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Sample records for integrative pathway analysis

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

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    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

  2. Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

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    Zhongqi Ge

    2018-04-01

    Full Text Available Summary: Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of the ubiquitin pathway in cancer development and lays a foundation for developing relevant therapeutic strategies. : Ge et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to provide a comprehensive characterization of the ubiquitin pathway. They detect somatic driver candidates in the ubiquitin pathway and identify a cluster of patients with poor survival, highlighting the importance of this pathway in cancer development. Keywords: ubiquitin pathway, pan-cancer analysis, The Cancer Genome Atlas, tumor subtype, cancer prognosis, therapeutic targets, biomarker, FBXW7

  3. Penalized differential pathway analysis of integrative oncogenomics studies.

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    van Wieringen, Wessel N; van de Wiel, Mark A

    2014-04-01

    Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving cancer patients. The two molecular levels involved are linked through the central dogma of molecular biology. DNA copy number aberrations abound in the cancer cell. Here we investigate how these aberrations affect gene expression levels within a pathway using observational integrative genomics data of cancer patients. In particular, we aim to identify differential edges between regulatory networks of two groups involving these molecular levels. Motivated by the rate equations, the regulatory mechanism between DNA copy number aberrations and gene expression levels within a pathway is modeled by a simultaneous-equations model, for the one- and two-group case. The latter facilitates the identification of differential interactions between the two groups. Model parameters are estimated by penalized least squares using the lasso (L1) penalty to obtain a sparse pathway topology. Simulations show that the inclusion of DNA copy number data benefits the discovery of gene-gene interactions. In addition, the simulations reveal that cis-effects tend to be over-estimated in a univariate (single gene) analysis. In the application to real data from integrative oncogenomic studies we show that inclusion of prior information on the regulatory network architecture benefits the reproducibility of all edges. Furthermore, analyses of the TP53 and TGFb signaling pathways between ER+ and ER- samples from an integrative genomics breast cancer study identify reproducible differential regulatory patterns that corroborate with existing literature.

  4. Integrative analysis of RUNX1 downstream pathways and target genes

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    Liu Marjorie

    2008-07-01

    Full Text Available Abstract Background The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML. The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia. Results Here we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1 cell lines with RUNX1 mutations from FPD-AML patients, 2 over-expression of RUNX1 and CBFβ, and 3 Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes significantly correlate with published microarray data from sporadic AML patients with mutations in either RUNX1 or its cofactor, CBFβ. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygous RUNX1 point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes. Conclusion This work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease

  5. Penalized differential pathway analysis of integrative oncogenomics studies

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    van Wieringen, W.N.; van de Wiel, M.A.

    2014-01-01

    Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving

  6. Integrated In Silico Analysis of Pathway Designs for Synthetic Photo-Electro-Autotrophy.

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    Michael Volpers

    Full Text Available The strong advances in synthetic biology enable the engineering of novel functions and complex biological features in unprecedented ways, such as implementing synthetic autotrophic metabolism into heterotrophic hosts. A key challenge for the sustainable production of fuels and chemicals entails the engineering of synthetic autotrophic organisms that can effectively and efficiently fix carbon dioxide by using sustainable energy sources. This challenge involves the integration of carbon fixation and energy uptake systems. A variety of carbon fixation pathways and several types of photosystems and other energy uptake systems can be chosen and, potentially, modularly combined to design synthetic autotrophic metabolism. Prior to implementation, these designs can be evaluated by the combination of several computational pathway analysis techniques. Here we present a systematic, integrated in silico analysis of photo-electro-autotrophic pathway designs, consisting of natural and synthetic carbon fixation pathways, a proton-pumping rhodopsin photosystem for ATP regeneration and an electron uptake pathway. We integrated Flux Balance Analysis of the heterotrophic chassis Escherichia coli with kinetic pathway analysis and thermodynamic pathway analysis (Max-min Driving Force. The photo-electro-autotrophic designs are predicted to have a limited potential for anaerobic, autotrophic growth of E. coli, given the relatively low ATP regenerating capacity of the proton pumping rhodopsin photosystems and the high ATP maintenance of E. coli. If these factors can be tackled, our analysis indicates the highest growth potential for the natural reductive tricarboxylic acid cycle and the synthetic pyruvate synthase-pyruvate carboxylate -glyoxylate bicycle. Both carbon fixation cycles are very ATP efficient, while maintaining fast kinetics, which also results in relatively low estimated protein costs for these pathways. Furthermore, the synthetic bicycles are highly

  7. Integrative Analysis of Gene Expression Data Including an Assessment of Pathway Enrichment for Predicting Prostate Cancer

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    Pingzhao Hu

    2006-01-01

    Full Text Available Background: Microarray technology has been previously used to identify genes that are differentially expressed between tumour and normal samples in a single study, as well as in syntheses involving multiple studies. When integrating results from several Affymetrix microarray datasets, previous studies summarized probeset-level data, which may potentially lead to a loss of information available at the probe-level. In this paper, we present an approach for integrating results across studies while taking probe-level data into account. Additionally, we follow a new direction in the analysis of microarray expression data, namely to focus on the variation of expression phenotypes in predefined gene sets, such as pathways. This targeted approach can be helpful for revealing information that is not easily visible from the changes in the individual genes. Results: We used a recently developed method to integrate Affymetrix expression data across studies. The idea is based on a probe-level based test statistic developed for testing for differentially expressed genes in individual studies. We incorporated this test statistic into a classic random-effects model for integrating data across studies. Subsequently, we used a gene set enrichment test to evaluate the significance of enriched biological pathways in the differentially expressed genes identified from the integrative analysis. We compared statistical and biological significance of the prognostic gene expression signatures and pathways identified in the probe-level model (PLM with those in the probeset-level model (PSLM. Our integrative analysis of Affymetrix microarray data from 110 prostate cancer samples obtained from three studies reveals thousands of genes significantly correlated with tumour cell differentiation. The bioinformatics analysis, mapping these genes to the publicly available KEGG database, reveals evidence that tumour cell differentiation is significantly associated with many

  8. Integration of multiple networks and pathways identifies cancer driver genes in pan-cancer analysis.

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    Cava, Claudia; Bertoli, Gloria; Colaprico, Antonio; Olsen, Catharina; Bontempi, Gianluca; Castiglioni, Isabella

    2018-01-06

    Modern high-throughput genomic technologies represent a comprehensive hallmark of molecular changes in pan-cancer studies. Although different cancer gene signatures have been revealed, the mechanism of tumourigenesis has yet to be completely understood. Pathways and networks are important tools to explain the role of genes in functional genomic studies. However, few methods consider the functional non-equal roles of genes in pathways and the complex gene-gene interactions in a network. We present a novel method in pan-cancer analysis that identifies de-regulated genes with a functional role by integrating pathway and network data. A pan-cancer analysis of 7158 tumour/normal samples from 16 cancer types identified 895 genes with a central role in pathways and de-regulated in cancer. Comparing our approach with 15 current tools that identify cancer driver genes, we found that 35.6% of the 895 genes identified by our method have been found as cancer driver genes with at least 2/15 tools. Finally, we applied a machine learning algorithm on 16 independent GEO cancer datasets to validate the diagnostic role of cancer driver genes for each cancer. We obtained a list of the top-ten cancer driver genes for each cancer considered in this study. Our analysis 1) confirmed that there are several known cancer driver genes in common among different types of cancer, 2) highlighted that cancer driver genes are able to regulate crucial pathways.

  9. Identification of differentially expressed genes and signaling pathways in ovarian cancer by integrated bioinformatics analysis

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    Yang X

    2018-03-01

    Full Text Available Xiao Yang,1 Shaoming Zhu,2 Li Li,3 Li Zhang,1 Shu Xian,1 Yanqing Wang,1 Yanxiang Cheng1 1Department of Obstetrics and Gynecology, 2Department of Urology, Renmin Hospital of Wuhan University, 3Department of Pharmacology, Wuhan University Health Science Center, Wuhan, Hubei, People’s Republic of China Background: The mortality rate associated with ovarian cancer ranks the highest among gynecological malignancies. However, the cause and underlying molecular events of ovarian cancer are not clear. Here, we applied integrated bioinformatics to identify key pathogenic genes involved in ovarian cancer and reveal potential molecular mechanisms. Results: The expression profiles of GDS3592, GSE54388, and GSE66957 were downloaded from the Gene Expression Omnibus (GEO database, which contained 115 samples, including 85 cases of ovarian cancer samples and 30 cases of normal ovarian samples. The three microarray datasets were integrated to obtain differentially expressed genes (DEGs and were deeply analyzed by bioinformatics methods. The gene ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichments of DEGs were performed by DAVID and KOBAS online analyses, respectively. The protein–protein interaction (PPI networks of the DEGs were constructed from the STRING database. A total of 190 DEGs were identified in the three GEO datasets, of which 99 genes were upregulated and 91 genes were downregulated. GO analysis showed that the biological functions of DEGs focused primarily on regulating cell proliferation, adhesion, and differentiation and intracellular signal cascades. The main cellular components include cell membranes, exosomes, the cytoskeleton, and the extracellular matrix. The molecular functions include growth factor activity, protein kinase regulation, DNA binding, and oxygen transport activity. KEGG pathway analysis showed that these DEGs were mainly involved in the Wnt signaling pathway, amino acid metabolism, and the

  10. Aligning ontologies and integrating textual evidence for pathway analysis of microarray data

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    Gopalan, Banu; Posse, Christian; Sanfilippo, Antonio P.; Stenzel-Poore, Mary; Stevens, S.L.; Castano, Jose; Beagley, Nathaniel; Riensche, Roderick M.; Baddeley, Bob; Simon, R.P.; Pustejovsky, James

    2006-10-08

    Expression arrays are introducing a paradigmatic change in biology by shifting experimental approaches from single gene studies to genome-level analysis, monitoring the ex-pression levels of several thousands of genes in parallel. The massive amounts of data obtained from the microarray data needs to be integrated and interpreted to infer biological meaning within the context of information-rich pathways. In this paper, we present a methodology that integrates textual information with annotations from cross-referenced ontolo-gies to map genes to pathways in a semi-automated way. We illustrate this approach and compare it favorably to other tools by analyzing the gene expression changes underlying the biological phenomena related to stroke. Stroke is the third leading cause of death and a major disabler in the United States. Through years of study, researchers have amassed a significant knowledge base about stroke, and this knowledge, coupled with new technologies, is providing a wealth of new scientific opportunities. The potential for neu-roprotective stroke therapy is enormous. However, the roles of neurogenesis, angiogenesis, and other proliferative re-sponses in the recovery process following ischemia and the molecular mechanisms that lead to these processes still need to be uncovered. Improved annotation of genomic and pro-teomic data, including annotation of pathways in which genes and proteins are involved, is required to facilitate their interpretation and clinical application. While our approach is not aimed at replacing existing curated pathway databases, it reveals multiple hidden relationships that are not evident with the way these databases analyze functional groupings of genes from the Gene Ontology.

  11. Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

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    Santiago, Jose A; Potashkin, Judith A

    2013-01-01

    Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients. These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that

  12. Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

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    Jose A Santiago

    Full Text Available Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level.Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP, previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS and the Prognostic Biomarker Study (PROBE, revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients.These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first

  13. Integrating eQTL data with GWAS summary statistics in pathway-based analysis with application to schizophrenia.

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    Wu, Chong; Pan, Wei

    2018-04-01

    Many genetic variants affect complex traits through gene expression, which can be exploited to boost statistical power and enhance interpretation in genome-wide association studies (GWASs) as demonstrated by the transcriptome-wide association study (TWAS) approach. Furthermore, due to polygenic inheritance, a complex trait is often affected by multiple genes with similar functions as annotated in gene pathways. Here, we extend TWAS from gene-based analysis to pathway-based analysis: we integrate public pathway collections, expression quantitative trait locus (eQTL) data and GWAS summary association statistics (or GWAS individual-level data) to identify gene pathways associated with complex traits. The basic idea is to weight the SNPs of the genes in a pathway based on their estimated cis-effects on gene expression, then adaptively test for association of the pathway with a GWAS trait by effectively aggregating possibly weak association signals across the genes in the pathway. The P values can be calculated analytically and thus fast. We applied our proposed test with the KEGG and GO pathways to two schizophrenia (SCZ) GWAS summary association data sets, denoted by SCZ1 and SCZ2 with about 20,000 and 150,000 subjects, respectively. Most of the significant pathways identified by analyzing the SCZ1 data were reproduced by the SCZ2 data. Importantly, we identified 15 novel pathways associated with SCZ, such as GABA receptor complex (GO:1902710), which could not be uncovered by the standard single SNP-based analysis or gene-based TWAS. The newly identified pathways may help us gain insights into the biological mechanism underlying SCZ. Our results showcase the power of incorporating gene expression information and gene functional annotations into pathway-based association testing for GWAS. © 2018 WILEY PERIODICALS, INC.

  14. Integrative Network Analysis Unveils Convergent Molecular Pathways in Parkinson's Disease and Diabetes

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    Santiago, Jose A.; Potashkin, Judith A.

    2013-01-01

    Background Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. ...

  15. Integrated bioinformatics analysis reveals key candidate genes and pathways in breast cancer.

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    Wang, Yuzhi; Zhang, Yi; Huang, Qian; Li, Chengwen

    2018-04-19

    Breast cancer (BC) is the leading malignancy in women worldwide, yet relatively little is known about the genes and signaling pathways involved in BC tumorigenesis and progression. The present study aimed to elucidate potential key candidate genes and pathways in BC. Five gene expression profile data sets (GSE22035, GSE3744, GSE5764, GSE21422 and GSE26910) were downloaded from the Gene Expression Omnibus (GEO) database, which included data from 113 tumorous and 38 adjacent non‑tumorous tissue samples. Differentially expressed genes (DEGs) were identified using t‑tests in the limma R package. These DEGs were subsequently investigated by pathway enrichment analysis and a protein‑protein interaction (PPI) network was constructed. The most significant module from the PPI network was selected for pathway enrichment analysis. In total, 227 DEGs were identified, of which 82 were upregulated and 145 were downregulated. Pathway enrichment analysis results revealed that the upregulated DEGs were mainly enriched in 'cell division', the 'proteinaceous extracellular matrix (ECM)', 'ECM structural constituents' and 'ECM‑receptor interaction', whereas downregulated genes were mainly enriched in 'response to drugs', 'extracellular space', 'transcriptional activator activity' and the 'peroxisome proliferator‑activated receptor signaling pathway'. The PPI network contained 174 nodes and 1,257 edges. DNA topoisomerase 2‑a, baculoviral inhibitor of apoptosis repeat‑containing protein 5, cyclin‑dependent kinase 1, G2/mitotic‑specific cyclin‑B1 and kinetochore protein NDC80 homolog were identified as the top 5 hub genes. Furthermore, the genes in the most significant module were predominantly involved in 'mitotic nuclear division', 'mid‑body', 'protein binding' and 'cell cycle'. In conclusion, the DEGs, relative pathways and hub genes identified in the present study may aid in understanding of the molecular mechanisms underlying BC progression and provide

  16. Discovery of new candidate genes for rheumatoid arthritis through integration of genetic association data with expression pathway analysis.

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    Shchetynsky, Klementy; Diaz-Gallo, Lina-Marcella; Folkersen, Lasse; Hensvold, Aase Haj; Catrina, Anca Irinel; Berg, Louise; Klareskog, Lars; Padyukov, Leonid

    2017-02-02

    Here we integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signaling networks, relevant for rheumatoid arthritis (RA). RNA-sequencing-(RNA-seq)-based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated patients with RA, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis. A set of "connector" genes derived from pathway analysis was tested for differential expression in the initial discovery cohort and validated in blood cells from 73 patients with RA and in 35 healthy controls. There were 11 qualifying genes selected for pathway analysis and these were grouped into two evidence-based functional networks, containing 29 and 27 additional connector molecules. The expression of genes, corresponding to connector molecules was then tested in the initial RNA-seq data. Differences in the expression of ERBB2, TP53 and THOP1 were similar in both treated and non-treated patients with RA and an additional nine genes were differentially expressed in at least one group of patients compared to healthy controls. The ERBB2, TP53. THOP1 expression profile was successfully replicated in RNA-seq data from peripheral blood mononuclear cells from healthy controls and non-treated patients with RA, in an independent collection of samples. Integration of RNA-seq data with findings from association studies, and consequent pathway analysis implicate new candidate genes, ERBB2, TP53 and THOP1 in the pathogenesis of RA.

  17. Integrated bioinformatic analysis unveils significant genes and pathways in the pathogenesis of supratentorial primitive neuroectodermal tumor

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    Wang G

    2018-04-01

    Full Text Available Guang-Yu Wang,1,* Ling Li,2,* Bo Liu,1 Xiao Han,1 Chun-Hua Wang,1 Ji-Wen Wang3 1Department of Neurosurgery, 2Department of Pediatrics, Qilu Children’s Hospital of Shandong University, Jinan, Shandong, 3Department of Neurology, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Pudong New District, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: This study aimed to explore significant genes and pathways involved in the pathogenesis of supratentorial primitive neuroectodermal tumor (sPNET. Materials and methods: Gene expression profile of GSE14295 was downloaded from publicly available Gene Expression Omnibus (GEO database. Differentially expressed genes (DEGs were screened out in primary sPNET samples compared with normal fetal and adult brain reference samples (sPNET vs fetal brain and sPNET vs adult brain. Pathway enrichment analysis of these DEGs was conducted, followed by protein–protein interaction (PPI network construction and significant module selection. Additionally, transcription factors (TFs regulating the common DEGs in the two comparison groups were identified, and the regulatory network was constructed. Results: In total, 526 DEGs (99 up- and 427 downregulated in sPNET vs fetal brain and 815 DEGs (200 up- and 615 downregulated in sPNET vs adult brain were identified. DEGs in sPNET vs fetal brain and sPNET vs adult brain were associated with calcium signaling pathway, cell cycle, and p53 signaling pathway. CDK1, CDC20, BUB1B, and BUB1 were hub nodes in the PPI networks of DEGs in sPNET vs fetal brain and sPNET vs adult brain. Significant modules were extracted from the PPI networks. In addition, 64 upregulated and 200 downregulated overlapping DEGs were identified in both sPNET vs fetal brain and sPNET vs adult brain. The genes involved in the regulatory network upon overlapping DEGs and the TFs were correlated with calcium signaling pathway

  18. Integrating Multiple Microarray Data for Cancer Pathway Analysis Using Bootstrapping K-S Test

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    Bing Han

    2009-01-01

    Full Text Available Previous applications of microarray technology for cancer research have mostly focused on identifying genes that are differentially expressed between a particular cancer and normal cells. In a biological system, genes perform different molecular functions and regulate various biological processes via interactions with other genes thus forming a variety of complex networks. Therefore, it is critical to understand the relationship (e.g., interactions between genes across different types of cancer in order to gain insights into the molecular mechanisms of cancer. Here we propose an integrative method based on the bootstrapping Kolmogorov-Smirnov test and a large set of microarray data produced with various types of cancer to discover common molecular changes in cells from normal state to cancerous state. We evaluate our method using three key pathways related to cancer and demonstrate that it is capable of finding meaningful alterations in gene relations.

  19. Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer

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    Chung Jae

    2009-06-01

    Full Text Available Abstract Background Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s underlying the development of platinum resistance in late-stage ovarian cancer patients currently remains unknown, CpG-island (CGI methylation, a phenomenon strongly associated with aberrant gene silencing and ovarian tumorigenesis, may contribute to this devastating condition. Methods To model the onset of drug resistance, and investigate DNA methylation and gene expression alterations associated with platinum resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation and mRNA expression microarray analyses. To identify chemoresistance-associated, biological pathways likely impacted by DNA methylation, promoter CGI methylation and mRNA expression profiles were integrated and subjected to pathway enrichment analysis. Results Promoter CGI methylation revealed a positive association (Spearman correlation of 0.99 between the total number of hypermethylated CGIs and GI50 values (i.e., increased drug resistance following successive cisplatin treatment cycles. In accord with that result, chemoresistance was reversible by DNA methylation inhibitors. Pathway enrichment analysis revealed hypermethylation-mediated repression of cell adhesion and tight junction pathways and hypomethylation-mediated activation of the cell growth-promoting pathways PI3K/Akt, TGF-beta, and cell cycle progression, which may contribute to the onset of chemoresistance in ovarian cancer cells. Conclusion Selective epigenetic disruption of distinct biological

  20. An integrated approach for a dynamic energy and environmental system analysis of biogas production pathways

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    Pierie, Frank; Liu, Wen; Moll, Henri C.

    2014-01-01

    Abstract written to Biogas Science for oral presentation. Regarding a new methodology for determining the energy efficiency, carbon footprint and environmental impact of anaerobic biogas production pathways. Additionally, results are given regarding the impacts of energy crops and waste products

  1. Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas

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    Beltrami, Caroline Moraes; Dos Reis, Mariana Bisarro; Barros-Filho, Mateus Camargo

    2017-01-01

    and positive correlation, respectively. Genes showing negative correlation underlined FGF and retinoic acid signaling as critical canonical pathways disrupted by DNA methylation in PTC. BRAF mutation was detected in 68% (28 of 41) of the tumors, which presented a higher level of demethylation (95...

  2. Integrated analysis of breast cancer cell lines reveals unique signaling pathways

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    Heiser, Laura M.; Wang, Nicholas J.; Talcott, Carolyn L.; Laderoute, Keith R.; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L.; Laquerre, Sylvie; Jackson, Jeffrey R.; Wooster, Richard F.; Kuo, Wen-Lin; Gray, Joe W.; Spellman, Paul T.

    2009-03-31

    Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EGFR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EGFR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EGFR-MEK signaling. This model was comprised of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype specific subnetworks, including one that suggested PAK1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that PAK1 overexpressing cell lines would have increased sensitivity to MEK inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three MEK inhibitors. We found that PAK1 over-expressing luminal breast cancer cell lines are significantly more sensitive to MEK inhibition as compared to those that express PAK1 at low levels. This indicates that PAK1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to MEK inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

  3. Integrated analysis of breast cancer cell lines reveals unique signaling pathways.

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    Heiser, Laura M; Wang, Nicholas J; Talcott, Carolyn L; Laderoute, Keith R; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L; Laquerre, Sylvie; Jackson, Jeffrey R; Wooster, Richard F; Kuo, Wen Lin; Gray, Joe W; Spellman, Paul T

    2009-01-01

    Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EgfR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EgfR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EgfR-MAPK signaling. This model was composed of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype-specific subnetworks, including one that suggested Pak1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that Pak1 over-expressing cell lines would have increased sensitivity to Mek inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three Mek inhibitors. We found that Pak1 over-expressing luminal breast cancer cell lines are significantly more sensitive to Mek inhibition compared to those that express Pak1 at low levels. This indicates that Pak1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to Mek inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

  4. Integrated analysis of transportation demand pathway options for hydrogen production, storage, and distribution

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, C.E.S. [Directed Technologies Inc., Arlington, VA (United States)

    1996-10-01

    Directed Technologies, Inc. has begun the development of a computer model with the goal of providing guidance to the Hydrogen Program Office regarding the most cost effective use of limited resources to meet national energy security and environmental goals through the use of hydrogen as a major energy carrier. The underlying assumption of this programmatic pathway model is that government and industry must work together to bring clean hydrogen energy devices into the marketplace. Industry cannot provide the long term resources necessary to overcome technological, regulatory, institutional, and perceptual barriers to the use of hydrogen as an energy carrier, and government cannot provide the substantial investments required to develop hydrogen energy products and increased hydrogen production capacity. The computer model recognizes this necessary government/industry partnership by determining the early investments required by government to bring hydrogen energy end uses within the time horizon and profitability criteria of industry, and by estimating the subsequent investments required by industry. The model then predicts the cost/benefit ratio for government, based on contributions of each hydrogen project to meeting societal goals, and it predicts the return on investment for industry. Sensitivity analyses with respect to various government investments such as hydrogen research and development and demonstration projects will then provide guidance as to the most cost effective mix of government actions. The initial model considers the hydrogen transportation market, but this programmatic pathway methodology will be extended to other market segments in the future.

  5. MelanomaDB: a Web Tool for Integrative Analysis of Melanoma Genomic Information to Identify Disease-Associated Molecular Pathways

    Directory of Open Access Journals (Sweden)

    Alexander Joseph Trevarton

    2013-07-01

    Full Text Available Despite on-going research, metastatic melanoma survival rates remain low and treatment options are limited. Researchers can now access a rapidly growing amount of molecular and clinical information about melanoma. This information is becoming difficult to assemble and interpret due to its dispersed nature, yet as it grows it becomes increasingly valuable for understanding melanoma. Integration of this information into a comprehensive resource to aid rational experimental design and patient stratification is needed. As an initial step in this direction, we have assembled a web-accessible melanoma database, MelanomaDB, which incorporates clinical and molecular data from publically available sources, which will be regularly updated as new information becomes available. This database allows complex links to be drawn between many different aspects of melanoma biology: genetic changes (e.g. mutations in individual melanomas revealed by DNA sequencing, associations between gene expression and patient survival, data concerning drug targets, biomarkers, druggability and clinical trials, as well as our own statistical analysis of relationships between molecular pathways and clinical parameters that have been produced using these data sets. The database is freely available at http://genesetdb.auckland.ac.nz/melanomadb/about.html . A subset of the information in the database can also be accessed through a freely available web application in the Illumina genomic cloud computing platform BaseSpace at http://www.biomatters.com/apps/melanoma-profiler-for-research . This illustrates dysregulation of specific signalling pathways, both across 310 exome-sequenced melanomas and in individual tumours and identifies novel features about the distribution of somatic variants in melanoma. We suggest that this database can provide a context in which to interpret the tumour molecular profiles of individual melanoma patients relative to biological information and available

  6. Pathway analysis of IMC

    DEFF Research Database (Denmark)

    Skrypnyuk, Nataliya; Nielson, Flemming; Pilegaard, Henrik

    2009-01-01

    We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced into the...... into the syntax of IMC in order to make our analysis feasible. Finally we describe the analysis itself together with several theoretical results that we have proved for it.......We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced...

  7. Thermodynamic analysis of computed pathways integrated into the metabolic networks of E. coli and Synechocystis reveals contrasting expansion potential.

    Science.gov (United States)

    Asplund-Samuelsson, Johannes; Janasch, Markus; Hudson, Elton P

    2018-01-01

    Introducing biosynthetic pathways into an organism is both reliant on and challenged by endogenous biochemistry. Here we compared the expansion potential of the metabolic network in the photoautotroph Synechocystis with that of the heterotroph E. coli using the novel workflow POPPY (Prospecting Optimal Pathways with PYthon). First, E. coli and Synechocystis metabolomic and fluxomic data were combined with metabolic models to identify thermodynamic constraints on metabolite concentrations (NET analysis). Then, thousands of automatically constructed pathways were placed within each network and subjected to a network-embedded variant of the max-min driving force analysis (NEM). We found that the networks had different capabilities for imparting thermodynamic driving forces toward certain compounds. Key metabolites were constrained differently in Synechocystis due to opposing flux directions in glycolysis and carbon fixation, the forked tri-carboxylic acid cycle, and photorespiration. Furthermore, the lysine biosynthesis pathway in Synechocystis was identified as thermodynamically constrained, impacting both endogenous and heterologous reactions through low 2-oxoglutarate levels. Our study also identified important yet poorly covered areas in existing metabolomics data and provides a reference for future thermodynamics-based engineering in Synechocystis and beyond. The POPPY methodology represents a step in making optimal pathway-host matches, which is likely to become important as the practical range of host organisms is diversified. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact

    DEFF Research Database (Denmark)

    Kuasne, Hellen; Barros-Filho, Mateus Camargo; Busso-Lopes, Ariane F

    2017-01-01

    Penile carcinoma (PeCa) is an important public health issue in poor and developing countries, and has only recently been explored in terms of genetic and epigenetic studies. Integrative data analysis is a powerful method for the identification of molecular drivers involved in cancer development...

  9. An integrated analysis of genes and pathways exhibiting metabolic differences between estrogen receptor positive breast cancer cells

    International Nuclear Information System (INIS)

    Mandal, Soma; Davie, James R

    2007-01-01

    The sex hormone estrogen (E2) is pivotal to normal mammary gland growth and differentiation and in breast carcinogenesis. In this in silico study, we examined metabolic differences between ER(+)ve breast cancer cells during E2 deprivation. Public repositories of SAGE and MA gene expression data generated from E2 deprived ER(+)ve breast cancer cell lines, MCF-7 and ZR75-1 were compared with normal breast tissue. We analyzed gene ontology (GO), enrichment, clustering, chromosome localization, and pathway profiles and performed multiple comparisons with cell lines and tumors with different ER status. In all GO terms, biological process (BP), molecular function (MF), and cellular component (CC), MCF-7 had higher gene utilization than ZR75-1. Various analyses showed a down-regulated immune function, an up-regulated protein (ZR75-1) and glucose metabolism (MCF-7). A greater percentage of 77 common genes localized to the q arm of all chromosomes, but in ZR75-1 chromosomes 11, 16, and 19 harbored more overexpressed genes. Despite differences in gene utilization (electron transport, proteasome, glycolysis/gluconeogenesis) and expression (ribosome) in both cells, there was an overall similarity of ZR75-1 with ER(-)ve cell lines and ER(+)ve/ER(-)ve breast tumors. This study demonstrates integral metabolic differences may exist within the same cell subtype (luminal A) in representative ER(+)ve cell line models. Selectivity of gene and pathway usage for strategies such as energy requirement minimization, sugar utilization by ZR75-1 contrasted with MCF-7 cells, expressing genes whose protein products require ATP utilization. Such characteristics may impart aggressiveness to ZR75-1 and may be prognostic determinants of ER(+)ve breast tumors

  10. Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE

    Directory of Open Access Journals (Sweden)

    Constantinos Yeles

    2017-11-01

    Full Text Available Ionizing radiation-induced bystander effects (RIBE encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR, something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization, and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, the negative regulation of growth, cellular response to Zn2+-Cd2+, and Wnt and NIK/NF-kappaB signaling, thus refining the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations, like α-particles and carbon-ions.

  11. Pathview Web: user friendly pathway visualization and data integration.

    Science.gov (United States)

    Luo, Weijun; Pant, Gaurav; Bhavnasi, Yeshvant K; Blanchard, Steven G; Brouwer, Cory

    2017-07-03

    Pathway analysis is widely used in omics studies. Pathway-based data integration and visualization is a critical component of the analysis. To address this need, we recently developed a novel R package called Pathview. Pathview maps, integrates and renders a large variety of biological data onto molecular pathway graphs. Here we developed the Pathview Web server, as to make pathway visualization and data integration accessible to all scientists, including those without the special computing skills or resources. Pathview Web features an intuitive graphical web interface and a user centered design. The server not only expands the core functions of Pathview, but also provides many useful features not available in the offline R package. Importantly, the server presents a comprehensive workflow for both regular and integrated pathway analysis of multiple omics data. In addition, the server also provides a RESTful API for programmatic access and conveniently integration in third-party software or workflows. Pathview Web is openly and freely accessible at https://pathview.uncc.edu/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

    Science.gov (United States)

    Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

    2017-06-01

    Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RPpathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RPpathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017

  13. Environmental impact assessment for energy pathways: an integrated methodology

    International Nuclear Information System (INIS)

    Sommereux-Blanc, Isabelle

    2010-01-01

    This document presents the synthesis of my research work contributing to the development of an integrated methodology of environmental impact assessment for energy pathways. In the context of world globalization, environmental impact assessments issues are highly linked with the following questioning: Which environmental impacts? for which demand? at which location? at which temporal scale? My work is built upon the definition of a conceptual framework able to handle these issues and upon its progressive implementation. The integration of the spatial and temporal issues within the methodology are key elements. Fundamental cornerstones of this framework are presented along the DPSIR concept (Driving forces, Pressures, State, Impacts, Responses). They cover a comprehensive analysis of the limits and the relevance of life cycle analysis and the development of a geo-spatialized environmental performance approach for an electrical production pathway. Perspectives linked with the development of this integrated methodology are detailed for energy pathways. (author)

  14. kpath: integration of metabolic pathway linked data.

