have been proposed that require individual-level data. Here, we develop metaUSAT (where USAT is unified score-based association test), a novel unified association test of a single genetic variant with multiple traits that uses only summary statistics from existing GWAS. Although the existing methods either perform well when most correlated traits are affected by the genetic variant in the same direction or are powerful when only a few of the correlated traits are associated, metaUSAT is designed to be robust to the association structure of correlated traits. metaUSAT does not require individual-level data and can test genetic associations of categorical and/or continuous traits. One can also use metaUSAT to analyze a single trait over multiple studies, appropriately accounting for overlapping samples, if any. metaUSAT provides an approximate asymptotic P-value for association and is computationally efficient for implementation at a genome-wide level. Simulation experiments show that metaUSAT maintains proper type-I error at low error levels. It has similar and sometimes greater power to detect association across a wide array of scenarios compared to existing methods, which are usually powerful for some specific association scenarios only. When applied to plasma lipids summary data from the METSIM and the T2D-GENES studies, metaUSAT detected genome-wide significant loci beyond the ones identified by univariate analyses

Extending the use of GWAS data by combining data from different genetic platforms

NARCIS (Netherlands)

van Iperen, E. P. A.; Hovingh, G. K.; Asselbergs, F. W.; Zwinderman, A. H.

2017-01-01

In the past decade many Genome-wide Association Studies (GWAS) were performed that discovered new associations between single-nucleotide polymorphisms (SNPs) and various phenotypes. Imputation methods are widely used in GWAS. They facilitate the phenotype association with variants that are not

Estimating Effect Sizes and Expected Replication Probabilities from GWAS Summary Statistics

DEFF Research Database (Denmark)

Holland, Dominic; Wang, Yunpeng; Thompson, Wesley K

2016-01-01

Genome-wide Association Studies (GWAS) result in millions of summary statistics ("z-scores") for single nucleotide polymorphism (SNP) associations with phenotypes. These rich datasets afford deep insights into the nature and extent of genetic contributions to complex phenotypes such as psychiatric......-scores, as such knowledge would enhance causal SNP and gene discovery, help elucidate mechanistic pathways, and inform future study design. Here we present a parsimonious methodology for modeling effect sizes and replication probabilities, relying only on summary statistics from GWAS substudies, and a scheme allowing...... for estimating the degree of polygenicity of the phenotype and predicting the proportion of chip heritability explainable by genome-wide significant SNPs in future studies with larger sample sizes. We apply the model to recent GWAS of schizophrenia (N = 82,315) and putamen volume (N = 12,596), with approximately...

Genome-wide association studies (GWAS) of adiposity

DEFF Research Database (Denmark)

Oskari Kilpeläinen, Tuomas; Ingelsson, Erik

2016-01-01

Adiposity is strongly heritable and one of the leading risk factors for type 2 diabetes, cardiovascular disease, cancer, and premature death. In the past 8 years, genome-wide association studies (GWAS) have greatly increased our understanding of the genes and biological pathways that regulate...

Statistical methods to detect novel genetic variants using publicly available GWAS summary data.

Science.gov (United States)

Guo, Bin; Wu, Baolin

2018-03-01

We propose statistical methods to detect novel genetic variants using only genome-wide association studies (GWAS) summary data without access to raw genotype and phenotype data. With more and more summary data being posted for public access in the post GWAS era, the proposed methods are practically very useful to identify additional interesting genetic variants and shed lights on the underlying disease mechanism. We illustrate the utility of our proposed methods with application to GWAS meta-analysis results of fasting glucose from the international MAGIC consortium. We found several novel genome-wide significant loci that are worth further study. Copyright © 2018 Elsevier Ltd. All rights reserved.

Unsupervised text mining for assessing and augmenting GWAS results.

Science.gov (United States)

Ailem, Melissa; Role, François; Nadif, Mohamed; Demenais, Florence

2016-04-01

Text mining can assist in the analysis and interpretation of large-scale biomedical data, helping biologists to quickly and cheaply gain confirmation of hypothesized relationships between biological entities. We set this question in the context of genome-wide association studies (GWAS), an actively emerging field that contributed to identify many genes associated with multifactorial diseases. These studies allow to identify groups of genes associated with the same phenotype, but provide no information about the relationships between these genes. Therefore, our objective is to leverage unsupervised text mining techniques using text-based cosine similarity comparisons and clustering applied to candidate and random gene vectors, in order to augment the GWAS results. We propose a generic framework which we used to characterize the relationships between 10 genes reported associated with asthma by a previous GWAS. The results of this experiment showed that the similarities between these 10 genes were significantly stronger than would be expected by chance (one-sided p-value<0.01). The clustering of observed and randomly selected gene also allowed to generate hypotheses about potential functional relationships between these genes and thus contributed to the discovery of new candidate genes for asthma. Copyright © 2016 Elsevier Inc. All rights reserved.

Methods to improve genomic prediction and GWAS using combined Holstein populations

DEFF Research Database (Denmark)

Li, Xiujin

The thesis focuses on methods to improve GWAS and genomic prediction using combined Holstein populations and investigations G by E interaction. The conclusions are: 1) Prediction reliabilities for Brazilian Holsteins can be increased by adding Nordic and Frensh genotyped bulls and a large G by E...... interaction exists between populations. 2) Combining data from Chinese and Danish Holstein populations increases the power of GWAS and detects new QTL regions for milk fatty acid traits. 3) The novel multi-trait Bayesian model efficiently estimates region-specific genomic variances, covariances...

MZ twin pairs or MZ singletons in population family-based GWAS? More power in pairs

NARCIS (Netherlands)

Minica, C.C.; Boomsma, D.I.; Vink, J.M.; Dolan, C.V.

2014-01-01

Family-based genome-wide association studies (GWAS) involve testing the genetic association of (many) genetic variants with the phenotype of interest, while taking into account the relatedness among family members. Occasionally in family-based GWAS, including monozygotic (MZ) twins, the data from

Efficient Software for Multi-marker, Region-Based Analysis of GWAS Data

Directory of Open Access Journals (Sweden)

Jaleal S. Sanjak

2016-04-01

Full Text Available Genome-wide association studies (GWAS have associated many single variants with complex disease, yet the better part of heritable complex disease risk remains unexplained. Analytical tools designed to work under specific population genetic models are needed. Rare variants are increasingly shown to be important in human complex disease, but most existing GWAS data do not cover rare variants. Explicit population genetic models predict that genes contributing to complex traits and experiencing recurrent, unconditionally deleterious, mutation will harbor multiple rare, causative mutations of subtle effect. It is difficult to identify genes harboring rare variants of large effect that contribute to complex disease risk via the single marker association tests typically used in GWAS. Gene/region-based association tests may have the power detect associations by combining information from multiple markers, but have yielded limited success in practice. This is partially because many methods have not been widely applied. Here, we empirically demonstrate the utility of a procedure based on the rank truncated product (RTP method, filtered to reduce the effects of linkage disequilibrium. We apply the procedure to the Wellcome Trust Case Control Consortium (WTCCC data set, and uncover previously unidentified associations, some of which have been replicated in much larger studies. We show that, in the absence of significant rare variant coverage, RTP based methods still have the power to detect associated genes. We recommend that RTP-based methods be applied to all existing GWAS data to maximize the usefulness of those data. For this, we provide efficient software implementing our procedure.

IVAG: An Integrative Visualization Application for Various Types of Genomic Data Based on R-Shiny and the Docker Platform.

Science.gov (United States)

Lee, Tae-Rim; Ahn, Jin Mo; Kim, Gyuhee; Kim, Sangsoo

2017-12-01

Next-generation sequencing (NGS) technology has become a trend in the genomics research area. There are many software programs and automated pipelines to analyze NGS data, which can ease the pain for traditional scientists who are not familiar with computer programming. However, downstream analyses, such as finding differentially expressed genes or visualizing linkage disequilibrium maps and genome-wide association study (GWAS) data, still remain a challenge. Here, we introduce a dockerized web application written in R using the Shiny platform to visualize pre-analyzed RNA sequencing and GWAS data. In addition, we have integrated a genome browser based on the JBrowse platform and an automated intermediate parsing process required for custom track construction, so that users can easily build and navigate their personal genome tracks with in-house datasets. This application will help scientists perform series of downstream analyses and obtain a more integrative understanding about various types of genomic data by interactively visualizing them with customizable options.

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

NARCIS (Netherlands)

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

2017-01-01

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

qqman: an R package for visualizing GWAS results using Q-Q and manhattan plots

OpenAIRE

Turner, Stephen

2014-01-01

Summary: Genome-wide association studies (GWAS) have identified thousands of human trait-associated single nucleotide polymorphisms. Here, I describe a freely available R package for visualizing GWAS results using Q-Q and manhattan plots. The qqman package enables the flexible creation of manhattan plots, both genome-wide and for single chromosomes, with optional highlighting of SNPs of interest. Availability: qqman is released under the GNU General Public License, and is freely available on ...

GWAS as a Driver of Gene Discovery in Cardiometabolic Diseases

NARCIS (Netherlands)

Atanasovska, Biljana; Kumar, Vinod; Fu, Jingyuan; Wijmenga, Cisca; Hofker, Marten H.

2015-01-01

Cardiometabolic diseases represent a common complex disorder with a strong genetic component. Currently, genome-wide association studies (GWAS) have yielded some 755 single-nucleotide polymorphisms (SNPs) encompassing 366 independent loci that may help to decipher the molecular basis of

Testing Genetic Pleiotropy with GWAS Summary Statistics for Marginal and Conditional Analyses.

Science.gov (United States)

Deng, Yangqing; Pan, Wei

2017-12-01

There is growing interest in testing genetic pleiotropy, which is when a single genetic variant influences multiple traits. Several methods have been proposed; however, these methods have some limitations. First, all the proposed methods are based on the use of individual-level genotype and phenotype data; in contrast, for logistical, and other, reasons, summary statistics of univariate SNP-trait associations are typically only available based on meta- or mega-analyzed large genome-wide association study (GWAS) data. Second, existing tests are based on marginal pleiotropy, which cannot distinguish between direct and indirect associations of a single genetic variant with multiple traits due to correlations among the traits. Hence, it is useful to consider conditional analysis, in which a subset of traits is adjusted for another subset of traits. For example, in spite of substantial lowering of low-density lipoprotein cholesterol (LDL) with statin therapy, some patients still maintain high residual cardiovascular risk, and, for these patients, it might be helpful to reduce their triglyceride (TG) level. For this purpose, in order to identify new therapeutic targets, it would be useful to identify genetic variants with pleiotropic effects on LDL and TG after adjusting the latter for LDL; otherwise, a pleiotropic effect of a genetic variant detected by a marginal model could simply be due to its association with LDL only, given the well-known correlation between the two types of lipids. Here, we develop a new pleiotropy testing procedure based only on GWAS summary statistics that can be applied for both marginal analysis and conditional analysis. Although the main technical development is based on published union-intersection testing methods, care is needed in specifying conditional models to avoid invalid statistical estimation and inference. In addition to the previously used likelihood ratio test, we also propose using generalized estimating equations under the

Re-Ranking Sequencing Variants in the Post-GWAS Era for Accurate Causal Variant Identification

Science.gov (United States)

Faye, Laura L.; Machiela, Mitchell J.; Kraft, Peter; Bull, Shelley B.; Sun, Lei

2013-01-01

Next generation sequencing has dramatically increased our ability to localize disease-causing variants by providing base-pair level information at costs increasingly feasible for the large sample sizes required to detect complex-trait associations. Yet, identification of causal variants within an established region of association remains a challenge. Counter-intuitively, certain factors that increase power to detect an associated region can decrease power to localize the causal variant. First, combining GWAS with imputation or low coverage sequencing to achieve the large sample sizes required for high power can have the unintended effect of producing differential genotyping error among SNPs. This tends to bias the relative evidence for association toward better genotyped SNPs. Second, re-use of GWAS data for fine-mapping exploits previous findings to ensure genome-wide significance in GWAS-associated regions. However, using GWAS findings to inform fine-mapping analysis can bias evidence away from the causal SNP toward the tag SNP and SNPs in high LD with the tag. Together these factors can reduce power to localize the causal SNP by more than half. Other strategies commonly employed to increase power to detect association, namely increasing sample size and using higher density genotyping arrays, can, in certain common scenarios, actually exacerbate these effects and further decrease power to localize causal variants. We develop a re-ranking procedure that accounts for these adverse effects and substantially improves the accuracy of causal SNP identification, often doubling the probability that the causal SNP is top-ranked. Application to the NCI BPC3 aggressive prostate cancer GWAS with imputation meta-analysis identified a new top SNP at 2 of 3 associated loci and several additional possible causal SNPs at these loci that may have otherwise been overlooked. This method is simple to implement using R scripts provided on the author's website. PMID:23950724

Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development

Directory of Open Access Journals (Sweden)

Leah Y. Liu

2013-09-01

Genome-wide association studies (GWAS have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10 decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50 decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.

meQTL analysis of asthma GWAS loci and DNA methylation

NARCIS (Netherlands)

Kumar, Ashish; Soderhall, Cilla; Merid, Simon Kebede; Xu, Chengjian; Koppelman, Gerard; Melen, Erik; Gruzieva, Olena; Kere, Juha; Pershagen, Goran

2016-01-01

Background: Asthma is characterized as a chronic inflammation disease and has increased in prevalence over the decades. Genome-wide association studies (GWAS) have implicated several single nucleotide polymorphisms (SNPs) with varying risk estimates for asthma, but the etiology is still not fully

Identification of loci governing eight agronomic traits using a GBS-GWAS approach and validation by QTL mapping in soya bean.

Science.gov (United States)

Sonah, Humira; O'Donoughue, Louise; Cober, Elroy; Rajcan, Istvan; Belzile, François

2015-02-01

Soya bean is a major source of edible oil and protein for human consumption as well as animal feed. Understanding the genetic basis of different traits in soya bean will provide important insights for improving breeding strategies for this crop. A genome-wide association study (GWAS) was conducted to accelerate molecular breeding for the improvement of agronomic traits in soya bean. A genotyping-by-sequencing (GBS) approach was used to provide dense genome-wide marker coverage (>47,000 SNPs) for a panel of 304 short-season soya bean lines. A subset of 139 lines, representative of the diversity among these, was characterized phenotypically for eight traits under six environments (3 sites × 2 years). Marker coverage proved sufficient to ensure highly significant associations between the genes known to control simple traits (flower, hilum and pubescence colour) and flanking SNPs. Between one and eight genomic loci associated with more complex traits (maturity, plant height, seed weight, seed oil and protein) were also identified. Importantly, most of these GWAS loci were located within genomic regions identified by previously reported quantitative trait locus (QTL) for these traits. In some cases, the reported QTLs were also successfully validated by additional QTL mapping in a biparental population. This study demonstrates that integrating GBS and GWAS can be used as a powerful complementary approach to classical biparental mapping for dissecting complex traits in soya bean. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Hemoglobin genetics: recent contributions of GWAS and gene editing

Science.gov (United States)

Smith, Elenoe C.; Orkin, Stuart H.

2016-01-01

The β-hemoglobinopathies are inherited disorders resulting from altered coding potential or expression of the adult β-globin gene. Impaired expression of β-globin reduces adult hemoglobin (α2β2) production, the hallmark of β-thalassemia. A single-base mutation at codon 6 leads to formation of HbS (α2βS2) and sickle cell disease. While the basis of these diseases is known, therapy remains largely supportive. Bone marrow transplantation is the only curative therapy. Patients with elevated levels of fetal hemoglobin (HbF, α2γ2) as adults exhibit reduced symptoms and enhanced survival. The β-globin gene locus is a paradigm of cell- and developmental stage-specific regulation. Although the principal erythroid cell transcription factors are known, mechanisms responsible for silencing of the γ-globin gene were obscure until application of genome-wide association studies (GWAS). Here, we review findings in the field. GWAS identified BCL11A as a candidate negative regulator of γ-globin expression. Subsequent studies have established BCL11A as a quantitative repressor. GWAS-related single-nucleotide polymorphisms lie within an essential erythroid enhancer of the BCL11A gene. Disruption of a discrete region within the enhancer reduces BCL11A expression and induces HbF expression, providing the basis for gene therapy using gene editing tools. A recently identified, second silencing factor, leukemia/lymphoma-related factor/Pokemon, shares features with BCL11A, including interaction with the nucleosome remodeling deacetylase repressive complex. These findings suggest involvement of a common pathway for HbF silencing. In addition, we discuss other factors that may be involved in γ-globin gene silencing and their potential manipulation for therapeutic benefit in treating the β-hemoglobinopathies. PMID:27340226

Effect of sample stratification on dairy GWAS results

Directory of Open Access Journals (Sweden)

Ma Li

2012-10-01

Full Text Available Abstract Background Artificial insemination and genetic selection are major factors contributing to population stratification in dairy cattle. In this study, we analyzed the effect of sample stratification and the effect of stratification correction on results of a dairy genome-wide association study (GWAS. Three methods for stratification correction were used: the efficient mixed-model association expedited (EMMAX method accounting for correlation among all individuals, a generalized least squares (GLS method based on half-sib intraclass correlation, and a principal component analysis (PCA approach. Results Historical pedigree data revealed that the 1,654 contemporary cows in the GWAS were all related when traced through approximately 10–15 generations of ancestors. Genome and phenotype stratifications had a striking overlap with the half-sib structure. A large elite half-sib family of cows contributed to the detection of favorable alleles that had low frequencies in the general population and high frequencies in the elite cows and contributed to the detection of X chromosome effects. All three methods for stratification correction reduced the number of significant effects. EMMAX method had the most severe reduction in the number of significant effects, and the PCA method using 20 principal components and GLS had similar significance levels. Removal of the elite cows from the analysis without using stratification correction removed many effects that were also removed by the three methods for stratification correction, indicating that stratification correction could have removed some true effects due to the elite cows. SNP effects with good consensus between different methods and effect size distributions from USDA’s Holstein genomic evaluation included the DGAT1-NIBP region of BTA14 for production traits, a SNP 45kb upstream from PIGY on BTA6 and two SNPs in NIBP on BTA14 for protein percentage. However, most of these consensus effects had

Integration of liver gene co-expression networks and eGWAs analyses highlighted candidate regulators implicated in lipid metabolism in pigs.

Science.gov (United States)

Ballester, Maria; Ramayo-Caldas, Yuliaxis; Revilla, Manuel; Corominas, Jordi; Castelló, Anna; Estellé, Jordi; Fernández, Ana I; Folch, Josep M

2017-04-19

In the present study, liver co-expression networks and expression Genome Wide Association Study (eGWAS) were performed to identify DNA variants and molecular pathways implicated in the functional regulatory mechanisms of meat quality traits in pigs. With this purpose, the liver mRNA expression of 44 candidates genes related with lipid metabolism was analysed in 111 Iberian x Landrace backcross animals. The eGWAS identified 92 eSNPs located in seven chromosomal regions and associated with eight genes: CROT, CYP2U1, DGAT1, EGF, FABP1, FABP5, PLA2G12A, and PPARA. Remarkably, cis-eSNPs associated with FABP1 gene expression which may be determining the C18:2(n-6)/C18:3(n-3) ratio in backfat through the multiple interaction of DNA variants and genes were identified. Furthermore, a hotspot on SSC8 associated with the gene expression of eight genes was identified and the TBCK gene was pointed out as candidate gene regulating it. Our results also suggested that the PI3K-Akt-mTOR pathway plays an important role in the control of the analysed genes highlighting nuclear receptors as the NR3C1 or PPARA. Finally, sex-dimorphism associated with hepatic lipid metabolism was identified with over-representation of female-biased genes. These results increase our knowledge of the genetic architecture underlying fat composition traits.

Gene-Based Analysis of Regionally Enriched Cortical Genes in GWAS Data Sets of Cognitive Traits and Psychiatric Disorders

DEFF Research Database (Denmark)

Ersland, Kari M; Christoforou, Andrea; Stansberg, Christine

2012-01-01

the regionally enriched cortical genes to mine a genome-wide association study (GWAS) of the Norwegian Cognitive NeuroGenetics (NCNG) sample of healthy adults for association to nine psychometric tests measures. In addition, we explored GWAS data sets for the serious psychiatric disorders schizophrenia (SCZ) (n...

SNPranker 2.0: a gene-centric data mining tool for diseases associated SNP prioritization in GWAS.

Science.gov (United States)

Merelli, Ivan; Calabria, Andrea; Cozzi, Paolo; Viti, Federica; Mosca, Ettore; Milanesi, Luciano

2013-01-01

The capability of correlating specific genotypes with human diseases is a complex issue in spite of all advantages arisen from high-throughput technologies, such as Genome Wide Association Studies (GWAS). New tools for genetic variants interpretation and for Single Nucleotide Polymorphisms (SNPs) prioritization are actually needed. Given a list of the most relevant SNPs statistically associated to a specific pathology as result of a genotype study, a critical issue is the identification of genes that are effectively related to the disease by re-scoring the importance of the identified genetic variations. Vice versa, given a list of genes, it can be of great importance to predict which SNPs can be involved in the onset of a particular disease, in order to focus the research on their effects. We propose a new bioinformatics approach to support biological data mining in the analysis and interpretation of SNPs associated to pathologies. This system can be employed to design custom genotyping chips for disease-oriented studies and to re-score GWAS results. The proposed method relies (1) on the data integration of public resources using a gene-centric database design, (2) on the evaluation of a set of static biomolecular annotations, defined as features, and (3) on the SNP scoring function, which computes SNP scores using parameters and weights set by users. We employed a machine learning classifier to set default feature weights and an ontological annotation layer to enable the enrichment of the input gene set. We implemented our method as a web tool called SNPranker 2.0 (http://www.itb.cnr.it/snpranker), improving our first published release of this system. A user-friendly interface allows the input of a list of genes, SNPs or a biological process, and to customize the features set with relative weights. As result, SNPranker 2.0 returns a list of SNPs, localized within input and ontologically enriched genes, combined with their prioritization scores. Different

Power in GWAS: lifting the curse of the clinical cut-off

NARCIS (Netherlands)

van der Sluis, S.; Posthuma, D.; Nivard, M.G.; Verhage, M.; Dolan, C.V.

2013-01-01

Although genome-wide association studies (GWAS), in general, facilitated important discovery of new biological knowledge about diseases,1, 2, 3 identified variants for psychiatric disorders explain little variation, and insight into the role of genes in highly heritable psychiatric traits remains

Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples

DEFF Research Database (Denmark)

den Hoed, M; Luan, J; Langenberg, C

2013-01-01

BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population-based sam......BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population......, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population....

Genetic variation in HTR4 and lung function: GWAS follow-up in mouse.

Science.gov (United States)

House, John S; Li, Huiling; DeGraff, Laura M; Flake, Gordon; Zeldin, Darryl C; London, Stephanie J

2015-01-01

Human genome-wide association studies (GWASs) have identified numerous associations between single nucleotide polymorphisms (SNPs) and pulmonary function. Proving that there is a causal relationship between GWAS SNPs, many of which are noncoding and without known functional impact, and these traits has been elusive. Furthermore, noncoding GWAS-identified SNPs may exert trans-regulatory effects rather than impact the proximal gene. Noncoding variants in 5-hydroxytryptamine (serotonin) receptor 4 (HTR4) are associated with pulmonary function in human GWASs. To gain insight into whether this association is causal, we tested whether Htr4-null mice have altered pulmonary function. We found that HTR4-deficient mice have 12% higher baseline lung resistance and also increased methacholine-induced airway hyperresponsiveness (AHR) as measured by lung resistance (27%), tissue resistance (48%), and tissue elastance (30%). Furthermore, Htr4-null mice were more sensitive to serotonin-induced AHR. In models of exposure to bacterial lipopolysaccharide, bleomycin, and allergic airway inflammation induced by house dust mites, pulmonary function and cytokine profiles in Htr4-null mice differed little from their wild-type controls. The findings of altered baseline lung function and increased AHR in Htr4-null mice support a causal relationship between genetic variation in HTR4 and pulmonary function identified in human GWAS. © FASEB.

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

OpenAIRE

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

2016-01-01

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

Emerging applications of genome-editing technology to examine functionality of GWAS-associated variants for complex traits.

Science.gov (United States)

Smith, Andrew J P; Deloukas, Panos; Munroe, Patricia B

2018-04-13

Over the last decade, genome-wide association studies (GWAS) have propelled the discovery of thousands of loci associated with complex diseases. The focus is now turning towards the function of these association signals, determining the causal variant(s) amongst those in strong linkage disequilibrium, and identifying their underlying mechanisms, such as long-range gene regulation. Genome-editing techniques utilising zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs) and clustered regularly-interspaced short palindromic repeats with Cas9 nuclease (CRISPR-Cas9), are becoming the tools of choice to establish functionality for these variants, due to the ability to assess effects of single variants in vivo. This review will discuss examples of how these technologies have begun to aid functional analysis of GWAS loci for complex traits such as cardiovascular disease, type 2 diabetes, cancer, obesity and autoimmune disease. We focus on analysis of variants occurring within non-coding genomic regions, as these comprise the majority of GWAS variants, providing the greatest challenges to determining functionality, and compare editing strategies that provide different levels of evidence for variant functionality. The review describes molecular insights into some of these potentially causal variants, and how these may relate to the pathology of the trait, and look towards future directions for these technologies in post-GWAS analysis, such as base-editing.

Results of a "GWAS plus:" general cognitive ability is substantially heritable and massively polygenic.

Directory of Open Access Journals (Sweden)

Robert M Kirkpatrick

Full Text Available We carried out a genome-wide association study (GWAS for general cognitive ability (GCA plus three other analyses of GWAS data that aggregate the effects of multiple single-nucleotide polymorphisms (SNPs in various ways. Our multigenerational sample comprised 7,100 Caucasian participants, drawn from two longitudinal family studies, who had been assessed with an age-appropriate IQ test and had provided DNA samples passing quality screens. We conducted the GWAS across ∼ 2.5 million SNPs (both typed and imputed, using a generalized least-squares method appropriate for the different family structures present in our sample, and subsequently conducted gene-based association tests. We also conducted polygenic prediction analyses under five-fold cross-validation, using two different schemes of weighting SNPs. Using parametric bootstrapping, we assessed the performance of this prediction procedure under the null. Finally, we estimated the proportion of variance attributable to all genotyped SNPs as random effects with software GCTA. The study is limited chiefly by its power to detect realistic single-SNP or single-gene effects, none of which reached genome-wide significance, though some genomic inflation was evident from the GWAS. Unit SNP weights performed about as well as least-squares regression weights under cross-validation, but the performance of both increased as more SNPs were included in calculating the polygenic score. Estimates from GCTA were 35% of phenotypic variance at the recommended biological-relatedness ceiling. Taken together, our results concur with other recent studies: they support a substantial heritability of GCA, arising from a very large number of causal SNPs, each of very small effect. We place our study in the context of the literature-both contemporary and historical-and provide accessible explication of our statistical methods.

Multispecies, Integrative GWAS for Focal Segmental Glomerulosclerosis

Science.gov (United States)

2017-09-01

for the phenotypic analysis of the newly generated transgenic F1 hybrids. Serum will be analyzed for blood urea nitrogen, albumin , cholesterol...under a particular item, state “Nothing to Report.”  Publications, conference papers , and presentations Report only the major publication(s...resulting from the work under this award. Journal publications. List peer-reviewed articles or papers appearing in scientific, technical, or

Effects of GWAS-associated genetic variants on lncRNAs within IBD and T1D candidate loci

DEFF Research Database (Denmark)

Mirza, Aashiq H; Kaur, Simranjeet; Brorsson, Caroline A

2014-01-01

-nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) lie outside of the protein coding regions, and map to the non-coding intervals. However, the relationship between phenotype-associated loci and the non-coding regions including the long non-coding RNAs (lncRNAs) is poorly understood. Here......, we systemically identified all annotated IBD and T1D loci-associated lncRNAs, and mapped nominally significant GWAS/ImmunoChip SNPs for IBD and T1D within these lncRNAs. Additionally, we identified tissue-specific cis-eQTLs, and strong linkage disequilibrium (LD) signals associated with these SNPs...... within and in close proximity (+/-5 kb flanking regions) of IBD and T1D loci-associated candidate genes, suggesting that these RNA conformation-altering polymorphisms might be associated with diseased-phenotype. Disruption of lncRNA secondary structure due to presence of GWAS SNPs provides valuable...

AprioriGWAS, a new pattern mining strategy for detecting genetic variants associated with disease through interaction effects.

Science.gov (United States)

Zhang, Qingrun; Long, Quan; Ott, Jurg

2014-06-01

Identifying gene-gene interaction is a hot topic in genome wide association studies. Two fundamental challenges are: (1) how to smartly identify combinations of variants that may be associated with the trait from astronomical number of all possible combinations; and (2) how to test epistatic interaction when all potential combinations are available. We developed AprioriGWAS, which brings two innovations. (1) Based on Apriori, a successful method in field of Frequent Itemset Mining (FIM) in which a pattern growth strategy is leveraged to effectively and accurately reduce search space, AprioriGWAS can efficiently identify genetically associated genotype patterns. (2) To test the hypotheses of epistasis, we adopt a new conditional permutation procedure to obtain reliable statistical inference of Pearson's chi-square test for the [Formula: see text] contingency table generated by associated variants. By applying AprioriGWAS to age-related macular degeneration (AMD) data, we found that: (1) angiopoietin 1 (ANGPT1) and four retinal genes interact with Complement Factor H (CFH). (2) GO term "glycosaminoglycan biosynthetic process" was enriched in AMD interacting genes. The epistatic interactions newly found by AprioriGWAS on AMD data are likely true interactions, since genes interacting with CFH are retinal genes, and GO term enrichment also verified that interaction between glycosaminoglycans (GAGs) and CFH plays an important role in disease pathology of AMD. By applying AprioriGWAS on Bipolar disorder in WTCCC data, we found variants without marginal effect show significant interactions. For example, multiple-SNP genotype patterns inside gene GABRB2 and GRIA1 (AMPA subunit 1 receptor gene). AMPARs are found in many parts of the brain and are the most commonly found receptor in the nervous system. The GABRB2 mediates the fastest inhibitory synaptic transmission in the central nervous system. GRIA1 and GABRB2 are relevant to mental disorders supported by multiple

Comprehensive evaluation of disease- and trait-specific enrichment for eight functional elements among GWAS-identified variants.

Science.gov (United States)

Markunas, Christina A; Johnson, Eric O; Hancock, Dana B

2017-07-01

Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

A Markov blanket-based method for detecting causal SNPs in GWAS

Directory of Open Access Journals (Sweden)

Han Bing

2010-04-01

Full Text Available Abstract Background Detecting epistatic interactions associated with complex and common diseases can help to improve prevention, diagnosis and treatment of these diseases. With the development of genome-wide association studies (GWAS, designing powerful and robust computational method for identifying epistatic interactions associated with common diseases becomes a great challenge to bioinformatics society, because the study of epistatic interactions often deals with the large size of the genotyped data and the huge amount of combinations of all the possible genetic factors. Most existing computational detection methods are based on the classification capacity of SNP sets, which may fail to identify SNP sets that are strongly associated with the diseases and introduce a lot of false positives. In addition, most methods are not suitable for genome-wide scale studies due to their computational complexity. Results We propose a new Markov Blanket-based method, DASSO-MB (Detection of ASSOciations using Markov Blanket to detect epistatic interactions in case-control GWAS. Markov blanket of a target variable T can completely shield T from all other variables. Thus, we can guarantee that the SNP set detected by DASSO-MB has a strong association with diseases and contains fewest false positives. Furthermore, DASSO-MB uses a heuristic search strategy by calculating the association between variables to avoid the time-consuming training process as in other machine-learning methods. We apply our algorithm to simulated datasets and a real case-control dataset. We compare DASSO-MB to other commonly-used methods and show that our method significantly outperforms other methods and is capable of finding SNPs strongly associated with diseases. Conclusions Our study shows that DASSO-MB can identify a minimal set of causal SNPs associated with diseases, which contains less false positives compared to other existing methods. Given the huge size of genomic dataset

A simulation study of gene-by-environment interactions in GWAS implies ample hidden effects

Science.gov (United States)

Marigorta, Urko M.; Gibson, Greg

2014-01-01

The switch to a modern lifestyle in recent decades has coincided with a rapid increase in prevalence of obesity and other diseases. These shifts in prevalence could be explained by the release of genetic susceptibility for disease in the form of gene-by-environment (GxE) interactions. Yet, the detection of interaction effects requires large sample sizes, little replication has been reported, and a few studies have demonstrated environmental effects only after summing the risk of GWAS alleles into genetic risk scores (GRSxE). We performed extensive simulations of a quantitative trait controlled by 2500 causal variants to inspect the feasibility to detect gene-by-environment interactions in the context of GWAS. The simulated individuals were assigned either to an ancestral or a modern setting that alters the phenotype by increasing the effect size by 1.05–2-fold at a varying fraction of perturbed SNPs (from 1 to 20%). We report two main results. First, for a wide range of realistic scenarios, highly significant GRSxE is detected despite the absence of individual genotype GxE evidence at the contributing loci. Second, an increase in phenotypic variance after environmental perturbation reduces the power to discover susceptibility variants by GWAS in mixed cohorts with individuals from both ancestral and modern environments. We conclude that a pervasive presence of gene-by-environment effects can remain hidden even though it contributes to the genetic architecture of complex traits. PMID:25101110

A seal analyzer for testing container integrity

International Nuclear Information System (INIS)

McDaniel, P.; Jenkins, C.

1988-01-01

This paper reports on the development of laboratory and production seal analyzer that offers a rapid, nondestructive method of assuring the seal integrity of virtually any type of single or double sealed container. The system can test a broad range of metal cans, drums and trays, membrane-lidded vessels, flexible pouches, aerosol containers, and glass or metal containers with twist-top lids that are used in the chemical/pesticide (hazardous materials/waste), beverage, food, medical and pharmaceutical industries

Using prior information from the medical literature in GWAS of oral cancer identifies novel susceptibility variant on chromosome 4--the AdAPT method.

LENUS (Irish Health Repository)

Johansson, Mattias

2012-01-01

Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS.

Meta-GWAS Accuracy and Power (MetaGAP Calculator Shows that Hiding Heritability Is Partially Due to Imperfect Genetic Correlations across Studies.

Directory of Open Access Journals (Sweden)

Ronald de Vlaming

2017-01-01

Full Text Available Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy of polygenic scores are attenuated, contributing to the so-called 'missing heritability'. Here, we describe the online Meta-GWAS Accuracy and Power (MetaGAP calculator (available at www.devlaming.eu which quantifies this attenuation based on a novel multi-study framework. By means of simulation studies, we show that under a wide range of genetic architectures, the statistical power and predictive accuracy provided by this calculator are accurate. We compare the predictions from the MetaGAP calculator with actual results obtained in the GWAS literature. Specifically, we use genomic-relatedness-matrix restricted maximum likelihood to estimate the SNP heritability and cross-study genetic correlation of height, BMI, years of education, and self-rated health in three large samples. These estimates are used as input parameters for the MetaGAP calculator. Results from the calculator suggest that cross-study heterogeneity has led to attenuation of statistical power and predictive accuracy in recent large-scale GWAS efforts on these traits (e.g., for years of education, we estimate a relative loss of 51-62% in the number of genome-wide significant loci and a relative loss in polygenic score R2 of 36-38%. Hence, cross-study heterogeneity contributes to the missing heritability.

GWAS for executive function and processing speed suggests involvement of the CADM2 gene

NARCIS (Netherlands)

C.A. Ibrahim-Verbaas (Carla); J. Bressler; S. Debette (Stéphanie); M. Schuur (Maaike); A.V. Smith; J.C. Bis (Joshua); G. Davies (Gail); S. Trompet (Stella); J.A. Smith; A. Björnsson (Asgeir); L.B. Chibnik (Lori); Y. Liu; V. Vitart (Veronique); M. Kirin (Mirna); K. Petrovic (Katja); O. Polasek (Ozren); L. Zgaga (Lina); C. Fawns-Ritchie; P. Hoffmann (Per); J. Karjalainen (Juha); J. Lahti; D.J. Llewellyn; C.O. Schmidt (Carsten O.); R. Mather; V. Chouraki (Vincent); Q. Sun; S. Resnick (Susan); L.M. Rose (Lynda M.); C. Oldmeadow (Christopher); M. Stewart; B.H. Smith; V. Gudnason (Vilmundur); Q. Yang (Qiong); S.S. Mirza (Saira); J.W. Jukema; P.L. DeJager (Philip L.); T.B. Harris (Tamara); D.C. Liewald (David C.); N. Amin (Najaf); L.H. Coker (Laura); O. Stegle (Oliver); O.L. Lopez; R. Schmidt; A. Teumer (Alexander); I. Ford; N. Karbalai (Nazanin); J.T. Becker (James); M.K. Jonsdottir (Maria K.); R. Au; R.S.N. Fehrmann (Rudolf); S. Herms (Stefan); M.A. Nalls (Michael); W. Zhao; S.T. Turner; K. Yaffe; K. Lohman (Kurt); J.C. van Swieten (John); S.L.R. Kardia; D.S. Knopman (David); W.M. Meeks (William); G. Heiss (Gerardo); E.G. Holliday (Elizabeth); P.W. Schofield; T. Tanaka (Toshiko); D.J. Stott (David J.); J. Wang (Jing); P.M. Ridker (Paul); A.J. Gow; A. Pattie (Alison); J.M. Starr (John); L.J. Hocking; N.J. Armstrong (Nicola J.); S. McLachlan (Stela); L. Shulman (Lee); L.C. Pilling (Luke); G. Eiriksdottir (Gudny); R.J. Scott; N.A. Kochan (Nicole A.); A. Palotie; Y.-C. Hsieh; J.G. Eriksson (Johan G.); A.D. Penman (Alan); R.F. Gottesman (Rebecca); B.A. Oostra (Ben); L. Yu; A.L. DeStefano (Anita L.); A. Beiser; M. Garcia; J.I. Rotter; M.M. Nöthen; A. Hofman (Albert); P.E. Slagboom (Eline); R.G.J. Westendorp; B.M. Buckley (Brendan M.); P.A. Wolf; A.G. Uitterlinden (André); B.M. Psaty (Bruce); H.J. Grabe (Hans Jörgen); S. Bandinelli (Stefania); D.I. Chasman (Daniel); F. Grodstein (Francine); K. Räikkönen (Katri); J.-C. Lambert; D.J. Porteous (David J.); J.F. Price (Jackie F.); P.S. Sachdev (Perminder); L. Ferrucci (Luigi); J. Attia (John); I. Rudan (Igor); C. Hayward; A.F. Wright; J.F. Wilson (James F); S. Cichon (Sven); L. Franke (Lude); H. Schmidt; J. Ding (Jingzhong); A.J. de Craen (Anton); M. Fornage (Myriam); D.A. Bennett (David); I.J. Deary (Ian); M.A. Ikram (Arfan); L.J. Launer (Lenore); A.L. Fitzpatrick; S. Seshadri (Sudha); C.M. van Duijn (Cornelia); T.H. Mosley (Thomas H.)

2016-01-01

textabstractTo identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and

Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics

NARCIS (Netherlands)

Feng, Yen Chen Anne; Cho, Kelly; Lindstrom, Sara; Kraft, Peter; Cormack, Jean; Blalock, Kendra; Campbell, Peter T.; Casey, Graham; Conti, David V.; Edlund, Christopher K.; Figueiredo, Jane; James Gauderman, W.; Gong, Jian; Green, Roger C.; Gruber, Stephen B.; Harju, John F.; Harrison, Tabitha A.; Jacobs, Eric J; Jenkins, Mark A.; Jiao, Shuo; Li, Li; Lin, Yi; Manion, Frank J.; Moreno, Victor; Mukherjee, Bhramar; Peters, Ulrike; Raskin, Leon; Schumacher, Fredrick R.; Seminara, Daniela; Severi, Gianluca; Stenzel, Stephanie L.; Thomas, Duncan C.; Hopper, John L.; Southey, Melissa C.; Makalic, Enes; Schmidt, Daniel F.; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Dos-Santos-Silva, Isabel; Hunter, David J.; Lindström, Sara; Kraft, Peter; Ahsan, Habib; Whittemore, Alice S.; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A.; van der Luijt, Rob B.; Uitterlinden, Andre G; Hofman, Albert; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Crisponi, Laura; Hall, Per; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Easton, Douglas F.; Turnbull, Clare A.; Rahman, Nazneen; Kote-Jarai, Zsofia; Muir, Kenneth; Giles, Graham G.; Severi, Gianluca; Neal, David E.; Donovan, Jenny L.; Hamdy, Freddie C.; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher; Schumacher, Fred; Travis, Ruth C.; Riboli, Elio; Kraft, Peter; Hunter, David J.; Gapstur, Susan M.; Berndt, Sonja I.; Chanock, Stephen J.; Han, Younghun; Su, Li; Wei, Yongyue; Hung, Rayjean J.; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; McKay, James D.; Bickeböller, Heike; Rosenberger, Albert; Houlston, Richard S.; Caporaso, Neil E; Landi, Maria Teresa; Heinrich, Joachim; Risch, Angela; Wu, Xifeng; Ye, Yuanqing; Christiani, David C.; Amos, Christopher I; Liang, Liming; Driver, Jane A.; IGAP Consortium, Colorectal Transdisciplinary Study (CORECT); Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE)

2017-01-01

Growing evidence from both epidemiology and basic science suggest an inverse association between Alzheimer’s disease (AD) and cancer. We examined the genetic relationship between AD and various cancer types using GWAS summary statistics from the IGAP and GAME-ON consortia. Sample size ranged from

Further support for association between GWAS variant for positive emotion and reward systems.

Science.gov (United States)

Lancaster, T M; Ihssen, N; Brindley, L M; Linden, D E J

2017-01-31

A recent genome-wide association study (GWAS) identified a significant single-nucleotide polymorphism (SNP) for trait-positive emotion at rs322931 on chromosome 1, which was also associated with brain activation in the reward system of healthy individuals when observing positive stimuli in a functional magnetic resonance imaging (fMRI) study. In the current study, we aimed to further validate the role of variation at rs322931 in reward processing. Using a similar fMRI approach, we use two paradigms that elicit a strong ventral striatum (VS) blood oxygen-level dependency (BOLD) response in a sample of young, healthy individuals (N=82). In the first study we use a similar picture-viewing task to the discovery sample (positive>neutral stimuli) to replicate an effect of the variant on emotion processing. In the second study we use a probabilistic reversal learning procedure to identify reward processing during decision-making under uncertainly (reward>punishment). In a region of interest (ROI) analysis of the bilateral VS, we show that the rs322931 genotype was associated with BOLD in the left VS during the positive>neutral contrast (P ROI-CORRECTED =0.045) and during the reward>punishment contrast (P ROI-CORRECTED =0.018), although the effect of passive picture viewing was in the opposite direction from that reported in the discovery sample. These findings suggest that the recently identified GWAS hit may influence positive emotion via individual differences in activity in the key hubs of the brain's reward system. Furthermore, these effects may not be limited to the passive viewing of positive emotional scenes, but may also be observed during dynamic decision-making. This study suggests that future studies of this GWAS locus may yield further insight into the biological mechanisms of psychopathologies characterised by deficits in reward processing and positive emotion.

The more from East-Asian, the better: risk prediction of colorectal cancer risk by GWAS-identified SNPs among Japanese.

Science.gov (United States)

Abe, Makiko; Ito, Hidemi; Oze, Isao; Nomura, Masatoshi; Ogawa, Yoshihiro; Matsuo, Keitaro

2017-12-01

Little is known about the difference of genetic predisposition for CRC between ethnicities; however, many genetic traits common to colorectal cancer have been identified. This study investigated whether more SNPs identified in GWAS in East Asian population could improve the risk prediction of Japanese and explored possible application of genetic risk groups as an instrument of the risk communication. 558 Patients histologically verified colorectal cancer and 1116 first-visit outpatients were included for derivation study, and 547 cases and 547 controls were for replication study. Among each population, we evaluated prediction models for the risk of CRC that combined the genetic risk group based on SNPs from GWASs in European-population and a similarly developed model adding SNPs from GWASs in East Asian-population. We examined whether adding East Asian-specific SNPs would improve the discrimination. Six SNPs (rs6983267, rs4779584, rs4444235, rs9929218, rs10936599, rs16969681) from 23 SNPs by European-based GWAS and five SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279) among ten SNPs by Asian-based GWAS were selected in CRC risk prediction model. Compared with a 6-SNP-based model, an 11-SNP model including Asian GWAS-SNPs showed improved discrimination capacity in Receiver operator characteristic analysis. A model with 11 SNPs resulted in statistically significant improvement in both derivation (P = 0.0039) and replication studies (P = 0.0018) compared with six SNP model. We estimated cumulative risk of CRC by using genetic risk group based on 11 SNPs and found that the cumulative risk at age 80 is approximately 13% in the high-risk group while 6% in the low-risk group. We constructed a more efficient CRC risk prediction model with 11 SNPs including newly identified East Asian-based GWAS SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279). Risk grouping based on 11 SNPs depicted lifetime difference of CRC risk. This might be useful for

Contrasting results from GWAS and QTL mapping on wing length in great reed warblers.

Science.gov (United States)

Hansson, Bengt; Sigeman, Hanna; Stervander, Martin; Tarka, Maja; Ponnikas, Suvi; Strandh, Maria; Westerdahl, Helena; Hasselquist, Dennis

2018-04-15

A major goal in evolutionary biology is to understand the genetic basis of adaptive traits. In migratory birds, wing morphology is such a trait. Our previous work on the great reed warbler (Acrocephalus arundinaceus) shows that wing length is highly heritable and under sexually antagonistic selection. Moreover, a quantitative trait locus (QTL) mapping analysis detected a pronounced QTL for wing length on chromosome 2, suggesting that wing morphology is partly controlled by genes with large effects. Here, we re-evaluate the genetic basis of wing length in great reed warblers using a genomewide association study (GWAS) approach based on restriction site-associated DNA sequencing (RADseq) data. We use GWAS models that account for relatedness between individuals and include covariates (sex, age and tarsus length). The resulting association landscape was flat with no peaks on chromosome 2 or elsewhere, which is in line with expectations for polygenic traits. Analysis of the distribution of p-values did not reveal biases, and the inflation factor was low. Effect sizes were however not uniformly distributed on some chromosomes, and the Z chromosome had weaker associations than autosomes. The level of linkage disequilibrium (LD) in the population decayed to background levels within c. 1 kbp. There could be several reasons to why our QTL study and GWAS gave contrasting results including differences in how associations are modelled (cosegregation in pedigree vs. LD associations), how covariates are accounted for in the models, type of marker used (multi- vs. biallelic), difference in power or a combination of these. Our study highlights that the genetic architecture even of highly heritable traits is difficult to characterize in wild populations. © 2018 John Wiley & Sons Ltd.

Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmacogenetic analyses

Directory of Open Access Journals (Sweden)

Stott David J

2011-10-01

Full Text Available Abstract Background The PHArmacogenetic study of Statins in the Elderly at risk (PHASE is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly. Methods The genome wide association study (GWAS was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification. Results Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5. The top SNP (rs445925, chromosome 19 with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19 with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results. Conclusion With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof

A genome-wide association scan (GWAS) for mean telomere length within the COGS project

DEFF Research Database (Denmark)

Pooley, Karen A; Bojesen, Stig E; Weischer, Maren

2013-01-01

Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the "iCOGS" custom genotyping array. All...

Differentiation and Integration: Guiding Principles for Analyzing Cognitive Change

Science.gov (United States)

Siegler, Robert S.; Chen, Zhe

2008-01-01

Differentiation and integration played large roles within classic developmental theories but have been relegated to obscurity within contemporary theories. However, they may have a useful role to play in modern theories as well, if conceptualized as guiding principles for analyzing change rather than as real-time mechanisms. In the present study,…

Targeted exonic sequencing of GWAS loci in the high extremes of the plasma lipids distribution

NARCIS (Netherlands)

Patel, Aniruddh P.; Peloso, Gina M.; Pirruccello, James P.; Johansen, Christopher T.; Dubé, Joseph B.; Larach, Daniel B.; Ban, Matthew R.; Dallinge-Thie, Geesje M.; Gupta, Namrata; Boehnke, Michael; Abecasis, Gonçalo R.; Kastelein, John J. P.; Hovingh, G. Kees; Hegele, Robert A.; Rader, Daniel J.; Kathiresan, Sekar

2016-01-01

Genome-wide association studies (GWAS) for plasma lipid levels have mapped numerous genomic loci, with each region often containing many protein-coding genes. Targeted re-sequencing of exons is a strategy to pinpoint causal variants and genes. We performed solution-based hybrid selection of 9008

Analyzing Developing Country Market Integration using Incomplete Price Data and Cluster Analysis

NARCIS (Netherlands)

Ansah, I.G.; Gardebroek, Koos; Ihle, R.; Jaletac, M.

2015-01-01

Recent global food price developments have spurred renewed interest in analyzing integration of local markets to global markets. A popular approach to quantify market integration is cointegration analysis. However, local market price data often has missing values, outliers, or short and incomplete

SU-D-204-06: Integration of Machine Learning and Bioinformatics Methods to Analyze Genome-Wide Association Study Data for Rectal Bleeding and Erectile Dysfunction Following Radiotherapy in Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Oh, J; Deasy, J [Memorial Sloan Kettering Cancer Center, New York, NY (United States); Kerns, S [University of Rochester Medical Center, Rochester, NY (United States); Ostrer, H [Albert Einstein College of Medicine, Bronx, NY (United States); Rosenstein, B [Mount Sinai School of Medicine, New York, NY (United States)

2016-06-15

Purpose: We investigated whether integration of machine learning and bioinformatics techniques on genome-wide association study (GWAS) data can improve the performance of predictive models in predicting the risk of developing radiation-induced late rectal bleeding and erectile dysfunction in prostate cancer patients. Methods: We analyzed a GWAS dataset generated from 385 prostate cancer patients treated with radiotherapy. Using genotype information from these patients, we designed a machine learning-based predictive model of late radiation-induced toxicities: rectal bleeding and erectile dysfunction. The model building process was performed using 2/3 of samples (training) and the predictive model was tested with 1/3 of samples (validation). To identify important single nucleotide polymorphisms (SNPs), we computed the SNP importance score, resulting from our random forest regression model. We performed gene ontology (GO) enrichment analysis for nearby genes of the important SNPs. Results: After univariate analysis on the training dataset, we filtered out many SNPs with p>0.001, resulting in 749 and 367 SNPs that were used in the model building process for rectal bleeding and erectile dysfunction, respectively. On the validation dataset, our random forest regression model achieved the area under the curve (AUC)=0.70 and 0.62 for rectal bleeding and erectile dysfunction, respectively. We performed GO enrichment analysis for the top 25%, 50%, 75%, and 100% SNPs out of the select SNPs in the univariate analysis. When we used the top 50% SNPs, more plausible biological processes were obtained for both toxicities. An additional test with the top 50% SNPs improved predictive power with AUC=0.71 and 0.65 for rectal bleeding and erectile dysfunction. A better performance was achieved with AUC=0.67 when age and androgen deprivation therapy were added to the model for erectile dysfunction. Conclusion: Our approach that combines machine learning and bioinformatics techniques

SU-D-204-06: Integration of Machine Learning and Bioinformatics Methods to Analyze Genome-Wide Association Study Data for Rectal Bleeding and Erectile Dysfunction Following Radiotherapy in Prostate Cancer

International Nuclear Information System (INIS)

Oh, J; Deasy, J; Kerns, S; Ostrer, H; Rosenstein, B

2016-01-01

Purpose: We investigated whether integration of machine learning and bioinformatics techniques on genome-wide association study (GWAS) data can improve the performance of predictive models in predicting the risk of developing radiation-induced late rectal bleeding and erectile dysfunction in prostate cancer patients. Methods: We analyzed a GWAS dataset generated from 385 prostate cancer patients treated with radiotherapy. Using genotype information from these patients, we designed a machine learning-based predictive model of late radiation-induced toxicities: rectal bleeding and erectile dysfunction. The model building process was performed using 2/3 of samples (training) and the predictive model was tested with 1/3 of samples (validation). To identify important single nucleotide polymorphisms (SNPs), we computed the SNP importance score, resulting from our random forest regression model. We performed gene ontology (GO) enrichment analysis for nearby genes of the important SNPs. Results: After univariate analysis on the training dataset, we filtered out many SNPs with p>0.001, resulting in 749 and 367 SNPs that were used in the model building process for rectal bleeding and erectile dysfunction, respectively. On the validation dataset, our random forest regression model achieved the area under the curve (AUC)=0.70 and 0.62 for rectal bleeding and erectile dysfunction, respectively. We performed GO enrichment analysis for the top 25%, 50%, 75%, and 100% SNPs out of the select SNPs in the univariate analysis. When we used the top 50% SNPs, more plausible biological processes were obtained for both toxicities. An additional test with the top 50% SNPs improved predictive power with AUC=0.71 and 0.65 for rectal bleeding and erectile dysfunction. A better performance was achieved with AUC=0.67 when age and androgen deprivation therapy were added to the model for erectile dysfunction. Conclusion: Our approach that combines machine learning and bioinformatics techniques

Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes

DEFF Research Database (Denmark)

de Jong, Simone; van Eijk, Kristel R; Zeegers, Dave W L H

2012-01-01

of the Psychiatric GWAS consortium (PGC) yielded five novel loci for schizophrenia. In this study, we aim to highlight additional schizophrenia susceptibility loci from the PGC study by combining the top association findings from the discovery stage (9394 schizophrenia cases and 12 462 controls) with expression QTLs...

Data analysis in the post-genome-wide association study era

Directory of Open Access Journals (Sweden)

Qiao-Ling Wang

2016-12-01

Full Text Available Since the first report of a genome-wide association study (GWAS on human age-related macular degeneration, GWAS has successfully been used to discover genetic variants for a variety of complex human diseases and/or traits, and thousands of associated loci have been identified. However, the underlying mechanisms for these loci remain largely unknown. To make these GWAS findings more useful, it is necessary to perform in-depth data mining. The data analysis in the post-GWAS era will include the following aspects: fine-mapping of susceptibility regions to identify susceptibility genes for elucidating the biological mechanism of action; joint analysis of susceptibility genes in different diseases; integration of GWAS, transcriptome, and epigenetic data to analyze expression and methylation quantitative trait loci at the whole-genome level, and find single-nucleotide polymorphisms that influence gene expression and DNA methylation; genome-wide association analysis of disease-related DNA copy number variations. Applying these strategies and methods will serve to strengthen GWAS data to enhance the utility and significance of GWAS in improving understanding of the genetics of complex diseases or traits and translate these findings for clinical applications. Keywords: Genome-wide association study, Data mining, Integrative data analysis, Polymorphism, Copy number variation

Identification of novel type 1 diabetes candidate genes by integrating genome-wide association data, protein-protein interactions, and human pancreatic islet gene expression

DEFF Research Database (Denmark)

Bergholdt, Regine; Brorsson, Caroline; Palleja, Albert

2012-01-01

Genome-wide association studies (GWAS) have heralded a new era in susceptibility locus discovery in complex diseases. For type 1 diabetes, >40 susceptibility loci have been discovered. However, GWAS do not inevitably lead to identification of the gene or genes in a given locus associated with dis......-cells. Our results provide novel insight to the mechanisms behind type 1 diabetes pathogenesis and, thus, may provide the basis for the design of novel treatment strategies.......Genome-wide association studies (GWAS) have heralded a new era in susceptibility locus discovery in complex diseases. For type 1 diabetes, >40 susceptibility loci have been discovered. However, GWAS do not inevitably lead to identification of the gene or genes in a given locus associated...... with disease, and they do not typically inform the broader context in which the disease genes operate. Here, we integrated type 1 diabetes GWAS data with protein-protein interactions to construct biological networks of relevance for disease. A total of 17 networks were identified. To prioritize...

Molecular genetic studies in Saudi population; identified variants from GWAS and meta-analysis in stroke.

Science.gov (United States)

Alharbi, Khalid Khalaf; Ali Khan, Imran; Alotaibi, Mohammad Abdullah; Saud Aloyaid, Abdullah; Al-Basheer, Haifa Abdulaziz; Alghamdi, Naelah Abdullah; Al-Baradie, Raid Saleem; Al-Sulaiman, A M

2018-01-01

Stroke is a multifactorial and heterogeneous disorder, correlates with heritability and considered as one of the major diseases. The prior reports performed the variable models such as genome-wide association studies (GWAS), replication, case-control, cross-sectional and meta-analysis studies and still, we lack diagnostic marker in the global world. There are limited studies were carried out in Saudi population, and we aim to investigate the molecular association of single nucleotide polymorphisms (SNPs) identified through GWAS and meta-analysis studies in stroke patients in the Saudi population. In this case-control study, we have opted gender equality of 207 cases and 207 controls from the capital city of Saudi Arabia in King Saud University Hospital. The peripheral blood (5 ml) sample will be collected in two different vacutainers, and three mL of the coagulated blood will be used for lipid analysis (biochemical tests) and two mL will be used for DNA analysis (molecular tests). Genomic DNA will be extracted with the collected blood samples, and specific primers will be designed for the opted SNPs ( SORT1 -rs646218 and OLR1 -rs11053646 polymorphisms) and PCR-RFLP will be performed and randomly DNA sequencing will be carried out to cross check the results. The rs646218 and rs11053646 polymorphisms were significantly associated with allele, genotype and dominant models with and without crude odds ratios (OR's) and Multiple logistic regression analysis (p Saudi population. The current results were in the association with the prior study results documented through GWAS and meta-analysis association. However, other ethnic population studies should be performed to rule out in the human hereditary diseases.

Genome-wide association mapping including phenotypes from relatives without genotypes in a single-step (ssGWAS for 6-week body weight in broiler chickens

Directory of Open Access Journals (Sweden)

Huiyu eWang

2014-05-01

Full Text Available The purpose of this study was to compare results obtained from various methodologies for genome-wide association studies, when applied to real data, in terms of number and commonality of regions identified and their genetic variance explained, computational speed, and possible pitfalls in interpretations of results. Methodologies include: two iteratively reweighted single-step genomic BLUP procedures (ssGWAS1 and ssGWAS2, a single-marker model (CGWAS, and BayesB. The ssGWAS methods utilize genomic breeding values (GEBVs based on combined pedigree, genomic and phenotypic information, while CGWAS and BayesB only utilize phenotypes from genotyped animals or pseudo-phenotypes. In this study, ssGWAS was performed by converting GEBVs to SNP marker effects. Unequal variances for markers were incorporated for calculating weights into a new genomic relationship matrix. SNP weights were refined iteratively. The data was body weight at 6 weeks on 274,776 broiler chickens, of which 4553 were genotyped using a 60k SNP chip. Comparison of genomic regions was based on genetic variances explained by local SNP regions (20 SNPs. After 3 iterations, the noise was greatly reduced of ssGWAS1 and results are similar to that of CGWAS, with 4 out of the top 10 regions in common. In contrast, for BayesB, the plot was dominated by a single region explaining 23.1% of the genetic variance. This same region was found by ssGWAS1 with the same rank, but the amount of genetic variation attributed to the region was only 3%. These finding emphasize the need for caution when comparing and interpreting results from various methods, and highlight that detected associations, and strength of association, strongly depends on methodologies and details of implementations. BayesB appears to overly shrink regions to zero, while overestimating the amount of genetic variation attributed to the remaining SNP effects. The real world is most likely a compromise between methods and remains to

Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

LENUS (Irish Health Repository)

Trompet, Stella

2011-10-06

Abstract Background The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER\\/PHASE project and second show that the PROSPER\\/PHASE study can be used to study pharmacogenetics in the elderly. Methods The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer\\'s instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification. Results Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE\\/APOC1; LDLR; FADS2\\/FEN1; HMGCR; PSRC1\\/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results. Conclusion With the GWAS in the PROSPER\\/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof

High-frequency acoustic spectrum analyzer based on polymer integrated optics

Science.gov (United States)

Yacoubian, Araz

This dissertation presents an acoustic spectrum analyzer based on nonlinear polymer-integrated optics. The device is used in a scanning heterodyne geometry by zero biasing a Michelson interferometer. It is capable of detecting vibrations from DC to the GHz range. Initial low frequency experiments show that the device is an effective tool for analyzing an acoustic spectrum even in noisy environments. Three generations of integrated sensors are presented, starting with a very lossy (86 dB total insertion loss) initial device that detects vibrations as low as λ/10, and second and third generation improvements with a final device of 44 dB total insertion loss. The sensor was further tested for detecting a pulsed laser-excited vibration and resonances due to the structure of the sample. The data are compared to the acoustic spectrum measured using a low loss passive fiber interferometer detection scheme which utilizes a high speed detector. The peaks present in the passive detection scheme are clearly visible with our sensor data, which have a lower noise floor. Hybrid integration of GHz electronics is also investigated in this dissertation. A voltage controlled oscillator (VCO) is integrated on a polymer device using a new approach. The VCO is shown to operate as specified by the manufacturer, and the RF signal is efficiently launched onto the micro-strip line used for EO modulation. In the future this technology can be used in conjunction with the presented sensor to produce a fully integrated device containing high frequency drive electronics controlled by low DC voltage. Issues related to device fabrication, loss analysis, RF power delivery to drive circuitry, efficient poling of large area samples, and optimizing poling conditions are also discussed throughout the text.