    Science.gov (United States)

    Navas-Delgado, Ismael; García-Godoy, María Jesús; López-Camacho, Esteban; Rybinski, Maciej; Reyes-Palomares, Armando; Medina, Miguel Ángel; Aldana-Montes, José F

    2015-01-01

    In the last few years, the Life Sciences domain has experienced a rapid growth in the amount of available biological databases. The heterogeneity of these databases makes data integration a challenging issue. Some integration challenges are locating resources, relationships, data formats, synonyms or ambiguity. The Linked Data approach partially solves the heterogeneity problems by introducing a uniform data representation model. Linked Data refers to a set of best practices for publishing and connecting structured data on the Web. This article introduces kpath, a database that integrates information related to metabolic pathways. kpath also provides a navigational interface that enables not only the browsing, but also the deep use of the integrated data to build metabolic networks based on existing disperse knowledge. This user interface has been used to showcase relationships that can be inferred from the information available in several public databases. © The Author(s) 2015. Published by Oxford University Press.

  15. Robust Selection Algorithm (RSA) for Multi-Omic Biomarker Discovery; Integration with Functional Network Analysis to Identify miRNA Regulated Pathways in Multiple Cancers.

    Science.gov (United States)

    Sehgal, Vasudha; Seviour, Elena G; Moss, Tyler J; Mills, Gordon B; Azencott, Robert; Ram, Prahlad T

    2015-01-01

    MicroRNAs (miRNAs) play a crucial role in the maintenance of cellular homeostasis by regulating the expression of their target genes. As such, the dysregulation of miRNA expression has been frequently linked to cancer. With rapidly accumulating molecular data linked to patient outcome, the need for identification of robust multi-omic molecular markers is critical in order to provide clinical impact. While previous bioinformatic tools have been developed to identify potential biomarkers in cancer, these methods do not allow for rapid classification of oncogenes versus tumor suppressors taking into account robust differential expression, cutoffs, p-values and non-normality of the data. Here, we propose a methodology, Robust Selection Algorithm (RSA) that addresses these important problems in big data omics analysis. The robustness of the survival analysis is ensured by identification of optimal cutoff values of omics expression, strengthened by p-value computed through intensive random resampling taking into account any non-normality in the data and integration into multi-omic functional networks. Here we have analyzed pan-cancer miRNA patient data to identify functional pathways involved in cancer progression that are associated with selected miRNA identified by RSA. Our approach demonstrates the way in which existing survival analysis techniques can be integrated with a functional network analysis framework to efficiently identify promising biomarkers and novel therapeutic candidates across diseases.

  16. Integrative analysis of circRNAs acting as ceRNAs involved in ethylene pathway in tomato.

    Science.gov (United States)

    Wang, Yunxiang; Wang, Qing; Gao, Lipu; Zhu, Benzhong; Luo, Yunbo; Deng, Zhiping; Zuo, Jinhua

    2017-11-01

    Circular RNAs (circRNAs) are a large class of non-coding endogenous RNAs that could act as competing endogenous RNAs (ceRNAs) to terminate the mRNA targets' suppression of miRNAs. To elucidate the intricate regulatory roles of circRNAs in the ethylene pathway in tomato fruit, deep sequencing and bioinformatics methods were performed. After strict screening, a total of 318 circRNAs were identified. Among these circRNAs, 282 were significantly differentially expressed among wild-type and sense-/antisense-LeERF1 transgenic tomato fruits. Besides, 1254 target genes were identified and a large amount of them were found to be involved in ethylene pathway. In addition, a sophisticated regulatory model consisting of circRNAs, target genes and ethylene was set up. Importantly, 61 circRNAs were found to be potential ceRNAs to combine with miRNAs and some of the miRNAs had been revealed to participate in the ethylene signaling pathway. This research further raised the possibility that the ethylene pathway in tomato fruit may be under the regulation of various circRNAs and provided a new perspective of the roles of circRNAs. © 2017 Scandinavian Plant Physiology Society.

  17. Integrated pathway clusters with coherent biological themes for target prioritisation.

    Directory of Open Access Journals (Sweden)

    Yi-An Chen

    Full Text Available Prioritising candidate genes for further experimental characterisation is an essential, yet challenging task in biomedical research. One way of achieving this goal is to identify specific biological themes that are enriched within the gene set of interest to obtain insights into the biological phenomena under study. Biological pathway data have been particularly useful in identifying functional associations of genes and/or gene sets. However, biological pathway information as compiled in varied repositories often differs in scope and content, preventing a more effective and comprehensive characterisation of gene sets. Here we describe a new approach to constructing biologically coherent gene sets from pathway data in major public repositories and employing them for functional analysis of large gene sets. We first revealed significant overlaps in gene content between different pathways and then defined a clustering method based on the shared gene content and the similarity of gene overlap patterns. We established the biological relevance of the constructed pathway clusters using independent quantitative measures and we finally demonstrated the effectiveness of the constructed pathway clusters in comparative functional enrichment analysis of gene sets associated with diverse human diseases gathered from the literature. The pathway clusters and gene mappings have been integrated into the TargetMine data warehouse and are likely to provide a concise, manageable and biologically relevant means of functional analysis of gene sets and to facilitate candidate gene prioritisation.

  18. DMPD: Signal integration between IFNgamma and TLR signalling pathways in macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16920490 Signal integration between IFNgamma and TLR signalling pathways in macroph...tml) (.csml) Show Signal integration between IFNgamma and TLR signalling pathways in macrophages. PubmedID 16920490 Title Signal inte...gration between IFNgamma and TLR signalling pathways in

  19. Pathway enrichment analysis approach based on topological structure and updated annotation of pathway.

    Science.gov (United States)

    Yang, Qian; Wang, Shuyuan; Dai, Enyu; Zhou, Shunheng; Liu, Dianming; Liu, Haizhou; Meng, Qianqian; Jiang, Bin; Jiang, Wei

    2017-08-16

    Pathway enrichment analysis has been widely used to identify cancer risk pathways, and contributes to elucidating the mechanism of tumorigenesis. However, most of the existing approaches use the outdated pathway information and neglect the complex gene interactions in pathway. Here, we first reviewed the existing widely used pathway enrichment analysis approaches briefly, and then, we proposed a novel topology-based pathway enrichment analysis (TPEA) method, which integrated topological properties and global upstream/downstream positions of genes in pathways. We compared TPEA with four widely used pathway enrichment analysis tools, including database for annotation, visualization and integrated discovery (DAVID), gene set enrichment analysis (GSEA), centrality-based pathway enrichment (CePa) and signaling pathway impact analysis (SPIA), through analyzing six gene expression profiles of three tumor types (colorectal cancer, thyroid cancer and endometrial cancer). As a result, we identified several well-known cancer risk pathways that could not be obtained by the existing tools, and the results of TPEA were more stable than that of the other tools in analyzing different data sets of the same cancer. Ultimately, we developed an R package to implement TPEA, which could online update KEGG pathway information and is available at the Comprehensive R Archive Network (CRAN): https://cran.r-project.org/web/packages/TPEA/. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Towards integrating extracellular matrix and immunological pathways.

    Science.gov (United States)

    Boyd, David F; Thomas, Paul G

    2017-10-01

    The extracellular matrix (ECM) is a complex and dynamic structure made up of an estimated 300 different proteins. The ECM is also a rich source of cytokines and growth factors in addition to numerous bioactive ECM degradation products that influence cell migration, proliferation, and differentiation. The ECM is constantly being remodeled during homeostasis and in a wide range of pathological contexts. Changes in the ECM modulate immune responses, which in turn regulate repair and regeneration of tissues. Here, we review the many components of the ECM, enzymes involved in ECM remodeling, and the signals that feed into immunological pathways in the context of a dynamic ECM. We highlight studies that have taken an integrative approach to studying immune responses in the context of the ECM and studies that use novel proteomic strategies. Finally, we discuss research challenges relevant to the integration of immune and ECM networks and propose experimental and translational approaches to resolve these issues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Integrated RNA-Seq and sRNA-Seq Analysis Identifies Chilling and Freezing Responsive Key Molecular Players and Pathways in Tea Plant (Camellia sinensis)

    Science.gov (United States)

    Zheng, Chao; Zhao, Lei; Wang, Yu; Shen, Jiazhi; Zhang, Yinfei; Jia, Sisi; Li, Yusheng; Ding, Zhaotang

    2015-01-01

    Tea [Camellia sinensis (L) O. Kuntze, Theaceae] is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants’ growth, survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃) and freezing (-5℃) stress. Differentially expressed (DE) miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., ‘Photosynthesis’), GO terms (e.g., ‘response to karrikin’) and transcriptional factors (TFs, e.g., DREB1b/CBF1) which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR), a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology. PMID:25901577

  2. Metabolic reconstruction of Setaria italica: a systems biology approach for integrating tissue-specific omics and pathway analysis of bioenergy grasses

    Directory of Open Access Journals (Sweden)

    Cristiana Gomes De Oliveira Dal'molin

    2016-08-01

    Full Text Available The urgent need for major gains in industrial crops productivity and in biofuel production from bioenergy grasses have reinforced attention on understanding C4 photosynthesis. Systems biology studies of C4 model plants may reveal important features of C4 metabolism. Here we chose foxtail millet (Setaria italica, as a C4 model plant and developed protocols to perform systems biology studies. As part of the systems approach, we have developed and used a genome-scale metabolic reconstruction in combination with the use of multi-omics technologies to gain more insights into the metabolism of S.italica. mRNA, protein and metabolite abundances, were measured in mature and immature stem/leaf phytomers and the multi-omics data were integrated into the metabolic reconstruction framework to capture key metabolic features in different developmental stages of the plant. RNA-Seq reads were mapped to the S. italica resulting for 83% coverage of the protein coding genes of S. italica. Besides revealing similarities and differences in central metabolism of mature and immature tissues, transcriptome analysis indicates significant gene expression of two malic enzyme isoforms (NADP- ME and NAD-ME. Although much greater expression levels of NADP-ME genes are observed and confirmed by the correspondent protein abundances in the samples, the expression of multiple genes combined to the significant abundance of metabolites that participates in C4 metabolism of NAD-ME and NADP-ME subtypes suggest that S. italica may use mixed decarboxylation modes of C4 photosynthetic pathways under different plant developmental stages. The overall analysis also indicates different levels of regulation in mature and immature tissues in carbon fixation, glycolysis, TCA cycle, amino acids, fatty acids, lignin and cellulose syntheses. Altogether, the multi-omics analysis reveals different biological entities and their interrelation and regulation over plant development. With this study

  3. Metabolic Reconstruction of Setaria italica: A Systems Biology Approach for Integrating Tissue-Specific Omics and Pathway Analysis of Bioenergy Grasses.

    Science.gov (United States)

    de Oliveira Dal'Molin, Cristiana G; Orellana, Camila; Gebbie, Leigh; Steen, Jennifer; Hodson, Mark P; Chrysanthopoulos, Panagiotis; Plan, Manuel R; McQualter, Richard; Palfreyman, Robin W; Nielsen, Lars K

    2016-01-01

    The urgent need for major gains in industrial crops productivity and in biofuel production from bioenergy grasses have reinforced attention on understanding C4 photosynthesis. Systems biology studies of C4 model plants may reveal important features of C4 metabolism. Here we chose foxtail millet (Setaria italica), as a C4 model plant and developed protocols to perform systems biology studies. As part of the systems approach, we have developed and used a genome-scale metabolic reconstruction in combination with the use of multi-omics technologies to gain more insights into the metabolism of S. italica. mRNA, protein, and metabolite abundances, were measured in mature and immature stem/leaf phytomers, and the multi-omics data were integrated into the metabolic reconstruction framework to capture key metabolic features in different developmental stages of the plant. RNA-Seq reads were mapped to the S. italica resulting for 83% coverage of the protein coding genes of S. italica. Besides revealing similarities and differences in central metabolism of mature and immature tissues, transcriptome analysis indicates significant gene expression of two malic enzyme isoforms (NADP- ME and NAD-ME). Although much greater expression levels of NADP-ME genes are observed and confirmed by the correspondent protein abundances in the samples, the expression of multiple genes combined to the significant abundance of metabolites that participates in C4 metabolism of NAD-ME and NADP-ME subtypes suggest that S. italica may use mixed decarboxylation modes of C4 photosynthetic pathways under different plant developmental stages. The overall analysis also indicates different levels of regulation in mature and immature tissues in carbon fixation, glycolysis, TCA cycle, amino acids, fatty acids, lignin, and cellulose syntheses. Altogether, the multi-omics analysis reveals different biological entities and their interrelation and regulation over plant development. With this study, we demonstrated

  4. How Effective Are Clinical Pathways With and Without Online Peer-Review? An Analysis of Bone Metastases Pathway in a Large, Integrated National Cancer Institute-Designated Comprehensive Cancer Center Network

    Energy Technology Data Exchange (ETDEWEB)

    Beriwal, Sushil, E-mail: beriwals@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rajagopalan, Malolan S.; Flickinger, John C.; Rakfal, Susan M. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rodgers, Edwin [Via Oncology, Pittsburgh, PA (United States); Heron, Dwight E. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Clinical pathways are an important tool used to manage the quality in health care by standardizing processes. This study evaluated the impact of the implementation of a peer-reviewed clinical pathway in a large, integrated National Cancer Institute-Designated Comprehensive Cancer Center Network. Methods: In 2003, we implemented a clinical pathway for the management of bone metastases with palliative radiation therapy. In 2009, we required the entry of management decisions into an online tool that records pathway choices. The pathway specified 1 or 5 fractions for symptomatic bone metastases with the option of 10-14 fractions for certain clinical situations. The data were obtained from 13 integrated sites (3 central academic, 10 community locations) from 2003 through 2010. Results: In this study, 7905 sites were treated with 64% of courses delivered in community practice and 36% in academic locations. Academic practices were more likely than community practices to treat with 1-5 fractions (63% vs. 23%; p < 0.0001). The number of delivered fractions decreased gradually from 2003 to 2010 for both academic and community practices (p < 0.0001); however, greater numbers of fractions were selected more often in community practices (p < 0.0001). Using multivariate logistic regression, we found that a significantly greater selection of 1-5 fractions developed after implementation online pathway monitoring (2009) with an odds ratio of 1.2 (confidence interval, 1.1-1.4) for community and 1.3 (confidence interval, 1.1-1.6) for academic practices. The mean number of fractions also decreased after online peer review from 6.3 to 6.0 for academic (p = 0.07) and 9.4 to 9.0 for community practices (p < 0.0001). Conclusion: This is one of the first studies to examine the efficacy of a clinical pathway for radiation oncology in an integrated cancer network. Clinical pathway implementation appears to be effective in changing patterns of care, particularly with online clinical

  5. How Effective Are Clinical Pathways With and Without Online Peer-Review? An Analysis of Bone Metastases Pathway in a Large, Integrated National Cancer Institute–Designated Comprehensive Cancer Center Network

    International Nuclear Information System (INIS)

    Beriwal, Sushil; Rajagopalan, Malolan S.; Flickinger, John C.; Rakfal, Susan M.; Rodgers, Edwin; Heron, Dwight E.

    2012-01-01

    Purpose: Clinical pathways are an important tool used to manage the quality in health care by standardizing processes. This study evaluated the impact of the implementation of a peer-reviewed clinical pathway in a large, integrated National Cancer Institute–Designated Comprehensive Cancer Center Network. Methods: In 2003, we implemented a clinical pathway for the management of bone metastases with palliative radiation therapy. In 2009, we required the entry of management decisions into an online tool that records pathway choices. The pathway specified 1 or 5 fractions for symptomatic bone metastases with the option of 10–14 fractions for certain clinical situations. The data were obtained from 13 integrated sites (3 central academic, 10 community locations) from 2003 through 2010. Results: In this study, 7905 sites were treated with 64% of courses delivered in community practice and 36% in academic locations. Academic practices were more likely than community practices to treat with 1–5 fractions (63% vs. 23%; p < 0.0001). The number of delivered fractions decreased gradually from 2003 to 2010 for both academic and community practices (p < 0.0001); however, greater numbers of fractions were selected more often in community practices (p < 0.0001). Using multivariate logistic regression, we found that a significantly greater selection of 1–5 fractions developed after implementation online pathway monitoring (2009) with an odds ratio of 1.2 (confidence interval, 1.1–1.4) for community and 1.3 (confidence interval, 1.1–1.6) for academic practices. The mean number of fractions also decreased after online peer review from 6.3 to 6.0 for academic (p = 0.07) and 9.4 to 9.0 for community practices (p < 0.0001). Conclusion: This is one of the first studies to examine the efficacy of a clinical pathway for radiation oncology in an integrated cancer network. Clinical pathway implementation appears to be effective in changing patterns of care, particularly with

  6. Dysregulated Pathway Identification of Alzheimer's Disease Based on Internal Correlation Analysis of Genes and Pathways.

    Science.gov (United States)

    Kong, Wei; Mou, Xiaoyang; Di, Benteng; Deng, Jin; Zhong, Ruxing; Wang, Shuaiqun

    2017-11-20

    Dysregulated pathway identification is an important task which can gain insight into the underlying biological processes of disease. Current pathway-identification methods focus on a set of co-expression genes and single pathways and ignore the correlation between genes and pathways. The method proposed in this study, takes into account the internal correlations not only between genes but also pathways to identifying dysregulated pathways related to Alzheimer's disease (AD), the most common form of dementia. In order to find the significantly differential genes for AD, mutual information (MI) is used to measure interdependencies between genes other than expression valves. Then, by integrating the topology information from KEGG, the significant pathways involved in the feature genes are identified. Next, the distance correlation (DC) is applied to measure the pairwise pathway crosstalks since DC has the advantage of detecting nonlinear correlations when compared to Pearson correlation. Finally, the pathway pairs with significantly different correlations between normal and AD samples are known as dysregulated pathways. The molecular biology analysis demonstrated that many dysregulated pathways related to AD pathogenesis have been discovered successfully by the internal correlation detection. Furthermore, the insights of the dysregulated pathways in the development and deterioration of AD will help to find new effective target genes and provide important theoretical guidance for drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    NARCIS (Netherlands)

    Bousquet, J.; Addis, A.; Adcock, I.; Agache, I.; Agusti, A.; Alonso, A.; Annesi-Maesano, I.; Anto, J. M.; Bachert, C.; Baena-Cagnani, C. E.; Bai, C.; Baigenzhin, A.; Barbara, C.; Barnes, P. J.; Bateman, E. D.; Beck, L.; Bedbrook, A.; Bel, E. H.; Benezet, O.; Bennoor, K. S.; Benson, M.; Bernabeu-Wittel, M.; Bewick, M.; Bindslev-Jensen, C.; Blain, H.; Blasi, F.; Bonini, M.; Bonini, S.; Boulet, L. P.; Bourdin, A.; Bourret, R.; Bousquet, P. J.; Brightling, C. E.; Briggs, A.; Brozek, J.; Buhl, R.; Bush, A.; Caimmi, D.; Calderon, M.; Calverley, P.; Camargos, P. A.; Camuzat, T.; Canonica, G. W.; Carlsen, K. H.; Casale, T. B.; Cazzola, M.; Cepeda Sarabia, A. M.; Cesario, A.; Chen, Y. Z.; Chkhartishvili, E.; Chavannes, N. H.; Chiron, R.; Chuchalin, A.; Chung, K. F.; Cox, L.; Crooks, G.; Crooks, M. G.; Cruz, A. A.; Custovic, A.; Dahl, R.; Dahlen, S. E.; de Blay, F.; Dedeu, T.; Deleanu, D.; Demoly, P.; Devillier, P.; Didier, A.; Dinh-Xuan, A. T.; Djukanovic, R.; Dokic, D.; Douagui, H.; Dubakiene, R.; Eglin, S.; Elliot, F.; Emuzyte, R.; Fabbri, L.; Fink Wagner, A.; Fletcher, M.; Fokkens, W. J.; Fonseca, J.; Franco, A.; Frith, P.; Furber, A.; Gaga, M.; Garcés, J.; Garcia-Aymerich, J.; Gamkrelidze, A.; Gonzales-Diaz, S.; Gouzi, F.; Guzmán, M. A.; Haahtela, T.; Harrison, D.; Hayot, M.; Heaney, L. G.; Heinrich, J.; Hellings, P. W.; Hooper, J.; Humbert, M.; Hyland, M.; Iaccarino, G.; Jakovenko, D.; Jardim, J. R.; Jeandel, C.; Jenkins, C.; Johnston, S. L.; Jonquet, O.; Joos, G.; Jung, K. S.; Kalayci, O.; Karunanithi, S.; Keil, T.; Khaltaev, N.; Kolek, V.; Kowalski, M. L.; Kull, I.; Kuna, P.; Kvedariene, V.; Le, L. T.; Lodrup Carlsen, K. C.; Louis, R.; MacNee, W.; Mair, A.; Majer, I.; Manning, P.; de Manuel Keenoy, E.; Masjedi, M. R.; Melen, E.; Melo-Gomes, E.; Menzies-Gow, A.; Mercier, G.; Mercier, J.; Michel, J. P.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Molimard, M.; Momas, I.; Montilla-Santana, A.; Morais-Almeida, M.; Morgan, M.; N'Diaye, M.; Nafti, S.; Nekam, K.; Neou, A.; Nicod, L.; O'Hehir, R.; Ohta, K.; Paggiaro, P.; Palkonen, S.; Palmer, S.; Papadopoulos, N. G.; Papi, A.; Passalacqua, G.; Pavord, I.; Pigearias, B.; Plavec, D.; Postma, D. S.; Price, D.; Rabe, K. F.; Radier Pontal, F.; Redon, J.; Rennard, S.; Roberts, J.; Robine, J. M.; Roca, J.; Roche, N.; Rodenas, F.; Roggeri, A.; Rolland, C.; Rosado-Pinto, J.; Ryan, D.; Samolinski, B.; Sanchez-Borges, M.; Schünemann, H. J.; Sheikh, A.; Shields, M.; Siafakas, N.; Sibille, Y.; Similowski, T.; Small, I.; Sola-Morales, O.; Sooronbaev, T.; Stelmach, R.; Sterk, P. J.; Stiris, T.; Sud, P.; Tellier, V.; To, T.; Todo-Bom, A.; Triggiani, M.; Valenta, R.; Valero, A. L.; Valiulis, A.; Valovirta, E.; van Ganse, E.; Vandenplas, O.; Vasankari, T.; Vestbo, J.; Vezzani, G.; Viegi, G.; Visier, L.; Vogelmeier, C.; Vontetsianos, T.; Wagstaff, R.; Wahn, U.; Wallaert, B.; Whalley, B.; Wickman, M.; Williams, D. M.; Wilson, N.; Yawn, B. P.; Yiallouros, P. K.; Yorgancioglu, A.; Yusuf, O. M.; Zar, H. J.; Zhong, N.; Zidarn, M.; Zuberbier, T.

    2014-01-01

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will

  8. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    NARCIS (Netherlands)

    Bousquet, J.; Addis, A.; Adcock, I.; Agache, I.; Agusti, A.; Alonso, A.; Annesi-Maesano, I.; Anto, J. M.; Bachert, C.; Baena-Cagnani, C. E.; Bai, C.; Baigenzhin, A.; Barbara, C.; Barnes, P. J.; Bateman, E. D.; Beck, L.; Bedbrook, A.; Bel, E. H.; Benezet, O.; Bennoor, K. S.; Benson, M.; Bernabeu-Wittel, M.; Bewick, M.; Bindslev-Jensen, C.; Blain, H.; Blasi, F.; Bonini, M.; Bonini, S.; Boulet, L. P.; Bourdin, A.; Bourret, R.; Bousquet, P. J.; Brightling, C. E.; Briggs, A.; Brozek, J.; Buh, R.; Bush, A.; Caimmi, D.; Calderon, M.; Calverley, P.; Camargos, P. A.; Camuzat, T.; Canonica, G. W.; Carlsen, K. H.; Casale, T. B.; Cazzola, M.; Sarabia, A. M. Cepeda; Cesario, A.; Chen, Y. Z.; Chkhartishvili, E.; Chavannes, N. H.; Chiron, R.; Chuchalin, A.; Chung, K. F.; Cox, L.; Crooks, G.; Crooks, M. G.; Cruz, A. A.; Custovic, A.; Dahl, R.; Dahlen, S. E.; De Blay, F.; Dedeu, T.; Deleanu, D.; Demoly, P.; Devillier, P.; Didier, A.; Dinh-Xuan, A. T.; Djukanovic, R.; Dokic, D.; Douagui, H.; Dubakiene, R.; Eglin, S.; Elliot, F.; Emuzyte, R.; Fabbri, L.; Wagner, A. Fink; Fletcher, M.; Fokkens, W. J.; Fonseca, J.; Franco, A.; Frith, P.; Furber, A.; Gaga, M.; Garces, J.; Garcia-Aymerich, J.; Gamkrelidze, A.; Gonzales-Diaz, S.; Gouzi, F.; Guzman, M. A.; Haahtela, T.; Harrison, D.; Hayot, M.; Heaney, L. G.; Heinrich, J.; Hellings, P. W.; Hooper, J.; Humbert, M.; Hyland, M.; Iaccarino, G.; Jakovenko, D.; Jardim, J. R.; Jeandel, C.; Jenkins, C.; Johnston, S. L.; Jonquet, O.; Joos, G.; Jung, K. S.; Kalayci, O.; Karunanithi, S.; Keil, T.; Khaltaev, N.; Kolek, V.; Kowalski, M. L.; Kull, I.; Kuna, P.; Kvedariene, V.; Le, L. T.; Carlsen, K. C. Lodrup; Louis, R.; MacNee, W.; Mair, A.; Majer, I.; Manning, P.; Keenoy, E. de Manuel; Masjedi, M. R.; Meten, E.; Melo-Gomes, E.; Menzies-Gow, A.; Mercier, G.; Mercier, J.; Michel, J. P.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Molimard, M.; Mamas, I.; Montilla-Santana, A.; Morais-Almeida, M.; Morgan, M.; N'Diaye, M.; Nafti, S.; Nekam, K.; Neou, A.; Nicod, L.; O'Hehir, R.; Ohta, K.; Paggiaro, P.; Palkonen, S.; Palmer, S.; Papadopoulos, N. G.; Papi, A.; Passalacqua, G.; Pavord, I.; Pigearias, B.; Plavec, D.; Postma, D. S.; Price, D.; Rabe, K. F.; Pontal, F. Radier; Redon, J.; Rennard, S.; Roberts, J.; Robine, J. M.; Roca, J.; Roche, N.; Rodenas, F.; Roggeri, A.; Rolland, C.; Rosado-Pinto, J.; Ryan, D.; Samolinski, B.; Sanchez-Borges, M.; Schunemann, H. J.; Sheikh, A.; Shields, M.; Siafakas, N.; Sibille, Y.; Similowski, T.; Small, I.; Sola-Morales, O.; Sooronbaev, T.; Stelmach, R.; Sterk, P. J.; Stiris, T.; Sud, P.; Tellier, V.; To, T.; Todo-Bom, A.; Triggiani, M.; Valenta, R.; Valero, A. L.; Valiulis, A.; Valovirta, E.; Van Ganse, E.; Vandenplas, O.; Vasankari, T.; Vestbo, J.; Vezzani, G.; Viegi, G.; Visier, L.; Vogelmeier, C.; Vontetsianos, T.; Wagstaff, R.; Wahn, U.; Wallaert, B.; Whalley, B.; Wickman, M.; Williams, D. M.; Wilson, N.; Yawn, B. P.; Yiallouros, P. K.; Yorgancioglu, A.; Yusuf, O. M.; Zar, H. J.; Zhong, N.; Zidarn, M.; Zuberbier, T.

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will

  9. Primary Metabolic Pathways and Metabolic Flux Analysis

    DEFF Research Database (Denmark)

    Villadsen, John

    2015-01-01

    his chapter introduces the metabolic flux analysis (MFA) or stoichiometry-based MFA, and describes the quantitative basis for MFA. It discusses the catabolic pathways in which free energy is produced to drive the cell-building anabolic pathways. An overview of these primary pathways provides...... the reader who is primarily trained in the engineering sciences with atleast a preliminary introduction to biochemistry and also shows how carbon is drained off the catabolic pathways to provide precursors for cell mass building and sometimes for important industrial products. The primary pathways...... to be examined in the following are: glycolysis, primarily by the EMP pathway, but other glycolytic pathways is also mentioned; fermentative pathways in which the redox generated in the glycolytic reactions are consumed; reactions in the tricarboxylic acid (TCA) cycle, which produce biomass precursors and redox...

  10. Modeling Pathways of Character Development across the First Three Decades of Life: An Application of Integrative Data Analysis Techniques to Understanding the Development of Hopeful Future Expectations.

    Science.gov (United States)

    Callina, Kristina Schmid; Johnson, Sara K; Tirrell, Jonathan M; Batanova, Milena; Weiner, Michelle B; Lerner, Richard M

    2017-06-01

    There were two purposes of the present research: first, to add to scholarship about a key character virtue, hopeful future expectations; and second, to demonstrate a recent innovation in longitudinal methodology that may be especially useful in enhancing the understanding of the developmental course of hopeful future expectations and other character virtues that have been the focus of recent scholarship in youth development. Burgeoning interest in character development has led to a proliferation of short-term, longitudinal studies on character. These data sets are sometimes limited in their ability to model character development trajectories due to low power or relatively brief time spans assessed. However, the integrative data analysis approach allows researchers to pool raw data across studies in order to fit one model to an aggregated data set. The purpose of this article is to demonstrate the promises and challenges of this new tool for modeling character development. We used data from four studies evaluating youth character strengths in different settings to fit latent growth curve models of hopeful future expectations from participants aged 7 through 26 years. We describe the analytic strategy for pooling the data and modeling the growth curves. Implications for future research are discussed in regard to the advantages of integrative data analysis. Finally, we discuss issues researchers should consider when applying these techniques in their own work.

  11. PathJam: a new service for integrating biological pathway information

    Directory of Open Access Journals (Sweden)

    Glez-Peña Daniel

    2010-03-01

    Full Text Available Biological pathways are crucial to much of the scientific research today including the study of specific biological processes related with human diseases. PathJam is a new comprehensive and freely accessible web-server application integrating scattered human pathway annotation from several public sources. The tool has been designed for both (i being intuitive for wet-lab users providing statistical enrichment analysis of pathway annotations and (ii giving support to the development of new integrative pathway applications. PathJam’s unique features and advantages include interactive graphs linking pathways and genes of interest, downloadable results in fully compatible formats, GSEA compatible output files and a standardized RESTful API.

  12. Psychotherapy, psychopathology, research and practice: pathways of connections and integration.

    Science.gov (United States)

    Castonguay, Louis G

    2011-03-01

    This paper describes three pathways of connections between different communities of knowledge seekers: integration of psychotherapeutic approaches, integration of psychotherapy and psychopathology, and integration of science and practice. Some of the issues discussed involve the delineation and investigation of common factors (e.g., principles of change), improvement of major forms of psychotherapy, clinical implications of psychopathology research, as well as current and future directions related to practice-research networks. The aim of this paper is to suggest that building bridges across theoretical orientations, scientific fields, professional experiences, and epistemological views may be a fruitful strategy to improve our understanding and the impact of psychotherapy.

  13. Integrated genetic analysis microsystems

    International Nuclear Information System (INIS)

    Lagally, Eric T; Mathies, Richard A

    2004-01-01

    With the completion of the Human Genome Project and the ongoing DNA sequencing of the genomes of other animals, bacteria, plants and others, a wealth of new information about the genetic composition of organisms has become available. However, as the demand for sequence information grows, so does the workload required both to generate this sequence and to use it for targeted genetic analysis. Microfabricated genetic analysis systems are well poised to assist in the collection and use of these data through increased analysis speed, lower analysis cost and higher parallelism leading to increased assay throughput. In addition, such integrated microsystems may point the way to targeted genetic experiments on single cells and in other areas that are otherwise very difficult. Concomitant with these advantages, such systems, when fully integrated, should be capable of forming portable systems for high-speed in situ analyses, enabling a new standard in disciplines such as clinical chemistry, forensics, biowarfare detection and epidemiology. This review will discuss the various technologies available for genetic analysis on the microscale, and efforts to integrate them to form fully functional robust analysis devices. (topical review)

  14. Pathway Relevance Ranking for Tumor Samples through Network-Based Data Integration.

    Directory of Open Access Journals (Sweden)

    Lieven P C Verbeke

    Full Text Available The study of cancer, a highly heterogeneous disease with different causes and clinical outcomes, requires a multi-angle approach and the collection of large multi-omics datasets that, ideally, should be analyzed simultaneously. We present a new pathway relevance ranking method that is able to prioritize pathways according to the information contained in any combination of tumor related omics datasets. Key to the method is the conversion of all available data into a single comprehensive network representation containing not only genes but also individual patient samples. Additionally, all data are linked through a network of previously identified molecular interactions. We demonstrate the performance of the new method by applying it to breast and ovarian cancer datasets from The Cancer Genome Atlas. By integrating gene expression, copy number, mutation and methylation data, the method's potential to identify key pathways involved in breast cancer development shared by different molecular subtypes is illustrated. Interestingly, certain pathways were ranked equally important for different subtypes, even when the underlying (epi-genetic disturbances were diverse. Next to prioritizing universally high-scoring pathways, the pathway ranking method was able to identify subtype-specific pathways. Often the score of a pathway could not be motivated by a single mutation, copy number or methylation alteration, but rather by a combination of genetic and epi-genetic disturbances, stressing the need for a network-based data integration approach. The analysis of ovarian tumors, as a function of survival-based subtypes, demonstrated the method's ability to correctly identify key pathways, irrespective of tumor subtype. A differential analysis of survival-based subtypes revealed several pathways with higher importance for the bad-outcome patient group than for the good-outcome patient group. Many of the pathways exhibiting higher importance for the bad

  15. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    DEFF Research Database (Denmark)

    Bousquet, J; Addis, A; Adcock, I

    2014-01-01

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy...... and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking...... and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5...

  16. A strategy for evaluating pathway analysis methods.

    Science.gov (United States)

    Yu, Chenggang; Woo, Hyung Jun; Yu, Xueping; Oyama, Tatsuya; Wallqvist, Anders; Reifman, Jaques

    2017-10-13

    Researchers have previously developed a multitude of methods designed to identify biological pathways associated with specific clinical or experimental conditions of interest, with the aim of facilitating biological interpretation of high-throughput data. Before practically applying such pathway analysis (PA) methods, we must first evaluate their performance and reliability, using datasets where the pathways perturbed by the conditions of interest have been well characterized in advance. However, such 'ground truths' (or gold standards) are often unavailable. Furthermore, previous evaluation strategies that have focused on defining 'true answers' are unable to systematically and objectively assess PA methods under a wide range of conditions. In this work, we propose a novel strategy for evaluating PA methods independently of any gold standard, either established or assumed. The strategy involves the use of two mutually complementary metrics, recall and discrimination. Recall measures the consistency of the perturbed pathways identified by applying a particular analysis method to an original large dataset and those identified by the same method to a sub-dataset of the original dataset. In contrast, discrimination measures specificity-the degree to which the perturbed pathways identified by a particular method to a dataset from one experiment differ from those identifying by the same method to a dataset from a different experiment. We used these metrics and 24 datasets to evaluate six widely used PA methods. The results highlighted the common challenge in reliably identifying significant pathways from small datasets. Importantly, we confirmed the effectiveness of our proposed dual-metric strategy by showing that previous comparative studies corroborate the performance evaluations of the six methods obtained by our strategy. Unlike any previously proposed strategy for evaluating the performance of PA methods, our dual-metric strategy does not rely on any ground truth

  17. The impact of climate change mitigation on water demand for energy and food: An integrated analysis based on the Shared Socioeconomic Pathways

    NARCIS (Netherlands)

    Mouratiadou, Ioanna; Biewald, Anne; Pehl, Michaja; Bonsch, Markus; Baumstark, Lavinia; Klein, David; Popp, Alexander; Luderer, Gunnar; Kriegler, Elmar

    2016-01-01

    Abstract Climate change mitigation, in the context of growing population and ever increasing economic activity, will require a transformation of energy and agricultural systems, posing significant challenges to global water resources. We use an integrated modelling framework of the

  18. Pathway analysis: State of the art

    Directory of Open Access Journals (Sweden)

    Miguel Angel eGarcía-Campos

    2015-12-01

    Full Text Available Pathway analysis is a set of widely used tools for research in life sciences intended to give meaning to high-throughput biological data. The methodology of these tools settles in the gathering and usage of knowledge that comprise biomolecular functioning, coupled with statistical testing and other algorithms. Despite their wide employment, pathway analysis foundations and overall background may not be fully understood, leading to misinterpretation of analysis results. This review attempts to comprise the fundamental knowledge to take into consideration when using pathway analysis as a hypothesis generation tool. We discuss the key elements that are part of these methodologies, their capabilities and current deficiencies. We also present an overview of current and all-time popular methods, highlighting different classes across them. In doing so, we show the exploding diversity of methods that pathway analysis encompasses, point out commonly overlooked caveats, and direct attention to a potential new class of methods that attempt to zoom the analysis scope to the sample scale.

  19. Simplified analysis for liquid pathway studies

    International Nuclear Information System (INIS)

    Codell, R.B.

    1984-08-01

    The analysis of the potential contamination of surface water via groundwater contamination from severe nuclear accidents is routinely calculated during licensing reviews. This analysis is facilitated by the methods described in this report, which is codified into a BASIC language computer program, SCREENLP. This program performs simplified calculations for groundwater and surface water transport and calculates population doses to potential users for the contaminated water irrespective of possible mitigation methods. The results are then compared to similar analyses performed using data for the generic sites in NUREG-0440, Liquid Pathway Generic Study, to determine if the site being investigated would pose any unusual liquid pathway hazards

  20. Methods of assessing total doses integrated across pathways

    International Nuclear Information System (INIS)

    Grzechnik, M.; Camplin, W.; Clyne, F.; Allott, R.; Webbe-Wood, D.

    2006-01-01

    Calculated doses for comparison with limits resulting from discharges into the environment should be summed across all relevant pathways and food groups to ensure adequate protection. Current methodology for assessments used in the radioactivity in Food and the Environment (R.I.F.E.) reports separate doses from pathways related to liquid discharges of radioactivity to the environment from those due to gaseous releases. Surveys of local inhabitant food consumption and occupancy rates are conducted in the vicinity of nuclear sites. Information has been recorded in an integrated way, such that the data for each individual is recorded for all pathways of interest. These can include consumption of foods, such as fish, crustaceans, molluscs, fruit and vegetables, milk and meats. Occupancy times over beach sediments and time spent in close proximity to the site is also recorded for inclusion of external and inhalation radiation dose pathways. The integrated habits survey data may be combined with monitored environmental radionuclide concentrations to calculate total dose. The criteria for successful adoption of a method for this calculation were: Reproducibility can others easily use the approach and reassess doses? Rigour and realism how good is the match with reality?Transparency a measure of the ease with which others can understand how the calculations are performed and what they mean. Homogeneity is the group receiving the dose relatively homogeneous with respect to age, diet and those aspects that affect the dose received? Five methods of total dose calculation were compared and ranked according to their suitability. Each method was labelled (A to E) and given a short, relevant name for identification. The methods are described below; A) Individual doses to individuals are calculated and critical group selection is dependent on dose received. B) Individual Plus As in A, but consumption and occupancy rates for high dose is used to derive rates for application in

  1. Application of the critical pathway and integrated case teaching method to nursing orientation.

    Science.gov (United States)

    Goodman, D

    1997-01-01

    Nursing staff development programs must be responsive to current changes in healthcare. New nursing staff must be prepared to manage continuous change and to function competently in clinical practice. The orientation pathway, based on a case management model, is used as a structure for the orientation phase of staff development. The integrated case is incorporated as a teaching strategy in orientation. The integrated case method is based on discussion and analysis of patient situations with emphasis on role modeling and integration of theory and skill. The orientation pathway and integrated case teaching method provide a useful framework for orientation of new staff. Educators, preceptors and orientees find the structure provided by the orientation pathway very useful. Orientation that is developed, implemented and evaluated based on a case management model with the use of an orientation pathway and incorporation of an integrated case teaching method provides a standardized structure for orientation of new staff. This approach is designed for the adult learner, promotes conceptual reasoning, and encourages the social and contextual basis for continued learning.

  2. Final report on the Pathway Analysis Task

    International Nuclear Information System (INIS)

    Whicker, F.W.; Kirchner, T.B.

    1993-04-01

    The Pathway Analysis Task constituted one of several multi-laboratory efforts to estimate radiation doses to people, considering all important pathways of exposure, from the testing of nuclear devices at the Nevada Test Site (NTS). The primary goal of the Pathway Analysis Task was to predict radionuclide ingestion by residents of Utah, Nevada, and portions of seven other adjoining western states following radioactive fallout deposition from individual events at the NTS. This report provides comprehensive documentation of the activities and accomplishments of Colorado State University's Pathway Analysis Task during the entire period of support (1979--91). The history of the project will be summarized, indicating the principal dates and milestones, personnel involved, subcontractors, and budget information. Accomplishments, both primary and auxiliary, will be summarized with general results rather than technical details being emphasized. This will also serve as a guide to the reports and open literature publications produced, where the methodological details and specific results are documented. Selected examples of results on internal dose estimates are provided in this report because the data have not been published elsewhere

  3. Cleanup standards and pathways analysis methods

    International Nuclear Information System (INIS)

    Devgun, J.S.

    1993-01-01

    Remediation of a radioactively contaminated site requires that certain regulatory criteria be met before the site can be released for unrestricted future use. Since the ultimate objective of remediation is to protect the public health and safety, residual radioactivity levels remaining at a site after cleanup must be below certain preset limits or meet acceptable dose or risk criteria. Release of a decontaminated site requires proof that the radiological data obtained from the site meet the regulatory criteria for such a release. Typically release criteria consist of a composite of acceptance limits that depend on the radionuclides, the media in which they are present, and federal and local regulations. In recent years, the US Department of Energy (DOE) has developed a pathways analysis model to determine site-specific soil activity concentration guidelines for radionuclides that do not have established generic acceptance limits. The DOE pathways analysis computer code (developed by Argonne National Laboratory for the DOE) is called RESRAD (Gilbert et al. 1989). Similar efforts have been initiated by the US Nuclear Regulatory Commission (NRC) to develop and use dose-related criteria based on genetic pathways analyses rather than simplistic numerical limits on residual radioactivity. The focus of this paper is radionuclide contaminated soil. Cleanup standards are reviewed, pathways analysis methods are described, and an example is presented in which RESRAD was used to derive cleanup guidelines

  4. Final report on the Pathway Analysis Task

    Energy Technology Data Exchange (ETDEWEB)

    Whicker, F.W.; Kirchner, T.B. [Colorado State Univ., Fort Collins, CO (United States)

    1993-04-01

    The Pathway Analysis Task constituted one of several multi-laboratory efforts to estimate radiation doses to people, considering all important pathways of exposure, from the testing of nuclear devices at the Nevada Test Site (NTS). The primary goal of the Pathway Analysis Task was to predict radionuclide ingestion by residents of Utah, Nevada, and portions of seven other adjoining western states following radioactive fallout deposition from individual events at the NTS. This report provides comprehensive documentation of the activities and accomplishments of Colorado State University`s Pathway Analysis Task during the entire period of support (1979--91). The history of the project will be summarized, indicating the principal dates and milestones, personnel involved, subcontractors, and budget information. Accomplishments, both primary and auxiliary, will be summarized with general results rather than technical details being emphasized. This will also serve as a guide to the reports and open literature publications produced, where the methodological details and specific results are documented. Selected examples of results on internal dose estimates are provided in this report because the data have not been published elsewhere.

  5. Electronic patient information systems and care pathways: the organisational challenges of implementation and integration.

    Science.gov (United States)

    Dent, Mike; Tutt, Dylan

    2014-09-01

    Our interest here is with the 'marriage' of e-patient information systems with care pathways in order to deliver integrated care. We report on the development and implementation of four such pathways within two National Health Service primary care trusts in England: (a) frail elderly care, (b) stroke care, (c) diabetic retinopathy screening and (d) intermediate care. The pathways were selected because each represents a different type of information and data 'couplings', in terms of task interdependency with some pathways/systems reflecting more complex coordinating patterns than others. Our aim here is identify and explain how health professionals and information specialists in two organisational National Health Service primary care trusts organisationally construct and use such systems and, in particular, the implications this has for issues of professional and managerial control and autonomy. The article is informed by an institutionalist analysis. © The Author(s) 2013.

  6. IntPath--an integrated pathway gene relationship database for model organisms and important pathogens.

    Science.gov (United States)

    Zhou, Hufeng; Jin, Jingjing; Zhang, Haojun; Yi, Bo; Wozniak, Michal; Wong, Limsoon

    2012-01-01

    Pathway data are important for understanding the relationship between genes, proteins and many other molecules in living organisms. Pathway gene relationships are crucial information for guidance, prediction, reference and assessment in biochemistry, computational biology, and medicine. Many well-established databases--e.g., KEGG, WikiPathways, and BioCyc--are dedicated to collecting pathway data for public access. However, the effectiveness of these databases is hindered by issues such as incompatible data formats, inconsistent molecular representations, inconsistent molecular relationship representations, inconsistent referrals to pathway names, and incomprehensive data from different databases. In this paper, we overcome these issues through extraction, normalization and integration of pathway data from several major public databases (KEGG, WikiPathways, BioCyc, etc). We build a database that not only hosts our integrated pathway gene relationship data for public access but also maintains the necessary updates in the long run. This public repository is named IntPath (Integrated Pathway gene relationship database for model organisms and important pathogens). Four organisms--S. cerevisiae, M. tuberculosis H37Rv, H. Sapiens and M. musculus--are included in this version (V2.0) of IntPath. IntPath uses the "full unification" approach to ensure no deletion and no introduced noise in this process. Therefore, IntPath contains much richer pathway-gene and pathway-gene pair relationships and much larger number of non-redundant genes and gene pairs than any of the single-source databases. The gene relationships of each gene (measured by average node degree) per pathway are significantly richer. The gene relationships in each pathway (measured by average number of gene pairs per pathway) are also considerably richer in the integrated pathways. Moderate manual curation are involved to get rid of errors and noises from source data (e.g., the gene ID errors in WikiPathways and

  7. Integrating computational methods to retrofit enzymes to synthetic pathways.

    Science.gov (United States)

    Brunk, Elizabeth; Neri, Marilisa; Tavernelli, Ivano; Hatzimanikatis, Vassily; Rothlisberger, Ursula

    2012-02-01

    Microbial production of desired compounds provides an efficient framework for the development of renewable energy resources. To be competitive to traditional chemistry, one requirement is to utilize the full capacity of the microorganism to produce target compounds with high yields and turnover rates. We use integrated computational methods to generate and quantify the performance of novel biosynthetic routes that contain highly optimized catalysts. Engineering a novel reaction pathway entails addressing feasibility on multiple levels, which involves handling the complexity of large-scale biochemical networks while respecting the critical chemical phenomena at the atomistic scale. To pursue this multi-layer challenge, our strategy merges knowledge-based metabolic engineering methods with computational chemistry methods. By bridging multiple disciplines, we provide an integral computational framework that could accelerate the discovery and implementation of novel biosynthetic production routes. Using this approach, we have identified and optimized a novel biosynthetic route for the production of 3HP from pyruvate. Copyright © 2011 Wiley Periodicals, Inc.

  8. Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Neeraja Krishnan

    2015-11-01

    Full Text Available Oral tongue squamous cell carcinomas (OTSCC are a homogeneous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs is on the rise; many of whom lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on single nucleotide variations (SNVs, indels, regions with loss of heterozygosity (LOH, and copy number variations (CNVs from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including human papilloma virus (HPV infection and tumor recurrence. Apart from the frequent somatic variants harbored in TP53, CASP8, RASA1, NOTCH and CDKN2A genes, significant amplifications and/or deletions were detected in chromosomes 6-9, and 11 in the tumors. Variants in CASP8 and CDKN2A were mutually exclusive. CDKN2A, PIK3CA, RASA1 and DMD variants were exclusively linked to smoking, chewing, HPV infection and tumor stage. We also performed a whole-genome gene expression study that identified matrix metalloproteases to be highly expressed in tumors and linked pathways involving arachidonic acid and NF-k-B to habits and distant metastasis, respectively. Functional knockdown studies in cell lines demonstrated the role of CASP8 in a HPV-negative OTSCC cell line. Finally, we identified a 38-gene minimal signature that predicts tumor recurrence using an ensemble machine-learning method. Taken together, this study links molecular signatures to various clinical and epidemiological factors in a homogeneous tumor population with a relatively high HPV prevalence.

  9. Portuguese Older Gay Men: Pathways to Family Integrity

    Directory of Open Access Journals (Sweden)

    Filipa Daniela Marques

    2016-08-01

    Full Text Available Abstract Research in the field of older gay men remains scarce. This exploratory study examines older gay men's experiences in the construction of family integrity (versus disconnection and alienation. The family integrity approach is a developmental perspective that links ego integrity to a larger process of constructing meaning within the family system. The sample comprises ten participants (from 60 to 88 years old. A semi-structured interview was conducted and submitted to content analysis. The main findings suggest three experiences in older gay men's construction of family integrity: (i influence of homosexuality throughout life; (ii establishing a family of choice; (iii creating a legacy associated with homosexuality. Family integrity in older gay men seems to evolve from disclosure at a young age to making homosexuality a legacy in old age.

  10. Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Wufeng Fan

    2017-01-01

    Full Text Available In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM based on pathway interaction network (PIN which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs, and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

  11. Exploring the Unfolding Pathway of Maltose Binding Proteins: An Integrated Computational Approach

    KAUST Repository

    Guardiani, Carlo; Marino, Daniele Di; Tramontano, Anna; Chinappi, Mauro; Cecconi, Fabio

    2014-01-01

    © 2014 American Chemical Society. Recent single-molecule force spectroscopy experiments on the Maltose Binding Proteins (MBPs) identified four stable structural units, termed unfoldons, that resist mechanical stress and determine the intermediates of the unfolding pathway. In this work, we analyze the topological origin and the dynamical role of the unfoldons using an integrated approach which combines a graph-theoretical analysis of the interaction network of the MBP native-state with steered molecular dynamics simulations. The topological analysis of the native state, while revealing the structural nature of the unfoldons, provides a framework to interpret the MBP mechanical unfolding pathway. Indeed, the experimental pathway can be effectively predicted by means of molecular dynamics simulations with a simple topology-based and low-resolution model of the MBP. The results obtained from the coarse-grained approach are confirmed and further refined by all-atom molecular dynamics.

  12. Exploring the Unfolding Pathway of Maltose Binding Proteins: An Integrated Computational Approach

    KAUST Repository

    Guardiani, Carlo

    2014-09-09

    © 2014 American Chemical Society. Recent single-molecule force spectroscopy experiments on the Maltose Binding Proteins (MBPs) identified four stable structural units, termed unfoldons, that resist mechanical stress and determine the intermediates of the unfolding pathway. In this work, we analyze the topological origin and the dynamical role of the unfoldons using an integrated approach which combines a graph-theoretical analysis of the interaction network of the MBP native-state with steered molecular dynamics simulations. The topological analysis of the native state, while revealing the structural nature of the unfoldons, provides a framework to interpret the MBP mechanical unfolding pathway. Indeed, the experimental pathway can be effectively predicted by means of molecular dynamics simulations with a simple topology-based and low-resolution model of the MBP. The results obtained from the coarse-grained approach are confirmed and further refined by all-atom molecular dynamics.

  13. RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites.

    Science.gov (United States)

    Zhang, Bofei; Hu, Senyang; Baskin, Elizabeth; Patt, Andrew; Siddiqui, Jalal K; Mathé, Ewy A

    2018-02-22

    The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be

  14. Integrated Enrichment Analysis of Variants and Pathways in Genome-Wide Association Studies Indicates Central Role for IL-2 Signaling Genes in Type 1 Diabetes, and Cytokine Signaling Genes in Crohn's Disease

    Science.gov (United States)

    Carbonetto, Peter; Stephens, Matthew

    2013-01-01

    Pathway analyses of genome-wide association studies aggregate information over sets of related genes, such as genes in common pathways, to identify gene sets that are enriched for variants associated with disease. We develop a model-based approach to pathway analysis, and apply this approach to data from the Wellcome Trust Case Control Consortium (WTCCC) studies. Our method offers several benefits over existing approaches. First, our method not only interrogates pathways for enrichment of disease associations, but also estimates the level of enrichment, which yields a coherent way to promote variants in enriched pathways, enhancing discovery of genes underlying disease. Second, our approach allows for multiple enriched pathways, a feature that leads to novel findings in two diseases where the major histocompatibility complex (MHC) is a major determinant of disease susceptibility. Third, by modeling disease as the combined effect of multiple markers, our method automatically accounts for linkage disequilibrium among variants. Interrogation of pathways from eight pathway databases yields strong support for enriched pathways, indicating links between Crohn's disease (CD) and cytokine-driven networks that modulate immune responses; between rheumatoid arthritis (RA) and “Measles” pathway genes involved in immune responses triggered by measles infection; and between type 1 diabetes (T1D) and IL2-mediated signaling genes. Prioritizing variants in these enriched pathways yields many additional putative disease associations compared to analyses without enrichment. For CD and RA, 7 of 8 additional non-MHC associations are corroborated by other studies, providing validation for our approach. For T1D, prioritization of IL-2 signaling genes yields strong evidence for 7 additional non-MHC candidate disease loci, as well as suggestive evidence for several more. Of the 7 strongest associations, 4 are validated by other studies, and 3 (near IL-2 signaling genes RAF1, MAPK14

  15. Integrative pathway knowledge bases as a tool for systems molecular medicine.

    Science.gov (United States)

    Liang, Mingyu

    2007-08-20

    There exists a sense of urgency to begin to generate a cohesive assembly of biomedical knowledge as the pace of knowledge accumulation accelerates. The urgency is in part driven by the emergence of systems molecular medicine that emphasizes the combination of systems analysis and molecular dissection in the future of medical practice and research. A potentially powerful approach is to build integrative pathway knowledge bases that link organ systems function with molecules.

  16. Fostering development of nursing practices to support integrated care when implementing integrated care pathways: what levers to use?

    Science.gov (United States)

    Longpré, Caroline; Dubois, Carl-Ardy

    2017-11-29

    Care integration has been the focus of recent health system reforms. Given their functions at all levels of the care continuum, nurses have a substantial and primordial role to play in such integration processes. The aim of this study was to identify levers and strategies that organizations can use to support the development of a nursing practice aligned with the requirements of care integration in a health and social services centre (HSSC) in Quebec. The research design was a cross-sectional descriptive qualitative study based on a single case study with nested levels of analysis. The case was a public, multi-disciplinary HSSC in a semi-urban region of Quebec. Semi-structured interviews with 37 persons (nurses, professionals, managers, administrators) allowed for data saturation and ensured theoretical representation by covering four care pathways constituting different care integration contexts. Analysis involved four steps: preparing a predetermined list of codes based on the reference framework developed by Minkman (2011); coding transcript content; developing general and summary matrices to group observations for each care pathway; and creating a general model showing the overall results for the four pathways. The organization's capacity for response with regard to developing an integrated system of services resulted in two types of complementary interventions. The first involved investing in key resources and renewing organizational structures; the second involved deploying a series of organizational and clinical-administrative processes. In resource terms, integration efforts resulted in setting up new strategic services, re-arranging physical infrastructures, and deploying new technological resources. Organizational and clinical-administrative processes to promote integration involved renewing governance, improving the flow of care pathways, fostering continuous quality improvement, developing new roles, promoting clinician collaboration, and strengthening

  17. Analysis of Membrane Protein Topology in the Plant Secretory Pathway.

    Science.gov (United States)

    Guo, Jinya; Miao, Yansong; Cai, Yi

    2017-01-01

    Topology of membrane proteins provides important information for the understanding of protein function and intermolecular associations. Integrate membrane proteins are generally transported from endoplasmic reticulum (ER) to Golgi and downstream compartments in the plant secretory pathway. Here, we describe a simple method to study membrane protein topology along the plant secretory pathway by transiently coexpressing a fluorescent protein (XFP)-tagged membrane protein and an ER export inhibitor protein, ARF1 (T31N), in tobacco BY-2 protoplast. By fractionation, microsome isolation, and trypsin digestion, membrane protein topology could be easily detected by either direct confocal microscopy imaging or western-blot analysis using specific XFP antibodies. A similar strategy in determining membrane protein topology could be widely adopted and applied to protein analysis in a broad range of eukaryotic systems, including yeast cells and mammalian cells.

  18. Integrated pathway-based transcription regulation network mining and visualization based on gene expression profiles.

    Science.gov (United States)

    Kibinge, Nelson; Ono, Naoaki; Horie, Masafumi; Sato, Tetsuo; Sugiura, Tadao; Altaf-Ul-Amin, Md; Saito, Akira; Kanaya, Shigehiko

    2016-06-01

    Conventionally, workflows examining transcription regulation networks from gene expression data involve distinct analytical steps. There is a need for pipelines that unify data mining and inference deduction into a singular framework to enhance interpretation and hypotheses generation. We propose a workflow that merges network construction with gene expression data mining focusing on regulation processes in the context of transcription factor driven gene regulation. The pipeline implements pathway-based modularization of expression profiles into functional units to improve biological interpretation. The integrated workflow was implemented as a web application software (TransReguloNet) with functions that enable pathway visualization and comparison of transcription factor activity between sample conditions defined in the experimental design. The pipeline merges differential expression, network construction, pathway-based abstraction, clustering and visualization. The framework was applied in analysis of actual expression datasets related to lung, breast and prostrate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Pathway analysis concepts for radiological impact assessment

    International Nuclear Information System (INIS)

    Moroney, J.R.

    1992-06-01

    The concepts underlying exposure pathways analysis are outlined with reference to the features of the two broad types of radionuclide transport models now in use - dynamic and steady-state - and the methods for constructing and developing them. By way of illustration, representative radiation doses are estimated for the four main exposure pathways likely to be involved in the land application of effluent water from Retention Pond 2 of Ranger Uranium Mines. These include: external irradiation by 226 Ra and natural uranium (Un at) in soil, ingestion of 226 Ra and Un at in food, inhalation of 222 Rn daughter products from 226 Rn in soil, and inhalation of 226 Ra and Un at in airborne dust resuspended from soil. Consideration has been given to local residents pursuing a traditional lifestyle on conclusion of the land application program. Because of the possible importance of the contribution from resuspended dust, currently available data are explored in refining the methodology for the pathway and developing a more appropriate model for it. 37 refs., 9 tabs., 6 figs

  20. Integrative cluster analysis in bioinformatics

    CERN Document Server

    Abu-Jamous, Basel; Nandi, Asoke K

    2015-01-01

    Clustering techniques are increasingly being put to use in the analysis of high-throughput biological datasets. Novel computational techniques to analyse high throughput data in the form of sequences, gene and protein expressions, pathways, and images are becoming vital for understanding diseases and future drug discovery. This book details the complete pathway of cluster analysis, from the basics of molecular biology to the generation of biological knowledge. The book also presents the latest clustering methods and clustering validation, thereby offering the reader a comprehensive review o

  1. A novel dysregulated pathway-identification analysis based on global influence of within-pathway effects and crosstalk between pathways

    Science.gov (United States)

    Han, Junwei; Li, Chunquan; Yang, Haixiu; Xu, Yanjun; Zhang, Chunlong; Ma, Jiquan; Shi, Xinrui; Liu, Wei; Shang, Desi; Yao, Qianlan; Zhang, Yunpeng; Su, Fei; Feng, Li; Li, Xia

    2015-01-01

    Identifying dysregulated pathways from high-throughput experimental data in order to infer underlying biological insights is an important task. Current pathway-identification methods focus on single pathways in isolation; however, consideration of crosstalk between pathways could improve our understanding of alterations in biological states. We propose a novel method of pathway analysis based on global influence (PAGI) to identify dysregulated pathways, by considering both within-pathway effects and crosstalk between pathways. We constructed a global gene–gene network based on the relationships among genes extracted from a pathway database. We then evaluated the extent of differential expression for each gene, and mapped them to the global network. The random walk with restart algorithm was used to calculate the extent of genes affected by global influence. Finally, we used cumulative distribution functions to determine the significance values of the dysregulated pathways. We applied the PAGI method to five cancer microarray datasets, and compared our results with gene set enrichment analysis and five other methods. Based on these analyses, we demonstrated that PAGI can effectively identify dysregulated pathways associated with cancer, with strong reproducibility and robustness. We implemented PAGI using the freely available R-based and Web-based tools (http://bioinfo.hrbmu.edu.cn/PAGI). PMID:25551156

  2. Floral pathway integrator gene expression mediates gradual transmission of environmental and endogenous cues to flowering time.

    Science.gov (United States)

    van Dijk, Aalt D J; Molenaar, Jaap

    2017-01-01

    The appropriate timing of flowering is crucial for the reproductive success of plants. Hence, intricate genetic networks integrate various environmental and endogenous cues such as temperature or hormonal statues. These signals integrate into a network of floral pathway integrator genes. At a quantitative level, it is currently unclear how the impact of genetic variation in signaling pathways on flowering time is mediated by floral pathway integrator genes. Here, using datasets available from literature, we connect Arabidopsis thaliana flowering time in genetic backgrounds varying in upstream signalling components with the expression levels of floral pathway integrator genes in these genetic backgrounds. Our modelling results indicate that flowering time depends in a quite linear way on expression levels of floral pathway integrator genes. This gradual, proportional response of flowering time to upstream changes enables a gradual adaptation to changing environmental factors such as temperature and light.

  3. Floral pathway integrator gene expression mediates gradual transmission of environmental and endogenous cues to flowering time

    Directory of Open Access Journals (Sweden)

    Aalt D.J. van Dijk

    2017-04-01

    Full Text Available The appropriate timing of flowering is crucial for the reproductive success of plants. Hence, intricate genetic networks integrate various environmental and endogenous cues such as temperature or hormonal statues. These signals integrate into a network of floral pathway integrator genes. At a quantitative level, it is currently unclear how the impact of genetic variation in signaling pathways on flowering time is mediated by floral pathway integrator genes. Here, using datasets available from literature, we connect Arabidopsis thaliana flowering time in genetic backgrounds varying in upstream signalling components with the expression levels of floral pathway integrator genes in these genetic backgrounds. Our modelling results indicate that flowering time depends in a quite linear way on expression levels of floral pathway integrator genes. This gradual, proportional response of flowering time to upstream changes enables a gradual adaptation to changing environmental factors such as temperature and light.

  4. Life cycle analysis of transportation fuel pathways

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-02-24

    The purpose of this work is to improve the understanding of the concept of life cycle analysis (LCA) of transportation fuels and some of its pertinent issues among non-technical people, senior managers, and policy makers. This work should provide some guidance to nations considering LCA-based policies and to people who are affected by existing policies or those being developed. While the concept of employing LCA to evaluate fuel options is simple and straightforward, the act of putting the concept into practice is complex and fraught with issues. Policy makers need to understand the limitations inherent in carrying out LCA work for transportation fuel systems. For many systems, even those that have been employed for a 100 years, there is a lack of sound data on the performance of those systems. Comparisons between systems should ideally be made using the same tool, so that differences caused by system boundaries, allocation processes, and temporal issues can be minimized (although probably not eliminated). Comparing the results for fuel pathway 1 from tool A to those of fuel system 2 from tool B introduces significant uncertainty into the results. There is also the question of the scale of system changes. LCA will give more reliable estimates when it is used to examine small changes in transportation fuel pathways than when used to estimate large scale changes that replace current pathways with completely new pathways. Some LCA tools have been developed recently primarily for regulatory purposes. These tools may deviate from ISO principles in order to facilitate simplicity and ease of use. In a regulatory environment, simplicity and ease of use are worthy objectives and in most cases there is nothing inherently wrong with this approach, particularly for assessing relative performance. However, the results of these tools should not be confused with, or compared to, the results that are obtained from a more complex and rigorous ISO compliant LCA. It should be

  5. Sensitivity and uncertainty analysis of the PATHWAY radionuclide transport model

    International Nuclear Information System (INIS)

    Otis, M.D.