Analyzing Integrated Cost-Schedule Risk for Complex Product Systems R&D Projects

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Zhe Xu

2014-01-01

Full Text Available The vast majority of the research efforts in project risk management tend to assess cost risk and schedule risk independently. However, project cost and time are related in reality and the relationship between them should be analyzed directly. We propose an integrated cost and schedule risk assessment model for complex product systems R&D projects. Graphical evaluation review technique (GERT, Monte Carlo simulation, and probability distribution theory are utilized to establish the model. In addition, statistical analysis and regression analysis techniques are employed to analyze simulation outputs. Finally, a complex product systems R&D project as an example is modeled by the proposed approach and the simulation outputs are analyzed to illustrate the effectiveness of the risk assessment model. It seems that integrating cost and schedule risk assessment can provide more reliable risk estimation results.

Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci

Science.gov (United States)

Shen, Changbing; Gao, Jing; Sheng, Yujun; Dou, Jinfa; Zhou, Fusheng; Zheng, Xiaodong; Ko, Randy; Tang, Xianfa; Zhu, Caihong; Yin, Xianyong; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

2016-01-01

Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association study (GWAS). More than 40 robust susceptible loci have been identified and confirmed to be associated with vitiligo by using GWAS. Most of these associated genes participate in important pathways involved in the pathogenesis of vitiligo. Many susceptible loci with unknown functions in the pathogenesis of vitiligo have also been identified, indicating that additional molecular mechanisms may contribute to the risk of developing vitiligo. In this review, we summarize the key loci that are of genome-wide significance, which have been shown to influence vitiligo risk. These genetic loci may help build the foundation for genetic diagnosis and personalize treatment for patients with vitiligo in the future. However, substantial additional studies, including gene-targeted and functional studies, are required to confirm the causality of the genetic variants and their biological relevance in the development of vitiligo. PMID:26870082

A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics.

Science.gov (United States)

Lu, Qiongshi; Li, Boyang; Ou, Derek; Erlendsdottir, Margret; Powles, Ryan L; Jiang, Tony; Hu, Yiming; Chang, David; Jin, Chentian; Dai, Wei; He, Qidu; Liu, Zefeng; Mukherjee, Shubhabrata; Crane, Paul K; Zhao, Hongyu

2017-12-07

Despite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits' genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance between traits using GWAS summary statistics. Through theoretical and numerical analyses, we demonstrate that our method provides accurate covariance estimates, thereby enabling researchers to dissect both the shared and distinct genetic architecture across traits to better understand their etiologies. Among 50 complex traits with publicly accessible GWAS summary statistics (N total ≈ 4.5 million), we identified more than 170 pairs with statistically significant genetic covariance. In particular, we found strong genetic covariance between late-onset Alzheimer disease (LOAD) and amyotrophic lateral sclerosis (ALS), two major neurodegenerative diseases, in single-nucleotide polymorphisms (SNPs) with high minor allele frequencies and in SNPs located in the predicted functional genome. Joint analysis of LOAD, ALS, and other traits highlights LOAD's correlation with cognitive traits and hints at an autoimmune component for ALS. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis

NARCIS (Netherlands)

Kiryluk, Krzysztof; Li, Yifu; Sanna-Cherchi, Simone; Rohanizadegan, Mersedeh; Suzuki, Hitoshi; Eitner, Frank; Snyder, Holly J.; Choi, Murim; Hou, Ping; Scolari, Francesco; Izzi, Claudia; Gigante, Maddalena; Gesualdo, Loreto; Savoldi, Silvana; Amoroso, Antonio; Cusi, Daniele; Zamboli, Pasquale; Julian, Bruce A.; Novak, Jan; Wyatt, Robert J.; Mucha, Krzysztof; Perola, Markus; Kristiansson, Kati; Viktorin, Alexander; Magnusson, Patrik K.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari; Boland, Anne; Metzger, Marie; Thibaudin, Lise; Wanner, Christoph; Jager, Kitty J.; Goto, Shin; Maixnerova, Dita; Karnib, Hussein H.; Nagy, Judit; Panzer, Ulf; Xie, Jingyuan; Chen, Nan; Tesar, Vladimir; Narita, Ichiei; Berthoux, Francois; Floege, Jürgen; Stengel, Benedicte; Zhang, Hong; Lifton, Richard P.; Gharavi, Ali G.

2012-01-01

IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility

Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets

Directory of Open Access Journals (Sweden)

Max Lam

2017-11-01

Full Text Available Here, we present a large (n = 107,207 genome-wide association study (GWAS of general cognitive ability (“g”, further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum. Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.

Two‐phase designs for joint quantitative‐trait‐dependent and genotype‐dependent sampling in post‐GWAS regional sequencing

Science.gov (United States)

Espin‐Garcia, Osvaldo; Craiu, Radu V.

2017-01-01

ABSTRACT We evaluate two‐phase designs to follow‐up findings from genome‐wide association study (GWAS) when the cost of regional sequencing in the entire cohort is prohibitive. We develop novel expectation‐maximization‐based inference under a semiparametric maximum likelihood formulation tailored for post‐GWAS inference. A GWAS‐SNP (where SNP is single nucleotide polymorphism) serves as a surrogate covariate in inferring association between a sequence variant and a normally distributed quantitative trait (QT). We assess test validity and quantify efficiency and power of joint QT‐SNP‐dependent sampling and analysis under alternative sample allocations by simulations. Joint allocation balanced on SNP genotype and extreme‐QT strata yields significant power improvements compared to marginal QT‐ or SNP‐based allocations. We illustrate the proposed method and evaluate the sensitivity of sample allocation to sampling variation using data from a sequencing study of systolic blood pressure. PMID:29239496

Assessment of Five Chilling Tolerance Traits and GWAS Mapping in Rice Using the USDA Mini-Core Collection

Directory of Open Access Journals (Sweden)

Michael R. Schläppi

2017-06-01

Full Text Available Rice (Oryza sativa L. is often exposed to cool temperatures during spring planting in temperate climates. A better understanding of genetic pathways regulating chilling tolerance will enable breeders to develop varieties with improved tolerance during germination and young seedling stages. To dissect chilling tolerance, five assays were developed; one assay for the germination stage, one assay for the germination and seedling stage, and three for the seedling stage. Based on these assays, five chilling tolerance indices were calculated and assessed using 202 O. sativa accessions from the Rice Mini-Core (RMC collection. Significant differences between RMC accessions made the five indices suitable for genome-wide association study (GWAS based quantitative trait loci (QTL mapping. For young seedling stage indices, japonica and indica subspecies clustered into chilling tolerant and chilling sensitive accessions, respectively, while both subspecies had similar low temperature germinability distributions. Indica subspecies were shown to have chilling acclimation potential. GWAS mapping uncovered 48 QTL at 39 chromosome regions distributed across all 12 rice chromosomes. Interestingly, there was no overlap between the germination and seedling stage QTL. Also, 18 QTL and 32 QTL were in regions discovered in previously reported bi-parental and GWAS based QTL mapping studies, respectively. Two novel low temperature seedling survivability (LTSS–QTL, qLTSS3-4 and qLTSS4-1, were not in a previously reported QTL region. QTL with strong effect alleles identified in this study will be useful for marker assisted breeding efforts to improve chilling tolerance in rice cultivars and enhance gene discovery for chilling tolerance.

A fully integrated standalone portable cavity ringdown breath acetone analyzer

Science.gov (United States)

Sun, Meixiu; Jiang, Chenyu; Gong, Zhiyong; Zhao, Xiaomeng; Chen, Zhuying; Wang, Zhennan; Kang, Meiling; Li, Yingxin; Wang, Chuji

2015-09-01

Breath analysis is a promising new technique for nonintrusive disease diagnosis and metabolic status monitoring. One challenging issue in using a breath biomarker for potential particular disease screening is to find a quantitative relationship between the concentration of the breath biomarker and clinical diagnostic parameters of the specific disease. In order to address this issue, we need a new instrument that is capable of conducting real-time, online breath analysis with high data throughput, so that a large scale of clinical test (more subjects) can be achieved in a short period of time. In this work, we report a fully integrated, standalone, portable analyzer based on the cavity ringdown spectroscopy technique for near-real time, online breath acetone measurements. The performance of the portable analyzer in measurements of breath acetone was interrogated and validated by using the certificated gas chromatography-mass spectrometry. The results show that this new analyzer is useful for reliable online (online introduction of a breath sample without pre-treatment) breath acetone analysis with high sensitivity (57 ppb) and high data throughput (one data per second). Subsequently, the validated breath analyzer was employed for acetone measurements in 119 human subjects under various situations. The instrument design, packaging, specifications, and future improvements were also described. From an optical ringdown cavity operated by the lab-set electronics reported previously to this fully integrated standalone new instrument, we have enabled a new scientific tool suited for large scales of breath acetone analysis and created an instrument platform that can even be adopted for study of other breath biomarkers by using different lasers and ringdown mirrors covering corresponding spectral fingerprints.

A fully integrated standalone portable cavity ringdown breath acetone analyzer.

Science.gov (United States)

Sun, Meixiu; Jiang, Chenyu; Gong, Zhiyong; Zhao, Xiaomeng; Chen, Zhuying; Wang, Zhennan; Kang, Meiling; Li, Yingxin; Wang, Chuji

2015-09-01

Breath analysis is a promising new technique for nonintrusive disease diagnosis and metabolic status monitoring. One challenging issue in using a breath biomarker for potential particular disease screening is to find a quantitative relationship between the concentration of the breath biomarker and clinical diagnostic parameters of the specific disease. In order to address this issue, we need a new instrument that is capable of conducting real-time, online breath analysis with high data throughput, so that a large scale of clinical test (more subjects) can be achieved in a short period of time. In this work, we report a fully integrated, standalone, portable analyzer based on the cavity ringdown spectroscopy technique for near-real time, online breath acetone measurements. The performance of the portable analyzer in measurements of breath acetone was interrogated and validated by using the certificated gas chromatography-mass spectrometry. The results show that this new analyzer is useful for reliable online (online introduction of a breath sample without pre-treatment) breath acetone analysis with high sensitivity (57 ppb) and high data throughput (one data per second). Subsequently, the validated breath analyzer was employed for acetone measurements in 119 human subjects under various situations. The instrument design, packaging, specifications, and future improvements were also described. From an optical ringdown cavity operated by the lab-set electronics reported previously to this fully integrated standalone new instrument, we have enabled a new scientific tool suited for large scales of breath acetone analysis and created an instrument platform that can even be adopted for study of other breath biomarkers by using different lasers and ringdown mirrors covering corresponding spectral fingerprints.

Integrated analyzing method for the progress event based on subjects and predicates in events

International Nuclear Information System (INIS)

Minowa, Hirotsugu; Munesawa, Yoshiomi

2014-01-01

It is expected to make use of the knowledge that was extracted by analyzing the mistakes of the past to prevent recurrence of accidents. Currently main analytic style is an analytic style that experts decipher deeply the accident cases, but cross-analysis has come to an end with extracting the common factors in the accident cases. We propose an integrated analyzing method for progress events to analyze among accidents in this study. Our method realized the integration of many accident cases by the integration connecting the common keyword called as 'Subject' or 'Predicate' that are extracted from each progress event in accident cases or near-miss cases. Our method can analyze and visualize the partial risk identification and the frequency to cause accidents and the risk assessment from the data integrated accident cases. The result of applying our method to PEC-SAFER accident cases identified 8 hazardous factors which can be caused from tank again, and visualized the high frequent factors that the first factor was damage of tank 26% and the second factor was the corrosion 21%, and visualized the high risks that the first risk was the damage 3.3 x 10 -2 [risk rank / year] and the second risk was the destroy 2.5 x 10 -2 [risk rank / year]. (author)

Accounting for eXentricities: analysis of the X chromosome in GWAS reveals X-linked genes implicated in autoimmune diseases.

Directory of Open Access Journals (Sweden)

Diana Chang

Full Text Available Many complex human diseases are highly sexually dimorphic, suggesting a potential contribution of the X chromosome to disease risk. However, the X chromosome has been neglected or incorrectly analyzed in most genome-wide association studies (GWAS. We present tailored analytical methods and software that facilitate X-wide association studies (XWAS, which we further applied to reanalyze data from 16 GWAS of different autoimmune and related diseases (AID. We associated several X-linked genes with disease risk, among which (1 ARHGEF6 is associated with Crohn's disease and replicated in a study of ulcerative colitis, another inflammatory bowel disease (IBD. Indeed, ARHGEF6 interacts with a gastric bacterium that has been implicated in IBD. (2 CENPI is associated with three different AID, which is compelling in light of known associations with AID of autosomal genes encoding centromere proteins, as well as established autosomal evidence of pleiotropy between autoimmune diseases. (3 We replicated a previous association of FOXP3, a transcription factor that regulates T-cell development and function, with vitiligo; and (4 we discovered that C1GALT1C1 exhibits sex-specific effect on disease risk in both IBDs. These and other X-linked genes that we associated with AID tend to be highly expressed in tissues related to immune response, participate in major immune pathways, and display differential gene expression between males and females. Combined, the results demonstrate the importance of the X chromosome in autoimmunity, reveal the potential of extensive XWAS, even based on existing data, and provide the tools and incentive to properly include the X chromosome in future studies.

Using crosscorrelation to mitigate analog/RF impairments for integrated spectrum analyzers

NARCIS (Netherlands)

Oude Alink, M.S.; Klumperink, Eric A.M.; Kokkeler, Andre B.J.; Ru, Z.; Cheng, W.; Nauta, Bram

2013-01-01

An integrated spectrum analyzer is useful for built-in self-test purposes, software-defined radios, or dynamic spectrum access in cognitive radio. The analog/RF performance is impaired by a number of factors, including thermal noise, phase noise, and nonlinearity. In this paper, we present an

Tiny Integrated Network Analyzer for Noninvasive Measurements of Electrically Small Antennas

DEFF Research Database (Denmark)

Buskgaard, Emil Feldborg; Krøyer, Ben; Tatomirescu, Alexandru

2016-01-01

the system. The tiny integrated network analyzer is a stand-alone Arduino-based measurement system that utilizes the transmit signal of the system under test as its reference. It features a power meter with triggering ability, on-board memory, universal serial bus, and easy extendibility with general...

Genetic dissection of photoperiod response based on GWAS of pre-anthesis phase duration in spring barley.

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Ahmad M Alqudah

Full Text Available Heading time is a complex trait, and natural variation in photoperiod responses is a major factor controlling time to heading, adaptation and grain yield. In barley, previous heading time studies have been mainly conducted under field conditions to measure total days to heading. We followed a novel approach and studied the natural variation of time to heading in a world-wide spring barley collection (218 accessions, comprising of 95 photoperiod-sensitive (Ppd-H1 and 123 accessions with reduced photoperiod sensitivity (ppd-H1 to long-day (LD through dissecting pre-anthesis development into four major stages and sub-phases. The study was conducted under greenhouse (GH conditions (LD; 16/8 h; ∼20/∼16°C day/night. Genotyping was performed using a genome-wide high density 9K single nucleotide polymorphisms (SNPs chip which assayed 7842 SNPs. We used the barley physical map to identify candidate genes underlying genome-wide association scans (GWAS. GWAS for pre-anthesis stages/sub-phases in each photoperiod group provided great power for partitioning genetic effects on floral initiation and heading time. In addition to major genes known to regulate heading time under field conditions, several novel QTL with medium to high effects, including new QTL having major effects on developmental stages/sub-phases were found to be associated in this study. For example, highly associated SNPs tagged the physical regions around HvCO1 (barley CONSTANS1 and BFL (BARLEY FLORICAULA/LEAFY genes. Based upon our GWAS analysis, we propose a new genetic network model for each photoperiod group, which includes several newly identified genes, such as several HvCO-like genes, belonging to different heading time pathways in barley.

Analyzing the Feasibility of Using Secure Application Integration Methodology (SAIM) for Integrating DON Enterprise Resource Planning (ERP) Applications

National Research Council Canada - National Science Library

Marin, Ramon

2004-01-01

...) would provide useful information about a beneficial methodology. SAIM is analyzed, by accessing its step by step directions, for suitability in the integration of the Enterprise Resource Planning (ERP...

Pseudocode Interpreter (Pseudocode Integrated Development Environment with Lexical Analyzer and Syntax Analyzer using Recursive Descent Parsing Algorithm

Directory of Open Access Journals (Sweden)

Christian Lester D. Gimeno

2017-11-01

Full Text Available –This research study focused on the development of a software that helps students design, write, validate and run their pseudocode in a semi Integrated Development Environment (IDE instead of manually writing it on a piece of paper.Specifically, the study aimed to develop lexical analyzer or lexer, syntax analyzer or parser using recursive descent parsing algorithm and an interpreter. The lexical analyzer reads pseudocodesource in a sequence of symbols or characters as lexemes.The lexemes are then analyzed by the lexer that matches a pattern for valid tokens and passes to the syntax analyzer or parser. The syntax analyzer or parser takes those valid tokens and builds meaningful commands using recursive descent parsing algorithm in a form of an abstract syntax tree. The generation of an abstract syntax tree is based on the specified grammar rule created by the researcher expressed in Extended Backus-Naur Form. The Interpreter takes the generated abstract syntax tree and starts the evaluation or interpretation to produce pseudocode output. The software was evaluated using white-box testing by several ICT professionals and black-box testing by several computer science students based on the International Organization for Standardization (ISO 9126 software quality standards. The overall results of the evaluation both for white-box and black-box were described as “Excellent in terms of functionality, reliability, usability, efficiency, maintainability and portability”.

GWAS in a box: statistical and visual analytics of structured associations via GenAMap.

Directory of Open Access Journals (Sweden)

Eric P Xing

Full Text Available With the continuous improvement in genotyping and molecular phenotyping technology and the decreasing typing cost, it is expected that in a few years, more and more clinical studies of complex diseases will recruit thousands of individuals for pan-omic genetic association analyses. Hence, there is a great need for algorithms and software tools that could scale up to the whole omic level, integrate different omic data, leverage rich structure information, and be easily accessible to non-technical users. We present GenAMap, an interactive analytics software platform that 1 automates the execution of principled machine learning methods that detect genome- and phenome-wide associations among genotypes, gene expression data, and clinical or other macroscopic traits, and 2 provides new visualization tools specifically designed to aid in the exploration of association mapping results. Algorithmically, GenAMap is based on a new paradigm for GWAS and PheWAS analysis, termed structured association mapping, which leverages various structures in the omic data. We demonstrate the function of GenAMap via a case study of the Brem and Kruglyak yeast dataset, and then apply it on a comprehensive eQTL analysis of the NIH heterogeneous stock mice dataset and report some interesting findings. GenAMap is available from http://sailing.cs.cmu.edu/genamap.

Analysis of 60 reported glioma risk SNPs replicates published GWAS findings but fails to replicate associations from published candidate-gene studies.

Science.gov (United States)

Walsh, Kyle M; Anderson, Erik; Hansen, Helen M; Decker, Paul A; Kosel, Matt L; Kollmeyer, Thomas; Rice, Terri; Zheng, Shichun; Xiao, Yuanyuan; Chang, Jeffrey S; McCoy, Lucie S; Bracci, Paige M; Wiemels, Joe L; Pico, Alexander R; Smirnov, Ivan; Lachance, Daniel H; Sicotte, Hugues; Eckel-Passow, Jeanette E; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R

2013-02-01

Genomewide association studies (GWAS) and candidate-gene studies have implicated single-nucleotide polymorphisms (SNPs) in at least 45 different genes as putative glioma risk factors. Attempts to validate these associations have yielded variable results and few genetic risk factors have been consistently replicated. We conducted a case-control study of Caucasian glioma cases and controls from the University of California San Francisco (810 cases, 512 controls) and the Mayo Clinic (852 cases, 789 controls) in an attempt to replicate previously reported genetic risk factors for glioma. Sixty SNPs selected from the literature (eight from GWAS and 52 from candidate-gene studies) were successfully genotyped on an Illumina custom genotyping panel. Eight SNPs in/near seven different genes (TERT, EGFR, CCDC26, CDKN2A, PHLDB1, RTEL1, TP53) were significantly associated with glioma risk in the combined dataset (P 0.05). Although several confirmed associations are located near genes long known to be involved in gliomagenesis (e.g., EGFR, CDKN2A, TP53), these associations were first discovered by the GWAS approach and are in noncoding regions. These results highlight that the deficiencies of the candidate-gene approach lay in selecting both appropriate genes and relevant SNPs within these genes. © 2012 WILEY PERIODICALS, INC.

A population genetic interpretation of GWAS findings for human quantitative traits

Science.gov (United States)

Bullaughey, Kevin; Hudson, Richard R.; Sella, Guy

2018-01-01

Human genome-wide association studies (GWASs) are revealing the genetic architecture of anthropomorphic and biomedical traits, i.e., the frequencies and effect sizes of variants that contribute to heritable variation in a trait. To interpret these findings, we need to understand how genetic architecture is shaped by basic population genetics processes—notably, by mutation, natural selection, and genetic drift. Because many quantitative traits are subject to stabilizing selection and because genetic variation that affects one trait often affects many others, we model the genetic architecture of a focal trait that arises under stabilizing selection in a multidimensional trait space. We solve the model for the phenotypic distribution and allelic dynamics at steady state and derive robust, closed-form solutions for summary statistics of the genetic architecture. Our results provide a simple interpretation for missing heritability and why it varies among traits. They predict that the distribution of variances contributed by loci identified in GWASs is well approximated by a simple functional form that depends on a single parameter: the expected contribution to genetic variance of a strongly selected site affecting the trait. We test this prediction against the results of GWASs for height and body mass index (BMI) and find that it fits the data well, allowing us to make inferences about the degree of pleiotropy and mutational target size for these traits. Our findings help to explain why the GWAS for height explains more of the heritable variance than the similarly sized GWAS for BMI and to predict the increase in explained heritability with study sample size. Considering the demographic history of European populations, in which these GWASs were performed, we further find that most of the associations they identified likely involve mutations that arose shortly before or during the Out-of-Africa bottleneck at sites with selection coefficients around s = 10−3. PMID

Time-domain single-source integral equations for analyzing scattering from homogeneous penetrable objects

KAUST Repository

Valdé s, Felipe; Andriulli, Francesco P.; Bagci, Hakan; Michielssen, Eric

2013-01-01

Single-source time-domain electric-and magnetic-field integral equations for analyzing scattering from homogeneous penetrable objects are presented. Their temporal discretization is effected by using shifted piecewise polynomial temporal basis

ICSNPathway: identify candidate causal SNPs and pathways from genome-wide association study by one analytical framework.

Science.gov (United States)

Zhang, Kunlin; Chang, Suhua; Cui, Sijia; Guo, Liyuan; Zhang, Liuyan; Wang, Jing

2011-07-01

Genome-wide association study (GWAS) is widely utilized to identify genes involved in human complex disease or some other trait. One key challenge for GWAS data interpretation is to identify causal SNPs and provide profound evidence on how they affect the trait. Currently, researches are focusing on identification of candidate causal variants from the most significant SNPs of GWAS, while there is lack of support on biological mechanisms as represented by pathways. Although pathway-based analysis (PBA) has been designed to identify disease-related pathways by analyzing the full list of SNPs from GWAS, it does not emphasize on interpreting causal SNPs. To our knowledge, so far there is no web server available to solve the challenge for GWAS data interpretation within one analytical framework. ICSNPathway is developed to identify candidate causal SNPs and their corresponding candidate causal pathways from GWAS by integrating linkage disequilibrium (LD) analysis, functional SNP annotation and PBA. ICSNPathway provides a feasible solution to bridge the gap between GWAS and disease mechanism study by generating hypothesis of SNP → gene → pathway(s). The ICSNPathway server is freely available at http://icsnpathway.psych.ac.cn/.

Integration of mouse and human genome-wide association data identifies KCNIP4 as an asthma gene.

Directory of Open Access Journals (Sweden)

Blanca E Himes

Full Text Available Asthma is a common chronic respiratory disease characterized by airway hyperresponsiveness (AHR. The genetics of asthma have been widely studied in mouse and human, and homologous genomic regions have been associated with mouse AHR and human asthma-related phenotypes. Our goal was to identify asthma-related genes by integrating AHR associations in mouse with human genome-wide association study (GWAS data. We used Efficient Mixed Model Association (EMMA analysis to conduct a GWAS of baseline AHR measures from males and females of 31 mouse strains. Genes near or containing SNPs with EMMA p-values <0.001 were selected for further study in human GWAS. The results of the previously reported EVE consortium asthma GWAS meta-analysis consisting of 12,958 diverse North American subjects from 9 study centers were used to select a subset of homologous genes with evidence of association with asthma in humans. Following validation attempts in three human asthma GWAS (i.e., Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG and two human AHR GWAS (i.e., SHARP, DAG, the Kv channel interacting protein 4 (KCNIP4 gene was identified as nominally associated with both asthma and AHR at a gene- and SNP-level. In EVE, the smallest KCNIP4 association was at rs6833065 (P-value 2.9e-04, while the strongest associations for Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG were 1.5e-03, 1.0e-03, 3.1e-03 at rs7664617, rs4697177, rs4696975, respectively. At a SNP level, the strongest association across all asthma GWAS was at rs4697177 (P-value 1.1e-04. The smallest P-values for association with AHR were 2.3e-03 at rs11947661 in SHARP and 2.1e-03 at rs402802 in DAG. Functional studies are required to validate the potential involvement of KCNIP4 in modulating asthma susceptibility and/or AHR. Our results suggest that a useful approach to identify genes associated with human asthma is to leverage mouse AHR association data.

Interactions between household air pollution and GWAS-identified lung cancer susceptibility markers in the Female Lung Cancer Consortium in Asia (FLCCA).

Science.gov (United States)

Hosgood, H Dean; Song, Minsun; Hsiung, Chao Agnes; Yin, Zhihua; Shu, Xiao-Ou; Wang, Zhaoming; Chatterjee, Nilanjan; Zheng, Wei; Caporaso, Neil; Burdette, Laurie; Yeager, Meredith; Berndt, Sonja I; Landi, Maria Teresa; Chen, Chien-Jen; Chang, Gee-Chen; Hsiao, Chin-Fu; Tsai, Ying-Huang; Chien, Li-Hsin; Chen, Kuan-Yu; Huang, Ming-Shyan; Su, Wu-Chou; Chen, Yuh-Min; Chen, Chung-Hsing; Yang, Tsung-Ying; Wang, Chih-Liang; Hung, Jen-Yu; Lin, Chien-Chung; Perng, Reury-Perng; Chen, Chih-Yi; Chen, Kun-Chieh; Li, Yao-Jen; Yu, Chong-Jen; Chen, Yi-Song; Chen, Ying-Hsiang; Tsai, Fang-Yu; Kim, Christopher; Seow, Wei Jie; Bassig, Bryan A; Wu, Wei; Guan, Peng; He, Qincheng; Gao, Yu-Tang; Cai, Qiuyin; Chow, Wong-Ho; Xiang, Yong-Bing; Lin, Dongxin; Wu, Chen; Wu, Yi-Long; Shin, Min-Ho; Hong, Yun-Chul; Matsuo, Keitaro; Chen, Kexin; Wong, Maria Pik; Lu, Dara; Jin, Li; Wang, Jiu-Cun; Seow, Adeline; Wu, Tangchun; Shen, Hongbing; Fraumeni, Joseph F; Yang, Pan-Chyr; Chang, I-Shou; Zhou, Baosen; Chanock, Stephen J; Rothman, Nathaniel; Lan, Qing

2015-03-01

We previously carried out a multi-stage genome-wide association study (GWAS) on lung cancer among never smokers in the Female Lung Cancer Consortium in Asia (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at 5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning for heating and cooking, is the leading cause of the overall disease burden in Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene-HAP interactions associated with lung cancer in loci independent of smoking, we analyzed data from studies participating in FLCCA with fuel use information available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a 30% increased risk of lung cancer (OR 1.3, 95% CI 1.0-1.6). Among the five a priori SNPs identified by our GWAS, two showed a significant interaction with coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04). The risk of lung cancer associated with coal exposure varied with the respective alleles for these two SNPs. Our observations provide evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk. The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations.

Integrative modeling of eQTLs and cis-regulatory elements suggests mechanisms underlying cell type specificity of eQTLs.

Directory of Open Access Journals (Sweden)

Christopher D Brown

Full Text Available Genetic variants in cis-regulatory elements or trans-acting regulators frequently influence the quantity and spatiotemporal distribution of gene transcription. Recent interest in expression quantitative trait locus (eQTL mapping has paralleled the adoption of genome-wide association studies (GWAS for the analysis of complex traits and disease in humans. Under the hypothesis that many GWAS associations tag non-coding SNPs with small effects, and that these SNPs exert phenotypic control by modifying gene expression, it has become common to interpret GWAS associations using eQTL data. To fully exploit the mechanistic interpretability of eQTL-GWAS comparisons, an improved understanding of the genetic architecture and causal mechanisms of cell type specificity of eQTLs is required. We address this need by performing an eQTL analysis in three parts: first we identified eQTLs from eleven studies on seven cell types; then we integrated eQTL data with cis-regulatory element (CRE data from the ENCODE project; finally we built a set of classifiers to predict the cell type specificity of eQTLs. The cell type specificity of eQTLs is associated with eQTL SNP overlap with hundreds of cell type specific CRE classes, including enhancer, promoter, and repressive chromatin marks, regions of open chromatin, and many classes of DNA binding proteins. These associations provide insight into the molecular mechanisms generating the cell type specificity of eQTLs and the mode of regulation of corresponding eQTLs. Using a random forest classifier with cell specific CRE-SNP overlap as features, we demonstrate the feasibility of predicting the cell type specificity of eQTLs. We then demonstrate that CREs from a trait-associated cell type can be used to annotate GWAS associations in the absence of eQTL data for that cell type. We anticipate that such integrative, predictive modeling of cell specificity will improve our ability to understand the mechanistic basis of human

Comparing Analytic Methods for Longitudinal GWAS and a Case-Study Evaluating Chemotherapy Course Length in Pediatric AML. A Report from the Children’s Oncology Group.

Directory of Open Access Journals (Sweden)

Marijana Vujkovic

2016-08-01

Full Text Available Regression analysis is commonly used in genome-wide association studies (GWAS to test genotype-phenotype associations but restricts the phenotype to a single observation for each individual. There is an increasing need for analytic methods for longitudinally collected phenotype data. Several methods have been proposed to perform longitudinal GWAS for family-based studies but few methods are described for unrelated populations. We compared the performance of three statistical approaches for longitudinal GWAS in unrelated subjectes: (1 principal component-based generalized estimating equations (PC-GEE; (2 principal component-based linear mixed effects model (PC-LMEM; (3 kinship coefficient matrix-based linear mixed effects model (KIN-LMEM, in a study of single-nucleotide polymorphisms (SNPs on the duration of 4 courses of chemotherapy in 624 unrelated children with de novo acute myeloid leukemia (AML genotyped on the Illumina 2.5M OmniQuad from the COG studies AAML0531 and AAML1031.In this study we observed an exaggerated type I error with PC-GEE in SNPs with minor allele frequencies < 0.05, wheras KIN-LMEM produces more than expected type II errors. PC-MEM showed balanced type I and type II errors for the observed versus expected P-values in comparison to competing approaches. In general, a strong concordance was observed between the P-values with the different approaches, in particular among P-values < 0.01 where the between-method AUCs exceed 99%. PC-LMEM accounts for genetic relatedness and correlations among repeated phenotype measures, shows minimal genome-wide inflation of type I errors, and yields high power. We therefore recommend PC-LMEM as a robust analytic approach for GWAS of longitudinal data in unrelated populations.

ANALYZING THE CONSUMER PROFILING FOR IMPROVING EFFORTS OF INTEGRATED MARKETING COMMUNICATION

Directory of Open Access Journals (Sweden)

Olimpia OANCEA

2014-06-01

Full Text Available In an economy with a strong concurential character, organizations must capitalize the integrated marketing communication in the most effective way, to ensure the creation and maintenance of long-term relationships with current and potential customers. Building and managing the relationships with customers can have a direct and favourable effect on the efficiency of an organization's communication efforts. The integrated marketing communication identifies with the nowadays market dynamics and learns the organizations how easy can be to prosper in an environment where changes occur in an alarming way. Therefore, the purpose of this paper is to analyze the socio-demographic profile of the consumers of bread in Arges County, as well as the preferences and purchasing behaviour at the level of the market segments identified using the K-Means Cluster Analysis method.

Fasting Glucose GWAS Candidate Region Analysis across Ethnic Groups in the Multi-Ethnic Study of Atherosclerosis (MESA)

OpenAIRE

Rasmussen-Torvik, L. J.; Guo, X.; Bowden, D. W.; Bertoni, A. G.; Sale, M. M.; Yao, J.; Bluemke, D. A.; Goodarzi, M. O.; Chen, Y. I.; Vaidya, D.; Raffel, L. J.; Papanicolaou, G.J.; Meigs, J. B.; Pankow, J. S.

2012-01-01

Genetic variants associated with fasting glucose in European ancestry populations are increasingly well understood. However, the nature of the associations between these SNPs and fasting glucose in other racial and ethnic groups is unclear. We sought to examine regions previously identified to be associated with fasting glucose in Caucasian GWAS across multiple ethnicities in the Multi-Ethnic Study of Atherosclerosis (MESA). Non-diabetic MESA participants with fasting glucose measured at the ...

GWAS for plant growth stages and yield components in spring wheat (Triticum aestivum L.) harvested in three regions of Kazakhstan.

Science.gov (United States)

Turuspekov, Yerlan; Baibulatova, Aida; Yermekbayev, Kanat; Tokhetova, Laura; Chudinov, Vladimir; Sereda, Grigoriy; Ganal, Martin; Griffiths, Simon; Abugalieva, Saule

2017-11-14

Spring wheat is the largest agricultural crop grown in Kazakhstan with an annual sowing area of 12 million hectares in 2016. Annually, the country harvests around 15 million tons of high quality grain. Despite environmental stress factors it is predicted that the use of new technologies may lead to increases in productivity from current levels of 1.5 to up to 3 tons per hectare. One way of improving wheat productivity is by the application of new genomic oriented approaches in plant breeding projects. Genome wide association studies (GWAS) are emerging as powerful tools for the understanding of the inheritance of complex traits via utilization of high throughput genotyping technologies and phenotypic assessments of plant collections. In this study, phenotyping and genotyping data on 194 spring wheat accessions from Kazakhstan, Russia, Europe, and CIMMYT were assessed for the identification of marker-trait associations (MTA) of agronomic traits by using GWAS. Field trials in Northern, Central and Southern regions of Kazakhstan using 194 spring wheat accessions revealed strong correlations of yield with booting date, plant height, biomass, number of spikes per plant, and number of kernels per spike. The accessions from Europe and CIMMYT showed high breeding potential for Southern and Central regions of the country in comparison with the performance of the local varieties. The GGE biplot method, using average yield per plant, suggested a clear separation of accessions into their three breeding origins in relationship to the three environments in which they were evaluated. The genetic variation in the three groups of accessions was further studied using 3245 polymorphic SNP (single nucleotide polymorphism) markers. The application of Principal Coordinate analysis clearly grouped the 194 accessions into three clades according to their breeding origins. GWAS on data from nine field trials allowed the identification of 114 MTAs for 12 different agronomic traits. Field

Ion-beam apparatus and method for analyzing and controlling integrated circuits

Science.gov (United States)

Campbell, Ann N.; Soden, Jerry M.

1998-01-01

An ion-beam apparatus and method for analyzing and controlling integrated circuits. The ion-beam apparatus comprises a stage for holding one or more integrated circuits (ICs); a source means for producing a focused ion beam; and a beam-directing means for directing the focused ion beam to irradiate a predetermined portion of the IC for sufficient time to provide an ion-beam-generated electrical input signal to a predetermined element of the IC. The apparatus and method have applications to failure analysis and developmental analysis of ICs and permit an alteration, control, or programming of logic states or device parameters within the IC either separate from or in combination with applied electrical stimulus to the IC for analysis thereof. Preferred embodiments of the present invention including a secondary particle detector and an electron floodgun further permit imaging of the IC by secondary ions or electrons, and allow at least a partial removal or erasure of the ion-beam-generated electrical input signal.

Heritability and GWAS Analyses of Acne in Australian Adolescent Twins.

Science.gov (United States)

Mina-Vargas, Angela; Colodro-Conde, Lucía; Grasby, Katrina; Zhu, Gu; Gordon, Scott; Medland, Sarah E; Martin, Nicholas G

2017-12-01

Acne vulgaris is a skin disease with a multifactorial and complex pathology. While several twin studies have estimated that acne has a heritability of up to 80%, the genomic elements responsible for the origin and pathology of acne are still undiscovered. Here we performed a twin-based structural equation model, using available data on acne severity for an Australian sample of 4,491 twins and their siblings aged from 10 to 24. This study extends by a factor of 3 an earlier analysis of the genetic factors of acne. Acne severity was rated by nurses on a 4-point scale (1 = absent to 4 = severe) on up to three body sites (face, back, chest) and on up to three occasions (age 12, 14, and 16). The phenotype that we analyzed was the most severe rating at any site or age. The polychoric correlation for monozygotic twins was higher (r MZ = 0.86, 95% CI [0.81, 0.90]) than for dizygotic twins (r DZ = 0.42, 95% CI [0.35, 0.47]). A model that includes additive genetic effects and unique environmental effects was the most parsimonious model to explain the genetic variance of acne severity, and the estimated heritability was 0.85 (95% CI [0.82, 0.87]). We then conducted a genome-wide analysis including an additional 271 siblings - for a total of 4,762 individuals. A genome-wide association study (GWAS) scan did not detect loci associated with the severity of acne at the threshold of 5E-08 but suggestive association was found for three SNPs: rs10515088 locus 5q13.1 (p = 3.9E-07), rs12738078 locus 1p35.5 (p = 6.7E-07), and rs117943429 locus 18q21.2 (p = 9.1E-07). The 5q13.1 locus is close to PIK3R1, a gene that has a potential regulatory effect on sebocyte differentiation.

Properties and modeling of GWAS when complex disease risk is due to non-complementing, deleterious mutations in genes of large effect.

Directory of Open Access Journals (Sweden)

Kevin R Thornton

Full Text Available Current genome-wide association studies (GWAS have high power to detect intermediate frequency SNPs making modest contributions to complex disease, but they are underpowered to detect rare alleles of large effect (RALE. This has led to speculation that the bulk of variation for most complex diseases is due to RALE. One concern with existing models of RALE is that they do not make explicit assumptions about the evolution of a phenotype and its molecular basis. Rather, much of the existing literature relies on arbitrary mapping of phenotypes onto genotypes obtained either from standard population-genetic simulation tools or from non-genetic models. We introduce a novel simulation of a 100-kilobase gene region, based on the standard definition of a gene, in which mutations are unconditionally deleterious, are continuously arising, have partially recessive and non-complementing effects on phenotype (analogous to what is widely observed for most Mendelian disorders, and are interspersed with neutral markers that can be genotyped. Genes evolving according to this model exhibit a characteristic GWAS signature consisting of an excess of marginally significant markers. Existing tests for an excess burden of rare alleles in cases have low power while a simple new statistic has high power to identify disease genes evolving under our model. The structure of linkage disequilibrium between causative mutations and significantly associated markers under our model differs fundamentally from that seen when rare causative markers are assumed to be neutral. Rather than tagging single haplotypes bearing a large number of rare causative alleles, we find that significant SNPs in a GWAS tend to tag single causative mutations of small effect relative to other mutations in the same gene. Our results emphasize the importance of evaluating the power to detect associations under models that are genetically and evolutionarily motivated.

GWAS of agronomic traits in soybean collection included in breeding pool in Kazakhstan.

Science.gov (United States)

Zatybekov, Alibek; Abugalieva, Saule; Didorenko, Svetlana; Gerasimova, Yelena; Sidorik, Ivan; Anuarbek, Shynar; Turuspekov, Yerlan

2017-11-14

In recent years soybean is becoming one of the most important oilseed crops in Kazakhstan. Only within the last ten years (2006-2016), the area under soybean is expanded from 45 thousand hectares (ha) in 2006 to 120 thousand ha in 2016. The general trend of soybean expansion is from south-eastern to eastern and northern regions of the country, where average temperatures are lower and growing seasons are shorter. These new soybean growing territories were poorly examined in terms of general effects on productivity level among the diverse sample of soybean accessions. In this study, phenotypic data were collected in three separate regions of Kazakhstan and entire soybean sample was genotyped for identification of marker-trait associations (MTA). In this study, the collection of 113 accessions representing five different regions of the World was planted in 2015-2016 in northern, eastern, and south-eastern regions of Kazakhstan. It was observed that North American accessions showed the highest yield in four out of six trials especially in Northern Kazakhstan in both years. The entire sample was genotyped with 6 K SNP Illumina array. 4442 SNPs found to be polymorphic and were used for whole genome genotyping purposes. Obtained SNP markers data and field data were used for GWAS (genome-wide association study). 30 SNPs appear to be very significant in 42 MTAs in six studied environments. The study confirms the efficiency of GWAS for the identification of molecular markers which tag important agronomic traits. Overall thirty SNP markers associated with time to flowering and maturation, plant height, number of fertile nodes, seeds per plant and yield were identified. Physical locations of 32 identified out of 42 total MTAs coincide well with positions of known analogous QTLs. This result indicates importance of revealed MTAs for soybean growing regions in Kazakhstan. Obtained results would serve as required prerequisite for forming and realization of specific breeding

Education and leisure: analyzing the Integrated School Program in Belo Horizonte

Directory of Open Access Journals (Sweden)

Marcília de Sousa Silva

2015-01-01

Full Text Available This article aims to analyze the concepts of leisure and education that permeate the documents in the Integrated School Program in Belo Horizonte. The analysis was based on the Policy cycle approach and emphasized the contexts of influence and the policy text production. Thus, the formation of the political agenda, the Political Pedagogical Project Program and the Strategic Plan 2010-2030 BH were investigated. The policy context is not organized in a linear fashion; it is a process of groups of interest interaction. With the discourse of coping with school failure, revealed by the students’ yield and flow evaluation indices (approval, repetition and dropout, the Integrated School education documents announce education and leisure as forms of production, strengthening links between public and private. The right to education is restricted to children’s and youth’s access and permanence in school without creating a perspective of universalization and quality. The documents address the leisure with a simplistic view of construction and maintenance of equipment and the idea of activity

AnalyzeHOLE: An Integrated Wellbore Flow Analysis Tool

Energy Technology Data Exchange (ETDEWEB)

Keith J. Halford

2009-10-01

Conventional interpretation of flow logs assumes that hydraulic conductivity is directly proportional to flow change with depth. However, well construction can significantly alter the expected relation between changes in fluid velocity and hydraulic conductivity. Strong hydraulic conductivity contrasts between lithologic intervals can be masked in continuously screened wells. Alternating intervals of screen and blank casing also can greatly complicate the relation between flow and hydraulic properties. More permeable units are not necessarily associated with rapid fluid-velocity increases. Thin, highly permeable units can be misinterpreted as thick and less permeable intervals or not identified at all. These conditions compromise standard flow-log interpretation because vertical flow fields are induced near the wellbore. AnalyzeHOLE, an integrated wellbore analysis tool for simulating flow and transport in wells and aquifer systems, provides a better alternative for simulating and evaluating complex well-aquifer system interaction. A pumping well and adjacent aquifer system are simulated with an axisymmetric, radial geometry in a two-dimensional MODFLOW model. Hydraulic conductivities are distributed by depth and estimated with PEST by minimizing squared differences between simulated and measured flows and drawdowns. Hydraulic conductivity can vary within a lithology but variance is limited with regularization. Transmissivity of the simulated system also can be constrained to estimates from single-well, pumping tests. Water-quality changes in the pumping well are simulated with simple mixing models between zones of differing water quality. These zones are differentiated by backtracking thousands of particles from the well screens with MODPATH. An Excel spreadsheet is used to interface the various components of AnalyzeHOLE by (1) creating model input files, (2) executing MODFLOW, MODPATH, PEST, and supporting FORTRAN routines, and (3) importing and graphically

Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations

NARCIS (Netherlands)

Seow, Wei Jie; Matsuo, Keitaro; Hsiung, Chao Agnes; Shiraishi, Kouya; Song, Minsun; Kim, Hee Nam; Wong, Maria Pik; Hong, Yun-Chul; Hosgood, H. Dean; Wang, Zhaoming; Chang, I-Shou; Wang, Jiu-Cun; Chatterjee, Nilanjan; Tucker, Margaret; Wei, Hu; Mitsudomi, Tetsuya; Zheng, Wei; Kim, Jin Hee; Zhou, Baosen; Caporaso, Neil E; Albanes, Demetrius; Shin, Min-Ho; Chung, Lap Ping; An, She-Juan; Wang, Ping; Zheng, Hong; Yatabe, Yasushi; Zhang, Xu-Chao; Kim, Young Tae; Shu, Xiao Ou; Kim, Young-Chul; Bassig, Bryan A.; Chang, Jiang; Ho, James Chung Man; Ji, Bu Tian; Kubo, Michiaki; Daigo, Yataro; Ito, Hidemi; Momozawa, Yukihide; Ashikawa, Kyota; Kamatani, Yoichiro; Honda, Takayuki; Sakamoto, Hiromi; Kunitoh, Hideo; Tsuta, Koji; Watanabe, Shun-Ichi; Nokihara, Hiroshi; Miyagi, Yohei; Nakayama, Haruhiko; Matsumoto, Shingo; Tsuboi, Masahiro; Goto, Koichi; Yin, Zhihua; Shi, Jianxin; Takahashi, Atsushi; Goto, Akiteru; Minamiya, Yoshihiro; Shimizu, Kimihiro; Tanaka, Kazumi; Wu, Tangchun; Wei, Fusheng; Wong, Jason Y Y; Matsuda, Fumihiko; Su, Jian; Kim, Yeul Hong; Oh, In-Jae; Song, Fengju; Lee, Victor Ho Fun; Su, Wu-Chou; Chen, Yuh-Min; Chang, Gee-Chen; Chen, Kuan-Yu; Huang, Ming-Shyan; Yang, Pan-Chyr; Lin, Hsien-Chih; Xiang, Yong-Bing; Seow, Adeline; Park, Jae Yong; Kweon, Sun-Seog; Chen, Chien-Jen; Li, Haixin; Gao, Yu Tang; Wu, Chen; Qian, Biyun; Lu, Daru; Liu, Jianjun; Jeon, Hyo-Sung; Hsiao, Chin-Fu; Sung, Jae Sook; Tsai, Ying-Huang; Jung, Yoo Jin; Guo, Huan; Hu, Zhibin; Wang, Wen-Chang; Chung, Charles C.; Lawrence, Charles; Burdett, Laurie; Yeager, Meredith; Jacobs, Kevin B.; Hutchinson, Amy; Berndt, Sonja I.; He, Xingzhou; Wu, Wei; Wang, Junwen; Li, Yuqing; Choi, Jin Eun; Park, Kyong Hwa; Sung, Sook Whan; Liu, Li; Kang, Chang Hyun; Hu, Lingmin; Chen, Chung-Hsing; Yang, Tsung-Ying; Xu, Jun; Guan, Peng; Tan, Wen; Wang, Chih-Liang; Sihoe, Alan Dart Loon; Chen, Ying; Choi, Yi Young; Hung, Jen-Yu; Kim, Jun Suk; Yoon, Ho-Il; Cai, Qiuyin; Lin, Chien-Chung; Park, In Kyu; Xu, Ping; Dong, Jing; Kim, Christopher; He, Qincheng; Perng, Reury-Perng; Chen, Chih-Yi; Vermeulen, Roel; Wu, Junjie; Lim, Wei-Yen; Chen, Kun-Chieh; Chan, John K C; Chu, Minjie; Li, Yao-Jen; Li, Jihua; Chen, Hongyan; Yu, Chong-Jen; Jin, Li; Lo, Yen-Li; Chen, Ying-Hsiang; Fraumeni, Joseph F.; Liu, Jie; Yamaji, Taiki; Yang, Yang; Hicks, Belynda; Wyatt, Kathleen; Li, Shengchao A; Dai, Juncheng; Ma, Hongxia; Jin, Guangfu; Song, Bao; Wang, Zhehai; Cheng, Sensen; Li, Xuelian; Ren, Yangwu; Cui, Ping; Iwasaki, Motoki; Shimazu, Taichi; Tsugane, Shoichiro; Zhu, Junjie; Jiang, Gening; Fei, Ke; Wu, Guoping; Chien, Li-Hsin; Chen, Hui-Ling; Su, Yu-Chun; Tsai, Fang-Yu; Chen, Yi-Song; Yu, Jinming; Stevens, Victoria L; Laird-Offringa, Ite A; Marconett, Crystal N; Lin, Dongxin; Chen, Kexin; Wu, Yi-Long; Landi, Maria Teresa; Shen, Hongbing; Rothman, Nathaniel; Kohno, Takashi; Chanock, Stephen J.; Lan, Qing

2017-01-01

To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking

Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers--results from BPC3.

Directory of Open Access Journals (Sweden)

Sara Lindstrom

2011-02-01

Full Text Available Genome-wide association studies (GWAS have identified multiple single nucleotide polymorphisms (SNPs associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3. We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10⁻²⁸. Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test, where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade < 8 tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined.

Integrating genome-wide association study and expression quantitative trait loci data identifies multiple genes and gene set associated with neuroticism.

Science.gov (United States)

Fan, Qianrui; Wang, Wenyu; Hao, Jingcan; He, Awen; Wen, Yan; Guo, Xiong; Wu, Cuiyan; Ning, Yujie; Wang, Xi; Wang, Sen; Zhang, Feng

2017-08-01

Neuroticism is a fundamental personality trait with significant genetic determinant. To identify novel susceptibility genes for neuroticism, we conducted an integrative analysis of genomic and transcriptomic data of genome wide association study (GWAS) and expression quantitative trait locus (eQTL) study. GWAS summary data was driven from published studies of neuroticism, totally involving 170,906 subjects. eQTL dataset containing 927,753 eQTLs were obtained from an eQTL meta-analysis of 5311 samples. Integrative analysis of GWAS and eQTL data was conducted by summary data-based Mendelian randomization (SMR) analysis software. To identify neuroticism associated gene sets, the SMR analysis results were further subjected to gene set enrichment analysis (GSEA). The gene set annotation dataset (containing 13,311 annotated gene sets) of GSEA Molecular Signatures Database was used. SMR single gene analysis identified 6 significant genes for neuroticism, including MSRA (p value=2.27×10 -10 ), MGC57346 (p value=6.92×10 -7 ), BLK (p value=1.01×10 -6 ), XKR6 (p value=1.11×10 -6 ), C17ORF69 (p value=1.12×10 -6 ) and KIAA1267 (p value=4.00×10 -6 ). Gene set enrichment analysis observed significant association for Chr8p23 gene set (false discovery rate=0.033). Our results provide novel clues for the genetic mechanism studies of neuroticism. Copyright © 2017. Published by Elsevier Inc.

GWAS-based machine learning approach to predict duloxetine response in major depressive disorder.

Science.gov (United States)

Maciukiewicz, Malgorzata; Marshe, Victoria S; Hauschild, Anne-Christin; Foster, Jane A; Rotzinger, Susan; Kennedy, James L; Kennedy, Sidney H; Müller, Daniel J; Geraci, Joseph

2018-04-01

Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders and is commonly treated with antidepressant drugs. However, large variability is observed in terms of response to antidepressants. Machine learning (ML) models may be useful to predict treatment outcomes. A sample of 186 MDD patients received treatment with duloxetine for up to 8 weeks were categorized as "responders" based on a MADRS change >50% from baseline; or "remitters" based on a MADRS score ≤10 at end point. The initial dataset (N = 186) was randomly divided into training and test sets in a nested 5-fold cross-validation, where 80% was used as a training set and 20% made up five independent test sets. We performed genome-wide logistic regression to identify potentially significant variants related to duloxetine response/remission and extracted the most promising predictors using LASSO regression. Subsequently, classification-regression trees (CRT) and support vector machines (SVM) were applied to construct models, using ten-fold cross-validation. With regards to response, none of the pairs performed significantly better than chance (accuracy p > .1). For remission, SVM achieved moderate performance with an accuracy = 0.52, a sensitivity = 0.58, and a specificity = 0.46, and 0.51 for all coefficients for CRT. The best performing SVM fold was characterized by an accuracy = 0.66 (p = .071), sensitivity = 0.70 and a sensitivity = 0.61. In this study, the potential of using GWAS data to predict duloxetine outcomes was examined using ML models. The models were characterized by a promising sensitivity, but specificity remained moderate at best. The inclusion of additional non-genetic variables to create integrated models may improve prediction. Copyright © 2017. Published by Elsevier Ltd.

Digital pulse-shape analyzer based on fast sampling of an integrated charge pulse

International Nuclear Information System (INIS)

Jordanov, V.T.; Knoll, G.F.

1995-01-01

A novel configuration for pulse-shape analysis and discrimination has been developed. The current pulse from detector is sent to a gated integrator and then sampled by a flash analog-to-digital converter (ADC). The sampled data are processed digitally, thus allowing implementation of a near-optimum weighting function and elimination some of the instabilities associated with the gated integrator. The analyzer incorporates pileup rejection circuit that reduces the pileup effects at high counting rates. The system was tested liquid scintillator. Figures of merit for neutron-gamma pulse-shape discrimination were found to be: 0.78 for 25 keV (electron equivalent energy) and 3.5 for 500 keV. The technique described in this paper was developed to be used in a near tissue-equivalent neutron-gamma dosimeter which employs a liquid scintillator detector

pKWmEB: integration of Kruskal-Wallis test with empirical Bayes under polygenic background control for multi-locus genome-wide association study.

Science.gov (United States)

Ren, Wen-Long; Wen, Yang-Jun; Dunwell, Jim M; Zhang, Yuan-Ming

2018-03-01

Although nonparametric methods in genome-wide association studies (GWAS) are robust in quantitative trait nucleotide (QTN) detection, the absence of polygenic background control in single-marker association in genome-wide scans results in a high false positive rate. To overcome this issue, we proposed an integrated nonparametric method for multi-locus GWAS. First, a new model transformation was used to whiten the covariance matrix of polygenic matrix K and environmental noise. Using the transferred model, Kruskal-Wallis test along with least angle regression was then used to select all the markers that were potentially associated with the trait. Finally, all the selected markers were placed into multi-locus model, these effects were estimated by empirical Bayes, and all the nonzero effects were further identified by a likelihood ratio test for true QTN detection. This method, named pKWmEB, was validated by a series of Monte Carlo simulation studies. As a result, pKWmEB effectively controlled false positive rate, although a less stringent significance criterion was adopted. More importantly, pKWmEB retained the high power of Kruskal-Wallis test, and provided QTN effect estimates. To further validate pKWmEB, we re-analyzed four flowering time related traits in Arabidopsis thaliana, and detected some previously reported genes that were not identified by the other methods.

Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility

NARCIS (Netherlands)

Chang, Chia-Jung; Kuo, Ho-Chang; Chang, Jeng-Sheng; Lee, Jong-Keuk; Tsai, Fuu-Jen; Khor, Chiea Chuen; Chang, Li-Ching; Chen, Shih-Ping; Ko, Tai-Ming; Liu, Yi-Min; Chen, Ying-Ju; Hong, Young Mi; Jang, Gi Young; Hibberd, Martin L.; Kuijpers, Taco; Burgner, David; Levin, Michael; Burns, Jane C.; Davila, Sonia; Chen, Yuan-Tsong; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Lee, Yi-Ching; Liang, Chi-Di; Hwang, Kao-Pin; Chang, Luan-Yin; Huang, Li-Min; Chen, Ming-Ren; Chi, Hsin; Huang, Fu-Yuan; Chiu, Nan-Chang; Lee, Meng-Luen; Huang, Yhu-Chering; Hwang, Betau; Lee, Pi-Chang; Yoo, Jeong-Jin; Park, In-Sook; Hong, Soo-Jong; Kim, Kwi-Joo; Kim, Jae-Jung; Sohn, Saejung; Young Jang, Gi; Ha, Kee-Soo; Nam, Hyo-Kyoung; Byeon, Jung-Hye; Yun, Sin Weon; Han, Myung Ki; Kuipers, Irene M.; Ottenkamp, Jaap J.; Biezeveld, Maarten

2013-01-01

The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in

Port supply chain integration : analyzing biofuel supply chains

NARCIS (Netherlands)

Stevens, Leonie C. E.; Vis, Iris F. A.

2016-01-01

This paper focuses on port supply chain integration to strengthen operational and business performance. We provide a structured and comprehensive method to enable port supply chain integration and demonstrate its applicability to the biofuel supply chain. We define the value proposition, role,

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

Science.gov (United States)

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

2017-05-01

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

An integrated simulation tool for analyzing the Operation and Interdependency of Natural Gas and Electric Power Systems

OpenAIRE

PAMBOUR Kwabena A.; CAKIR BURCIN; BOLADO LAVIN Ricardo; DIJKEMA Gerard

2016-01-01

In this paper, we present an integrated simulation tool for analyzing the interdependency of natural gas and electric power systems in terms of security of energy supply. In the first part, we develop mathematical models for the individual systems. In part two, we identify the interconnections between both systems and propose a method for coupling the combined simulation model. Next, we develop the algorithm for solving the combined system and integrate this algorithm into a simulation softwa...

Time-domain single-source integral equations for analyzing scattering from homogeneous penetrable objects

KAUST Repository

Valdés, Felipe

2013-03-01

Single-source time-domain electric-and magnetic-field integral equations for analyzing scattering from homogeneous penetrable objects are presented. Their temporal discretization is effected by using shifted piecewise polynomial temporal basis functions and a collocation testing procedure, thus allowing for a marching-on-in-time (MOT) solution scheme. Unlike dual-source formulations, single-source equations involve space-time domain operator products, for which spatial discretization techniques developed for standalone operators do not apply. Here, the spatial discretization of the single-source time-domain integral equations is achieved by using the high-order divergence-conforming basis functions developed by Graglia alongside the high-order divergence-and quasi curl-conforming (DQCC) basis functions of Valdés The combination of these two sets allows for a well-conditioned mapping from div-to curl-conforming function spaces that fully respects the space-mapping properties of the space-time operators involved. Numerical results corroborate the fact that the proposed procedure guarantees accuracy and stability of the MOT scheme. © 2012 IEEE.

An integrative conceptual framework for analyzing customer satisfaction with shopping trip experiences in grocery retailing

DEFF Research Database (Denmark)

Esbjerg, Lars; Jensen, Birger Boutrup; Bech-Larsen, Tino

2012-01-01

Grocery retailers aim to satisfy customers, and because grocery shopping trips are frequently recurring, they must do socontinuously. Surprisingly, little research has addressed satisfaction with individual grocery shopping trips. This article therefore develops a conceptual framework for analyzing...... customer satisfaction with individual grocery shopping trip experiences within a overall ‘disconfirmation of expectations model’ of customer satisfaction. The contribution of the framework is twofold. First, by focusing on satisfaction with individual grocery shopping trips, previous research...... on satisfaction in the retailing literature. Second, the framework synthesizes and integrates multiple central concepts from different research streams into a common framework for analyzing shopping trip satisfaction. Propositions are derived regarding the relationships among the different concepts...

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data.

Directory of Open Access Journals (Sweden)

Anna Gerasimova

Full Text Available Genome-wide association studies (GWASs identify single nucleotide polymorphisms (SNPs that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease.