    1983-01-01

    Procedures were developed for the uncertainty and sensitivity analysis of a dynamic model of radionuclide transport through human food chains. Uncertainty in model predictions was estimated by propagation of parameter uncertainties using a Monte Carlo simulation technique. Sensitivity of model predictions to individual parameters was investigated using the partial correlation coefficient of each parameter with model output. Random values produced for the uncertainty analysis were used in the correlation analysis for sensitivity. These procedures were applied to the PATHWAY model which predicts concentrations of radionuclides in foods grown in Nevada and Utah and exposed to fallout during the period of atmospheric nuclear weapons testing in Nevada. Concentrations and time-integrated concentrations of iodine-131, cesium-136, and cesium-137 in milk and other foods were investigated. 9 figs., 13 tabs

  6. User Interface Requirements for Web-Based Integrated Care Pathways: Evidence from the Evaluation of an Online Care Pathway Investigation Tool.

    Science.gov (United States)

    Balatsoukas, Panos; Williams, Richard; Davies, Colin; Ainsworth, John; Buchan, Iain

    2015-11-01

    Integrated care pathways (ICPs) define a chronological sequence of steps, most commonly diagnostic or treatment, to be followed in providing care for patients. Care pathways help to ensure quality standards are met and to reduce variation in practice. Although research on the computerisation of ICP progresses, there is still little knowledge on what are the requirements for designing user-friendly and usable electronic care pathways, or how users (normally health care professionals) interact with interfaces that support design, analysis and visualisation of ICPs. The purpose of the study reported in this paper was to address this gap by evaluating the usability of a novel web-based tool called COCPIT (Collaborative Online Care Pathway Investigation Tool). COCPIT supports the design, analysis and visualisation of ICPs at the population level. In order to address the aim of this study, an evaluation methodology was designed based on heuristic evaluations and a mixed method usability test. The results showed that modular visualisation and direct manipulation of information related to the design and analysis of ICPs is useful for engaging and stimulating users. However, designers should pay attention to issues related to the visibility of the system status and the match between the system and the real world, especially in relation to the display of statistical information about care pathways and the editing of clinical information within a care pathway. The paper concludes with recommendations for interface design.

  7. Computational Chemical Synthesis Analysis and Pathway Design

    Directory of Open Access Journals (Sweden)

    Fan Feng

    2018-06-01

    Full Text Available With the idea of retrosynthetic analysis, which was raised in the 1960s, chemical synthesis analysis and pathway design have been transformed from a complex problem to a regular process of structural simplification. This review aims to summarize the developments of computer-assisted synthetic analysis and design in recent years, and how machine-learning algorithms contributed to them. LHASA system started the pioneering work of designing semi-empirical reaction modes in computers, with its following rule-based and network-searching work not only expanding the databases, but also building new approaches to indicating reaction rules. Programs like ARChem Route Designer replaced hand-coded reaction modes with automatically-extracted rules, and programs like Chematica changed traditional designing into network searching. Afterward, with the help of machine learning, two-step models which combine reaction rules and statistical methods became the main stream. Recently, fully data-driven learning methods using deep neural networks which even do not require any prior knowledge, were applied into this field. Up to now, however, these methods still cannot replace experienced human organic chemists due to their relatively low accuracies. Future new algorithms with the aid of powerful computational hardware will make this topic promising and with good prospects.

  8. Mergeomics: a web server for identifying pathological pathways, networks, and key regulators via multidimensional data integration.

    Science.gov (United States)

    Arneson, Douglas; Bhattacharya, Anindya; Shu, Le; Mäkinen, Ville-Petteri; Yang, Xia

    2016-09-09

    Human diseases are commonly the result of multidimensional changes at molecular, cellular, and systemic levels. Recent advances in genomic technologies have enabled an outpour of omics datasets that capture these changes. However, separate analyses of these various data only provide fragmented understanding and do not capture the holistic view of disease mechanisms. To meet the urgent needs for tools that effectively integrate multiple types of omics data to derive biological insights, we have developed Mergeomics, a computational pipeline that integrates multidimensional disease association data with functional genomics and molecular networks to retrieve biological pathways, gene networks, and central regulators critical for disease development. To make the Mergeomics pipeline available to a wider research community, we have implemented an online, user-friendly web server ( http://mergeomics. idre.ucla.edu/ ). The web server features a modular implementation of the Mergeomics pipeline with detailed tutorials. Additionally, it provides curated genomic resources including tissue-specific expression quantitative trait loci, ENCODE functional annotations, biological pathways, and molecular networks, and offers interactive visualization of analytical results. Multiple computational tools including Marker Dependency Filtering (MDF), Marker Set Enrichment Analysis (MSEA), Meta-MSEA, and Weighted Key Driver Analysis (wKDA) can be used separately or in flexible combinations. User-defined summary-level genomic association datasets (e.g., genetic, transcriptomic, epigenomic) related to a particular disease or phenotype can be uploaded and computed real-time to yield biologically interpretable results, which can be viewed online and downloaded for later use. Our Mergeomics web server offers researchers flexible and user-friendly tools to facilitate integration of multidimensional data into holistic views of disease mechanisms in the form of tissue-specific key regulators

  9. Identifying novel glioma associated pathways based on systems biology level meta-analysis.

    Science.gov (United States)

    Hu, Yangfan; Li, Jinquan; Yan, Wenying; Chen, Jiajia; Li, Yin; Hu, Guang; Shen, Bairong

    2013-01-01

    With recent advances in microarray technology, including genomics, proteomics, and metabolomics, it brings a great challenge for integrating this "-omics" data to analysis complex disease. Glioma is an extremely aggressive and lethal form of brain tumor, and thus the study of the molecule mechanism underlying glioma remains very important. To date, most studies focus on detecting the differentially expressed genes in glioma. However, the meta-analysis for pathway analysis based on multiple microarray datasets has not been systematically pursued. In this study, we therefore developed a systems biology based approach by integrating three types of omics data to identify common pathways in glioma. Firstly, the meta-analysis has been performed to study the overlapping of signatures at different levels based on the microarray gene expression data of glioma. Among these gene expression datasets, 12 pathways were found in GeneGO database that shared by four stages. Then, microRNA expression profiles and ChIP-seq data were integrated for the further pathway enrichment analysis. As a result, we suggest 5 of these pathways could be served as putative pathways in glioma. Among them, the pathway of TGF-beta-dependent induction of EMT via SMAD is of particular importance. Our results demonstrate that the meta-analysis based on systems biology level provide a more useful approach to study the molecule mechanism of complex disease. The integration of different types of omics data, including gene expression microarrays, microRNA and ChIP-seq data, suggest some common pathways correlated with glioma. These findings will offer useful potential candidates for targeted therapeutic intervention of glioma.

  10. A systems biology approach for pathway level analysis

    OpenAIRE

    Draghici, Sorin; Khatri, Purvesh; Tarca, Adi Laurentiu; Amin, Kashyap; Done, Arina; Voichita, Calin; Georgescu, Constantin; Romero, Roberto

    2007-01-01

    A common challenge in the analysis of genomics data is trying to understand the underlying phenomenon in the context of all complex interactions taking place on various signaling pathways. A statistical approach using various models is universally used to identify the most relevant pathways in a given experiment. Here, we show that the existing pathway analysis methods fail to take into consideration important biological aspects and may provide incorrect results in certain situations. By usin...

  11. Separate enrichment analysis of pathways for up- and downregulated genes.

    Science.gov (United States)

    Hong, Guini; Zhang, Wenjing; Li, Hongdong; Shen, Xiaopei; Guo, Zheng

    2014-03-06

    Two strategies are often adopted for enrichment analysis of pathways: the analysis of all differentially expressed (DE) genes together or the analysis of up- and downregulated genes separately. However, few studies have examined the rationales of these enrichment analysis strategies. Using both microarray and RNA-seq data, we show that gene pairs with functional links in pathways tended to have positively correlated expression levels, which could result in an imbalance between the up- and downregulated genes in particular pathways. We then show that the imbalance could greatly reduce the statistical power for finding disease-associated pathways through the analysis of all-DE genes. Further, using gene expression profiles from five types of tumours, we illustrate that the separate analysis of up- and downregulated genes could identify more pathways that are really pertinent to phenotypic difference. In conclusion, analysing up- and downregulated genes separately is more powerful than analysing all of the DE genes together.

  12. Network Expansion and Pathway Enrichment Analysis towards Biologically Significant Findings from Microarrays

    Directory of Open Access Journals (Sweden)

    Wu Xiaogang

    2012-06-01

    Full Text Available In many cases, crucial genes show relatively slight changes between groups of samples (e.g. normal vs. disease, and many genes selected from microarray differential analysis by measuring the expression level statistically are also poorly annotated and lack of biological significance. In this paper, we present an innovative approach - network expansion and pathway enrichment analysis (NEPEA for integrative microarray analysis. We assume that organized knowledge will help microarray data analysis in significant ways, and the organized knowledge could be represented as molecular interaction networks or biological pathways. Based on this hypothesis, we develop the NEPEA framework based on network expansion from the human annotated and predicted protein interaction (HAPPI database, and pathway enrichment from the human pathway database (HPD. We use a recently-published microarray dataset (GSE24215 related to insulin resistance and type 2 diabetes (T2D as case study, since this study provided a thorough experimental validation for both genes and pathways identified computationally from classical microarray analysis and pathway analysis. We perform our NEPEA analysis for this dataset based on the results from the classical microarray analysis to identify biologically significant genes and pathways. Our findings are not only consistent with the original findings mostly, but also obtained more supports from other literatures.

  13. The future use of pathway analysis in IAEA safeguards

    International Nuclear Information System (INIS)

    Budlong Sylvester, Kory; Pilat, J.; Murphy, Chantell

    2013-01-01

    Pathway analysis has the potential to play an important role in the development of a safeguards system that is more information driven, leveraging all the information available to the International Atomic Energy Agency (IAEA). Pathway analysis should be seen as an extension of traditional hypothesis testing used by the Agency in the past. The most attractive pathways based on the assessed capabilities of a given state can be identified and used in the development of state-level safeguards approaches. This ranking of pathways can be revised based on evidence of pathway use, or preparations for use, allowing limited safeguards resources to flow to the areas of highest concern. The possible uses of pathway analysis in the implementation of the IAEA's state-level concept are described along with implementation issues that will likely arise. The paper is followed by the slides of the presentation. (authors)

  14. ComPath: comparative enzyme analysis and annotation in pathway/subsystem contexts

    Directory of Open Access Journals (Sweden)

    Kim Sun

    2008-03-01

    Full Text Available Abstract Background Once a new genome is sequenced, one of the important questions is to determine the presence and absence of biological pathways. Analysis of biological pathways in a genome is a complicated task since a number of biological entities are involved in pathways and biological pathways in different organisms are not identical. Computational pathway identification and analysis thus involves a number of computational tools and databases and typically done in comparison with pathways in other organisms. This computational requirement is much beyond the capability of biologists, so information systems for reconstructing, annotating, and analyzing biological pathways are much needed. We introduce a new comparative pathway analysis workbench, ComPath, which integrates various resources and computational tools using an interactive spreadsheet-style web interface for reliable pathway analyses. Results ComPath allows users to compare biological pathways in multiple genomes using a spreadsheet style web interface where various sequence-based analysis can be performed either to compare enzymes (e.g. sequence clustering and pathways (e.g. pathway hole identification, to search a genome for de novo prediction of enzymes, or to annotate a genome in comparison with reference genomes of choice. To fill in pathway holes or make de novo enzyme predictions, multiple computational methods such as FASTA, Whole-HMM, CSR-HMM (a method of our own introduced in this paper, and PDB-domain search are integrated in ComPath. Our experiments show that FASTA and CSR-HMM search methods generally outperform Whole-HMM and PDB-domain search methods in terms of sensitivity, but FASTA search performs poorly in terms of specificity, detecting more false positive as E-value cutoff increases. Overall, CSR-HMM search method performs best in terms of both sensitivity and specificity. Gene neighborhood and pathway neighborhood (global network visualization tools can be used

  15. Genetic variants in two pathways influence serum urate levels and gout risk: a systematic pathway analysis.

    Science.gov (United States)

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

    2018-03-01

    The aims of this study were to identify candidate pathways associated with serum urate and to explore the genetic effect of those pathways on the risk of gout. Pathway analysis of the loci identified in genome-wide association studies (GWASs) showed that the ion transmembrane transporter activity pathway (GO: 0015075) and the secondary active transmembrane transporter activity pathway (GO: 0015291) were both associated with serum urate concentrations, with P FDR values of 0.004 and 0.007, respectively. In a Chinese population of 4,332 individuals, the two pathways were also found to be associated with serum urate (P FDR  = 1.88E-05 and 3.44E-04, separately). In addition, these two pathways were further associated with the pathogenesis of gout (P FDR  = 1.08E-08 and 2.66E-03, respectively) in the Chinese population and a novel gout-associated gene, SLC17A2, was identified (OR = 0.83, P FDR  = 0.017). The mRNA expression of candidate genes also showed significant differences among different groups at pathway level. The present study identified two transmembrane transporter activity pathways (GO: 0015075 and GO: 0015291) were associations with serum urate concentrations and the risk of gout. SLC17A2 was identified as a novel gene that influenced the risk of gout.

  16. Bayesian network model for identification of pathways by integrating protein interaction with genetic interaction data.

    Science.gov (United States)

    Fu, Changhe; Deng, Su; Jin, Guangxu; Wang, Xinxin; Yu, Zu-Guo

    2017-09-21

    Molecular interaction data at proteomic and genetic levels provide physical and functional insights into a molecular biosystem and are helpful for the construction of pathway structures complementarily. Despite advances in inferring biological pathways using genetic interaction data, there still exists weakness in developed models, such as, activity pathway networks (APN), when integrating the data from proteomic and genetic levels. It is necessary to develop new methods to infer pathway structure by both of interaction data. We utilized probabilistic graphical model to develop a new method that integrates genetic interaction and protein interaction data and infers exquisitely detailed pathway structure. We modeled the pathway network as Bayesian network and applied this model to infer pathways for the coherent subsets of the global genetic interaction profiles, and the available data set of endoplasmic reticulum genes. The protein interaction data were derived from the BioGRID database. Our method can accurately reconstruct known cellular pathway structures, including SWR complex, ER-Associated Degradation (ERAD) pathway, N-Glycan biosynthesis pathway, Elongator complex, Retromer complex, and Urmylation pathway. By comparing N-Glycan biosynthesis pathway and Urmylation pathway identified from our approach with that from APN, we found that our method is able to overcome its weakness (certain edges are inexplicable). According to underlying protein interaction network, we defined a simple scoring function that only adopts genetic interaction information to avoid the balance difficulty in the APN. Using the effective stochastic simulation algorithm, the performance of our proposed method is significantly high. We developed a new method based on Bayesian network to infer detailed pathway structures from interaction data at proteomic and genetic levels. The results indicate that the developed method performs better in predicting signaling pathways than previously

  17. Integration of deep geothermal energy and woody biomass conversion pathways in urban systems

    International Nuclear Information System (INIS)

    Moret, Stefano; Peduzzi, Emanuela; Gerber, Léda; Maréchal, François

    2016-01-01

    Highlights: • Novel optimization-based methodology to integrate renewable energy systems in cities. • Multiperiod model including storage, heat integration and Life Cycle Assessment. • Case study: systematic assessment of deep geothermal and wood conversion pathways. • Identification of novel wood-geothermal hybrid systems leading to higher efficiencies. • Extensive Supplementary Material to ensure full reproducibility of the work. - Abstract: Urban systems account for about two-thirds of global primary energy consumption and energy-related greenhouse gas emissions, with a projected increasing trend. Deep geothermal energy and woody biomass can be used for the production of heat, electricity and biofuels, thus constituting a renewable alternative to fossil fuels for all end-uses in cities: heating, cooling, electricity and mobility. This paper presents a methodology to assess the potential for integrating deep geothermal energy and woody biomass in an urban energy system. The city is modeled in its entirety as a multiperiod optimization problem with the total annual cost as an objective, assessing as well the environmental impact with a Life Cycle Assessment approach. For geothermal energy, deep aquifers and Enhanced Geothermal Systems are considered for stand-alone production of heat and electricity, and for cogeneration. For biomass, besides direct combustion and cogeneration, conversion to biofuels by a set of alternative processes (pyrolysis, Fischer-Tropsch synthesis and synthetic natural gas production) is studied. With a scenario-based approach, all pathways are first individually evaluated. Secondly, all possible combinations between geothermal and biomass options are systematically compared, taking into account the possibility of hybrid systems. Results show that integrating these two resources generates configurations featuring both lower costs and environmental impacts. In particular, synergies are found in innovative hybrid systems using

  18. Safety assessment for deep underground disposal vault-pathways analysis

    International Nuclear Information System (INIS)

    Lyon, R.B.; Rosinger, E.L.J.

    1980-01-01

    The concept verification phase of the Canadian programme for the disposal of nuclear fuel waste encompasses a period of about three years before the start of site selection. During this time, the methodology for Environmental and Safety Assessment studies is being developed by focusing on a model site. Pathways analysis is an important component of these studies. It involves the prediction of the rate at which radionuclides might be released from a disposal vault and travel through the geosphere and biosphere to reach man. The pathways analysis studies cover three major topics: geosphere pathways analysis, biosphere pathways analysis and potentially-disruptive-phenomena analysis. Geosphere pathways analysis includes a total systems analysis, using the computer program GARD2, vault analysis, which considers container failure and waste leaching, hydrogeological modelling and geochemical modelling. Biosphere pathways analysis incorporates a compartmental modelling approach using the computer program RAMM, and a food chain analysis using the computer program FOOD II. Potentially-disruptive-phenomena analysis involves the estimation of the probability and consequences of events such as earthquakes which might reduce the effectiveness of the barriers preventing the release of radionuclides. The current stage of development of the required methodology and data is discussed in each of the three areas and preliminary results are presented. (author)

  19. A novel bi-level meta-analysis approach: applied to biological pathway analysis.

    Science.gov (United States)

    Nguyen, Tin; Tagett, Rebecca; Donato, Michele; Mitrea, Cristina; Draghici, Sorin

    2016-02-01

    The accumulation of high-throughput data in public repositories creates a pressing need for integrative analysis of multiple datasets from independent experiments. However, study heterogeneity, study bias, outliers and the lack of power of available methods present real challenge in integrating genomic data. One practical drawback of many P-value-based meta-analysis methods, including Fisher's, Stouffer's, minP and maxP, is that they are sensitive to outliers. Another drawback is that, because they perform just one statistical test for each individual experiment, they may not fully exploit the potentially large number of samples within each study. We propose a novel bi-level meta-analysis approach that employs the additive method and the Central Limit Theorem within each individual experiment and also across multiple experiments. We prove that the bi-level framework is robust against bias, less sensitive to outliers than other methods, and more sensitive to small changes in signal. For comparative analysis, we demonstrate that the intra-experiment analysis has more power than the equivalent statistical test performed on a single large experiment. For pathway analysis, we compare the proposed framework versus classical meta-analysis approaches (Fisher's, Stouffer's and the additive method) as well as against a dedicated pathway meta-analysis package (MetaPath), using 1252 samples from 21 datasets related to three human diseases, acute myeloid leukemia (9 datasets), type II diabetes (5 datasets) and Alzheimer's disease (7 datasets). Our framework outperforms its competitors to correctly identify pathways relevant to the phenotypes. The framework is sufficiently general to be applied to any type of statistical meta-analysis. The R scripts are available on demand from the authors. sorin@wayne.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e

  20. Integrated systems approach identifies risk regulatory pathways and key regulators in coronary artery disease.

    Science.gov (United States)

    Zhang, Yan; Liu, Dianming; Wang, Lihong; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Liu, Xinyi; Luo, Shanshun; Jiang, Wei

    2015-12-01

    Coronary artery disease (CAD) is the most common type of heart disease. However, the molecular mechanisms of CAD remain elusive. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, inferring risk regulatory pathways is an important step toward elucidating the mechanisms underlying CAD. With advances in high-throughput data, we developed an integrated systems approach to identify CAD risk regulatory pathways and key regulators. Firstly, a CAD-related core subnetwork was identified from a curated transcription factor (TF) and microRNA (miRNA) regulatory network based on a random walk algorithm. Secondly, candidate risk regulatory pathways were extracted from the subnetwork by applying a breadth-first search (BFS) algorithm. Then, risk regulatory pathways were prioritized based on multiple CAD-associated data sources. Finally, we also proposed a new measure to prioritize upstream regulators. We inferred that phosphatase and tensin homolog (PTEN) may be a key regulator in the dysregulation of risk regulatory pathways. This study takes a closer step than the identification of disease subnetworks or modules. From the risk regulatory pathways, we could understand the flow of regulatory information in the initiation and progression of the disease. Our approach helps to uncover its potential etiology. We developed an integrated systems approach to identify risk regulatory pathways. We proposed a new measure to prioritize the key regulators in CAD. PTEN may be a key regulator in dysregulation of the risk regulatory pathways.

  1. Pathway Analysis in Attention Deficit Hyperactivity Disorder: An Ensemble Approach

    Science.gov (United States)

    Mooney, Michael A.; McWeeney, Shannon K.; Faraone, Stephen V.; Hinney, Anke; Hebebrand, Johannes; Nigg, Joel T.; Wilmot, Beth

    2016-01-01

    Despite a wealth of evidence for the role of genetics in attention deficit hyperactivity disorder (ADHD), specific and definitive genetic mechanisms have not been identified. Pathway analyses, a subset of gene-set analyses, extend the knowledge gained from genome-wide association studies (GWAS) by providing functional context for genetic associations. However, there are numerous methods for association testing of gene sets and no real consensus regarding the best approach. The present study applied six pathway analysis methods to identify pathways associated with ADHD in two GWAS datasets from the Psychiatric Genomics Consortium. Methods that utilize genotypes to model pathway-level effects identified more replicable pathway associations than methods using summary statistics. In addition, pathways implicated by more than one method were significantly more likely to replicate. A number of brain-relevant pathways, such as RhoA signaling, glycosaminoglycan biosynthesis, fibroblast growth factor receptor activity, and pathways containing potassium channel genes, were nominally significant by multiple methods in both datasets. These results support previous hypotheses about the role of regulation of neurotransmitter release, neurite outgrowth and axon guidance in contributing to the ADHD phenotype and suggest the value of cross-method convergence in evaluating pathway analysis results. PMID:27004716

  2. Integrated piping structural analysis system

    International Nuclear Information System (INIS)

    Motoi, Toshio; Yamadera, Masao; Horino, Satoshi; Idehata, Takamasa

    1979-01-01

    Structural analysis of the piping system for nuclear power plants has become larger in scale and in quantity. In addition, higher quality analysis is regarded as of major importance nowadays from the point of view of nuclear plant safety. In order to fulfill to the above requirements, an integrated piping structural analysis system (ISAP-II) has been developed. Basic philosophy of this system is as follows: 1. To apply the date base system. All information is concentrated. 2. To minimize the manual process in analysis, evaluation and documentation. Especially to apply the graphic system as much as possible. On the basis of the above philosophy four subsystems were made. 1. Data control subsystem. 2. Analysis subsystem. 3. Plotting subsystem. 4. Report subsystem. Function of the data control subsystem is to control all information of the data base. Piping structural analysis can be performed by using the analysis subsystem. Isometric piping drawing and mode shape, etc. can be plotted by using the plotting subsystem. Total analysis report can be made without the manual process through the reporting subsystem. (author)

  3. Can Cultural Behavior Have a Negative Impact on the Development of Visual Integration Pathways?

    Science.gov (United States)

    Pretorius, E.; Naude, H.; van Vuuren, C. J.

    2002-01-01

    Contends that cultural practices such as carrying the baby on the mother's back for prolonged periods can impact negatively on development of visual integration during the sensorimotor stage pathways by preventing adequate or enough crawling. Maintains that crawling is essential for cross- modality integration and that higher mental functions may…

  4. Patients' experiences and care needs during the diagnostic phase of an Integrated Brain Cancer Pathway

    DEFF Research Database (Denmark)

    Vedelø, Tina Wang; Sørensen, Jens Christian Hedemann; Delmar, Charlotte

    2018-01-01

    of brain cancer, not knowing what to expect and participants' perceptions of the relationship with the health care providers. The analysis revealed that participants were in risk of having unmet information needs and that contextual factors seemed to cause fragmented care that led to feelings...... that the shock of the diagnosis, combined with the multiple symptoms, affect patients' ability to understand information and express needs of care and support. Unmet needs have been reported within this group of patients, however, the experiences and care needs of patients going through the diagnostic phase...... of a standardised Integrated Brain Cancer Pathway have not previously been explored. DESIGN: A Case Study design was used to provide detailed information of the complex needs of patients being diagnosed with a malignant brain tumour. METHODS: Research interviews and direct participant observation of four patients...

  5. GenMAPP 2: new features and resources for pathway analysis

    Directory of Open Access Journals (Sweden)

    Dahlquist Kam D

    2007-06-01

    Full Text Available Abstract Background Microarray technologies have evolved rapidly, enabling biologists to quantify genome-wide levels of gene expression, alternative splicing, and sequence variations for a variety of species. Analyzing and displaying these data present a significant challenge. Pathway-based approaches for analyzing microarray data have proven useful for presenting data and for generating testable hypotheses. Results To address the growing needs of the microarray community we have released version 2 of Gene Map Annotator and Pathway Profiler (GenMAPP, a new GenMAPP database schema, and integrated resources for pathway analysis. We have redesigned the GenMAPP database to support multiple gene annotations and species as well as custom species database creation for a potentially unlimited number of species. We have expanded our pathway resources by utilizing homology information to translate pathway content between species and extending existing pathways with data derived from conserved protein interactions and coexpression. We have implemented a new mode of data visualization to support analysis of complex data, including time-course, single nucleotide polymorphism (SNP, and splicing. GenMAPP version 2 also offers innovative ways to display and share data by incorporating HTML export of analyses for entire sets of pathways as organized web pages. Conclusion GenMAPP version 2 provides a means to rapidly interrogate complex experimental data for pathway-level changes in a diverse range of organisms.

  6. minepath.org: a free interactive pathway analysis web server.

    Science.gov (United States)

    Koumakis, Lefteris; Roussos, Panos; Potamias, George

    2017-07-03

    ( www.minepath.org ) is a web-based platform that elaborates on, and radically extends the identification of differentially expressed sub-paths in molecular pathways. Besides the network topology, the underlying MinePath algorithmic processes exploit exact gene-gene molecular relationships (e.g. activation, inhibition) and are able to identify differentially expressed pathway parts. Each pathway is decomposed into all its constituent sub-paths, which in turn are matched with corresponding gene expression profiles. The highly ranked, and phenotype inclined sub-paths are kept. Apart from the pathway analysis algorithm, the fundamental innovation of the MinePath web-server concerns its advanced visualization and interactive capabilities. To our knowledge, this is the first pathway analysis server that introduces and offers visualization of the underlying and active pathway regulatory mechanisms instead of genes. Other features include live interaction, immediate visualization of functional sub-paths per phenotype and dynamic linked annotations for the engaged genes and molecular relations. The user can download not only the results but also the corresponding web viewer framework of the performed analysis. This feature provides the flexibility to immediately publish results without publishing source/expression data, and get all the functionality of a web based pathway analysis viewer. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus aureus: Comparing Behavior of Pathogen Perturbed and Unperturbed Pathway

    Science.gov (United States)

    Tomar, Namrata; De, Rajat K.

    2013-01-01

    Response of an immune system to a pathogen attack depends on the balance between the host immune defense and the virulence of the pathogen. Investigation of molecular interactions between the proteins of a host and a pathogen helps in identifying the pathogenic proteins. It is necessary to understand the dynamics of a normally behaved host system to evaluate the capacity of its immune system upon pathogen attack. In this study, we have compared the behavior of an unperturbed and pathogen perturbed host system. Moreover, we have developed a formalism under Flux Balance Analysis (FBA) for the optimization of conflicting objective functions. We have constructed an integrated pathway system, which includes Staphylococcal Superantigen (SAg) expression regulatory pathway and TCR signaling pathway of Homo sapiens. We have implemented the method on this pathway system and observed the behavior of host signaling molecules upon pathogen attack. The entire study has been divided into six different cases, based on the perturbed/unperturbed conditions. In other words, we have investigated unperturbed and pathogen perturbed human TCR signaling pathway, with different combinations of optimization of concentrations of regulatory and signaling molecules. One of these cases has aimed at finding out whether minimization of the toxin production in a pathogen leads to the change in the concentration levels of the proteins coded by TCR signaling pathway genes in the infected host. Based on the computed results, we have hypothesized that the balance between TCR signaling inhibitory and stimulatory molecules can keep TCR signaling system into resting/stimulating state, depending upon the perturbation. The proposed integrated host-pathogen interaction pathway model has accurately reflected the experimental evidences, which we have used for validation purpose. The significance of this kind of investigation lies in revealing the susceptible interaction points that can take back the

  8. Integrated sequence analysis. Final report

    International Nuclear Information System (INIS)

    Andersson, K.; Pyy, P.

    1998-02-01

    The NKS/RAK subprojet 3 'integrated sequence analysis' (ISA) was formulated with the overall objective to develop and to test integrated methodologies in order to evaluate event sequences with significant human action contribution. The term 'methodology' denotes not only technical tools but also methods for integration of different scientific disciplines. In this report, we first discuss the background of ISA and the surveys made to map methods in different application fields, such as man machine system simulation software, human reliability analysis (HRA) and expert judgement. Specific event sequences were, after the surveys, selected for application and testing of a number of ISA methods. The event sequences discussed in the report were cold overpressure of BWR, shutdown LOCA of BWR, steam generator tube rupture of a PWR and BWR disturbed signal view in the control room after an external event. Different teams analysed these sequences by using different ISA and HRA methods. Two kinds of results were obtained from the ISA project: sequence specific and more general findings. The sequence specific results are discussed together with each sequence description. The general lessons are discussed under a separate chapter by using comparisons of different case studies. These lessons include areas ranging from plant safety management (design, procedures, instrumentation, operations, maintenance and safety practices) to methodological findings (ISA methodology, PSA,HRA, physical analyses, behavioural analyses and uncertainty assessment). Finally follows a discussion about the project and conclusions are presented. An interdisciplinary study of complex phenomena is a natural way to produce valuable and innovative results. This project came up with structured ways to perform ISA and managed to apply the in practice. The project also highlighted some areas where more work is needed. In the HRA work, development is required for the use of simulators and expert judgement as

  9. Integrated GWAS and Pathway profiling for feed efficiency traits in pigs leads to novel genes and their molecular pathways

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Ostersen, Tage; Strathe, Anders Bjerring

    2013-01-01

    Genome wide association studies (GWAS) are being extensively used in revealing genetic architecture of complex traits. However, GWAS offer limited understanding of the biological role of significant single nucleotide polymorphisms (SNPs) affecting complex traits. Pathway analysis using GWAS results...... is an important step where we firstly detect genes located near GWAS-detected SNPs and subsequently we detect enrichment of these genes in various biological processes and pathways. The objective of this study was to apply these steps to identify relevant pathways involved in residual feed intake (RFI) in pigs....... Residual feed intake is a feed efficiency measure and is highly economically important in animal production. In our study, a total of 596 Yorkshire boars had phenotypic and genotypic records. After quality control, 37,915 SNPs were available for GWAS which was implemented in the DMU software package...

  10. Integrated Network Analysis and Effective Tools in Plant Systems Biology

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2014-11-01

    Full Text Available One of the ultimate goals in plant systems biology is to elucidate the genotype-phenotype relationship in plant cellular systems. Integrated network analysis that combines omics data with mathematical models has received particular attention. Here we focus on the latest cutting-edge computational advances that facilitate their combination. We highlight (1 network visualization tools, (2 pathway analyses, (3 genome-scale metabolic reconstruction, and (4 the integration of high-throughput experimental data and mathematical models. Multi-omics data that contain the genome, transcriptome, proteome, and metabolome and mathematical models are expected to integrate and expand our knowledge of complex plant metabolisms.

  11. Sustainable BECCS pathways evaluated by an integrated assessment model

    Science.gov (United States)

    Kato, E.

    2017-12-01

    Negative emissions technologies, particularly Bioenergy with Carbon Capture and Storage (BECCS), are key components of mitigation strategies in ambitious future socioeconomic scenarios analysed by integrated assessment models. Generally, scenarios aiming to keep mean global temperature rise below 2°C above pre-industrial would require net negative carbon emissions in the end of the 21st century. Also, in the context of Paris agreement which acknowledges "a balance between anthropogenic emissions by sources and removals by sinks of greenhouse gases in the second half of this century", RD&D for the negative emissions technologies in this decade has a crucial role for the possibility of early deployment of the technology. Because of the requirement of potentially extensive use of land and water for producing the bioenergy feedstock to get the anticipated level of gross negative emissions, researches on how to develop sustainable scenarios of BECCS is needed. Here, we present BECCS deployment scenarios that consider economically viable flow of bioenergy system including power generation and conversion process to liquid and gaseous fuels for transportation and heat with consideration of sustainable global biomass use. In the modelling process, detailed bioenergy representations, i.e. various feedstock and conversion technologies with and without CCS, are implemented in an integrated assessment (IA) model GRAPE (Global Relationship Assessment to Protect the Environment). Also, to overcome a general discrepancy about assumed future agricultural yield between 'top-down' IA models and 'bottom-up' estimates, which would crucially affect the land-use pattern, we applied yields change of food and energy crops consistent with process-based biophysical crop models in consideration of changing climate conditions. Using the framework, economically viable strategy for implementing sustainable bioenergy and BECCS flow are evaluated in the scenarios targeting to keep global average

  12. Integrating nitric oxide into salicylic acid and jasmonic acid/ethylene plant defense pathways

    DEFF Research Database (Denmark)

    Mur, Luis A J; Prats, Elena; Pierre, Sandra

    2013-01-01

    to be tailored to particular biotic stresses. Nitric oxide (NO) has emerged as a major signal influencing resistance mediated by both signalling pathways but no attempt has been made to integrate NO into established SA/JA/ET interactions. NO has been shown to act as an inducer or suppressor of signalling along......Plant defence against pests and pathogens is known to be conferred by either salicylic acid (SA) or jasmonic acid (JA)/ethylene (ET) pathways, depending on infection or herbivore-grazing strategy. It is well attested that SA and JA/ET pathways are mutually antagonistic allowing defence responses...

  13. Critical assessment of human metabolic pathway databases: a stepping stone for future integration

    Directory of Open Access Journals (Sweden)

    Stobbe Miranda D

    2011-10-01

    Full Text Available Abstract Background Multiple pathway databases are available that describe the human metabolic network and have proven their usefulness in many applications, ranging from the analysis and interpretation of high-throughput data to their use as a reference repository. However, so far the various human metabolic networks described by these databases have not been systematically compared and contrasted, nor has the extent to which they differ been quantified. For a researcher using these databases for particular analyses of human metabolism, it is crucial to know the extent of the differences in content and their underlying causes. Moreover, the outcomes of such a comparison are important for ongoing integration efforts. Results We compared the genes, EC numbers and reactions of five frequently used human metabolic pathway databases. The overlap is surprisingly low, especially on reaction level, where the databases agree on 3% of the 6968 reactions they have combined. Even for the well-established tricarboxylic acid cycle the databases agree on only 5 out of the 30 reactions in total. We identified the main causes for the lack of overlap. Importantly, the databases are partly complementary. Other explanations include the number of steps a conversion is described in and the number of possible alternative substrates listed. Missing metabolite identifiers and ambiguous names for metabolites also affect the comparison. Conclusions Our results show that each of the five networks compared provides us with a valuable piece of the puzzle of the complete reconstruction of the human metabolic network. To enable integration of the networks, next to a need for standardizing the metabolite names and identifiers, the conceptual differences between the databases should be resolved. Considerable manual intervention is required to reach the ultimate goal of a unified and biologically accurate model for studying the systems biology of human metabolism. Our comparison

  14. Functional analysis of the MAPK pathways in fungi.

    Science.gov (United States)

    Martínez-Soto, Domingo; Ruiz-Herrera, José

    The Mitogen-Activated Protein Kinase (MAPK) signaling pathways constitute one of the most important and evolutionarily conserved mechanisms for the perception of extracellular information in all the eukaryotic organisms. The MAPK pathways are involved in the transfer to the cell of the information perceived from extracellular stimuli, with the final outcome of activation of different transcription factors that regulate gene expression in response to them. In all species of fungi, the MAPK pathways have important roles in their physiology and development; e.g. cell cycle control, mating, morphogenesis, response to different stresses, resistance to UV radiation and to temperature changes, cell wall assembly and integrity, degradation of cellular organelles, virulence, cell-cell signaling, fungus-plant interaction, and response to damage-associated molecular patterns (DAMPs). Considering the importance of the phylogenetically conserved MAPK pathways in fungi, an updated review of the knowledge on them is discussed in this article. This information reveals their importance, their distribution in fungal species evolutionarily distant and with different lifestyles, their organization and function, and the interactions occurring between different MAPK pathways, and with other signaling pathways, for the regulation of the most complex cellular processes. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Chapter 7. Cloning and analysis of natural product pathways.

    Science.gov (United States)

    Gust, Bertolt

    2009-01-01

    The identification of gene clusters of natural products has lead to an enormous wealth of information about their biosynthesis and its regulation, and about self-resistance mechanisms. Well-established routine techniques are now available for the cloning and sequencing of gene clusters. The subsequent functional analysis of the complex biosynthetic machinery requires efficient genetic tools for manipulation. Until recently, techniques for the introduction of defined changes into Streptomyces chromosomes were very time-consuming. In particular, manipulation of large DNA fragments has been challenging due to the absence of suitable restriction sites for restriction- and ligation-based techniques. The homologous recombination approach called recombineering (referred to as Red/ET-mediated recombination in this chapter) has greatly facilitated targeted genetic modifications of complex biosynthetic pathways from actinomycetes by eliminating many of the time-consuming and labor-intensive steps. This chapter describes techniques for the cloning and identification of biosynthetic gene clusters, for the generation of gene replacements within such clusters, for the construction of integrative library clones and their expression in heterologous hosts, and for the assembly of entire biosynthetic gene clusters from the inserts of individual library clones. A systematic approach toward insertional mutation of a complete Streptomyces genome is shown by the use of an in vitro transposon mutagenesis procedure.

  16. Integrated sequence analysis. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, K.; Pyy, P

    1998-02-01

    The NKS/RAK subprojet 3 `integrated sequence analysis` (ISA) was formulated with the overall objective to develop and to test integrated methodologies in order to evaluate event sequences with significant human action contribution. The term `methodology` denotes not only technical tools but also methods for integration of different scientific disciplines. In this report, we first discuss the background of ISA and the surveys made to map methods in different application fields, such as man machine system simulation software, human reliability analysis (HRA) and expert judgement. Specific event sequences were, after the surveys, selected for application and testing of a number of ISA methods. The event sequences discussed in the report were cold overpressure of BWR, shutdown LOCA of BWR, steam generator tube rupture of a PWR and BWR disturbed signal view in the control room after an external event. Different teams analysed these sequences by using different ISA and HRA methods. Two kinds of results were obtained from the ISA project: sequence specific and more general findings. The sequence specific results are discussed together with each sequence description. The general lessons are discussed under a separate chapter by using comparisons of different case studies. These lessons include areas ranging from plant safety management (design, procedures, instrumentation, operations, maintenance and safety practices) to methodological findings (ISA methodology, PSA,HRA, physical analyses, behavioural analyses and uncertainty assessment). Finally follows a discussion about the project and conclusions are presented. An interdisciplinary study of complex phenomena is a natural way to produce valuable and innovative results. This project came up with structured ways to perform ISA and managed to apply the in practice. The project also highlighted some areas where more work is needed. In the HRA work, development is required for the use of simulators and expert judgement as

  17. Assembly and Multiplex Genome Integration of Metabolic Pathways in Yeast Using CasEMBLR

    DEFF Research Database (Denmark)

    Jakočiūnas, Tadas; Jensen, Emil D.; Jensen, Michael Krogh

    2018-01-01

    and marker-free integration of the carotenoid pathway from 15 exogenously supplied DNA parts into three targeted genomic loci. As a second proof-of-principle, a total of ten DNA parts were assembled and integrated in two genomic loci to construct a tyrosine production strain, and at the same time knocking......Genome integration is a vital step for implementing large biochemical pathways to build a stable microbial cell factory. Although traditional strain construction strategies are well established for the model organism Saccharomyces cerevisiae, recent advances in CRISPR/Cas9-mediated genome...... engineering allow much higher throughput and robustness in terms of strain construction. In this chapter, we describe CasEMBLR, a highly efficient and marker-free genome engineering method for one-step integration of in vivo assembled expression cassettes in multiple genomic sites simultaneously. Cas...

  18. Modelling and Analysis of Biochemical Signalling Pathway Cross-talk

    Directory of Open Access Journals (Sweden)

    Robin Donaldson

    2010-02-01

    Full Text Available Signalling pathways are abstractions that help life scientists structure the coordination of cellular activity. Cross-talk between pathways accounts for many of the complex behaviours exhibited by signalling pathways and is often critical in producing the correct signal-response relationship. Formal models of signalling pathways and cross-talk in particular can aid understanding and drive experimentation. We define an approach to modelling based on the concept that a pathway is the (synchronising parallel composition of instances of generic modules (with internal and external labels. Pathways are then composed by (synchronising parallel composition and renaming; different types of cross-talk result from different combinations of synchronisation and renaming. We define a number of generic modules in PRISM and five types of cross-talk: signal flow, substrate availability, receptor function, gene expression and intracellular communication. We show that Continuous Stochastic Logic properties can both detect and distinguish the types of cross-talk. The approach is illustrated with small examples and an analysis of the cross-talk between the TGF-b/BMP, WNT and MAPK pathways.

  19. 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

  20. 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.

  1. Integrative Workflows for Metagenomic Analysis

    Directory of Open Access Journals (Sweden)

    Efthymios eLadoukakis

    2014-11-01

    Full Text Available The rapid evolution of all sequencing technologies, described by the term Next Generation Sequencing (NGS, have revolutionized metagenomic analysis. They constitute a combination of high-throughput analytical protocols, coupled to delicate measuring techniques, in order to potentially discover, properly assemble and map allelic sequences to the correct genomes, achieving particularly high yields for only a fraction of the cost of traditional processes (i.e. Sanger. From a bioinformatic perspective, this boils down to many gigabytes of data being generated from each single sequencing experiment, rendering the management or even the storage, critical bottlenecks with respect to the overall analytical endeavor. The enormous complexity is even more aggravated by the versatility of the processing steps available, represented by the numerous bioinformatic tools that are essential, for each analytical task, in order to fully unveil the genetic content of a metagenomic dataset. These disparate tasks range from simple, nonetheless non-trivial, quality control of raw data to exceptionally complex protein annotation procedures, requesting a high level of expertise for their proper application or the neat implementation of the whole workflow. Furthermore, a bioinformatic analysis of such scale, requires grand computational resources, imposing as the sole realistic solution, the utilization of cloud computing infrastructures. In this review article we discuss different, integrative, bioinformatic solutions available, which address the aforementioned issues, by performing a critical assessment of the available automated pipelines for data management, quality control and annotation of metagenomic data, embracing various, major sequencing technologies and applications.

  2. Pathway analysis for alternate low-level waste disposal methods

    International Nuclear Information System (INIS)

    Rao, R.R.; Kozak, M.W.; McCord, J.T.; Olague, N.E.

    1992-01-01

    The purpose of this paper is to evaluate a complete set of environmental pathways for disposal options and conditions that the Nuclear Regulatory Commission (NRC) may analyze for a low-level radioactive waste (LLW) license application. The regulations pertaining In the past, shallow-land burial has been used for the disposal of low-level radioactive waste. However, with the advent of the State Compact system of LLW disposal, many alternative technologies may be used. The alternative LLW disposal facilities include below- ground vault, tumulus, above-ground vault, shaft, and mine disposal This paper will form the foundation of an update of the previously developed Sandia National Laboratories (SNL)/NRC LLW performance assessment methodology. Based on the pathway assessment for alternative disposal methods, a determination will be made about whether the current methodology can satisfactorily analyze the pathways and phenomena likely to be important for the full range of potential disposal options. We have attempted to be conservative in keeping pathways in the lists that may usually be of marginal importance. In this way we can build confidence that we have spanned the range of cases likely to be encountered at a real site. Results of the pathway assessment indicate that disposal methods can be categorized in groupings based on their depth of disposal. For the deep disposal options of shaft and mine disposal, the key pathways are identical. The shallow disposal options, such as tumulus, shallow-land, and below-ground vault disposal also may be grouped together from a pathway analysis perspective. Above-ground vault disposal cannot be grouped with any of the other disposal options. The pathway analysis shows a definite trend concerning depth of disposal. The above-ground option has the largest number of significant pathways. As the waste becomes more isolated, the number of significant pathways is reduced. Similar to shallow-land burial, it was found that for all

  3. Integrated Radiation Analysis and Design Tools

    Data.gov (United States)

    National Aeronautics and Space Administration — The Integrated Radiation Analysis and Design Tools (IRADT) Project develops and maintains an integrated tool set that collects the current best practices, databases,...

  4. Re-Structuring Preservice Teacher Education: Introducing the School-Community Integrated Learning (SCIL) Pathway

    Science.gov (United States)

    Hudson, Sue; Hudson, Peter

    2013-01-01

    Reviews into teacher education call for new models that develop preservice teachers' practical knowledge and skills. The study involved 9 mentor teachers and 14 mentees (final-year preservice teachers) working in a new teacher education model, the School-Community Integrated Learning (SCIL) pathway, and analysed data from a Likert survey with…

  5. White matter integrity deficits in prefrontal-amygdala pathways in Williams syndrome.

    Science.gov (United States)

    Avery, Suzanne N; Thornton-Wells, Tricia A; Anderson, Adam W; Blackford, Jennifer Urbano

    2012-01-16

    Williams syndrome is a neurodevelopmental disorder associated with significant non-social fears. Consistent with this elevated non-social fear, individuals with Williams syndrome have an abnormally elevated amygdala response when viewing threatening non-social stimuli. In typically-developing individuals, amygdala activity is inhibited through dense, reciprocal white matter connections with the prefrontal cortex. Neuroimaging studies suggest a functional uncoupling of normal prefrontal-amygdala inhibition in individuals with Williams syndrome, which might underlie both the extreme amygdala activity and non-social fears. This functional uncoupling might be caused by structural deficits in underlying white matter pathways; however, prefrontal-amygdala white matter deficits have yet to be explored in Williams syndrome. We used diffusion tensor imaging to investigate prefrontal-amygdala white matter integrity differences in individuals with Williams syndrome and typically-developing controls with high levels of non-social fear. White matter pathways between the amygdala and several prefrontal regions were isolated using probabilistic tractography. Within each pathway, we tested for between-group differences in three measures of white matter integrity: fractional anisotropy (FA), radial diffusivity (RD), and parallel diffusivity (λ(1)). Individuals with Williams syndrome had lower FA, compared to controls, in several of the prefrontal-amygdala pathways investigated, indicating a reduction in white matter integrity. Lower FA in Williams syndrome was explained by significantly higher RD, with no differences in λ(1), suggestive of lower fiber density or axon myelination in prefrontal-amygdala pathways. These results suggest that deficits in the structural integrity of prefrontal-amygdala white matter pathways might underlie the increased amygdala activity and extreme non-social fears observed in Williams syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Sensitivity analysis of intracellular signaling pathway kinetics predicts targets for stem cell fate control.

    Directory of Open Access Journals (Sweden)

    Alborz Mahdavi

    2007-07-01

    Full Text Available Directing stem cell fate requires knowledge of how signaling networks integrate temporally and spatially segregated stimuli. We developed and validated a computational model of signal transducer and activator of transcription-3 (Stat3 pathway kinetics, a signaling network involved in embryonic stem cell (ESC self-renewal. Our analysis identified novel pathway responses; for example, overexpression of the receptor glycoprotein-130 results in reduced pathway activation and increased ESC differentiation. We used a systematic in silico screen to identify novel targets and protein interactions involved in Stat3 activation. Our analysis demonstrates that signaling activation and desensitization (the inability to respond to ligand restimulation is regulated by balancing the activation state of a distributed set of parameters including nuclear export of Stat3, nuclear phosphatase activity, inhibition by suppressor of cytokine signaling, and receptor trafficking. This knowledge was used to devise a temporally modulated ligand delivery strategy that maximizes signaling activation and leads to enhanced ESC self-renewal.

  7. Integrated minicomputer alpha analysis system

    International Nuclear Information System (INIS)

    Vasilik, D.G.; Coy, D.E.; Seamons, M.; Henderson, R.W.; Romero, L.L.; Thomson, D.A.

    1978-01-01

    Approximately 1,000 stack and occupation air samples from plutonium and uranium facilities at LASL are analyzed daily. The concentrations of radio-nuclides in air are determined by measuring absolute alpha activities of particulates collected on air sample filter media. The Integrated Minicomputer Pulse system (IMPULSE) is an interface between many detectors of extremely simple design and a Digital Equipment Corporation (DEC) PDP-11/04 minicomputer. The detectors are photomultiplier tubes faced with zinc sulfide (ZnS). The average detector background is approximately 0.07 cpm. The IMPULSE system includes two mainframes, each of which can hold up to 64 detectors. The current hardware configuration includes 64 detectors in one mainframe and 40 detectors in the other. Each mainframe contains a minicomputer with 28K words of Random Access Memory. One minicomputer controls the detectors in both mainframes. A second computer was added for fail-safe redundancy and to support other laboratory computer requirements. The main minicomputer includes a dual floppy disk system and a dual DEC 'RK05' disk system for mass storage. The RK05 facilitates report generation and trend analysis. The IMPULSE hardware provides for passage of data from the detectors to the computer, and for passage of status and control information from the computer to the detector stations

  8. Integrated omics analysis of specialized metabolism in medicinal plants.

    Science.gov (United States)

    Rai, Amit; Saito, Kazuki; Yamazaki, Mami

    2017-05-01

    Medicinal plants are a rich source of highly diverse specialized metabolites with important pharmacological properties. Until recently, plant biologists were limited in their ability to explore the biosynthetic pathways of these metabolites, mainly due to the scarcity of plant genomics resources. However, recent advances in high-throughput large-scale analytical methods have enabled plant biologists to discover biosynthetic pathways for important plant-based medicinal metabolites. The reduced cost of generating omics datasets and the development of computational tools for their analysis and integration have led to the elucidation of biosynthetic pathways of several bioactive metabolites of plant origin. These discoveries have inspired synthetic biology approaches to develop microbial systems to produce bioactive metabolites originating from plants, an alternative sustainable source of medicinally important chemicals. Since the demand for medicinal compounds are increasing with the world's population, understanding the complete biosynthesis of specialized metabolites becomes important to identify or develop reliable sources in the future. Here, we review the contributions of major omics approaches and their integration to our understanding of the biosynthetic pathways of bioactive metabolites. We briefly discuss different approaches for integrating omics datasets to extract biologically relevant knowledge and the application of omics datasets in the construction and reconstruction of metabolic models. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  9. PathText: a text mining integrator for biological pathway visualizations

    Science.gov (United States)

    Kemper, Brian; Matsuzaki, Takuya; Matsuoka, Yukiko; Tsuruoka, Yoshimasa; Kitano, Hiroaki; Ananiadou, Sophia; Tsujii, Jun'ichi

    2010-01-01

    Motivation: Metabolic and signaling pathways are an increasingly important part of organizing knowledge in systems biology. They serve to integrate collective interpretations of facts scattered throughout literature. Biologists construct a pathway by reading a large number of articles and interpreting them as a consistent network, but most of the models constructed currently lack direct links to those articles. Biologists who want to check the original articles have to spend substantial amounts of time to collect relevant articles and identify the sections relevant to the pathway. Furthermore, with the scientific literature expanding by several thousand papers per week, keeping a model relevant requires a continuous curation effort. In this article, we present a system designed to integrate a pathway visualizer, text mining systems and annotation tools into a seamless environment. This will enable biologists to freely move between parts of a pathway and relevant sections of articles, as well as identify relevant papers from large text bases. The system, PathText, is developed by Systems Biology Institute, Okinawa Institute of Science and Technology, National Centre for Text Mining (University of Manchester) and the University of Tokyo, and is being used by groups of biologists from these locations. Contact: brian@monrovian.com. PMID:20529930

  10. Regulation of Cell Wall Biogenesis in Saccharomyces cerevisiae: The Cell Wall Integrity Signaling Pathway

    Science.gov (United States)

    Levin, David E.

    2011-01-01

    The yeast cell wall is a strong, but elastic, structure that is essential not only for the maintenance of cell shape and integrity, but also for progression through the cell cycle. During growth and morphogenesis, and in response to environmental challenges, the cell wall is remodeled in a highly regulated and polarized manner, a process that is principally under the control of the cell wall integrity (CWI) signaling pathway. This pathway transmits wall stress signals from the cell surface to the Rho1 GTPase, which mobilizes a physiologic response through a variety of effectors. Activation of CWI signaling regulates the production of various carbohydrate polymers of the cell wall, as well as their polarized delivery to the site of cell wall remodeling. This review article centers on CWI signaling in Saccharomyces cerevisiae through the cell cycle and in response to cell wall stress. The interface of this signaling pathway with other pathways that contribute to the maintenance of cell wall integrity is also discussed. PMID:22174182

  11. Atmospheric Pathway Screening Analysis for Saltstone Disposal Facility Vault 4

    International Nuclear Information System (INIS)

    COOK, JAMES

    2004-01-01

    A sequential screening process using a methodology developed by the National Council on Radiation Protection and Measurements, professional judgment and process knowledge has been used to produce a list of radionuclides requiring detailed analysis to derive disposal limits for the Saltstone Disposal Facility based on the atmospheric pathway

  12. Comparative analysis of programmed cell death pathways in filamentous fungi

    Directory of Open Access Journals (Sweden)

    Wortman Jennifer R

    2005-12-01

    Full Text Available Abstract Background Fungi can undergo autophagic- or apoptotic-type programmed cell death (PCD on exposure to antifungal agents, developmental signals, and stress factors. Filamentous fungi can also exhibit a form of cell death called heterokaryon incompatibility (HI triggered by fusion between two genetically incompatible individuals. With the availability of recently sequenced genomes of Aspergillus fumigatus and several related species, we were able to define putative components of fungi-specific death pathways and the ancestral core apoptotic machinery shared by all fungi and metazoa. Results Phylogenetic profiling of HI-associated proteins from four Aspergilli and seven other fungal species revealed lineage-specific protein families, orphan genes, and core genes conserved across all fungi and metazoa. The Aspergilli-specific domain architectures include NACHT family NTPases, which may function as key integrators of stress and nutrient availability signals. They are often found fused to putative effector domains such as Pfs, SesB/LipA, and a newly identified domain, HET-s/LopB. Many putative HI inducers and mediators are specific to filamentous fungi and not found in unicellular yeasts. In addition to their role in HI, several of them appear to be involved in regulation of cell cycle, development and sexual differentiation. Finally, the Aspergilli possess many putative downstream components of the mammalian apoptotic machinery including several proteins not found in the model yeast, Saccharomyces cerevisiae. Conclusion Our analysis identified more than 100 putative PCD associated genes in the Aspergilli, which may help expand the range of currently available treatments for aspergillosis and other invasive fungal diseases. The list includes species-specific protein families as well as conserved core components of the ancestral PCD machinery shared by fungi and metazoa.

  13. Expression profiling on soybean leaves reveals integration of ER- and osmotic-stress pathways

    Directory of Open Access Journals (Sweden)

    Dewey Ralph E

    2007-11-01

    Full Text Available Abstract Background Despite the potential of the endoplasmic reticulum (ER stress response to accommodate adaptive pathways, its integration with other environmental-induced responses is poorly understood in plants. We have previously demonstrated that the ER-stress sensor binding protein (BiP from soybean exhibits an unusual response to drought. The members of the soybean BiP gene family are differentially regulated by osmotic stress and soybean BiP confers tolerance to drought. While these results may reflect crosstalk between the osmotic and ER-stress signaling pathways, the lack of mutants, transcriptional response profiles to stresses and genome sequence information of this relevant crop has limited our attempts to identify integrated networks between osmotic and ER stress-induced adaptive responses. As a fundamental step towards this goal, we performed global expression profiling on soybean leaves exposed to polyethylene glycol treatment (osmotic stress or to ER stress inducers. Results The up-regulated stress-specific changes unmasked the major branches of the ER-stress response, which include enhancing protein folding and degradation in the ER, as well as specific osmotically regulated changes linked to cellular responses induced by dehydration. However, a small proportion (5.5% of total up-regulated genes represented a shared response that seemed to integrate the two signaling pathways. These co-regulated genes were considered downstream targets based on similar induction kinetics and a synergistic response to the combination of osmotic- and ER-stress-inducing treatments. Genes in this integrated pathway with the strongest synergistic induction encoded proteins with diverse roles, such as plant-specific development and cell death (DCD domain-containing proteins, an ubiquitin-associated (UBA protein homolog and NAC domain-containing proteins. This integrated pathway diverged further from characterized specific branches of ER-stress as

  14. Analysis of Geothermal Pathway in the Metamorphic Area, Northeastern Taiwan

    Science.gov (United States)

    Wang, C.; Wu, M. Y.; Song, S. R.; Lo, W.

    2016-12-01

    A quantitative measure by play fairway analysis in geothermal energy development is an important tool that can present the probability map of potential resources through the uncertainty studies in geology for early phase decision making purpose in the related industries. While source, pathway, and fluid are the three main geologic factors in traditional geothermal systems, identifying the heat paths is critical to reduce drilling cost. Taiwan is in East Asia and the western edge of Pacific Ocean, locating on the convergent boundary of Eurasian Plate and Philippine Sea Plate with many earthquake activities. This study chooses a metamorphic area in the western corner of Yi-Lan plain in northeastern Taiwan with high geothermal potential and several existing exploration sites. Having high subsurface temperature gradient from the mountain belts, and plenty hydrologic systems through thousands of millimeters annual precipitation that would bring up heats closer to the surface, current geothermal conceptual model indicates the importance of pathway distribution which affects the possible concentration of extractable heat location. The study conducts surface lineation analysis using analytic hierarchy process to determine weights among various fracture types for their roles in geothermal pathways, based on the information of remote sensing data, published geologic maps and field work measurements, to produce regional fracture distribution probability map. The results display how the spatial distribution of pathways through various fractures could affect geothermal systems, identify the geothermal plays using statistical data analysis, and compare against the existing drilling data.

  15. Using the Semantic Web for Rapid Integration of WikiPathways with Other Biological Online Data Resources.

    Science.gov (United States)

    Waagmeester, Andra; Kutmon, Martina; Riutta, Anders; Miller, Ryan; Willighagen, Egon L; Evelo, Chris T; Pico, Alexander R

    2016-06-01

    The diversity of online resources storing biological data in different formats provides a challenge for bioinformaticians to integrate and analyse their biological data. The semantic web provides a standard to facilitate knowledge integration using statements built as triples describing a relation between two objects. WikiPathways, an online collaborative pathway resource, is now available in the semantic web through a SPARQL endpoint at http://sparql.wikipathways.org. Having biological pathways in the semantic web allows rapid integration with data from other resources that contain information about elements present in pathways using SPARQL queries. In order to convert WikiPathways content into meaningful triples we developed two new vocabularies that capture the graphical representation and the pathway logic, respectively. Each gene, protein, and metabolite in a given pathway is defined with a standard set of identifiers to support linking to several other biological resources in the semantic web. WikiPathways triples were loaded into the Open PHACTS discovery platform and are available through its Web API (https://dev.openphacts.org/docs) to be used in various tools for drug development. We combined various semantic web resources with the newly converted WikiPathways content using a variety of SPARQL query types and third-party resources, such as the Open PHACTS API. The ability to use pathway information to form new links across diverse biological data highlights the utility of integrating WikiPathways in the semantic web.

  16. Using the Semantic Web for Rapid Integration of WikiPathways with Other Biological Online Data Resources.

    Directory of Open Access Journals (Sweden)

    Andra Waagmeester

    2016-06-01

    Full Text Available The diversity of online resources storing biological data in different formats provides a challenge for bioinformaticians to integrate and analyse their biological data. The semantic web provides a standard to facilitate knowledge integration using statements built as triples describing a relation between two objects. WikiPathways, an online collaborative pathway resource, is now available in the semantic web through a SPARQL endpoint at http://sparql.wikipathways.org. Having biological pathways in the semantic web allows rapid integration with data from other resources that contain information about elements present in pathways using SPARQL queries. In order to convert WikiPathways content into meaningful triples we developed two new vocabularies that capture the graphical representation and the pathway logic, respectively. Each gene, protein, and metabolite in a given pathway is defined with a standard set of identifiers to support linking to several other biological resources in the semantic web. WikiPathways triples were loaded into the Open PHACTS discovery platform and are available through its Web API (https://dev.openphacts.org/docs to be used in various tools for drug development. We combined various semantic web resources with the newly converted WikiPathways content using a variety of SPARQL query types and third-party resources, such as the Open PHACTS API. The ability to use pathway information to form new links across diverse biological data highlights the utility of integrating WikiPathways in the semantic web.

  17. Using the Semantic Web for Rapid Integration of WikiPathways with Other Biological Online Data Resources

    Science.gov (United States)

    Waagmeester, Andra; Pico, Alexander R.

    2016-01-01

    The diversity of online resources storing biological data in different formats provides a challenge for bioinformaticians to integrate and analyse their biological data. The semantic web provides a standard to facilitate knowledge integration using statements built as triples describing a relation between two objects. WikiPathways, an online collaborative pathway resource, is now available in the semantic web through a SPARQL endpoint at http://sparql.wikipathways.org. Having biological pathways in the semantic web allows rapid integration with data from other resources that contain information about elements present in pathways using SPARQL queries. In order to convert WikiPathways content into meaningful triples we developed two new vocabularies that capture the graphical representation and the pathway logic, respectively. Each gene, protein, and metabolite in a given pathway is defined with a standard set of identifiers to support linking to several other biological resources in the semantic web. WikiPathways triples were loaded into the Open PHACTS discovery platform and are available through its Web API (https://dev.openphacts.org/docs) to be used in various tools for drug development. We combined various semantic web resources with the newly converted WikiPathways content using a variety of SPARQL query types and third-party resources, such as the Open PHACTS API. The ability to use pathway information to form new links across diverse biological data highlights the utility of integrating WikiPathways in the semantic web. PMID:27336457

  18. Effect of curcumin on aged Drosophila melanogaster: a pathway prediction analysis.

    Science.gov (United States)

    Zhang, Zhi-guo; Niu, Xu-yan; Lu, Ai-ping; Xiao, Gary Guishan

    2015-02-01

    To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpring GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection (MCODE) were used to establish the protein-protein interaction (PPI) network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for pathway analysis. A total of 87 genes expressed differentially in D. melanogaster melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. Genes and their associated pathways in D. melanogaster melanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curcumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

  19. Pathway analysis of kidney cancer using proteomics and metabolic profiling

    Directory of Open Access Journals (Sweden)

    Fiehn Oliver

    2006-11-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the sixth leading cause of cancer death and is responsible for 11,000 deaths per year in the US. Approximately one-third of patients present with disease which is already metastatic and for which there is currently no adequate treatment, and no biofluid screening tests exist for RCC. In this study, we have undertaken a comprehensive proteomic analysis and subsequently a pathway and network approach to identify biological processes involved in clear cell RCC (ccRCC. We have used these data to investigate urinary markers of RCC which could be applied to high-risk patients, or to those being followed for recurrence, for early diagnosis and treatment, thereby substantially reducing mortality of this disease. Results Using 2-dimensional electrophoresis and mass spectrometric analysis, we identified 31 proteins which were differentially expressed with a high degree of significance in ccRCC as compared to adjacent non-malignant tissue, and we confirmed some of these by immunoblotting, immunohistochemistry, and comparison to published transcriptomic data. When evaluated by several pathway and biological process analysis programs, these proteins are demonstrated to be involved with a high degree of confidence (p values Conclusion Extensive pathway and network analysis allowed for the discovery of highly significant pathways from a set of clear cell RCC samples. Knowledge of activation of these processes will lead to novel assays identifying their proteomic and/or metabolomic signatures in biofluids of patient at high risk for this disease; we provide pilot data for such a urinary bioassay. Furthermore, we demonstrate how the knowledge of networks, processes, and pathways altered in kidney cancer may be used to influence the choice of optimal therapy.