A calderón-preconditioned single source combined field integral equation for analyzing scattering from homogeneous penetrable objects

KAUST Repository

Valdé s, Felipe; Andriulli, Francesco P.; Bagci, Hakan; Michielssen, Eric

2011-01-01

A new regularized single source equation for analyzing scattering from homogeneous penetrable objects is presented. The proposed equation is a linear combination of a Calderón-preconditioned single source electric field integral equation and a

Analyzing the effects of information technology on supply chain integration: The role of ERP success mediator

Directory of Open Access Journals (Sweden)

Samaneh Alimohamadian

2014-04-01

Full Text Available This research analyzes the effects of Information Technology (IT on Supply Chain Integration (SCI through ERP mediator by proposing a conceptual model among these components. We also hypothesize that three constructs of IT influence on enterprise resource planning (ERP success and one construct of ERP success influences on SCI. To clarify the relationships among the constructs, structural equation model (SEM is conducted to examine the model fit and seven hypotheses. The data was collected from three Iranian firms through questionnaire with 23 questions adopted by past researches. The results confirmed that top management support of IT and employees’ general IT skills factors of IT enhance ERP success, and ERP success positively influences on Supply Chain Integration, so these two IT factors influence Supply Chain Integration through ERP success. Our data unsupported negative impact of satisfaction with legacy IT system on ERP success.

GWAS signals across the HLA regions: revealing a clue for common etiology underlying infectious tumors and other immunity diseases

Institute of Scientific and Technical Information of China (English)

Yin Yao Shugart; Ying Wang; Wei-Hua Jia; Yi-Xin Zeng

2011-01-01

Increasing evidence suggests that multiple genes in the human leukocyte antigen (HLA) regions play an important role in development of cancers and immunity disorders. However, the biological mechanisms of the HLA associations are not well understood. We recently conducted a survey of all genome-wide association studies (GWAS) with significant findings in the HLA regions and concluded that diseases such as cancer and immune disorders are more likely to be associated with genetic variants located in the HLA regions than other diseases. This finding is suggestive for testing a hypothesis of a common etiology of infectious tumors and other immunity diseases.

Transient analyzer

International Nuclear Information System (INIS)

Muir, M.D.

1975-01-01

The design and design philosophy of a high performance, extremely versatile transient analyzer is described. This sub-system was designed to be controlled through the data acquisition computer system which allows hands off operation. Thus it may be placed on the experiment side of the high voltage safety break between the experimental device and the control room. This analyzer provides control features which are extremely useful for data acquisition from PPPL diagnostics. These include dynamic sample rate changing, which may be intermixed with multiple post trigger operations with variable length blocks using normal, peak to peak or integrate modes. Included in the discussion are general remarks on the advantages of adding intelligence to transient analyzers, a detailed description of the characteristics of the PPPL transient analyzer, a description of the hardware, firmware, control language and operation of the PPPL transient analyzer, and general remarks on future trends in this type of instrumentation both at PPPL and in general

[Integrated Development of Full-automatic Fluorescence Analyzer].

Science.gov (United States)

Zhang, Mei; Lin, Zhibo; Yuan, Peng; Yao, Zhifeng; Hu, Yueming

2015-10-01

In view of the fact that medical inspection equipment sold in the domestic market is mainly imported from abroad and very expensive, we developed a full-automatic fluorescence analyzer in our center, presented in this paper. The present paper introduces the hardware architecture design of FPGA/DSP motion controlling card+PC+ STM32 embedded micro processing unit, software system based on C# multi thread, design and implementation of double-unit communication in detail. By simplifying the hardware structure, selecting hardware legitimately and adopting control system software to object-oriented technology, we have improved the precision and velocity of the control system significantly. Finally, the performance test showed that the control system could meet the needs of automated fluorescence analyzer on the functionality, performance and cost.

Note: A portable Raman analyzer for microfluidic chips based on a dichroic beam splitter for integration of imaging and signal collection light paths

Energy Technology Data Exchange (ETDEWEB)

Geng, Yijia; Xu, Shuping; Xu, Weiqing, E-mail: xuwq@jlu.edu.cn [State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130012 (China); Chen, Lei [State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130012 (China); College of Physics, Jilin University, Changchun 130012 (China); Chen, Gang [State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130012 (China); College of Chemistry, Jilin University, Changchun 130012 (China); Bi, Wenbin [State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130012 (China); School of Chemistry and Environmental Engineering, Changchun University of Science and Technology, Changchun 130022 (China); Cui, Haining [College of Physics, Jilin University, Changchun 130012 (China)

2015-05-15

An integrated and portable Raman analyzer featuring an inverted probe fixed on a motor-driving adjustable optical module was designed for the combination of a microfluidic system. It possesses a micro-imaging function. The inverted configuration is advantageous to locate and focus microfluidic channels. Different from commercial micro-imaging Raman spectrometers using manual switchable light path, this analyzer adopts a dichroic beam splitter for both imaging and signal collection light paths, which avoids movable parts and improves the integration and stability of optics. Combined with surface-enhanced Raman scattering technique, this portable Raman micro-analyzer is promising as a powerful tool for microfluidic analytics.

Integrative methods for analyzing big data in precision medicine.

Science.gov (United States)

Gligorijević, Vladimir; Malod-Dognin, Noël; Pržulj, Nataša

2016-03-01

We provide an overview of recent developments in big data analyses in the context of precision medicine and health informatics. With the advance in technologies capturing molecular and medical data, we entered the area of "Big Data" in biology and medicine. These data offer many opportunities to advance precision medicine. We outline key challenges in precision medicine and present recent advances in data integration-based methods to uncover personalized information from big data produced by various omics studies. We survey recent integrative methods for disease subtyping, biomarkers discovery, and drug repurposing, and list the tools that are available to domain scientists. Given the ever-growing nature of these big data, we highlight key issues that big data integration methods will face. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Integrative Analysis of Genetic, Genomic, and Phenotypic Data for Ethanol Behaviors: A Network-Based Pipeline for Identifying Mechanisms and Potential Drug Targets.

Science.gov (United States)

Bogenpohl, James W; Mignogna, Kristin M; Smith, Maren L; Miles, Michael F

2017-01-01

Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans. However, treatments for AUD remain largely ineffective and few medications for this disease state have been licensed. Genome-wide genetic polymorphism analysis (GWAS) in humans, behavioral genetic studies in animal models and brain gene expression studies produced by microarrays or RNA-seq have the potential to produce nonbiased and novel insight into the underlying neurobiology of AUD. However, the complexity of such information, both statistical and informational, has slowed progress toward identifying new targets for intervention in AUD. This chapter describes one approach for integrating behavioral, genetic, and genomic information across animal model and human studies. The goal of this approach is to identify networks of genes functioning in the brain that are most relevant to the underlying mechanisms of a complex disease such as AUD. We illustrate an example of how genomic studies in animal models can be used to produce robust gene networks that have functional implications, and to integrate such animal model genomic data with human genetic studies such as GWAS for AUD. We describe several useful analysis tools for such studies: ComBAT, WGCNA, and EW_dmGWAS. The end result of this analysis is a ranking of gene networks and identification of their cognate hub genes, which might provide eventual targets for future therapeutic development. Furthermore, this combined approach may also improve our understanding of basic mechanisms underlying gene x

Simulation Tools and Techniques for Analyzing the Impacts of Photovoltaic System Integration

Science.gov (United States)

Hariri, Ali

Solar photovoltaic (PV) energy integration in distribution networks is one of the fastest growing sectors of distributed energy integration. The growth in solar PV integration is incentivized by various clean power policies, global interest in solar energy, and reduction in manufacturing and installation costs of solar energy systems. The increase in solar PV integration has raised a number of concerns regarding the potential impacts that might arise as a result of high PV penetration. Some impacts have already been recorded in networks with high PV penetration such as in China, Germany, and USA (Hawaii and California). Therefore, network planning is becoming more intricate as new technologies are integrated into the existing electric grid. The integrated new technologies pose certain compatibility concerns regarding the existing electric grid infrastructure. Therefore, PV integration impact studies are becoming more essential in order to have a better understanding of how to advance the solar PV integration efforts without introducing adverse impacts into the network. PV impact studies are important for understanding the nature of the new introduced phenomena. Understanding the nature of the potential impacts is a key factor for mitigating and accommodating for said impacts. Traditionally, electric power utilities relied on phasor-based power flow simulations for planning their electric networks. However, the conventional, commercially available, phasor-based simulation tools do not provide proper visibility across a wide spectrum of electric phenomena. Moreover, different types of simulation approaches are suitable for specific types of studies. For instance, power flow software cannot be used for studying time varying phenomena. At the same time, it is not practical to use electromagnetic transient (EMT) tools to perform power flow solutions. Therefore, some electric phenomena caused by the variability of PV generation are not visible using the conventional

PR Interval Associated Genes, Atrial Remodeling and Rhythm Outcome of Catheter Ablation of Atrial Fibrillation—A Gene-Based Analysis of GWAS Data

Directory of Open Access Journals (Sweden)

Daniela Husser

2017-12-01

Full Text Available Background: PR interval prolongation has recently been shown to associate with advanced left atrial remodeling and atrial fibrillation (AF recurrence after catheter ablation. While different genome-wide association studies (GWAS have implicated 13 loci to associate with the PR interval as an AF endophenotype their subsequent associations with AF remodeling and response to catheter ablation are unknown. Here, we perform a gene-based analysis of GWAS data to test the hypothesis that PR interval candidate genes also associate with left atrial remodeling and arrhythmia recurrence following AF catheter ablation.Methods and Results: Samples from 660 patients with paroxysmal (n = 370 or persistent AF (n = 290 undergoing AF catheter ablation were genotyped for ~1,000,000 SNPs. Gene-based association was investigated using VEGAS (versatile gene-based association study. Among the 13 candidate genes, SLC8A1, MEIS1, ITGA9, SCN5A, and SOX5 associated with the PR interval. Of those, ITGA9 and SOX5 were significantly associated with left atrial low voltage areas and left atrial diameter and subsequently with AF recurrence after radiofrequency catheter ablation.Conclusion: This study suggests contributions of ITGA9 and SOX5 to AF remodeling expressed as PR interval prolongation, low voltage areas and left atrial dilatation and subsequently to response to catheter ablation. Future and larger studies are necessary to replicate and apply these findings with the aim of designing AF pathophysiology-based multi-locus risk scores.

Analyzing the concept of disruptive behavior in healthcare work: an integrative review*

Directory of Open Access Journals (Sweden)

Roberta Meneses Oliveira

Full Text Available Abstract OBJECTIVE To analyze the concept of disruptive behavior in healthcare work. METHOD An integrative review carried out in the theoretical phase of a qualitative research substantiated by the theoretical framework of the Hybrid Model of Concept Development. The search for articles was conducted in the CINAHL, LILACS, PsycINFO, PubMed and SciVerse Scopus databases in 2013. RESULTS 70 scientific articles answered the guiding question and lead to attributes of disruptive behavior, being: incivility, psychological violence and physical/sexual violence; with their main antecedents (intrapersonal, interpersonal and organizational being: personality characteristics, stress and work overload; and consequences of: workers' moral/mental distress, compromised patient safety, labor loss, and disruption of communication, collaboration and teamwork. CONCLUSION Analysis of the disruptive behavior concept in healthcare work showed a construct in its theoretical stage that encompasses different disrespectful conduct adopted by health workers in the hospital context, which deserve the attention of leadership for better recognition and proper handling of cases and their consequences.

GWAS-based pathway analysis differentiates between fluid and crystallized intelligence.

Science.gov (United States)

Christoforou, A; Espeseth, T; Davies, G; Fernandes, C P D; Giddaluru, S; Mattheisen, M; Tenesa, A; Harris, S E; Liewald, D C; Payton, A; Ollier, W; Horan, M; Pendleton, N; Haggarty, P; Djurovic, S; Herms, S; Hoffman, P; Cichon, S; Starr, J M; Lundervold, A; Reinvang, I; Steen, V M; Deary, I J; Le Hellard, S

2014-09-01

Cognitive abilities vary among people. About 40-50% of this variability is due to general intelligence (g), which reflects the positive correlation among individuals' scores on diverse cognitive ability tests. g is positively correlated with many life outcomes, such as education, occupational status and health, motivating the investigation of its underlying biology. In psychometric research, a distinction is made between general fluid intelligence (gF) - the ability to reason in novel situations - and general crystallized intelligence (gC) - the ability to apply acquired knowledge. This distinction is supported by developmental and cognitive neuroscience studies. Classical epidemiological studies and recent genome-wide association studies (GWASs) have established that these cognitive traits have a large genetic component. However, no robust genetic associations have been published thus far due largely to the known polygenic nature of these traits and insufficient sample sizes. Here, using two GWAS datasets, in which the polygenicity of gF and gC traits was previously confirmed, a gene- and pathway-based approach was undertaken with the aim of characterizing and differentiating their genetic architecture. Pathway analysis, using genes selected on the basis of relaxed criteria, revealed notable differences between these two traits. gF appeared to be characterized by genes affecting the quantity and quality of neurons and therefore neuronal efficiency, whereas long-term depression (LTD) seemed to underlie gC. Thus, this study supports the gF-gC distinction at the genetic level and identifies functional annotations and pathways worthy of further investigation. © 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Analyzing inflation in Nigeria: a fractionally integrated ARFIMA ...

African Journals Online (AJOL)

The study looked into the stochastic properties of CPI-inflation rate for Nigeria from 1995Q1 to 2016Q4. The study employed an autoregressive fractionally integrated moving average and a general autoregressive conditional heteroskedasticity (ARFIMA-GARCH) methodology as well as ADF/KPSS to investigate the ...

ITHNA.SYS: An Integrated Thermal Hydraulic and Neutronic Analyzer SYStem for NUR research reactor

Energy Technology Data Exchange (ETDEWEB)

Mazidi, S., E-mail: samirmazidi@gmail.com [Division Physique et Applications Nucléaires, Centre de Recherche Nucléaire de Draria (CRND), BP 43 Sebala, Draria, Alger (Algeria); Meftah, B., E-mail: b_meftah@yahoo.com [Division Physique et Applications Nucléaires, Centre de Recherche Nucléaire de Draria (CRND), BP 43 Sebala, Draria, Alger (Algeria); Belgaid, M., E-mail: belgaidm@yahoo.com [Faculté de Physique, Université Houari Boumediene, USTHB, BP 31, Bab Ezzouar, Alger (Algeria); Letaim, F., E-mail: fletaim@yahoo.fr [Faculté des Sciences et Technologies, Université d’El-oued, PO Box 789, El-oued (Algeria); Halilou, A., E-mail: hal_rane@yahoo.fr [Division Réacteur NUR, Centre de Recherche Nucléaire de Draria, BP 43 Sebala, Draria, Alger (Algeria)

2015-08-15

Highlights: • We develop a neutronic and thermal hydraulic MTR reactor analyzer. • The analyzer allows a rapid determination of the reactor core parameters. • Some NUR reactor parameters have been analyzed. - Abstract: This paper introduces the Integrated Thermal Hydraulic and Neutronic Analyzer SYStem (ITHNA.SYS) that has been developed for the Algerian research reactor NUR. It is used both as an operating aid tool and as a core physics engineering analysis tool. The system embeds three modules of the MTR-PC software package developed by INVAP SE: the cell calculation code WIMSD, the core calculation code CITVAP and the program TERMIC for thermal hydraulic analysis of a material testing reactor (MTR) core in forced convection. ITHNA.SYS operates both in on-line and off-line modes. In the on-line mode, the system is linked, via the computer parallel port, to the data acquisition console of the reactor control room and allows a real time monitoring of major physical and safety parameters of the NUR core. PC-based ITHNA.SYS provides a viable and convenient way of using an accumulated and often complex reactor physics stock of knowledge and frees the user from the intricacy of adequate reactor core modeling. This guaranties an accurate, though rapid, determination of a variety of neutronic and thermal hydraulic parameters of importance for the operation and safety analysis of the NUR research reactor. Instead of the several hours usually required, the processing time for the determination of such parameters is now reduced to few seconds. Validation of the system was performed with respect to experimental measurements and to calculations using reference codes. ITHNA.SYS can be easily adapted to accommodate other kinds of MTR reactors.

A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk

OpenAIRE

Pooley, K. A.; Bojesen, S. E.; Weischer, M.; Nielsen, S. F.; Thompson, D.; Amin Al Olama, A.; Michailidou, K.; Tyrer, J. P.; Benlloch, S.; Brown, J.; Audley, T.; Luben, R.; Khaw, K.-T.; Neal, D. E.; Hamdy, F. C.

2013-01-01

Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the ?iCOGS? custom genotyping array. All ?200 000 iCOGS variants were analysed with TL, and those displaying associations in healthy controls (n = 15 065) were further tested in breast cancer cases (n = 11 024). We found a novel TL associatio...

A Bayesian Framework for Multiple Trait Colo-calization from Summary Association Statistics.

Science.gov (United States)

Giambartolomei, Claudia; Zhenli Liu, Jimmy; Zhang, Wen; Hauberg, Mads; Shi, Huwenbo; Boocock, James; Pickrell, Joe; Jaffe, Andrew E; Pasaniuc, Bogdan; Roussos, Panos

2018-03-19

Most genetic variants implicated in complex diseases by genome-wide association studies (GWAS) are non-coding, making it challenging to understand the causative genes involved in disease. Integrating external information such as quantitative trait locus (QTL) mapping of molecular traits (e.g., expression, methylation) is a powerful approach to identify the subset of GWAS signals explained by regulatory effects. In particular, expression QTLs (eQTLs) help pinpoint the responsible gene among the GWAS regions that harbor many genes, while methylation QTLs (mQTLs) help identify the epigenetic mechanisms that impact gene expression which in turn affect disease risk. In this work we propose multiple-trait-coloc (moloc), a Bayesian statistical framework that integrates GWAS summary data with multiple molecular QTL data to identify regulatory effects at GWAS risk loci. We applied moloc to schizophrenia (SCZ) and eQTL/mQTL data derived from human brain tissue and identified 52 candidate genes that influence SCZ through methylation. Our method can be applied to any GWAS and relevant functional data to help prioritize disease associated genes. moloc is available for download as an R package (https://github.com/clagiamba/moloc). We also developed a web site to visualize the biological findings (icahn.mssm.edu/moloc). The browser allows searches by gene, methylation probe, and scenario of interest. claudia.giambartolomei@gmail.com. Supplementary data are available at Bioinformatics online.

Scalable privacy-preserving data sharing methodology for genome-wide association studies: an application to iDASH healthcare privacy protection challenge.

Science.gov (United States)

Yu, Fei; Ji, Zhanglong

2014-01-01

In response to the growing interest in genome-wide association study (GWAS) data privacy, the Integrating Data for Analysis, Anonymization and SHaring (iDASH) center organized the iDASH Healthcare Privacy Protection Challenge, with the aim of investigating the effectiveness of applying privacy-preserving methodologies to human genetic data. This paper is based on a submission to the iDASH Healthcare Privacy Protection Challenge. We apply privacy-preserving methods that are adapted from Uhler et al. 2013 and Yu et al. 2014 to the challenge's data and analyze the data utility after the data are perturbed by the privacy-preserving methods. Major contributions of this paper include new interpretation of the χ2 statistic in a GWAS setting and new results about the Hamming distance score, a key component for one of the privacy-preserving methods.

A comparison of multivariate genome-wide association methods

DEFF Research Database (Denmark)

Galesloot, Tessel E; Van Steen, Kristel; Kiemeney, Lambertus A L M

2014-01-01

Joint association analysis of multiple traits in a genome-wide association study (GWAS), i.e. a multivariate GWAS, offers several advantages over analyzing each trait in a separate GWAS. In this study we directly compared a number of multivariate GWAS methods using simulated data. We focused on six...... methods that are implemented in the software packages PLINK, SNPTEST, MultiPhen, BIMBAM, PCHAT and TATES, and also compared them to standard univariate GWAS, analysis of the first principal component of the traits, and meta-analysis of univariate results. We simulated data (N = 1000) for three...... for scenarios with an opposite sign of genetic and residual correlation. All multivariate analyses resulted in a higher power than univariate analyses, even when only one of the traits was associated with the QTL. Hence, use of multivariate GWAS methods can be recommended, even when genetic correlations between...

A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: genetic risk is modulated by obesity.

Science.gov (United States)

Been, L F; Hatfield, J L; Shankar, A; Aston, C E; Ralhan, S; Wander, G S; Mehra, N K; Singh, J R; Mulvihill, J J; Sanghera, D K

2012-11-01

Two common variants (rs1387153, rs10830963) in MTNR1B have been reported to have independent effects on fasting blood glucose (FBG) levels with increased risk to type 2 diabetes (T2D) in recent genome-wide association studies (GWAS). In this investigation, we report the association of these two variants, and an additional variant (rs1374645) within the GWAS locus of MTNR1B with FBG, 2h glucose, insulin resistance (HOMA IR), β-cell function (HOMA B), and T2D in our sample of Asian Sikhs from India. Our cohort comprised 2222 subjects [1201 T2D, 1021 controls]. None of these SNPs was associated with T2D in this cohort. Our data also could not confirm association of rs1387153 and rs10830963 with FBG phenotype. However, upon stratifying data according to body mass index (BMI) (low ≤ 25 kg/m(2) and high > 25 kg/m(2)) in normoglycemic subjects (n = 1021), the rs1374645 revealed a strong association with low FBG levels in low BMI group (β = -0.073, p = 0.002, Bonferroni p = 0.01) compared to the high BMI group (β = 0.015, p = 0.50). We also detected a strong evidence of interaction between rs1374645 and BMI with respect to FBG levels (p = 0.002). Our data provide new information about the significant impact of another MTNR1B variant on FBG levels that appears to be modulated by BMI. Future confirmation on independent datasets and functional studies will be required to define the role of this variant in fasting glucose variation. Published by Elsevier B.V.

Bacterial Genetic Architecture of Ecological Interactions in Co-culture by GWAS-Taking Escherichia coli and Staphylococcus aureus as an Example.

Science.gov (United States)

He, Xiaoqing; Jin, Yi; Ye, Meixia; Chen, Nan; Zhu, Jing; Wang, Jingqi; Jiang, Libo; Wu, Rongling

2017-01-01

How a species responds to such a biotic environment in the community, ultimately leading to its evolution, has been a topic of intense interest to ecological evolutionary biologists. Until recently, limited knowledge was available regarding the genotypic changes that underlie phenotypic changes. Our study implemented GWAS (Genome-Wide Association Studies) to illustrate the genetic architecture of ecological interactions that take place in microbial populations. By choosing 45 such interspecific pairs of Escherichia coli and Staphylococcus aureus strains that were all genotyped throughout the entire genome, we employed Q-ROADTRIPS to analyze the association between single SNPs and microbial abundance measured at each time point for bacterial populations reared in monoculture and co-culture, respectively. We identified a large number of SNPs and indels across the genomes (35.69 G clean data of E. coli and 50.41 G of S. aureus ). We reported 66 and 111 SNPs that were associated with interaction in E. coli and S. aureus , respectively. 23 out of 66 polymorphic changes resulted in amino acid alterations.12 significant genes, such as murE, treA, argS , and relA , which were also identified in previous evolutionary studies. In S. aureus , 111 SNPs detected in coding sequences could be divided into 35 non-synonymous and 76 synonymous SNPs. Our study illustrated the potential of genome-wide association methods for studying rapidly evolving traits in bacteria. Genetic association study methods will facilitate the identification of genetic elements likely to cause phenotypes of interest and provide targets for further laboratory investigation.

Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study

DEFF Research Database (Denmark)

Gudmundsdottir, Valborg; Pedersen, Helle Krogh; Allebrandt, Karla Viviani

2018-01-01

Glucagon-like peptide 1 (GLP-1) stimulated insulin secretion has a considerable heritable component as estimated from twin studies, yet few genetic variants influencing this phenotype have been identified. We performed the first genome-wide association study (GWAS) of GLP-1 stimulated insulin...... secretion in non-diabetic individuals from the Netherlands Twin register (n = 126). This GWAS was enhanced using a tissue-specific protein-protein interaction network approach. We identified a beta-cell protein-protein interaction module that was significantly enriched for low gene scores based on the GWAS...... P-values and found support at the network level in an independent cohort from Tübingen, Germany (n = 100). Additionally, a polygenic risk score based on SNPs prioritized from the network was associated (P

Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

Directory of Open Access Journals (Sweden)

Mengmeng Du

Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

Integrated circuit manufacture and tuning of subassemblies of a statistical analyzer of voltage oscillations (AKON). Izgotovleniye na integral'nykh skhemakh i nastroyka uzlov statisticheskogo analizatora kolebaniy napryazheniya (AKON)

Energy Technology Data Exchange (ETDEWEB)

Yermakov, V.F.; Oleynik, V.I.; Sambarov, Yu.M.

1982-01-01

The basic circuits and instructions for tuning subassemblies of a statistical analyzer of voltage oscillation are described. The device is intended for monitoring quality of voltage in electric networks in accordance with GOST13109-67. The component base of the device includes integrated circuits of the series 140, 155, 218 and 228.

Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals.

Science.gov (United States)

Coleman, Jonathan R I; Bryois, Julien; Gaspar, Héléna A; Jansen, Philip R; Savage, Jeanne E; Skene, Nathan; Plomin, Robert; Muñoz-Manchado, Ana B; Linnarsson, Sten; Crawford, Greg; Hjerling-Leffler, Jens; Sullivan, Patrick F; Posthuma, Danielle; Breen, Gerome

2018-03-08

Variance in IQ is associated with a wide range of health outcomes, and 1% of the population are affected by intellectual disability. Despite a century of research, the fundamental neural underpinnings of intelligence remain unclear. We integrate results from genome-wide association studies (GWAS) of intelligence with brain tissue and single cell gene expression data to identify tissues and cell types associated with intelligence. GWAS data for IQ (N = 78,308) were meta-analyzed with a study comparing 1247 individuals with mean IQ ~170 to 8185 controls. Genes associated with intelligence implicate pyramidal neurons of the somatosensory cortex and CA1 region of the hippocampus, and midbrain embryonic GABAergic neurons. Tissue-specific analyses find the most significant enrichment for frontal cortex brain expressed genes. These results suggest specific neuronal cell types and genes may be involved in intelligence and provide new hypotheses for neuroscience experiments using model systems.

Genome-Wide Association Study (GWAS) and Genome-Wide Environment Interaction Study (GWEIS) of Depressive Symptoms in African American and Hispanic/Latina Women

Science.gov (United States)

Dunn, Erin C.; Wiste, Anna; Radmanesh, Farid; Almli, Lynn M.; Gogarten, Stephanie M.; Sofer, Tamar; Faul, Jessica D.; Kardia, Sharon L.R.; Smith, Jennifer A.; Weir, David R.; Zhao, Wei; Soare, Thomas W.; Mirza, Saira S.; Hek, Karin; Tiemeier, Henning W.; Goveas, Joseph S.; Sarto, Gloria E.; Snively, Beverly M.; Cornelis, Marilyn; Koenen, Karestan C.; Kraft, Peter; Purcell, Shaun; Ressler, Kerry J.; Rosand, Jonathan; Wassertheil-Smoller, Sylvia; Smoller, Jordan W.

2016-01-01

Background Genome-wide association studies (GWAS) have been unable to identify variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (G×E) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide environment interaction study (GWEIS) of depressive symptoms. Methods Using data from the SHARe cohort of the Women’s Health Initiative, comprising African Americans (n=7179) and Hispanics/Latinas (n=3138), we examined genetic main effects and G×E with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts. Results No SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20kb from GPR139, p=5.75×10−8) and rs75407252 (intronic to CACNA2D3, p=6.99×10−7). In Hispanics/Latinas, the top signals were rs2532087 (located 27kb from CD38, p=2.44×10−7) and rs4542757 (intronic to DCC, p=7.31×10−7). In the GWEIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; p=4.10×10−10; located 14kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG=0.95), suggesting that common variation underlying depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample. Conclusions Our results underscore the need for larger samples, more GWEIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities. PMID:27038408

Systems Pharmacology-Based Approach of Connecting Disease Genes in Genome-Wide Association Studies with Traditional Chinese Medicine.

Science.gov (United States)

Kim, Jihye; Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kang, Jaewoo; Tan, Aik Choon

2018-01-01

Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies. We applied a systems pharmacology approach to prioritize disease-target genes. Using this bioinformatics approach, we analyzed 14,713 GWAS disease-TCM-target gene pairs and identified 115 disease-gene pairs with q value < 0.2. We validated several of these GWAS disease-TCM-target gene pairs with literature evidence, demonstrating that this computational approach could reveal novel indications for TCM. We also develop TCM-Disease web application to facilitate the traditional Chinese medicine drug repurposing efforts. Systems pharmacology is a promising approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. The computational approaches described in this study could be easily expandable to other disease-gene network analysis.

BioSMACK: a linux live CD for genome-wide association analyses.

Science.gov (United States)

Hong, Chang Bum; Kim, Young Jin; Moon, Sanghoon; Shin, Young-Ah; Go, Min Jin; Kim, Dong-Joon; Lee, Jong-Young; Cho, Yoon Shin

2012-01-01

Recent advances in high-throughput genotyping technologies have enabled us to conduct a genome-wide association study (GWAS) on a large cohort. However, analyzing millions of single nucleotide polymorphisms (SNPs) is still a difficult task for researchers conducting a GWAS. Several difficulties such as compatibilities and dependencies are often encountered by researchers using analytical tools, during the installation of software. This is a huge obstacle to any research institute without computing facilities and specialists. Therefore, a proper research environment is an urgent need for researchers working on GWAS. We developed BioSMACK to provide a research environment for GWAS that requires no configuration and is easy to use. BioSMACK is based on the Ubuntu Live CD that offers a complete Linux-based operating system environment without installation. Moreover, we provide users with a GWAS manual consisting of a series of guidelines for GWAS and useful examples. BioSMACK is freely available at http://ksnp.cdc. go.kr/biosmack.

Advances in Integrating Traditional and Omic Biomarkers When Analyzing the Effects of the Mediterranean Diet Intervention in Cardiovascular Prevention

Science.gov (United States)

Fitó, Montserrat; Melander, Olle; Martínez, José Alfredo; Toledo, Estefanía; Carpéné, Christian; Corella, Dolores

2016-01-01

Intervention with Mediterranean diet (MedDiet) has provided a high level of evidence in primary prevention of cardiovascular events. Besides enhancing protection from classical risk factors, an improvement has also been described in a number of non-classical ones. Benefits have been reported on biomarkers of oxidation, inflammation, cellular adhesion, adipokine production, and pro-thrombotic state. Although the benefits of the MedDiet have been attributed to its richness in antioxidants, the mechanisms by which it exercises its beneficial effects are not well known. It is thought that the integration of omics including genomics, transcriptomics, epigenomics, and metabolomics, into studies analyzing nutrition and cardiovascular diseases will provide new clues regarding these mechanisms. However, omics integration is still in its infancy. Currently, some single-omics analyses have provided valuable data, mostly in the field of genomics. Thus, several gene-diet interactions in determining both intermediate (plasma lipids, etc.) and final cardiovascular phenotypes (stroke, myocardial infarction, etc.) have been reported. However, few studies have analyzed changes in gene expression and, moreover very few have focused on epigenomic or metabolomic biomarkers related to the MedDiet. Nevertheless, these preliminary results can help to better understand the inter-individual differences in cardiovascular risk and dietary response for further applications in personalized nutrition. PMID:27598147

A calderón-preconditioned single source combined field integral equation for analyzing scattering from homogeneous penetrable objects

KAUST Repository

Valdés, Felipe

2011-06-01

A new regularized single source equation for analyzing scattering from homogeneous penetrable objects is presented. The proposed equation is a linear combination of a Calderón-preconditioned single source electric field integral equation and a single source magnetic field integral equation. The equation is immune to low-frequency and dense-mesh breakdown, and free from spurious resonances. Unlike dual source formulations, this equation involves operator products that cannot be discretized using standard procedures for discretizing standalone electric, magnetic, and combined field operators. Instead, the single source equation proposed here is discretized using a recently developed technique that achieves a well-conditioned mapping from div- to curl-conforming function spaces, thereby fully respecting the space mapping properties of the operators involved, and guaranteeing accuracy and stability. Numerical results show that the proposed equation and discretization technique give rise to rapidly convergent solutions. They also validate the equation\\'s resonant free character. © 2006 IEEE.

Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations.

Science.gov (United States)

Seow, Wei Jie; Matsuo, Keitaro; Hsiung, Chao Agnes; Shiraishi, Kouya; Song, Minsun; Kim, Hee Nam; Wong, Maria Pik; Hong, Yun-Chul; Hosgood, H Dean; Wang, Zhaoming; Chang, I-Shou; Wang, Jiu-Cun; Chatterjee, Nilanjan; Tucker, Margaret; Wei, Hu; Mitsudomi, Tetsuya; Zheng, Wei; Kim, Jin Hee; Zhou, Baosen; Caporaso, Neil E; Albanes, Demetrius; Shin, Min-Ho; Chung, Lap Ping; An, She-Juan; Wang, Ping; Zheng, Hong; Yatabe, Yasushi; Zhang, Xu-Chao; Kim, Young Tae; Shu, Xiao-Ou; Kim, Young-Chul; Bassig, Bryan A; Chang, Jiang; Ho, James Chung Man; Ji, Bu-Tian; Kubo, Michiaki; Daigo, Yataro; Ito, Hidemi; Momozawa, Yukihide; Ashikawa, Kyota; Kamatani, Yoichiro; Honda, Takayuki; Sakamoto, Hiromi; Kunitoh, Hideo; Tsuta, Koji; Watanabe, Shun-Ichi; Nokihara, Hiroshi; Miyagi, Yohei; Nakayama, Haruhiko; Matsumoto, Shingo; Tsuboi, Masahiro; Goto, Koichi; Yin, Zhihua; Shi, Jianxin; Takahashi, Atsushi; Goto, Akiteru; Minamiya, Yoshihiro; Shimizu, Kimihiro; Tanaka, Kazumi; Wu, Tangchun; Wei, Fusheng; Wong, Jason Y Y; Matsuda, Fumihiko; Su, Jian; Kim, Yeul Hong; Oh, In-Jae; Song, Fengju; Lee, Victor Ho Fun; Su, Wu-Chou; Chen, Yuh-Min; Chang, Gee-Chen; Chen, Kuan-Yu; Huang, Ming-Shyan; Yang, Pan-Chyr; Lin, Hsien-Chih; Xiang, Yong-Bing; Seow, Adeline; Park, Jae Yong; Kweon, Sun-Seog; Chen, Chien-Jen; Li, Haixin; Gao, Yu-Tang; Wu, Chen; Qian, Biyun; Lu, Daru; Liu, Jianjun; Jeon, Hyo-Sung; Hsiao, Chin-Fu; Sung, Jae Sook; Tsai, Ying-Huang; Jung, Yoo Jin; Guo, Huan; Hu, Zhibin; Wang, Wen-Chang; Chung, Charles C; Lawrence, Charles; Burdett, Laurie; Yeager, Meredith; Jacobs, Kevin B; Hutchinson, Amy; Berndt, Sonja I; He, Xingzhou; Wu, Wei; Wang, Junwen; Li, Yuqing; Choi, Jin Eun; Park, Kyong Hwa; Sung, Sook Whan; Liu, Li; Kang, Chang Hyun; Hu, Lingmin; Chen, Chung-Hsing; Yang, Tsung-Ying; Xu, Jun; Guan, Peng; Tan, Wen; Wang, Chih-Liang; Sihoe, Alan Dart Loon; Chen, Ying; Choi, Yi Young; Hung, Jen-Yu; Kim, Jun Suk; Yoon, Ho-Il; Cai, Qiuyin; Lin, Chien-Chung; Park, In Kyu; Xu, Ping; Dong, Jing; Kim, Christopher; He, Qincheng; Perng, Reury-Perng; Chen, Chih-Yi; Vermeulen, Roel; Wu, Junjie; Lim, Wei-Yen; Chen, Kun-Chieh; Chan, John K C; Chu, Minjie; Li, Yao-Jen; Li, Jihua; Chen, Hongyan; Yu, Chong-Jen; Jin, Li; Lo, Yen-Li; Chen, Ying-Hsiang; Fraumeni, Joseph F; Liu, Jie; Yamaji, Taiki; Yang, Yang; Hicks, Belynda; Wyatt, Kathleen; Li, Shengchao A; Dai, Juncheng; Ma, Hongxia; Jin, Guangfu; Song, Bao; Wang, Zhehai; Cheng, Sensen; Li, Xuelian; Ren, Yangwu; Cui, Ping; Iwasaki, Motoki; Shimazu, Taichi; Tsugane, Shoichiro; Zhu, Junjie; Jiang, Gening; Fei, Ke; Wu, Guoping; Chien, Li-Hsin; Chen, Hui-Ling; Su, Yu-Chun; Tsai, Fang-Yu; Chen, Yi-Song; Yu, Jinming; Stevens, Victoria L; Laird-Offringa, Ite A; Marconett, Crystal N; Lin, Dongxin; Chen, Kexin; Wu, Yi-Long; Landi, Maria Teresa; Shen, Hongbing; Rothman, Nathaniel; Kohno, Takashi; Chanock, Stephen J; Lan, Qing

2017-01-15

To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US.

On-Demand Urine Analyzer, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — The overall goal of this program (through Phase III) is to develop an analyzer that can be integrated into International Space Station (ISS) toilets to measure key...

IPAD: the Integrated Pathway Analysis Database for Systematic Enrichment Analysis.

Science.gov (United States)

Zhang, Fan; Drabier, Renee

2012-01-01

Next-Generation Sequencing (NGS) technologies and Genome-Wide Association Studies (GWAS) generate millions of reads and hundreds of datasets, and there is an urgent need for a better way to accurately interpret and distill such large amounts of data. Extensive pathway and network analysis allow for the discovery of highly significant pathways from a set of disease vs. healthy samples in the NGS and GWAS. Knowledge of activation of these processes will lead to elucidation of the complex biological pathways affected by drug treatment, to patient stratification studies of new and existing drug treatments, and to understanding the underlying anti-cancer drug effects. There are approximately 141 biological human pathway resources as of Jan 2012 according to the Pathguide database. However, most currently available resources do not contain disease, drug or organ specificity information such as disease-pathway, drug-pathway, and organ-pathway associations. Systematically integrating pathway, disease, drug and organ specificity together becomes increasingly crucial for understanding the interrelationships between signaling, metabolic and regulatory pathway, drug action, disease susceptibility, and organ specificity from high-throughput omics data (genomics, transcriptomics, proteomics and metabolomics). We designed the Integrated Pathway Analysis Database for Systematic Enrichment Analysis (IPAD, http://bioinfo.hsc.unt.edu/ipad), defining inter-association between pathway, disease, drug and organ specificity, based on six criteria: 1) comprehensive pathway coverage; 2) gene/protein to pathway/disease/drug/organ association; 3) inter-association between pathway, disease, drug, and organ; 4) multiple and quantitative measurement of enrichment and inter-association; 5) assessment of enrichment and inter-association analysis with the context of the existing biological knowledge and a "gold standard" constructed from reputable and reliable sources; and 6) cross-linking of

Replication study for the association of 9 East Asian GWAS-derived loci with susceptibility to type 2 diabetes in a Japanese population.

Directory of Open Access Journals (Sweden)

Kensuke Sakai

Full Text Available AIMS: East Asian genome-wide association studies (GWAS for type 2 diabetes identified 8 loci with genome-wide significance, and 2 loci with a borderline association. However, the associations of these loci except MAEA locus with type 2 diabetes have not been evaluated in independent East Asian cohorts. We performed a replication study to investigate the association of these susceptibility loci with type 2 diabetes in an independent Japanese population. METHODS: We genotyped 7,379 Japanese participants (5,315 type 2 diabetes and 2,064 controls for each of the 9 single nucleotide polymorphisms (SNPs, rs7041847 in GLIS3, rs6017317 in FITM2-R3HDML-HNF4A, rs6467136 near GCCI-PAX4, rs831571 near PSMD6, rs9470794 in ZFAND3, rs3786897 in PEPD, rs1535500 in KCNK16, rs16955379 in CMIP, and rs17797882 near WWOX. Because the sample size in this study was not sufficient to replicate single SNP associations, we constructed a genetic risk score (GRS by summing a number of risk alleles of the 9 SNPs, and examined the association of the GRS with type 2 diabetes using logistic regression analysis. RESULTS: With the exception of rs1535500 in KCNK16, all SNPs had the same direction of effect (odds ratio [OR]>1.0 as in the original reports. The GRS constructed from the 9 SNPs was significantly associated with type 2 diabetes in the Japanese population (p = 4.0 × 10(-4, OR = 1.05, 95% confidence interval: 1.02-1.09. In quantitative trait analyses, rs16955379 in CMIP was nominally associated with a decreased homeostasis model assessment of β-cell function and with increased fasting plasma glucose, but neither the individual SNPs nor the GRS showed a significant association with the glycemic traits. CONCLUSIONS: These results indicate that 9 loci that were identified in the East Asian GWAS meta-analysis have a significant effect on the susceptibility to type 2 diabetes in the Japanese population.

Association between the European GWAS-identified susceptibility locus at chromosome 4p16 and the risk of atrial septal defect: a case-control study in Southwest China and a meta-analysis.

Directory of Open Access Journals (Sweden)

Li Zhao

Full Text Available Atrial septal defect (ASD is the third most frequent type of congenital heart anomaly, featuring shunting of blood between the two atria. Gene-environment interaction remains to be an acknowledged cause for ASD occurrence. A recent European genome-wide association study (GWAS of congenital heart disease (CHD identified 3 susceptibility SNPs at chromosome 4p16 associated with ASD: rs870142, rs16835979 and rs6824295. A Chinese-GWAS of CHD conducted in the corresponding period did not reveal the 3 susceptibility SNPs, but reported 2 different risk SNPs: rs2474937 and rs1531070. Therefore, we aimed to investigate the associations between the 3 European GWAS-identified susceptibility SNPs and ASD risk in the Han population in southwest China. Additionally, to increase the robustness of our current analysis, we conducted a meta-analysis combining published studies and our current case-control study. We performed association, linkage disequilibrium, and haplotype analysis among the 3 SNPs in 190 ASD cases and 225 age-, sex-, and ethnicity-matched healthy controls. Genotype and allele frequencies among the 3 SNPs showed statistically significant differences between the cases and controls. Our study found that individuals carrying the allele T of rs870142, the allele A of rs16835979, and the allele T of rs6824295 had a respective 50.1% (odds ratio (OR = 1.501, 95% confidence interval (CI = 1.122-2.009, PFDR-BH = 0.018, 48.5% (OR = 1.485, 95%CI = 1.109-1.987, PFDR-BH = 0.012, and 38.6% (OR = 1.386, 95%CI = 1.042-1.844, PFDR-BH = 0.025 increased risk to develop ASD than wild-type allele carriers in our study cohort. In the haplotype analysis, we identified a disease-risk haplotype (TAT (OR = 1.540, 95%CI = 1.030-2.380, PFDR-BH = 0.016. Our meta-analysis also showed that the investigated SNP was associated with ASD risk (combined OR (95%CI = 1.35 (1.24-1.46, P < 0.00001. Our study provides compelling evidence to motivate better understanding of the etiology

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

Science.gov (United States)

Chasman, Daniel I; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary F; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid B; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Kao, W H Linda; Fox, Caroline S; Köttgen, Anna

2012-12-15

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS.

Science.gov (United States)

Pan, David Z; Garske, Kristina M; Alvarez, Marcus; Bhagat, Yash V; Boocock, James; Nikkola, Elina; Miao, Zong; Raulerson, Chelsea K; Cantor, Rita M; Civelek, Mete; Glastonbury, Craig A; Small, Kerrin S; Boehnke, Michael; Lusis, Aldons J; Sinsheimer, Janet S; Mohlke, Karen L; Laakso, Markku; Pajukanta, Päivi; Ko, Arthur

2018-04-17

Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression. We further intersect these data with published genome-wide association studies for BMI and BMI-related metabolic traits to identify the genes that are under genetic cis regulation in human adipocytes via chromosomal interactions. This integrative genomics approach identifies four cis-eQTL-eGene relationships associated with BMI or obesity-related traits, including rs4776984 and MAP2K5, which we further confirm by EMSA, and highlights 38 additional candidate genes.

Using CForest to Analyze Diffusion Tensor Imaging Data: A Study of White Matter Integrity in Healthy Aging.

Science.gov (United States)

McWhinney, Sean R; Tremblay, Antoine; Chevalier, Thérèse M; Lim, Vanessa K; Newman, Aaron J

2016-12-01

Healthy aging has been associated with a global reduction in white matter integrity, which is thought to reflect cognitive decline. The present study aimed to investigate this reduction over a broad range of the life span, using diffusion tensor imaging analyzed with conditional inference random forest modeling (CForest). This approach is sensitive to subtle and potentially nonlinear effects over the age continuum and was used to characterize the progression of decline in greater detail than has been possible in the past. Data were collected from 45 healthy individuals ranging in age from 19 to 67 years. Fractional anisotropy (FA) was estimated using probabilistic tractography for a number of major tracts across the brain. Age coincided with a nonlinear decrease in FA, with onset beginning at ∼30 years of age and the steepest declines occurring later in life. However, several tracts showed a transient increase before this decline. The progression of decline varied by tract, with steeper but later decline occurring in more anterior tracts. Finally, strongly right-handed individuals demonstrated relatively preserved FA until more than a decade following the onset of decline of others. These results demonstrate that using a novel, nonparametric analysis approach, previously reported reductions in FA with healthy aging were confirmed, while at the same time, new insight was provided into the onset and progression of decline, with evidence suggesting increases in integrity continuing into adulthood.

Interaction debugging : an integral approach to analyze human-robot interaction

NARCIS (Netherlands)

Kooijmans, T.; Kanda, T.; Bartneck, C.; Ishiguro, H.; Hagita, N.

2006-01-01

Along with the development of interactive robots, controlled experiments and field trials are regularly conducted to stage human-robot interaction. Experience in this field has shown that analyzing human-robot interaction for evaluation purposes fosters the development of improved systems and the

Analyzing an Integrated Planning Approach Among Planning Scale and Sector A Case Study of Malang City’s Vision as The City of Education

Directory of Open Access Journals (Sweden)

Akhmad Amirudin

2014-04-01

Full Text Available Integrated planning is more needed by government today because of the complexity of problems and limited resources. Integrated planning can undertake the problems by giving comprehensive solution and provide how much resources are needed to reach the goal. Integrated planning approach is implied to provide better tools to guide actions towards the development of cities, improvement of human conditions, and ultimately a better urbanism. So the research focused on integrated planning in Malang City based on Malang City’s vision, strategic planning, operational planning, budgeting planning in Malang City to achieve Malang City’s vision as the city of Education. In this study, researcher used qualitative method with descriptive research, which is a research process aims to describe the exact nature / something happened and took place on the research conducted. The research purpose is to identify and describe and analyze the process of Malang City Planning Agency integrate other planning scale and sector in developing planning; and to identify, describe and analyze the process of Malang City Planning Agency integrated all stakeholders in Integrated Planning process. This research use descriptive research method. The reason to use descriptive research method in this study because the principle objectives of this study aimed to describe, illustrate in a systematic, factual and accurate statement of the facts and the relationship between phenomenon. Then qualitative method was directed at the individual's background and a holistic (whole. So in this case should not isolate the individual or organization into a variable or hypothesis, but should view it as part of wholeness. The result of this research in the case study of Malang City has shown thatThe case study of Malang City showed that various sectors recognized but did not pay much attention to Malang City’s vision as City of Education in their plans; however, Regional Mid-term Development

Immigrant Integration: Acculturation and Social Integration

Directory of Open Access Journals (Sweden)

Astrid HAMBERGER

2009-11-01

Full Text Available This article tackles the concept of “immigrant integration” as it is analyzed by different authors in the international migration field. In this article, I will use the terms “refugee” and “immigrant” as equivalent to each other due to the interchangeable character of these concepts throughout the integration literature. First, the article brings into discussion the definitional and conceptual battle around the concept of immigrant “integration”, and second, it will describe and analyze cultural and social integration with their presupposing processes.

SNPpy--database management for SNP data from genome wide association studies.

Directory of Open Access Journals (Sweden)

Faheem Mitha

Full Text Available BACKGROUND: We describe SNPpy, a hybrid script database system using the Python SQLAlchemy library coupled with the PostgreSQL database to manage genotype data from Genome-Wide Association Studies (GWAS. This system makes it possible to merge study data with HapMap data and merge across studies for meta-analyses, including data filtering based on the values of phenotype and Single-Nucleotide Polymorphism (SNP data. SNPpy and its dependencies are open source software. RESULTS: The current version of SNPpy offers utility functions to import genotype and annotation data from two commercial platforms. We use these to import data from two GWAS studies and the HapMap Project. We then export these individual datasets to standard data format files that can be imported into statistical software for downstream analyses. CONCLUSIONS: By leveraging the power of relational databases, SNPpy offers integrated management and manipulation of genotype and phenotype data from GWAS studies. The analysis of these studies requires merging across GWAS datasets as well as patient and marker selection. To this end, SNPpy enables the user to filter the data and output the results as standardized GWAS file formats. It does low level and flexible data validation, including validation of patient data. SNPpy is a practical and extensible solution for investigators who seek to deploy central management of their GWAS data.

Metrics for Analyzing Quantifiable Differentiation of Designs with Varying Integrity for Hardware Assurance

Science.gov (United States)

2017-03-01

Keywords — Trojan; integrity; trust; quantify; hardware; assurance; verification; metrics ; reference, quality ; profile I. INTRODUCTION A. The Rising...as a framework for benchmarking Trusted Part certifications. Previous work conducted in Trust Metric development has focused on measures at the...the lowest integrities. Based on the analysis, the DI metric shows measurable differentiation between all five Test Article Error Location Error

Methyl-Analyzer--whole genome DNA methylation profiling.

Science.gov (United States)

Xin, Yurong; Ge, Yongchao; Haghighi, Fatemeh G

2011-08-15

Methyl-Analyzer is a python package that analyzes genome-wide DNA methylation data produced by the Methyl-MAPS (methylation mapping analysis by paired-end sequencing) method. Methyl-MAPS is an enzymatic-based method that uses both methylation-sensitive and -dependent enzymes covering >80% of CpG dinucleotides within mammalian genomes. It combines enzymatic-based approaches with high-throughput next-generation sequencing technology to provide whole genome DNA methylation profiles. Methyl-Analyzer processes and integrates sequencing reads from methylated and unmethylated compartments and estimates CpG methylation probabilities at single base resolution. Methyl-Analyzer is available at http://github.com/epigenomics/methylmaps. Sample dataset is available for download at http://epigenomicspub.columbia.edu/methylanalyzer_data.html. fgh3@columbia.edu Supplementary data are available at Bioinformatics online.

Analyzing Unsaturated Flow Patterns in Fractured Rock Using an Integrated Modeling Approach

International Nuclear Information System (INIS)

Y.S. Wu; G. Lu; K. Zhang; L. Pan; G.S. Bodvarsson

2006-01-01

Characterizing percolation patterns in unsaturated fractured rock has posed a greater challenge to modeling investigations than comparable saturated zone studies, because of the heterogeneous nature of unsaturated media and the great number of variables impacting unsaturated flow. This paper presents an integrated modeling methodology for quantitatively characterizing percolation patterns in the unsaturated zone of Yucca Mountain, Nevada, a proposed underground repository site for storing high-level radioactive waste. The modeling approach integrates a wide variety of moisture, pneumatic, thermal, and isotopic geochemical field data into a comprehensive three-dimensional numerical model for modeling analyses. It takes into account the coupled processes of fluid and heat flow and chemical isotopic transport in Yucca Mountain's highly heterogeneous, unsaturated fractured tuffs. Modeling results are examined against different types of field-measured data and then used to evaluate different hydrogeological conceptualizations and their results of flow patterns in the unsaturated zone. In particular, this model provides a much clearer understanding of percolation patterns and flow behavior through the unsaturated zone, both crucial issues in assessing repository performance. The integrated approach for quantifying Yucca Mountain's flow system is demonstrated to provide a practical modeling tool for characterizing flow and transport processes in complex subsurface systems

An Open Access Database of Genome-wide Association Results

Directory of Open Access Journals (Sweden)

Johnson Andrew D

2009-01-01

which was not perturbed by a sensitivity analysis. Conclusion We provide access to a full gene-annotated GWAS database which could be used for further querying, analyses or integration with other genomic information. We make a number of general observations. Of reported associated SNPs, 40% lie within the boundaries of a RefSeq gene and 68% are within 60 kb of one, indicating a bias toward gene-centricity in the findings. We found considerable heterogeneity in information available from GWAS suggesting the wider community could benefit from standardization and centralization of results reporting.

Pathway analysis of GWAS provides new insights into genetic susceptibility to 3 inflammatory diseases.

Directory of Open Access Journals (Sweden)

Hariklia Eleftherohorinou

2009-11-01

Full Text Available Although the introduction of genome-wide association studies (GWAS have greatly increased the number of genes associated with common diseases, only a small proportion of the predicted genetic contribution has so far been elucidated. Studying the cumulative variation of polymorphisms in multiple genes acting in functional pathways may provide a complementary approach to the more common single SNP association approach in understanding genetic determinants of common disease. We developed a novel pathway-based method to assess the combined contribution of multiple genetic variants acting within canonical biological pathways and applied it to data from 14,000 UK individuals with 7 common diseases. We tested inflammatory pathways for association with Crohn's disease (CD, rheumatoid arthritis (RA and type 1 diabetes (T1D with 4 non-inflammatory diseases as controls. Using a variable selection algorithm, we identified variants responsible for the pathway association and evaluated their use for disease prediction using a 10 fold cross-validation framework in order to calculate out-of-sample area under the Receiver Operating Curve (AUC. The generalisability of these predictive models was tested on an independent birth cohort from Northern Finland. Multiple canonical inflammatory pathways showed highly significant associations (p 10(-3-10(-20 with CD, T1D and RA. Variable selection identified on average a set of 205 SNPs (149 genes for T1D, 350 SNPs (189 genes for RA and 493 SNPs (277 genes for CD. The pattern of polymorphisms at these SNPS were found to be highly predictive of T1D (91% AUC and RA (85% AUC, and weakly predictive of CD (60% AUC. The predictive ability of the T1D model (without any parameter refitting had good predictive ability (79% AUC in the Finnish cohort. Our analysis suggests that genetic contribution to common inflammatory diseases operates through multiple genes interacting in functional pathways.

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

DEFF Research Database (Denmark)

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

2014-01-01

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

Reprogramming neurodegeneration in the big data era.

Science.gov (United States)

Zhou, Lujia; Verstreken, Patrik

2018-02-01

Recent genome-wide association studies (GWAS) have identified numerous genetic risk variants for late-onset Alzheimer's disease (AD) and Parkinson's disease (PD). However, deciphering the functional consequences of GWAS data is challenging due to a lack of reliable model systems to study the genetic variants that are often of low penetrance and non-coding identities. Pluripotent stem cell (PSC) technologies offer unprecedented opportunities for molecular phenotyping of GWAS variants in human neurons and microglia. Moreover, rapid technological advances in whole-genome RNA-sequencing and epigenome mapping fuel comprehensive and unbiased investigations of molecular alterations in PSC-derived disease models. Here, we review and discuss how integrated studies that utilize PSC technologies and genome-wide approaches may bring new mechanistic insight into the pathogenesis of AD and PD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mechanistic phenotypes: an aggregative phenotyping strategy to identify disease mechanisms using GWAS data.

Directory of Open Access Journals (Sweden)

Jonathan D Mosley

Full Text Available A single mutation can alter cellular and global homeostatic mechanisms and give rise to multiple clinical diseases. We hypothesized that these disease mechanisms could be identified using low minor allele frequency (MAF<0.1 non-synonymous SNPs (nsSNPs associated with "mechanistic phenotypes", comprised of collections of related diagnoses. We studied two mechanistic phenotypes: (1 thrombosis, evaluated in a population of 1,655 African Americans; and (2 four groupings of cancer diagnoses, evaluated in 3,009 white European Americans. We tested associations between nsSNPs represented on GWAS platforms and mechanistic phenotypes ascertained from electronic medical records (EMRs, and sought enrichment in functional ontologies across the top-ranked associations. We used a two-step analytic approach whereby nsSNPs were first sorted by the strength of their association with a phenotype. We tested associations using two reverse genetic models and standard additive and recessive models. In the second step, we employed a hypothesis-free ontological enrichment analysis using the sorted nsSNPs to identify functional mechanisms underlying the diagnoses comprising the mechanistic phenotypes. The thrombosis phenotype was solely associated with ontologies related to blood coagulation (Fisher's p = 0.0001, FDR p = 0.03, driven by the F5, P2RY12 and F2RL2 genes. For the cancer phenotypes, the reverse genetics models were enriched in DNA repair functions (p = 2×10-5, FDR p = 0.03 (POLG/FANCI, SLX4/FANCP, XRCC1, BRCA1, FANCA, CHD1L while the additive model showed enrichment related to chromatid segregation (p = 4×10-6, FDR p = 0.005 (KIF25, PINX1. We were able to replicate nsSNP associations for POLG/FANCI, BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping using collections of EMR-derived diagnoses can elucidate fundamental disease mechanisms.

Organization of a multichannel analyzer for gamma ray spectrometry

International Nuclear Information System (INIS)

Robinet, Genevieve

1988-06-01

This report describes the software organization of a medium scale multichannel analyzer for qualitative and quantitative measurements of the gamma rays emitted by radioactive samples. The first part reminds basis of radioactivity, principle of gamma ray detection, and data processing used for interpretation of a nuclear spectrum. The second part describes first the general organization of the software and then gives some details on interactivity, multidetector capabilites, and integration of complex algorithms for peak search and nuclide identification;problems encountered during the design phase are mentioned and solutions are given. Basic ideas are presented for further developments, such as expert system which should improve interpretation of the results. This present software has been integrated in a manufactured multichannel analyzer named 'POLYGAM NU416'. [fr

An Integrative Bioinformatics Framework for Genome-scale Multiple Level Network Reconstruction of Rice

Directory of Open Access Journals (Sweden)

Liu Lili

2013-06-01

Full Text Available Understanding how metabolic reactions translate the genome of an organism into its phenotype is a grand challenge in biology. Genome-wide association studies (GWAS statistically connect genotypes to phenotypes, without any recourse to known molecular interactions, whereas a molecular mechanistic description ties gene function to phenotype through gene regulatory networks (GRNs, protein-protein interactions (PPIs and molecular pathways. Integration of different regulatory information levels of an organism is expected to provide a good way for mapping genotypes to phenotypes. However, the lack of curated metabolic model of rice is blocking the exploration of genome-scale multi-level network reconstruction. Here, we have merged GRNs, PPIs and genome-scale metabolic networks (GSMNs approaches into a single framework for rice via omics’ regulatory information reconstruction and integration. Firstly, we reconstructed a genome-scale metabolic model, containing 4,462 function genes, 2,986 metabolites involved in 3,316 reactions, and compartmentalized into ten subcellular locations. Furthermore, 90,358 pairs of protein-protein interactions, 662,936 pairs of gene regulations and 1,763 microRNA-target interactions were integrated into the metabolic model. Eventually, a database was developped for systematically storing and retrieving the genome-scale multi-level network of rice. This provides a reference for understanding genotype-phenotype relationship of rice, and for analysis of its molecular regulatory network.

Comparison of fabric analysis of snow samples by Computer-Integrated Polarization Microscopy and Automatic Ice Texture Analyzer

Science.gov (United States)

Leisinger, Sabine; Montagnat, Maurine; Heilbronner, Renée; Schneebeli, Martin

2014-05-01

Accurate knowledge of fabric anisotropy is crucial to understand the mechanical behavior of snow and firn, but is also important for understanding metamorphism. Computer-Integrated Polarization Microscopy (CIP) method used for the fabric analysis was developed by Heilbronner and Pauli in the early 1990ies and uses a slightly modified traditional polarization microscope for the fabric analysis. First developed for quartz, it can be applied to other uniaxial minerals. Up to now this method was mainly used in structural geology. However, it is also well suited for the fabric analysis of snow, firn and ice. The method is based on the analysis of first- order interference colors images by a slightly modified optical polarization microscope, a grayscale camera and a computer. The optical polarization microscope is featured with high quality objectives, a rotating table and two polarizers that can be introduced above and below the thin section, as well as a full wave plate. Additionally, two quarter-wave plates for circular polarization are needed. Otherwise it is also possible to create circular polarization from a set of crossed polarized images through image processing. A narrow band interference filter transmitting a wavelength between 660 and 700 nm is also required. Finally a monochrome digital camera is used to capture the input images. The idea is to record the change of interference colors while the thin section is being rotated once through 180°. The azimuth and inclination of the c-axis are defined by the color change. Recording the color change through a red filter produces a signal with a well-defined amplitude and phase angle. An advantage of this method lies in the simple conversion of an ordinary optical microscope to a fabric analyzer. The Automatic Ice Texture Analyzer (AITA) as the first fully functional instrument to measure c-axis orientation was developed by Wilson and other (2003). Most recent fabric analysis of snow and firn samples was carried

One for all and all for One: Improving replication of genetic studies through network diffusion.

Directory of Open Access Journals (Sweden)

Daniel Lancour

2018-04-01

Full Text Available Improving accuracy in genetic studies would greatly accelerate understanding the genetic basis of complex diseases. One approach to achieve such an improvement for risk variants identified by the genome wide association study (GWAS approach is to incorporate previously known biology when screening variants across the genome. We developed a simple approach for improving the prioritization of candidate disease genes that incorporates a network diffusion of scores from known disease genes using a protein network and a novel integration with GWAS risk scores, and tested this approach on a large Alzheimer disease (AD GWAS dataset. Using a statistical bootstrap approach, we cross-validated the method and for the first time showed that a network approach improves the expected replication rates in GWAS studies. Several novel AD genes were predicted including CR2, SHARPIN, and PTPN2. Our re-prioritized results are enriched for established known AD-associated biological pathways including inflammation, immune response, and metabolism, whereas standard non-prioritized results were not. Our findings support a strategy of considering network information when investigating genetic risk factors.

Fiscal 1998 achievement report on regional consortium research and development project. Venture business fostering regional consortium--Creation of key industries (Development of a ultrahigh-sensitivity micro-integrated analyzing system); 1998 nendo chokokando micro shusekika bunseki system no kaihatsu seika hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-03-01

Biotechnology and micro-machining technology are merged into the above-named system capable of high-speed high-precision clinical examination of trace specimens. In the development of element technologies indispensable for system construction, research and development is conducted of laser processing technology for integration, extremely weak signal detecting technology, micro-electrode manufacturing technology for micro-sensors, micro-contact printing technology, micro-sensors, integrated coatings and micro-columns, elucidation of blood flow characteristics in micro-scale elements, micro-integrated analyzing system control technology, etc. These element technologies are integrated for a success in the development of a micro-scale polymerase chain reaction (PCR) device which is necessary for the development of micro-integrated blood analyzing system for various blood components and for the demagnification of a gene analyzing system. Surveys etc. are conducted for the commercialization of the devices mentioned above. (NEDO)

The Integrated Approach versus the Traditional Approach: Analyzing the Benefits of a Dance and Transportation Integrated Curriculum

Science.gov (United States)

LaMotte, Megan

2018-01-01

The purpose of the study was to examine the effects of a dance and transportation integrated curriculum on student learning and engagement. The curriculum, entitled Consequences of Our Actions: Dance and Transportation, synthesized transportation content with the art form of dance. The experimental and control groups were comprised of fifth-grade…

ANALYZING THE INTEGRITY OF PUBLIC ACCOUNTANT AT “CEMERLANG” PUBLIC ACCOUNTANT FIRM IN SURABAYA (PHENOMENOLOGY STUDY

Directory of Open Access Journals (Sweden)

Ratna Anggraini Aripratiwi

2017-12-01

Full Text Available This study aims to explore the deep meaning of the integrity attitudes that is experienced, felt, and performed by a public accountant in one of the famous KAP in Surabaya, KAP "Cemerlang". Revealing the attitude of the integrity of public accountant is important since there are large number of public accountants who are still dragged into fraud and violations, resulting in unethical decisions. Every public accountant has a different perspective in determining and practicing an attitude of integrity, whether to defend or even release it for a particular purpose that ultimately raises a variety of meanings of pure integrity and pragmatic integrity.

Identification and Verification of QTL Associated with Frost Tolerance Using Linkage Mapping and GWAS in Winter Faba Bean

Science.gov (United States)

Sallam, Ahmed; Arbaoui, Mustapha; El-Esawi, Mohamed; Abshire, Nathan; Martsch, Regina

2016-01-01

Frost stress is one of the abiotic stresses that causes a significant reduction in winter faba bean yield in Europe. The main objective of this work is to genetically improve frost tolerance in winter faba bean by identifying and validating QTL associated with frost tolerance to be used in marker-assisted selection (MAS). Two different genetic backgrounds were used: a biparental population (BPP) consisting of 101 inbred lines, and 189 genotypes from single seed descent (SSD) from the Gottingen Winter bean Population (GWBP). All experiments were conducted in a frost growth chamber under controlled conditions. Both populations were genotyped using the same set of 189 SNP markers. Visual scoring for frost stress symptoms was used to define frost tolerance in both populations. In addition, leaf fatty acid composition (FAC) and proline content were analyzed in BPP as physiological traits. QTL mapping (for BPP) and genome wide association studies (for GWBP) were performed to detect QTL associated with frost tolerance. High genetic variation between genotypes, and repeatability estimates, were found for all traits. QTL mapping and GWAS identified new putative QTL associated with promising frost tolerance and related traits. A set of 54 SNP markers common in both genetic backgrounds showed a high genetic diversity with polymorphic information content (PIC) ranging from 0.31 to 0.37 and gene diversity ranging from 0.39 to 0.50. This indicates that these markers may be polymorphic for many faba bean populations. Five SNP markers showed a significant marker-trait association with frost tolerance and related traits in both populations. Moreover, synteny analysis between Medicago truncatula (a model legume) and faba bean genomes was performed to identify candidate genes for these markers. Collinearity was evaluated between the faba bean genetic map constructed in this study and the faba bean consensus map, resulting in identifying possible genomic regions in faba bean which may

Identification and Verification of QTL Associated with Frost Tolerance Using Linkage Mapping and GWAS in Winter Faba Bean.

Science.gov (United States)

Sallam, Ahmed; Arbaoui, Mustapha; El-Esawi, Mohamed; Abshire, Nathan; Martsch, Regina

2016-01-01

Frost stress is one of the abiotic stresses that causes a significant reduction in winter faba bean yield in Europe. The main objective of this work is to genetically improve frost tolerance in winter faba bean by identifying and validating QTL associated with frost tolerance to be used in marker-assisted selection (MAS). Two different genetic backgrounds were used: a biparental population (BPP) consisting of 101 inbred lines, and 189 genotypes from single seed descent (SSD) from the Gottingen Winter bean Population (GWBP). All experiments were conducted in a frost growth chamber under controlled conditions. Both populations were genotyped using the same set of 189 SNP markers. Visual scoring for frost stress symptoms was used to define frost tolerance in both populations. In addition, leaf fatty acid composition (FAC) and proline content were analyzed in BPP as physiological traits. QTL mapping (for BPP) and genome wide association studies (for GWBP) were performed to detect QTL associated with frost tolerance. High genetic variation between genotypes, and repeatability estimates, were found for all traits. QTL mapping and GWAS identified new putative QTL associated with promising frost tolerance and related traits. A set of 54 SNP markers common in both genetic backgrounds showed a high genetic diversity with polymorphic information content (PIC) ranging from 0.31 to 0.37 and gene diversity ranging from 0.39 to 0.50. This indicates that these markers may be polymorphic for many faba bean populations. Five SNP markers showed a significant marker-trait association with frost tolerance and related traits in both populations. Moreover, synteny analysis between Medicago truncatula (a model legume) and faba bean genomes was performed to identify candidate genes for these markers. Collinearity was evaluated between the faba bean genetic map constructed in this study and the faba bean consensus map, resulting in identifying possible genomic regions in faba bean which may

Analyzing composability of applications on MPSoC platforms

NARCIS (Netherlands)

Kumar, A.; Mesman, B.; Theelen, B.D.; Corporaal, H.; Yajun, H.

2008-01-01

Modern day applications require use of multi-processor systems for reasons of erformance, scalability and power efficiency. As more and more applications are integrated in a single system, mapping and analyzing them on a multi-processor platform becomes a multidimensional problem. Each possible set

Analyzing and completing middleware designs for enterprise integration using coloured Petri nets

NARCIS (Netherlands)

Fahland, D.; Gierds, C.; Salinesi, C.; Norrie, M.C.; Pastor, O.

2013-01-01

Enterprise Integration Patterns allow us to design a middleware system conceptually before actually implementing it. So far, the in-depth analysis of such a design was not feasible, as these patterns are only described informally. We introduce a translation of each of these patterns into a Coloured

Genome-wide network-based pathway analysis of CSF t-tau/Aβ1-42 ratio in the ADNI cohort.

Science.gov (United States)

Cong, Wang; Meng, Xianglian; Li, Jin; Zhang, Qiushi; Chen, Feng; Liu, Wenjie; Wang, Ying; Cheng, Sipu; Yao, Xiaohui; Yan, Jingwen; Kim, Sungeun; Saykin, Andrew J; Liang, Hong; Shen, Li

2017-05-30

The cerebrospinal fluid (CSF) levels of total tau (t-tau) and Aβ 1-42 are potential early diagnostic markers for probable Alzheimer's disease (AD). The influence of genetic variation on these CSF biomarkers has been investigated in candidate or genome-wide association studies (GWAS). However, the investigation of statistically modest associations in GWAS in the context of biological networks is still an under-explored topic in AD studies. The main objective of this study is to gain further biological insights via the integration of statistical gene associations in AD with physical protein interaction networks. The CSF and genotyping data of 843 study subjects (199 CN, 85 SMC, 239 EMCI, 207 LMCI, 113 AD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed. PLINK was used to perform GWAS on the t-tau/Aβ 1-42 ratio using quality controlled genotype data, including 563,980 single nucleotide polymorphisms (SNPs), with age, sex and diagnosis as covariates. Gene-level p-values were obtained by VEGAS2. Genes with p-value ≤ 0.05 were mapped on to a protein-protein interaction (PPI) network (9,617 nodes, 39,240 edges, from the HPRD Database). We integrated a consensus model strategy into the iPINBPA network analysis framework, and named it as CM-iPINBPA. Four consensus modules (CMs) were discovered by CM-iPINBPA, and were functionally annotated using the pathway analysis tool Enrichr. The intersection of four CMs forms a common subnetwork of 29 genes, including those related to tau phosphorylation (GSK3B, SUMO1, AKAP5, CALM1 and DLG4), amyloid beta production (CASP8, PIK3R1, PPA1, PARP1, CSNK2A1, NGFR, and RHOA), and AD (BCL3, CFLAR, SMAD1, and HIF1A). This study coupled a consensus module (CM) strategy with the iPINBPA network analysis framework, and applied it to the GWAS of CSF t-tau/Aβ1-42 ratio in an AD study. The genome-wide network analysis yielded 4 enriched CMs that share not only genes related to tau phosphorylation or amyloid beta

An integrated graphic–taxonomic–associative approach to analyze human factors in aviation accidents

Directory of Open Access Journals (Sweden)

Gong Lei

2014-04-01

Full Text Available Human factors are critical causes of modern aviation accidents. However, existing accident analysis methods encounter limitations in addressing aviation human factors, especially in complex accident scenarios. The existing graphic approaches are effective for describing accident mechanisms within various categories of human factors, but cannot simultaneously describe inadequate human–aircraft–environment interactions and organizational deficiencies effectively, and highly depend on analysts’ skills and experiences. Moreover, the existing methods do not emphasize latent unsafe factors outside accidents. This paper focuses on the above three limitations and proposes an integrated graphic–taxonomic–associative approach. A new graphic model named accident tree (AcciTree, with a two-mode structure and a reaction-based concept, is developed for accident modeling and safety defense identification. The AcciTree model is then integrated with the well-established human factors analysis and classification system (HFACS to enhance both reliability of the graphic part and logicality of the taxonomic part for improving completeness of analysis. An associative hazard analysis technique is further put forward to extend analysis to factors outside accidents, to form extended safety requirements for proactive accident prevention. Two crash examples, a research flight demonstrator by our team and an industrial unmanned aircraft, illustrate that the integrated approach is effective for identifying more unsafe factors and safety requirements.

A case study of analyzing student teachers' concept images of the ...

African Journals Online (AJOL)

This paper presents a tool for analyzing student teachers' concept images of the definite integral. The tool shows the basic concepts that underpin the concept of the definite integral and displays them in terms of process and object conceptions within various representations in the context of area under a curve. The use of ...

A 40 GHz fully integrated circuit with a vector network analyzer and a coplanar-line-based detection area for circulating tumor cell analysis using 65 nm CMOS technology

Science.gov (United States)

Nakanishi, Taiki; Matsunaga, Maya; Kobayashi, Atsuki; Nakazato, Kazuo; Niitsu, Kiichi

2018-03-01

A 40-GHz fully integrated CMOS-based circuit for circulating tumor cells (CTC) analysis, consisting of an on-chip vector network analyzer (VNA) and a highly sensitive coplanar-line-based detection area is presented in this paper. In this work, we introduce a fully integrated architecture that eliminates unwanted parasitic effects. The proposed analyzer was designed using 65 nm CMOS technology, and SPICE and MWS simulations were used to validate its operation. The simulation confirmed that the proposed circuit can measure S-parameter shifts resulting from the addition of various types of tumor cells to the detection area, the data of which are provided in a previous study: the |S 21| values for HepG2, A549, and HEC-1-A cells are -0.683, -0.580, and -0.623 dB, respectively. Additionally, the measurement demonstrated an S-parameters reduction of -25.7% when a silicone resin was put on the circuit. Hence, the proposed system is expected to contribute to cancer diagnosis.

Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness

DEFF Research Database (Denmark)

Bigdeli, Tim B.; Ripke, Stephan; Bacanu, Silviu-Alin

2016-01-01

Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence...... of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N...... history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke's R2=0.0021; P=0.00331; P-value threshold

Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder.

Science.gov (United States)

Andrews, Shan V; Ellis, Shannon E; Bakulski, Kelly M; Sheppard, Brooke; Croen, Lisa A; Hertz-Picciotto, Irva; Newschaffer, Craig J; Feinberg, Andrew P; Arking, Dan E; Ladd-Acosta, Christine; Fallin, M Daniele

2017-10-24

Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly.

Analyzing the Biology on the System Level

OpenAIRE

Tong, Wei

2016-01-01

Although various genome projects have provided us enormous static sequence information, understanding of the sophisticated biology continues to require integrating the computational modeling, system analysis, technology development for experiments, and quantitative experiments all together to analyze the biology architecture on various levels, which is just the origin of systems biology subject. This review discusses the object, its characteristics, and research attentions in systems biology,...

A Highly Stable Marching-on-in-Time Volume Integral Equation Solver for Analyzing Transient Wave Interactions on High-Contrast Scatterers

KAUST Repository

Bagci, Hakan

2014-01-06

Time domain integral equation (TDIE) solvers represent an attractive alternative to finite difference (FDTD) and finite element (FEM) schemes for analyzing transient electromagnetic interactions on composite scatterers. Current induced on a scatterer, in response to a transient incident field, generates a scattered field. First, the scattered field is expressed as a spatio-temporal convolution of the current and the Green function of the background medium. Then, a TDIE is obtained by enforcing boundary conditions and/or fundamental field relations. TDIEs are often solved for the unknown current using marching on-in-time (MOT) schemes. MOT-TDIE solvers expand the current using local spatio-temporal basis functions. Inserting this expansion into the TDIE and testing the resulting equation in space and time yields a lower triangular system of equations (termed MOT system), which can be solved by marching in time for the coefficients of the current expansion. Stability of the MOT scheme often depends on how accurately the spatio-temporal convolution of the current and the Green function is discretized. In this work, band-limited prolate-based interpolation functions are used as temporal bases in expanding the current and discretizing the spatio-temporal convolution. Unfortunately, these functions are two sided, i.e., they require ”future” current samples for interpolation, resulting in a non-causal MOT system. To alleviate the effect of non-causality and restore the ability to march in time, an extrapolation scheme can be used to estimate the future values of the currents from their past values. Here, an accurate, stable and band-limited extrapolation scheme is developed for this purpose. This extrapolation scheme uses complex exponents, rather than commonly used harmonics, so that propagating and decaying mode fields inside the dielectric scatterers are accurately modeled. The resulting MOT scheme is applied to solving the time domain volume integral equation (VIE

Gendermetrics.NET: a novel software for analyzing the gender representation in scientific authoring.

Science.gov (United States)

Bendels, Michael H K; Brüggmann, Dörthe; Schöffel, Norman; Groneberg, David A

2016-01-01

Imbalances in female career promotion are believed to be strong in the field of academic science. A primary parameter to analyze gender inequalities is the gender authoring in scientific publications. Since the presently available data on gender distribution is largely limited to underpowered studies, we here develop a new approach to analyze authors' genders in large bibliometric databases. A SQL-Server based multiuser software suite was developed that serves as an integrative tool for analyzing bibliometric data with a special emphasis on gender and topographical analysis. The presented system allows seamless integration, inspection, modification, evaluation and visualization of bibliometric data. By providing an adaptive and almost fully automatic integration and analysis process, the inter-individual variability of analysis is kept at a low level. Depending on the scientific question, the system enables the user to perform a scientometric analysis including its visualization within a short period of time. In summary, a new software suite for analyzing gender representations in scientific articles was established. The system is suitable for the comparative analysis of scientific structures on the level of continents, countries, cities, city regions, institutions, research fields and journals.

An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits.

Directory of Open Access Journals (Sweden)

Yi-Hsiang Hsu

2010-06-01

Full Text Available Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD at the lumbar spine (LS and femoral neck (FN, as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW. A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6x10(-8, 2q11.2 (TBC1D8, and 18q11.2 (OSBPL1A, and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6x10(-13; SOX6, p = 6.4x10(-10 associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant

Handheld Fluorescence Microscopy based Flow Analyzer.

Science.gov (United States)

Saxena, Manish; Jayakumar, Nitin; Gorthi, Sai Siva

2016-03-01

Fluorescence microscopy has the intrinsic advantages of favourable contrast characteristics and high degree of specificity. Consequently, it has been a mainstay in modern biological inquiry and clinical diagnostics. Despite its reliable nature, fluorescence based clinical microscopy and diagnostics is a manual, labour intensive and time consuming procedure. The article outlines a cost-effective, high throughput alternative to conventional fluorescence imaging techniques. With system level integration of custom-designed microfluidics and optics, we demonstrate fluorescence microscopy based imaging flow analyzer. Using this system we have imaged more than 2900 FITC labeled fluorescent beads per minute. This demonstrates high-throughput characteristics of our flow analyzer in comparison to conventional fluorescence microscopy. The issue of motion blur at high flow rates limits the achievable throughput in image based flow analyzers. Here we address the issue by computationally deblurring the images and show that this restores the morphological features otherwise affected by motion blur. By further optimizing concentration of the sample solution and flow speeds, along with imaging multiple channels simultaneously, the system is capable of providing throughput of about 480 beads per second.

From organizational integration to clinical integration: analysis of the path between one level of integration to another using official documents

Science.gov (United States)

Mandza, Matey; Gagnon, Dominique; Carrier, Sébastien; Belzile, Louise; Demers, Louis

2010-01-01

Purpose Services’ integration comprises organizational, normative, economic, informational and clinical dimensions. Since 2004, the province of Quebec has devoted significant efforts to unify the governance of the main health and social care organizations of its various territories. Notwithstanding the uniformity of the national plan’s prescription, the territorial integration modalities greatly vary across the province. Theory This research is based upon a conceptual model of integration that comprises six components: inter-organizational partnership, case management, standardized assessment, a single entry point, a standardized service planning tool and a shared clinical file. Methods We conducted an embedded case study in six contrasted sites in terms of their level of integration. All documents prescribing the implementation of integration were retrieved and analyzed. Results and conclusions The analyzed documents demonstrate a growing local appropriation of the current integrative reform. Interestingly however, no link seems to exist between the quality of local prescriptions and the level of integration achieved in each site. This finding leads us to hypothesize that the variable quality of the operational accompaniment offered to implement these prescriptions is a variable in play.

A network-based approach to prioritize results from genome-wide association studies.

Directory of Open Access Journals (Sweden)

Nirmala Akula

Full Text Available Genome-wide association studies (GWAS are a valuable approach to understanding the genetic basis of complex traits. One of the challenges of GWAS is the translation of genetic association results into biological hypotheses suitable for further investigation in the laboratory. To address this challenge, we introduce Network Interface Miner for Multigenic Interactions (NIMMI, a network-based method that combines GWAS data with human protein-protein interaction data (PPI. NIMMI builds biological networks weighted by connectivity, which is estimated by use of a modification of the Google PageRank algorithm. These weights are then combined with genetic association p-values derived from GWAS, producing what we call 'trait prioritized sub-networks.' As a proof of principle, NIMMI was tested on three GWAS datasets previously analyzed for height, a classical polygenic trait. Despite differences in sample size and ancestry, NIMMI captured 95% of the known height associated genes within the top 20% of ranked sub-networks, far better than what could be achieved by a single-locus approach. The top 2% of NIMMI height-prioritized sub-networks were significantly enriched for genes involved in transcription, signal transduction, transport, and gene expression, as well as nucleic acid, phosphate, protein, and zinc metabolism. All of these sub-networks were ranked near the top across all three height GWAS datasets we tested. We also tested NIMMI on a categorical phenotype, Crohn's disease. NIMMI prioritized sub-networks involved in B- and T-cell receptor, chemokine, interleukin, and other pathways consistent with the known autoimmune nature of Crohn's disease. NIMMI is a simple, user-friendly, open-source software tool that efficiently combines genetic association data with biological networks, translating GWAS findings into biological hypotheses.

A Network-Based Approach to Prioritize Results from Genome-Wide Association Studies

Science.gov (United States)

Akula, Nirmala; Baranova, Ancha; Seto, Donald; Solka, Jeffrey; Nalls, Michael A.; Singleton, Andrew; Ferrucci, Luigi; Tanaka, Toshiko; Bandinelli, Stefania; Cho, Yoon Shin; Kim, Young Jin; Lee, Jong-Young; Han, Bok-Ghee; McMahon, Francis J.

2011-01-01

Genome-wide association studies (GWAS) are a valuable approach to understanding the genetic basis of complex traits. One of the challenges of GWAS is the translation of genetic association results into biological hypotheses suitable for further investigation in the laboratory. To address this challenge, we introduce Network Interface Miner for Multigenic Interactions (NIMMI), a network-based method that combines GWAS data with human protein-protein interaction data (PPI). NIMMI builds biological networks weighted by connectivity, which is estimated by use of a modification of the Google PageRank algorithm. These weights are then combined with genetic association p-values derived from GWAS, producing what we call ‘trait prioritized sub-networks.’ As a proof of principle, NIMMI was tested on three GWAS datasets previously analyzed for height, a classical polygenic trait. Despite differences in sample size and ancestry, NIMMI captured 95% of the known height associated genes within the top 20% of ranked sub-networks, far better than what could be achieved by a single-locus approach. The top 2% of NIMMI height-prioritized sub-networks were significantly enriched for genes involved in transcription, signal transduction, transport, and gene expression, as well as nucleic acid, phosphate, protein, and zinc metabolism. All of these sub-networks were ranked near the top across all three height GWAS datasets we tested. We also tested NIMMI on a categorical phenotype, Crohn’s disease. NIMMI prioritized sub-networks involved in B- and T-cell receptor, chemokine, interleukin, and other pathways consistent with the known autoimmune nature of Crohn’s disease. NIMMI is a simple, user-friendly, open-source software tool that efficiently combines genetic association data with biological networks, translating GWAS findings into biological hypotheses. PMID:21915301

Analyzing the non-smooth dynamics induced by a split-path nonlinear integral controller

NARCIS (Netherlands)

Hunnekens, B.G.B.; van Loon, S.J.L.M.; van de Wouw, N.; Heemels, W.P.M.H.; Nijmeijer, H.; Ecker, Horst; Steindl, Alois; Jakubek, Stefan

2014-01-01

In this paper, we introduce a novel non-smooth integral controller, which aims at achieving a better transient response in terms of overshoot of a feedback controlled dynamical system. The resulting closed-loop system can be represented as a non-smooth system with different continuous dynamics being

Partitioning heritability by functional category using GWAS summary statistics

DEFF Research Database (Denmark)

Finucane, Hilary K.; Bulik-Sullivan, Brendan; Gusev, Alexander

2015-01-01

Recent work has demonstrated that some functional categories of the genome contribute disproportionately to the heritability of complex diseases. Here we analyze a broad set of functional elements, including cell type-specific elements, to estimate their polygenic contributions to heritability in...

SEAscan 3.5: A simulator performance analyzer

International Nuclear Information System (INIS)

Dennis, T.; Eisenmann, S.

1990-01-01

SEAscan 3.5 is a personal computer based tool developed to analyze the dynamic performance of nuclear power plant training simulators. The system has integrated features to provide its own human featured performance. In this paper, the program is described as a tool for the analysis of training simulator performance. The structure and operating characteristics of SEAscan 3.5 are described. The hardcopy documents are shown to aid in verification of conformance to ANSI/ANS-3.5-1985

Financial integration and liquidity crises

NARCIS (Netherlands)

Castiglionesi, Fabio; Feriozzi, F.; Lorenzoni, G.

2017-01-01

This paper analyzes the effects of financial integration on the stability of the banking system. Financial integration allows banks in different regions to smooth local liquidity shocks by borrowing and lending on a common interbank market. We show under which conditions financial integration

Economic integration in NAFTA and the EU

DEFF Research Database (Denmark)

Bislev, Sven

This te×t critically analyzes the institutions of the EU and NAFTA. It covers both the general problems of building new and integrated markets, and several policy areas that are related to economic integration. The institutions established in both Europe and America are seen as deficient in several...... of the market economies institutions upon the integration process itself depends. This te×t analyzes the institutions of the EU and NAFTA. It covers both the general problems of building new and integrated markets, and several policy areas that are related to economic integration. The institutions established...

ELISA-BASE: an integrated bioinformatics tool for analyzing and tracking ELISA microarray data

OpenAIRE

White, Amanda M.; Collett, James R.; Seurynck-Servoss, Shannon L.; Daly, Don S.; Zangar, Richard C.

2009-01-01

Summary:ELISA-BASE is an open source database for capturing, organizing and analyzing enzyme-linked immunosorbent assay (ELISA) microarray data. ELISA-BASE is an extension of the BioArray Software Environment (BASE) database system.

Market Integration Dynamics and Asymptotic Price Convergence in Distribution

NARCIS (Netherlands)

A. García-Hiernaux (Alfredo); D.E. Guerrero (David); M.J. McAleer (Michael)

2015-01-01

textabstractThis paper analyzes the market integration process of nominal prices, develops a model to analyze market integration, and presents a test of increasing market integration. A distinction is made between the economic concepts of price conver- gence in mean and variance. When both types of

IMPACT_S: integrated multiprogram platform to analyze and combine tests of selection.

Directory of Open Access Journals (Sweden)

Emanuel Maldonado

Full Text Available Among the major goals of research in evolutionary biology are the identification of genes targeted by natural selection and understanding how various regimes of evolution affect the fitness of an organism. In particular, adaptive evolution enables organisms to adapt to changing ecological factors such as diet, temperature, habitat, predatory pressures and prey abundance. An integrative approach is crucial for the identification of non-synonymous mutations that introduce radical changes in protein biochemistry and thus in turn influence the structure and function of proteins. Performing such analyses manually is often a time-consuming process, due to the large number of statistical files generated from multiple approaches, especially when assessing numerous taxa and/or large datasets. We present IMPACT_S, an easy-to-use Graphical User Interface (GUI software, which rapidly and effectively integrates, filters and combines results from three widely used programs for assessing the influence of selection: Codeml (PAML package, Datamonkey and TreeSAAP. It enables the identification and tabulation of sites detected by these programs as evolving under the influence of positive, neutral and/or negative selection in protein-coding genes. IMPACT_S further facilitates the automatic mapping of these sites onto the three-dimensional structures of proteins. Other useful tools incorporated in IMPACT_S include Jmol, Archaeopteryx, Gnuplot, PhyML, a built-in Swiss-Model interface and a PDB downloader. The relevance and functionality of IMPACT_S is shown through a case study on the toxicoferan-reptilian Cysteine-rich Secretory Proteins (CRiSPs. IMPACT_S is a platform-independent software released under GPLv3 license, freely available online from http://impact-s.sourceforge.net.

IMPACT_S: integrated multiprogram platform to analyze and combine tests of selection.

Science.gov (United States)

Maldonado, Emanuel; Sunagar, Kartik; Almeida, Daniela; Vasconcelos, Vitor; Antunes, Agostinho

2014-01-01

Among the major goals of research in evolutionary biology are the identification of genes targeted by natural selection and understanding how various regimes of evolution affect the fitness of an organism. In particular, adaptive evolution enables organisms to adapt to changing ecological factors such as diet, temperature, habitat, predatory pressures and prey abundance. An integrative approach is crucial for the identification of non-synonymous mutations that introduce radical changes in protein biochemistry and thus in turn influence the structure and function of proteins. Performing such analyses manually is often a time-consuming process, due to the large number of statistical files generated from multiple approaches, especially when assessing numerous taxa and/or large datasets. We present IMPACT_S, an easy-to-use Graphical User Interface (GUI) software, which rapidly and effectively integrates, filters and combines results from three widely used programs for assessing the influence of selection: Codeml (PAML package), Datamonkey and TreeSAAP. It enables the identification and tabulation of sites detected by these programs as evolving under the influence of positive, neutral and/or negative selection in protein-coding genes. IMPACT_S further facilitates the automatic mapping of these sites onto the three-dimensional structures of proteins. Other useful tools incorporated in IMPACT_S include Jmol, Archaeopteryx, Gnuplot, PhyML, a built-in Swiss-Model interface and a PDB downloader. The relevance and functionality of IMPACT_S is shown through a case study on the toxicoferan-reptilian Cysteine-rich Secretory Proteins (CRiSPs). IMPACT_S is a platform-independent software released under GPLv3 license, freely available online from http://impact-s.sourceforge.net.

Analyzing Big Data in Psychology: A Split/Analyze/Meta-Analyze Approach

Directory of Open Access Journals (Sweden)

Mike W.-L. Cheung

2016-05-01

Full Text Available Big data is a field that has traditionally been dominated by disciplines such as computer science and business, where mainly data-driven analyses have been performed. Psychology, a discipline in which a strong emphasis is placed on behavioral theories and empirical research, has the potential to contribute greatly to the big data movement. However, one challenge to psychologists – and probably the most crucial one – is that most researchers may not have the necessary programming and computational skills to analyze big data. In this study we argue that psychologists can also conduct big data research and that, rather than trying to acquire new programming and computational skills, they should focus on their strengths, such as performing psychometric analyses and testing theories using multivariate analyses to explain phenomena. We propose a split/analyze/meta-analyze approach that allows psychologists to easily analyze big data. Two real datasets are used to demonstrate the proposed procedures in R. A new research agenda related to the analysis of big data in psychology is outlined at the end of the study.

Analyzing Big Data in Psychology: A Split/Analyze/Meta-Analyze Approach.

Science.gov (United States)

Cheung, Mike W-L; Jak, Suzanne

2016-01-01

Big data is a field that has traditionally been dominated by disciplines such as computer science and business, where mainly data-driven analyses have been performed. Psychology, a discipline in which a strong emphasis is placed on behavioral theories and empirical research, has the potential to contribute greatly to the big data movement. However, one challenge to psychologists-and probably the most crucial one-is that most researchers may not have the necessary programming and computational skills to analyze big data. In this study we argue that psychologists can also conduct big data research and that, rather than trying to acquire new programming and computational skills, they should focus on their strengths, such as performing psychometric analyses and testing theories using multivariate analyses to explain phenomena. We propose a split/analyze/meta-analyze approach that allows psychologists to easily analyze big data. Two real datasets are used to demonstrate the proposed procedures in R. A new research agenda related to the analysis of big data in psychology is outlined at the end of the study.

Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals

NARCIS (Netherlands)

Coleman, Jonathan R.I.; Bryois, Julien; Gaspar, Héléna A.; Jansen, Philip R.; Savage, Jeanne E.; Skene, Nathan; Plomin, Robert; Muñoz-Manchado, Ana B.; Linnarsson, Sten; Crawford, Greg; Hjerling-Leffler, Jens; Sullivan, Patrick F.; Posthuma, Danielle; Breen, Gerome

2018-01-01

Variance in IQ is associated with a wide range of health outcomes, and 1% of the population are affected by intellectual disability. Despite a century of research, the fundamental neural underpinnings of intelligence remain unclear. We integrate results from genome-wide association studies (GWAS) of

Four integration patterns

DEFF Research Database (Denmark)

Bygstad, Bendik; Nielsen, Peter Axel; Munkvold, Bjørn Erik

2010-01-01

This paper aims to contribute to a theory of integration within the field of IS project management. Integration is a key IS project management issue when new systems are developed and implemented into an increasingly integrated information infrastructure in corporate and governmental organizations....... Expanding the perspective of traditional project management research, we draw extensively on central insights from IS research. Building on socio-technical IS research and Software Engineering research we suggest four generic patterns of integration: Big Bang, Stakeholder Integration, Technical Integration...... and Socio-Technical Integration. We analyze and describe the advantages and disadvantages of each pattern. The four patterns are ideal types. To explore the forces and challenges in these patterns three longitudinal case studies were conducted. In particular we investigate the management challenges for each...

Diffractive interference optical analyzer (DiOPTER)

Science.gov (United States)

Sasikumar, Harish; Prasad, Vishnu; Pal, Parama; Varma, Manoj M.

2016-03-01

This report demonstrates a method for high-resolution refractometric measurements using, what we have termed as, a Diffractive Interference Optical Analyzer (DiOpter). The setup consists of a laser, polarizer, a transparent diffraction grating and Si-photodetectors. The sensor is based on the differential response of diffracted orders to bulk refractive index changes. In these setups, the differential read-out of the diffracted orders suppresses signal drifts and enables time-resolved determination of refractive index changes in the sample cell. A remarkable feature of this device is that under appropriate conditions, the measurement sensitivity of the sensor can be enhanced by more than two orders of magnitude due to interference between multiply reflected diffracted orders. A noise-equivalent limit of detection (LoD) of 6x10-7 RIU was achieved in glass. This work focuses on devices with integrated sample well, made on low-cost PDMS. As the detection methodology is experimentally straightforward, it can be used across a wide array of applications, ranging from detecting changes in surface adsorbates via binding reactions to estimating refractive index (and hence concentration) variations in bulk samples. An exciting prospect of this technique is the potential integration of this device to smartphones using a simple interface based on transmission mode configuration. In a transmission configuration, we were able to achieve an LoD of 4x10-4 RIU which is sufficient to explore several applications in food quality testing and related fields. We are envisioning the future of this platform as a personal handheld optical analyzer for applications ranging from environmental sensing to healthcare and quality testing of food products.

THE INTEGRATION PROCESS MERCOSUR IN 2007 BY MODEL OF GLOBAL DIMENSION OF REGIONAL INTEGRATION

Directory of Open Access Journals (Sweden)

André Bechlin

2013-04-01

Full Text Available This paper aimed to analyze the advance of the regional integration process in the MERCOSUR (Southern Common Market, using a model developed for Professor Mario Ruiz Estrada, of the College of Economy and Administration of the University of Kuala Lumpur in Malaysia, the GDRI (Global Dimension of Regional Integration Model and that as characteristic has differentiated the use of other variable for analysis, that not specifically of economic origin, derivatives of the evolution of the commerce processes. When inferring and comparing the external performance of the economies that compose the Mercosur, evaluating itself the impacts of the advance of the process of regional and commercial integration, are evidents the inequalities that exist in the block. However, a common evolution is observed, in the direction of intensification of the integration between the economies, mainly after the process of opening lived for the continent, beyond the advance of the integration in the context of the Mercosur, from the decade of 1990. The analyzed data show that, in the generality, these economies are if integrating to the world-wide market, and in parallel, accenting the integration degree enters the members of the block.

Exploring the genetics underlying autoimmune diseases with network analysis and link prediction

KAUST Repository

Alanis Lobato, Gregorio; Cannistraci, Carlo; Ravasi, Timothy

2014-01-01

Ever since the first Genome Wide Association Study (GWAS) was carried out we have seen an important number of discoveries of biological and clinical relevance. However, there are some scientists that consider that these research outcomes and their utility are far from what was expected from this experimental design. We instead believe that the thousands of genetic variants associated with complex disorders by means of GWASs are an extremely valuable source of information that needs to be mined in a different way. Based on this philosophy, we followed a holistic perspective to analyze GWAS data and explored the structural properties of the network representation of one of these datasets with the aim to advance our understanding of the genetic intricacies underlying autoimmune human diseases. The simplicity, computational efficiency and precision of the tools proposed in this paper represent a new means to address GWAS data and contribute to the better exploitation of these rich sources of information. © 2014 IEEE.

Exploring the genetics underlying autoimmune diseases with network analysis and link prediction

KAUST Repository

Alanis Lobato, Gregorio

2014-02-01

Ever since the first Genome Wide Association Study (GWAS) was carried out we have seen an important number of discoveries of biological and clinical relevance. However, there are some scientists that consider that these research outcomes and their utility are far from what was expected from this experimental design. We instead believe that the thousands of genetic variants associated with complex disorders by means of GWASs are an extremely valuable source of information that needs to be mined in a different way. Based on this philosophy, we followed a holistic perspective to analyze GWAS data and explored the structural properties of the network representation of one of these datasets with the aim to advance our understanding of the genetic intricacies underlying autoimmune human diseases. The simplicity, computational efficiency and precision of the tools proposed in this paper represent a new means to address GWAS data and contribute to the better exploitation of these rich sources of information. © 2014 IEEE.

Does energy integrate?

International Nuclear Information System (INIS)

Hira, Anil; Amaya, Libardo

2003-01-01

Amidst the international movement to privatize and deregulate electricity and gas sectors of economies, the question of the integration of those sectors has been somewhat underestimated. In fact, the integration of energy markets across boundaries is occurring. We examine this process in three regions: Europe, Central America, and South America. We analyze the forces driving integration in each area, and estimate the prospects for progress. We take a close look at Nordpool, which is now the most integrated market in the world, to see if it can serve as a model for other regions. We close with a set of conditions that we suggest are necessary for a successful international integration of energy markets

Does energy integrate?

International Nuclear Information System (INIS)

Hira, A.; Amaya, L.

2003-01-01

Amidst the international movement to privatize and deregulate electricity and gas sectors of economics, the question of the integration of those sectors has been somewhat underestimated. In fact, the integration of energy markets across boundaries is occurring. We examine this process in three regions: Europe, Central America, and South America. We analyze the forces driving integration in each area, and estimate the prospects for progress. We take a close look at Nordpool, which is now the most integrated market in the world, to see if it can serve as a model for other regions. We close with a set of conditions that we suggest are necessary for a successful international integration of energy markets. (author)

Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study

International Nuclear Information System (INIS)

Niu, Nifang; Cunningham, Julie M; Li, Liang; Sun, Zhifu; Yang, Ping; Wang, Liewei; Schaid, Daniel J; Abo, Ryan P; Kalari, Krishna; Fridley, Brooke L; Feng, Qiping; Jenkins, Gregory; Batzler, Anthony; Brisbin, Abra G

2012-01-01

Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs) that might contribute to taxane response, we performed a genome-wide association study (GWAS) for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs), followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel. GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC) patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196) and NSCLC (A549) cell lines. 147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values <10 -4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value < 0.05) associated with either SCLC or NSCLC patient overall survival. Knockdown of PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667), significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA) hsa-miR-584 or hsa-miR-1468. GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel

Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study

Directory of Open Access Journals (Sweden)

Niu Nifang

2012-09-01

Full Text Available Abstract Background Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs that might contribute to taxane response, we performed a genome-wide association study (GWAS for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs, followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel. Methods GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196 and NSCLC (A549 cell lines. Results 147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values -4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667, significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA hsa-miR-584 or hsa-miR-1468. Conclusions GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel.

Analyzing a single nucleotide polymorphism in schizophrenia: a meta-analysis approach

Directory of Open Access Journals (Sweden)

Falola O

2017-08-01

Full Text Available Oluwadamilare Falola,1 Victor Chukwudi Osamor,1,2 Marion Adebiyi,1,2 Ezekiel Adebiyi1,2 1Covenant University Bioinformatics Research (CUBRe, 2Department of Computer and Information Sciences, College of Science and Technology, Covenant University, Ota, Ogun State, Nigeria Background: Schizophrenia is a severe mental disorder affecting >21 million people worldwide. Some genetic studies reported that single nucleotide polymorphism (SNP involving variant rs1344706 from the ZNF804A gene in human beings is associated with the risk of schizophrenia in several populations. Similar results tend to conflict with other reports in literature, indicating that no true significant association exists between rs1344706 and schizophrenia. We seek to determine the level of association of this SNP with schizophrenia in the Asian population using more recent genome-wide association study (GWAS datasets. Methods: Applying a computational approach with inclusion of more recent GWAS datasets, we conducted a meta-analysis to examine the level of association of SNP rs1344706 and the risk of schizophrenia disorder among the Asian population constituting Chinese, Indonesians, Japanese, Kazakhs and Singaporeans. For a total of 21 genetic studies, including a total of 28,842 cases and 35,630 controls, regression analysis, publication bias, Cochran’s Q and I2 tests were performed. The DerSimonian and Laird random-effects model was used to assess the association of the genetic variant to schizophrenia. Leave-one-out sensitivity analysis was also conducted to determine the influence of each study on the final outcome of the association study. Results: Our summarized analysis for Asian population revealed a pooled odds ratio of 1.06, 95% confidence interval of 1.01–1.11 and two-tailed P-value of 0.0228. Our test for heterogeneity showed the presence of large heterogeneity (I2=53.44%, P =0.00207 and Egger’s regression test (P =0.8763 and Begg’s test (P =0

TypingSuite: Integrated Software for Presenting Stimuli, and Collecting and Analyzing Typing Data

Science.gov (United States)

Mazerolle, Erin L.; Marchand, Yannick

2015-01-01

Research into typing patterns has broad applications in both psycholinguistics and biometrics (i.e., improving security of computer access via each user's unique typing patterns). We present a new software package, TypingSuite, which can be used for presenting visual and auditory stimuli, collecting typing data, and summarizing and analyzing the…

Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia.

Science.gov (United States)

Devor, A; Andreassen, O A; Wang, Y; Mäki-Marttunen, T; Smeland, O B; Fan, C-C; Schork, A J; Holland, D; Thompson, W K; Witoelar, A; Chen, C-H; Desikan, R S; McEvoy, L K; Djurovic, S; Greengard, P; Svenningsson, P; Einevoll, G T; Dale, A M

2017-06-01

The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.

Polymer quantum mechanics some examples using path integrals

International Nuclear Information System (INIS)

Parra, Lorena; Vergara, J. David

2014-01-01

In this work we analyze several physical systems in the context of polymer quantum mechanics using path integrals. First we introduce the group averaging method to quantize constrained systems with path integrals and later we use this procedure to compute the effective actions for the polymer non-relativistic particle and the polymer harmonic oscillator. We analyze the measure of the path integral and we describe the semiclassical dynamics of the systems

Integrating and analyzing medical and environmental data using ETL and Business Intelligence tools

Science.gov (United States)

Villar, Alejandro; Zarrabeitia, María T.; Fdez-Arroyabe, Pablo; Santurtún, Ana

2018-06-01

Processing data that originates from different sources (such as environmental and medical data) can prove to be a difficult task, due to the heterogeneity of variables, storage systems, and file formats that can be used. Moreover, once the amount of data reaches a certain threshold, conventional mining methods (based on spreadsheets or statistical software) become cumbersome or even impossible to apply. Data Extract, Transform, and Load (ETL) solutions provide a framework to normalize and integrate heterogeneous data into a local data store. Additionally, the application of Online Analytical Processing (OLAP), a set of Business Intelligence (BI) methodologies and practices for multidimensional data analysis, can be an invaluable tool for its examination and mining. In this article, we describe a solution based on an ETL + OLAP tandem used for the on-the-fly analysis of tens of millions of individual medical, meteorological, and air quality observations from 16 provinces in Spain provided by 20 different national and regional entities in a diverse array for file types and formats, with the intention of evaluating the effect of several environmental variables on human health in future studies. Our work shows how a sizable amount of data, spread across a wide range of file formats and structures, and originating from a number of different sources belonging to various business domains, can be integrated in a single system that researchers can use for global data analysis and mining.

Integrating and analyzing medical and environmental data using ETL and Business Intelligence tools.

Science.gov (United States)

Villar, Alejandro; Zarrabeitia, María T; Fdez-Arroyabe, Pablo; Santurtún, Ana

2018-03-07

Processing data that originates from different sources (such as environmental and medical data) can prove to be a difficult task, due to the heterogeneity of variables, storage systems, and file formats that can be used. Moreover, once the amount of data reaches a certain threshold, conventional mining methods (based on spreadsheets or statistical software) become cumbersome or even impossible to apply. Data Extract, Transform, and Load (ETL) solutions provide a framework to normalize and integrate heterogeneous data into a local data store. Additionally, the application of Online Analytical Processing (OLAP), a set of Business Intelligence (BI) methodologies and practices for multidimensional data analysis, can be an invaluable tool for its examination and mining. In this article, we describe a solution based on an ETL + OLAP tandem used for the on-the-fly analysis of tens of millions of individual medical, meteorological, and air quality observations from 16 provinces in Spain provided by 20 different national and regional entities in a diverse array for file types and formats, with the intention of evaluating the effect of several environmental variables on human health in future studies. Our work shows how a sizable amount of data, spread across a wide range of file formats and structures, and originating from a number of different sources belonging to various business domains, can be integrated in a single system that researchers can use for global data analysis and mining.

Integrating and analyzing medical and environmental data using ETL and Business Intelligence tools

Science.gov (United States)

Villar, Alejandro; Zarrabeitia, María T.; Fdez-Arroyabe, Pablo; Santurtún, Ana

2018-03-01

Processing data that originates from different sources (such as environmental and medical data) can prove to be a difficult task, due to the heterogeneity of variables, storage systems, and file formats that can be used. Moreover, once the amount of data reaches a certain threshold, conventional mining methods (based on spreadsheets or statistical software) become cumbersome or even impossible to apply. Data Extract, Transform, and Load (ETL) solutions provide a framework to normalize and integrate heterogeneous data into a local data store. Additionally, the application of Online Analytical Processing (OLAP), a set of Business Intelligence (BI) methodologies and practices for multidimensional data analysis, can be an invaluable tool for its examination and mining. In this article, we describe a solution based on an ETL + OLAP tandem used for the on-the-fly analysis of tens of millions of individual medical, meteorological, and air quality observations from 16 provinces in Spain provided by 20 different national and regional entities in a diverse array for file types and formats, with the intention of evaluating the effect of several environmental variables on human health in future studies. Our work shows how a sizable amount of data, spread across a wide range of file formats and structures, and originating from a number of different sources belonging to various business domains, can be integrated in a single system that researchers can use for global data analysis and mining.

Speed limiter integrated fatigue analyzer (SLIFA) for speed and fatigue control on diesel engine truck and bus

Science.gov (United States)

Wahyudi, Haris; Pranoto, Hadi; Leman, A. M.; Sebayang, Darwin; Baba, I.

2017-09-01

Every second, the number of road traffic deaths is increased globally with millions more sustaining severe injuries and living with long-term adverse health consequences. Jakarta alone in year 2015 had recorded 556 people died due to road accidents, approximately reached 6.231 road accident cases. The identified major contributory factors of such unfortunate events are both driver fatigue and over speeding habit especially related to the driving of truck and bus. This paper presents the idea on how to control the electronic system from input fuel system of injection pump and the combustion chamber engine will control the valve solenoid in injection pump which can lock and fuel will stop for moment, and speed limit can be success, by using sensor heart rate we can input reduce speed limit when fatigue detection driver. Integration process this tool can be relevant when Speed Limiter Integrated Fatigue Analyser (SLIFA) trial in the diesel engine for truck and bus, the result of this research Speed Limiter Integrated Fatigue Analyser (SLIFA) able to control speed of diesel engine for truck and bus almost 30km/h, 60km/h, and until 70 km/h. The installation of the sensor heart rate as the input speed limit SLIFA would work when the driver is detected to be in the fatigue condition. We make Speed Limiter Integrated Fatigue Analyser (SLIFA) for control and monitoring system for diesel engine in truck and bus. Speed Limiter Integrated Fatigue Analyser (SLIFA) system can save the historical of the speed record, fatigue, rpm, and body temperature of the driver.

SECAD-- a Schema-based Environment for Configuring, Analyzing and Documenting Integrated Fusion Simulations. Final report

International Nuclear Information System (INIS)

Shasharina, Svetlana

2012-01-01

SECAD is a project that developed a GUI for running integrated fusion simulations as implemented in FACETS and SWIM SciDAC projects. Using the GUI users can submit simulations locally and remotely and visualize the simulation results

Shared genetic variants suggest common pathways in allergy and autoimmune diseases

DEFF Research Database (Denmark)

Kreiner-Møller, Eskil; Waage, Johannes; Standl, Marie

2017-01-01

Background: The relationship between allergy and autoimmune disorders is complex and poorly understood. Objective: To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. Methods: We meta-analyzed two GWAS on self-r...

GRIMP: A web- and grid-based tool for high-speed analysis of large-scale genome-wide association using imputed data.

NARCIS (Netherlands)

K. Estrada Gil (Karol); A. Abuseiris (Anis); F.G. Grosveld (Frank); A.G. Uitterlinden (André); T.A. Knoch (Tobias); F. Rivadeneira Ramirez (Fernando)

2009-01-01

textabstractThe current fast growth of genome-wide association studies (GWAS) combined with now common computationally expensive imputation requires the online access of large user groups to high-performance computing resources capable of analyzing rapidly and efficiently millions of genetic

ASDA - Advanced Suit Design Analyzer computer program

Science.gov (United States)

Bue, Grant C.; Conger, Bruce C.; Iovine, John V.; Chang, Chi-Min

1992-01-01

An ASDA model developed to evaluate the heat and mass transfer characteristics of advanced pressurized suit design concepts for low pressure or vacuum planetary applications is presented. The model is based on a generalized 3-layer suit that uses the Systems Integrated Numerical Differencing Analyzer '85 in conjunction with a 41-node FORTRAN routine. The latter simulates the transient heat transfer and respiratory processes of a human body in a suited environment. The user options for the suit encompass a liquid cooled garment, a removable jacket, a CO2/H2O permeable layer, and a phase change layer.

Statistical Methods in Integrative Genomics

Science.gov (United States)

Richardson, Sylvia; Tseng, George C.; Sun, Wei

2016-01-01

Statistical methods in integrative genomics aim to answer important biology questions by jointly analyzing multiple types of genomic data (vertical integration) or aggregating the same type of data across multiple studies (horizontal integration). In this article, we introduce different types of genomic data and data resources, and then review statistical methods of integrative genomics, with emphasis on the motivation and rationale of these methods. We conclude with some summary points and future research directions. PMID:27482531

New ultra small battery operated portable multi-channel analyzer

International Nuclear Information System (INIS)

Wolf, M.A.; Umbarger, C.J.

1979-01-01

A newly designed portable multi-channel analyzer (MCA) has been developd at Los Alamos that has much improved physical and performance characteristics over previous designs. Namely, the instrument is very compact (25 cm wide x 14 cm deep x 21 cm high) and has a mass of 4.2 Kg (9.2 lb). The device has 1024 channels and is microprocessor controlled. The instrument has most of the standard features of present laboratory-based pulse height analyzers, including CRT display, region of interest integration, etc. Battery life of the MCA is nearly eight hours, with full charging over night. An accessory case carries a small audio cassette recorder for data storage. The case also contains two different NaI(Tl) detectors

A novel integrative method for analyzing eye and hand behaviour during reaching and grasping in an MRI environment.

Science.gov (United States)

Lawrence, Jane M; Abhari, Kamyar; Prime, Steven L; Meek, Benjamin P; Desanghere, Loni; Baugh, Lee A; Marotta, Jonathan J

2011-06-01

The development of noninvasive neuroimaging techniques, such as fMRI, has rapidly advanced our understanding of the neural systems underlying the integration of visual and motor information. However, the fMRI experimental design is restricted by several environmental elements, such as the presence of the magnetic field and the restricted view of the participant, making it difficult to monitor and measure behaviour. The present article describes a novel, specialized software package developed in our laboratory called Biometric Integration Recording and Analysis (BIRA). BIRA integrates video with kinematic data derived from the hand and eye, acquired using MRI-compatible equipment. The present article demonstrates the acquisition and analysis of eye and hand data using BIRA in a mock (0 Tesla) scanner. A method for collecting and integrating gaze and kinematic data in fMRI studies on visuomotor behaviour has several advantages: Specifically, it will allow for more sophisticated, behaviourally driven analyses and eliminate potential confounds of gaze or kinematic data.

Investigation on caloric requirement of biomass pyrolysis using TG-DSC analyzer

Energy Technology Data Exchange (ETDEWEB)

He Fang [Institute of Utilization of Biomass, Shandong University of Technology, No. 12, Zhangzhou Road, Zibo, Shandong 255049 (China)]. E-mail: hf@sdut.edu.cn; Yi Weiming [Institute of Utilization of Biomass, Shandong University of Technology, No. 12, Zhangzhou Road, Zibo, Shandong 255049 (China); Bai Xueyuan [Institute of Utilization of Biomass, Shandong University of Technology, No. 12, Zhangzhou Road, Zibo, Shandong 255049 (China)

2006-09-15

The caloric requirement of biomass pyrolysis has an important influence on the course of the thermal conversion. However, precise data are difficult to achieve by the current calculation method because of the complexity of the process. A new method for achieving the caloric requirement of the process by integrating the differential scanning calorimetry (DSC) curves was proposed after the simultaneous thermal analyzer (TG-DSC) and DSC curves were investigated. Experiments were conducted for wheat straw, cotton stalk, pine and peanut shell on a Netsch STA 449C analyzer. Powder samples were put into a platinum crucible with a lid on a high accuracy DSC-cp sample holder in the furnace and then heated from ambient temperature up to the maximum temperature of 973 K at the heating rate of 10 K/min in the analyzer. The product gases were swept away by 25 ml/min nitrogen. Mass changes (TG) and calorimetric effects (DSC) were recorded and analyzed. The process was investigated in detail through comparison of the DTG (differential thermogravimetric) and DSC curves of wheat straw. After the water influence in the DSC was eliminated, the relationship of the caloric requirement with the temperature of the aforementioned dry biomass was obtained by integrating the DSC curve. The results showed that 523 kJ, 459 kJ, 646 kJ and 385 kJ were required, respectively, to increase the temperature of 1 kg of dried wheat straw, cotton stalk, pine and peanut from 303 K to 673 K.

Retroviral DNA Integration Directed by HIV Integration Protein in Vitro

Science.gov (United States)

Bushman, Frederic D.; Fujiwara, Tamio; Craigie, Robert

1990-09-01

Efficient retroviral growth requires integration of a DNA copy of the viral RNA genome into a chromosome of the host. As a first step in analyzing the mechanism of integration of human immunodeficiency virus (HIV) DNA, a cell-free system was established that models the integration reaction. The in vitro system depends on the HIV integration (IN) protein, which was partially purified from insect cells engineered to express IN protein in large quantities. Integration was detected in a biological assay that scores the insertion of a linear DNA containing HIV terminal sequences into a λ DNA target. Some integration products generated in this assay contained five-base pair duplications of the target DNA at the recombination junctions, a characteristic of HIV integration in vivo; the remaining products contained aberrant junctional sequences that may have been produced in a variation of the normal reaction. These results indicate that HIV IN protein is the only viral protein required to insert model HIV DNA sequences into a target DNA in vitro.

OpenMSI Arrayed Analysis Toolkit: Analyzing Spatially Defined Samples Using Mass Spectrometry Imaging

DEFF Research Database (Denmark)

de Raad, Markus; de Rond, Tristan; Rübel, Oliver

2017-01-01

://openmsinersc.gov), a platform for storing, sharing, and analyzing MSI data. By using a web-based python notebook (Jupyter), OMAAT is accessible to anyone without programming experience yet allows experienced users to leverage all features. OMAAT was :evaluated by analyzing an MSI data set of a high-throughput glycoside...... processing tools for the analysis of large arrayed MSI sample sets. The OpenMSI Arrayed Analysis Toolkit (OMAAT) is a software package that addresses the challenges of analyzing spatially defined samples in MSI data sets. OMAAT is written in Python and is integrated with OpenMSI (http...

Analyzing Inflation and Its Control: A Resource Guide. Economics-Political Science Series.

Science.gov (United States)

Salemi, Michael K.; Leak, Sarah

Background information for teachers on inflation and self-contained learning activities to help students view inflation from both economic and political perspectives are provided. The introduction contains economics and political science frameworks for analyzing policy issues. How to integrate economics and political science is also discussed.…

Analyzing the Genotoxicity of Retroviral Vectors in Hematopoietic Cell Gene Therapy

Directory of Open Access Journals (Sweden)

Luca Biasco

2018-03-01

Full Text Available Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face severe adverse events in the form of leukemias and myelodysplastic syndromes, related to the semi-random vector integration into the host cell genome that caused deregulation of neighboring proto-oncogenes. Although improvements in vector design clearly lowered the risk of this insertional mutagenesis, analysis of potential genotoxicity and the consequences of vector integration remain important parameters for basic and translational research and most importantly for the clinic. Here, we review current assays to analyze biodistribution and genotoxicity in the pre-clinical setting and describe tools to monitor vector integration sites in vector-treated patients as a biosafety readout.

On genome-wide association studies for family-based designs: an integrative analysis approach combining ascertained family samples with unselected controls.

NARCIS (Netherlands)

Lasky-Su, J.; Won, S.; Mick, E.; Anney, R.J.; Franke, B.; Neale, B.; Biederman, J.; Smalley, S.L.; Loo, S.K.; Todorov, A.A.; Faraone, S.V.; Weiss, S.T.; Lange, C.

2010-01-01

Large numbers of control individuals with genome-wide genotype data are now available through various databases. These controls are regularly used in case-control genome-wide association studies (GWAS) to increase the statistical power. Controls are often "unselected" for the disease of interest and

The design of multi-channel pulse amplitude analyzer based on ARM micro controller

International Nuclear Information System (INIS)

Li Hai; Li Xiang; Liu Caixue

2010-01-01

It introduces the design of multi-channel pulse amplitude analyzer based on embedded ARM micro-controller. The embedded and real-time system μC/OS-II builds up the real-time and stability of the system and advances the integration. (authors)

ARE METHODS USED TO INTEGRATE STANDARDIZED MANAGEMENT SYSTEMS A CONDITIONING FACTOR OF THE LEVEL OF INTEGRATION? AN EMPIRICAL STUDY

Directory of Open Access Journals (Sweden)

Merce Bernardo

2011-09-01

Full Text Available Organizations are increasingly implementing multiple Management System Standards (M SSs and considering managing the related Management Systems (MSs as a single system.The aim of this paper is to analyze if methods us ed to integrate standardized MSs condition the level of integration of those MSs. A descriptive methodology has been applied to 343 Spanish organizations registered to, at least, ISO 9001 and ISO 14001. Seven groups of these organizations using different combinations of methods have been analyzed Results show that these organizations have a high level of integration of their MSs. The most common method used, was the process map. Organizations using a combination of different methods achieve higher levels of integration than those using a single method. However, no evidence has been found to confirm the relationship between the method used and the integration level achieved.

CAPL: an efficient association software package using family and case-control data and accounting for population stratification.

Science.gov (United States)

Chung, Ren-Hua; Schmidt, Michael A; Martin, Eden R

2011-05-25

With many genome-wide association study (GWAS) datasets available, it is critical that we have statistical tools that are both flexible to accommodate different study designs and fast. We recently proposed the combined APL (CAPL) method, which can use family and case-control datasets and can account for population stratification in the data. Because computationally intensive algorithms are used in CAPL, implementing CAPL with efficient parallel algorithms is essential. We used a hybrid of open message passing interface (open MPI) and POSIX threads to parallelize CAPL, which enable the program to operate in a cluster environment. We used simulations to demonstrate that the parallel implementation of CAPL can analyze a large GWAS dataset in a reasonable time frame when a parallel computing resource is available. As many GWAS datasets based on both family and case-control designs are available, a flexible and efficient tool such as CAPL will be very helpful to combine the datasets to greatly increase statistical power and finish the analysis in a reasonable time frame.

Local Genetic Correlation Gives Insights into the Shared Genetic Architecture of Complex Traits.

Science.gov (United States)

Shi, Huwenbo; Mancuso, Nicholas; Spendlove, Sarah; Pasaniuc, Bogdan

2017-11-02

Although genetic correlations between complex traits provide valuable insights into epidemiological and etiological studies, a precise quantification of which genomic regions disproportionately contribute to the genome-wide correlation is currently lacking. Here, we introduce ρ-HESS, a technique to quantify the correlation between pairs of traits due to genetic variation at a small region in the genome. Our approach requires GWAS summary data only and makes no distributional assumption on the causal variant effect sizes while accounting for linkage disequilibrium (LD) and overlapping GWAS samples. We analyzed large-scale GWAS summary data across 36 quantitative traits, and identified 25 genomic regions that contribute significantly to the genetic correlation among these traits. Notably, we find 6 genomic regions that contribute to the genetic correlation of 10 pairs of traits that show negligible genome-wide correlation, further showcasing the power of local genetic correlation analyses. Finally, we report the distribution of local genetic correlations across the genome for 55 pairs of traits that show putative causal relationships. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

An integrated strategy for analyzing the unique developmental programs of different myoblast subtypes.