  20. Problems in mathematical analysis III integration

    CERN Document Server

    Kaczor, W J

    2003-01-01

    We learn by doing. We learn mathematics by doing problems. This is the third volume of Problems in Mathematical Analysis. The topic here is integration for real functions of one real variable. The first chapter is devoted to the Riemann and the Riemann-Stieltjes integrals. Chapter 2 deals with Lebesgue measure and integration. The authors include some famous, and some not so famous, integral inequalities related to Riemann integration. Many of the problems for Lebesgue integration concern convergence theorems and the interchange of limits and integrals. The book closes with a section on Fourier series, with a concentration on Fourier coefficients of functions from particular classes and on basic theorems for convergence of Fourier series. The book is primarily geared toward students in analysis, as a study aid, for problem-solving seminars, or for tutorials. It is also an excellent resource for instructors who wish to incorporate problems into their lectures. Solutions for the problems are provided in the boo...

  1. Chiropractic Integrated Care Pathway for Low Back Pain in Veterans: Results of a Delphi Consensus Process.

    Science.gov (United States)

    Lisi, Anthony J; Salsbury, Stacie A; Hawk, Cheryl; Vining, Robert D; Wallace, Robert B; Branson, Richard; Long, Cynthia R; Burgo-Black, A Lucille; Goertz, Christine M

    2018-02-01

    The purpose of this study was to develop an integrated care pathway for doctors of chiropractic, primary care providers, and mental health professionals who manage veterans with low back pain, with or without mental health comorbidity, within Department of Veterans Affairs health care facilities. The research method used was a consensus process. A multidisciplinary investigative team reviewed clinical guidelines and Veterans Affairs pain and mental health initiatives to develop seed statements and care algorithms to guide chiropractic management and collaborative care of veterans with low back pain. A 5-member advisory committee approved initial recommendations. Veterans Affairs-based panelists (n = 58) evaluated the pathway via e-mail using a modified RAND/UCLA methodology. Consensus was defined as agreement by 80% of panelists. The modified Delphi process was conducted in July to December 2016. Most (93%) seed statements achieved consensus during the first round, with all statements reaching consensus after 2 rounds. The final care pathway addressed the topics of informed consent, clinical evaluation including history and examination, screening for red flags, documentation, diagnostic imaging, patient-reported outcomes, adverse event reporting, chiropractic treatment frequency and duration standards, tailored approaches to chiropractic care in veteran populations, and clinical presentation of common mental health conditions. Care algorithms outlined chiropractic case management and interprofessional collaboration and referrals between doctors of chiropractic and primary care and mental health providers. This study offers an integrative care pathway that includes chiropractic care for veterans with low back pain. Copyright © 2018. Published by Elsevier Inc.

  2. Assembly and Multiplex Genome Integration of Metabolic Pathways in Yeast Using CasEMBLR.

    Science.gov (United States)

    Jakočiūnas, Tadas; Jensen, Emil D; Jensen, Michael K; Keasling, Jay D

    2018-01-01

    Genome integration is a vital step for implementing large biochemical pathways to build a stable microbial cell factory. Although traditional strain construction strategies are well established for the model organism Saccharomyces cerevisiae, recent advances in CRISPR/Cas9-mediated genome engineering allow much higher throughput and robustness in terms of strain construction. In this chapter, we describe CasEMBLR, a highly efficient and marker-free genome engineering method for one-step integration of in vivo assembled expression cassettes in multiple genomic sites simultaneously. CasEMBLR capitalizes on the CRISPR/Cas9 technology to generate double-strand breaks in genomic loci, thus prompting native homologous recombination (HR) machinery to integrate exogenously derived homology templates. As proof-of-principle for microbial cell factory development, CasEMBLR was used for one-step assembly and marker-free integration of the carotenoid pathway from 15 exogenously supplied DNA parts into three targeted genomic loci. As a second proof-of-principle, a total of ten DNA parts were assembled and integrated in two genomic loci to construct a tyrosine production strain, and at the same time knocking out two genes. This new method complements and improves the field of genome engineering in S. cerevisiae by providing a more flexible platform for rapid and precise strain building.

  3. The base excision repair pathway is required for efficient lentivirus integration.

    Directory of Open Access Journals (Sweden)

    Kristine E Yoder

    Full Text Available An siRNA screen has identified several proteins throughout the base excision repair (BER pathway of oxidative DNA damage as important for efficient HIV infection. The proteins identified included early repair factors such as the base damage recognition glycosylases OGG1 and MYH and the late repair factor POLß, implicating the entire BER pathway. Murine cells with deletions of the genes Ogg1, Myh, Neil1 and Polß recapitulate the defect of HIV infection in the absence of BER. Defective infection in the absence of BER proteins was also seen with the lentivirus FIV, but not the gammaretrovirus MMLV. BER proteins do not affect HIV infection through its accessory genes nor the central polypurine tract. HIV reverse transcription and nuclear entry appear unaffected by the absence of BER proteins. However, HIV integration to the host chromosome is reduced in the absence of BER proteins. Pre-integration complexes from BER deficient cell lines show reduced integration activity in vitro. Integration activity is restored by addition of recombinant BER protein POLß. Lentiviral infection and integration efficiency appears to depend on the presence of BER proteins.

  4. The Vehicle Integrated Performance Analysis Experience: Reconnecting With Technical Integration

    Science.gov (United States)

    McGhee, D. S.

    2006-01-01

    Very early in the Space Launch Initiative program, a small team of engineers at MSFC proposed a process for performing system-level assessments of a launch vehicle. Aimed primarily at providing insight and making NASA a smart buyer, the Vehicle Integrated Performance Analysis (VIPA) team was created. The difference between the VIPA effort and previous integration attempts is that VIPA a process using experienced people from various disciplines, which focuses them on a technically integrated assessment. The foundations of VIPA s process are described. The VIPA team also recognized the need to target early detailed analysis toward identifying significant systems issues. This process is driven by the T-model for technical integration. VIPA s approach to performing system-level technical integration is discussed in detail. The VIPA process significantly enhances the development and monitoring of realizable project requirements. VIPA s assessment validates the concept s stated performance, identifies significant issues either with the concept or the requirements, and then reintegrates these issues to determine impacts. This process is discussed along with a description of how it may be integrated into a program s insight and review process. The VIPA process has gained favor with both engineering and project organizations for being responsive and insightful

  5. CRITICAL RADIONUCLIDE AND PATHWAY ANALYSIS FOR THE SAVANNAH RIVER SITE

    Energy Technology Data Exchange (ETDEWEB)

    Jannik, T.

    2011-08-30

    This report is an update to the analysis, Assessment of SRS Radiological Liquid and Airborne Contaminants and Pathways, that was performed in 1997. An electronic version of this large original report is included in the attached CD to this report. During the operational history (1954 to the present) of the Savannah River Site (SRS), many different radionuclides have been released to the environment from the various production facilities. However, as will be shown by this updated radiological critical contaminant/critical pathway analysis, only a small number of the released radionuclides have been significant contributors to potential doses and risks to offsite people. The analysis covers radiological releases to the atmosphere and to surface waters, the principal media that carry contaminants offsite. These releases potentially result in exposure to offsite people. The groundwater monitoring performed at the site shows that an estimated 5 to 10% of SRS has been contaminated by radionuclides, no evidence exists from the extensive monitoring performed that groundwater contaminated with these constituents has migrated off the site (SRS 2011). Therefore, with the notable exception of radiological source terms originating from shallow surface water migration into site streams, onsite groundwater was not considered as a potential exposure pathway to offsite people. In addition, in response to the Department of Energy's (DOE) Order 435.1, several Performance Assessments (WSRC 2008; LWO 2009; SRR 2010; SRR 2011) and a Comprehensive SRS Composite Analysis (SRNO 2010) have recently been completed at SRS. The critical radionuclides and pathways identified in these extensive reports are discussed and, where applicable, included in this analysis.

  6. Pathway Processor 2.0: a web resource for pathway-based analysis of high-throughput data.

    Science.gov (United States)

    Beltrame, Luca; Bianco, Luca; Fontana, Paolo; Cavalieri, Duccio

    2013-07-15

    Pathway Processor 2.0 is a web application designed to analyze high-throughput datasets, including but not limited to microarray and next-generation sequencing, using a pathway centric logic. In addition to well-established methods such as the Fisher's test and impact analysis, Pathway Processor 2.0 offers innovative methods that convert gene expression into pathway expression, leading to the identification of differentially regulated pathways in a dataset of choice. Pathway Processor 2.0 is available as a web service at http://compbiotoolbox.fmach.it/pathwayProcessor/. Sample datasets to test the functionality can be used directly from the application. duccio.cavalieri@fmach.it Supplementary data are available at Bioinformatics online.

  7. Integrated logistic support analysis system

    International Nuclear Information System (INIS)

    Carnicero Iniguez, E.J.; Garcia de la Sen, R.

    1993-01-01

    Integrating logic support into a system results in a large volume of information having to be managed which can only be achieved with the help of computer applications. Both past experience and growing needs in such tasks have led Emperesarios Agrupados to undertake an ambitious development project which is described in this paper. (author)

  8. Analysis of integrated energy systems

    International Nuclear Information System (INIS)

    Matsuhashi, Takaharu; Kaya, Yoichi; Komiyama, Hiroshi; Hayashi, Taketo; Yasukawa, Shigeru.

    1988-01-01

    World attention is now attracted to the concept of Novel Horizontally Integrated Energy System (NHIES). In NHIES, all fossil fuels are fist converted into CO and H 2 . Potential environmental contaminants such as sulfur are removed during this process. CO turbines are mainly used to generate electric power. Combustion is performed in pure oxygen produced through air separation, making it possible to completely prevent the formation of thermal NOx. Thus, NHIES would release very little amount of such substances that would contribute to acid rain. In this system, the intermediate energy sources of CO, H 2 and O 2 are integrated horizontally. They are combined appropriately to produce a specific form of final energy source. The integration of intermediate energy sources can provide a wide variety of final energy sources, allowing any type of fossil fuel to serve as an alternative to other types of fossil fuel. Another feature of NHIES is the positive use of nuclear fuel to reduce the formation of CO 2 . Studies are under way in Japan to develop a new concept of integrated energy system. These studies are especially aimed at decreased overall efficiency and introduction of new liquid fuels that are high in conversion efficiency. Considerations are made on the final form of energy source, robust control, acid fallout, and CO 2 reduction. (Nogami, K.)

  9. Building integrated pathways to independence for diverse biomedical researchers: Project Pathways, the BUILD program at Xavier University of Louisiana.

    Science.gov (United States)

    Foroozesh, Maryam; Giguette, Marguerite; Morgan, Kathleen; Johanson, Kelly; D'Amour, Gene; Coston, Tiera; Wilkins-Green, Clair

    2017-01-01

    Xavier University of Louisiana is a historically Black and Catholic university that is nationally recognized for its science, technology, engineering and mathematics (STEM) curricula. Approximately 73% of Xavier's students are African American, and about 77% major in the biomedical sciences. Xavier is a national leader in the number of STEM majors who go on to receive M.D. degrees and Ph.D. degrees in science and engineering. Despite Xavier's advances in this area, African Americans still earn about 7.5% of the Bachelor's degrees, less than 8% of the Master's degrees, and less than 5% of the doctoral degrees conferred in STEM disciplines in the United States. Additionally, although many well-prepared, highly-motivated students are attracted by Xavier's reputation in the sciences, many of these students, though bright and capable, come from underperforming public school systems and receive substandard preparation in STEM disciplines. The purpose of this article is to describe how Xavier works to overcome unequal education backgrounds and socioeconomic challenges to develop student talent through expanding biomedical training opportunities and build on an established reputation in science education. The National Institutes of Health (NIH)/National Institute of General Medical Sciences (NIGMS)-funded BUILD (Building Infrastructure Leading to Diversity) Program at Xavier University of Louisiana, Project Pathways , is a highly-innovative program designed to broaden the career interests of students early on, and to engage them in activities that entice them to continue their education towards biomedical research careers. Project strategies involve a transformation of Xavier's academic and non-academic programs through the redesign, supplementation and integration of academic advising, tutoring, career services, personal counseling, undergraduate research training, faculty research mentoring, and development of new biomedical and research skills courses. The Program also

  10. Mining pathway associations for disease-related pathway activity analysis based on gene expression and methylation data.

    Science.gov (United States)

    Lee, Hyeonjeong; Shin, Miyoung

    2017-01-01

    The problem of discovering genetic markers as disease signatures is of great significance for the successful diagnosis, treatment, and prognosis of complex diseases. Even if many earlier studies worked on identifying disease markers from a variety of biological resources, they mostly focused on the markers of genes or gene-sets (i.e., pathways). However, these markers may not be enough to explain biological interactions between genetic variables that are related to diseases. Thus, in this study, our aim is to investigate distinctive associations among active pathways (i.e., pathway-sets) shown each in case and control samples which can be observed from gene expression and/or methylation data. The pathway-sets are obtained by identifying a set of associated pathways that are often active together over a significant number of class samples. For this purpose, gene expression or methylation profiles are first analyzed to identify significant (active) pathways via gene-set enrichment analysis. Then, regarding these active pathways, an association rule mining approach is applied to examine interesting pathway-sets in each class of samples (case or control). By doing so, the sets of associated pathways often working together in activity profiles are finally chosen as our distinctive signature of each class. The identified pathway-sets are aggregated into a pathway activity network (PAN), which facilitates the visualization of differential pathway associations between case and control samples. From our experiments with two publicly available datasets, we could find interesting PAN structures as the distinctive signatures of breast cancer and uterine leiomyoma cancer, respectively. Our pathway-set markers were shown to be superior or very comparable to other genetic markers (such as genes or gene-sets) in disease classification. Furthermore, the PAN structure, which can be constructed from the identified markers of pathway-sets, could provide deeper insights into

  11. Integrative Analysis of Omics Big Data.

    Science.gov (United States)

    Yu, Xiang-Tian; Zeng, Tao

    2018-01-01

    The diversity and huge omics data take biology and biomedicine research and application into a big data era, just like that popular in human society a decade ago. They are opening a new challenge from horizontal data ensemble (e.g., the similar types of data collected from different labs or companies) to vertical data ensemble (e.g., the different types of data collected for a group of person with match information), which requires the integrative analysis in biology and biomedicine and also asks for emergent development of data integration to address the great changes from previous population-guided to newly individual-guided investigations.Data integration is an effective concept to solve the complex problem or understand the complicate system. Several benchmark studies have revealed the heterogeneity and trade-off that existed in the analysis of omics data. Integrative analysis can combine and investigate many datasets in a cost-effective reproducible way. Current integration approaches on biological data have two modes: one is "bottom-up integration" mode with follow-up manual integration, and the other one is "top-down integration" mode with follow-up in silico integration.This paper will firstly summarize the combinatory analysis approaches to give candidate protocol on biological experiment design for effectively integrative study on genomics and then survey the data fusion approaches to give helpful instruction on computational model development for biological significance detection, which have also provided newly data resources and analysis tools to support the precision medicine dependent on the big biomedical data. Finally, the problems and future directions are highlighted for integrative analysis of omics big data.

  12. Containment integrity analysis under accidents

    International Nuclear Information System (INIS)

    Lin Chengge; Zhao Ruichang; Liu Zhitao

    2010-01-01

    Containment integrity analyses for current nuclear power plants (NPPs) mainly focus on the internal pressure caused by design basis accidents (DBAs). In addition to the analyses of containment pressure response caused by DBAs, the behavior of containment during severe accidents (SAs) are also evaluated for AP1000 NPP. Since the conservatism remains in the assumptions,boundary conditions and codes, margin of the results of containment integrity analyses may be overestimated. Along with the improvements of the knowledge to the phenomena and process of relevant accidents, the margin overrated can be appropriately reduced by using the best estimate codes combined with the uncertainty methods, which could be beneficial to the containment design and construction of large passive plants (LPP) in China. (authors)

  13. Integrative biological analysis for neuropsychopharmacology.

    Science.gov (United States)

    Emmett, Mark R; Kroes, Roger A; Moskal, Joseph R; Conrad, Charles A; Priebe, Waldemar; Laezza, Fernanda; Meyer-Baese, Anke; Nilsson, Carol L

    2014-01-01

    Although advances in psychotherapy have been made in recent years, drug discovery for brain diseases such as schizophrenia and mood disorders has stagnated. The need for new biomarkers and validated therapeutic targets in the field of neuropsychopharmacology is widely unmet. The brain is the most complex part of human anatomy from the standpoint of number and types of cells, their interconnections, and circuitry. To better meet patient needs, improved methods to approach brain studies by understanding functional networks that interact with the genome are being developed. The integrated biological approaches--proteomics, transcriptomics, metabolomics, and glycomics--have a strong record in several areas of biomedicine, including neurochemistry and neuro-oncology. Published applications of an integrated approach to projects of neurological, psychiatric, and pharmacological natures are still few but show promise to provide deep biological knowledge derived from cells, animal models, and clinical materials. Future studies that yield insights based on integrated analyses promise to deliver new therapeutic targets and biomarkers for personalized medicine.

  14. Analysis of Stomatal Patterning in Selected Mutants of MAPK Pathways

    KAUST Repository

    Felemban, Abrar

    2016-05-01

    Stomata are cellular valves in plants that play an essential role in the regulation of gas exchange and are distributed in the epidermis of aerial organs. In Arabidopsis thaliana, stomatal production and development are coordinated by the mitogen-activated protein kinase (MAPK) signalling pathway, which modulates a variety of other processes, including cell proliferation, regulation of cytokinesis, programed cell death, and response to abiotic and biotic stress. The environment also plays a role in stomatal development, by influencing the frequency at which stomata develop in leaves. This thesis presents an analysis of stomatal development in Arabidopsis mutants in two MAPK pathways: MEKK1-MKK1/MKK2-MPK4, and MAP3K17/18-MKK3. Obtained results demonstrate the effect of stress conditions on stomatal development and specify the involvement of analysed MAPK in stomatal patterning. First, both analysed pathways modulate stomatal patterning in Arabidopsis cotyledons. Second, plant growth-promoting bacteria tested enhance stomatal density and affect guard cell morphology. Third, the sucrose or mannitol treatment increases defects in stomatal patterning. Finally, salt stress or high temperature can suppress stomatal defects in mutants of the MEKK1-MKK1/MKK2-MPK4 pathway.

  15. Evolution of the New Pathway curriculum at Harvard Medical School: the new integrated curriculum.

    Science.gov (United States)

    Dienstag, Jules L

    2011-01-01

    In 1985, Harvard Medical School adopted a "New Pathway" curriculum, based on active, adult learning through problem-based, faculty-facilitated small-group tutorials designed to promote lifelong skills of self-directed learning. Despite the successful integration of clinically relevant material in basic science courses, the New Pathway goals were confined primarily to the preclinical years. In addition, the shifting balance in the delivery of health care from inpatient to ambulatory settings limited the richness of clinical education in clinical clerkships, creating obstacles for faculty in their traditional roles as teachers. In 2006, Harvard Medical School adopted a more integrated curriculum based on four principles that emerged after half a decade of self-reflection and planning: (1) integrate the teaching of basic/population science and clinical medicine throughout the entire student experience; (2) reestablish meaningful and intensive faculty-student interactions and reengage the faculty; (3) develop a new model of clinical education that offers longitudinal continuity of patient experience, cross-disciplinary curriculum, faculty mentoring, and student evaluation; and (4) provide opportunities for all students to pursue an in-depth, faculty-mentored scholarly project. These principles of our New Integrated Curriculum reflect our vision for a curriculum that fosters a partnership between students and faculty in the pursuit of scholarship and leadership.

  16. Integrating reliability analysis and design

    International Nuclear Information System (INIS)

    Rasmuson, D.M.

    1980-10-01

    This report describes the Interactive Reliability Analysis Project and demonstrates the advantages of using computer-aided design systems (CADS) in reliability analysis. Common cause failure problems require presentations of systems, analysis of fault trees, and evaluation of solutions to these. Results have to be communicated between the reliability analyst and the system designer. Using a computer-aided design system saves time and money in the analysis of design. Computer-aided design systems lend themselves to cable routing, valve and switch lists, pipe routing, and other component studies. At EG and G Idaho, Inc., the Applicon CADS is being applied to the study of water reactor safety systems

  17. Integration of Pathway Knowledge and Dynamic Bayesian Networks for the Prediction of Oral Cancer Recurrence.

    Science.gov (United States)

    Kourou, Konstantina; Papaloukas, Costas; Fotiadis, Dimitrios I

    2017-03-01

    Oral squamous cell carcinoma has been characterized as a complex disease which involves dynamic genomic changes at the molecular level. These changes indicate the worth to explore the interactions of the molecules and especially of differentially expressed genes that contribute to cancer progression. Moreover, based on this knowledge the identification of differentially expressed genes and related molecular pathways is of great importance. In the present study, we exploit differentially expressed genes in order to further perform pathway enrichment analysis. According to our results we found significant pathways in which the disease associated genes have been identified as strongly enriched. Furthermore, based on the results of the pathway enrichment analysis we propose a methodology for predicting oral cancer recurrence using dynamic Bayesian networks. The methodology takes into consideration time series gene expression data in order to predict a disease recurrence. Subsequently, we are able to conjecture about the causal interactions between genes in consecutive time intervals. Concerning the performance of the predictive models, the overall accuracy of the algorithm is 81.8% and the area under the ROC curve 89.2% regarding the knowledge from the overrepresented pre-NOTCH Expression and processing pathway.

  18. Using Formal Concept Analysis to Create Pathways through Museum Collections

    DEFF Research Database (Denmark)

    Wray, Tim; Eklund, Peter

    2014-01-01

    This paper presents A Place for Art - an iPad app that allows users to explore an art collection via semantically linked pathways that are generated using Formal Concept Analysis. The app embraces the information seeking approach of exploration and is based on the idea that showing context...... and relationships among objects in a museum collection augments an interpretive experience. The fundamental interaction metaphor inherent in A Place for Art relies on Formal Concept Analysis so the interface has embedded within it the semantic clustering features of machine learning in artificial intelligence....

  19. Integrating nitric oxide into salicylic acid and jasmonic acid/ ethylene plant defense pathways.

    Science.gov (United States)

    Mur, Luis A J; Prats, Elena; Pierre, Sandra; Hall, Michael A; Hebelstrup, Kim H

    2013-01-01

    Plant defense against pests and pathogens is known to be conferred by either salicylic acid (SA) or jasmonic acid (JA)/ethylene (ET) pathways, depending on infection or herbivore-grazing strategy. It is well attested that SA and JA/ET pathways are mutually antagonistic allowing defense responses to be tailored to particular biotic stresses. Nitric oxide (NO) has emerged as a major signal influencing resistance mediated by both signaling pathways but no attempt has been made to integrate NO into established SA/JA/ET interactions. NO has been shown to act as an inducer or suppressor of signaling along each pathway. NO will initiate SA biosynthesis and nitrosylate key cysteines on TGA-class transcription factors to aid in the initiation of SA-dependent gene expression. Against this, S-nitrosylation of NONEXPRESSOR OF PATHOGENESIS-RELATED PROTEINS1 (NPR1) will promote the NPR1 oligomerization within the cytoplasm to reduce TGA activation. In JA biosynthesis, NO will initiate the expression of JA biosynthetic enzymes, presumably to over-come any antagonistic effects of SA on JA-mediated transcription. NO will also initiate the expression of ET biosynthetic genes but a suppressive role is also observed in the S-nitrosylation and inhibition of S-adenosylmethionine transferases which provides methyl groups for ET production. Based on these data a model for NO action is proposed but we have also highlighted the need to understand when and how inductive and suppressive steps are used.

  20. Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia

    NARCIS (Netherlands)

    Juraeva, Dilafruz; Haenisch, Britta; Zapatka, Marc; Frank, Josef; Witt, Stephanie H.; Mühleisen, Thomas W.; Treutlein, Jens; Strohmaier, Jana; Meier, Sandra; Degenhardt, Franziska; Giegling, Ina; Ripke, Stephan; Leber, Markus; Lange, Christoph; Schulze, Thomas G.; Mössner, Rainald; Nenadic, Igor; Sauer, Heinrich; Rujescu, Dan; Maier, Wolfgang; Børglum, Anders; Ophoff, Roel; Cichon, Sven; Nöthen, Markus M.; Rietschel, Marcella; Mattheisen, Manuel; Brors, Benedikt; Kahn, René S.; Cahn, Wiepke; Linszen, Don H.; de Haan, Lieuwe; van Os, Jim; Krabbendam, Lydia; Myin-Germeys, Inez; Wiersma, Durk; Bruggeman, Richard; Mors, O.; Børglum, A. D.; Mortensen, P. B.; Pedersen, C. B.; Demontis, D.; Grove, J.; Mattheisen, M.; Hougaard, D. M.

    2014-01-01

    In the present study, an integrated hierarchical approach was applied to: (1) identify pathways associated with susceptibility to schizophrenia; (2) detect genes that may be potentially affected in these pathways since they contain an associated polymorphism; and (3) annotate the functional

  1. Integral data analysis for resonance parameters determination

    International Nuclear Information System (INIS)

    Larson, N.M.; Leal, L.C.; Derrien, H.

    1997-09-01

    Neutron time-of-flight experiments have long been used to determine resonance parameters. Those resonance parameters have then been used in calculations of integral quantities such as Maxwellian averages or resonance integrals, and results of those calculations in turn have been used as a criterion for acceptability of the resonance analysis. However, the calculations were inadequate because covariances on the parameter values were not included in the calculations. In this report an effort to correct for that deficiency is documented: (1) the R-matrix analysis code SAMMY has been modified to include integral quantities of importance, (2) directly within the resonance parameter analysis, and (3) to determine the best fit to both differential (microscopic) and integral (macroscopic) data simultaneously. This modification was implemented because it is expected to have an impact on the intermediate-energy range that is important for criticality safety applications

  2. A knowledge-based T2-statistic to perform pathway analysis for quantitative proteomic data.

    Science.gov (United States)

    Lai, En-Yu; Chen, Yi-Hau; Wu, Kun-Pin

    2017-06-01

    Approaches to identify significant pathways from high-throughput quantitative data have been developed in recent years. Still, the analysis of proteomic data stays difficult because of limited sample size. This limitation also leads to the practice of using a competitive null as common approach; which fundamentally implies genes or proteins as independent units. The independent assumption ignores the associations among biomolecules with similar functions or cellular localization, as well as the interactions among them manifested as changes in expression ratios. Consequently, these methods often underestimate the associations among biomolecules and cause false positives in practice. Some studies incorporate the sample covariance matrix into the calculation to address this issue. However, sample covariance may not be a precise estimation if the sample size is very limited, which is usually the case for the data produced by mass spectrometry. In this study, we introduce a multivariate test under a self-contained null to perform pathway analysis for quantitative proteomic data. The covariance matrix used in the test statistic is constructed by the confidence scores retrieved from the STRING database or the HitPredict database. We also design an integrating procedure to retain pathways of sufficient evidence as a pathway group. The performance of the proposed T2-statistic is demonstrated using five published experimental datasets: the T-cell activation, the cAMP/PKA signaling, the myoblast differentiation, and the effect of dasatinib on the BCR-ABL pathway are proteomic datasets produced by mass spectrometry; and the protective effect of myocilin via the MAPK signaling pathway is a gene expression dataset of limited sample size. Compared with other popular statistics, the proposed T2-statistic yields more accurate descriptions in agreement with the discussion of the original publication. We implemented the T2-statistic into an R package T2GA, which is available at https

  3. An efficient tool for metabolic pathway construction and gene integration for Aspergillus niger.

    Science.gov (United States)

    Sarkari, Parveen; Marx, Hans; Blumhoff, Marzena L; Mattanovich, Diethard; Sauer, Michael; Steiger, Matthias G

    2017-12-01

    Metabolic engineering requires functional genetic tools for easy and quick generation of multiple pathway variants. A genetic engineering toolbox for A. niger is presented, which facilitates the generation of strains carrying heterologous expression cassettes at a defined genetic locus. The system is compatible with Golden Gate cloning, which facilitates the DNA construction process and provides high design flexibility. The integration process is mediated by a CRISPR/Cas9 strategy involving the cutting of both the genetic integration locus (pyrG) as well as the integrating plasmid. Only a transient expression of Cas9 is necessary and the carrying plasmid is readily lost using a size-reduced AMA1 variant. A high integration efficiency into the fungal genome of up to 100% can be achieved, thus reducing the screening process significantly. The feasibility of the approach was demonstrated by the integration of an expression cassette enabling the production of aconitic acid in A. niger. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Interleukin-2 signaling pathway analysis by quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Osinalde, Nerea; Moss, Helle; Arrizabalaga, Onetsine

    2011-01-01

    among which 79 were found with increased abundance in the tyrosine-phosphorylated complexes, including several previously not reported IL-2 downstream effectors. Combinatorial site-specific phosphoproteomic analysis resulted in identification of 99 phosphorylated sites mapping to the identified proteins...... with increased abundance in the tyrosine-phosphorylated complexes, of which 34 were not previously described. In addition, chemical inhibition of the identified IL-2-mediated JAK, PI3K and MAPK signaling pathways, resulted in distinct alteration on the IL-2 dependent proliferation....

  5. Preliminary Integrated Safety Analysis Status Report

    International Nuclear Information System (INIS)

    Gwyn, D.

    2001-01-01

    This report provides the status of the potential Monitored Geologic Repository (MGR) Integrated Safety Analysis (EA) by identifying the initial work scope scheduled for completion during the ISA development period, the schedules associated with the tasks identified, safety analysis issues encountered, and a summary of accomplishments during the reporting period. This status covers the period from October 1, 2000 through March 30, 2001

  6. International Space Station Configuration Analysis and Integration

    Science.gov (United States)

    Anchondo, Rebekah

    2016-01-01

    Ambitious engineering projects, such as NASA's International Space Station (ISS), require dependable modeling, analysis, visualization, and robotics to ensure that complex mission strategies are carried out cost effectively, sustainably, and safely. Learn how Booz Allen Hamilton's Modeling, Analysis, Visualization, and Robotics Integration Center (MAVRIC) team performs engineering analysis of the ISS Configuration based primarily on the use of 3D CAD models. To support mission planning and execution, the team tracks the configuration of ISS and maintains configuration requirements to ensure operational goals are met. The MAVRIC team performs multi-disciplinary integration and trade studies to ensure future configurations meet stakeholder needs.

  7. A case study to illustrate the utility of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks for integrating human health and ecological data into cumulative risk assessment

    Science.gov (United States)

    Cumulative risk assessment (CRA) methods, which evaluate the risk of multiple adverse outcomes (AOs) from multiple chemicals, promote the use of a conceptual site model (CSM) to integrate risk from relevant stressors. The Adverse Outcome Pathway (AOP) framework can inform these r...

  8. Integrability of dynamical systems algebra and analysis

    CERN Document Server

    Zhang, Xiang

    2017-01-01

    This is the first book to systematically state the fundamental theory of integrability and its development of ordinary differential equations with emphasis on the Darboux theory of integrability and local integrability together with their applications. It summarizes the classical results of Darboux integrability and its modern development together with their related Darboux polynomials and their applications in the reduction of Liouville and elementary integrabilty and in the center—focus problem, the weakened Hilbert 16th problem on algebraic limit cycles and the global dynamical analysis of some realistic models in fields such as physics, mechanics and biology. Although it can be used as a textbook for graduate students in dynamical systems, it is intended as supplementary reading for graduate students from mathematics, physics, mechanics and engineering in courses related to the qualitative theory, bifurcation theory and the theory of integrability of dynamical systems.