Directory of Open Access Journals (Sweden)

2006-02-01

Full Text Available An important but largely unmet challenge in understanding the mechanisms that govern the formation of specific organs is to decipher the complex and dynamic genetic programs exhibited by the diversity of cell types within the tissue of interest. Here, we use an integrated genetic, genomic, and computational strategy to comprehensively determine the molecular identities of distinct myoblast subpopulations within the Drosophila embryonic mesoderm at the time that cell fates are initially specified. A compendium of gene expression profiles was generated for primary mesodermal cells purified by flow cytometry from appropriately staged wild-type embryos and from 12 genotypes in which myogenesis was selectively and predictably perturbed. A statistical meta-analysis of these pooled datasets--based on expected trends in gene expression and on the relative contribution of each genotype to the detection of known muscle genes--provisionally assigned hundreds of differentially expressed genes to particular myoblast subtypes. Whole embryo in situ hybridizations were then used to validate the majority of these predictions, thereby enabling true-positive detection rates to be estimated for the microarray data. This combined analysis reveals that myoblasts exhibit much greater gene expression heterogeneity and overall complexity than was previously appreciated. Moreover, it implicates the involvement of large numbers of uncharacterized, differentially expressed genes in myogenic specification and subsequent morphogenesis. These findings also underscore a requirement for considerable regulatory specificity for generating diverse myoblast identities. Finally, to illustrate how the developmental functions of newly identified myoblast genes can be efficiently surveyed, a rapid RNA interference assay that can be scored in living embryos was developed and applied to selected genes. This integrated strategy for examining embryonic gene expression and function provides

Integrative Pedagogical Bioethics

Directory of Open Access Journals (Sweden)

Anna Hubenko

2014-07-01

Full Text Available The state of bioethics in Ukraine, as well as in the world has been analyzed in this article. The author offers a model of integrative pedagogical bioethics and substantiates the necessity of the organization of the bioethics education and confirms the topicality of adoption of the new specialty – educator-bioethicist. The author defines the structure and method of the educational process and the new curriculum «Integrative Bioethics» for preparing educator-bioethicist specialist.

Genes Linked to Endometriosis by GWAS Are Integral to Cytoskeleton Regulation and Suggests That Mesothelial Barrier Homeostasis Is a Factor in the Pathogenesis of Endometriosis.

Science.gov (United States)

Albertsen, Hans M; Ward, Kenneth

2017-06-01

Endometriosis, defined by the presence of ectopic endometrial lesions, is a common disease in reproductive-age women that profoundly affects patients' quality of life. Various pathogenic models have been proposed, but the origin of endometriosis remains elusive. In this article, we propose that the mesothelial barrier, which protects the underlying stroma from endometrial transplants present in retrograde menstrual fluid, can be compromised by activation of the epithelial to mesenchymal transition (EMT) repair mechanism that lead to temporary loss of barrier integrity. Absent of the mesothelial barrier, endometrial cells can more readily adhere to the underlying peritoneal stroma and establish endometrial lesions. The hypothesis is based on the clinical and experimental observations that correlate the location of endometrial lesions with areas of mesothelial damage, together with genetic evidence that 4 genes associated with endometriosis are direct regulators of the actin-cytoskeleton, which coordinates mesothelial barrier integrity. It supports past observations that implicate the peritoneum in the pathogenesis of endometriosis and unifies previously disparate theories that endometriosis may be triggered by infection, mechanical damage, and inflammation since each of these mechanisms can induce EMT in the mesothelium. If the hypothesis is correct, inhibition of EMT in the mesothelial barrier provides a novel paradigm for the prevention and treatment of endometriosis.

Semantics based approach for analyzing disease-target associations.

Science.gov (United States)

Kaalia, Rama; Ghosh, Indira

2016-08-01

A complex disease is caused by heterogeneous biological interactions between genes and their products along with the influence of environmental factors. There have been many attempts for understanding the cause of these diseases using experimental, statistical and computational methods. In the present work the objective is to address the challenge of representation and integration of information from heterogeneous biomedical aspects of a complex disease using semantics based approach. Semantic web technology is used to design Disease Association Ontology (DAO-db) for representation and integration of disease associated information with diabetes as the case study. The functional associations of disease genes are integrated using RDF graphs of DAO-db. Three semantic web based scoring algorithms (PageRank, HITS (Hyperlink Induced Topic Search) and HITS with semantic weights) are used to score the gene nodes on the basis of their functional interactions in the graph. Disease Association Ontology for Diabetes (DAO-db) provides a standard ontology-driven platform for describing genes, proteins, pathways involved in diabetes and for integrating functional associations from various interaction levels (gene-disease, gene-pathway, gene-function, gene-cellular component and protein-protein interactions). An automatic instance loader module is also developed in present work that helps in adding instances to DAO-db on a large scale. Our ontology provides a framework for querying and analyzing the disease associated information in the form of RDF graphs. The above developed methodology is used to predict novel potential targets involved in diabetes disease from the long list of loose (statistically associated) gene-disease associations. Copyright © 2016 Elsevier Inc. All rights reserved.

Digital Microfluidics Sample Analyzer

Science.gov (United States)

Pollack, Michael G.; Srinivasan, Vijay; Eckhardt, Allen; Paik, Philip Y.; Sudarsan, Arjun; Shenderov, Alex; Hua, Zhishan; Pamula, Vamsee K.

2010-01-01

Three innovations address the needs of the medical world with regard to microfluidic manipulation and testing of physiological samples in ways that can benefit point-of-care needs for patients such as premature infants, for which drawing of blood for continuous tests can be life-threatening in their own right, and for expedited results. A chip with sample injection elements, reservoirs (and waste), droplet formation structures, fluidic pathways, mixing areas, and optical detection sites, was fabricated to test the various components of the microfluidic platform, both individually and in integrated fashion. The droplet control system permits a user to control droplet microactuator system functions, such as droplet operations and detector operations. Also, the programming system allows a user to develop software routines for controlling droplet microactuator system functions, such as droplet operations and detector operations. A chip is incorporated into the system with a controller, a detector, input and output devices, and software. A novel filler fluid formulation is used for the transport of droplets with high protein concentrations. Novel assemblies for detection of photons from an on-chip droplet are present, as well as novel systems for conducting various assays, such as immunoassays and PCR (polymerase chain reaction). The lab-on-a-chip (a.k.a., lab-on-a-printed-circuit board) processes physiological samples and comprises a system for automated, multi-analyte measurements using sub-microliter samples of human serum. The invention also relates to a diagnostic chip and system including the chip that performs many of the routine operations of a central labbased chemistry analyzer, integrating, for example, colorimetric assays (e.g., for proteins), chemiluminescence/fluorescence assays (e.g., for enzymes, electrolytes, and gases), and/or conductometric assays (e.g., for hematocrit on plasma and whole blood) on a single chip platform.

GlobAl Distribution of GEnetic Traits (GADGET) web server: polygenic trait scores worldwide.

Science.gov (United States)

Chande, Aroon T; Wang, Lu; Rishishwar, Lavanya; Conley, Andrew B; Norris, Emily T; Valderrama-Aguirre, Augusto; Jordan, I King

2018-05-18

Human populations from around the world show striking phenotypic variation across a wide variety of traits. Genome-wide association studies (GWAS) are used to uncover genetic variants that influence the expression of heritable human traits; accordingly, population-specific distributions of GWAS-implicated variants may shed light on the genetic basis of human phenotypic diversity. With this in mind, we developed the GlobAl Distribution of GEnetic Traits web server (GADGET http://gadget.biosci.gatech.edu). The GADGET web server provides users with a dynamic visual platform for exploring the relationship between worldwide genetic diversity and the genetic architecture underlying numerous human phenotypes. GADGET integrates trait-implicated single nucleotide polymorphisms (SNPs) from GWAS, with population genetic data from the 1000 Genomes Project, to calculate genome-wide polygenic trait scores (PTS) for 818 phenotypes in 2504 individual genomes. Population-specific distributions of PTS are shown for 26 human populations across 5 continental population groups, with traits ordered based on the extent of variation observed among populations. Users of GADGET can also upload custom trait SNP sets to visualize global PTS distributions for their own traits of interest.

High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

NARCIS (Netherlands)

Eyre, Steve; Bowes, John; Diogo, Dorothee; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I.; Padyukov, Leonid; Toes, Rene E. M.; Huizinga, Tom W. J.; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I. W.; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E.; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S.; Deloukas, Panos; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Arlsetig, Lisbeth; Martin, Javier; Rantapaa-Dahlqvist, Solbritt; Plenge, Robert M.; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K.; Worthington, Jane

2012-01-01

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data

Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study.

Directory of Open Access Journals (Sweden)

Valborg Gudmundsdottir

Full Text Available Glucagon-like peptide 1 (GLP-1 stimulated insulin secretion has a considerable heritable component as estimated from twin studies, yet few genetic variants influencing this phenotype have been identified. We performed the first genome-wide association study (GWAS of GLP-1 stimulated insulin secretion in non-diabetic individuals from the Netherlands Twin register (n = 126. This GWAS was enhanced using a tissue-specific protein-protein interaction network approach. We identified a beta-cell protein-protein interaction module that was significantly enriched for low gene scores based on the GWAS P-values and found support at the network level in an independent cohort from Tübingen, Germany (n = 100. Additionally, a polygenic risk score based on SNPs prioritized from the network was associated (P < 0.05 with glucose-stimulated insulin secretion phenotypes in up to 5,318 individuals in MAGIC cohorts. The network contains both known and novel genes in the context of insulin secretion and is enriched for members of the focal adhesion, extracellular-matrix receptor interaction, actin cytoskeleton regulation, Rap1 and PI3K-Akt signaling pathways. Adipose tissue is, like the beta-cell, one of the target tissues of GLP-1 and we thus hypothesized that similar networks might be functional in both tissues. In order to verify peripheral effects of GLP-1 stimulation, we compared the transcriptome profiling of ob/ob mice treated with liraglutide, a clinically used GLP-1 receptor agonist, versus baseline controls. Some of the upstream regulators of differentially expressed genes in the white adipose tissue of ob/ob mice were also detected in the human beta-cell network of genes associated with GLP-1 stimulated insulin secretion. The findings provide biological insight into the mechanisms through which the effects of GLP-1 may be modulated and highlight a potential role of the beta-cell expressed genes RYR2, GDI2, KIAA0232, COL4A1 and COL4A2 in GLP-1 stimulated

A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk

Science.gov (United States)

Pooley, Karen A.; Bojesen, Stig E.; Weischer, Maren; Nielsen, Sune F.; Thompson, Deborah; Amin Al Olama, Ali; Michailidou, Kyriaki; Tyrer, Jonathan P.; Benlloch, Sara; Brown, Judith; Audley, Tina; Luben, Robert; Khaw, K-T; Neal, David E.; Hamdy, Freddie C.; Donovan, Jenny L.; Kote-Jarai, Zsofia; Baynes, Caroline; Shah, Mitul; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dicks, Ed; Yang, Rongxi; Rudolph, Anja; Schildkraut, Joellen; Chang-Claude, Jenny; Burwinkel, Barbara; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Berchuck, Andrew; Eeles, Rosalind A.; Easton, Douglas F.; Dunning, Alison M.; Nordestgaard, Børge G.

2013-01-01

Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the “iCOGS” custom genotyping array. All ∼200 000 iCOGS variants were analysed with TL, and those displaying associations in healthy controls (n = 15 065) were further tested in breast cancer cases (n = 11 024). We found a novel TL association (Ptrend < 4 × 10−10) at 3p14.4 close to PXK and evidence (Ptrend < 7 × 10−7) for TL loci at 6p22.1 (ZNF311) and 20q11.2 (BCL2L1). We additionally confirmed (Ptrend < 5 × 10−14) the previously reported loci at 3q26.2 (TERC), 5p15.3 (TERT) and 10q24.3 (OBFC1) and found supportive evidence (Ptrend < 5 × 10−4) for the published loci at 2p16.2 (ACYP2), 4q32.2 (NAF1) and 20q13.3 (RTEL1). SNPs tagging these loci explain TL differences of up to 731 bp (corresponding to 18% of total TL in healthy individuals), however, they display little direct evidence for association with breast, ovarian or prostate cancer risks. PMID:23900074

A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk.

Science.gov (United States)

Pooley, Karen A; Bojesen, Stig E; Weischer, Maren; Nielsen, Sune F; Thompson, Deborah; Amin Al Olama, Ali; Michailidou, Kyriaki; Tyrer, Jonathan P; Benlloch, Sara; Brown, Judith; Audley, Tina; Luben, Robert; Khaw, K-T; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Kote-Jarai, Zsofia; Baynes, Caroline; Shah, Mitul; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Yang, Rongxi; Rudolph, Anja; Schildkraut, Joellen; Chang-Claude, Jenny; Burwinkel, Barbara; Chenevix-Trench, Georgia; Pharoah, Paul D P; Berchuck, Andrew; Eeles, Rosalind A; Easton, Douglas F; Dunning, Alison M; Nordestgaard, Børge G

2013-12-15

Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the "iCOGS" custom genotyping array. All ∼200 000 iCOGS variants were analysed with TL, and those displaying associations in healthy controls (n = 15 065) were further tested in breast cancer cases (n = 11 024). We found a novel TL association (Ptrend < 4 × 10(-10)) at 3p14.4 close to PXK and evidence (Ptrend < 7 × 10(-7)) for TL loci at 6p22.1 (ZNF311) and 20q11.2 (BCL2L1). We additionally confirmed (Ptrend < 5 × 10(-14)) the previously reported loci at 3q26.2 (TERC), 5p15.3 (TERT) and 10q24.3 (OBFC1) and found supportive evidence (Ptrend < 5 × 10(-4)) for the published loci at 2p16.2 (ACYP2), 4q32.2 (NAF1) and 20q13.3 (RTEL1). SNPs tagging these loci explain TL differences of up to 731 bp (corresponding to 18% of total TL in healthy individuals), however, they display little direct evidence for association with breast, ovarian or prostate cancer risks.

Kernel machine methods for integrative analysis of genome-wide methylation and genotyping studies.

Science.gov (United States)

Zhao, Ni; Zhan, Xiang; Huang, Yen-Tsung; Almli, Lynn M; Smith, Alicia; Epstein, Michael P; Conneely, Karen; Wu, Michael C

2018-03-01

Many large GWAS consortia are expanding to simultaneously examine the joint role of DNA methylation in addition to genotype in the same subjects. However, integrating information from both data types is challenging. In this paper, we propose a composite kernel machine regression model to test the joint epigenetic and genetic effect. Our approach works at the gene level, which allows for a common unit of analysis across different data types. The model compares the pairwise similarities in the phenotype to the pairwise similarities in the genotype and methylation values; and high correspondence is suggestive of association. A composite kernel is constructed to measure the similarities in the genotype and methylation values between pairs of samples. We demonstrate through simulations and real data applications that the proposed approach can correctly control type I error, and is more robust and powerful than using only the genotype or methylation data in detecting trait-associated genes. We applied our method to investigate the genetic and epigenetic regulation of gene expression in response to stressful life events using data that are collected from the Grady Trauma Project. Within the kernel machine testing framework, our methods allow for heterogeneity in effect sizes, nonlinear, and interactive effects, as well as rapid P-value computation. © 2017 WILEY PERIODICALS, INC.

Electric field studies of a 2 MeV electrostatic energy analyzer

International Nuclear Information System (INIS)

McLaren, P.E.; Connor, K.A.; Lewis, J.F.; Hickok, R.L.; Crowley, T.P.; Schatz, J.G.; Vilardi, G.H.

1990-01-01

An energy analyzer based on the Proca and Green parallel-plate design is being developed for use with the 2 MeV heavy ion beam probe on TEXT. In a departure from the conventional configuration, guard ring electrodes will not be used. Instead, a shaped top plate will provide for comparable, or improved, uniformity of the analyzer electric field region. To quantify this effect, and to characterize the electrostatic field, numerical solution methods have been utilized. Simulations have included effects of top plate shape, wire screens, vacuum chamber design, and dielectric support structures. The modeling has permitted us to design an analyzer electrode structure that is an integral part of a uniquely shaped vacuum vessel. The design electric field is 20 kV/cm with less than 1% error in uniformity within the parallel plate region. To examine the electric field structure experimentally, a quarter-scale prototype analyzer has been constructed and tested. The electric field characteristics are examined by varying the path of a heavy ion beam through the analyzer and examining the resulting analyzer performance. A simulated vacuum wall can be positioned to examine the effects of different vessel configurations and to determine the sensitivity of the analyzer to this boundary condition. The experimental results show excellent agreement with the numerically predicted fields and confirm the validity of the shaped top plate electrode concept

Solar Probe ANalyzer for Ions - Laboratory Performance

Science.gov (United States)

Livi, R.; Larson, D. E.; Kasper, J. C.; Korreck, K. E.; Whittlesey, P. L.

2017-12-01

The Parker Solar Probe (PSP) mission is a heliospheric satellite that will orbit the Sun closer than any prior mission to date with a perihelion of 35 solar radii (RS) and an aphelion of 10 RS. PSP includes the Solar Wind Electrons Alphas and Protons (SWEAP) instrument suite, which in turn consists of four instruments: the Solar Probe Cup (SPC) and three Solar Probe ANalyzers (SPAN) for ions and electrons. Together, this suite will take local measurements of particles and electromagnetic fields within the Sun's corona. SPAN-Ai has completed flight calibration and spacecraft integration and is set to be launched in July of 2018. The main mode of operation consists of an electrostatic analyzer (ESA) at its aperture followed by a Time-of-Flight section to measure the energy and mass per charge (m/q) of the ambient ions. SPAN-Ai's main objective is to measure solar wind ions within an energy range of 5 eV - 20 keV, a mass/q between 1-60 [amu/q] and a field of view of 2400x1200. Here we will show flight calibration results and performance.

Nuclear plant analyzer development at INEL

International Nuclear Information System (INIS)

Laats, E.T.; Russell, K.D.; Stewart, H.D.

1983-01-01

The Office of Nuclear Regulatory Research of the US Nuclear Regulatory Commission (NRC) has sponsored development of a software-hardware system called the Nuclear Plant Analyzer (NPA). This paper describes the status of the NPA project at the INEL after one year of development. When completed, the NPA will be an integrated network of analytical tools for performing reactor plant analyses. Development of the NPA in FY-1983 progressed along two parallel pathways; namely, conceptual planning and software development. Regarding NPA planning, and extensive effort was conducted to define the function requirements of the NPA, conceptual design, and hardware needs. Regarding software development conducted in FY-1983, all development was aimed toward demonstrating the basic concept and feasibility of the NPA. Nearly all software was developed and resides on the INEL twin Control Data Corporation 176 mainframe computers

A new approach to analyze strategy map using an integrated BSC and FUZZY DEMATEL

Directory of Open Access Journals (Sweden)

Seyed Abdollah Heydariyeh

2012-01-01

Full Text Available Today, with ever-increasing competition in global economic conditions, the necessity of effective implementation of strategy map has become an inevitable and necessary. The strategy map represents a general and structured framework for strategic objectives and plays an important role in forming competitive advantages for organizations. It is important to find important factors influencing strategy map and prioritize them based on suitable factors. In this paper, we propose an integration of BSC and Fuzzy DEMATEL technique to rank different items influencing strategy of a production plan. The proposed technique is implemented for real-world case study of glass production.

A novel Alzheimer disease locus located near the gene encoding tau protein

NARCIS (Netherlands)

Y. Jun (Yang); C.A. Ibrahim-Verbaas (Carla); M. Vronskaya; J.-C. Lambert; J. Chung; A.C. Naj (Adam); B. Kunkle (Brian); L.-S. Wang; J.C. Bis (Joshua); C. Bellenguez (Céline); D. Harold (Denise); K.L. Lunetta (Kathryn); A.L. DeStefano (Anita L.); B. Grenier-Boley (Benjamin); R. Sims (Rebecca); G.W. Beecham; A.V. Smith; V. Chouraki (Vincent); K.L. Hamilton-Nelson (Kara); M.A. Ikram (Arfan); N. Fiévet (Nathalie); N. Denning (Nicola); E.R. Martin; H. Schmidt; Y. Kamatani; M.L. Dunstan; O. Valladares (Otto); A.R. Laza; D. Zelenika (Diana); A. Ramirez (Alfredo); T. Foroud (Tatiana); S.-H. Choi (Seung-Hoan); A. Boland; T. Becker; W.A. Kukull; S.J. van der Lee (Sven); F. Pasquier (Florence); C. Cruchaga (Carlos); D. Beekly (Duane); A.L. Fitzpatrick (Annette); O. Hanon (Olivier); M. Gill; R. Barber (Rachel); V. Gudnason (Vilmundur); D. Campion; S. Love; D.A. Bennett (David A.); N. Amin (Najaf); C. Berr (Claudine); M. Tsolaki (Magda); J.D. Buxbaum; O.L. Lopez; V. Deramecourt (Vincent); N.C. Fox; L.B. Cantwell (Laura B.); L. Tárraga (L.); C. Dufouil (Carole); J. Hardy; L.M.A. Crane; G. Eiriksdottir (Gudny); D. Hannequin (Didier); R. Clarke (Robert); D. Evans; T.H. Mosley (Thomas H.); L. Letenneur; C. Brayne (Carol); W. Maier; P. De Jager; V. Emilsson (Valur); J.-F. Dartigues (Jean-François); H. Hampel; M.I. Kamboh (M. Ilyas); R.F.A.G. de Bruijn (Renée); C. Tzourio (Christophe); P. Pastor (Pau); E.B. Larson (Eric B.); J.I. Rotter; M.C. O'donovan (Michael); T.J. Montine (Thomas J.); M.A. Nalls (Michael); S. Mead (Simon); E.M. Reiman (Eric); P.V. Jonsson; C. Holmes; P.H. St George-Hyslop; M. Boada (Mercè); P. Passmore (Peter); A. Wendland (Annika); R. Schmidt; K. Morgan (Kevin); A.R. Winslow; J.F. Powell; M. Carasquillo; S. Younkin; M. Jakobsdottir (Margret); J.S.K. Kauwe; K.C. Wilhelmsen; D. Rujescu (Dan); M.M. Nöthen (Markus M.); A. Hofman (Albert); L. Jones (Louisa); J.L. Haines (Jonathan); B.M. Psaty (Bruce); C. Van Broeckhoven; P. Holmans; L.J. Launer (Lenore); R. Mayeux (Richard); M. Lathrop; A.M. Goate (Alison M.); V. Escott-Price (Valentina); S. Seshadri (Sudha); M.A. Pericak-Vance (Margaret); P. Amouyel (Philippe); J. Williams; C.M. van Duijn (Cornelia); G.D. Schellenberg (Gerard D.); L.A. Farrer (Lindsay)

2016-01-01

textabstractAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and

Proton--proton analyzing power measurements at 16 MeV

International Nuclear Information System (INIS)

Lovoi, P.A.

1975-01-01

Few attempts have been made to measure accurately the proton--proton analyzing powers at low energies. With the advent of polarized particle beams the measurement can now be made with high accuracy. Analyzing powers were measured at nine scattering angles from 10 0 to 35 0 in the laboratory system. As a check on systematic errors, analyzing power measurements were also made by scattering protons from 4 He. In the p vector-p case the measured values are in very good agreement with the phase shift predictions. The p vector- 4 He measurements, while giving the same form and sign as the phase shift predictions, differ from the predictions by as much as 11 standard deviations. The p vector-p analyzing powers had a maximum value of -0.0043 +- 0.0004 at 10 0 (laboratory) and decreased to zero near 25 0 . A new technique to measure analyzing powers without symmetric detectors is explained. This technique preserves the advantages of the symmetric arm method in that current integration, target density, detector efficiencies, and geometry are cancelled from the final expressions. A new scattering chamber, named the Supercube, is described. The Supercube was designed primarily to perform scattering experiments with a polarized beam. It contains both left-right and up-down detectors for use with both spin- 1 / 2 and spin-1 measurements. The Supercube was designed to make analyzing power measurements to an accuracy of 0.001 routine. The Supercube has proved to have low systematic errors and to perform as expected. The systematic errors were found to be equal to or less than 0.0002

Proton--proton analyzing power measurements at 16 MeV

International Nuclear Information System (INIS)

Lovoi, P.A.

1975-07-01

Few attempts have been made to measure accurately the proton-proton analyzing powers at low energies. With the advent of polarized particle beams the measurement can now be made with high accuracy. Analyzing powers were measured at nine scattering angles from 10 0 to 35 0 in the laboratory system. As a check on systematic errors, analyzing power measurements were also made by scattering protons from 4 He. In the p Vector-p case the measured values are in very good agreement with the phase shift predictions. The p Vector- 4 He measurements, while giving the same form and sign as the phase shift predictions, differ from the predictions by as much as 11 standard deviations. The p Vector-p analyzing powers had a maximum value of -0.0043 +- 0.0004 at 10 0 (laboratory) and decreased to zero near 25 0 . A new technique to measure analyzing powers without symmetric detectors is explained. This technique preserves the advantages of the symmetric arm method in that current integration, target density, detector efficiencies, and geometry are cancelled from the final expressions. A new scattering chamber, named the Supercube, is described. The Supercube was designed primarily to perform scattering experiments with a polarized beam. It contains both left-right and up-down detectors for use with both spin-1/2 and spin-1 measurements. The Supercube was designed to make analyzing power measurements to an accuracy of 0.001 routine. The Supercube has proved to have low systematic errors and to perform as expected. The systematic errors were found to be equal to or less than 0.0002. (23 figures, 14 tables) (auth)

Integrating and Analyzing Psychosocial and Stage Theories To Challenge the Development of the Injured Collegiate Athlete.

Science.gov (United States)

Harris, Laura L.

2003-01-01

Integrated a psychosocial developmental theory (the Kubler-Ross Stage Theory) and a psychological stage theory (the Ross Stage Theory) and a psychological stage theory (the Chickering and Reisser psychosocial and developmental theory) for challenging injured collegiate student-athletes' personal development. A search of online databases from…

Evaluation of novel candidate variations and their interactions related to bipolar disorders: Analysis of GWAS data

Directory of Open Access Journals (Sweden)

Acikel C

2016-11-01

, have prioritized similar SNP profiles as predictors of bipolar disorders, in contrast to MDR, which has found different SNPs through analysis of two-way and three-way interactions. The reduced number of associated SNPs discovered by MDR, without loss in the classification performance, would facilitate validation studies and decision support models, and would reduce the cost to develop predictive and diagnostic tests. Nevertheless, we need to emphasize that translation of genomic models to the clinical setting requires models with higher classification performance. Keywords: Bipolar disorders, GWAS, MDR, Data Mining, SNP, Decision Support

Data integration approaches using ETL

Directory of Open Access Journals (Sweden)

Alexandra Maria Ioana FLOREA

2016-01-01

Full Text Available Traditional data warehouses and ETL tools have been slowly pushed to expand their limits as big data has become a more and more prominent actor on the analytics stage. This paper analyzes and compares the features of Pentaho Data Integration and Oracle Data Integrator, two of the main data integration platforms. Such tools are relevant in the context of the evolution of the analytics field, which is expanding from classical business intelligence activities to the use and analysis of big data.

Improving integration for integrated coastal zone management: an eight country study.

Science.gov (United States)

Portman, M E; Esteves, L S; Le, X Q; Khan, A Z

2012-11-15

Integrated coastal zone management (ICZM) is a widely accepted approach for sustainable management of the coastal environment. ICZM emphasizes integration across sectors, levels of government, uses, stakeholders, and spatial and temporal scales. While improving integration is central to progress in ICZM, the role of and the achievement of integration remain understudied. To further study these two points, our research analyzes the performance of specific mechanisms used to support ICZM in eight countries (Belgium, India, Israel, Italy, Portugal, Sweden, UK, and Vietnam). The assessment is based on a qualitative comparative analysis conducted through the use of two surveys. It focuses on five ICZM mechanisms (environmental impact assessment; planning hierarchy; setback lines; marine spatial planning, and regulatory commission) and their role in improving integration. Our findings indicate that certain mechanisms enhance specific types of integration more effectively than others. Environmental impact assessment enhances science-policy integration and can be useful to integrate knowledge across sectors. Planning hierarchy and regulatory commissions are effective mechanisms to integrate policies across government levels, with the latter also promoting public-government integration. Setback lines can be applied to enhance integration across landscape units. Marine spatial planning is a multi-faceted mechanism with the potential to promote all types of integration. Policy-makers should adopt the mechanisms that are suited to the type of integration needed. Results of this study also contribute to evidence-based coastal management by identifying the most common impediments related to the mechanisms of integration in the eight studied countries. Copyright © 2012 Elsevier B.V. All rights reserved.

Integrating cognitive (neuroscience using mechanisms

Directory of Open Access Journals (Sweden)

Marcin Miłkowski

2016-11-01

Full Text Available In this paper, an account of theoretical integration in cognitive (neuroscience from the mechanistic perspective is defended. It is argued that mechanistic patterns of integration can be better understood in terms of constraints on representations of mechanisms, not just on the space of possible mechanisms, as previous accounts of integration had it. This way, integration can be analyzed in more detail with the help of constraintsatisfaction account of coherence between scientific represen-tations. In particular, the account has resources to talk of idealizations and research heuristics employed by researchers to combine separate results and theoretical frameworks. The account is subsequently applied to an example of successful integration in the research on hippocampus and memory, and to a failure of integration in the research on mirror neurons as purportedly explanatory of sexual orientation.

Convergent functional genomics in addiction research - a translational approach to study candidate genes and gene networks.

Science.gov (United States)

Spanagel, Rainer

2013-01-01

Convergent functional genomics (CFG) is a translational methodology that integrates in a Bayesian fashion multiple lines of evidence from studies in human and animal models to get a better understanding of the genetics of a disease or pathological behavior. Here the integration of data sets that derive from forward genetics in animals and genetic association studies including genome wide association studies (GWAS) in humans is described for addictive behavior. The aim of forward genetics in animals and association studies in humans is to identify mutations (e.g. SNPs) that produce a certain phenotype; i.e. "from phenotype to genotype". Most powerful in terms of forward genetics is combined quantitative trait loci (QTL) analysis and gene expression profiling in recombinant inbreed rodent lines or genetically selected animals for a specific phenotype, e.g. high vs. low drug consumption. By Bayesian scoring genomic information from forward genetics in animals is then combined with human GWAS data on a similar addiction-relevant phenotype. This integrative approach generates a robust candidate gene list that has to be functionally validated by means of reverse genetics in animals; i.e. "from genotype to phenotype". It is proposed that studying addiction relevant phenotypes and endophenotypes by this CFG approach will allow a better determination of the genetics of addictive behavior.

GOoDA: The Generic Optimization Data Analyzer

International Nuclear Information System (INIS)

Calafiura, P; Vitillo, R A; Eranian, S; Levinthal, D; Kama, S

2012-01-01

Modern superscalar, out-of-order microprocessors dominate large scale server computing. Monitoring their activity, during program execution, has become complicated due to the complexity of the microarchitectures and their IO interactions. Recent processors have thousands of performance monitoring events. These are required to actually provide coverage for all of the complex interactions and performance issues that can occur. Knowing which data to collect and how to interpret the results has become an unreasonable burden for code developers whose tasks are already hard enough. It becomes the task of the analysis tool developer to bridge this gap. To address this issue, a generic decomposition of how a microprocessor is using the consumed cycles allows code developers to quickly understand which of the myriad of microarchitectural complexities they are battling, without requiring a detailed knowledge of the microarchitecture. When this approach is intrinsically integrated into a performance data analysis tool, it enables software developers to take advantage of the microarchitectural methodology that has only been available to experts. The Generic Optimization Data Analyzer (GOoDA) project integrates this expertise into a profiling tool in order to lower the required expertise of the user and, being designed from the ground up with large-scale object-oriented applications in mind, it will be particularly useful for large HENP codebases

Electricity sector integration in West Africa

International Nuclear Information System (INIS)

Pineau, Pierre-Olivier

2008-01-01

Regional and global integration initiatives push for more electricity sector integration everywhere in the world, including West Africa. The creation of the West African Power Pool (WAPP) in 2000 and important investments under this new structure in 2006 are concrete actions that will result in a more integrated West African electricity sector. But will this integrated sector be more functional than the previous ones? Will the identified electricity sector problems be solved with the new power pool? This paper analyzes how power sector integration is presented by international institutions (the UN Economic Commission for Africa, World Energy Council and World Bank) and identifies three problematic issues with the current integration approach: lack of African ownership, unclear and conflicting reform objectives and uncertainty of integration outcomes

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

Science.gov (United States)

Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; van der Veen, JP Wietze; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W.; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R.; Santorico, Stephanie A; Spritz, Richard A

2016-01-01

Vitiligo is an autoimmune disease in which depigmented skin results from destruction of melanocytes1, with epidemiologic association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1, GWAS2), we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We carried out a third GWAS (GWAS3) in EUR subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new loci and 7 suggestive loci, most encoding immune and apoptotic regulators, some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some corresponding to eQTL at these loci. Together, the identified genes provide a framework for vitiligo genetic architecture and pathobiology, highlight relationships to other autoimmune diseases and melanoma, and offer potential targets for treatment. PMID:27723757

Integration of radiation monitoring for nuclear emergency response teams

Energy Technology Data Exchange (ETDEWEB)

Olsen, J T; Thompson, N Y [Royal Military Coll. of Canada, Kingston, ON (Canada)

1994-12-31

The Canadian Forces have established Nuclear Emergency Response Teams to cope with potential radiation accidents. Previously, only gamma and high-energy beta radiation could be detected. Recently, new radiation sampling, detecting, and analytical equipment has been bought, including air samplers, beta counters, high-purity germanium gamma detectors, and multi-channel analyzers together with Gamma Vision Software to analyze gamma spectra. The purpose of the present study is to propose a way to use the new equipment, to analyze the results from the gamma and beta detectors, and to integrate the results into a format for decision making. Integration is achieved through the creation of a computer program, Radiation Integration Program (RIP). This program analyzes gross beta counts, and uses them to estimate danger to the thyroid. As well the results from Gamma Vision are converted from Bq to dose rate for several parts of the body. Overall gamma results affecting the thyroid are compared to the beta results to verify the initial estimations.

A discontinuous galerkin time domain-boundary integral method for analyzing transient electromagnetic scattering

KAUST Repository

Li, Ping

2014-07-01

This paper presents an algorithm hybridizing discontinuous Galerkin time domain (DGTD) method and time domain boundary integral (BI) algorithm for 3-D open region electromagnetic scattering analysis. The computational domain of DGTD is rigorously truncated by analytically evaluating the incoming numerical flux from the outside of the truncation boundary through BI method based on the Huygens\\' principle. The advantages of the proposed method are that it allows the truncation boundary to be conformal to arbitrary (convex/ concave) scattering objects, well-separated scatters can be truncated by their local meshes without losing the physics (such as coupling/multiple scattering) of the problem, thus reducing the total mesh elements. Furthermore, low frequency waves can be efficiently absorbed, and the field outside the truncation domain can be conveniently calculated using the same BI formulation. Numerical examples are benchmarked to demonstrate the accuracy and versatility of the proposed method.

Radiation sensitivity of integrated circuits Pt. 1

International Nuclear Information System (INIS)

Bereczkine Kerenyi, Ilona

1986-01-01

The cosmic ray sensitivity of CMOS integrated circuits are overviewed in three parts. The aim is to analyze the effects of ionizing radiation on the degradation of electronic parameters, the effects of the electric state during irradiation, and the radiation hardening of ICs. In this Part 1 a general introduction of the response of semiconductors to cosmic radiation is given, and the radiation tolerance and hardening of small-scale integrated CMOS ICs is analyzed in detail. The devices include various basic inverters and simple gate ICs. (R.P.)

An integrative approach to ortholog prediction for disease-focused and other functional studies.

Science.gov (United States)

Hu, Yanhui; Flockhart, Ian; Vinayagam, Arunachalam; Bergwitz, Clemens; Berger, Bonnie; Perrimon, Norbert; Mohr, Stephanie E

2011-08-31

Mapping of orthologous genes among species serves an important role in functional genomics by allowing researchers to develop hypotheses about gene function in one species based on what is known about the functions of orthologs in other species. Several tools for predicting orthologous gene relationships are available. However, these tools can give different results and identification of predicted orthologs is not always straightforward. We report a simple but effective tool, the Drosophila RNAi Screening Center Integrative Ortholog Prediction Tool (DIOPT; http://www.flyrnai.org/diopt), for rapid identification of orthologs. DIOPT integrates existing approaches, facilitating rapid identification of orthologs among human, mouse, zebrafish, C. elegans, Drosophila, and S. cerevisiae. As compared to individual tools, DIOPT shows increased sensitivity with only a modest decrease in specificity. Moreover, the flexibility built into the DIOPT graphical user interface allows researchers with different goals to appropriately 'cast a wide net' or limit results to highest confidence predictions. DIOPT also displays protein and domain alignments, including percent amino acid identity, for predicted ortholog pairs. This helps users identify the most appropriate matches among multiple possible orthologs. To facilitate using model organisms for functional analysis of human disease-associated genes, we used DIOPT to predict high-confidence orthologs of disease genes in Online Mendelian Inheritance in Man (OMIM) and genes in genome-wide association study (GWAS) data sets. The results are accessible through the DIOPT diseases and traits query tool (DIOPT-DIST; http://www.flyrnai.org/diopt-dist). DIOPT and DIOPT-DIST are useful resources for researchers working with model organisms, especially those who are interested in exploiting model organisms such as Drosophila to study the functions of human disease genes.

Market Integration Dynamics and Asymptotic Price Convergence in Distribution

NARCIS (Netherlands)

A. García-Hiernaux (Alfredo); D.E. Guerrero (David); M.J. McAleer (Michael)

2013-01-01

textabstractIn this paper we analyse the market integration process of the relative price distribution, develop a model to analyze market integration, and present a formal test of increasing market integration. We distinguish between the economic concepts of price convergence in mean and in

Nuclear plant analyzer desktop workstation

International Nuclear Information System (INIS)

Beelman, R.J.

1990-01-01

In 1983 the U.S. Nuclear Regulatory Commission (USNRC) commissioned the Idaho National Engineering Laboratory (INEL) to develop a Nuclear Plant Analyzer (NPA). The NPA was envisioned as a graphical aid to assist reactor safety analysts in comprehending the results of thermal-hydraulic code calculations. The development was to proceed in three distinct phases culminating in a desktop reactor safety workstation. The desktop NPA is now complete. The desktop NPA is a microcomputer based reactor transient simulation, visualization and analysis tool developed at INEL to assist an analyst in evaluating the transient behavior of nuclear power plants by means of graphic displays. The NPA desktop workstation integrates advanced reactor simulation codes with online computer graphics allowing reactor plant transient simulation and graphical presentation of results. The graphics software, written exclusively in ANSI standard C and FORTRAN 77 and implemented over the UNIX/X-windows operating environment, is modular and is designed to interface to the NRC's suite of advanced thermal-hydraulic codes to the extent allowed by that code. Currently, full, interactive, desktop NPA capabilities are realized only with RELAP5

Systematic identification of regulatory variants associated with cancer risk.

Science.gov (United States)

Liu, Song; Liu, Yuwen; Zhang, Qin; Wu, Jiayu; Liang, Junbo; Yu, Shan; Wei, Gong-Hong; White, Kevin P; Wang, Xiaoyue

2017-10-23

Most cancer risk-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are noncoding and it is challenging to assess their functional impacts. To systematically identify the SNPs that affect gene expression by modulating activities of distal regulatory elements, we adapt the self-transcribing active regulatory region sequencing (STARR-seq) strategy, a high-throughput technique to functionally quantify enhancer activities. From 10,673 SNPs linked with 996 cancer risk-associated SNPs identified in previous GWAS studies, we identify 575 SNPs in the fragments that positively regulate gene expression, and 758 SNPs in the fragments with negative regulatory activities. Among them, 70 variants are regulatory variants for which the two alleles confer different regulatory activities. We analyze in depth two regulatory variants-breast cancer risk SNP rs11055880 and leukemia risk-associated SNP rs12142375-and demonstrate their endogenous regulatory activities on expression of ATF7IP and PDE4B genes, respectively, using a CRISPR-Cas9 approach. By identifying regulatory variants associated with cancer susceptibility and studying their molecular functions, we hope to help the interpretation of GWAS results and provide improved information for cancer risk assessment.

Integrated Public Education, Fertility and Human Capital

Science.gov (United States)

Azarnert, Leonid V.

2014-01-01

This paper analyzes the consequences of integration in public education. I show that the flight from the integrated multicultural public schools to private education increases private educational expenditures and, as a result, decreases fertility among more affluent parents whose children flee. In contrast, among less prosperous parents…

Influence of DC arc jets on flow fields analyzed by an integrated numerical model for a DC-RF hybrid plasma

International Nuclear Information System (INIS)

Seo, Jun Ho; Park, Jin Myung; Hong, Sang Hee

2008-01-01

The influence of DC arc jets on the flow fields in a hybrid plasma torch is numerically analyzed by an integrated direct current-radio frequency (DC-RF) plasma model based on magneto-hydrodynamic formulations. The calculated results reveal that the increase in DC arc gas flow rate raises the axial flow velocity along the central column of the DC-RF hybrid plasma together with the enhanced backflow streams in the peripheral wall region. The temperature profiles on the torch exit plane are little affected due to the reheating process of the central column by the combined RF plasma. Accordingly, the exit enthalpy emitted from the DC-RF hybrid torch can be concentrated to the central column of the plasma and controlled by adjusting the DC arc gas flow rate. The swirl in the sheath gas flow turns out to have the opposite effect on the DC arc gas flow rate. The swirling motion of the sheath gas can reduce the back flows near the induction tube wall as well as the axial velocities in the central column of the plasma. Accordingly, the swirl in the sheath gas flow can be used for the functional operation of the DC-RF hybrid plasma along with the DC arc gas flow rate to suppress the back flows at the wall region and to reduce the excessive interactions between the DC arc jet and the ambient RF plasmas. The effects of DC input current on the flow fields of hybrid plasma are similar to those of the DC arc gas flow rate, but the axial velocities for the higher current relatively quickly decay along the centerline. This is in contrast to the increase in the axial velocity remaining in proportion to the increase in the DC arc gas flow rate all the way up to the exit of the DC-RF hybrid plasma. Accordingly, the present integrated numerical analysis suggests that the hybrid plasma field profiles and the entrainment of ambient air from the torch exit are controllable by adjusting the DC arc gas flow rate, the DC input current and swirl in the sheath gas flow taking advantage of

Waste Management: An integrated modeling approach for analyzing change in NWC production processes

International Nuclear Information System (INIS)

Christensen, D.C.; Sohn, C.L.; Helm, T.M.; Farish, T.J.; Reid, R.A.

1991-01-01

A problem-driven, integrated modeling, decision-support framework has been conceptualized to aid a team of experts determine the set of evolving technologies that should receive additional developmental support. This conceptual framework utilizes a variety of decision aiding models including Flowsheeting, Analytical Hierarchy Process, Linear and Goal Programming, and Object-Oriented Discrete Event Simulation. A number of the technologies under consideration are strong candidates to overcome current plutonium processing problems so that effective technology will be available for implementation in Complex 21. Complex 21 is a participatory, inter-installation planning effort sponsored by US DOE to consolidate and revitalize the nuclear weapons complex facilities by the 21st century. A computer-based dynamic simulation model has been constructed that will allow testing of alternative combinations of developing technologies. The modeling of new configurations of technologies under a number of different operating conditions and material flow assumptions provides information needed for effective decision making for Complex 21. 4 figs

How Important is the Integration of Public Passenger Transport

Directory of Open Access Journals (Sweden)

Mrníková Michaela

2017-11-01

Full Text Available The significance of the issue of an effective mode of passenger transport is currently increasing. On the one hand, there is the increasing economic demand of public passenger transport, on the other hand, there is the growing traffic share of individual automobile transport. The objective of the paper is to analyze public passenger transport without mutual integration of individual transport systems resulting in the fact that it is not sufficiently able to compete with individual automobile transport. It is proposed the integration of different modes of public passenger transport as a way to increase the competitiveness of public passenger transport. Aim of this paper is to analyze the individual elements of integration systems and describe why integration of public passenger transport systems is needed.

Biomedical data integration in computational drug design and bioinformatics.

Science.gov (United States)

Seoane, Jose A; Aguiar-Pulido, Vanessa; Munteanu, Cristian R; Rivero, Daniel; Rabunal, Juan R; Dorado, Julian; Pazos, Alejandro

2013-03-01

In recent years, in the post genomic era, more and more data is being generated by biological high throughput technologies, such as proteomics and transcriptomics. This omics data can be very useful, but the real challenge is to analyze all this data, as a whole, after integrating it. Biomedical data integration enables making queries to different, heterogeneous and distributed biomedical data sources. Data integration solutions can be very useful not only in the context of drug design, but also in biomedical information retrieval, clinical diagnosis, system biology, etc. In this review, we analyze the most common approaches to biomedical data integration, such as federated databases, data warehousing, multi-agent systems and semantic technology, as well as the solutions developed using these approaches in the past few years.

Analyzing an Integrated Planning Approach Among Planning Scale and Sector a Case Study of Malang City's Vision as the City of Education

OpenAIRE

Amirudin, Akhmad; Fefta Wijaya, Andy; Yossomsakdi, Samrit

2014-01-01

Integrated planning is more needed by government today because of the complexity of problems and limited resources. Integrated planning can undertake the problems by giving comprehensive solution and provide how much resources are needed to reach the goal. Integrated planning approach is implied to provide better tools to guide actions towards the development of cities, improvement of human conditions, and ultimately a better urbanism. So the research focused on integrated planning in Malang ...

How powerful are summary-based methods for identifying expression-trait associations under different genetic architectures?

Science.gov (United States)

Veturi, Yogasudha; Ritchie, Marylyn D

2018-01-01

set. Subsequently, we integrated the GWAS summary statistics derived from the testing set with the weights (or eQTLs) derived from the training set to identify expression-trait associations using (a) TWAS-MP (b) TWAS-SMR (c) eQTL-based GWAS, or (d) standalone GWAS. Finally, we examined the power to detect functionally relevant genes using the different approaches under the considered simulation scenarios. In general, we observed great similarities among TWAS-MP methods although the Bayesian methods resulted in improved power in comparison to LASSO and elastic net as the trait architecture grew more complex while training sample sizes and expression heritability remained small. Finally, we observed high power under causality but very low to moderate power under pleiotropy.

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies

Science.gov (United States)

Manitz, Juliane; Burger, Patricia; Amos, Christopher I.; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike

2017-01-01

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility. PMID:28785300

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies.

Science.gov (United States)

Friedrichs, Stefanie; Manitz, Juliane; Burger, Patricia; Amos, Christopher I; Risch, Angela; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike; Hofner, Benjamin

2017-01-01

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.

GUESS-ing polygenic associations with multiple phenotypes using a GPU-based evolutionary stochastic search algorithm.

Directory of Open Access Journals (Sweden)

Leonardo Bottolo

Full Text Available Genome-wide association studies (GWAS yielded significant advances in defining the genetic architecture of complex traits and disease. Still, a major hurdle of GWAS is narrowing down multiple genetic associations to a few causal variants for functional studies. This becomes critical in multi-phenotype GWAS where detection and interpretability of complex SNP(s-trait(s associations are complicated by complex Linkage Disequilibrium patterns between SNPs and correlation between traits. Here we propose a computationally efficient algorithm (GUESS to explore complex genetic-association models and maximize genetic variant detection. We integrated our algorithm with a new Bayesian strategy for multi-phenotype analysis to identify the specific contribution of each SNP to different trait combinations and study genetic regulation of lipid metabolism in the Gutenberg Health Study (GHS. Despite the relatively small size of GHS (n  =  3,175, when compared with the largest published meta-GWAS (n > 100,000, GUESS recovered most of the major associations and was better at refining multi-trait associations than alternative methods. Amongst the new findings provided by GUESS, we revealed a strong association of SORT1 with TG-APOB and LIPC with TG-HDL phenotypic groups, which were overlooked in the larger meta-GWAS and not revealed by competing approaches, associations that we replicated in two independent cohorts. Moreover, we demonstrated the increased power of GUESS over alternative multi-phenotype approaches, both Bayesian and non-Bayesian, in a simulation study that mimics real-case scenarios. We showed that our parallel implementation based on Graphics Processing Units outperforms alternative multi-phenotype methods. Beyond multivariate modelling of multi-phenotypes, our Bayesian model employs a flexible hierarchical prior structure for genetic effects that adapts to any correlation structure of the predictors and increases the power to identify

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

Science.gov (United States)

Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; Wietze van der Veen, J P; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R; Santorico, Stephanie A; Spritz, Richard A

2016-11-01

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.

WINS. Market Simulation Tool for Facilitating Wind Energy Integration

Energy Technology Data Exchange (ETDEWEB)

Shahidehpour, Mohammad [Illinois Inst. of Technology, Chicago, IL (United States)

2012-10-30

results are often text-based demonstrations. WINS includes a powerful visualization tool and user interface capability for transmission analyses, planning, and assessment, which will be of great interest to power market participants, power system planners and operators, and state and federal regulatory entities; and (3) WINS can handle extended transmission models for wind integration studies. WINS models include limitations on transmission flow as well as bus voltage for analyzing power system states. The existing decision tools often consider transmission flow constraints (dc power flow) alone which could result in the over-utilization of existing resources when analyzing wind integration. WINS can be used to assist power market participants including transmission companies, independent system operators, power system operators in vertically integrated utilities, wind energy developers, and regulatory agencies to analyze economics, security, and reliability of various options for wind integration including transmission upgrades and the planning of new transmission facilities. WINS can also be used by industry for the offline training of reliability and operation personnel when analyzing wind integration uncertainties, identifying critical spots in power system operation, analyzing power system vulnerabilities, and providing credible decisions for examining operation and planning options for wind integration. Researches in this project on wind integration included (1) Development of WINS; (2) Transmission Congestion Analysis in the Eastern Interconnection; (3) Analysis of 2030 Large-Scale Wind Energy Integration in the Eastern Interconnection; (4) Large-scale Analysis of 2018 Wind Energy Integration in the Eastern U.S. Interconnection. The research resulted in 33 papers, 9 presentations, 9 PhD degrees, 4 MS degrees, and 7 awards. The education activities in this project on wind energy included (1) Wind Energy Training Facility Development; (2) Wind Energy Course

Analyzing Cyber-Physical Threats on Robotic Platforms.

Science.gov (United States)

Ahmad Yousef, Khalil M; AlMajali, Anas; Ghalyon, Salah Abu; Dweik, Waleed; Mohd, Bassam J

2018-05-21

Robots are increasingly involved in our daily lives. Fundamental to robots are the communication link (or stream) and the applications that connect the robots to their clients or users. Such communication link and applications are usually supported through client/server network connection. This networking system is amenable of being attacked and vulnerable to the security threats. Ensuring security and privacy for robotic platforms is thus critical, as failures and attacks could have devastating consequences. In this paper, we examine several cyber-physical security threats that are unique to the robotic platforms; specifically the communication link and the applications. Threats target integrity, availability and confidential security requirements of the robotic platforms, which use MobileEyes/arnlServer client/server applications. A robot attack tool (RAT) was developed to perform specific security attacks. An impact-oriented approach was adopted to analyze the assessment results of the attacks. Tests and experiments of attacks were conducted in simulation environment and physically on the robot. The simulation environment was based on MobileSim; a software tool for simulating, debugging and experimenting on MobileRobots/ActivMedia platforms and their environments. The robot platform PeopleBot TM was used for physical experiments. The analysis and testing results show that certain attacks were successful at breaching the robot security. Integrity attacks modified commands and manipulated the robot behavior. Availability attacks were able to cause Denial-of-Service (DoS) and the robot was not responsive to MobileEyes commands. Integrity and availability attacks caused sensitive information on the robot to be hijacked. To mitigate security threats, we provide possible mitigation techniques and suggestions to raise awareness of threats on the robotic platforms, especially when the robots are involved in critical missions or applications.

Analyzing Cyber-Physical Threats on Robotic Platforms

Directory of Open Access Journals (Sweden)

Khalil M. Ahmad Yousef

2018-05-01

Full Text Available Robots are increasingly involved in our daily lives. Fundamental to robots are the communication link (or stream and the applications that connect the robots to their clients or users. Such communication link and applications are usually supported through client/server network connection. This networking system is amenable of being attacked and vulnerable to the security threats. Ensuring security and privacy for robotic platforms is thus critical, as failures and attacks could have devastating consequences. In this paper, we examine several cyber-physical security threats that are unique to the robotic platforms; specifically the communication link and the applications. Threats target integrity, availability and confidential security requirements of the robotic platforms, which use MobileEyes/arnlServer client/server applications. A robot attack tool (RAT was developed to perform specific security attacks. An impact-oriented approach was adopted to analyze the assessment results of the attacks. Tests and experiments of attacks were conducted in simulation environment and physically on the robot. The simulation environment was based on MobileSim; a software tool for simulating, debugging and experimenting on MobileRobots/ActivMedia platforms and their environments. The robot platform PeopleBotTM was used for physical experiments. The analysis and testing results show that certain attacks were successful at breaching the robot security. Integrity attacks modified commands and manipulated the robot behavior. Availability attacks were able to cause Denial-of-Service (DoS and the robot was not responsive to MobileEyes commands. Integrity and availability attacks caused sensitive information on the robot to be hijacked. To mitigate security threats, we provide possible mitigation techniques and suggestions to raise awareness of threats on the robotic platforms, especially when the robots are involved in critical missions or applications.

Development of a Simulation Framework for Analyzing Security of Supply in Integrated Gas and Electric Power Systems

NARCIS (Netherlands)

Pambour, Kwabena Addo; Erdener, Burcin Cakir; Bolado-Lavin, Ricardo; Dijkema, Gerhard

2017-01-01

Gas and power networks are tightly coupled and interact with each other due to physically interconnected facilities. In an integrated gas and power network, a contingency observed in one system may cause iterative cascading failures, resulting in network wide disruptions. Therefore, understanding

An Integrated Solution for Performing Thermo-fluid Conjugate Analysis

Science.gov (United States)

Kornberg, Oren

2009-01-01

A method has been developed which integrates a fluid flow analyzer and a thermal analyzer to produce both steady state and transient results of 1-D, 2-D, and 3-D analysis models. The Generalized Fluid System Simulation Program (GFSSP) is a one dimensional, general purpose fluid analysis code which computes pressures and flow distributions in complex fluid networks. The MSC Systems Improved Numerical Differencing Analyzer (MSC.SINDA) is a one dimensional general purpose thermal analyzer that solves network representations of thermal systems. Both GFSSP and MSC.SINDA have graphical user interfaces which are used to build the respective model and prepare it for analysis. The SINDA/GFSSP Conjugate Integrator (SGCI) is a formbase graphical integration program used to set input parameters for the conjugate analyses and run the models. The contents of this paper describes SGCI and its thermo-fluids conjugate analysis techniques and capabilities by presenting results from some example models including the cryogenic chill down of a copper pipe, a bar between two walls in a fluid stream, and a solid plate creating a phase change in a flowing fluid.

Electron attachment analyzer

International Nuclear Information System (INIS)

Popp, P.; Grosse, H.J.; Leonhardt, J.; Mothes, S.; Oppermann, G.

1984-01-01

The invention concerns an electron attachment analyzer for detecting traces of electroaffine substances in electronegative gases, especially in air. The analyzer can be used for monitoring working places, e. g., in operating theatres. The analyzer consists of two electrodes inserted in a base frame of insulating material (quartz or ceramics) and a high-temperature resistant radiation source ( 85 Kr, 3 H, or 63 Ni)

System Dynamics Model for VMI&TPL Integrated Supply Chains

Directory of Open Access Journals (Sweden)

Guo Li

2013-01-01

Full Text Available This paper establishes VMI-APIOBPCS II model by extending VMI-APIOBPCS model from serial supply chain to distribution supply chain. Then TPL is introduced to this VMI distribution supply chain, and operational framework and process of VMI&TPL integrated supply chain are analyzed deeply. On this basis VMI-APIOBPCS II model is then changed to VMI&TPL-APIOBPCS model and VMI&TPL integrated operation mode is simulated. Finally, compared with VMI-APIOBPCS model, the TPL’s important role of goods consolidation and risk sharing in VMI&TPL integrated supply chain is analyzed in detail from the aspects of bullwhip effect, inventory level, service level, and so on.

Differentiating between precursor and control variables when analyzing reasoned action theories.

Science.gov (United States)

Hennessy, Michael; Bleakley, Amy; Fishbein, Martin; Brown, Larry; Diclemente, Ralph; Romer, Daniel; Valois, Robert; Vanable, Peter A; Carey, Michael P; Salazar, Laura

2010-02-01

This paper highlights the distinction between precursor and control variables in the context of reasoned action theory. Here the theory is combined with structural equation modeling to demonstrate how age and past sexual behavior should be situated in a reasoned action analysis. A two wave longitudinal survey sample of African-American adolescents is analyzed where the target behavior is having vaginal sex. Results differ when age and past behavior are used as control variables and when they are correctly used as precursors. Because control variables do not appear in any form of reasoned action theory, this approach to including background variables is not correct when analyzing data sets based on the theoretical axioms of the Theory of Reasoned Action, the Theory of Planned Behavior, or the Integrative Model.

Development of system integration technology for integral reactor

Energy Technology Data Exchange (ETDEWEB)

Chang, Moon Hee; Kang, D. J.; Kim, K. K. and others

1999-03-01

The objective of this report is to integrate the conceptual design of an integral reactor, SMART producing thermal energy of 330 MW, which will be utilized to supply energy for seawater desalination and small-scale power generation. This project also aims to develop system integration technology for effective design of the reactor. For the conceptual design of SMART, preliminary design requirements including the top-tier requirements and design bases were evaluated and established. Furthermore, in the view of the application of codes and standards to the SMART design, existing laws, codes and standards were analyzed and evaluated with respect to its applicability. As a part of this evaluation, directions and guidelines were proposed for the development of new codes and standards which shall be applied to the SMART design. Regarding the integration of SMART conceptual designs, major design activities and interfaces between design departments were established and coordinated through the design process. For the effective management of all design schedules, a work performance evaluation system was developed and applied to the design process. As the results of this activity, an integrated output of SMART designs was produced. Two additional scopes performed in this project include the preliminary economic analysis on the SMART utilization for seawater desalination, and the planning of verification tests for technology implemented into SMART and establishing development plan of the computer codes to be used for SMART design in the next phase. The technical cooperation with foreign country and international organization for securing technologies for integral reactor design and its application was coordinated and managed through this project. (author)

A deletion in the Hermansky-Pudlak syndrome 4 (Hps4) gene appears to be responsible for albinism in channel catfish.

Science.gov (United States)

Li, Yueru; Geng, Xin; Bao, Lisui; Elaswad, Ahmed; Huggins, Kevin W; Dunham, Rex; Liu, Zhanjiang

2017-06-01

Albinism is caused by a series of genetic abnormalities leading to reduction of melanin production. Albinism is quite frequent in catfish, but the causative gene and the molecular basis were unknown. In this study, we conducted a genome-wide association study (GWAS) using the 250 K SNP array. The GWAS analysis allowed mapping of the albino phenotype in the Hermansky-Pudlak syndrome 4 (Hps4) gene, which is known to be involved in melanosome biosynthesis. Sequencing analysis revealed that a 99-bp deletion was present in all analyzed albino catfish at the intron 2 and exon 3 junction. This deletion led to the skipping of the entire exon 3 which was confirmed by RT-PCR. Therefore, Hps4 was determined to be the candidate gene of the catfish albinism.

Association Between Variants of PRDM1 and NDP52 and Crohn's Disease, Based on Exome Sequencing and Functional Studies

DEFF Research Database (Denmark)

Ellinghaus, David; Zhang, Hu; Zeissig, Sebastian

2013-01-01

BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through...... detailed sequencing, genetic association, expression, and functional studies. METHODS: We sequenced whole exomes of 42 unrelated subjects with CD and 5 healthy subjects (controls) and then filtered single nucleotide variants by incorporating association results from meta-analyses of CD GWAS and in silico...... mutation effect prediction algorithms. We then genotyped 9348 subjects with CD, 2868 subjects with ulcerative colitis, and 14,567 control subjects and associated variants analyzed in functional studies using materials from subjects and controls and in vitro model systems. RESULTS: We identified rare...

Genetic susceptibility to feline infectious peritonitis in Birman cats.

Science.gov (United States)

Golovko, Lyudmila; Lyons, Leslie A; Liu, Hongwei; Sørensen, Anne; Wehnert, Suzanne; Pedersen, Niels C

2013-07-01

Genetic factors are presumed to influence the incidence of feline infectious peritonitis (FIP), especially among pedigreed cats. However, proof for the existence of such factors has been limited and mainly anecdotal. Therefore, we sought evidence for genetic susceptibility to FIP using feline high density single nucleotide polymorphism (SNP) arrays in a genome-wide association study (GWAS). Birman cats were chosen for GWAS because they are highly inbred and suffer a high incidence of FIP. DNA from 38 Birman cats that died of FIP and 161 healthy cats from breeders in Denmark and USA were selected for genotyping using 63K SNPs distributed across the feline genome. Danish and American Birman cats were closely related and the populations were therefore combined and analyzed in two manners: (1) all cases (FIP) vs. all controls (healthy) regardless of age, and (2) cases 1½ years of age and younger (most susceptible) vs. controls 2 years of age and older (most resistant). GWAS of the second cohort was most productive in identifying significant genome-wide associations between case and control cats. Four peaks of association with FIP susceptibility were identified, with two being identified on both analyses. Five candidate genes ELMO1, RRAGA, TNFSF10, ERAP1 and ERAP2, all relevant to what is known about FIP virus pathogenesis, were identified but no single association was fully concordant with the disease phenotype. Difficulties in doing GWAS in cats and interrogating complex genetic traits were discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Analyzing the Drivers of Advanced Sustainable Manufacturing System Using AHP Approach

Directory of Open Access Journals (Sweden)

K. Madan Shankar

2016-08-01

Full Text Available A number of current manufacturing sectors are striving hard to introduce innovative long-term strategies into their operations. As a result, many scholarly studies have found it fruitful to investigate advanced manufacturing strategies such as agile, computer-integrated, and cellular manufacturing. Through the example of downstream cases, manufacturing sectors have learned that financial benefits garnered through automated technologies cannot be counted on as a sole measure to ensure their success in today’s competitive and fluctuating marketplaces. The objective of this study is to integrate those advanced techniques with sustainable operations, to promote advanced sustainable manufacturing so those manufacturing sectors can thrive even in uncertain markets. To establish this connection, this study analyzes the drivers of advanced sustainable manufacturing through a proposed framework validated through a case study in India. Common drivers are collected from the literature, calibrated with opinions from experts, and analyzed through an analytical hierarchy process (AHP, which is a multi-criteria decision making (MCDM approach. This study reveals that quality is the primary driver that pressures manufacturing sectors to adopt advanced sustainable manufacturing. Manufacturers can easily note the top ranked driver and adopt it to soundly implement advanced sustainable manufacturing. In addition, some key future scopes are explored along with possible recommendations for effective implementation of advanced sustainable manufacturing systems.

Contribution of genome-wide association studies to scientific research: a pragmatic approach to evaluate their impact.

Directory of Open Access Journals (Sweden)

Vito A G Ricigliano

Full Text Available The factual value of genome-wide association studies (GWAS for the understanding of multifactorial diseases is a matter of intense debate. Practical consequences for the development of more effective therapies do not seem to be around the corner. Here we propose a pragmatic and objective evaluation of how much new biology is arising from these studies, with particular attention to the information that can help prioritize therapeutic targets. We chose multiple sclerosis (MS as a paradigm disease and assumed that, in pre-GWAS candidate-gene studies, the knowledge behind the choice of each gene reflected the understanding of the disease prior to the advent of GWAS. Importantly, this knowledge was based mainly on non-genetic, phenotypic grounds. We performed single-gene and pathway-oriented comparisons of old and new knowledge in MS by confronting an unbiased list of candidate genes in pre-GWAS association studies with those genes exceeding the genome-wide significance threshold in GWAS published from 2007 on. At the single gene level, the majority (94 out of 125 of GWAS-discovered variants had never been contemplated as plausible candidates in pre-GWAS association studies. The 31 genes that were present in both pre- and post-GWAS lists may be of particular interest in that they represent disease-associated variants whose pathogenetic relevance is supported at the phenotypic level (i.e. the phenotypic information that steered their selection as candidate genes in pre-GWAS association studies. As such they represent attractive therapeutic targets. Interestingly, our analysis shows that some of these variants are targets of pharmacologically active compounds, including drugs that are already registered for human use. Compared with the above single-gene analysis, at the pathway level GWAS results appear more coherent with previous knowledge, reinforcing some of the current views on MS pathogenesis and related therapeutic research. This study presents a

Hospital-physician collaboration: landscape of economic integration and impact on clinical integration.

Science.gov (United States)

Burns, Lawton Robert; Muller, Ralph W

2008-09-01

Hospital-physician relationships (HPRs) are an important area of academic research, given their impact on hospitals' financial success. HPRs also are at the center of several federal policy proposals such as gain sharing, bundled payments, and pay-for-performance (P4P). This article analyzes the HPRs that focus on the economic integration of hospitals and physicians and the goals that HPRs are designed to achieve. It then reviews the literature on the impact of HPRs on cost, quality, and clinical integration. The goals of the two parties in HPRs overlap only partly, and their primary aim is not reducing cost or improving quality. The evidence base for the impact of many models of economic integration is either weak or nonexistent, with only a few models of economic integration having robust effects. The relationship between economic and clinical integration also is weak and inconsistent. There are several possible reasons for this weak linkage and many barriers to further integration between hospitals and physicians. Successful HPRs may require better financial conditions for physicians, internal changes to clinical operations, application of behavioral skills to the management of HPRs, changes in how providers are paid, and systemic changes encompassing several types of integration simultaneously.

An innovative procedure of genome-wide association analysis fits studies on germplasm population and plant breeding.

Science.gov (United States)

He, Jianbo; Meng, Shan; Zhao, Tuanjie; Xing, Guangnan; Yang, Shouping; Li, Yan; Guan, Rongzhan; Lu, Jiangjie; Wang, Yufeng; Xia, Qiuju; Yang, Bing; Gai, Junyi

2017-11-01

The innovative RTM-GWAS procedure provides a relatively thorough detection of QTL and their multiple alleles for germplasm population characterization, gene network identification, and genomic selection strategy innovation in plant breeding. The previous genome-wide association studies (GWAS) have been concentrated on finding a handful of major quantitative trait loci (QTL), but plant breeders are interested in revealing the whole-genome QTL-allele constitution in breeding materials/germplasm (in which tremendous historical allelic variation has been accumulated) for genome-wide improvement. To match this requirement, two innovations were suggested for GWAS: first grouping tightly linked sequential SNPs into linkage disequilibrium blocks (SNPLDBs) to form markers with multi-allelic haplotypes, and second utilizing two-stage association analysis for QTL identification, where the markers were preselected by single-locus model followed by multi-locus multi-allele model stepwise regression. Our proposed GWAS procedure is characterized as a novel restricted two-stage multi-locus multi-allele GWAS (RTM-GWAS, https://github.com/njau-sri/rtm-gwas ). The Chinese soybean germplasm population (CSGP) composed of 1024 accessions with 36,952 SNPLDBs (generated from 145,558 SNPs, with reduced linkage disequilibrium decay distance) was used to demonstrate the power and efficiency of RTM-GWAS. Using the CSGP marker information, simulation studies demonstrated that RTM-GWAS achieved the highest QTL detection power and efficiency compared with the previous procedures, especially under large sample size and high trait heritability conditions. A relatively thorough detection of QTL with their multiple alleles was achieved by RTM-GWAS compared with the linear mixed model method on 100-seed weight in CSGP. A QTL-allele matrix (402 alleles of 139 QTL × 1024 accessions) was established as a compact form of the population genetic constitution. The 100-seed weight QTL-allele matrix was

Integrated system for testing, investigation and analyzing of nuclear materials, TIAMAT-N

International Nuclear Information System (INIS)

Roth, Maria; Pitigoi, Vasile; Ionescu, Viorel; Constantin, Mihai; Babusi, Octavian

2010-01-01

Full text: The paper presents the results obtained in the framework of the project carried out as part of the National Program PNII, Modulus Capacities I, Competition 2008, concerning the performances of the Testing, Investigation and Analyzing System, used in the nuclear materials field. The system will ensure the evaluation of the nuclear structures, including the thermo-mechanical behaviour in connection with the physical-chemical analysis, microstructure and nondestructive investigations. Using last generation equipment and its interconnection to an IT system of monitoring, acquisition and data storage, it aims to implement the investigation methodologies applied in the nuclear area, to harmonize working practices according to the standards and procedures at European and international level. In addition, the system helps to develop a database, which will be continuously updated, with the materials investigated in the different types of tests and specific analyses. The project achievements will be capitalized at national level, sustaining the R and D studies of the National Nuclear Plan but also in the European and International Programs, including EURATOM Projects and Networks of Excellence, collaboration with AECL and COG Canada and participation in the AIEA Program. (authors)

Integrative gene network construction to analyze cancer recurrence using semi-supervised learning.

Science.gov (United States)

Park, Chihyun; Ahn, Jaegyoon; Kim, Hyunjin; Park, Sanghyun

2014-01-01

The prognosis of cancer recurrence is an important research area in bioinformatics and is challenging due to the small sample sizes compared to the vast number of genes. There have been several attempts to predict cancer recurrence. Most studies employed a supervised approach, which uses only a few labeled samples. Semi-supervised learning can be a great alternative to solve this problem. There have been few attempts based on manifold assumptions to reveal the detailed roles of identified cancer genes in recurrence. In order to predict cancer recurrence, we proposed a novel semi-supervised learning algorithm based on a graph regularization approach. We transformed the gene expression data into a graph structure for semi-supervised learning and integrated protein interaction data with the gene expression data to select functionally-related gene pairs. Then, we predicted the recurrence of cancer by applying a regularization approach to the constructed graph containing both labeled and unlabeled nodes. The average improvement rate of accuracy for three different cancer datasets was 24.9% compared to existing supervised and semi-supervised methods. We performed functional enrichment on the gene networks used for learning. We identified that those gene networks are significantly associated with cancer-recurrence-related biological functions. Our algorithm was developed with standard C++ and is available in Linux and MS Windows formats in the STL library. The executable program is freely available at: http://embio.yonsei.ac.kr/~Park/ssl.php.

Integrative gene network construction to analyze cancer recurrence using semi-supervised learning.

Directory of Open Access Journals (Sweden)

Chihyun Park

Full Text Available BACKGROUND: The prognosis of cancer recurrence is an important research area in bioinformatics and is challenging due to the small sample sizes compared to the vast number of genes. There have been several attempts to predict cancer recurrence. Most studies employed a supervised approach, which uses only a few labeled samples. Semi-supervised learning can be a great alternative to solve this problem. There have been few attempts based on manifold assumptions to reveal the detailed roles of identified cancer genes in recurrence. RESULTS: In order to predict cancer recurrence, we proposed a novel semi-supervised learning algorithm based on a graph regularization approach. We transformed the gene expression data into a graph structure for semi-supervised learning and integrated protein interaction data with the gene expression data to select functionally-related gene pairs. Then, we predicted the recurrence of cancer by applying a regularization approach to the constructed graph containing both labeled and unlabeled nodes. CONCLUSIONS: The average improvement rate of accuracy for three different cancer datasets was 24.9% compared to existing supervised and semi-supervised methods. We performed functional enrichment on the gene networks used for learning. We identified that those gene networks are significantly associated with cancer-recurrence-related biological functions. Our algorithm was developed with standard C++ and is available in Linux and MS Windows formats in the STL library. The executable program is freely available at: http://embio.yonsei.ac.kr/~Park/ssl.php.

Integration of Multilocus Genetic Risk into the Default Mode Network Longitudinal Trajectory during the Alzheimer's Disease Process.

Science.gov (United States)

Su, Fan; Shu, Hao; Ye, Qing; Xie, Chunming; Yuan, Baoyu; Zhang, Zhijun; Bai, Feng

2017-01-01

The aim of the study was to investigate the cognitive significance of the changes in default mode network (DMN) during the process of Alzheimer's disease (AD) and the genetic basis that drives the alteration. Eighty-seven subjects with mild cognitive impairment (MCI) and 131 healthy controls (HC) were employed at baseline, and they had the genetic risk scores (GRS) based on the GWAS-validated AD-related top loci. Eleven MCIs who converted to AD (c-MCIs), 32 subjects who remained stable (nc-MCIs), and 56 HCs participated in the follow-up analyses after an average of 35 months. Decreased functional connectivity (FC) within temporal cortex was identified for MCIs at baseline, which was partially determined by the GRS; moreover, compensations may occur within the frontal-parietal brain to maintain relatively intact cognition. During the follow-ups, c-MCIs exhibited more FC declines within the prefrontal-parietal lobes and parahippocampal gyrus/hippocampus than the HCs and nc-MCIs. The GRS did not significantly vary among the three groups, whereas associations were identified at risky alleles and FC declines in all AD spectra. Interestingly, the influence of APOEɛ4 varied as the disease progressed; APOEɛ4 was associated with longitudinal FC decreases only for HCs in the single variance-based analyses and deteriorated DMN integration in nc-MCIs by combining the effects of other loci. However, the GRS without APOEɛ4 predicted FC decline for converters. It is suggested that the integration of multilocus genetic risk predicted the longitudinal trajectory of DMN and may be used as a clinical strategy to track AD progression.

Chapter 10: Mining genome-wide genetic markers.

Directory of Open Access Journals (Sweden)

Xiang Zhang

Full Text Available Genome-wide association study (GWAS aims to discover genetic factors underlying phenotypic traits. The large number of genetic factors poses both computational and statistical challenges. Various computational approaches have been developed for large scale GWAS. In this chapter, we will discuss several widely used computational approaches in GWAS. The following topics will be covered: (1 An introduction to the background of GWAS. (2 The existing computational approaches that are widely used in GWAS. This will cover single-locus, epistasis detection, and machine learning methods that have been recently developed in biology, statistic, and computer science communities. This part will be the main focus of this chapter. (3 The limitations of current approaches and future directions.

Genomewide Association Studies: History, Rationale, and Prospects for Psychiatric Disorders

NARCIS (Netherlands)

Cichon, S.; Craddock, N.; Daly, M.J.; Faraone, S.V.; Gejman, P.V.; Kelsoe, J.; Lehner, T.; Levinson, D.F.; Moran, A.P.; Sklar, P.; Sullivan, P.F.; Boomsma, D.I.; de Geus, E.J.C.; Posthuma, D.; Willemsen, G.

2009-01-01

Objective: The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. Method: A literature review was carried out, power and other issues

Genomewide association studies: history, rationale, and prospects for psychiatric disorders.

NARCIS (Netherlands)

Franke, B.; Buitelaar, J.K.; Cichon, S.; Craddock, N.; Daly, M.; Faraone, S.V.; Gejman, P.V.; Kelsoe, J.; Lehner, T.; Levinson, D.F.; Moran, A.; Sklar, P.; Sullivan, P.F.

2009-01-01

OBJECTIVE: The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. METHOD: A literature review was carried out, power and other issues

Analyzing rare diseases terms in biomedical terminologies

Directory of Open Access Journals (Sweden)

Erika Pasceri

2012-03-01

Full Text Available Rare disease patients too often face common problems, including the lack of access to correct diagnosis, lack of quality information on the disease, lack of scientific knowledge of the disease, inequities and difficulties in access to treatment and care. These things could be changed by implementing a comprehensive approach to rare diseases, increasing international cooperation in scientific research, by gaining and sharing scientific knowledge about and by developing tools for extracting and sharing knowledge. A significant aspect to analyze is the organization of knowledge in the biomedical field for the proper management and recovery of health information. For these purposes, the sources needed have been acquired from the Office of Rare Diseases Research, the National Organization of Rare Disorders and Orphanet, organizations that provide information to patients and physicians and facilitate the exchange of information among different actors involved in this field. The present paper shows the representation of rare diseases terms in biomedical terminologies such as MeSH, ICD-10, SNOMED CT and OMIM, leveraging the fact that these terminologies are integrated in the UMLS. At the first level, it was analyzed the overlap among sources and at a second level, the presence of rare diseases terms in target sources included in UMLS, working at the term and concept level. We found that MeSH has the best representation of rare diseases terms.

Novel genetic loci associated with hippocampal volume

OpenAIRE

Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivieres, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf

2017-01-01

International audience; The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal ...

An integrative approach to ortholog prediction for disease-focused and other functional studies

Directory of Open Access Journals (Sweden)

Perrimon Norbert

2011-08-01

Full Text Available Abstract Background Mapping of orthologous genes among species serves an important role in functional genomics by allowing researchers to develop hypotheses about gene function in one species based on what is known about the functions of orthologs in other species. Several tools for predicting orthologous gene relationships are available. However, these tools can give different results and identification of predicted orthologs is not always straightforward. Results We report a simple but effective tool, the Drosophila RNAi Screening Center Integrative Ortholog Prediction Tool (DIOPT; http://www.flyrnai.org/diopt, for rapid identification of orthologs. DIOPT integrates existing approaches, facilitating rapid identification of orthologs among human, mouse, zebrafish, C. elegans, Drosophila, and S. cerevisiae. As compared to individual tools, DIOPT shows increased sensitivity with only a modest decrease in specificity. Moreover, the flexibility built into the DIOPT graphical user interface allows researchers with different goals to appropriately 'cast a wide net' or limit results to highest confidence predictions. DIOPT also displays protein and domain alignments, including percent amino acid identity, for predicted ortholog pairs. This helps users identify the most appropriate matches among multiple possible orthologs. To facilitate using model organisms for functional analysis of human disease-associated genes, we used DIOPT to predict high-confidence orthologs of disease genes in Online Mendelian Inheritance in Man (OMIM and genes in genome-wide association study (GWAS data sets. The results are accessible through the DIOPT diseases and traits query tool (DIOPT-DIST; http://www.flyrnai.org/diopt-dist. Conclusions DIOPT and DIOPT-DIST are useful resources for researchers working with model organisms, especially those who are interested in exploiting model organisms such as Drosophila to study the functions of human disease genes.

Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors

DEFF Research Database (Denmark)

Melin, Beatrice S; Barnholtz-Sloan, Jill S; Wrensch, Margaret R

2017-01-01

Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified fi...

SDCCAG8 obesity alleles and reduced weight loss after a lifestyle intervention in overweight children and adolescents

DEFF Research Database (Denmark)

Scherag, André; Kleber, Michaela; Boes, Tanja

2012-01-01

-analysis of GWAS reported five genomic loci near or in the genes FTO, MC4R, TMEM18, SDCCAG8, TNKS/MSRA that were associated with obesity in children and adolescents. Here, we analyzed the effect of the 10 SNPs representative of the five loci on measures of weight loss and cardiometabolic risk after a 1-year...

Identification of a regulatory variant that binds FOXA1 and FOXA2 at the CDC123/CAMK1D type 2 diabetes GWAS locus.

Directory of Open Access Journals (Sweden)

Marie P Fogarty

2014-09-01

Full Text Available Many of the type 2 diabetes loci identified through genome-wide association studies localize to non-protein-coding intronic and intergenic regions and likely contain variants that regulate gene transcription. The CDC123/CAMK1D type 2 diabetes association signal on chromosome 10 spans an intergenic region between CDC123 and CAMK1D and also overlaps the CDC123 3'UTR. To gain insight into the molecular mechanisms underlying the association signal, we used open chromatin, histone modifications and transcription factor ChIP-seq data sets from type 2 diabetes-relevant cell types to identify SNPs overlapping predicted regulatory regions. Two regions containing type 2 diabetes-associated variants were tested for enhancer activity using luciferase reporter assays. One SNP, rs11257655, displayed allelic differences in transcriptional enhancer activity in 832/13 and MIN6 insulinoma cells as well as in human HepG2 hepatocellular carcinoma cells. The rs11257655 risk allele T showed greater transcriptional activity than the non-risk allele C in all cell types tested. Using electromobility shift and supershift assays we demonstrated that the rs11257655 risk allele showed allele-specific binding to FOXA1 and FOXA2. We validated FOXA1 and FOXA2 enrichment at the rs11257655 risk allele using allele-specific ChIP in human islets. These results suggest that rs11257655 affects transcriptional activity through altered binding of a protein complex that includes FOXA1 and FOXA2, providing a potential molecular mechanism at this GWAS locus.

Analyzing Clickstreams

DEFF Research Database (Denmark)

Andersen, Jesper; Giversen, Anders; Jensen, Allan H.

in modern enterprises. In the data warehousing pproach, selected information is extracted in advance and stored in a repository. This approach is used because of its high performance. However, in many situations a logical (rather than physical) integration of data is preferable. Previous web-based data......On-Line Analytical Processing (OLAP) enables analysts to gain insight into data through fast and interactive access to a variety of possible views on information, organized in a dimensional model. The demand for data integration is rapidly becoming larger as more and more information sources appear....... Extensible Markup Language (XML) is fast becoming the new standard for data representation and exchange on the World Wide Web. The rapid emergence of XML data on the web, e.g., business-to-business (B2B) ecommerce, is making it necessary for OLAP and other data analysis tools to handleXML data as well...

Extended integration the key to future productivity leap

International Nuclear Information System (INIS)

Peebler, R.P.

1996-01-01

This paper reviews the economic benefits and trends in integration of information technology. The paper assesses the historical technologies of simple structure interpretation to complex three- and four-dimensional simulation. It presents historical methods of collecting and analyzing data and a hierarchy of integration that has developed. It shows the economic benefits of integrating computer data bases with multidisciplinary teams to engineer and monitor oil and gas depletion

Research on the Method of Big Data Collecting, Storing and Analyzing of Tongue Diagnosis System

Science.gov (United States)

Chen, Xiaowei; Wu, Qingfeng

2018-03-01

This paper analyzes the contents of the clinical data of tongue diagnosis of TCM (Traditional Chinese Medicine), and puts forward a method to collect, store and analyze the clinical data of tongue diagnosis. Under the guidance of TCM theory of syndrome differentiation and treatment, this method combines with Hadoop, which is a distributed computing system with strong expansibility, and integrates the functions of analysis and conversion of big data of clinic tongue diagnosis. At the same time, the consistency, scalability and security of big data in tongue diagnosis are realized.

Nuclear Plant Analyzer desktop workstation: An integrated interactive simulation, visualization and analysis tool

International Nuclear Information System (INIS)

Beelman, R.J.

1991-01-01

The advanced, best-estimate, reactor thermal-hydraulic codes were originally developed as mainframe computer applications because of speed, precision, memory and mass storage requirements. However, the productivity of numerical reactor safety analysts has historically been hampered by mainframe dependence due to limited mainframe CPU allocation, accessibility and availability, poor mainframe job throughput, and delays in obtaining and difficulty comprehending printed numerical results. The Nuclear Plant Analyzer (NPA) was originally developed as a mainframe computer-graphics aid for reactor safety analysts in addressing the latter consideration. Rapid advances in microcomputer technology have since enabled the installation and execution of these reactor safety codes on desktop computers thereby eliminating mainframe dependence. The need for a complementary desktop graphics display generation and presentation capability, coupled with the need for software standardization and portability, has motivated the redesign of the NPA as a UNIX/X-Windows application suitable for both mainframe and microcomputer

Possibility of Integrated Data Mining of Clinical Data

Directory of Open Access Journals (Sweden)

Akinori Abe

2007-03-01

Full Text Available In this paper, we introduce integrated data mining. Because of recent rapid progress in medical science as well as clinical diagnosis and treatment, integrated and cooperative research among medical researchers, biology, engineering, cultural science, and sociology is required. Therefore, we propose a framework called Cyber Integrated Medical Infrastructure (CIMI. Within this framework, we can deal with various types of data and consequently need to integrate those data prior to analysis. In this study, for medical science, we analyze the features and relationships among various types of data and show the possibility of integrated data mining.

Genome Wide Association Studies (GWAS Identify QTL on SSC2 and SSC17 Affecting Loin Peak Shear Force in Crossbred Commercial Pigs.

Directory of Open Access Journals (Sweden)

Chunyan Zhang

Full Text Available Of all the meat quality traits, tenderness is considered the most important with regard to eating quality and market value. In this study we have utilised genome wide association studies (GWAS for peak shear force (PSF of loin muscle as a measure of tenderness for 1,976 crossbred commercial pigs, genotyped for 42,721 informative SNPs using the Illumina PorcineSNP60 Beadchip. Four 1 Mb genomic regions, three on SSC2 (at 4 Mb, 5 Mb and 109 Mb and one on SSC17 (at 20 Mb, were detected which collectively explained about 15.30% and 3.07% of the total genetic and phenotypic variance for PSF respectively. Markers ASGA0008566, ASGA0008695, DRGA0003285 and ASGA0075615 in the four regions were strongly associated with the effects. Analysis of the reference genome sequence in the region with the most important SNPs for SSC2_5 identified FRMD8, SLC25A45 and LTBP3 as potential candidate genes for meat tenderness on the basis of functional annotation of these genes. The region SSC2_109 was close to a previously reported candidate gene CAST; however, the very weak LD between DRGA0003285 (the best marker representing region SSC2_109 and CAST indicated the potential for additional genes which are distinct from, or interact with, CAST to affect meat tenderness. Limited information of known genes in regions SSC2_109 and SSC17_20 restricts further analysis. Re-sequencing of these regions for informative animals may help to resolve the molecular architecture and identify new candidate genes and causative mutations affecting this trait. These findings contribute significantly to our knowledge of the genomic regions affecting pork shear force and will potentially lead to new insights into the molecular mechanisms regulating meat tenderness.

IT Consultants in Acquisition IT Integration

DEFF Research Database (Denmark)

Henningsson, Stefan; Øhrgaard, Christian

2016-01-01

strategic IT initiatives and how companies can draw effectively on their services. The paper investigates the use of consultants in relation to one type of major strategic IT initiative: acquisition IT integration. Acquisition IT integration, which is the integration of the acquirer’s and target......’s IT following a corporate acquisition, presents a difficult but crucial IT challenge for the many acquiring organizations. Through a comparative case study of four acquirers, theoretically grounded in the resource-based view of the firm, it is analyzed how acquirers draw on external consultants to realize...... acquisition IT integration. Two complementary and two supplementary roles consultants assume in these projects are identified. Additionally, three characteristics of the acquisition IT integration strategy are identified that influence how the acquirers assign different roles to IT consultants. The resulting...

Milestones of European Integration: Which matters most for Export Openness?

DEFF Research Database (Denmark)

Hiller, Sanne; Kruse, Robinson

The European integration process has removed barriers to trade within Europe. We analyze which integration step has most profoundly influenced the trending behavior of export openness. We endogenously determine the single most decisive break in the trend, account for strong cross-country heteroge......The European integration process has removed barriers to trade within Europe. We analyze which integration step has most profoundly influenced the trending behavior of export openness. We endogenously determine the single most decisive break in the trend, account for strong cross...... and the Netherlands are the Euro introduction, the Maastricht Treaty, the Exchange Rate Mechanism I and the merge of EFTA and EEC to the European Economic Area, respectively. Our empirical results have important implications for inner-European economic development, as export openness feeds back into growth...

Nature vs. nurture in human sociality: multi-level genomic analyses of social conformity.

Science.gov (United States)

Chen, Biqing; Zhu, Zijian; Wang, Yingying; Ding, Xiaohu; Guo, Xiaobo; He, Mingguang; Fang, Wan; Zhou, Qin; Zhou, Shanbi; Lei, Han; Huang, Ailong; Chen, Tingmei; Ni, Dongsheng; Gu, Yuping; Liu, Jianing; Rao, Yi

2018-05-01

Social conformity is fundamental to human societies and has been studied for more than six decades, but our understanding of its mechanisms remains limited. Individual differences in conformity have been attributed to social and cultural environmental influences, but not to genes. Here we demonstrate a genetic contribution to conformity after analyzing 1,140 twins and single-nucleotide polymorphism (SNP)-based studies of 2,130 young adults. A two-step genome-wide association study (GWAS) revealed replicable associations in 9 genomic loci, and a meta-analysis of three GWAS with a sample size of ~2,600 further confirmed one locus, corresponding to the NAV3 (Neuron Navigator 3) gene which encodes a protein important for axon outgrowth and guidance. Further multi-level (haplotype, gene, pathway) GWAS strongly associated genes including NAV3, PTPRD (protein tyrosine phosphatase receptor type D), ARL10 (ADP ribosylation factor-like GTPase 10), and CTNND2 (catenin delta 2), with conformity. Magnetic resonance imaging of 64 subjects shows correlation of activation or structural features of brain regions with the SNPs of these genes, supporting their functional significance. Our results suggest potential moderate genetic influence on conformity, implicate several specific genetic elements in conformity and will facilitate further research on cellular and molecular mechanisms underlying human conformity.

Post-Acquisition IT Integration

DEFF Research Database (Denmark)

Henningsson, Stefan; Yetton, Philip

2013-01-01

The extant research on post-acquisition IT integration analyzes how acquirers realize IT-based value in individual acquisitions. However, serial acquirers make 60% of acquisitions. These acquisitions are not isolated events, but are components in growth-by-acquisition programs. To explain how...... serial acquirers realize IT-based value, we develop three propositions on the sequential effects on post-acquisition IT integration in acquisition programs. Their combined explanation is that serial acquirers must have a growth-by-acquisition strategy that includes the capability to improve...... IT integration capabilities, to sustain high alignment across acquisitions and to maintain a scalable IT infrastructure with a flat or decreasing cost structure. We begin the process of validating the three propositions by investigating a longitudinal case study of a growth-by-acquisition program....

The transformation techniques in path integration

International Nuclear Information System (INIS)

Inomata, A.

1989-01-01

In this paper general remarks are made concerning the time transformation techniques in path integration and their implementations. Time transformations may be divided into two classes: global (integrable) time transformations and local (nonintegrable) time transformations. Although a brief account of global time transformations is given, attention is focused on local transformations. First, time transformations in the classical Kepler problem are reviewed. Then, problems encountered in implementing a local time transformation in quantum mechanics are analyzed. A several propositions pertinent to the implementation of local time transformations, particularly basic to the local time rescaling trick in a discretized path integral, are presented

Development and Operation of Dual-Mode Analyzers for Wireless Power Consortium/Power Matters Alliance Wireless Power Systems.

Science.gov (United States)

Um, Keehong

2016-05-01

We have designed a protocol analyzer to be used in wireless power systems and analyzed the operation of wireless chargers defined by standards of Qi of Wireless Power Consortium (WPC) and Power Matters Alliance (PMA) protocols. The integrated circuit (IC, or microchip) developed so far for wireless power transmission is not easily adopted by chargers for specific purposes. A device for measuring the performance of test equipment currently available is required to transform and expand the types of protocol. Since a protocol analyzer with these functions is required, we have developed a device that can analyze the two protocols of WPC and PMA at the same time. As a result of our research, we present a dual-mode system that can analyze the protocols of both WPC and PMA.

Miniature mass analyzer

CERN Document Server

Cuna, C; Lupsa, N; Cuna, S; Tuzson, B

2003-01-01

The paper presents the concept of different mass analyzers that were specifically designed as small dimension instruments able to detect with great sensitivity and accuracy the main environmental pollutants. The mass spectrometers are very suited instrument for chemical and isotopic analysis, needed in environmental surveillance. Usually, this is done by sampling the soil, air or water followed by laboratory analysis. To avoid drawbacks caused by sample alteration during the sampling process and transport, the 'in situ' analysis is preferred. Theoretically, any type of mass analyzer can be miniaturized, but some are more appropriate than others. Quadrupole mass filter and trap, magnetic sector, time-of-flight and ion cyclotron mass analyzers can be successfully shrunk, for each of them some performances being sacrificed but we must know which parameters are necessary to be kept unchanged. To satisfy the miniaturization criteria of the analyzer, it is necessary to use asymmetrical geometries, with ion beam obl...

The Model of Integrated Marketing Communication: Who has the Role to Influence Consumer Behaviour

OpenAIRE

Olimpia Elena Mihaela Oancea

2015-01-01

The purpose of this paper is proposes a theoretical framework to investigate the models of integrated marketing communication that can influence the consumer behaviour, and the development a model of integrated marketing communication. The research goals aim the following aspects: (a) The analyze of the IMC concept; (b) Identifying and analyzing the main models of integrated marketing communication that can influence the consumer behaviour; (c) Identifying the variables that wi...

An integration strategy for large enterprises

Directory of Open Access Journals (Sweden)

Risimić Dejan

2007-01-01

Full Text Available Integration is the process of enabling a communication between disparate software components. Integration has been the burning issue for large enterprises in the last twenty years, due to the fact that 70% of the development and deployment budget is spent on integrating complex and heterogeneous back-end and front-end IT systems. The need to integrate existing applications is to support newer, faster, more accurate business processes and to provide meaningful, consistent management information. Historically, integration started with the introduction of point-to-point approaches evolving into simpler hub-and spoke topologies. These topologies were combined with custom remote procedure calls, distributed object technologies and message-oriented middleware (MOM, continued with enterprise application integration (EAI and used an application server as a primary vehicle for integration. The current phase of the evolution is service-oriented architecture (SOA combined with an enterprise service bus (ESB. Technical aspects of the comparison between the aforementioned technologies are analyzed and presented. The result of the study is the recommended integration strategy for large enterprises.

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia

DEFF Research Database (Denmark)

Witt, S H; Streit, F; Jungkunz, M

2017-01-01

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report...... describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic...... overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score...

Analysis Method for Integrating Components of Product

Energy Technology Data Exchange (ETDEWEB)

Choi, Jun Ho [Inzest Co. Ltd, Seoul (Korea, Republic of); Lee, Kun Sang [Kookmin Univ., Seoul (Korea, Republic of)

2017-04-15

This paper presents some of the methods used to incorporate the parts constituting a product. A new relation function concept and its structure are introduced to analyze the relationships of component parts. This relation function has three types of information, which can be used to establish a relation function structure. The relation function structure of the analysis criteria was established to analyze and present the data. The priority components determined by the analysis criteria can be integrated. The analysis criteria were divided based on their number and orientation, as well as their direct or indirect characteristic feature. This paper presents a design algorithm for component integration. This algorithm was applied to actual products, and the components inside the product were integrated. Therefore, the proposed algorithm was used to conduct research to improve the brake discs for bicycles. As a result, an improved product similar to the related function structure was actually created.

Analysis Method for Integrating Components of Product

International Nuclear Information System (INIS)

Choi, Jun Ho; Lee, Kun Sang

2017-01-01

This paper presents some of the methods used to incorporate the parts constituting a product. A new relation function concept and its structure are introduced to analyze the relationships of component parts. This relation function has three types of information, which can be used to establish a relation function structure. The relation function structure of the analysis criteria was established to analyze and present the data. The priority components determined by the analysis criteria can be integrated. The analysis criteria were divided based on their number and orientation, as well as their direct or indirect characteristic feature. This paper presents a design algorithm for component integration. This algorithm was applied to actual products, and the components inside the product were integrated. Therefore, the proposed algorithm was used to conduct research to improve the brake discs for bicycles. As a result, an improved product similar to the related function structure was actually created.

Coal Integrated Gasification Fuel Cell System Study

Energy Technology Data Exchange (ETDEWEB)

Chellappa Balan; Debashis Dey; Sukru-Alper Eker; Max Peter; Pavel Sokolov; Greg Wotzak

2004-01-31

This study analyzes the performance and economics of power generation systems based on Solid Oxide Fuel Cell (SOFC) technology and fueled by gasified coal. System concepts that integrate a coal gasifier with a SOFC, a gas turbine, and a steam turbine were developed and analyzed for plant sizes in excess of 200 MW. Two alternative integration configurations were selected with projected system efficiency of over 53% on a HHV basis, or about 10 percentage points higher than that of the state-of-the-art Integrated Gasification Combined Cycle (IGCC) systems. The initial cost of both selected configurations was found to be comparable with the IGCC system costs at approximately $1700/kW. An absorption-based CO2 isolation scheme was developed, and its penalty on the system performance and cost was estimated to be less approximately 2.7% and $370/kW. Technology gaps and required engineering development efforts were identified and evaluated.

Application of a New Integrated Decision Support Tool (i-DST) for Urban Water Infrastructure: Analyzing Water Quality Compliance Pathways for Three Los Angeles Watersheds

Science.gov (United States)

Gallo, E. M.; Hogue, T. S.; Bell, C. D.; Spahr, K.; McCray, J. E.

2017-12-01

The water quality of receiving streams and waterbodies in urban watersheds are increasingly polluted from stormwater runoff. The implementation of Green Infrastructure (GI), which includes Low Impact Developments (LIDs) and Best Management Practices (BMPs), within a watershed aim to mitigate the effects of urbanization by reducing pollutant loads, runoff volume, and storm peak flow. Stormwater modeling is generally used to assess the impact of GIs implemented within a watershed. These modeling tools are useful for determining the optimal suite of GIs to maximize pollutant load reduction and minimize cost. However, stormwater management for most resource managers and communities also includes the implementation of grey and hybrid stormwater infrastructure. An integrated decision support tool, called i-DST, that allows for the optimization and comprehensive life-cycle cost assessment of grey, green, and hybrid stormwater infrastructure, is currently being developed. The i-DST tool will evaluate optimal stormwater runoff management by taking into account the diverse economic, environmental, and societal needs associated with watersheds across the United States. Three watersheds from southern California will act as a test site and assist in the development and initial application of the i-DST tool. The Ballona Creek, Dominguez Channel, and Los Angeles River Watersheds are located in highly urbanized Los Angeles County. The water quality of the river channels flowing through each are impaired by heavy metals, including copper, lead, and zinc. However, despite being adjacent to one another within the same county, modeling results, using EPA System for Urban Stormwater Treatment and Analysis INtegration (SUSTAIN), found that the optimal path to compliance in each watershed differs significantly. The differences include varied costs, suites of BMPs, and ancillary benefits. This research analyzes how the economic, physical, and hydrological differences between the three

Study on diagnostic plant analyzer method for support of emergency operation

International Nuclear Information System (INIS)

Yoshikawa, H.; Gofuku, A.; Itoh, K.; Wakabayashi, J.

1986-01-01

Methods of time-critical diagnostic plant analyzer are investigated which would serve as support to emergency operation of nuclear power plant. A faster-than-real-time simulator code TOKRAC is developed for analyzing PWR primary loop thermo-hydraulics of small-break LOCA and it is applied for a numerical experiment of initial phase of TMI-2 accident. TOKRAC resulted in a good agreement with a RELAP4/MOD6 calculation and the plant record with as fast as can one-tenth of real time. A real-time estimator of SG heat transfer rate based on Kalman filter is proposed and its applicability is verified using LOFT ATWS experimental data. With regards to how to integrate those methods into the software system in operation support center, a new concept of module-based simulation system is proposed which aims at offering a flexible and human-cognitive oriented environment for various analytical tool development

A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese.

Directory of Open Access Journals (Sweden)

Yukinori Okada

2012-01-01

Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8% compared to the genome-wide SNPs (6.9%. In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1 gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10(-9, odds ratio = 1.21. The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05. As AFF1 transcripts were prominently expressed in CD4(+ and CD19(+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset.

Analyzing the Interprofessional Working of a Home-Based Primary Care Team.

Science.gov (United States)

Smith-Carrier, Tracy; Neysmith, Sheila

2014-09-01

Increasingly, interprofessional teams are responsible for providing integrated health care services. Effective teams, however, are not the result of chance but require careful planning and ongoing attention to team processes. Based on a case study involving interviews, participant observation, and a survey, we identified key attributes for effective interprofessional working (IPW) within a home-based primary care (HBPC) setting. Recognizing the importance of a theoretical model that reflects the multidimensional nature of team effectiveness research, we employed the integrated team effectiveness model to analyze our findings. The results indicated that a shared vision, common goals, respect, and trust among team members – as well as processes for ongoing communication, effective leadership, and mechanisms for conflict resolution – are vital in the development of a high-functioning IPW team. The ambiguity and uncertainty surrounding the context of service provision (clients' homes), as well the negotiation of external relationships in the HBPC field, require further investigation.

FPGA based high-performance multi-channel analyzer with local histogram memory

International Nuclear Information System (INIS)

Kulkarni, C.P.; Vaidya, P.P.; Paulson, M.

2004-01-01

Modern nuclear spectroscopy systems demand for a Multi-Channel Analyzer (MCA) with higher resolution, faster speed and other advanced features. The MCA described here is targeted for such demanding applications. The MCA has an in-built local histogram memory and a memory management unit integrated in an FPGA (Field Programmable Gate Array) chip. In addition to the integrated low power digital circuitry, the system utilizes state of the art advanced analog circuits like low power, high speed and high precision comparators, op-amps, ADC and DAC. The operating resolution is selectable from 256 channels to 16384 channels for pulse height analysis. It supports high count rate applications (typically 100 KHz) without significant dead time penalty. It can have an USB bus interface with simple changes. In general, the MCA gives a high performance, compact and low power alternative for portable and battery operated systems as well as for high end laboratory instruments. (author)

Mapping of HKT1;5 Gene in Barley Using GWAS Approach and Its Implication in Salt Tolerance Mechanism

Science.gov (United States)

Hazzouri, Khaled M.; Khraiwesh, Basel; Amiri, Khaled M. A.; Pauli, Duke; Blake, Tom; Shahid, Mohammad; Mullath, Sangeeta K.; Nelson, David; Mansour, Alain L.; Salehi-Ashtiani, Kourosh; Purugganan, Michael; Masmoudi, Khaled

2018-01-01

Sodium (Na+) accumulation in the cytosol will result in ion homeostasis imbalance and toxicity of transpiring leaves. Studies of salinity tolerance in the diploid wheat ancestor Triticum monococcum showed that HKT1;5-like gene was a major gene in the QTL for salt tolerance, named Nax2. In the present study, we were interested in investigating the molecular mechanisms underpinning the role of the HKT1;5 gene in salt tolerance in barley (Hordeum vulgare). A USDA mini-core collection of 2,671 barley lines, part of a field trial was screened for salinity tolerance, and a Genome Wide Association Study (GWAS) was performed. Our results showed important SNPs that are correlated with salt tolerance that mapped to a region where HKT1;5 ion transporter located on chromosome four. Furthermore, sodium (Na+) and potassium (K+) content analysis revealed that tolerant lines accumulate more sodium in roots and leaf sheaths, than in the sensitive ones. In contrast, sodium concentration was reduced in leaf blades of the tolerant lines under salt stress. In the absence of NaCl, the concentration of Na+ and K+ were the same in the roots, leaf sheaths and leaf blades between the tolerant and the sensitive lines. In order to study the molecular mechanism behind that, alleles of the HKT1;5 gene from five tolerant and five sensitive barley lines were cloned and sequenced. Sequence analysis did not show the presence of any polymorphism that distinguishes between the tolerant and sensitive alleles. Our real-time RT-PCR experiments, showed that the expression of HKT1;5 gene in roots of the tolerant line was significantly induced after challenging the plants with salt stress. In contrast, in leaf sheaths the expression was decreased after salt treatment. In sensitive lines, there was no difference in the expression of HKT1;5 gene in leaf sheath under control and saline conditions, while a slight increase in the expression was observed in roots after salt treatment. These results provide

Mapping of HKT1;5 Gene in Barley Using GWAS Approach and Its Implication in Salt Tolerance Mechanism

Directory of Open Access Journals (Sweden)

Khaled M. Hazzouri

2018-02-01

Full Text Available Sodium (Na+ accumulation in the cytosol will result in ion homeostasis imbalance and toxicity of transpiring leaves. Studies of salinity tolerance in the diploid wheat ancestor Triticum monococcum showed that HKT1;5-like gene was a major gene in the QTL for salt tolerance, named Nax2. In the present study, we were interested in investigating the molecular mechanisms underpinning the role of the HKT1;5 gene in salt tolerance in barley (Hordeum vulgare. A USDA mini-core collection of 2,671 barley lines, part of a field trial was screened for salinity tolerance, and a Genome Wide Association Study (GWAS was performed. Our results showed important SNPs that are correlated with salt tolerance that mapped to a region where HKT1;5 ion transporter located on chromosome four. Furthermore, sodium (Na+ and potassium (K+ content analysis revealed that tolerant lines accumulate more sodium in roots and leaf sheaths, than in the sensitive ones. In contrast, sodium concentration was reduced in leaf blades of the tolerant lines under salt stress. In the absence of NaCl, the concentration of Na+ and K+ were the same in the roots, leaf sheaths and leaf blades between the tolerant and the sensitive lines. In order to study the molecular mechanism behind that, alleles of the HKT1;5 gene from five tolerant and five sensitive barley lines were cloned and sequenced. Sequence analysis did not show the presence of any polymorphism that distinguishes between the tolerant and sensitive alleles. Our real-time RT-PCR experiments, showed that the expression of HKT1;5 gene in roots of the tolerant line was significantly induced after challenging the plants with salt stress. In contrast, in leaf sheaths the expression was decreased after salt treatment. In sensitive lines, there was no difference in the expression of HKT1;5 gene in leaf sheath under control and saline conditions, while a slight increase in the expression was observed in roots after salt treatment. These

Analyzing Peace Pedagogies

Science.gov (United States)

Haavelsrud, Magnus; Stenberg, Oddbjorn

2012-01-01

Eleven articles on peace education published in the first volume of the Journal of Peace Education are analyzed. This selection comprises peace education programs that have been planned or carried out in different contexts. In analyzing peace pedagogies as proposed in the 11 contributions, we have chosen network analysis as our method--enabling…

Analyzing Cyber-Physical Threats on Robotic Platforms †

Science.gov (United States)

2018-01-01

Robots are increasingly involved in our daily lives. Fundamental to robots are the communication link (or stream) and the applications that connect the robots to their clients or users. Such communication link and applications are usually supported through client/server network connection. This networking system is amenable of being attacked and vulnerable to the security threats. Ensuring security and privacy for robotic platforms is thus critical, as failures and attacks could have devastating consequences. In this paper, we examine several cyber-physical security threats that are unique to the robotic platforms; specifically the communication link and the applications. Threats target integrity, availability and confidential security requirements of the robotic platforms, which use MobileEyes/arnlServer client/server applications. A robot attack tool (RAT) was developed to perform specific security attacks. An impact-oriented approach was adopted to analyze the assessment results of the attacks. Tests and experiments of attacks were conducted in simulation environment and physically on the robot. The simulation environment was based on MobileSim; a software tool for simulating, debugging and experimenting on MobileRobots/ActivMedia platforms and their environments. The robot platform PeopleBotTM was used for physical experiments. The analysis and testing results show that certain attacks were successful at breaching the robot security. Integrity attacks modified commands and manipulated the robot behavior. Availability attacks were able to cause Denial-of-Service (DoS) and the robot was not responsive to MobileEyes commands. Integrity and availability attacks caused sensitive information on the robot to be hijacked. To mitigate security threats, we provide possible mitigation techniques and suggestions to raise awareness of threats on the robotic platforms, especially when the robots are involved in critical missions or applications. PMID:29883403

A computer program integrating a multichannel analyzer with gamma analysis for the estimation of 226 Ra concentration in soil samples

International Nuclear Information System (INIS)

Wilson, J. E.

1992-08-01

A new hardware/software system has been implemented using the existing three-regions-of-interest method for determining the concentration of 226 Ra in soil samples for the Pollutant Assessment Group of the Oak Ridge National Laboratory. Consisting of a personal computer containing a multichannel analyzer, the system utilizes a new program combining the multichannel analyzer with a program analyzing gamma-radiation spectra for 226 Ra concentrations. This program uses a menu interface to minimize and simplify the tasks of system operation

A framework for analyzing the impact of data integrity/quality on electricity market operations

Science.gov (United States)

Choi, Dae Hyun

This dissertation examines the impact of data integrity/quality in the supervisory control and data acquisition (SCADA) system on real-time locational marginal price (LMP) in electricity market operations. Measurement noise and/or manipulated sensor errors in a SCADA system may mislead system operators about real-time conditions in a power system, which, in turn, may impact the price signals in real-time power markets. This dissertation serves as a first attempt to analytically investigate the impact of bad/malicious data on electric power market operations. In future power system operations, which will probably involve many more sensors, the impact of sensor data integrity/quality on grid operations will become increasingly important. The first part of this dissertation studies from a market participant's perspective a new class of malicious data attacks on state estimation, which subsequently influences the result of the newly emerging look-ahead dispatch models in the real-time power market. In comparison with prior work of cyber-attack on static dispatch where no inter-temporal ramping constraint is considered, we propose a novel attack strategy, named ramp-induced data (RID) attack, with which the attacker can manipulate the limits of ramp constraints of generators in look-ahead dispatch. It is demonstrated that the proposed attack can lead to financial profits via malicious capacity withholding of selected generators, while being undetected by the existing bad data detection algorithm embedded in today's state estimation software. In the second part, we investigate from a system operator's perspective the sensitivity of locational marginal price (LMP) with respect to data corruption-induced state estimation error in real-time power market. Two data corruption scenarios are considered, in which corrupted continuous data (e.g., the power injection/flow and voltage magnitude) falsify power flow estimate whereas corrupted discrete data (e.g., the on/off status of

Analyzing maintenance strategies by agent-based simulations: A feasibility study

International Nuclear Information System (INIS)

Kaegi, M.; Mock, R.; Kroeger, W.

2009-01-01

Thoroughly planned and implemented maintenance strategies save time and cost. However, the integration of maintenance work into reliability analysis is difficult as common modeling techniques are often not applicable due to state explosion which calls for restrictive model assumptions and oversimplification. From authors' point of view, agent-based modeling (ABM) of technical and organizational systems is a promising approach to overcome such problems. But since ABM is not well established in reliability analysis its feasibility in this area still has to be demonstrated. For this purpose ABM is compared with Markov chains, namely by analyzing the reliability of a maintained n-unit system with dependent repair events, applying both modeling approaches. Although ABM and Markov chains lead to the same numerical results, the former points out the potentiality of an improved system state handling. This is demonstrated by extending the ABM with operators as additional 'agents' featuring their location (x;y) availability (0;1) and different maintenance strategies. This extension highlights the capability of ABM to analyze complex emergent system behavior and allows a systematic refinement and optimization of the maintenance strategies.

Integrating bathymetric and topographic data

Science.gov (United States)

Teh, Su Yean; Koh, Hock Lye; Lim, Yong Hui; Tan, Wai Kiat

2017-11-01

The quality of bathymetric and topographic resolution significantly affect the accuracy of tsunami run-up and inundation simulation. However, high resolution gridded bathymetric and topographic data sets for Malaysia are not freely available online. It is desirable to have seamless integration of high resolution bathymetric and topographic data. The bathymetric data available from the National Hydrographic Centre (NHC) of the Royal Malaysian Navy are in scattered form; while the topographic data from the Department of Survey and Mapping Malaysia (JUPEM) are given in regularly spaced grid systems. Hence, interpolation is required to integrate the bathymetric and topographic data into regularly-spaced grid systems for tsunami simulation. The objective of this research is to analyze the most suitable interpolation methods for integrating bathymetric and topographic data with minimal errors. We analyze four commonly used interpolation methods for generating gridded topographic and bathymetric surfaces, namely (i) Kriging, (ii) Multiquadric (MQ), (iii) Thin Plate Spline (TPS) and (iv) Inverse Distance to Power (IDP). Based upon the bathymetric and topographic data for the southern part of Penang Island, our study concluded, via qualitative visual comparison and Root Mean Square Error (RMSE) assessment, that the Kriging interpolation method produces an interpolated bathymetric and topographic surface that best approximate the admiralty nautical chart of south Penang Island.

STINGRAY: system for integrated genomic resources and analysis.

Science.gov (United States)

Wagner, Glauber; Jardim, Rodrigo; Tschoeke, Diogo A; Loureiro, Daniel R; Ocaña, Kary A C S; Ribeiro, Antonio C B; Emmel, Vanessa E; Probst, Christian M; Pitaluga, André N; Grisard, Edmundo C; Cavalcanti, Maria C; Campos, Maria L M; Mattoso, Marta; Dávila, Alberto M R

2014-03-07

The STINGRAY system has been conceived to ease the tasks of integrating, analyzing, annotating and presenting genomic and expression data from Sanger and Next Generation Sequencing (NGS) platforms. STINGRAY includes: (a) a complete and integrated workflow (more than 20 bioinformatics tools) ranging from functional annotation to phylogeny; (b) a MySQL database schema, suitable for data integration and user access control; and (c) a user-friendly graphical web-based interface that makes the system intuitive, facilitating the tasks of data analysis and annotation. STINGRAY showed to be an easy to use and complete system for analyzing sequencing data. While both Sanger and NGS platforms are supported, the system could be faster using Sanger data, since the large NGS datasets could potentially slow down the MySQL database usage. STINGRAY is available at http://stingray.biowebdb.org and the open source code at http://sourceforge.net/projects/stingray-biowebdb/.

DEBATE ON ROMANIA INTEGRATION IN EUROPEAN UNION

Directory of Open Access Journals (Sweden)

Roxana M. SÎRBU

2014-04-01

Full Text Available The purpose of this paper is to analyze the current state of Romanian integration into the European Union through the analysis of statistical data related to the absorption way of structural and cohesion funds available in 2007-2013 (absorption indicators and economic competitiveness indicators: Gross Domestic Product, employment rate, unemployment, population. In addition there are analyzed the structural and cohesion funds available for Romania in 2014-2020, for each category of available operational program and also the measures that must be implemented for Romania to adapt in a performance way to Europe 2020. The analysis results are considered as prerequisites for the development of an underlying model of investment decisions in the integrated sustainable development of Romania.

Ubiquitous Integrity via Network Integration and Parallelism—Sustaining Pedestrian/Bike Urbanism

Directory of Open Access Journals (Sweden)

Li-Yen Hsu

2013-08-01

Full Text Available Nowadays, due to the concern regarding environmental issues, establishing pedestrian/bike friendly urbanism is widely encouraged. To promote safety-assured, mobile communication environments, efficient, reliable maintenance, and information integrity need to be designed, especially in highly possibly interfered places. For busy traffic areas, regular degree-3 dedicated short range communication (DSRC networks are safety and information featured with availability, reliability, and maintainability in paths of multi-lanes. For sparsely populated areas, probes of wireless sensors are rational, especially if sensor nodes can be organized to enhance security, reliability, and flexibility. Applying alternative network topologies, such as spider-webs, generalized honeycomb tori, and cube-connected cycles, for comparing and analyzing is proposed in DSRC and cellular communications to enhance integrity in communications.

Demand Response and Energy Storage Integration Study

Energy Technology Data Exchange (ETDEWEB)

Ma, Ookie; Cheung, Kerry; Olsen, Daniel J.; Matson, Nance; Sohn, Michael D.; Rose, Cody M.; Dudley, Junqiao Han; Goli, Sasank; Kiliccote, Sila; Cappers, Peter; MacDonald, Jason; Denholm, Paul; Hummon, Marissa; Jorgenson, Jennie; Palchak, David; Starke, Michael; Alkadi, Nasr; Bhatnagar, Dhruv; Currier, Aileen; Hernandez, Jaci; Kirby, Brendan; O' Malley, Mark

2016-03-01

Demand response and energy storage resources present potentially important sources of bulk power system services that can aid in integrating variable renewable generation. While renewable integration studies have evaluated many of the challenges associated with deploying large amounts of variable wind and solar generation technologies, integration analyses have not yet fully incorporated demand response and energy storage resources. This report represents an initial effort in analyzing the potential integration value of demand response and energy storage, focusing on the western United States. It evaluates two major aspects of increased deployment of demand response and energy storage: (1) Their operational value in providing bulk power system services and (2) Market and regulatory issues, including potential barriers to deployment.

Integration of genomic information with biological networks using Cytoscape.

Science.gov (United States)

Bauer-Mehren, Anna

2013-01-01

Cytoscape is an open-source software for visualizing, analyzing, and modeling biological networks. This chapter explains how to use Cytoscape to analyze the functional effect of sequence variations in the context of biological networks such as protein-protein interaction networks and signaling pathways. The chapter is divided into five parts: (1) obtaining information about the functional effect of sequence variation in a Cytoscape readable format, (2) loading and displaying different types of biological networks in Cytoscape, (3) integrating the genomic information (SNPs and mutations) with the biological networks, and (4) analyzing the effect of the genomic perturbation onto the network structure using Cytoscape built-in functions. Finally, we briefly outline how the integrated data can help in building mathematical network models for analyzing the effect of the sequence variation onto the dynamics of the biological system. Each part is illustrated by step-by-step instructions on an example use case and visualized by many screenshots and figures.

KEEFEKTIFAN MODEL CONNECTED DAN INTEGRATED DALAM PEMBELAJARAN IPS SMP DI KOTA YOGYAKARTA

OpenAIRE

Idrus idrus

2011-01-01

This research aimed to: (1) analyze the differences in social studies learning achievement between the students using connected and integrated models and those using conventional model; and (2) analyze the hierarchy of the effect of the learning models  among the connected, integrated, and conventional. This experimental research employed a matching post-test comparison group design. The population of this research was National Standardized Schools of Junior Secondary Schools in Yogya...

The LEAN Payload Integration Process

Science.gov (United States)

Jordan, Lee P.; Young, Yancy; Rice, Amanda

2011-01-01

It is recognized that payload development and integration with the International Space Station (ISS) can be complex. This streamlined integration approach is a first step toward simplifying payload integration; making it easier to fly payloads on ISS, thereby increasing feasibility and interest for more research and commercial organizations to sponsor ISS payloads and take advantage of the ISS as a National Laboratory asset. The streamlined integration approach was addressed from the perspective of highly likely initial payload types to evolve from the National Lab Pathfinder program. Payloads to be accommodated by the Expedite the Processing of Experiments for Space Station (EXPRESS) Racks and Microgravity Sciences Glovebox (MSG) pressurized facilities have been addressed. It is hoped that the streamlined principles applied to these types of payloads will be analyzed and implemented in the future for other host facilities as well as unpressurized payloads to be accommodated by the EXPRESS Logistics Carrier (ELC). Further, a payload does not have to be classified as a National Lab payload in order to be processed according to the lean payload integration process; any payload that meets certain criteria can follow the lean payload integration process.

Research on Integration of NPP Operational Safety Management Performance Systems

International Nuclear Information System (INIS)

Chi, Miao; Shi, Liping

2014-01-01

The operational safety management of Nuclear Power Plants demands systematic planning and integrated control. NPPs are following the well-developed safety indicator systems proposed by IAEA Operational Safety Performance Indicator Programme, NRC Reactor Oversight Process or the other institutions. Integration of the systems is proposed to benefiting from the advantages of both systems and avoiding improper application into the real world. The authors analyzed the possibility and necessity for system integration, and propose an indicator system integrating method

Computer aided process planning system based on workflow technology and integrated bill of material tree

Institute of Scientific and Technical Information of China (English)

LU Chun-guang; MENG Li-li

2006-01-01

It is extremely important for procedure of process design and management of process data for product life cycle in Computer Aided Process Planning (CAPP) system,but there are many shortcomings with traditional CAPP system in these respects.To solve these questions,application of workflow technology in CAPP system based on web-integrated Bill of Material (BOM) tree is discussed,and a concept of integrated BOM tree was brought forward.Taking integrated BOM as the thread,CAPP systematic technological process is analyzed.The function,system architecture,and implementation mechanism of CAPP system based on Browser/Server and Customer/Server model are expatiated.Based on it,the key technologies of workflow management device were analyzed.Eventually,the implementation mechanism of integrated BOM tree was analyzed from viewpoints of material information encoding,organization node design of integrated BOM tree,transformation from Engineering BOM (EBOM)to Process BOM (PBOM),and the programming implementation technology.

Thromboelastography platelet mapping in healthy dogs using 1 analyzer versus 2 analyzers.