  9. Nonassociative learning as gated neural integrator and differentiator in stimulus-response pathways

    Directory of Open Access Journals (Sweden)

    Young Daniel L

    2006-08-01

    Full Text Available Abstract Nonassociative learning is a basic neuroadaptive behavior exhibited across animal phyla and sensory modalities but its role in brain intelligence is unclear. Current literature on habituation and sensitization, the classic "dual process" of nonassociative learning, gives highly incongruous accounts between varying experimental paradigms. Here we propose a general theory of nonassociative learning featuring four base modes: habituation/primary sensitization in primary stimulus-response pathways, and desensitization/secondary sensitization in secondary stimulus-response pathways. Primary and secondary modes of nonassociative learning are distinguished by corresponding activity-dependent recall, or nonassociative gating, of neurotransmission memory. From the perspective of brain computation, nonassociative learning is a form of integral-differential calculus whereas nonassociative gating is a form of Boolean logic operator – both dynamically transforming the stimulus-response relationship. From the perspective of sensory integration, nonassociative gating provides temporal filtering whereas nonassociative learning affords low-pass, high-pass or band-pass/band-stop frequency filtering – effectively creating an intelligent sensory firewall that screens all stimuli for attention and resultant internal model adaptation and reaction. This unified framework ties together many salient characteristics of nonassociative learning and nonassociative gating and suggests a common kernel that correlates with a wide variety of sensorimotor integration behaviors such as central resetting and self-organization of sensory inputs, fail-safe sensorimotor compensation, integral-differential and gated modulation of sensorimotor feedbacks, alarm reaction, novelty detection and selective attention, as well as a variety of mental and neurological disorders such as sensorimotor instability, attention deficit hyperactivity, sensory defensiveness, autism

  10. Importance of Mediator complex in the regulation and integration of diverse signaling pathways in plants

    Directory of Open Access Journals (Sweden)

    Subhasis eSamanta

    2015-09-01

    Full Text Available Basic transcriptional machinery in eukaryotes is assisted by a number of cofactors, which either increase or decrease the rate of transcription. Mediator complex is one such cofactor, and recently has drawn a lot of interest because of its integrative power to converge different signaling pathways before channelling the transcription instructions to the RNA polymerase II machinery. Like yeast and metazoans, plants do possess the Mediator complex across the kingdom, and its isolation and subunit analyses have been reported from the model plant, Arabidopsis. Genetic and molecular analyses have unravelled important regulatory roles of Mediator subunits at every stage of plant life cycle starting from flowering to embryo and organ development, to even size determination. It also contributes immensely to the survival of plants against different environmental vagaries by the timely activation of its resistance mechanisms. Here, we have provided an overview of plant Mediator complex starting from its discovery to regulation of stoichiometry of its subunits. We have also reviewed involvement of different Mediator subunits in different processes and pathways including defense response pathways evoked by diverse biotic cues. Wherever possible, attempts have been made to provide mechanistic insight of Mediator’s involvement in these processes.

  11. Importance of Mediator complex in the regulation and integration of diverse signaling pathways in plants.

    Science.gov (United States)

    Samanta, Subhasis; Thakur, Jitendra K

    2015-01-01

    Basic transcriptional machinery in eukaryotes is assisted by a number of cofactors, which either increase or decrease the rate of transcription. Mediator complex is one such cofactor, and recently has drawn a lot of interest because of its integrative power to converge different signaling pathways before channeling the transcription instructions to the RNA polymerase II machinery. Like yeast and metazoans, plants do possess the Mediator complex across the kingdom, and its isolation and subunit analyses have been reported from the model plant, Arabidopsis. Genetic, and molecular analyses have unraveled important regulatory roles of Mediator subunits at every stage of plant life cycle starting from flowering to embryo and organ development, to even size determination. It also contributes immensely to the survival of plants against different environmental vagaries by the timely activation of its resistance mechanisms. Here, we have provided an overview of plant Mediator complex starting from its discovery to regulation of stoichiometry of its subunits. We have also reviewed involvement of different Mediator subunits in different processes and pathways including defense response pathways evoked by diverse biotic cues. Wherever possible, attempts have been made to provide mechanistic insight of Mediator's involvement in these processes.

  12. Comparative expression pathway analysis of human and canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Marconato Laura

    2009-03-01

    Full Text Available Abstract Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

  13. Strategic Analysis of Technology Integration at Allstream

    OpenAIRE

    Brown, Jeff

    2011-01-01

    Innovation has been defined as the combination of invention and commercialization. Invention without commercialization is rarely, if ever, profitable. For the purposes of this paper the definition of innovation will be further expanded into the concept of technology integration. Successful technology integration not only includes new technology introduction, but also the operationalization of the new technology within each business unit of the enterprise. This paper conducts an analysis of Al...

  14. Evaluation of additional biogeochemical impacts on mitigation pathways in an energy sytem integrated assessment model.

    Science.gov (United States)

    Dessens, O.

    2017-12-01

    Within the last IPCC AR5 a large and systematic sensitivity study around available technologies and timing of policies applied in IAMs to achieve the 2°C target has been conducted. However the simple climate representations included in IAMs are generally tuned to the results of ensemble means. This may result in hiding within the ensemble mean results possible challenging mitigation pathways for the economy or the technology future scenarios. This work provides new insights on the sensitivity of the socio-economic response to different climate factors under a 2°C climate change target in order to help guide future efforts to reduce uncertainty in the climate mitigation decisions. The main objective is to understand and bring new insights on how future global warming will affect the natural biochemical feedbacks on the climate system and what could be the consequences of these feedbacks on the anthropogenic emission pathways with a specific focus on the energy-economy system. It specifically focuses on three issues of the climate representation affecting the energy system transformation and GHG emissions pathways: 1- Impacts of the climate sensitivity (or TCR); 2- Impacts of warming on the radiative forcing (cloudiness,...); 3- Impacts of warming on the carbon cycle (carbon cycle feedback). We use the integrated assessment model TIAM-UCL to examine the mitigation pathways compatible with the 2C target depending on assumptions regarding the 3 issues of the climate representation introduced above. The following key conclusions drawn from this study are that mitigation to 2°C is still possible under strong climate sensitivity (TCR), strong carbon cycle amplification or positive radiative forcing feedback. However, this level of climate mitigation will require a significant transformation in the way we produce and consume energy. Carbon capture and sequestration on electricity generation, industry and biomass is part of the technology pool needed to achieve this

  15. RAMM: a system of computer programs for radionuclide pathway analysis calculations

    International Nuclear Information System (INIS)

    Lyon, R.B.

    1976-09-01

    A generalized system of computer programs, designated RAMM (Radioactive Materials Management) system, has been developed to assist in the analysis of the movement of radionuclides through the environment to man. RAMM incorporates the GASP IV continuous/discrete simulation system. A nodal approach is used whereby the system to be analyzed is split up into parts small enough that the distribution of nuclides within the node may be taken to be homogeneous. Pathways are defined between nodes, and appropriate transfer coefficients are input or generated. Output includes the time dependent contents of the nodes and dose rates, integrated doses and dose commitments of selected nodes. (author)

  16. Bioinformatic Integration of Molecular Networks and Major Pathways Involved in Mice Cochlear and Vestibular Supporting Cells.

    Science.gov (United States)

    Requena, Teresa; Gallego-Martinez, Alvaro; Lopez-Escamez, Jose A

    2018-01-01

    Background : Cochlear and vestibular epithelial non-hair cells (ENHCs) are the supporting elements of the cellular architecture in the organ of Corti and the vestibular neuroepithelium in the inner ear. Intercellular and cell-extracellular matrix interactions are essential to prevent an abnormal ion redistribution leading to hearing and vestibular loss. The aim of this study is to define the main pathways and molecular networks in the mouse ENHCs. Methods : We retrieved microarray and RNA-seq datasets from mouse epithelial sensory and non-sensory cells from gEAR portal (http://umgear.org/index.html) and obtained gene expression fold-change between ENHCs and non-epithelial cells (NECs) against HCs for each gene. Differentially expressed genes (DEG) with a log2 fold change between 1 and -1 were discarded. The remaining genes were selected to search for interactions using Ingenuity Pathway Analysis and STRING platform. Specific molecular networks for ENHCs in the cochlea and the vestibular organs were generated and significant pathways were identified. Results : Between 1723 and 1559 DEG were found in the mouse cochlear and vestibular tissues, respectively. Six main pathways showed enrichment in the supporting cells in both tissues: (1) "Inhibition of Matrix Metalloproteases"; (2) "Calcium Transport I"; (3) "Calcium Signaling"; (4) "Leukocyte Extravasation Signaling"; (5) "Signaling by Rho Family GTPases"; and (6) "Axonal Guidance Si". In the mouse cochlea, ENHCs showed a significant enrichment in 18 pathways highlighting "axonal guidance signaling (AGS)" ( p = 4.37 × 10 -8 ) and "RhoGDI Signaling" ( p = 3.31 × 10 -8 ). In the vestibular dataset, there were 20 enriched pathways in ENHCs, the most significant being "Leukocyte Extravasation Signaling" ( p = 8.71 × 10 -6 ), "Signaling by Rho Family GTPases" ( p = 1.20 × 10 -5 ) and "Calcium Signaling" ( p = 1.20 × 10 -5 ). Among the top ranked networks, the most biologically significant network contained the

  17. IT-supported integrated care pathways for diabetes: A compilation and review of good practices.

    Science.gov (United States)

    Vrijhoef, Hubertus Jm; de Belvis, Antonio Giulio; de la Calle, Matias; de Sabata, Maria Stella; Hauck, Bastian; Montante, Sabrina; Moritz, Annette; Pelizzola, Dario; Saraheimo, Markku; Guldemond, Nick A

    2017-06-01

    Integrated Care Pathways (ICPs) are a method for the mutual decision-making and organization of care for a well-defined group of patients during a well-defined period. The aim of a care pathway is to enhance the quality of care by improving patient outcomes, promoting patient safety, increasing patient satisfaction, and optimizing the use of resources. To describe this concept, different names are used, e.g. care pathways and integrated care pathways. Modern information technologies (IT) can support ICPs by enabling patient empowerment, better management, and the monitoring of care provided by multidisciplinary teams. This study analyses ICPs across Europe, identifying commonalities and success factors to establish good practices for IT-supported ICPs in diabetes care. A mixed-method approach was applied, combining desk research on 24 projects from the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) with follow-up interviews of project participants, and a non-systematic literature review. We applied a Delphi technique to select process and outcome indicators, derived from different literature sources which were compiled and applied for the identification of successful good practices. Desk research identified sixteen projects featuring IT-supported ICPs, mostly derived from the EIP on AHA, as good practices based on our criteria. Follow-up interviews were then conducted with representatives from 9 of the 16 projects to gather information not publicly available and understand how these projects were meeting the identified criteria. In parallel, the non-systematic literature review of 434 PubMed search results revealed a total of eight relevant projects. On the basis of the selected EIP on AHA project data and non-systematic literature review, no commonalities with regard to defined process or outcome indicators could be identified through our approach. Conversely, the research produced a heterogeneous picture in all aspects of the projects

  18. Evidence-based educational pathway for the integration of first aid training in school curricula.

    Science.gov (United States)

    De Buck, Emmy; Van Remoortel, Hans; Dieltjens, Tessa; Verstraeten, Hans; Clarysse, Matthieu; Moens, Olaf; Vandekerckhove, Philippe

    2015-09-01

    "Calling for help, performing first aid and providing Cardiopulmonary Resuscitation (CPR)" is part of the educational goals in secondary schools in Belgium (Flanders). However, for teachers it is not always clear at what age children can be taught which aspects of first aid. In addition, it is not clear what constitutes "performing first aid" and we strongly advocate that the first aid curriculum is broader than CPR training alone. To develop an evidence-based educational pathway to enable the integration of first aid into the school curriculum by defining the goals to be achieved for knowledge, skills and attitudes, for different age groups. Studies were identified through electronic databases research (The Cochrane Library, MEDLINE, Embase). We included studies on first aid education for children and adolescents up to 18 years old. A multidisciplinary expert panel formulated their practice experience and expert opinion and discussed the available evidence. We identified 5822 references and finally retained 30 studies (13 experimental and 17 observational studies), including studies concerning emergency call (7 studies), cardiopulmonary resuscitation (18 studies), AED (Automated External Defibrillator) use (6 studies), recovery position (5 studies), choking (2 studies), injuries (5 studies), and poisoning (2 studies). Recommendations (educational goals) were derived after carefully discussing the currently available evidence in the literature and balancing the skills and attitudes of children of different ages. An evidence-based educational pathway with educational goals concerning learning first aid for each age group was developed. This educational pathway can be used for the integration of first aid training in school curricula. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  19. 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.

  20. 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.

  1. Pathways of topological rank analysis (PoTRA): a novel method to detect pathways involved in hepatocellular carcinoma.

    Science.gov (United States)

    Li, Chaoxing; Liu, Li; Dinu, Valentin

    2018-01-01

    Complex diseases such as cancer are usually the result of a combination of environmental factors and one or several biological pathways consisting of sets of genes. Each biological pathway exerts its function by delivering signaling through the gene network. Theoretically, a pathway is supposed to have a robust topological structure under normal physiological conditions. However, the pathway's topological structure could be altered under some pathological condition. It is well known that a normal biological network includes a small number of well-connected hub nodes and a large number of nodes that are non-hubs. In addition, it is reported that the loss of connectivity is a common topological trait of cancer networks, which is an assumption of our method. Hence, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal or the distribution of topological ranks of genes might be altered. Based on this, we propose a new PageRank-based method called Pathways of Topological Rank Analysis (PoTRA) to detect pathways involved in cancer. We use PageRank to measure the relative topological ranks of genes in each biological pathway, then select hub genes for each pathway, and use Fisher's exact test to test if the number of hub genes in each pathway is altered from normal to cancer. Alternatively, if the distribution of topological ranks of gene in a pathway is altered between normal and cancer, this pathway might also be involved in cancer. Hence, we use the Kolmogorov-Smirnov test to detect pathways that have an altered distribution of topological ranks of genes between two phenotypes. We apply PoTRA to study hepatocellular carcinoma (HCC) and several subtypes of HCC. Very interestingly, we discover that all significant pathways in HCC are cancer-associated generally, while several significant pathways in subtypes

  2. PathwaySplice: An R package for unbiased pathway analysis of alternative splicing in RNA-Seq data.

    Science.gov (United States)

    Yan, Aimin; Ban, Yuguang; Gao, Zhen; Chen, Xi; Wang, Lily

    2018-04-24

    Pathway analysis of alternative splicing would be biased without accounting for the different number of exons or junctions associated with each gene, because genes with higher number of exons or junctions are more likely to be included in the "significant" gene list in alternative splicing. We present PathwaySplice, an R package that (1) Performs pathway analysis that explicitly adjusts for the number of exons or junctions associated with each gene; (2) Visualizes selection bias due to different number of exons or junctions for each gene and formally tests for presence of bias using logistic regression; (3) Supports gene sets based on the Gene Ontology terms, as well as more broadly defined gene sets (e.g. MSigDB) or user defined gene sets; (4) Identifies the significant genes driving pathway significance and (5) Organizes significant pathways with an enrichment map, where pathways with large number of overlapping genes are grouped together in a network graph. https://bioconductor.org/packages/release/bioc/html/PathwaySplice.html. lily.wangg@gmail.com, xi.steven.chen@gmail.com.

  3. An integrated acquisition, display, and analysis system

    International Nuclear Information System (INIS)

    Ahmad, T.; Huckins, R.J.

    1987-01-01

    The design goal of the ND9900/Genuie was to integrate a high performance data acquisition and display subsystem with a state-of-the-art 32-bit supermicrocomputer. This was achieved by integrating a Digital Equipment Corporation MicroVAX II CPU board with acquisition and display controllers via the Q-bus. The result is a tightly coupled processing and analysis system for Pulse Height Analysis and other applications. The system architecture supports distributed processing, so that acquisition and display functions are semi-autonomous, making the VAX concurrently available for applications programs

  4. An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer

    Directory of Open Access Journals (Sweden)

    Lockwood William W

    2010-05-01

    Full Text Available Abstract Background Genomics has substantially changed our approach to cancer research. Gene expression profiling, for example, has been utilized to delineate subtypes of cancer, and facilitated derivation of predictive and prognostic signatures. The emergence of technologies for the high resolution and genome-wide description of genetic and epigenetic features has enabled the identification of a multitude of causal DNA events in tumors. This has afforded the potential for large scale integration of genome and transcriptome data generated from a variety of technology platforms to acquire a better understanding of cancer. Results Here we show how multi-dimensional genomics data analysis would enable the deciphering of mechanisms that disrupt regulatory/signaling cascades and downstream effects. Since not all gene expression changes observed in a tumor are causal to cancer development, we demonstrate an approach based on multiple concerted disruption (MCD analysis of genes that facilitates the rational deduction of aberrant genes and pathways, which otherwise would be overlooked in single genomic dimension investigations. Conclusions Notably, this is the first comprehensive study of breast cancer cells by parallel integrative genome wide analyses of DNA copy number, LOH, and DNA methylation status to interpret changes in gene expression pattern. Our findings demonstrate the power of a multi-dimensional approach to elucidate events which would escape conventional single dimensional analysis and as such, reduce the cohort sample size for cancer gene discovery.

  5. Abel integral equations analysis and applications

    CERN Document Server

    Gorenflo, Rudolf

    1991-01-01

    In many fields of application of mathematics, progress is crucially dependent on the good flow of information between (i) theoretical mathematicians looking for applications, (ii) mathematicians working in applications in need of theory, and (iii) scientists and engineers applying mathematical models and methods. The intention of this book is to stimulate this flow of information. In the first three chapters (accessible to third year students of mathematics and physics and to mathematically interested engineers) applications of Abel integral equations are surveyed broadly including determination of potentials, stereology, seismic travel times, spectroscopy, optical fibres. In subsequent chapters (requiring some background in functional analysis) mapping properties of Abel integral operators and their relation to other integral transforms in various function spaces are investi- gated, questions of existence and uniqueness of solutions of linear and nonlinear Abel integral equations are treated, and for equatio...

  6. Pathways and impacts of nitrogen in water bodies: establishing a framework for integrated assessment modelling of management benefits

    DEFF Research Database (Denmark)

    Andersen, Mikael Skou; Kronvang, Brian; Carstensen, Jacob

    Monetization of environmental benefits has become relevant as an element of proportionality tests required for justifications under the EU’s Water Framework Directive article 4 (relating to benefits andcosts of measures). This study extends an impact pathway approach to analysis of aquatic...... the study demonstrates how state-of-the-art environmental modelling can be linked with valuation to provide an adequate cross-media assessment framework relevant to integrated water quality management. The results must be regarded as illustrative and more research is required in several areas to consolidate...... relationships relating to exposures. The findings nevertheless suggest the significance of health effects for overall monetary benefits related to ecological quality objectives for water....

  7. Pathway Analysis of miR-181a in Hypopharyngeal Squamous Cell ...

    African Journals Online (AJOL)

    syakima

    2012-03-15

    Mar 15, 2012 ... Key words: MicroRNA, head and neck cancer, miR-181a, pathway analysis, luciferase assay, FaDu cell line, transfection ..... prostate carcinoma and glioblastoma cells. Nucleic Acids .... WNT pathway in oral cancer: epigenetic.

  8. Network Analysis Tools: from biological networks to clusters and pathways.

    Science.gov (United States)

    Brohée, Sylvain; Faust, Karoline; Lima-Mendez, Gipsi; Vanderstocken, Gilles; van Helden, Jacques

    2008-01-01

    Network Analysis Tools (NeAT) is a suite of computer tools that integrate various algorithms for the analysis of biological networks: comparison between graphs, between clusters, or between graphs and clusters; network randomization; analysis of degree distribution; network-based clustering and path finding. The tools are interconnected to enable a stepwise analysis of the network through a complete analytical workflow. In this protocol, we present a typical case of utilization, where the tasks above are combined to decipher a protein-protein interaction network retrieved from the STRING database. The results returned by NeAT are typically subnetworks, networks enriched with additional information (i.e., clusters or paths) or tables displaying statistics. Typical networks comprising several thousands of nodes and arcs can be analyzed within a few minutes. The complete protocol can be read and executed in approximately 1 h.

  9. Pathways of topological rank analysis (PoTRA: a novel method to detect pathways involved in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Chaoxing Li

    2018-04-01

    Full Text Available Complex diseases such as cancer are usually the result of a combination of environmental factors and one or several biological pathways consisting of sets of genes. Each biological pathway exerts its function by delivering signaling through the gene network. Theoretically, a pathway is supposed to have a robust topological structure under normal physiological conditions. However, the pathway’s topological structure could be altered under some pathological condition. It is well known that a normal biological network includes a small number of well-connected hub nodes and a large number of nodes that are non-hubs. In addition, it is reported that the loss of connectivity is a common topological trait of cancer networks, which is an assumption of our method. Hence, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal or the distribution of topological ranks of genes might be altered. Based on this, we propose a new PageRank-based method called Pathways of Topological Rank Analysis (PoTRA to detect pathways involved in cancer. We use PageRank to measure the relative topological ranks of genes in each biological pathway, then select hub genes for each pathway, and use Fisher’s exact test to test if the number of hub genes in each pathway is altered from normal to cancer. Alternatively, if the distribution of topological ranks of gene in a pathway is altered between normal and cancer, this pathway might also be involved in cancer. Hence, we use the Kolmogorov–Smirnov test to detect pathways that have an altered distribution of topological ranks of genes between two phenotypes. We apply PoTRA to study hepatocellular carcinoma (HCC and several subtypes of HCC. Very interestingly, we discover that all significant pathways in HCC are cancer-associated generally, while several

  10. Final Report: Hydrogen Production Pathways Cost Analysis (2013 – 2016)

    Energy Technology Data Exchange (ETDEWEB)

    James, Brian David [Strategic Analysis Inc., Arlington, VA (United States); DeSantis, Daniel Allan [Strategic Analysis Inc., Arlington, VA (United States); Saur, Genevieve [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-09-30

    This report summarizes work conducted under a three year Department of Energy (DOE) funded project to Strategic Analysis, Inc. (SA) to analyze multiple hydrogen (H2) production technologies and project their corresponding levelized production cost of H2. The analysis was conducted using the H2A Hydrogen Analysis Tool developed by the DOE and National Renewable Energy Laboratory (NREL). The project was led by SA but conducted in close collaboration with the NREL and Argonne National Laboratory (ANL). In-depth techno-economic analysis (TEA) of five different H2 production methods was conducted. These TEAs developed projections for capital costs, fuel/feedstock usage, energy usage, indirect capital costs, land usage, labor requirements, and other parameters, for each H2 production pathway, and use the resulting cost and system parameters as inputs into the H2A discounted cash flow model to project the production cost of H2 ($/kgH2). Five technologies were analyzed as part of the project and are summarized in this report: Proton Exchange Membrane technology (PEM), High temperature solid oxide electrolysis cell technology (SOEC), Dark fermentation of biomass for H2 production, H2 production via Monolithic Piston-Type Reactors with rapid swing reforming and regeneration reactions, and Reformer-Electrolyzer-Purifier (REP) technology developed by Fuel Cell Energy, Inc. (FCE).

  11. Nonlinear structural analysis using integrated force method

    Indian Academy of Sciences (India)

    A new formulation termed the Integrated Force Method (IFM) was proposed by Patnaik ... nated ``Structure (nY m)'' where (nY m) are the force and displacement degrees of ..... Patnaik S N, Yadagiri S 1976 Frequency analysis of structures.

  12. Pathway analysis for a contaminated landfill in Middlesex, New Jersey

    International Nuclear Information System (INIS)

    Yu, C.; Merry-Libby, P.; Yang, J.Y.

    1985-01-01

    Under the Formerly Utilized Sites Remedial Action Program, the US Department of Energy began excavating contaminated materials from the Middlesex Municipal landfill in 1984. A total of 16,000 m 3 of landfill materials covering a 0.2-ha area was excavated, of which 11,000 m 3 was contaminated and has been transported to the nearby sampling plant site for interim storage. Based on the pathway analysis for the onsite and near-site resident scenarios, the radiation dose rates and radionuclide concentrations in groundwater would be below the regulatory requirements for both the short-term and long-term scenarios. Hence, the potential health risks to maximally exposed individuals due to radioactive releases from the Middlesex landfill would be insignificant

  13. In silico tools for the analysis of antibiotic biosynthetic pathways

    DEFF Research Database (Denmark)

    Weber, Tilmann

    2014-01-01

    Natural products of bacteria and fungi are the most important source for antimicrobial drug leads. For decades, such compounds were exclusively found by chemical/bioactivity-guided screening approaches. The rapid progress in sequencing technologies only recently allowed the development of novel...... screening methods based on the genome sequences of potential producing organisms. The basic principle of such genome mining approaches is to identify genes, which are involved in the biosynthesis of such molecules, and to predict the products of the identified pathways. Thus, bioinformatics methods...... and tools are crucial for genome mining. In this review, a comprehensive overview is given on programs and databases for the identification and analysis of antibiotic biosynthesis gene clusters in genomic data....

  14. Development of an open platform system for environmental pathway analysis

    International Nuclear Information System (INIS)

    LePoire, D. J.; Arnish, J. J.; Gnanapragasam, E.; Chen, S. Y.

    2001-01-01

    Most existing computer codes for environmental pathway modeling have been developed to satisfy a specific objective (e.g., perform analyses to demonstrate regulatory compliance). These codes were written in various computer languages and software environments over time and often are not mutually compatible. In recent years, largely driven by advancements in industrial software development, a new concept based on ''modularization'' has emerged. This approach entails the development of common ''modules,'' or components, that can be shared by and used in different applications that have certain common needs. For instance, an air dispersion model can be written as a common component to be shared by several different applications, each with the need to model air dispersion of some material release. When this concept is fully developed, modeling applications would become an exercise of selecting, integrating, and applying a consistent combination of appropriate pre-existing modules for a specific problem. Although modularization holds promising advantages over the traditional approach, a number of issues do exist. These issues must be fully addressed and resolved before the approach can be accepted as a new paradigm for environmental modeling. This paper discusses these issues and provides recommendations and a course of actions for future development

  15. The Cardiopulmonary Effects of Ambient Air Pollution and Mechanistic Pathways: A Comparative Hierarchical Pathway Analysis

    Science.gov (United States)

    Thomas, Duncan C.; Zhang, Junfeng; Kipen, Howard M.; Rich, David Q.; Zhu, Tong; Huang, Wei; Hu, Min; Wang, Guangfa; Wang, Yuedan; Zhu, Ping; Lu, Shou-En; Ohman-Strickland, Pamela; Diehl, Scott R.; Eckel, Sandrah P.

    2014-01-01

    Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001) and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005). These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours) and the hemostasis pathway responds gradually over a 2–3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system. PMID:25502951

  16. The cardiopulmonary effects of ambient air pollution and mechanistic pathways: a comparative hierarchical pathway analysis.

    Directory of Open Access Journals (Sweden)

    Ananya Roy

    Full Text Available Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001 and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005. These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours and the hemostasis pathway responds gradually over a 2-3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system.

  17. Integration of Signaling Pathways with the Epigenetic Machinery in the Maintenance of Stem Cells

    Directory of Open Access Journals (Sweden)

    Luca Fagnocchi

    2016-01-01

    Full Text Available Stem cells balance their self-renewal and differentiation potential by integrating environmental signals with the transcriptional regulatory network. The maintenance of cell identity and/or cell lineage commitment relies on the interplay of multiple factors including signaling pathways, transcription factors, and the epigenetic machinery. These regulatory modules are strongly interconnected and they influence the pattern of gene expression of stem cells, thus guiding their cellular fate. Embryonic stem cells (ESCs represent an invaluable tool to study this interplay, being able to indefinitely self-renew and to differentiate towards all three embryonic germ layers in response to developmental cues. In this review, we highlight those mechanisms of signaling to chromatin, which regulate chromatin modifying enzymes, histone modifications, and nucleosome occupancy. In addition, we report the molecular mechanisms through which signaling pathways affect both the epigenetic and the transcriptional state of ESCs, thereby influencing their cell identity. We propose that the dynamic nature of oscillating signaling and the different regulatory network topologies through which those signals are encoded determine specific gene expression programs, leading to the fluctuation of ESCs among multiple pluripotent states or to the establishment of the necessary conditions to exit pluripotency.

  18. The Notch ligand Delta-like 1 integrates inputs from TGFbeta/Activin and Wnt pathways

    Energy Technology Data Exchange (ETDEWEB)

    Bordonaro, Michael, E-mail: mbordonaro@tcmedc.org; Tewari, Shruti, E-mail: stewari@tcmedc.org; Atamna, Wafa, E-mail: watamna@tcmedc.org; Lazarova, Darina L., E-mail: dlazarova@tcmedc.org

    2011-06-10

    Unlike the well-characterized nuclear function of the Notch intracellular domain, it has been difficult to identify a nuclear role for the ligands of Notch. Here we provide evidence for the nuclear function of the Notch ligand Delta-like 1 in colon cancer (CC) cells exposed to butyrate. We demonstrate that the intracellular domain of Delta-like 1 (Dll1icd) augments the activity of Wnt signaling-dependent reporters and that of the promoter of the connective tissue growth factor (CTGF) gene. Data suggest that Dll1icd upregulates CTGF promoter activity through both direct and indirect mechanisms. The direct mechanism is supported by co-immunoprecipitation of endogenous Smad2/3 proteins and Dll1 and by chromatin immunoprecipitation analyses that revealed the occupancy of Dll1icd on CTGF promoter sequences containing a Smad binding element. The indirect upregulation of CTGF expression by Dll1 is likely due to the ability of Dll1icd to increase Wnt signaling, a pathway that targets CTGF. CTGF expression is induced in butyrate-treated CC cells and results from clonal growth assays support a role for CTGF in the cell growth-suppressive role of butyrate. In conclusion, integration of the Notch, Wnt, and TGFbeta/Activin signaling pathways is in part mediated by the interactions of Dll1 with Smad2/3 and Tcf4.

  19. Integrative Governance of Environmental Water in Australia's Murray-Darling Basin: Evolving Challenges and Emerging Pathways.

    Science.gov (United States)

    Bischoff-Mattson, Zachary; Lynch, Amanda H

    2017-07-01

    Integration, a widely promoted response to the multi-scale complexities of social-environmental sustainability, is diversely and sometimes poorly conceptualized. In this paper we explore integrative governance, which we define as an iterative and contextual process for negotiating and advancing the common interest. We ground this definition in a discussion of institutional factors conditioning integrative governance of environmental water in Australia's Murray-Darling Basin. The Murray-Darling Basin is an iconic system of social-ecological complexity, evocative of large-scale conservation challenges in other developed arid river basins. Our critical assessment of integrative governance practices in that context emerges through analysis of interviews with policy participants and documents pertaining to environmental water management in the tri-state area of southwestern New South Wales, northwestern Victoria, and the South Australian Riverland. We identify four linked challenges: (i) decision support for developing socially robust environmental water management goals, (ii) resource constraints on adaptive practice, (iii) inter-state differences in participatory decision-making and devolution of authority, and (iv) representative inclusion in decision-making. Our appraisal demonstrates these as pivotal challenges for integrative governance in the common interest. We conclude by offering a perspective on the potential for supporting integrative governance through the bridging capacity of Australia's Commonwealth Environmental Water Holder.

  20. Functional Analysis of OMICs Data and Small Molecule Compounds in an Integrated "Knowledge-Based" Platform.

    Science.gov (United States)

    Dubovenko, Alexey; Nikolsky, Yuri; Rakhmatulin, Eugene; Nikolskaya, Tatiana

    2017-01-01

    Analysis of NGS and other sequencing data, gene variants, gene expression, proteomics, and other high-throughput (OMICs) data is challenging because of its biological complexity and high level of technical and biological noise. One way to deal with both problems is to perform analysis with a high fidelity annotated knowledgebase of protein interactions, pathways, and functional ontologies. This knowledgebase has to be structured in a computer-readable format and must include software tools for managing experimental data, analysis, and reporting. Here, we present MetaCore™ and Key Pathway Advisor (KPA), an integrated platform for functional data analysis. On the content side, MetaCore and KPA encompass a comprehensive database of molecular interactions of different types, pathways, network models, and ten functional ontologies covering human, mouse, and rat genes. The analytical toolkit includes tools for gene/protein list enrichment analysis, statistical "interactome" tool for the identification of over- and under-connected proteins in the dataset, and a biological network analysis module made up of network generation algorithms and filters. The suite also features Advanced Search, an application for combinatorial search of the database content, as well as a Java-based tool called Pathway Map Creator for drawing and editing custom pathway maps. Applications of MetaCore and KPA include molecular mode of action of disease research, identification of potential biomarkers and drug targets, pathway hypothesis generation, analysis of biological effects for novel small molecule compounds and clinical applications (analysis of large cohorts of patients, and translational and personalized medicine).