Science.gov (United States)

Blois, Shauna L; Banerjee, Amrita; Wood, R Darren; Park, Fiona M

2013-07-01

The objective of this study was to describe the results of thromboelastography platelet mapping (TEG-PM) carried out using 2 techniques in 20 healthy dogs. Maximum amplitudes (MA) generated by thrombin (MAthrombin), fibrin (MAfibrin), adenosine diphosphate (ADP) receptor activity (MAADP), and thromboxane A2 (TxA2) receptor activity (stimulated by arachidonic acid, MAAA) were recorded. Thromboelastography platelet mapping was carried out according to the manufacturer's guidelines (2-analyzer technique) and using a variation of this method employing only 1 analyzer (1-analyzer technique) on 2 separate blood samples obtained from each dog. Mean [± standard deviation (SD)] MA values for the 1-analyzer/2-analyzer techniques were: MAthrombin = 51.9 mm (± 7.1)/52.5 mm (± 8.0); MAfibrin = 20.7 mm (± 21.8)/23.0 mm (± 26.1); MAADP = 44.5 mm (± 15.6)/45.6 mm (± 17.0); and MAAA = 45.7 mm (± 11.6)/45.0 mm (± 15.4). Mean (± SD) percentage aggregation due to ADP receptor activity was 70.4% (± 32.8)/67.6% (± 33.7). Mean percentage aggregation due to TxA2 receptor activity was 77.3% (± 31.6)/78.1% (± 50.2). Results of TEG-PM were not significantly different for the 1-analyzer and 2-analyzer methods. High correlation was found between the 2 methods for MAfibrin [concordance correlation coefficient (r) = 0.930]; moderate correlation was found for MAthrombin (r = 0.70) and MAADP (r = 0.57); correlation between the 2 methods for MAAA was lower (r = 0.32). Thromboelastography platelet mapping (TEG-PM) should be further investigated to determine if it is a suitable method for measuring platelet dysfunction in dogs with thrombopathy.

Integration process and logistics results

International Nuclear Information System (INIS)

2004-01-01

The Procurement and Logistics functions have gone through a process of integration since the beginning of integrated management of Asco and Vandellos II up to the present. These are functions that are likely to be designed for delivering a single product to the rest of the organization, defined from a high level of expectations, and that admit simplifications and materialization of synergy's as they are approached from an integrated perspective. The analyzed functions are as follows: Service and Material Purchasing, Warehouse and Material Management, and Documentation and General Services Management. In all case, to accomplish the integration, objectives, procedures and information systems were unified. As for the organization, a decision was made in each case on whether or not to out source. The decisive corporate strategy to integrate, resulting in actions such as moving corporate headquarters to Vandellos II, corporate consolidation, regulation of employment and implementation of the ENDESA Group Economic Information System (SIE) , has shaped this process, which at present can be considered as practically complete. (Author)

Relativistic effects in the calibration of electrostatic electron analyzers. I. Toroidal analyzers

Energy Technology Data Exchange (ETDEWEB)

Keski Rahkonen, O [Helsinki University of Technology, Espoo (Finland). Laboratory of Physics; Krause, M O [Oak Ridge National Lab., Tenn. (USA)

1978-02-01

Relativistic correction terms up to the second order are derived for the kinetic energy of an electron travelling along the circular central trajectory of a toroidal analyzer. Furthermore, a practical energy calibration equation of the spherical sector plate analyzer is written for the variable-plate-voltage recording mode. Accurate measurements with a spherical analyzer performed using kinetic energies from 600 to 2100 eV are in good agreement with this theory showing our approximation (neglect of fringing fields, and source and detector geometry) is realistic enough for actual calibration purposes.

Multichannel analyzer development in CAMAC

International Nuclear Information System (INIS)

Nagy, J.Z.; Zarandy, A.

1988-01-01

The data acquisition in TOKAMAK experiments some CAMAC modules have been developed. The modules are the following: 64 K analyzer memory, 32 K analyzer memory, 6-channel pulse peak analyzer memory which contains the 32 K analyzer memory and eight AD-converters

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration)

DEFF Research Database (Denmark)

Traylor, Matthew; Farrall, Martin; Holliday, Elizabeth G

2012-01-01

Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS...... and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes....

How to statistically analyze nano exposure measurement results: using an ARIMA time series approach

International Nuclear Information System (INIS)

Klein Entink, Rinke H.; Fransman, Wouter; Brouwer, Derk H.

2011-01-01

Measurement strategies for exposure to nano-sized particles differ from traditional integrated sampling methods for exposure assessment by the use of real-time instruments. The resulting measurement series is a time series, where typically the sequential measurements are not independent from each other but show a pattern of autocorrelation. This article addresses the statistical difficulties when analyzing real-time measurements for exposure assessment to manufactured nano objects. To account for autocorrelation patterns, Autoregressive Integrated Moving Average (ARIMA) models are proposed. A simulation study shows the pitfalls of using a standard t-test and the application of ARIMA models is illustrated with three real-data examples. Some practical suggestions for the data analysis of real-time exposure measurements conclude this article.

Genome-Wide Association Study of Major Agronomic Traits Related to Domestication in Peanut

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Xingguo Zhang

2017-09-01

Full Text Available Peanut (Arachis hypogaea consists of two subspecies, hypogaea and fastigiata, and has been cultivated worldwide for hundreds of years. Here, 158 peanut accessions were selected to dissect the molecular footprint of agronomic traits related to domestication using specific-locus amplified fragment sequencing (SLAF-seq method. Then, a total of 17,338 high-quality single nucleotide polymorphisms (SNPs in the whole peanut genome were revealed. Eleven agronomic traits in 158 peanut accessions were subsequently analyzed using genome-wide association studies (GWAS. Candidate genes responsible for corresponding traits were then analyzed in genomic regions surrounding the peak SNPs, and 1,429 genes were found within 200 kb windows centerd on GWAS-identified peak SNPs related to domestication. Highly differentiated genomic regions were observed between hypogaea and fastigiata accessions using FST values and sequence diversity (π ratios. Among the 1,429 genes, 662 were located on chromosome A3, suggesting the presence of major selective sweeps caused by artificial selection during long domestication. These findings provide a promising insight into the complicated genetic architecture of domestication-related traits in peanut, and reveal whole-genome SNP markers of beneficial candidate genes for marker-assisted selection (MAS in future breeding programs.

Univariate/multivariate genome-wide association scans using data from families and unrelated samples.

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Lei Zhang

2009-08-01

Full Text Available As genome-wide association studies (GWAS are becoming more popular, two approaches, among others, could be considered in order to improve statistical power for identifying genes contributing subtle to moderate effects to human diseases. The first approach is to increase sample size, which could be achieved by combining both unrelated and familial subjects together. The second approach is to jointly analyze multiple correlated traits. In this study, by extending generalized estimating equations (GEEs, we propose a simple approach for performing univariate or multivariate association tests for the combined data of unrelated subjects and nuclear families. In particular, we correct for population stratification by integrating principal component analysis and transmission disequilibrium test strategies. The proposed method allows for multiple siblings as well as missing parental information. Simulation studies show that the proposed test has improved power compared to two popular methods, EIGENSTRAT and FBAT, by analyzing the combined data, while correcting for population stratification. In addition, joint analysis of bivariate traits has improved power over univariate analysis when pleiotropic effects are present. Application to the Genetic Analysis Workshop 16 (GAW16 data sets attests to the feasibility and applicability of the proposed method.

Analyzing internal barriers for automotive parts remanufacturers in China using grey-DEMATEL approach

DEFF Research Database (Denmark)

Xia, Xiqiang; Govindan, Kannan; Zhu, Qinghua

2015-01-01

analyzes internal barriers met by automotive parts remanufacturers and evaluates causal barriers by a proposed model framework. This objective is illustrated by employing the Grey Decision Making Trial and Evaluation Laboratory (DEMATEL) approach. By virtue of these findings, remanufacturers can eradicate......Automotive industries have attracted attention from international sectors recently. This attention to the industry results in many innovative technologies being integrated in these manufacturing arenas. In developing countries such as the BRIC (Brazil, Russia, India, and China) countries...

The Genome-Scale Integrated Networks in Microorganisms

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Tong Hao

2018-02-01

Full Text Available The genome-scale cellular network has become a necessary tool in the systematic analysis of microbes. In a cell, there are several layers (i.e., types of the molecular networks, for example, genome-scale metabolic network (GMN, transcriptional regulatory network (TRN, and signal transduction network (STN. It has been realized that the limitation and inaccuracy of the prediction exist just using only a single-layer network. Therefore, the integrated network constructed based on the networks of the three types attracts more interests. The function of a biological process in living cells is usually performed by the interaction of biological components. Therefore, it is necessary to integrate and analyze all the related components at the systems level for the comprehensively and correctly realizing the physiological function in living organisms. In this review, we discussed three representative genome-scale cellular networks: GMN, TRN, and STN, representing different levels (i.e., metabolism, gene regulation, and cellular signaling of a cell’s activities. Furthermore, we discussed the integration of the networks of the three types. With more understanding on the complexity of microbial cells, the development of integrated network has become an inevitable trend in analyzing genome-scale cellular networks of microorganisms.

Integrative approach to analyze biodiversity and anti-inflammatory bioactivity of Wedelia medicinal plants.

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Wen-Ching Lin

Full Text Available For the development of "medical foods" and/or botanical drugs as defined USA FDA, clear and systemic characterizations of the taxonomy, index phytochemical components, and the functional or medicinal bioactivities of the reputed or candidate medicinal plant are needed. In this study, we used an integrative approach, including macroscopic and microscopic examination, marker gene analysis, and chemical fingerprinting, to authenticate and validate various species/varieties of Wedelia, a reputed medicinal plant that grows naturally and commonly used in Asian countries. The anti-inflammatory bioactivities of Wedelia extracts were then evaluated in a DSS-induced murine colitis model. Different species/varieties of Wedelia exhibited distinguishable morphology and histological structures. Analysis of the ribosomal DNA internal transcribed spacer (ITS region revealed significant differences among these plants. Chemical profiling of test Wedelia species demonstrated candidate index compounds and distinguishable secondary metabolites, such as caffeic acid derivatives, which may serve as phytochemical markers or index for quality control and identification of specific Wedelia species. In assessing their effect on treating DSS induced-murine colitis, we observed that only the phytoextract from W. chinensis species exhibited significant anti-inflammatory bioactivity on DSS-induced murine colitis among the various Wedelia species commonly found in Taiwan. Our results provide a translational research approach that may serve as a useful reference platform for biotechnological applications of traditional phytomedicines. Our findings indicate that specific Wedelia species warrant further investigation for potential treatment of human inflammatory bowel disease.

Corporate Culture Assessments in Integrative Oncology: A Qualitative Case Study of Two Integrative Oncology Centers

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Nadine Mittring

2013-01-01

Full Text Available The offer of “integrative oncology” is one option for clinics to provide safe and evidence-based complementary medicine treatments to cancer patients. As known from merger theories, corporate culture and integration models have a strong influence on the success of such integration. To identify relevant corporate culture aspects that might influence the success in two highly visible integrative oncology clinics, we interviewed physicians, nurses, practitioners, and managers. All interviews (11 in a German breast cancer clinic and 9 in an integrative medicine cancer service in the USA were audio-recorded, transcribed and analyzed with content analysis. According to the theoretical framework of mergers, each clinic selected a different integration type (“best of both worlds” and “linking”. Nonetheless, each developed a similar corporate culture that has a strong focus on research and safe and evidence-based treatments, and fosters a holistic and patient-centered approach. Structured communication within the team and with other departments had high relevance. Research was highlighted as a way to open doors and to facilitate a more general acceptance within the hospital. Conventional physicians felt unburdened by the provision of integrative medicine service but also saw problems in the time required for scheduled treatments, which often resulted in long waiting lists.

Corporate culture assessments in integrative oncology: a qualitative case study of two integrative oncology centers.

Science.gov (United States)

Mittring, Nadine; Pérard, Marion; Witt, Claudia M

2013-01-01

The offer of "integrative oncology" is one option for clinics to provide safe and evidence-based complementary medicine treatments to cancer patients. As known from merger theories, corporate culture and integration models have a strong influence on the success of such integration. To identify relevant corporate culture aspects that might influence the success in two highly visible integrative oncology clinics, we interviewed physicians, nurses, practitioners, and managers. All interviews (11 in a German breast cancer clinic and 9 in an integrative medicine cancer service in the USA) were audio-recorded, transcribed and analyzed with content analysis. According to the theoretical framework of mergers, each clinic selected a different integration type ("best of both worlds" and "linking"). Nonetheless, each developed a similar corporate culture that has a strong focus on research and safe and evidence-based treatments, and fosters a holistic and patient-centered approach. Structured communication within the team and with other departments had high relevance. Research was highlighted as a way to open doors and to facilitate a more general acceptance within the hospital. Conventional physicians felt unburdened by the provision of integrative medicine service but also saw problems in the time required for scheduled treatments, which often resulted in long waiting lists.

The relation between Polyakov's and Fradkin's path integrals for bosonic string

International Nuclear Information System (INIS)

Jaskolski, Z.; Rytel, L.; Klimek, M.

1987-04-01

The relation between Polyakov's path integral and Fradkin's integral in extended phase space is analyzed on an example of a free closed bosonic string. It is shown in D=26 that locally, in every Teichmueller sector, both methods provide the same result. Beyond D=26 Fradkin's integral appears to be depending on the gauge fixing. (author). 12 refs

Web server attack analyzer

OpenAIRE

Mižišin, Michal

2013-01-01

Web server attack analyzer - Abstract The goal of this work was to create prototype of analyzer of injection flaws attacks on web server. Proposed solution combines capabilities of web application firewall and web server log analyzer. Analysis is based on configurable signatures defined by regular expressions. This paper begins with summary of web attacks, followed by detection techniques analysis on web servers, description and justification of selected implementation. In the end are charact...

Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci.

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Celeste M Karch

Full Text Available Late onset Alzheimer's disease (LOAD is a genetically complex and clinically heterogeneous disease. Recent large-scale genome wide association studies (GWAS have identified more than twenty loci that modify risk for AD. Despite the identification of these loci, little progress has been made in identifying the functional variants that explain the association with AD risk. Thus, we sought to determine whether the novel LOAD GWAS single nucleotide polymorphisms (SNPs alter expression of LOAD GWAS genes and whether expression of these genes is altered in AD brains. The majority of LOAD GWAS SNPs occur in gene dense regions under large linkage disequilibrium (LD blocks, making it unclear which gene(s are modified by the SNP. Thus, we tested for brain expression quantitative trait loci (eQTLs between LOAD GWAS SNPs and SNPs in high LD with the LOAD GWAS SNPs in all of the genes within the GWAS loci. We found a significant eQTL between rs1476679 and PILRB and GATS, which occurs within the ZCWPW1 locus. PILRB and GATS expression levels, within the ZCWPW1 locus, were also associated with AD status. Rs7120548 was associated with MTCH2 expression, which occurs within the CELF1 locus. Additionally, expression of several genes within the CELF1 locus, including MTCH2, were highly correlated with one another and were associated with AD status. We further demonstrate that PILRB, as well as other genes within the GWAS loci, are most highly expressed in microglia. These findings together with the function of PILRB as a DAP12 receptor supports the critical role of microglia and neuroinflammation in AD risk.

Integrated Microwave Photonics

OpenAIRE

Marpaung, David; Roeloffzen, Chris; Heideman, René; Leinse, Arne; Sales Maicas, Salvador; Capmany Francoy, José

2013-01-01

Microwave photonics (MWP) is an emerging field in which radio frequency (RF) signals are generated, distributed, processed and analyzed using the strength of photonic techniques. It is a technology that enables various functionalities which are not feasible to achieve only in the microwave domain. A particular aspect that recently gains significant interests is the use of photonic integrated circuit (PIC) technology in the MWP field for enhanced functionalities and robustness as well as the r...

ABCG2 contributes to the development of gout and hyperuricemia in a genome-wide association study.

Science.gov (United States)

Chen, Chung-Jen; Tseng, Chia-Chun; Yen, Jeng-Hsien; Chang, Jan-Gowth; Chou, Wen-Cheng; Chu, Hou-Wei; Chang, Shun-Jen; Liao, Wei-Ting

2018-02-16

Although many genome-wide association studies (GWASs) of hyperuricemia or gout have been reported, the related genetic factors and the mechanisms from hyperuricemia to gouty attack remain unclear. This study aimed to identify genetic factors and pathogenesis of gout from hyperuricemia by genome-wide association study (GWAS). 747 gout patients, 747 hyperuricemia and 2071 age-matched controls were recruited and analyzed with Affymetrix 650 K chip to find the related genetic variants. The functions of the related genes were investigated in an endothelial cell (EC) with urate crystal stimulation. The GWAS results showed 36 SNPs to be strongly associated with gout compared to controls (all p-values gene had significant associations between gout and controls, between gout and hyperuricemia, and between hyperuricemia and controls (all p-values gene contributed to hyperuricemia but also gout, and that it was involved in the inflammation dysregulation via augmented IL-8 release in EC.

INTEGRATION POLICY TOWARDS IMMIGRANTS: CURRENT EXPERIENCE

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Nadiia Bureiko

2012-03-01

Full Text Available In the contemporary world the intensity of the immigration movements is constantly increasing. Countries which experience great immigrant flows are facing numerous problems which should be solved. The article studies the current immigration flows in EU countries, the United States of America and Canada and presents three main models of integration policy towards immigrants – political assimilation, functional integration and multicultural model. Separate models are distinguished for the Muslims’ integration. The author examines the peculiarities of every model and examines the conclusions provided by the Migrant Integration Policy Index (MIPEX concerning the situation of the immigrants’ integration in 31 countries in 2011. Among all the policy indicators the first that are defined are as follows: political participation, education, labour market mobility and anti-discrimination. The situation with immigrants’ integration in Ukraine is also studied as it is gaining a great attention of the authorities and the public. The measures and practical steps done regarding this situation in Ukraine in recent years are analyzed using the information offered by the State Migration Service of Ukraine.

Irradiated-Microsphere Gamma Analyzer (IMGA): an integrated system for HTGR coated particle fuel performance assessment

International Nuclear Information System (INIS)

Kania, M.J.; Valentine, K.H.

1980-02-01

The Irradiated-Microsphere Gamma Analyzer (IMGA) System, designed and built at ORNL, provides the capability of making statistically accurate failure fraction measurements on irradiated HTGR coated particle fuel. The IMGA records the gamma-ray energy spectra from fuel particles and performs quantitative analyses on these spectra; then, using chemical and physical properties of the gamma emitters it makes a failed-nonfailed decision concerning the ability of the coatings to retain fission products. Actual retention characteristics for the coatings are determined by measuring activity ratios for certain gamma emitters such as 137 Cs/ 95 Zr and 144 Ce/ 95 Zr for metallic fission product retention and 134 Cs/ 137 Cs for an indirect measure of gaseous fission product retention. Data from IMGA (which can be put in the form of n failures observed in N examinations) can be accurately described by the binomial probability distribution model. Using this model, a mathematical relationship between IMGA data (n,N), failure fraction, and confidence level was developed. To determine failure fractions of less than or equal to 1% at confidence levels near 95%, this model dictates that from several hundred to several thousand particles must be examined. The automated particle handler of the IMGA system provides this capability. As a demonstration of failure fraction determination, fuel rod C-3-1 from the OF-2 irradiation capsule was analyzed and failure fraction statistics were applied. Results showed that at the 1% failure fraction level, with a 95% confidence level, the fissile particle batch could not meet requirements; however, the fertile particle exceeded these requirements for the given irradiation temperature and burnup

Modeling disease risk through analysis of physical interactions between genetic variants within chromatin regulatory circuitry.

Science.gov (United States)

Corradin, Olivia; Cohen, Andrea J; Luppino, Jennifer M; Bayles, Ian M; Schumacher, Fredrick R; Scacheri, Peter C

2016-11-01

SNPs associated with disease susceptibility often reside in enhancer clusters, or super-enhancers. Constituents of these enhancer clusters cooperate to regulate target genes and often extend beyond the linkage disequilibrium (LD) blocks containing risk SNPs identified in genome-wide association studies (GWAS). We identified 'outside variants', defined as SNPs in weak LD with GWAS risk SNPs that physically interact with risk SNPs as part of a target gene's regulatory circuitry. These outside variants further explain variation in target gene expression beyond that explained by GWAS-associated SNPs. Additionally, the clinical risk associated with GWAS SNPs is considerably modified by the genotype of outside variants. Collectively, these findings suggest a potential model in which outside variants and GWAS SNPs that physically interact in 3D chromatin collude to influence target transcript levels as well as clinical risk. This model offers an additional hypothesis for the source of missing heritability for complex traits.

UVB DNA dosimeters analyzed by polymerase chain reactors

International Nuclear Information System (INIS)

Yoshida, Hiroko; Regan, J.D.; Florida Inst. of Tech., Melbourne, FL

1997-01-01

Purified bacteriophage λ DNA was dried on a UV-transparent polymer film and served as a UVB dosimeter for personal and ecological applications. Bacteriophage λ DNA was chosen because it is commercially available and inexpensive, and its entire sequence is known. Each dosimeter contained two sets of DNA sandwiched between UV-transparent polymer films, one exposed to solar radiation (experimental) and another protected from UV radiation by black paper (control). The DNA dosimeter was then analyzed by a polymerase chain reaction (PCR) that amplifies a 500 base pair specific region of λ DNA. Photoinduced damage in DNA blocks polymerase from synthesizing a new strand; therefore, the amount of amplified product in UV-exposed DNA was reduced from that found in control DNA. The dried λ DNA dosimeter is compact, robust, safe and transportable, stable over long storage times and provides the total UVB dose integrated over the exposure time. (author)

Analyzing the Bitcoin Network: The First Four Years

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Matthias Lischke

2016-03-01

Full Text Available In this explorative study, we examine the economy and transaction network of the decentralized digital currency Bitcoin during the first four years of its existence. The objective is to develop insights into the evolution of the Bitcoin economy during this period. For this, we establish and analyze a novel integrated dataset that enriches data from the Bitcoin blockchain with off-network data such as business categories and geo-locations. Our analyses reveal the major Bitcoin businesses and markets. Our results also give insights on the business distribution by countries and how businesses evolve over time. We also show that there is a gambling network that features many very small transactions. Furthermore, regional differences in the adoption and business distribution could be found. In the network analysis, the small world phenomenon is investigated and confirmed for several subgraphs of the Bitcoin network.

A note on unionized firms' incentive to integrate vertically

OpenAIRE

Grandner, Thomas

2000-01-01

In this paper I analyze a vertically structured monopolized market with unionized firms. I compare two types of contracts: vertical integration and franchising. With franchising and wage bargaining at the firm level the union in the downstream firm is either very powerful or has no bargaining power at all, depending on the specific time structure of the model. These arguments could make integration preferable for the profit owners even if integration is accompanied by small transaction costs....

Supply chain integration, risk management and manufacturing flexibility

DEFF Research Database (Denmark)

Chaudhuri, Atanu; Boer, Harry; Taran, Yariv

2018-01-01

, respectively, and manufacturing flexibility. Design/methodology/approach – Using hierarchical regression, data are analyzed from a sample of 343 manufacturing plants in Asia collected in 2013-2014 as part of the International Manufacturing Strategy Survey (IMSS VI). Findings – Internal integration and supply......Purpose – The purpose of this paper is to investigate the impact of internal integration, external integration and supply chain risk management on manufacturing flexibility, and the moderating effect of supply chain risk management on the relationships between internal and external integration...... chain risk management have a direct effect on manufacturing flexibility. Supply chain risk management moderates the relationship between external integration and flexibility. Research limitations/implications – Further research is needed to generalize beyond the flexibility performance of discrete...

Solving Simple Kinetics without Integrals

Science.gov (United States)

de la Pen~a, Lisandro Herna´ndez

2016-01-01

The solution of simple kinetic equations is analyzed without referencing any topic from differential equations or integral calculus. Guided by the physical meaning of the rate equation, a systematic procedure is used to generate an approximate solution that converges uniformly to the exact solution in the case of zero, first, and second order…

Long-lasting modulation of feature integration by transcranial magnetic stimulation

NARCIS (Netherlands)

Scharnowski, Frank; Rueter, Johannes; Jolij, Jacob; Hermens, Frouke; Kammer, Thomas; Herzog, Michael H.

The human brain analyzes a visual object first by basic feature detectors. On the objects way to a conscious percept, these features are integrated in subsequent stages of the visual hierarchy. The time course of this feature integration is largely unknown. To shed light on the temporal dynamics of

Long-lasting modulation of feature integration by transcranial magnetic stimulation

NARCIS (Netherlands)

Scharnowski, Frank; Rueter, Johannes; Jolij, Jacob; Hermens, Frouke; Kammer, Thomas; Herzog, Michael H.

2009-01-01

The human brain analyzes a visual object first by basic feature detectors. On the objects way to a conscious percept, these features are integrated in subsequent stages of the visual hierarchy. The time course of this feature integration is largely unknown. To shed light on the temporal dynamics of

Vertical integration in the nuclear fuel cycle

International Nuclear Information System (INIS)

Mommsen, J.T.

1977-01-01

Vertical integration in the nuclear fuel cycle and its contribution to market power of integrated fuel suppliers were studied. The industry subdivision analyzed is the uranium raw materials sector. The hypotheses demonstrated are that (1) this sector of the industry is trending toward vertical integration between production of uranium raw materials and the manufacture of nuclear fuel elements, and (2) this vertical integration confers upon integrated firms a significant market advantage over non-integrated fuel manufacturers. Under microeconomic concepts the rationale for vertical integration is the pursuit of efficiency, and it is beneficial because it increases physical output and decreases price. The Market Advantage Model developed is an arithmetical statement of the relative market power (in terms of price) between non-integrated nuclear fuel manufacturers and integrated raw material/fuel suppliers, based on the concept of the ''squeeze.'' In operation, the model compares net profit and return on sales of nuclear fuel elements between the competitors, under different price and cost circumstances. The model shows that, if integrated and non-integrated competitors sell their final product at identical prices, the non-integrated manufacturer returns a net profit only 17% of the integrated firm. Also, the integrated supplier can price his product 35% below the non-integrated producer's price and still return the same net profit. Vertical integration confers a definite market advantage to the integrated supplier, and the basic source of that advantage is the cost-price differential of the raw material, uranium

Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia.

Science.gov (United States)

Mansour, Hader A; Talkowski, Michael E; Wood, Joel; Chowdari, Kodavali V; McClain, Lora; Prasad, Konasale; Montrose, Debra; Fagiolini, Andrea; Friedman, Edward S; Allen, Michael H; Bowden, Charles L; Calabrese, Joseph; El-Mallakh, Rif S; Escamilla, Michael; Faraone, Stephen V; Fossey, Mark D; Gyulai, Laszlo; Loftis, Jennifer M; Hauser, Peter; Ketter, Terence A; Marangell, Lauren B; Miklowitz, David J; Nierenberg, Andrew A; Patel, Jayendra; Sachs, Gary S; Sklar, Pamela; Smoller, Jordan W; Laird, Nan; Keshavan, Matcheri; Thase, Michael E; Axelson, David; Birmaher, Boris; Lewis, David; Monk, Tim; Frank, Ellen; Kupfer, David J; Devlin, Bernie; Nimgaonkar, Vishwajit L

2009-11-01

Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.

A Framework for Understanding Post-Merger Information Systems Integration

DEFF Research Database (Denmark)

Alaranta, Maria; Kautz, Karlheinz

2012-01-01

This paper develops a theoretical framework for the integration of information systems (IS) after a merger or an acquisition. The framework integrates three perspectives: a structuralist, an individualist, and an interactive process perspective to analyze and understand such integrations....... The framework is applied to a longitudinal case study of a manufacturing company that grew through an acquisition. The management decided to integrate the production control IS via tailoring a new system that blends together features of existing IS. The application of the framework in the case study confirms...... several known impediments to IS integrations. It also identifies a number of new inhibitors, as well as known and new facilitators that can bring post-merger IS integration to a success. Our findings provide relevant insights to researching and managing post-merger IS integrations. They emphasize...

Genome-Wide Association Study Reveals Greater Polygenic Loading for Schizophrenia in Cases With a Family History of Illness

Science.gov (United States)

Bigdeli, Tim B.; Ripke, Stephan; Bacanu, Silviu-Alin; Lee, Sang Hong; Wray, Naomi R.; Gejman, Pablo V.; Rietschel, Marcella; Cichon, Sven; St Clair, David; Corvin, Aiden; Kirov, George; McQuillin, Andrew; Gurling, Hugh; Rujescu, Dan; Andreassen, Ole A.; Werge, Thomas; Blackwood, Douglas H.R.; Pato, Carlos N.; Pato, Michele T.; Malhotra, Anil K.; O’Donovan, Michael C.; Kendler, Kenneth S.; Fanous, Ayman H.

2018-01-01

Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N = 978), cases reporting no such family history (N = 4,503), and unscreened controls (N = 8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke’s R2 = 0.0021; P = 0.00331; P-value threshold history positive compared to family history negative cases (0.32 and 0.22, respectively; P = 0.031).We found suggestive evidence of allelic effects detectable in large GWAS of schizophrenia that might be specific to particular family history subgroups. However, consideration of a polygenic risk score indicated a significant enrichment among family history positive cases for common allelic effects. Familial illness might, therefore, represent a more heritable form of schizophrenia, as suggested by

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

Directory of Open Access Journals (Sweden)

Renato Polimanti

2017-02-01

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

Quadratic integrals of motion for identical particle systems in quantum case

International Nuclear Information System (INIS)

Brije, I.; Gonera, S.; Kosinski, P.; Maslanka, P.; Giller, S.

2005-01-01

One studied quantum dynamic systems of identical particles allowing for additional integral of motion being quadratic in pulses. It was found that there was an appropriate way to ensure order that enabled to convert the classical integrals of motion into their quantum analogues. One analyzed relation of the mentioned integrals with splitting of the variables in the Schroedinger equation [ru

Drosophila and genome-wide association studies: a review and resource for the functional dissection of human complex traits

Science.gov (United States)

Wangler, Michael F.; Hu, Yanhui

2017-01-01

ABSTRACT Human genome-wide association studies (GWAS) have successfully identified thousands of susceptibility loci for common diseases with complex genetic etiologies. Although the susceptibility variants identified by GWAS usually have only modest effects on individual disease risk, they contribute to a substantial burden of trait variation in the overall population. GWAS also offer valuable clues to disease mechanisms that have long proven to be elusive. These insights could lead the way to breakthrough treatments; however, several challenges hinder progress, making innovative approaches to accelerate the follow-up of results from GWAS an urgent priority. Here, we discuss the largely untapped potential of the fruit fly, Drosophila melanogaster, for functional investigation of findings from human GWAS. We highlight selected examples where strong genomic conservation with humans along with the rapid and powerful genetic tools available for flies have already facilitated fine mapping of association signals, elucidated gene mechanisms, and revealed novel disease-relevant biology. We emphasize current research opportunities in this rapidly advancing field, and present bioinformatic analyses that systematically explore the applicability of Drosophila for interrogation of susceptibility signals implicated in more than 1000 human traits, based on all GWAS completed to date. Thus, our discussion is targeted at both human geneticists seeking innovative strategies for experimental validation of findings from GWAS, as well as the Drosophila research community, by whom ongoing investigations of the implicated genes will powerfully inform our understanding of human disease. PMID:28151408

Integration of Multiple Data Sources for predicting the Engagement of Students in Practical Activities

Directory of Open Access Journals (Sweden)

Llanos Tobarra

2014-09-01

Full Text Available This work presents the integration of an automatic assessment system for virtual/remote laboratories and the institutional Learning Management System (LMS, in order to analyze the students’ progress and their collaborative learning in virtual/remote laboratories. As a result of this integration, it is feasible to extract useful information for the characterization of the students’ learning process and detecting the students’ engagement with the practical activities of our subjects. From this integration, a dashboard has been created to graphically present to lecturers the analyzed results. Thanks to this, faculty can use the analyzed information in order to guide the learning/teaching process of each student. As an example, a subject focused on the configuration of network services has been chosen to implement our proposal.

Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK in disease susceptibility.

Directory of Open Access Journals (Sweden)

Chia-Jung Chang

Full Text Available The BLK and CD40 loci have been associated with Kawasaki disease (KD in two genome-wide association studies (GWAS conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354-1.657; P = 4.74×10(-31. We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC population and the expression of BLK in the peripheral blood leukocytes (leukocytes of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD.

METHODOLOGY FRAMEWORK FOR PROCESS INTEGRATION AND SERVICE MANAGEMENT

Directory of Open Access Journals (Sweden)

Darko Galinec

2007-06-01

Full Text Available History of information systems development was driven by business system's functions automation and mergers and acquisitions - business subjects integration into a whole. Modern business requires business processes integration through their dynamics and thus enterprise application integration (EAI as well. In this connection it is necessary to find ways and means of application integration and interaction in a consistent and reliable way. The real-time enterprise (RTE monitors, captures and analyzes root causes and overt events that are critical to its success the instant those events occur [6]. EAI is determined by business needs and business requirements. It must be based on business process repository and models, business integration methodology (BIM and information flow as well. Decisions concerning technology must be in function of successful application integration. In this paper EAI methodological framework and technological concepts for its achievements are introduced.

Regional Logistics Information Resources Integration Patterns and Countermeasures

Science.gov (United States)

Wu, Hui; Shangguan, Xu-ming

Effective integration of regional logistics information resources can provide collaborative services in information flow, business flow and logistics for regional logistics enterprises, which also can reduce operating costs and improve market responsiveness. First, this paper analyzes the realistic significance on the integration of regional logistics information. Second, this paper brings forward three feasible patterns on the integration of regional logistics information resources, These three models have their own strengths and the scope of application and implementation, which model is selected will depend on the specific business and the regional distribution of enterprises. Last, this paper discusses the related countermeasures on the integration of regional logistics information resources, because the integration of regional logistics information is a systems engineering, when the integration is advancing, the countermeasures should pay close attention to the current needs and long-term development of regional enterprises.

The security analyzer: A security analyzer program written in Prolog

International Nuclear Information System (INIS)

Zimmerman, B.D.; Densley, P.J.

1986-09-01

The Security Analyzer is a software tool capable of analyzing the effectiveness of a facility's security system. It is written in the Prolog logic programming computer language, using entity-relationship data modeling techniques. The program performs the following functions: (1) provides descriptive, locational and operational status information about intrusion detectors and assessment devices (i.e., ''sensors'' and ''cameras'') upon request; (2) provides for storage and retrieval of maintenance history information for various components of the security system (including intrusion detectors), and allows for changing that information as desired; (3) provides a ''search'' mode, wherein all paths are found from any specified physical location to another specified location which satisfy user chosen ''intruder detection'' probability and elapsed time criteria (i.e., the program finds the ''weakest paths'' from a security point of view). The first two of these functions can be provided fairly easily with a conventional database program; the third function could be provided using Fortran or some similar language, though with substantial difficulty. In the Security Analyzer program, all these functions are provided in a simple and straight-forward manner. This simplicity is possible because the program is written in the symbolic (as opposed to numeric) processing language Prolog, and because the knowledge base is structured according to entity-relationship modeling principles. Also, the use of Prolog and the entity-relationship modeling technique allows the capabilities of the Security analyzer program, both for knowledge base interrogation and for searching-type operations, to be easily expanded in ways that would be very difficult for a numeric and more algorithmically deterministic language such as Fortran to duplicate. 4 refs

Co-simulation of innovative integrated HVAC systems in buildings

Energy Technology Data Exchange (ETDEWEB)

Trcka, Marija; Hensena, Jan L.M.; Wetter, Michael

2010-06-21

Integrated performance simulation of buildings HVAC systems can help in reducing energy consumption and increasing occupant comfort. However, no single building performance simulation (BPS) tool offers sufficient capabilities and flexibilities to analyze integrated building systems and to enable rapid prototyping of innovative building and system technologies. One way to alleviate this problem is to use co-simulation, as an integrated approach to simulation. This article elaborates on issues important for co-simulation realization and discusses multiple possibilities to justify the particular approach implemented in the here described co-simulation prototype. The prototype is validated with the results obtained from the traditional simulation approach. It is further used in a proof-of-concept case study to demonstrate the applicability of the method and to highlight its benefits. Stability and accuracy of different coupling strategies are analyzed to give a guideline for the required coupling time step.

Analysis on the integration of ERP and e-commerce

Science.gov (United States)

Wang, Yongqing; Shi, Yuliana

2017-08-01

With the continuous development of China's modern economic construction, a variety of information technology are emerging. The new economic development characterized by e-commerce has accelerated the globalization of the economy. In face of increasingly fierce market competition, for enterprises, the constructions of ERP and e-commerce are necessary ways to enhance the core competitiveness of enterprises. At present, most of the internal ERP systems and external e-commerce systems are in relatively independent state. However, with the increasing fierce market competition, a single mode of operation has been unable to meet the requirements of enterprise development. Accordingly, the effective integration of ERP and e-commerce in the new era has become one of the most important topics for enterprise development. This paper firstly analyzes the relationship between ERP and e-commerce, and then analyzes the necessity and feasibility of integration, and finally discusses the integration strategies and technologies.

A path-integral approach to inclusive processes

International Nuclear Information System (INIS)

Sukumar, C.V.

1995-01-01

The cross section for an inclusive scattering process may be expressed in terms of a double path integral. Evaluation of the double path integral by the stationary-phase approximation yields classical equations of motion for the stationary trajectories and a classical cross section for the inclusive process which depends on the polarization of the initial state. Polarization analyzing powers are calculated from this theory and the results are compared with those obtained in an earlier paper. ((orig.))

The Model of Integrated Marketing Communication: Who has the Role to Influence Consumer Behaviour

Directory of Open Access Journals (Sweden)

Olimpia Elena Mihaela Oancea

2015-02-01

Full Text Available The purpose of this paper is proposes a theoretical framework to investigate the models of integrated marketing communication that can influence the consumer behaviour, and the development a model of integrated marketing communication. The research goals aim the following aspects: (a The analyze of the IMC concept; (b Identifying and analyzing the main models of integrated marketing communication that can influence the consumer behaviour; (c Identifying the variables that will be included in the conceptual model of integrated marketing communication proposed. A review of the integrated marketing communication literature show the fact that were developed a series models of integrated marketing communication which has the role to influence the consumer buying behavior, but these not capture the correlation between the following factors: sociological variables, external stimuli, integrated marketing communication and consumer behavior. The method used was the secondary research in order to fulfill the research objectives established. The major result of this paper consists in proposing of a new conceptual model of integrated marketing communication that captures the correlation between external stimuli - sociological variables - integrated marketing communication - consumer behavior.

Single Molecule Analysis Research Tool (SMART: an integrated approach for analyzing single molecule data.

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Max Greenfeld

Full Text Available Single molecule studies have expanded rapidly over the past decade and have the ability to provide an unprecedented level of understanding of biological systems. A common challenge upon introduction of novel, data-rich approaches is the management, processing, and analysis of the complex data sets that are generated. We provide a standardized approach for analyzing these data in the freely available software package SMART: Single Molecule Analysis Research Tool. SMART provides a format for organizing and easily accessing single molecule data, a general hidden Markov modeling algorithm for fitting an array of possible models specified by the user, a standardized data structure and graphical user interfaces to streamline the analysis and visualization of data. This approach guides experimental design, facilitating acquisition of the maximal information from single molecule experiments. SMART also provides a standardized format to allow dissemination of single molecule data and transparency in the analysis of reported data.

Data-Intensive Science and Research Integrity.

Science.gov (United States)

Resnik, David B; Elliott, Kevin C; Soranno, Patricia A; Smith, Elise M

2017-01-01

In this commentary, we consider questions related to research integrity in data-intensive science and argue that there is no need to create a distinct category of misconduct that applies to deception related to processing, analyzing, or interpreting data. The best way to promote integrity in data-intensive science is to maintain a firm commitment to epistemological and ethical values, such as honesty, openness, transparency, and objectivity, which apply to all types of research, and to promote education, policy development, and scholarly debate concerning appropriate uses of statistics.

Alternative containment integrity test methods, an overview of possible techniques

International Nuclear Information System (INIS)

Spletzer, B.L.

1986-01-01

A study is being conducted to develop and analyze alternative methods for testing of containment integrity. The study is focused on techniques for continuously monitoring containment integrity to provide rapid detection of existing leaks, thus providing greater certainty of the integrity of the containment at any time. The study is also intended to develop techniques applicable to the currently required Type A integrated leakage rate tests. A brief discussion of the range of alternative methods currently being considered is presented. The methods include applicability to all major containment types, operating and shutdown plant conditions, and quantitative and qualitative leakage measurements. The techniques are analyzed in accordance with the current state of knowledge of each method. The bulk of the techniques discussed are in the conceptual stage, have not been tested in actual plant conditions, and are presented here as a possible future direction for evaluating containment integrity. Of the methods considered, no single method provides optimum performance for all containment types. Several methods are limited in the types of containment for which they are applicable. The results of the study to date indicate that techniques for continuous monitoring of containment integrity exist for many plants and may be implemented at modest cost

INTEGRATED TICKETING SYSTEM OF PUBLIC TRANSPORT IN JAKARTA VS VÄRMLAND, SWEDEN

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Teguh Himawan Ronggosusanto

2015-05-01

Full Text Available The heightened mobility of people in the DKI Jakarta province and surrounding area requires balance of the development public transport services. One of service attributes in public transportation is ticketing system. Currently, the ticketing system in Jakarta needs to be improved and still not integrated. Therefore, the importance to develop and implement a new integrated ticketing system to increase the competitiveness and attractiveness of public transports. It also gives an opportunity to the operators in order to implement several of ticket prices. There are some of barriers that faced by operators in development a new integrated ticketing system such as; institutional issue, resources integration, and financial problems. In order to describe and analyze the development of a new integrated ticketing system, this thesis uses a qualitative research approach and five sources of evidence i.e. documentation, archival records, an interview, direct and participant observations through a survey using the form of questionnaires that distributed to the public transport users. Further, this study also uses the case of Värmlandstrafik AB as the comparative study and the theoretical basis of the new services development as an approach to assess the possibility of implement a new integrated ticketing system. It aims to investigate the ticketing system phenomenon using information and data observations as materials to analyze, explore, and provide depth explanation. By analyzing data from a survey of passengers, this study gave a description and explanation related the characteristic and the travel behavior of passenger, also an assessment of ticketing system that underlies the development a new integrated ticketing system. Then, using the comparative case study of Värmlandstrafik AB that already implement an integrated ticketing system and the self-services in provision of public transport services gave an analysis what needs to prepare for implement a

Teachers' Perceptions of Technology Integration in a Unified School District

Science.gov (United States)

Bloodman, Suzette L.

2014-01-01

A unified school district (USD) continues to invest millions of dollars into its technology integration initiatives with minimal academic gains. Since teachers are essential to effective technology integration, the purpose of this phenomenological study was to analyze the perceptions of 13 teachers within the USD relative to how they could more…

Scaling to diversity: The DERECHOS distributed infrastructure for analyzing and sharing data

Science.gov (United States)

Rilee, M. L.; Kuo, K. S.; Clune, T.; Oloso, A.; Brown, P. G.

2016-12-01

Integrating Earth Science data from diverse sources such as satellite imagery and simulation output can be expensive and time-consuming, limiting scientific inquiry and the quality of our analyses. Reducing these costs will improve innovation and quality in science. The current Earth Science data infrastructure focuses on downloading data based on requests formed from the search and analysis of associated metadata. And while the data products provided by archives may use the best available data sharing technologies, scientist end-users generally do not have such resources (including staff) available to them. Furthermore, only once an end-user has received the data from multiple diverse sources and has integrated them can the actual analysis and synthesis begin. The cost of getting from idea to where synthesis can start dramatically slows progress. In this presentation we discuss a distributed computational and data storage framework that eliminates much of the aforementioned cost. The SciDB distributed array database is central as it is optimized for scientific computing involving very large arrays, performing better than less specialized frameworks like Spark. Adding spatiotemporal functions to the SciDB creates a powerful platform for analyzing and integrating massive, distributed datasets. SciDB allows Big Earth Data analysis to be performed "in place" without the need for expensive downloads and end-user resources. Spatiotemporal indexing technologies such as the hierarchical triangular mesh enable the compute and storage affinity needed to efficiently perform co-located and conditional analyses minimizing data transfers. These technologies automate the integration of diverse data sources using the framework, a critical step beyond current metadata search and analysis. Instead of downloading data into their idiosyncratic local environments, end-users can generate and share data products integrated from diverse multiple sources using a common shared environment

Type 1 diabetes genome-wide association studies

DEFF Research Database (Denmark)

Pociot, Flemming

2017-01-01

Genetic studies have identified >60 loci associated with the risk of developing type 1 diabetes (T1D). The vast majority of these are identified by genome-wide association studies (GWAS) using large case-control cohorts of European ancestry. More than 80% of the heritability of T1D can be explained...... by GWAS data in this population group. However, with few exceptions, their individual contribution to T1D risk is low and understanding their function in disease biology remains a huge challenge. GWAS on its own does not inform us in detail on disease mechanisms, but the combination of GWAS data...... with other omics-data is beginning to advance our understanding of T1D etiology and pathogenesis. Current knowledge supports the notion that genetic variation in both pancreatic β cells and in immune cells is central in mediating T1D risk. Advances, perspectives and limitations of GWAS are discussed...

Analyzing the User Behavior toward Electronic Commerce Stimuli.

Science.gov (United States)

Lorenzo-Romero, Carlota; Alarcón-Del-Amo, María-Del-Carmen; Gómez-Borja, Miguel-Ángel

2016-01-01

Based on the Stimulus-Organism-Response paradigm this research analyzes the main differences between the effects of two types of web technologies: Verbal web technology (i.e., navigational structure as utilitarian stimulus) versus non-verbal web technology (music and presentation of products as hedonic stimuli). Specific webmosphere stimuli have not been examined yet as separate variables and their impact on internal and behavioral responses seems unknown. Therefore, the objective of this research consists in analyzing the impact of these web technologies -which constitute the web atmosphere or webmosphere of a website- on shopping human behavior (i.e., users' internal states -affective, cognitive, and satisfaction- and behavioral responses - approach responses, and real shopping outcomes-) within the retail online store created by computer, taking into account some mediator variables (i.e., involvement, atmospheric responsiveness, and perceived risk). A 2 ("free" versus "hierarchical" navigational structure) × 2 ("on" versus "off" music) × 2 ("moving" versus "static" images) between-subjects computer experimental design is used to test empirically this research. In addition, an integrated methodology was developed allowing the simulation, tracking and recording of virtual user behavior within an online shopping environment. As main conclusion, this study suggests that the positive responses of online consumers might increase when they are allowed to freely navigate the online stores and their experience is enriched by animate gifts and music background. The effect caused by mediator variables modifies relatively the final shopping human behavior.

Analyzing the user behavior towards Electronic Commerce stimuli

Directory of Open Access Journals (Sweden)

Carlota Lorenzo-Romero

2016-11-01

Full Text Available Based on the Stimulus-Organism-Response paradigm this research analyzes the main differences between the effects of two types of web technologies: Verbal web technology (i.e. navigational structure as utilitarian stimulus versus nonverbal web technology (music and presentation of products as hedonic stimuli. Specific webmosphere stimuli have not been examined yet as separate variables and their impact on internal and behavioral responses seems unknown. Therefore, the objective of this research consists in analyzing the impact of these web technologies –which constitute the web atmosphere or webmosphere of a website– on shopping human bebaviour (i.e. users’ internal states -affective, cognitive, and satisfaction- and behavioral responses - approach responses, and real shopping outcomes- within the retail online store created by computer, taking into account some mediator variables (i.e. involvement, atmospheric responsiveness, and perceived risk. A 2(free versus hierarchical navigational structure x2(on versus off music x2(moving versus static images between-subjects computer experimental design is used to test empirically this research. In addition, an integrated methodology was developed allowing the simulation, tracking and recording of virtual user behavior within an online shopping environment. As main conclusion, this study suggests that the positive responses of online consumers might increase when they are allowed to freely navigate the online stores and their experience is enriched by animate gifts and music background. The effect caused by mediator variables modifies relatively the final shopping human behavior.

Analyzing the User Behavior toward Electronic Commerce Stimuli

Science.gov (United States)

Lorenzo-Romero, Carlota; Alarcón-del-Amo, María-del-Carmen; Gómez-Borja, Miguel-Ángel

2016-01-01

Based on the Stimulus-Organism-Response paradigm this research analyzes the main differences between the effects of two types of web technologies: Verbal web technology (i.e., navigational structure as utilitarian stimulus) versus non-verbal web technology (music and presentation of products as hedonic stimuli). Specific webmosphere stimuli have not been examined yet as separate variables and their impact on internal and behavioral responses seems unknown. Therefore, the objective of this research consists in analyzing the impact of these web technologies –which constitute the web atmosphere or webmosphere of a website– on shopping human behavior (i.e., users’ internal states -affective, cognitive, and satisfaction- and behavioral responses – approach responses, and real shopping outcomes-) within the retail online store created by computer, taking into account some mediator variables (i.e., involvement, atmospheric responsiveness, and perceived risk). A 2 (“free” versus “hierarchical” navigational structure) × 2 (“on” versus “off” music) × 2 (“moving” versus “static” images) between-subjects computer experimental design is used to test empirically this research. In addition, an integrated methodology was developed allowing the simulation, tracking and recording of virtual user behavior within an online shopping environment. As main conclusion, this study suggests that the positive responses of online consumers might increase when they are allowed to freely navigate the online stores and their experience is enriched by animate gifts and music background. The effect caused by mediator variables modifies relatively the final shopping human behavior. PMID:27965549

Genome-Wide Association Study for Identifying Loci that Affect Fillet Yield, Carcass, and Body Weight Traits in Rainbow Trout (Oncorhynchus mykiss).

Science.gov (United States)

Gonzalez-Pena, Dianelys; Gao, Guangtu; Baranski, Matthew; Moen, Thomas; Cleveland, Beth M; Kenney, P Brett; Vallejo, Roger L; Palti, Yniv; Leeds, Timothy D

2016-01-01

Fillet yield (FY, %) is an economically-important trait in rainbow trout aquaculture that affects production efficiency. Despite that, FY has received little attention in breeding programs because it is difficult to measure on a large number of fish and cannot be directly measured on breeding candidates. The recent development of a high-density SNP array for rainbow trout has provided the needed tool for studying the underlying genetic architecture of this trait. A genome-wide association study (GWAS) was conducted for FY, body weight at 10 (BW10) and 13 (BW13) months post-hatching, head-off carcass weight (CAR), and fillet weight (FW) in a pedigreed rainbow trout population selectively bred for improved growth performance. The GWAS analysis was performed using the weighted single-step GBLUP method (wssGWAS). Phenotypic records of 1447 fish (1.5 kg at harvest) from 299 full-sib families in three successive generations, of which 875 fish from 196 full-sib families were genotyped, were used in the GWAS analysis. A total of 38,107 polymorphic SNPs were analyzed in a univariate model with hatch year and harvest group as fixed effects, harvest weight as a continuous covariate, and animal and common environment as random effects. A new linkage map was developed to create windows of 20 adjacent SNPs for use in the GWAS. The two windows with largest effect for FY and FW were located on chromosome Omy9 and explained only 1.0-1.5% of genetic variance, thus suggesting a polygenic architecture affected by multiple loci with small effects in this population. One window on Omy5 explained 1.4 and 1.0% of the genetic variance for BW10 and BW13, respectively. Three windows located on Omy27, Omy17, and Omy9 (same window detected for FY) explained 1.7, 1.7, and 1.0%, respectively, of genetic variance for CAR. Among the detected 100 SNPs, 55% were located directly in genes (intron and exons). Nucleotide sequences of intragenic SNPs were blasted to the Mus musculus genome to create a

Crosstalk performance of integrated optical cross-connects

NARCIS (Netherlands)

Herben, C.G.P.; Leijtens, X.J.M.; Maat, D.H.P.; Blok, H.; Smit, M.K.

1999-01-01

Crosstalk performance of monolithically integrated multiwavelength optical cross-connects (OXC's) depends strongly on their architecture. In this paper, a semiquantitative analysis of crosstalk in 11 different architectures is presented. Two architectures are analyzed numerically in more detail and

The integration of law and integrality of the legislation as necessary conditions for the success of law enforcement in interstate integration

Directory of Open Access Journals (Sweden)

Sergey Baburin

2017-01-01

processes, it is more appropriate to talk about integrality.The author critically analyzes the features of an integrative understanding of law that are highlighted in the legal literature.The results of the study can be applied in the design of the constitutional-legal mechanisms of interstate Eurasian integration in the framework of the legal modernization of the modern Russian state.Conclusions. The author comes to the conclusion that the use of integral norms of the legislation makes the law alive and develop the integration models. Instability of legal regulation is a serious challenge to the integrity of Russian law. Emerging legislation of the Union State of Russia and Belarus and the Eurasian Economic Union are integral, but the law of these political and legal entities is not integrative today, it does not exist simply. As a consequence, law enforcement in the States participating in the interstate integration is carried out only through the implementation of national legislation.

Gearbox vibration diagnostic analyzer

Science.gov (United States)

1992-01-01

This report describes the Gearbox Vibration Diagnostic Analyzer installed in the NASA Lewis Research Center's 500 HP Helicopter Transmission Test Stand to monitor gearbox testing. The vibration of the gearbox is analyzed using diagnostic algorithms to calculate a parameter indicating damaged components.

Extraction spectrophotometric analyzer

International Nuclear Information System (INIS)

Batik, J.; Vitha, F.

1985-01-01

Automation is discussed of extraction spectrophotometric determination of uranium in a solution. Uranium is extracted from accompanying elements in an HCl medium with a solution of tributyl phosphate in benzene. The determination is performed by measuring absorbance at 655 nm in a single-phase ethanol-water-benzene-tributyl phosphate medium. The design is described of an analyzer consisting of an analytical unit and a control unit. The analyzer performance promises increased productivity of labour, improved operating and hygiene conditions, and mainly more accurate results of analyses. (J.C.)

A tandem parallel plate analyzer

International Nuclear Information System (INIS)

Hamada, Y.; Fujisawa, A.; Iguchi, H.; Nishizawa, A.; Kawasumi, Y.

1996-11-01

By a new modification of a parallel plate analyzer the second-order focus is obtained in an arbitrary injection angle. This kind of an analyzer with a small injection angle will have an advantage of small operational voltage, compared to the Proca and Green analyzer where the injection angle is 30 degrees. Thus, the newly proposed analyzer will be very useful for the precise energy measurement of high energy particles in MeV range. (author)

An explicit MOT-TDVIE scheme for analyzing electromagnetic field interactions on nonlinear scatterers

KAUST Repository

Ulku, Huseyin Arda

2015-02-01

An explicit marching on-in-time (MOT) based time domain electric field volume integral equation (TDVIE) solver for characterizing electromagnetic wave interactions on scatterers with nonlinear material properties is proposed. Discretization of the unknown electric field intensity and flux density is carried out by half and full Schaubert-Wilton-Glisson basis functions, respectively. Coupled system of spatially discretized TDVIE and the nonlinear constitutive relation between the field intensity and the flux density is integrated in time to compute the samples of the unknowns. An explicit PE(CE)m scheme is used for this purpose. Explicitness allows for \\'easy\\' incorporation of the nonlinearity as a function only to be evaluated on the right hand side of the coupled system of equations. A numerical example that demonstrates the applicability of the proposed MOT scheme to analyzing electromagnetic interactions on Kerr-nonlinear scatterers is presented. © 2015 IEEE.

Generalized Majority Logic Criterion to Analyze the Statistical Strength of S-Boxes

Science.gov (United States)

Hussain, Iqtadar; Shah, Tariq; Gondal, Muhammad Asif; Mahmood, Hasan

2012-05-01

The majority logic criterion is applicable in the evaluation process of substitution boxes used in the advanced encryption standard (AES). The performance of modified or advanced substitution boxes is predicted by processing the results of statistical analysis by the majority logic criteria. In this paper, we use the majority logic criteria to analyze some popular and prevailing substitution boxes used in encryption processes. In particular, the majority logic criterion is applied to AES, affine power affine (APA), Gray, Lui J, residue prime, S8 AES, Skipjack, and Xyi substitution boxes. The majority logic criterion is further extended into a generalized majority logic criterion which has a broader spectrum of analyzing the effectiveness of substitution boxes in image encryption applications. The integral components of the statistical analyses used for the generalized majority logic criterion are derived from results of entropy analysis, contrast analysis, correlation analysis, homogeneity analysis, energy analysis, and mean of absolute deviation (MAD) analysis.

Microgamma Scan System for analyzing radial isotopic profiles of irradiated transmutation fuels

International Nuclear Information System (INIS)

Hilton, Bruce A.; McGrath, Christopher A.

2008-01-01

The U. S. Global Nuclear Energy Partnership / Advanced Fuel Cycle Initiative (GNEP/AFCI) is developing metallic transmutation alloys as a fuel form to transmute the long-lived transuranic actinide isotopes contained in spent nuclear fuel into shorter-lived fission products. A micro-gamma scan system is being developed to analyze the radial distribution of fission products, such as Cs-137, Cs-134, Ru-106, and Zr-95, in irradiated fuel cross-sections. The micro-gamma scan system consists of a precision linear stage with integrated sample holder and a tungsten alloy collimator, which interfaces with the Idaho National Laboratory (INL) Analytical Laboratory Hot Cell (ALHC) Gamma Scan System high purity germanium detector, multichannel analyzer, and removable collimators. A simplified model of the micro-gamma scan system was developed in MCNP (Monte-Carlo N-Particle Transport Code) and used to investigate the system performance and to interpret data from the scoping studies. Preliminary measurements of the micro-gamma scan system are discussed. (authors)

Behavior of QQ-plots and genomic control in studies of gene-environment interaction.

Directory of Open Access Journals (Sweden)

Arend Voorman

2011-05-01

Full Text Available Genome-wide association studies of gene-environment interaction (GxE GWAS are becoming popular. As with main effects GWAS, quantile-quantile plots (QQ-plots and Genomic Control are being used to assess and correct for population substructure. However, in G x E work these approaches can be seriously misleading, as we illustrate; QQ-plots may give strong indications of substructure when absolutely none is present. Using simulation and theory, we show how and why spurious QQ-plot inflation occurs in G x E GWAS, and how this differs from main-effects analyses. We also explain how simple adjustments to standard regression-based methods used in G x E GWAS can alleviate this problem.

A Genome-Wide Association Study Primer for Clinicians

Directory of Open Access Journals (Sweden)

Tzu-Hao Wang

2009-06-01

Full Text Available Genome-wide association studies (GWAS use high-throughput genotyping technology to relate hundreds of thousands of genetic markers (genotypes to clinical conditions and measurable traits (phenotypes. This review is intended to serve as an introduction to GWAS for clinicians, to allow them to better appreciate the value and limitations of GWAS for genotype-disease association studies. The input of clinicians is vital for GWAS, since disease heterogeneity is frequently a confounding factor that can only really be solved by clinicians. For diseases that are difficult to diagnose, clinicians should ensure that the cases do indeed have the disease; for common diseases, clinicians should ensure that the controls are truly disease-free.

Analyzing in the present

DEFF Research Database (Denmark)

Revsbæk, Line; Tanggaard, Lene

2015-01-01

The article presents a notion of “analyzing in the present” as a source of inspiration in analyzing qualitative research materials. The term emerged from extensive listening to interview recordings during everyday commuting to university campus. Paying attention to the way different parts of vari...

Riemann type algebraic structures and their differential-algebraic integrability analysis

Directory of Open Access Journals (Sweden)

Prykarpatsky A.K.

2010-06-01

Full Text Available The differential-algebraic approach to studying the Lax type integrability of generalized Riemann type equations is devised. The differentiations and the associated invariant differential ideals are analyzed in detail. The approach is also applied to studying the Lax type integrability of the well known Korteweg-de Vries dynamical system.

Integrated Ecological River Health Assessments, Based on Water Chemistry, Physical Habitat Quality and Biological Integrity

Directory of Open Access Journals (Sweden)

Ji Yoon Kim

2015-11-01

Full Text Available This study evaluated integrative river ecosystem health using stressor-based models of physical habitat health, chemical water health, and biological health of fish and identified multiple-stressor indicators influencing the ecosystem health. Integrated health responses (IHRs, based on star-plot approach, were calculated from qualitative habitat evaluation index (QHEI, nutrient pollution index (NPI, and index of biological integrity (IBI in four different longitudinal regions (Groups I–IV. For the calculations of IHRs values, multi-metric QHEI, NPI, and IBI models were developed and their criteria for the diagnosis of the health were determined. The longitudinal patterns of the river were analyzed by a self-organizing map (SOM model and the key major stressors in the river were identified by principal component analysis (PCA. Our model scores of integrated health responses (IHRs suggested that mid-stream and downstream regions were impaired, and the key stressors were closely associated with nutrient enrichment (N and P and organic matter pollutions from domestic wastewater disposal plants and urban sewage. This modeling approach of IHRs may be used as an effective tool for evaluations of integrative ecological river health..

THE INTEGRATION AND INVESTMENT POTENTIAL OF BRICS

Directory of Open Access Journals (Sweden)

Sidorova E. A.

2016-06-01

Full Text Available In the modern global economy international integration associations are full subjects of it. However, the changing world is changing the integration inquiry: there is the transformation of the integration processes because of globalization. A key principle of the integration process is to accelerate the economic development of the system and its individual composes through the implementation of the integration potential. In this regard, the article researches the integration potential of BRICS (an informal association consists of Brazil, Russia, India, China and South Africa as a significant subject of the world economy, including it analyzes trade flows of these countries using the index method. Moreover, it researches the investment potential of BRICS as the part of the integration potential. Finally, it focuses on the association institutionalization in the monetary sphere. Research has shown that the integration potential of BRICS opens new prospects for cooperation and development of the member countries. At the same time the creation of new financial institutions in the framework of the association (in particular, the New Development Bank and the Contingent Reserve Arrangement can help to strengthen the cooperation among the countries and to promote more representative global governance.

State of art report for critical flow model to analyze a break flow in pressurizer of integral type reactor

Energy Technology Data Exchange (ETDEWEB)

Kang, Yeon Moon; Lee, D. J.; Yoon, J. H.; Kim, J. P.; Kim, H. Y

1999-03-01

At a critical flow condition, the flow rate can't exceed a maximum value for given upstream conditions and the limited flow rate is called as a critical flow rate. The phenomena of critical flow occur at the discharge of a single phase gas or subcooled water through nozzles and pipes. Among the previous researches on critical flow, many accurate correlations on pressure, temperature and flow rate are represented for the single phase gas. However, for the two phase critical flow, the results of previous work showed that there was a large discrepancy between the analytical and experimental data and the data were in agreement for the limited thermodynamic conditions. Thus, further studies are required to enhance the two phase critical flow model. In the integral reactor, the critical flows of nitrogen gas and subcooled water are expected for the break of gas cylinder pipeline connected to the pressurizer. It requires that the inlet shape of the pipe and the nitrogen gas effect should be considered for the critical flow of integral reactor. The nitrogen gas exist in the pressurizer may affect the flow rate of primary coolant, which has been considered only for a few previous researches. Thus, the evaluation of the effect of the nitrogen on the critical flow gas should be preceded for the proper analysis of the critical flow in the integral reactor. In this report, not only the essences of previous work on critical flow were investigated and summarized but also the effect of nitrogen gas and the inlet shape of the pipe on the critical flow were also investigated. (author)

State of art report for critical flow model to analyze a break flow in pressurizer of integral type reactor

International Nuclear Information System (INIS)

Kang, Yeon Moon; Lee, D. J.; Yoon, J. H.; Kim, J. P.; Kim, H. Y.

1999-03-01

At a critical flow condition, the flow rate can't exceed a maximum value for given upstream conditions and the limited flow rate is called as a critical flow rate. The phenomena of critical flow occur at the discharge of a single phase gas or subcooled water through nozzles and pipes. Among the previous researches on critical flow, many accurate correlations on pressure, temperature and flow rate are represented for the single phase gas. However, for the two phase critical flow, the results of previous work showed that there was a large discrepancy between the analytical and experimental data and the data were in agreement for the limited thermodynamic conditions. Thus, further studies are required to enhance the two phase critical flow model. In the integral reactor, the critical flows of nitrogen gas and subcooled water are expected for the break of gas cylinder pipeline connected to the pressurizer. It requires that the inlet shape of the pipe and the nitrogen gas effect should be considered for the critical flow of integral reactor. The nitrogen gas exist in the pressurizer may affect the flow rate of primary coolant, which has been considered only for a few previous researches. Thus, the evaluation of the effect of the nitrogen on the critical flow gas should be preceded for the proper analysis of the critical flow in the integral reactor. In this report, not only the essences of previous work on critical flow were investigated and summarized but also the effect of nitrogen gas and the inlet shape of the pipe on the critical flow were also investigated. (author)

Precise digital integration in wide time range: theory and realization

International Nuclear Information System (INIS)

Batrakov, A.M.; Pavlenko, A.V.

2017-01-01

The digital integration method based on using high-speed precision analog-to-digital converters (ADC) has become widely used over the recent years. The paper analyzes the limitations of this method that are caused by the signal properties, ADC sampling rate and noise spectral density of the ADC signal path. This analysis allowed creating digital integrators with accurate synchronization and achieving an integration error of less than 10 −5 in the time range from microseconds to tens of seconds. The structure of the integrator is described and its basic parameters are presented. The possibilities of different ADC chips in terms of their applicability to digital integrators are discussed. A comparison with other integrating devices is presented.

Measurements of volatile compound contents in resins using a moisture analyzer.

Science.gov (United States)

Hashimoto, Masanori; Nagano, Futami; Endo, Kazuhiko; Ohno, Hiroki

2010-02-01

The contents of volatile adhesive compounds, such as water, solvents, and residual unpolymerized monomers, affect the integrity and durability of adhesive bonding. However, there is no method available that can be used to rapidly assess the residual solvent or water contents of adhesive resins. This study examined the effectiveness of a digital moisture analyzer to measure the volatile compound contents of resins. Five self-etching adhesives and seven experimental light-cured resins prepared with different contents (0, 10, and 20% by weight) of water or solvents (acetone and ethanol) were examined in this study. The resins were prepared using different methods (with and without air blast or light-curing) to simulate the clinical conditions of adhesive application. Resin weight changes (% of weight loss) were determined as the residual volatile compound contents, using the moisture analyzer. After the measurements, the resin films were examined using a scanning electron microscope. The weight changes of the resins were found to depend on the amount of water or solvents evaporating from the resin. Water and solvents were evaporated by air blast or light-curing, but some of the water and solvents remained in the cured resin. The moisture analyzer is easy to operate and is a useful instrument for using to measure the residual volatile compound contents of adhesive resin.

Design and development of VHDL based IP core for coincidence analyzer for FPGA based TDCR system

International Nuclear Information System (INIS)

Agarwal, Shivam; Gupta, Ashutosh; Chaudhury, Probal; Sharma, M.K.; Kulkarni, M.S.

2018-01-01

The coincidence counting technique is used in activity measurement methods to determine the activity of radionuclide e.g. 4πβ-γ method and Triple to Double Coincidence Ratio (TDCR) method etc. The 4πβ-γ method requires two inputs Coincidence Analyzer (CA) whereas; TDCR method requires three inputs CA. A VHDL (Very High Speed Integrated Circuit Hardware Description Language) based IP (Intellectual Property) core for coincidence analyzer has been designed and implemented in FPGA (Field Programmable Gate Array) for TDCR system. The developed IP not only facilitates the coincidence counting of three channels simultaneously but also provides an extendable dead time feature

[Genetic factors in myocardial infarction].

Science.gov (United States)

Hara, Masahiko; Sakata, Yasuhiko; Sato, Hiroshi

2013-02-01

One of the main mechanisms of acute myocardial infarction (AMI) is plaque rupture or erosion followed by intraluminal thrombus formation and occlusion of the coronary arteries. Thus far, many underlying conditions or environmental factors, such as hypertension, diabetes, dyslipidemia, smoking or obesity, as well as a family history of coronary artery diseases have been identified as risks for the onset of AMI. These risks suggest that AMI occurs due to interactions between underlying conditions and multiple genetic susceptibilities. For this reason, many target gene-disease association studies have been performed with the recent introduction of genome-wide association studies (GWAS) that have further revealed new genetic susceptibilities for AMI. GWAS is a way to examine many common genetic variants in different individuals to see if any variant is associated with a trait in a case-control fashion, and typically focuses on associations between single-nucleotide polymorphisms (SNP) and traits. SNP on chromosome 9p21 is one of the robust susceptibility variants for AMI which has been identified by many GWAS. In this review, we overview the methodology of GWAS, introduce genetic variants identified by GWAS as those with susceptibility for AMI, and describe the foresight of using GWAS to investigate genetic susceptibility to AMI.

Outcomes of Diffusion Tensor Tractography-Integrated Stereotactic Radiosurgery

Energy Technology Data Exchange (ETDEWEB)

Koga, Tomoyuki, E-mail: kouga-tky@umin.ac.jp [Department of Neurosurgery, University of Tokyo Hospital, Tokyo (Japan); Maruyama, Keisuke; Kamada, Kyousuke; Ota, Takahiro; Shin, Masahiro [Department of Neurosurgery, University of Tokyo Hospital, Tokyo (Japan); Itoh, Daisuke [Department of Radiology, University of Tokyo Hospital, Tokyo (Japan); Kunii, Naoto [Department of Neurosurgery, University of Tokyo Hospital, Tokyo (Japan); Ino, Kenji; Terahara, Atsuro; Aoki, Shigeki; Masutani, Yoshitaka [Department of Radiology, University of Tokyo Hospital, Tokyo (Japan); Saito, Nobuhito [Department of Neurosurgery, University of Tokyo Hospital, Tokyo (Japan)

2012-02-01

Purpose: To analyze the effect of use of tractography of the critical brain white matter fibers created from diffusion tensor magnetic resonance imaging on reduction of morbidity associated with radiosurgery. Methods and Materials: Tractography of the pyramidal tract has been integrated since February 2004 if lesions are adjacent to it, the optic radiation since May 2006, and the arcuate fasciculus since October 2007. By visually confirming the precise location of these fibers, the dose to these fiber tracts was optimized. One hundred forty-four consecutive patients with cerebral arteriovenous malformations who underwent radiosurgery with this technique between February 2004 and December 2009 were analyzed. Results: Tractography was prospectively integrated in 71 of 155 treatments for 144 patients. The pyramidal tract was visualized in 45, the optic radiation in 22, and the arcuate fasciculus in 13 (two tracts in 9). During the follow-up period of 3 to 72 months (median, 23 months) after the procedure, 1 patient showed permanent worsening of pre-existing dysesthesia, and another patient exhibited mild transient hemiparesis 12 months later but fully recovered after oral administration of corticosteroid agents. Two patients had transient speech disturbance before starting integration of the arcuate fasciculus tractography, but no patient thereafter. Conclusion: Integrating tractography helped prevent morbidity of radiosurgery in patients with brain arteriovenous malformations.

An MOT-TDIE solver for analyzing transient fields on graphene-based devices

KAUST Repository

Shi, Yifei

2016-11-02

A marching on-in-time (MOT) scheme for analyzing transient electromagnetic wave interactions on devices consisting of graphene sheets and dielectric substrates is proposed. The MOT scheme discretizes time domain resistive boundary condition (TD-RBC) and Poggio-Miller-Chang-Harrington-Wu-Tsai (TD-PMCHWT) integral equation, which are enforced on the surfaces of the graphene and dielectric substrate, respectively. The expressions of the time domain resistivity and conductivity of the graphene sheet are obtained analytically from the intra-band contribution formulated in frequency domain. Numerical results, which demonstrate the applicability of the proposed scheme, are presented.

Integrated mobile robot control

Science.gov (United States)

Amidi, Omead; Thorpe, Chuck E.

1991-03-01

This paper describes the strucwre implementation and operation of a real-time mobile robot controller which integrates capabilities such as: position estimation path specification and hacking human interfaces fast communication and multiple client support The benefits of such high-level capabilities in a low-level controller was shown by its implementation for the Naviab autonomous vehicle. In addition performance results from positioning and tracking systems are reported and analyzed.

Analyzing regional geological setting of DS uranium deposit based on the extensional research of remote sensing information

International Nuclear Information System (INIS)

Liu Dechang; Ye Fawang; Zhao Yingjun

2006-01-01

Through analyzing remote sensing image, a special geological environment for uranium ore-formation in Dongsheng-Hangjinqi area consisting of fault-uplift, southern margin fault and annular structure is discovered in this paper. Then the extensional researches on fault-uplift, southern margin fault as well as annular structure are made by using the information-integrated technologies to overlap the remote sensing information with other geoscientific information such as geophysics, geology and so on. Finally, the unusual regional geological setting is analyzed in the view of uranium ore formation, and its influences on the occurrence of DS uranium deposit are also discussed. (authors)

Commonwealth of the independent states - the new formof interethnic integration

Directory of Open Access Journals (Sweden)

Ф У Айбазова

2008-06-01

Full Text Available In clause on a concrete historical material the new independent sovereign states are analyzed which have been formed after disintegration of the USSR. Forms of their integration in economic, military, cultural and social integration are shown. Conclusions are done and the offers directed on the further efficiency of their cooperation are formulated.

Comprehensive Assessment of Integration Activity of Business Structures in Russian Regions

Directory of Open Access Journals (Sweden)

Mariya Gennad’evna Karelina

2016-11-01

Full Text Available In the context of economic sanctions and growing international isolation, the research into regional differences in integration development acquires special relevance for Russia; this fact determines the need for a comprehensive assessment of integration activity of business structures in Russian regions. The diversity of approaches to the study of problems and prospects of economic integration and the current debate about the role of integration processes in the development of regional economies determined a comprehensive approach to the concepts of “integration” and “integration activity” in order to create objective prerequisites for analyzing integration activity of business structures in the regions of Russia. The information base of the research is the data of Russian information and analytical agencies. The tools used in the research include methods for analyzing structural changes, methods for analyzing economic differentiation and concentration, nonparametric statistics methods, and econometric analysis methods. The first part of the paper shows that socio-economic development in constituent entities of Russia is closely connected with the operation of integrated business structures located on their territory. Having studied the structure and dynamics of integration activity, we reveal the growing heterogeneity of integration activity of business structures in Russian regions. The hypothesis about significant divergence of mergers and acquisitions for corporate structures in Russian regions was confirmed by high values of the Gini coefficient, the Herfindahl index and the decile differentiation coefficient. The second part of the paper contains a comparative analysis and proposes an econometric approach to the measurement of integration activity of business structures in subjects of the Russian Federation on the basis of integral synthetic categories. The approach we propose focuses on the development of a system of indicators

Automated detection of analyzable metaphase chromosome cells depicted on scanned digital microscopic images

Science.gov (United States)

Qiu, Yuchen; Wang, Xingwei; Chen, Xiaodong; Li, Yuhua; Liu, Hong; Li, Shibo; Zheng, Bin

2010-02-01

Visually searching for analyzable metaphase chromosome cells under microscopes is quite time-consuming and difficult. To improve detection efficiency, consistency, and diagnostic accuracy, an automated microscopic image scanning system was developed and tested to directly acquire digital images with sufficient spatial resolution for clinical diagnosis. A computer-aided detection (CAD) scheme was also developed and integrated into the image scanning system to search for and detect the regions of interest (ROI) that contain analyzable metaphase chromosome cells in the large volume of scanned images acquired from one specimen. Thus, the cytogeneticists only need to observe and interpret the limited number of ROIs. In this study, the high-resolution microscopic image scanning and CAD performance was investigated and evaluated using nine sets of images scanned from either bone marrow (three) or blood (six) specimens for diagnosis of leukemia. The automated CAD-selection results were compared with the visual selection. In the experiment, the cytogeneticists first visually searched for the analyzable metaphase chromosome cells from specimens under microscopes. The specimens were also automated scanned and followed by applying the CAD scheme to detect and save ROIs containing analyzable cells while deleting the others. The automated selected ROIs were then examined by a panel of three cytogeneticists. From the scanned images, CAD selected more analyzable cells than initially visual examinations of the cytogeneticists in both blood and bone marrow specimens. In general, CAD had higher performance in analyzing blood specimens. Even in three bone marrow specimens, CAD selected 50, 22, 9 ROIs, respectively. Except matching with the initially visual selection of 9, 7, and 5 analyzable cells in these three specimens, the cytogeneticists also selected 41, 15 and 4 new analyzable cells, which were missed in initially visual searching. This experiment showed the feasibility of

Bicycle: a bioinformatics pipeline to analyze bisulfite sequencing data.

Science.gov (United States)

Graña, Osvaldo; López-Fernández, Hugo; Fdez-Riverola, Florentino; González Pisano, David; Glez-Peña, Daniel

2018-04-15

High-throughput sequencing of bisulfite-converted DNA is a technique used to measure DNA methylation levels. Although a considerable number of computational pipelines have been developed to analyze such data, none of them tackles all the peculiarities of the analysis together, revealing limitations that can force the user to manually perform additional steps needed for a complete processing of the data. This article presents bicycle, an integrated, flexible analysis pipeline for bisulfite sequencing data. Bicycle analyzes whole genome bisulfite sequencing data, targeted bisulfite sequencing data and hydroxymethylation data. To show how bicycle overtakes other available pipelines, we compared them on a defined number of features that are summarized in a table. We also tested bicycle with both simulated and real datasets, to show its level of performance, and compared it to different state-of-the-art methylation analysis pipelines. Bicycle is publicly available under GNU LGPL v3.0 license at http://www.sing-group.org/bicycle. Users can also download a customized Ubuntu LiveCD including bicycle and other bisulfite sequencing data pipelines compared here. In addition, a docker image with bicycle and its dependencies, which allows a straightforward use of bicycle in any platform (e.g. Linux, OS X or Windows), is also available. ograna@cnio.es or dgpena@uvigo.es. Supplementary data are available at Bioinformatics online.

KinomeXplorer: an integrated platform for kinome biology studies

DEFF Research Database (Denmark)

Horn, Heiko; Schoof, Erwin; Kim, Jinho

2014-01-01

A letter to the editor is presented related to the KinomeXplorer, an integrated platform providing workflows to efficiently analyze phosphorylation dependent interaction networks or kinase signaling networks....

The quality management system in leading organization of the integrated structure

Directory of Open Access Journals (Sweden)

Kunitsyn A. M.

2018-02-01

Full Text Available the article has analyzed the problem of integrated structure management. The author has noted that the implementation of recommendations outlined in the article will allow building and improving the quality management system in leading organization of integrated structure on a regular basis that meets the requirements.

Network-assisted crop systems genetics: network inference and integrative analysis.

Science.gov (United States)

Lee, Tak; Kim, Hyojin; Lee, Insuk

2015-04-01

Although next-generation sequencing (NGS) technology has enabled the decoding of many crop species genomes, most of the underlying genetic components for economically important crop traits remain to be determined. Network approaches have proven useful for the study of the reference plant, Arabidopsis thaliana, and the success of network-based crop genetics will also require the availability of a genome-scale functional networks for crop species. In this review, we discuss how to construct functional networks and elucidate the holistic view of a crop system. The crop gene network then can be used for gene prioritization and the analysis of resequencing-based genome-wide association study (GWAS) data, the amount of which will rapidly grow in the field of crop science in the coming years. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analyzing climate change impacts on water resources under uncertainty using an integrated simulation-optimization approach

Science.gov (United States)

Zhuang, X. W.; Li, Y. P.; Nie, S.; Fan, Y. R.; Huang, G. H.

2018-01-01

An integrated simulation-optimization (ISO) approach is developed for assessing climate change impacts on water resources. In the ISO, uncertainties presented as both interval numbers and probability distributions can be reflected. Moreover, ISO permits in-depth analyses of various policy scenarios that are associated with different levels of economic consequences when the promised water-allocation targets are violated. A snowmelt-precipitation-driven watershed (Kaidu watershed) in northwest China is selected as the study case for demonstrating the applicability of the proposed method. Results of meteorological projections disclose that the incremental trend of temperature (e.g., minimum and maximum values) and precipitation exist. Results also reveal that (i) the system uncertainties would significantly affect water resources allocation pattern (including target and shortage); (ii) water shortage would be enhanced from 2016 to 2070; and (iii) the more the inflow amount decreases, the higher estimated water shortage rates are. The ISO method is useful for evaluating climate change impacts within a watershed system with complicated uncertainties and helping identify appropriate water resources management strategies hedging against drought.

Multichannel Mars Organic Analyzer (McMOA): Microfluidic Networks for the Automated In Situ Microchip Electrophoretic Analysis of Organic Biomarkers on Mars

Science.gov (United States)

Chiesl, T. N.; Benhabib, M.; Stockton, A. M.; Mathies, R. A.

2010-04-01

We present the Multichannel Mars Organic Analyzer (McMOA) for the analysis of Amino Acids, PAHs, and Oxidized Carbon. Microfluidic architecures integrating automated metering, mixing, on chip reactions, and serial dilutions are also discussed.

The Application of Integrated Design System for HTR-PM Design

International Nuclear Information System (INIS)

Qi Shi; Xiaojing Kang

2014-01-01

SmartPlant Enterprise(SPE) developed by Intergraph from America is a new generation integrated solution for engineering design. Combined with the application in a nuclear engineering, this paper introduced the composition and the data flow of Integrated Design System established by SPE, analyzed the advantages and the insufficiency, and provided the direction of continuous improvement. (author)

Train integrity detection risk analysis based on PRISM

Science.gov (United States)

Wen, Yuan

2018-04-01

GNSS based Train Integrity Monitoring System (TIMS) is an effective and low-cost detection scheme for train integrity detection. However, as an external auxiliary system of CTCS, GNSS may be influenced by external environments, such as uncertainty of wireless communication channels, which may lead to the failure of communication and positioning. In order to guarantee the reliability and safety of train operation, a risk analysis method of train integrity detection based on PRISM is proposed in this article. First, we analyze the risk factors (in GNSS communication process and the on-board communication process) and model them. Then, we evaluate the performance of the model in PRISM based on the field data. Finally, we discuss how these risk factors influence the train integrity detection process.

Environmental benefits of the integrated production of ethanol and biodiesel

International Nuclear Information System (INIS)

Souza, Simone Pereira; Seabra, Joaquim E.A.

2013-01-01

Highlights: ► Integrated bioenergy systems can favor the sustainability of biofuels. ► We analyzed the integrated production of ethanol and biodiesel in Brazil. ► GHG emissions and fossil energy use in the ethanol life cycle would be reduced. ► Socio-economic and other environmental aspects must be analyzed in future works. -- Abstract: The biorefinery of the future will be an integrated complex that makes a variety of products (e.g., biofuels, chemicals, power and protein) from a variety of feedstocks. The objective of this work was to evaluate the environmental benefits, compared to the traditional sugarcane ethanol system, of the integrated production of ethanol and biodiesel through a sugarcane–soybean biorefinery concept in Brazil. The environmental aspects considered here were the fossil energy use and the greenhouse gases (GHGs) emissions associated with ethanol production. In the Integrated System, soybean would be cultivated in part of the sugarcane reforming areas, which represents ∼17% of the total sugarcane area. Sugarcane and soybean oil would be processed in a combined ethanol–biodiesel plant, which would use only bagasse as fuel. All the demand for utilities of the biodiesel plant would be provided by the distillery. The output products of the combined plant would comprise sugarcane ethanol, soybean biodiesel (which would be used as diesel (B5) substitute in the sugarcane cultivation), bioelectricity and glycerin. The results indicate that the Integrated System can reduce the fossil energy consumption from 75 to 37 kJ/MJ of ethanol, when compared to the traditional system. For GHG emissions, the value would drop from 22.5 to 19.7 g CO 2 eq/MJ of ethanol. This analysis shows that the Integrated System is an important option to contribute to ethanol’s life cycle independence from fossil resources. This is an attractive environmental aspect, but socio-economic (as well as other environmental) aspects should also be analyzed in order to

Sources and fate of antimicrobials in integrated fish-pig and non-integrated tilapia farms.

Science.gov (United States)

Li, Kang; Liu, Liping; Zhan, Jia; Scippo, Marie-Louise; Hvidtfeldt, Kristian; Liu, Yuan; Dalsgaard, Anders

2017-10-01

Antimicrobial contamination in aquaculture products constitutes a food safety hazard, but little is known about the introduction and accumulation of antimicrobials in integrated fish-pig aquaculture. This study, conducted in 2013, aimed to determine the residues of 11 types of antimicrobials by UPLC-MS/MS analysis in fish feed (n=37), pig feed (n=9), pig manure (n=9), pond sediment (n=20), fish skin (n=20) and muscle tissue (n=20) sampled from integrated tilapia-pig farms, non-integrated tilapia farms and fish feed supply shops. There was a higher occurrence of antimicrobial residues in fish skin from both integrated and non-integrated farms, and in pig manure. Enrofloxacin (3.9-129.3μg/kg) and sulfadiazine (0.7-7.8μg/kg) were commonly detected in fish skin and muscle, pig manure and pond sediment from integrated farms, with different types of antimicrobials found in pig manure and tilapia samples. In non-integrated farms, sulfadiazine (2.5-89.9μg/kg) was the predominant antimicrobial detected in fish skin and muscle, fish feed and pond sediment. In general, antimicrobials seemed not to be commonly transmitted from pig to fish in tilapia-pig integrated farms, and fish feed, pig feed and pond sediment did not seem as important sources of the antimicrobials found in fish from both systems. The frequent findings of antimicrobial residues in fish skin compared with fish muscle was probably due to different pharmacokinetics in different tissue types, which have practical food safety implications since antimicrobial residues monitoring is usually performed analyzing mixed skin and fish muscle samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Nuclear power plant analyzer

International Nuclear Information System (INIS)

Stritar, A.

1986-01-01

The development of Nuclear Power Plant Analyzers in USA is described. There are two different types of Analyzers under development in USA, the forst in Idaho and Los Alamos national Lab, the second in brookhaven National lab. That one is described in detail. The computer hardware and the mathematical models of the reactor vessel thermalhydraulics are described. (author)

Big Data Analytics Platforms analyze from startups to traditional database players

Directory of Open Access Journals (Sweden)

Ionut TARANU

2015-07-01

Full Text Available Big data analytics enables organizations to analyze a mix of structured, semi-structured and unstructured data in search of valuable business information and insights. The analytical findings can lead to more effective marketing, new revenue opportunities, better customer service, improved operational efficiency, competitive advantages over rival organizations and other business benefits. With so many emerging trends around big data and analytics, IT organizations need to create conditions that will allow analysts and data scientists to experiment. "You need a way to evaluate, prototype and eventually integrate some of these technologies into the business," says Chris Curran[1]. In this paper we are going to review 10 Top Big Data Analytics Platforms and compare the key-features.

A Portable, Field-Deployable Analyzer for Isotopic Water Measurements

Science.gov (United States)

Berman, E. S.; Gupta, M.; Huang, Y. W.; Lacelle, D.; McKay, C. P.; Fortson, S.

2015-12-01

Water stable isotopes have for many years been used to study the hydrological cycle, catchment hydrology, and polar climate among other applications. Typically, discrete water samples are collected and transported to a laboratory for isotope analysis. Due to the expense and labor associated with such sampling, isotope studies have generally been limited in scope and time-resolution. Field sampling of water isotopes has been shown in recent years to provide dense data sets with the increased time resolution illuminating substantially greater short term variability than is generally observed during discrete sampling. A truly portable instrument also opens the possibility to utilize the instrument as a tool for identifying which water samples would be particularly interesting for further laboratory investigation. To make possible such field measurements of liquid water isotopes, Los Gatos Research has developed a miniaturized, field-deployable liquid water isotope analyzer. The prototype miniature liquid water isotope analyzer (mini-LWIA) uses LGR's patented Off-Axis ICOS (Integrated Cavity Output Spectroscopy) technology in a rugged, Pelican case housing for easy transport and field operations. The analyzer simultaneously measures both δ2H and δ18O from liquid water, with both manual and automatic water introduction options. The laboratory precision for δ2H is 0.6 ‰, and for δ18O is 0.3 ‰. The mini-LWIA was deployed in the high Arctic during the summer of 2015 at Inuvik in the Canadian Northwest Territories. Samples were collected from Sachs Harbor, on the southwest coast of Banks Island, including buried basal ice from the Lurentide Ice Sheet, some ice wedges, and other types of ground ice. Methodology and water analysis results from this extreme field deployment will be presented.

A model system for analyzing the interrelations between the energy sector and the whole economy

International Nuclear Information System (INIS)

Strubegger, M.; Messner, S.

1989-01-01

This paper introduces an instrument for the analysis of interactions between economy, private consumption and the energy sector. It is realized as an integrated model system that helps to analyze scenarios concerning future developments of the energy system and the economy for their internal consistency. This model system could provide a methodological basis for rationalizing the present debates on the economic consequences of different energy supply strategies. (author). 24 refs, 2 figs, 7 tabs

Dependent failure analysis research for the US NRC Risk Methods Integration and Evaluation Program

International Nuclear Information System (INIS)

Bohn, M.P.; Stack, D.W.; Campbell, D.J.; Rooney, J.J.; Rasmuson, D.M.

1985-01-01

The Risk Methods Integration and Evaluation Program (RMIEP), which is being performed for the Nuclear Regulatory Commission by Sandia National Laboratories, has the goals of developing new risk assessment methods and integrating the new and existing methods in a uniform procedure for performing an in-depth probabilistic risk assessment (PRA) with consistent levels of analysis for internal, external, and dependent failure scenarios. An important part of RMIEP is the recognition of the crucial importance of dependent common cause failures (CCFs) and the pressing need to develop effective methods for analyzing CCFs as part of a PRA. The NRC-sponsored Integrated Dependent Failure Methodology Program at Sandia is addressing this need. This paper presents a preliminary approach for analyzing CCFs as part of a PRA. A nine-step procedure for efficiently screening and analyzing dependent failure scenarios is presented, and each step is discussed

Analyzing an Aging ISS

Science.gov (United States)

Scharf, R.

2014-01-01

The ISS External Survey integrates the requirements for photographic and video imagery of the International Space Station (ISS) for the engineering, operations, and science communities. An extensive photographic survey was performed on all Space Shuttle flights to the ISS and continues to be performed daily, though on a level much reduced by the limited available imagery. The acquired video and photo imagery is used for both qualitative and quantitative assessments of external deposition and contamination, surface degradation, dynamic events, and MMOD strikes. Many of these assessments provide important information about ISS surfaces and structural integrity as the ISS ages. The imagery is also used to assess and verify the physical configuration of ISS structure, appendages, and components.

Update on the USNRC's nuclear plant analyzer

International Nuclear Information System (INIS)

Laats, E.T.

1987-01-01

The Nuclear Plant Analyzer (NPA) is the U.S. Nuclear Regulatory Commission's (NRC's) state-of-the-art nuclear reactor simulation capability. This computer software package integrates high fidelity nuclear reactor simulation codes such as the TRAC and RELAPS series of codes with color graphics display techniques and advanced workstation hardware. An overview of this program was given at the 1984 Summer Computer Simulation Conference (SCSC), with selected topics discussed at the 1985 and 1986 SCSCs. This paper addresses these activities and related experiences. First, The Class VI computer implementation is discussed. The trade-offs between gaining significantly greater computational speed and central memory, with the loss of performance due to many more simultaneous users is shown. Second, the goal of the super-minicomputer implementation is to produce a very cost-effective system that utilizes advanced (multi-dimensional, two-phase coolant) simulation capabilities at real wall-clock simulation times. Benchmarking of the initial super-minicomputer implementation is discussed. Finally, the technical and economic feasibility is addressed for implementing the super-minicomputer version of the NPA with the RELAPS simulation code onto the Black Fox full scope nuclear power plant simulator

Integration versus Segregation--The Case of Slovenia.

Science.gov (United States)

Pecek, Mojca

2001-01-01

Analyzes the discourse used when dealing with educational integration via legislation, highlighting philosophical and political solutions used as the basis for new legislation regarding education for children with special needs in Slovenia. Emphasizes the importance of considering parent, teacher, and student attitudes toward inclusive education…

The path dependency theory: analytical framework to study institutional integration. The case of France.

Science.gov (United States)

Trouvé, Hélène; Couturier, Yves; Etheridge, Francis; Saint-Jean, Olivier; Somme, Dominique

2010-06-30

The literature on integration indicates the need for an enhanced theorization of institutional integration. This article proposes path dependence as an analytical framework to study the systems in which integration takes place. PRISMA proposes a model for integrating health and social care services for older adults. This model was initially tested in Quebec. The PRISMA France study gave us an opportunity to analyze institutional integration in France. A qualitative approach was used. Analyses were based on semi-structured interviews with actors of all levels of decision-making, observations of advisory board meetings, and administrative documents. Our analyses revealed the complexity and fragmentation of institutional integration. The path dependency theory, which analyzes the change capacity of institutions by taking into account their historic structures, allows analysis of this situation. The path dependency to the Bismarckian system and the incomplete reforms of gerontological policies generate the coexistence and juxtaposition of institutional systems. In such a context, no institution has sufficient ability to determine gerontology policy and build institutional integration by itself. Using path dependence as an analytical framework helps to understand the reasons why institutional integration is critical to organizational and clinical integration, and the complex construction of institutional integration in France.

Implementation of a revised numerical integration technique into QAD

International Nuclear Information System (INIS)

De Gangi, N.L.

1983-01-01

A technique for numerical integration through a uniform volume source is developed. It is applied to gamma radiation transport shielding problems. The method is based on performing a numerical angular and ray point kernel integration and is incorporated into the QAD-CG computer code (i.e. QAD-UE). Several test problems are analyzed with this technique. Convergence properties of the method are analyzed. Gamma dose rates from a large tank and post LOCA dose rates inside a containment building are evaluated. Results are consistent with data from other methods. The new technique provides several advantages. User setup requirements for large volume source problems are reduced from standard point kernel requirements. Calculational efficiencies are improved. An order of magnitude improvement is seen with a test problem

Integrated proteomic and genomic analysis of colorectal cancer

Science.gov (United States)

Investigators who analyzed 95 human colorectal tumor samples have determined how gene alterations identified in previous analyses of the same samples are expressed at the protein level. The integration of proteomic and genomic data, or proteogenomics, pro

Polygenic risk and the development and course of asthma: Evidence from a 4-decade longitudinal study

Science.gov (United States)

Belsky, DW; Sears, MR; Hancox, RJ; Harrington, HL; Houts, R; Moffitt, TE; Sugden, K; Williams, B; Poulton, R; Caspi, A

2013-01-01

BACKGROUND Genome-wide association studies (GWAS) have discovered loci that predispose to asthma. To integrate these new discoveries with emerging models of asthma pathobiology, research is needed to test how genetic discoveries relate to developmental and biological characteristics of asthma. METHODS We derived a multi-locus profile of genetic risk from published GWAS of asthma case status. We then tested associations between this “genetic risk score” and developmental and biological characteristics of asthma in a population-based long-running birth cohort, the Dunedin Longitudinal Study (n=1,037). We evaluated asthma onset, persistence, atopy, airway hyperresponsiveness, incompletely reversible airflow obstruction, and asthma-related school and work absenteeism and hospitalization during 9 prospective assessments spanning ages 9–38 years, when 95% of surviving cohort members were seen. INTERPRETATION Cohort members at higher genetic risk experienced asthma onset earlier in life (HR=1.12 [1.01–1.26]). Childhood-onset asthma cases at higher genetic risk were more likely to become life-course-persistent asthma cases (RR=1.36 [1.14–1.63]). Asthma cases at higher genetic risk more often manifested atopy (RR=1.07 [1.01–1.14]), airway hyperresponsiveness (RR=1.16 [1.03–1.32]), and incompletely reversible airflow obstruction (RR=1.28 [1.04–1.57]). They were also more likely to miss school or work due to asthma (IRR=1.38 [1.02–1.86]) and to be hospitalized with breathing problems (HR=1.38 [1.07–1.79]). Genotypic information about asthma risk was independent of and additive to information derived from cohort members’ family histories of asthma. CONCLUSIONS Findings from this population study confirm that GWAS-discoveries for asthma associate with a childhood-onset phenotype and advance asthma genetics beyond the original GWAS-discoveries in three ways: (1) We show that genetic risks predict which childhood-onset asthma cases remit and which become

Micro-Analyzer: automatic preprocessing of Affymetrix microarray data.

Science.gov (United States)

Guzzi, Pietro Hiram; Cannataro, Mario

2013-08-01

A current trend in genomics is the investigation of the cell mechanism using different technologies, in order to explain the relationship among genes, molecular processes and diseases. For instance, the combined use of gene-expression arrays and genomic arrays has been demonstrated as an effective instrument in clinical practice. Consequently, in a single experiment different kind of microarrays may be used, resulting in the production of different types of binary data (images and textual raw data). The analysis of microarray data requires an initial preprocessing phase, that makes raw data suitable for use on existing analysis platforms, such as the TIGR M4 (TM4) Suite. An additional challenge to be faced by emerging data analysis platforms is the ability to treat in a combined way those different microarray formats coupled with clinical data. In fact, resulting integrated data may include both numerical and symbolic data (e.g. gene expression and SNPs regarding molecular data), as well as temporal data (e.g. the response to a drug, time to progression and survival rate), regarding clinical data. Raw data preprocessing is a crucial step in analysis but is often performed in a manual and error prone way using different software tools. Thus novel, platform independent, and possibly open source tools enabling the semi-automatic preprocessing and annotation of different microarray data are needed. The paper presents Micro-Analyzer (Microarray Analyzer), a cross-platform tool for the automatic normalization, summarization and annotation of Affymetrix gene expression and SNP binary data. It represents the evolution of the μ-CS tool, extending the preprocessing to SNP arrays that were not allowed in μ-CS. The Micro-Analyzer is provided as a Java standalone tool and enables users to read, preprocess and analyse binary microarray data (gene expression and SNPs) by invoking TM4 platform. It avoids: (i) the manual invocation of external tools (e.g. the Affymetrix Power

DMET-analyzer: automatic analysis of Affymetrix DMET data.

Science.gov (United States)

Guzzi, Pietro Hiram; Agapito, Giuseppe; Di Martino, Maria Teresa; Arbitrio, Mariamena; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Cannataro, Mario

2012-10-05

Clinical Bioinformatics is currently growing and is based on the integration of clinical and omics data aiming at the development of personalized medicine. Thus the introduction of novel technologies able to investigate the relationship among clinical states and biological machineries may help the development of this field. For instance the Affymetrix DMET platform (drug metabolism enzymes and transporters) is able to study the relationship among the variation of the genome of patients and drug metabolism, detecting SNPs (Single Nucleotide Polymorphism) on genes related to drug metabolism. This may allow for instance to find genetic variants in patients which present different drug responses, in pharmacogenomics and clinical studies. Despite this, there is currently a lack in the development of open-source algorithms and tools for the analysis of DMET data. Existing software tools for DMET data generally allow only the preprocessing of binary data (e.g. the DMET-Console provided by Affymetrix) and simple data analysis operations, but do not allow to test the association of the presence of SNPs with the response to drugs. We developed DMET-Analyzer a tool for the automatic association analysis among the variation of the patient genomes and the clinical conditions of patients, i.e. the different response to drugs. The proposed system allows: (i) to automatize the workflow of analysis of DMET-SNP data avoiding the use of multiple tools; (ii) the automatic annotation of DMET-SNP data and the search in existing databases of SNPs (e.g. dbSNP), (iii) the association of SNP with pathway through the search in PharmaGKB, a major knowledge base for pharmacogenomic studies. DMET-Analyzer has a simple graphical user interface that allows users (doctors/biologists) to upload and analyse DMET files produced by Affymetrix DMET-Console in an interactive way. The effectiveness and easy use of DMET Analyzer is demonstrated through different case studies regarding the analysis of

Academic Integration of Mainland Chinese Students in Germany

Directory of Open Access Journals (Sweden)

Hanwei Li

2017-03-01

Full Text Available This article presents an analysis of the academic integration experiences of mainland Chinese tertiary-level students in Germany. Using Tinto’s model, the article explores the challenges that Chinese students face during their academic integration, the strategies they employ, and the relationship between academic and social integration. The data were collected in spring 2016 by interviewing 26 mainland Chinese students studying either in German universities or universities of applied sciences. Four major challenges were identified and analyzed: language barrier, knowledge gap, pedagogical differences, and cultural differences. An important outcome of the study presented is that social integration serves as a facilitator for enhancing academic integration, but is not a prerequisite for academic success. Group learning with peers was found to enhance learning outcomes. Overall, Chinese students have exploited their own advantages in academic integration by exploring feasible strategies and benefiting from their past learning experiences. It is suggested that academic integration as a long and challenging process for international students should be acknowledged by the German HEIs, and that more institutional support and guidance are needed.

Semantic web for integrated network analysis in biomedicine.

Science.gov (United States)

Chen, Huajun; Ding, Li; Wu, Zhaohui; Yu, Tong; Dhanapalan, Lavanya; Chen, Jake Y

2009-03-01

The Semantic Web technology enables integration of heterogeneous data on the World Wide Web by making the semantics of data explicit through formal ontologies. In this article, we survey the feasibility and state of the art of utilizing the Semantic Web technology to represent, integrate and analyze the knowledge in various biomedical networks. We introduce a new conceptual framework, semantic graph mining, to enable researchers to integrate graph mining with ontology reasoning in network data analysis. Through four case studies, we demonstrate how semantic graph mining can be applied to the analysis of disease-causal genes, Gene Ontology category cross-talks, drug efficacy analysis and herb-drug interactions analysis.

Consistency of differential and integral thermonuclear neutronics data

International Nuclear Information System (INIS)

Reupke, W.A.

1978-01-01

To increase the accuracy of the neutronics analysis of nuclear reactors, physicists and engineers have employed a variety of techniques, including the adjustment of multigroup differential data to improve consistency with integral data. Of the various adjustment strategies, a generalized least-squares procedure which adjusts the combined differential and integral data can significantly improve the accuracy of neutronics calculations compared to calculations employing only differential data. This investigation analyzes 14 MeV neutron-driven integral experiments, using a more extensively developed methodology and a newly developed computer code, to extend the domain of adjustment from the energy range of fission reactors to the energy range of fusion reactors

A genome-wide association analysis of a broad psychosis phenotype identifies three loci for further investigation

OpenAIRE

Bramon, Elvira; Pirinen, Matti; Strange, Amy; Lin, Kuang; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Band, Gavin; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge

2014-01-01

Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories.

Biana: a software framework for compiling biological interactions and analyzing networks.

Science.gov (United States)

Garcia-Garcia, Javier; Guney, Emre; Aragues, Ramon; Planas-Iglesias, Joan; Oliva, Baldo

2010-01-27

The analysis and usage of biological data is hindered by the spread of information across multiple repositories and the difficulties posed by different nomenclature systems and storage formats. In particular, there is an important need for data unification in the study and use of protein-protein interactions. Without good integration strategies, it is difficult to analyze the whole set of available data and its properties. We introduce BIANA (Biologic Interactions and Network Analysis), a tool for biological information integration and network management. BIANA is a Python framework designed to achieve two major goals: i) the integration of multiple sources of biological information, including biological entities and their relationships, and ii) the management of biological information as a network where entities are nodes and relationships are edges. Moreover, BIANA uses properties of proteins and genes to infer latent biomolecular relationships by transferring edges to entities sharing similar properties. BIANA is also provided as a plugin for Cytoscape, which allows users to visualize and interactively manage the data. A web interface to BIANA providing basic functionalities is also available. The software can be downloaded under GNU GPL license from http://sbi.imim.es/web/BIANA.php. BIANA's approach to data unification solves many of the nomenclature issues common to systems dealing with biological data. BIANA can easily be extended to handle new specific data repositories and new specific data types. The unification protocol allows BIANA to be a flexible tool suitable for different user requirements: non-expert users can use a suggested unification protocol while expert users can define their own specific unification rules.

Multiscale integration schemes for jump-diffusion systems

Energy Technology Data Exchange (ETDEWEB)

Givon, D.; Kevrekidis, I.G.

2008-12-09

We study a two-time-scale system of jump-diffusion stochastic differential equations. We analyze a class of multiscale integration methods for these systems, which, in the spirit of [1], consist of a hybridization between a standard solver for the slow components and short runs for the fast dynamics, which are used to estimate the effect that the fast components have on the slow ones. We obtain explicit bounds for the discrepancy between the results of the multiscale integration method and the slow components of the original system.

Integrated 60GHz RF beamforming in CMOS

CERN Document Server

Yu, Yikun; van Roermund, Arthur H M

2011-01-01

""Integrated 60GHz RF Beamforming in CMOS"" describes new concepts and design techniques that can be used for 60GHz phased array systems. First, general trends and challenges in low-cost high data-rate 60GHz wireless system are studied, and the phased array technique is introduced to improve the system performance. Second, the system requirements of phase shifters are analyzed, and different phased array architectures are compared. Third, the design and implementation of 60GHz passive and active phase shifters in a CMOS technology are presented. Fourth, the integration of 60GHz phase shifters

Calibration-measurement unit for the automation of vector network analyzer measurements

Directory of Open Access Journals (Sweden)

I. Rolfes

2008-05-01

Full Text Available With the availability of multi-port vector network analyzers, the need for automated, calibrated measurement facilities increases. In this contribution, a calibration-measurement unit is presented which realizes a repeatable automated calibration of the measurement setup as well as a user-friendly measurement of the device under test (DUT. In difference to commercially available calibration units, which are connected to the ports of the vector network analyzer preceding a measurement and which are then removed so that the DUT can be connected, the presented calibration-measurement unit is permanently connected to the ports of the VNA for the calibration as well as for the measurement of the DUT. This helps to simplify the calibrated measurement of complex scattering parameters. Moreover, a full integration of the calibration unit into the analyzer setup becomes possible. The calibration-measurement unit is based on a multiport switch setup of e.g. electromechanical relays. Under the assumption of symmetry of a switch, on the one hand the unit realizes the connection of calibration standards like one-port reflection standards and two-port through connections between different ports and on the other hand it enables the connection of the DUT. The calibration-measurement unit is applicable for two-port VNAs as well as for multiport VNAs. For the calibration of the unit, methods with completely known calibration standards like SOLT (short, open, load, through as well as self-calibration procedures like TMR or TLR can be applied.

The integrated circuit IC EMP transient state disturbance effect experiment method investigates

International Nuclear Information System (INIS)

Li Xiaowei

2004-01-01

Transient state disturbance characteristic study on the integrated circuit, IC, need from its coupling path outset. Through cable (aerial) coupling, EMP converts to an pulse current voltage and results in the impact to the integrated circuit I/O orifice passing the cable. Aiming at the armament system construction feature, EMP effect to the integrated circuit, IC inside the system is analyzed. The integrated circuit, IC EMP effect experiment current injection method is investigated and a few experiments method is given. (authors)

Using Groupware to Gather and Analyze Intelligence in a Public Setting: Development of Integral Safety Plans in an Electronic Meeting

NARCIS (Netherlands)

Rouwette, E.A.J.A.; Vennix, J.A.M.; Vriens, D.J.

2003-01-01

This chapter focuses on the use of groupware to support local governments in activities in the intelligence cycle. Local governments in The Netherlands have a central role in developing integral safety plans for their district. However, in the implementation of safety plans the contribution of

Mid-infrared integrated photonics on silicon: a perspective

Directory of Open Access Journals (Sweden)

Lin Hongtao

2017-12-01

Full Text Available The emergence of silicon photonics over the past two decades has established silicon as a preferred substrate platform for photonic integration. While most silicon-based photonic components have so far been realized in the near-infrared (near-IR telecommunication bands, the mid-infrared (mid-IR, 2–20-μm wavelength band presents a significant growth opportunity for integrated photonics. In this review, we offer our perspective on the burgeoning field of mid-IR integrated photonics on silicon. A comprehensive survey on the state-of-the-art of key photonic devices such as waveguides, light sources, modulators, and detectors is presented. Furthermore, on-chip spectroscopic chemical sensing is quantitatively analyzed as an example of mid-IR photonic system integration based on these basic building blocks, and the constituent component choices are discussed and contrasted in the context of system performance and integration technologies.

REALIZAREA LEGĂTURILOR INTERDISCIPLINARE PRIN LECŢII INTEGRATE

Directory of Open Access Journals (Sweden)

Teodora VASCAN

2017-07-01

Full Text Available În articol este abordată problema integrării disciplinelor de învăţământ, accentul fiind pus pe legătura dintre infor­ma­tică şi matematică. Sunt identificate şi analizate avantajele şi rolul profesorului şi al studenţilor în organizarea lecţiilor integrate. Autorul propune o metodologie de realizare a legăturilor interdisciplinare dintre cursurile Grafica asistată de calculator şi Geometrie.REALIZATION OF THE INTERDISCIPLINARY CONNECTIONS BY INTEGRATED LESSONSThe article discussed the problem of integrating the disciplines of education, focusing on the connection between computer science and mathematics. They are identified and analyzed the benefits and role of the teacher and students in organizing integrated lessons. The author proposes a methodology for realization interdisciplinary connections between courses Computer Graphics and Geometry.

Market integration: The EU experience and implications for regulatory reform in China

NARCIS (Netherlands)

Philipsen, N.J.; Weishaar, Stefan; Xu, G.

2016-01-01

This book examines the relationship between regulation and market integration, with a special focus on China. It pursues a Law and Economics and Comparative Law approach (China and EU) to analyze the current obstacles to market integration and domestic economic growth in China. Topics covered at the

Macroscopic cross sections for analyzing the transport of neutral particles in plasmas

International Nuclear Information System (INIS)

Suzuki, Tadakazu; Taji, Yuukichi; Nakahara, Yasuaki

1975-05-01

Algorithms have been developed for calculating the ionization and charge exchange cross sections required for analyzing the neutral transport in plasmas. In our algorithms, the integration of the expression for reaction rate of neutrals with plasmas is performed by expanding the integrand with the use of polynomials. At present, multi-energy-group sets of the cross sections depending on plasma temperature and energy of neutrals can be prepared by means of Maxwellian averages over energy. Calculational results are printed out in the FIDO format. Some numerical examples are given for several forms of spatial distributions assumed for the plasma ion temperature and source neutral energy. (auth.)

PM 3655 PHILIPS Logic analyzer

CERN Multimedia

A logic analyzer is an electronic instrument that captures and displays multiple signals from a digital system or digital circuit. A logic analyzer may convert the captured data into timing diagrams, protocol decodes, state machine traces, assembly language, or may correlate assembly with source-level software. Logic Analyzers have advanced triggering capabilities, and are useful when a user needs to see the timing relationships between many signals in a digital system.

A Categorization of Dynamic Analyzers

Science.gov (United States)

Lujan, Michelle R.

1997-01-01

Program analysis techniques and tools are essential to the development process because of the support they provide in detecting errors and deficiencies at different phases of development. The types of information rendered through analysis includes the following: statistical measurements of code, type checks, dataflow analysis, consistency checks, test data,verification of code, and debugging information. Analyzers can be broken into two major categories: dynamic and static. Static analyzers examine programs with respect to syntax errors and structural properties., This includes gathering statistical information on program content, such as the number of lines of executable code, source lines. and cyclomatic complexity. In addition, static analyzers provide the ability to check for the consistency of programs with respect to variables. Dynamic analyzers in contrast are dependent on input and the execution of a program providing the ability to find errors that cannot be detected through the use of static analysis alone. Dynamic analysis provides information on the behavior of a program rather than on the syntax. Both types of analysis detect errors in a program, but dynamic analyzers accomplish this through run-time behavior. This paper focuses on the following broad classification of dynamic analyzers: 1) Metrics; 2) Models; and 3) Monitors. Metrics are those analyzers that provide measurement. The next category, models, captures those analyzers that present the state of the program to the user at specified points in time. The last category, monitors, checks specified code based on some criteria. The paper discusses each classification and the techniques that are included under them. In addition, the role of each technique in the software life cycle is discussed. Familiarization with the tools that measure, model and monitor programs provides a framework for understanding the program's dynamic behavior from different, perspectives through analysis of the input

KEEFEKTIFAN MODEL CONNECTED DAN INTEGRATED DALAM PEMBELAJARAN IPS SMP DI KOTA YOGYAKARTA

Directory of Open Access Journals (Sweden)

Idrus idrus

2011-01-01

Full Text Available This research aimed to: (1 analyze the differences in social studies learning achievement between the students using connected and integrated models and those using conventional model; and (2 analyze the hierarchy of the effect of the learning models  among the connected, integrated, and conventional. This experimental research employed a matching post-test comparison group design. The population of this research was National Standardized Schools of Junior Secondary Schools in Yogyakarta. The technique used for sample drawing was multistage sampling. In this research, the independent variable was the learning model which consisted of three categories: integrated, connected, and conventional models. The dependent variable was the mean score of students’ learning achievement in social studies subject. Data collection was done by means of an achievement test. Instrument validation was done by discriminating power and difficulty index, while the reliability was calculated by KR-20. The pre-requisite  test included normality and homogeneity tests. The normality test used Kolmogorov-Smirnov and the homogeneity test used Levene Test. Data were analyzed in one way anova analysis and continued with Scheffe comparison test on the significance level of 0.05. The results of the experiment show that there are  significant difference among the students’ learning achievement who used integrated, connected, and conventional models. The continued test using Scheffe ensured that the integrated model was more effective than the connected and conventional models, while the connected model was more effective in improving the students’ learning achievement in social studies subject compared with the conventional model. Therefore, the hierarchy of the effect of the learning models is first the integrated model followed by connected and conventional models. Key words: Connected, Integrated Models, Social Studies Learning

A tone analyzer based on a piezoelectric polymer and organic thin film transistors.

Science.gov (United States)

Hsu, Yu-Jen; Kymissis, Ioannis

2012-12-01

A tone analyzer is demonstrated using a distributed resonator architecture on a tensioned piezoelectric polyvinyledene diuoride (PVDF) sheet. This sheet is used as both the resonator and detection element. Two architectures are demonstrated; one uses distributed, directly addressed elements as a proof of concept, and the other integrates organic thin film transistor-based transimpedance amplifiers directly with the PVDF to convert the piezoelectric charge signal into a current signal. The PVDF sheet material is instrumented along its length, and the amplitude response at 15 sites is recorded and analyzed as a function of the frequency of excitation. The determination of the dominant component of an incoming tone is demonstrated using linear system decomposition of the time-averaged response of the sheet and is performed without any time domain analysis. This design allows for the determination of the spectral composition of a sound using the mechanical signal processing provided by the amplitude response and eliminates the need for time-domain downstream signal processing of the incoming signal.

Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia

Science.gov (United States)

Mansour, Hader A; Talkowski, Michael E; Wood, Joel; Chowdari, Kodavali V; McClain, Lora; Prasad, Konasale; Montrose, Debra; Fagiolini, Andrea; Friedman, Edward S; Allen, Michael H; Bowden, Charles L; Calabrese, Joseph; El-Mallakh, Rif S; Escamilla, Michael; Faraone, Stephen V; Fossey, Mark D; Gyulai, Laszlo; Loftis, Jennifer M; Hauser, Peter; Ketter, Terence A; Marangell, Lauren B; Miklowitz, David J; Nierenberg, Andrew A; Patel, Jayendra; Sachs, Gary S; Sklar, Pamela; Smoller, Jordan W; Laird, Nan; Keshavan, Matcheri; Thase, Michael E; Axelson, David; Birmaher, Boris; Lewis, David; Monk, Tim; Frank, Ellen; Kupfer, David J; Devlin, Bernie; Nimgaonkar, Vishwajit L

2012-01-01

Objective Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. Methods We assayed 276 publicly available ‘tag’ single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Results Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Conclusions Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results. PMID:19839995

Analyzing the Anomalous Dipole Moment Type Couplings of Heavy Quarks with FCNC Interactions at the CLIC

International Nuclear Information System (INIS)

Senol, A.; Tasci, A. T.; Verep, C.

2014-01-01

We examine both anomalous magnetic and dipole moment type couplings of a heavy quark via its single production with subsequent dominant standard model decay modes at the compact linear collider (CLIC). The signal and background cross sections are analyzed for heavy quark masses 600 and 700 GeV. We make the analysis to delimitate these couplings as well as to find the attainable integrated luminosities for 3σ observation limit

Symplectic integrators with adaptive time steps

Science.gov (United States)

Richardson, A. S.; Finn, J. M.

2012-01-01

In recent decades, there have been many attempts to construct symplectic integrators with variable time steps, with rather disappointing results. In this paper, we identify the causes for this lack of performance, and find that they fall into two categories. In the first, the time step is considered a function of time alone, Δ = Δ(t). In this case, backward error analysis shows that while the algorithms remain symplectic, parametric instabilities may arise because of resonance between oscillations of Δ(t) and the orbital motion. In the second category the time step is a function of phase space variables Δ = Δ(q, p). In this case, the system of equations to be solved is analyzed by introducing a new time variable τ with dt = Δ(q, p) dτ. The transformed equations are no longer in Hamiltonian form, and thus do not benefit from integration methods which would be symplectic for Hamiltonian systems. We analyze two methods for integrating the transformed equations which do, however, preserve the structure of the original equations. The first is an extended phase space method, which has been successfully used in previous studies of adaptive time step symplectic integrators. The second, novel, method is based on a non-canonical mixed-variable generating function. Numerical trials for both of these methods show good results, without parametric instabilities or spurious growth or damping. It is then shown how to adapt the time step to an error estimate found by backward error analysis, in order to optimize the time-stepping scheme. Numerical results are obtained using this formulation and compared with other time-stepping schemes for the extended phase space symplectic method.

Fuels planning: science synthesis and integration; environmental consequences fact sheet 13: Root Disease Analyzer-Armillaria Response Tool (ART)

Science.gov (United States)

Geral I. McDonald; Philip D. Tanimoto; Thomas M. Rice; David E. Hall; Jane E. Stewart; Paul J. Zambino; Jonalea R. Tonn; Ned B. Klopfenstein; Mee-Sook Kim

2005-01-01

The Root Disease Analyzer-Armillaria Response Tool (ART) is a Web-based tool that estimates Armillaria root disease risk in dry forests of the Western United States. This fact sheet identifies the intended users and uses, required inputs, what the model does and does not do, and tells the user how to obtain the model.

Developing rapid methods for analyzing upland riparian functions and values.

Science.gov (United States)

Hruby, Thomas

2009-06-01

Regulators protecting riparian areas need to understand the integrity, health, beneficial uses, functions, and values of this resource. Up to now most methods providing information about riparian areas are based on analyzing condition or integrity. These methods, however, provide little information about functions and values. Different methods are needed that specifically address this aspect of riparian areas. In addition to information on functions and values, regulators have very specific needs that include: an analysis at the site scale, low cost, usability, and inclusion of policy interpretations. To meet these needs a rapid method has been developed that uses a multi-criteria decision matrix to categorize riparian areas in Washington State, USA. Indicators are used to identify the potential of the site to provide a function, the potential of the landscape to support the function, and the value the function provides to society. To meet legal needs fixed boundaries for assessment units are established based on geomorphology, the distance from "Ordinary High Water Mark" and different categories of land uses. Assessment units are first classified based on ecoregions, geomorphic characteristics, and land uses. This simplifies the data that need to be collected at a site, but it requires developing and calibrating a separate model for each "class." The approach to developing methods is adaptable to other locations as its basic structure is not dependent on local conditions.

Investigation for connecting waveguide in off-planar integrated circuits.

Science.gov (United States)

Lin, Jie; Feng, Zhifang

2017-09-01

The transmission properties of a vertical waveguide connected by different devices in off-planar integrated circuits are designed, investigated, and analyzed in detail by the finite-difference time-domain method. The results show that both guide bandwidth and transmission efficiency can be adjusted effectively by shifting the vertical waveguide continuously. Surprisingly, the wide guide band (0.385[c/a]∼0.407[c/a]) and well transmission (-6  dB) are observed simultaneously in several directions when the vertical waveguide is located at a specific location. The results are very important for all-optical integrated circuits, especially in compact integration.

FRAPCON-3: Integral assessment

Energy Technology Data Exchange (ETDEWEB)

Lanning, D.D.; Berna, G.A.; Berna, G.A.

1997-12-01

An integral assessment has been performed for the U.S. Nuclear Regulatory Commission by Pacific Northwest National Laboratory to quantify the predictive capabilities of FRAPCON-3, a steady-state fuel behavior code designed to analyze fuel behavior from beginning-of-life to burnup levels of 65 GWd/MTU. FRAPCON-3 code calculations are shown to compare satisfactorily to a pre-selected set of experimental data with steady-state operating conditions. 30 refs., 27 figs., 18 tabs.

Heritability in inflammatory bowel disease

DEFF Research Database (Denmark)

Gordon, Hannah; Trier Moller, Frederik; Andersen, Vibeke

2015-01-01

for ulcerative colitis. Heritability estimates for Crohn's disease and ulcerative colitis from pooled twin studies are 0.75 and 0.67, respectively. However, this is at odds with the much lower heritability estimates from Genome-Wide Association Studies (GWAS). This "missing heritability" is likely due...... to shortfalls in both family studies and GWAS. The coefficient of heritability fails to account for familial shared environment. Heritability calculations from twin data are based on Falconer's method, with premises that are increasingly understood to be flawed. GWAS based heritability estimates may...... underestimate heritability due to incomplete linkage disequilibrium, and because some single nucleotide polypeptides (SNPs) do not reach a level of significance to allow detection. SNPs missed by GWAS include common SNPs with low penetrance and rare SNPs with high penetrance. All methods of heritability...

Polynomial solutions of nonlinear integral equations

International Nuclear Information System (INIS)

Dominici, Diego

2009-01-01

We analyze the polynomial solutions of a nonlinear integral equation, generalizing the work of Bender and Ben-Naim (2007 J. Phys. A: Math. Theor. 40 F9, 2008 J. Nonlinear Math. Phys. 15 (Suppl. 3) 73). We show that, in some cases, an orthogonal solution exists and we give its general form in terms of kernel polynomials