  1. An evaluation of the implementation of maternal obesity pathways of care: a mixed methods study with data integration.

    Directory of Open Access Journals (Sweden)

    Nicola Heslehurst

    Full Text Available Maternal obesity has multiple associated risks and requires substantial intervention. This research evaluated the implementation of maternal obesity care pathways from multiple stakeholder perspectives.A simultaneous mixed methods model with data integration was used. Three component studies were given equal priority. 1: Semi-structured qualitative interviews explored obese pregnant women's experiences of being on the pathways. 2: A quantitative and qualitative postal survey explored healthcare professionals' experiences of delivering the pathways. 3: A case note audit quantitatively assessed pathway compliance. Data were integrated using following a thread and convergence coding matrix methods to search for agreement and disagreement between studies.Study 1: Four themes were identified: women's overall (positive and negative views of the pathways; knowledge and understanding of the pathways; views on clinical and weight management advice and support; and views on the information leaflet. Key results included positive views of receiving additional clinical care, negative experiences of risk communication, and weight management support was considered a priority. Study 2: Healthcare professionals felt the pathways were worthwhile, facilitated good practice, and increased confidence. Training was consistently identified as being required. Healthcare professionals predominantly focussed on women's response to sensitive obesity communication. Study 3: There was good compliance with antenatal clinical interventions. However, there was poor compliance with public health and postnatal interventions. There were some strong areas of agreement between component studies which can inform future development of the pathways. However, disagreement between studies included a lack of shared priorities between healthcare professionals and women, different perspectives on communication issues, and different perspectives on women's prioritisation of weight

  2. An Evaluation of the Implementation of Maternal Obesity Pathways of Care: A Mixed Methods Study with Data Integration

    Science.gov (United States)

    Heslehurst, Nicola; Dinsdale, Sarah; Sedgewick, Gillian; Simpson, Helen; Sen, Seema; Summerbell, Carolyn Dawn; Rankin, Judith

    2015-01-01

    Objectives Maternal obesity has multiple associated risks and requires substantial intervention. This research evaluated the implementation of maternal obesity care pathways from multiple stakeholder perspectives. Study Design A simultaneous mixed methods model with data integration was used. Three component studies were given equal priority. 1: Semi-structured qualitative interviews explored obese pregnant women’s experiences of being on the pathways. 2: A quantitative and qualitative postal survey explored healthcare professionals’ experiences of delivering the pathways. 3: A case note audit quantitatively assessed pathway compliance. Data were integrated using following a thread and convergence coding matrix methods to search for agreement and disagreement between studies. Results Study 1: Four themes were identified: women’s overall (positive and negative) views of the pathways; knowledge and understanding of the pathways; views on clinical and weight management advice and support; and views on the information leaflet. Key results included positive views of receiving additional clinical care, negative experiences of risk communication, and weight management support was considered a priority. Study 2: Healthcare professionals felt the pathways were worthwhile, facilitated good practice, and increased confidence. Training was consistently identified as being required. Healthcare professionals predominantly focussed on women’s response to sensitive obesity communication. Study 3: There was good compliance with antenatal clinical interventions. However, there was poor compliance with public health and postnatal interventions. There were some strong areas of agreement between component studies which can inform future development of the pathways. However, disagreement between studies included a lack of shared priorities between healthcare professionals and women, different perspectives on communication issues, and different perspectives on women

  3. Integrating neural network technology and noise analysis

    International Nuclear Information System (INIS)

    Uhrig, R.E.; Oak Ridge National Lab., TN

    1995-01-01

    The integrated use of neural network and noise analysis technologies offers advantages not available by the use of either technology alone. The application of neural network technology to noise analysis offers an opportunity to expand the scope of problems where noise analysis is useful and unique ways in which the integration of these technologies can be used productively. The two-sensor technique, in which the responses of two sensors to an unknown driving source are related, is used to demonstration such integration. The relationship between power spectral densities (PSDs) of accelerometer signals is derived theoretically using noise analysis to demonstrate its uniqueness. This relationship is modeled from experimental data using a neural network when the system is working properly, and the actual PSD of one sensor is compared with the PSD of that sensor predicted by the neural network using the PSD of the other sensor as an input. A significant deviation between the actual and predicted PSDs indicate that system is changing (i.e., failing). Experiments carried out on check values and bearings illustrate the usefulness of the methodology developed. (Author)

  4. Higher integrity of the motor and visual pathways in long-term video game players.

    Science.gov (United States)

    Zhang, Yang; Du, Guijin; Yang, Yongxin; Qin, Wen; Li, Xiaodong; Zhang, Quan

    2015-01-01

    Long term video game players (VGPs) exhibit superior visual and motor skills compared with non-video game control subjects (NVGCs). However, the neural basis underlying the enhanced behavioral performance remains largely unknown. To clarify this issue, the present study compared the whiter matter integrity within the corticospinal tracts (CST), the superior longitudinal fasciculus (SLF), the inferior longitudinal fasciculus (ILF), and the inferior fronto-occipital fasciculus (IFOF) between the VGPs and the NVGCs using diffusion tensor imaging. Compared with the NVGCs, voxel-wise comparisons revealed significantly higher fractional anisotropy (FA) values in some regions within the left CST, left SLF, bilateral ILF, and IFOF in VGPs. Furthermore, higher FA values in the left CST at the level of cerebral peduncle predicted a faster response in visual attention tasks. These results suggest that higher white matter integrity in the motor and higher-tier visual pathways is associated with long-term video game playing, which may contribute to the understanding on how video game play influences motor and visual performance.

  5. Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA).

    Science.gov (United States)

    Tollefsen, Knut Erik; Scholz, Stefan; Cronin, Mark T; Edwards, Stephen W; de Knecht, Joop; Crofton, Kevin; Garcia-Reyero, Natalia; Hartung, Thomas; Worth, Andrew; Patlewicz, Grace

    2014-12-01

    Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or already on the market. The need for timely and robust decision making demands that regulatory toxicity testing becomes more cost-effective and efficient. One way to realize this goal is by being more strategic in directing testing resources; focusing on chemicals of highest concern, limiting testing to the most probable hazards, or targeting the most vulnerable species. Hypothesis driven Integrated Approaches to Testing and Assessment (IATA) have been proposed as practical solutions to such strategic testing. In parallel, the development of the Adverse Outcome Pathway (AOP) framework, which provides information on the causal links between a molecular initiating event (MIE), intermediate key events (KEs) and an adverse outcome (AO) of regulatory concern, offers the biological context to facilitate development of IATA for regulatory decision making. This manuscript summarizes discussions at the Workshop entitled "Advancing AOPs for Integrated Toxicology and Regulatory Applications" with particular focus on the role AOPs play in informing the development of IATA for different regulatory purposes. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Solution of fractional kinetic equation by a class of integral transform of pathway type

    Science.gov (United States)

    Kumar, Dilip

    2013-04-01

    Solutions of fractional kinetic equations are obtained through an integral transform named Pα-transform introduced in this paper. The Pα-transform is a binomial type transform containing many class of transforms including the well known Laplace transform. The paper is motivated by the idea of pathway model introduced by Mathai [Linear Algebra Appl. 396, 317-328 (2005), 10.1016/j.laa.2004.09.022]. The composition of the transform with differential and integral operators are proved along with convolution theorem. As an illustration of applications to the general theory of differential equations, a simple differential equation is solved by the new transform. Being a new transform, the Pα-transform of some elementary functions as well as some generalized special functions such as H-function, G-function, Wright generalized hypergeometric function, generalized hypergeometric function, and Mittag-Leffler function are also obtained. The results for the classical Laplace transform is retrieved by letting α → 1.

  7. [Integrated health care organizations: guideline for analysis].

    Science.gov (United States)

    Vázquez Navarrete, M Luisa; Vargas Lorenzo, Ingrid; Farré Calpe, Joan; Terraza Núñez, Rebeca

    2005-01-01

    There has been a tendency recently to abandon competition and to introduce policies that promote collaboration between health providers as a means of improving the efficiency of the system and the continuity of care. A number of countries, most notably the United States, have experienced the integration of health care providers to cover the continuum of care of a defined population. Catalonia has witnessed the steady emergence of increasing numbers of integrated health organisations (IHO) but, unlike the United States, studies on health providers' integration are scarce. As part of a research project currently underway, a guide was developed to study Catalan IHOs, based on a classical literature review and the development of a theoretical framework. The guide proposes analysing the IHO's performance in relation to their final objectives of improving the efficiency and continuity of health care by an analysis of the integration type (based on key characteristics); external elements (existence of other suppliers, type of services' payment mechanisms); and internal elements (model of government, organization and management) that influence integration. Evaluation of the IHO's performance focuses on global strategies and results on coordination of care and efficiency. Two types of coordination are evaluated: information coordination and coordination of care management. Evaluation of the efficiency of the IHO refers to technical and allocative efficiency. This guide may have to be modified for use in the Catalan context.

  8. Integrated tools for control-system analysis

    Science.gov (United States)

    Ostroff, Aaron J.; Proffitt, Melissa S.; Clark, David R.

    1989-01-01

    The basic functions embedded within a user friendly software package (MATRIXx) are used to provide a high level systems approach to the analysis of linear control systems. Various control system analysis configurations are assembled automatically to minimize the amount of work by the user. Interactive decision making is incorporated via menu options and at selected points, such as in the plotting section, by inputting data. There are five evaluations such as the singular value robustness test, singular value loop transfer frequency response, Bode frequency response, steady-state covariance analysis, and closed-loop eigenvalues. Another section describes time response simulations. A time response for random white noise disturbance is available. The configurations and key equations used for each type of analysis, the restrictions that apply, the type of data required, and an example problem are described. One approach for integrating the design and analysis tools is also presented.

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

    Directory of Open Access Journals (Sweden)

    Brett A McKinney

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

  10. A microRNA activity map of human mesenchymal tumors: connections to oncogenic pathways; an integrative transcriptomic study

    Directory of Open Access Journals (Sweden)

    Fountzilas Elena

    2012-07-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are nucleic acid regulators of many human mRNAs, and are associated with many tumorigenic processes. miRNA expression levels have been used in profiling studies, but some evidence suggests that expression levels do not fully capture miRNA regulatory activity. In this study we integrate multiple gene expression datasets to determine miRNA activity patterns associated with cancer phenotypes and oncogenic pathways in mesenchymal tumors – a very heterogeneous class of malignancies. Results Using a computational method, we identified differentially activated miRNAs between 77 normal tissue specimens and 135 sarcomas and we validated many of these findings with microarray interrogation of an independent, paraffin-based cohort of 18 tumors. We also showed that miRNA activity is imperfectly correlated with miRNA expression levels. Using next-generation miRNA sequencing we identified potential base sequence alterations which may explain differential activity. We then analyzed miRNA activity changes related to the RAS-pathway and found 21 miRNAs that switch from silenced to activated status in parallel with RAS activation. Importantly, nearly half of these 21 miRNAs were predicted to regulate integral parts of the miRNA processing machinery, and our gene expression analysis revealed significant reductions of these transcripts in RAS-active tumors. These results suggest an association between RAS signaling and miRNA processing in which miRNAs may attenuate their own biogenesis. Conclusions Our study represents the first gene expression-based investigation of miRNA regulatory activity in human sarcomas, and our findings indicate that miRNA activity patterns derived from integrated transcriptomic data are reproducible and biologically informative in cancer. We identified an association between RAS signaling and miRNA processing, and demonstrated sequence alterations as plausible causes for differential miRNA activity

  11. An integrated system for genetic analysis

    Directory of Open Access Journals (Sweden)

    Duan Xiao

    2006-04-01

    Full Text Available Abstract Background Large-scale genetic mapping projects require data management systems that can handle complex phenotypes and detect and correct high-throughput genotyping errors, yet are easy to use. Description We have developed an Integrated Genotyping System (IGS to meet this need. IGS securely stores, edits and analyses genotype and phenotype data. It stores information about DNA samples, plates, primers, markers and genotypes generated by a genotyping laboratory. Data are structured so that statistical genetic analysis of both case-control and pedigree data is straightforward. Conclusion IGS can model complex phenotypes and contain genotypes from whole genome association studies. The database makes it possible to integrate genetic analysis with data curation. The IGS web site http://bioinformatics.well.ox.ac.uk/project-igs.shtml contains further information.

  12. Integrated Reliability and Risk Analysis System (IRRAS)

    International Nuclear Information System (INIS)

    Russell, K.D.; McKay, M.K.; Sattison, M.B.; Skinner, N.L.; Wood, S.T.; Rasmuson, D.M.

    1992-01-01

    The Integrated Reliability and Risk Analysis System (IRRAS) is a state-of-the-art, microcomputer-based probabilistic risk assessment (PRA) model development and analysis tool to address key nuclear plant safety issues. IRRAS is an integrated software tool that gives the user the ability to create and analyze fault trees and accident sequences using a microcomputer. This program provides functions that range from graphical fault tree construction to cut set generation and quantification. Version 1.0 of the IRRAS program was released in February of 1987. Since that time, many user comments and enhancements have been incorporated into the program providing a much more powerful and user-friendly system. This version has been designated IRRAS 4.0 and is the subject of this Reference Manual. Version 4.0 of IRRAS provides the same capabilities as Version 1.0 and adds a relational data base facility for managing the data, improved functionality, and improved algorithm performance

  13. Integrative pathway dissection of molecular mechanisms of moxLDL-induced vascular smooth muscle phenotype transformation

    Directory of Open Access Journals (Sweden)

    Karagiannis George S

    2013-01-01

    Full Text Available Abstract Background Atherosclerosis (AT is a chronic inflammatory disease characterized by the accumulation of inflammatory cells, lipoproteins and fibrous tissue in the walls of arteries. AT is the primary cause of heart attacks and stroke and is the leading cause of death in Western countries. To date, the pathogenesis of AT is not well-defined. Studies have shown that the dedifferentiation of contractile and quiescent vascular smooth muscle cells (SMC to the proliferative, migratory and synthetic phenotype in the intima is pivotal for the onset and progression of AT. To further delineate the mechanisms underlying the pathogenesis of AT, we analyzed the early molecular pathways and networks involved in the SMC phenotype transformation. Methods Quiescent human coronary artery SMCs were treated with minimally-oxidized LDL (moxLDL, for 3 hours and 21 hours, respectively. Transcriptomic data was generated for both time-points using microarrays and was subjected to pathway analysis using Gene Set Enrichment Analysis, GeneMANIA and Ingenuity software tools. Gene expression heat maps and pathways enriched in differentially expressed genes were compared to identify functional biological themes to elucidate early and late molecular mechanisms of moxLDL-induced SMC dedifferentiation. Results Differentially expressed genes were found to be enriched in cholesterol biosynthesis, inflammatory cytokines, chemokines, growth factors, cell cycle control and myogenic contraction themes. These pathways are consistent with inflammatory responses, cell proliferation, migration and ECM production, which are characteristic of SMC dedifferentiation. Furthermore, up-regulation of cholesterol synthesis and dysregulation of cholesterol metabolism was observed in moxLDL-induced SMC. These observations are consistent with the accumulation of cholesterol and oxidized cholesterol esters, which induce proinflammatory reactions during atherogenesis. Our data implicate for the

  14. Integrity Analysis of Damaged Steam Generator Tubes

    International Nuclear Information System (INIS)

    Stanic, D.

    1998-01-01

    Variety of degradation mechanisms affecting steam generator tubes makes steam generators as one of the critical components in the nuclear power plants. Depending of their nature, degradation mechanisms cause different types of damages. It requires performance of extensive integrity analysis in order to access various conditions of crack behavior under operating and accidental conditions. Development and application of advanced eddy current techniques for steam generator examination provide good characterization of found damages. Damage characteristics (shape, orientation and dimensions) may be defined and used for further evaluation of damage influence on tube integrity. In comparison with experimental and analytical methods, numerical methods are also efficient tools for integrity assessment. Application of finite element methods provides relatively simple modeling of different type of damages and simulation of various operating conditions. The stress and strain analysis may be performed for elastic and elasto-plastic state with good ability for visual presentation of results. Furthermore, the fracture mechanics parameters may be calculated. Results obtained by numerical analysis supplemented with experimental results are the base for definition of alternative plugging criteria which may significantly reduce the number of plugged tubes. (author)

  15. Point Analysis in Java applied to histological images of the perforant pathway: a user's account.

    Science.gov (United States)

    Scorcioni, Ruggero; Wright, Susan N; Patrick Card, J; Ascoli, Giorgio A; Barrionuevo, Germán

    2008-01-01

    The freeware Java tool Point Analysis in Java (PAJ), created to perform 3D point analysis, was tested in an independent laboratory setting. The input data consisted of images of the hippocampal perforant pathway from serial immunocytochemical localizations of the rat brain in multiple views at different resolutions. The low magnification set (x2 objective) comprised the entire perforant pathway, while the high magnification set (x100 objective) allowed the identification of individual fibers. A preliminary stereological study revealed a striking linear relationship between the fiber count at high magnification and the optical density at low magnification. PAJ enabled fast analysis for down-sampled data sets and a friendly interface with automated plot drawings. Noted strengths included the multi-platform support as well as the free availability of the source code, conducive to a broad user base and maximum flexibility for ad hoc requirements. PAJ has great potential to extend its usability by (a) improving its graphical user interface, (b) increasing its input size limit, (c) improving response time for large data sets, and (d) potentially being integrated with other Java graphical tools such as ImageJ.

  16. The integrated microbial genome resource of analysis.

    Science.gov (United States)

    Checcucci, Alice; Mengoni, Alessio

    2015-01-01

    Integrated Microbial Genomes and Metagenomes (IMG) is a biocomputational system that allows to provide information and support for annotation and comparative analysis of microbial genomes and metagenomes. IMG has been developed by the US Department of Energy (DOE)-Joint Genome Institute (JGI). IMG platform contains both draft and complete genomes, sequenced by Joint Genome Institute and other public and available genomes. Genomes of strains belonging to Archaea, Bacteria, and Eukarya domains are present as well as those of viruses and plasmids. Here, we provide some essential features of IMG system and case study for pangenome analysis.

  17. Integrated analysis of genetic data with R

    Directory of Open Access Journals (Sweden)

    Zhao Jing

    2006-01-01

    Full Text Available Abstract Genetic data are now widely available. There is, however, an apparent lack of concerted effort to produce software systems for statistical analysis of genetic data compared with other fields of statistics. It is often a tremendous task for end-users to tailor them for particular data, especially when genetic data are analysed in conjunction with a large number of covariates. Here, R http://www.r-project.org, a free, flexible and platform-independent environment for statistical modelling and graphics is explored as an integrated system for genetic data analysis. An overview of some packages currently available for analysis of genetic data is given. This is followed by examples of package development and practical applications. With clear advantages in data management, graphics, statistical analysis, programming, internet capability and use of available codes, it is a feasible, although challenging, task to develop it into an integrated platform for genetic analysis; this will require the joint efforts of many researchers.

  18. Advancing Alternative Analysis: Integration of Decision Science

    DEFF Research Database (Denmark)

    Malloy, Timothy F; Zaunbrecher, Virginia M; Batteate, Christina

    2016-01-01

    Decision analysis-a systematic approach to solving complex problems-offers tools and frameworks to support decision making that are increasingly being applied to environmental challenges. Alternatives analysis is a method used in regulation and product design to identify, compare, and evaluate......, and civil society and included experts in toxicology, decision science, alternatives assessment, engineering, and law and policy. Participants were divided into two groups and prompted with targeted questions. Throughout the workshop, the groups periodically came together in plenary sessions to reflect......) engaging the systematic development and evaluation of decision approaches and tools; (2) using case studies to advance the integration of decision analysis into alternatives analysis; (3) supporting transdisciplinary research; and (4) supporting education and outreach efforts....

  19. Regulatory pathway analysis by high-throughput in situ hybridization.

    Directory of Open Access Journals (Sweden)

    Axel Visel

    2007-10-01

    Full Text Available Automated in situ hybridization enables the construction of comprehensive atlases of gene expression patterns in mammals. Such atlases can become Web-searchable digital expression maps of individual genes and thus offer an entryway to elucidate genetic interactions and signaling pathways. Towards this end, an atlas housing approximately 1,000 spatial gene expression patterns of the midgestation mouse embryo was generated. Patterns were textually annotated using a controlled vocabulary comprising >90 anatomical features. Hierarchical clustering of annotations was carried out using distance scores calculated from the similarity between pairs of patterns across all anatomical structures. This process ordered hundreds of complex expression patterns into a matrix that reflects the embryonic architecture and the relatedness of patterns of expression. Clustering yielded 12 distinct groups of expression patterns. Because of the similarity of expression patterns within a group, members of each group may be components of regulatory cascades. We focused on the group containing Pax6, an evolutionary conserved transcriptional master mediator of development. Seventeen of the 82 genes in this group showed a change of expression in the developing neocortex of Pax6-deficient embryos. Electromobility shift assays were used to test for the presence of Pax6-paired domain binding sites. This led to the identification of 12 genes not previously known as potential targets of Pax6 regulation. These findings suggest that cluster analysis of annotated gene expression patterns obtained by automated in situ hybridization is a novel approach for identifying components of signaling cascades.

  20. Supply Chain Sustainability Analysis of Three Biofuel Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Jacob J. Jacobson; Erin Searcy; Kara Cafferty; Jennifer B. Dunn; Michael Johnson; Zhichao Wang; Michael Wang; Mary Biddy; Abhijit Dutta; Daniel Inman; Eric Tan; Sue Jones; Lesley Snowden-Swan

    2013-11-01

    The Department of Energy’s (DOE) Bioenergy Technologies Office (BETO) collaborates with industrial, agricultural, and non-profit partners to develop and deploy biofuels and other biologically-derived products. As part of this effort, BETO and its national laboratory teams conduct in-depth techno-economic assessments (TEA) of technologies to produce biofuels as part state of technology (SOT) analyses. An SOT assesses progress within and across relevant technology areas based on actual experimental results relative to technical targets and cost goals from design cases and includes technical, economic, and environmental criteria as available. Overall assessments of biofuel pathways begin with feedstock production and the logistics of transporting the feedstock from the farm or plantation to the conversion facility or biorefinery. The conversion process itself is modeled in detail as part of the SOT analysis. The teams then develop an estimate of the biofuel minimum selling price (MSP) and assess the cost competitiveness of the biofuel with conventional fuels such as gasoline.

  1. Integration and segregation in auditory scene analysis

    Science.gov (United States)

    Sussman, Elyse S.

    2005-03-01

    Assessment of the neural correlates of auditory scene analysis, using an index of sound change detection that does not require the listener to attend to the sounds [a component of event-related brain potentials called the mismatch negativity (MMN)], has previously demonstrated that segregation processes can occur without attention focused on the sounds and that within-stream contextual factors influence how sound elements are integrated and represented in auditory memory. The current study investigated the relationship between the segregation and integration processes when they were called upon to function together. The pattern of MMN results showed that the integration of sound elements within a sound stream occurred after the segregation of sounds into independent streams and, further, that the individual streams were subject to contextual effects. These results are consistent with a view of auditory processing that suggests that the auditory scene is rapidly organized into distinct streams and the integration of sequential elements to perceptual units takes place on the already formed streams. This would allow for the flexibility required to identify changing within-stream sound patterns, needed to appreciate music or comprehend speech..

  2. Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality.

    Science.gov (United States)

    Jiang, Yue; Xiong, Xuejian; Danska, Jayne; Parkinson, John

    2016-01-12

    Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. At the same time, our findings show how microbiome complexity and availability of

  3. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    International Nuclear Information System (INIS)

    Fukunaga, Satoki; Kakehashi, Anna; Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki; Gi, Min; Wanibuchi, Hideki

    2015-01-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis

  4. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    Energy Technology Data Exchange (ETDEWEB)

    Fukunaga, Satoki [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Kakehashi, Anna [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki [Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Gi, Min [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2015-08-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis.

  5. Diagnostic pathway of integrated SPECT/CT for coronary artery disease

    International Nuclear Information System (INIS)

    Slart, Riemer H.J.A.; Tio, Rene A.; Zijlstra, Felix; Dierckx, Rudi A.

    2009-01-01

    . The development of SPECT/CT hybrid systems is therefore of important value for the nuclear cardiology armamentarium. This editorial commentary outlines a diagnostic pathway of integrated SPECT/CT for CAD assessment in symptomatic patients at intermediate risk for CAD. (orig.)

  6. Integrated framework for dynamic safety analysis

    International Nuclear Information System (INIS)

    Kim, Tae Wan; Karanki, Durga R.

    2012-01-01

    In the conventional PSA (Probabilistic Safety Assessment), detailed plant simulations by independent thermal hydraulic (TH) codes are used in the development of accident sequence models. Typical accidents in a NPP involve complex interactions among process, safety systems, and operator actions. As independent TH codes do not have the models of operator actions and full safety systems, they cannot literally simulate the integrated and dynamic interactions of process, safety systems, and operator responses. Offline simulation with pre decided states and time delays may not model the accident sequences properly. Moreover, when stochastic variability in responses of accident models is considered, defining all the combinations for simulations will be cumbersome task. To overcome some of these limitations of conventional safety analysis approach, TH models are coupled with the stochastic models in the dynamic event tree (DET) framework, which provides flexibility to model the integrated response due to better communication as all the accident elements are in the same model. The advantages of this framework also include: Realistic modeling in dynamic scenarios, comprehensive results, integrated approach (both deterministic and probabilistic models), and support for HRA (Human Reliability Analysis)

  7. Integrating publicly-available data to generate computationally-predicted adverse outcome pathways for hepatic steatosis

    Science.gov (United States)

    The adverse outcome pathway (AOP) framework provides a way of organizing knowledge related to the key biological events that result in a particular health outcome. For the majority of environmental chemicals, the availability of curated pathways characterizing potential toxicity ...

  8. The School-Community Integrated Learning Pathway: Exploring a New Way to Prepare and Induct Final-Year Preservice Teachers

    Science.gov (United States)

    Hudson, Suzanne; Hudson, Peter; Adie, Lenore

    2015-01-01

    Universities and teacher employment bodies seek new, cost-effective ways for graduating classroom-ready teachers. This study involved 32 final-year preservice teachers in an innovative school--university partnership teacher education programme titled, the School-Community Integrated Learning (SCIL) pathway. Data were collected using a five-part…

  9. Integrated marketing communications:pathway for enhancing client-costomer relationships

    Directory of Open Access Journals (Sweden)

    Kehinde Oladele Joseph

    2010-12-01

    Full Text Available The strategic coordination of marketing communication tools is vital and highly crucial for every result driven organization today. Companies must be able to deliver the right message to their target audience in order to elicit the right results. The objectives of this paper amongst others are to: (i ascertain whether proper implementation of Integrated Marketing Communications can help reduce the cost of marketing communication or promotional budget. (ii Establish whether the use of integrated marketing communications by firm through its advertising agencies can bring about profitable long-term client-customer relationships. The paper raises two hypotheses, which are stated in the null form. These are: The more an organization adopts Integrated Marketing communications, the more fund it will spend on promotional activities in the long run, and the less an organization adopts IMC principles, the more profitable Client-Customer relationship it will build. The paper uses survey method with structured questionnaire to obtain data that were later analyzed with correlation coefficient and analysis of variance test statistics. (ANOVA. Findings show that company will be able to save cost on marketing communication and promote lasting long-term client-customer relationships, if they properly adopt integrated marketing communication principles. The paper makes valuable recommendations which users of IMC will find useful in the ever dynamic and highly competitive world of marketing

  10. Integrative analysis of the mitochondrial proteome in yeast.

    Directory of Open Access Journals (Sweden)

    Holger Prokisch

    2004-06-01

    Full Text Available In this study yeast mitochondria were used as a model system to apply, evaluate, and integrate different genomic approaches to define the proteins of an organelle. Liquid chromatography mass spectrometry applied to purified mitochondria identified 546 proteins. By expression analysis and comparison to other proteome studies, we demonstrate that the proteomic approach identifies primarily highly abundant proteins. By expanding our evaluation to other types of genomic approaches, including systematic deletion phenotype screening, expression profiling, subcellular localization studies, protein interaction analyses, and computational predictions, we show that an integration of approaches moves beyond the limitations of any single approach. We report the success of each approach by benchmarking it against a reference set of known mitochondrial proteins, and predict approximately 700 proteins associated with the mitochondrial organelle from the integration of 22 datasets. We show that a combination of complementary approaches like deletion phenotype screening and mass spectrometry can identify over 75% of the known mitochondrial proteome. These findings have implications for choosing optimal genome-wide approaches for the study of other cellular systems, including organelles and pathways in various species. Furthermore, our systematic identification of genes involved in mitochondrial function and biogenesis in yeast expands the candidate genes available for mapping Mendelian and complex mitochondrial disorders in humans.

  11. Integrating health and environmental impact analysis

    DEFF Research Database (Denmark)

    Reis, S; Morris, G.; Fleming, L. E.

    2015-01-01

    which addresses human activity in all its social, economic and cultural complexity. The new approach must be integral to, and interactive, with the natural environment. We see the continuing failure to truly integrate human health and environmental impact analysis as deeply damaging, and we propose...... while equally emphasizing the health of the environment, and the growing calls for 'ecological public health' as a response to global environmental concerns now suffusing the discourse in public health. More revolution than evolution, ecological public health will demand new perspectives regarding...... the interconnections among society, the economy, the environment and our health and well-being. Success must be built on collaborations between the disparate scientific communities of the environmental sciences and public health as well as interactions with social scientists, economists and the legal profession...

  12. Advancing Alternative Analysis: Integration of Decision Science.

    Science.gov (United States)

    Malloy, Timothy F; Zaunbrecher, Virginia M; Batteate, Christina M; Blake, Ann; Carroll, William F; Corbett, Charles J; Hansen, Steffen Foss; Lempert, Robert J; Linkov, Igor; McFadden, Roger; Moran, Kelly D; Olivetti, Elsa; Ostrom, Nancy K; Romero, Michelle; Schoenung, Julie M; Seager, Thomas P; Sinsheimer, Peter; Thayer, Kristina A

    2017-06-13

    Decision analysis-a systematic approach to solving complex problems-offers tools and frameworks to support decision making that are increasingly being applied to environmental challenges. Alternatives analysis is a method used in regulation and product design to identify, compare, and evaluate the safety and viability of potential substitutes for hazardous chemicals. We assessed whether decision science may assist the alternatives analysis decision maker in comparing alternatives across a range of metrics. A workshop was convened that included representatives from government, academia, business, and civil society and included experts in toxicology, decision science, alternatives assessment, engineering, and law and policy. Participants were divided into two groups and were prompted with targeted questions. Throughout the workshop, the groups periodically came together in plenary sessions to reflect on other groups' findings. We concluded that the further incorporation of decision science into alternatives analysis would advance the ability of companies and regulators to select alternatives to harmful ingredients and would also advance the science of decision analysis. We advance four recommendations: a ) engaging the systematic development and evaluation of decision approaches and tools; b ) using case studies to advance the integration of decision analysis into alternatives analysis; c ) supporting transdisciplinary research; and d ) supporting education and outreach efforts. https://doi.org/10.1289/EHP483.

  13. Structural integrity analysis of a steam turbine

    International Nuclear Information System (INIS)

    Villagarcia, Maria P.

    1997-01-01

    One of the most critical components of a power utility is the rotor of the steam turbine. Catastrophic failures of the last decades have promoted the development of life assessment procedures for rotors. The present study requires the knowledge of operating conditions, component geometry, the properties of materials, history of the component, size, location and nature of the existing flaws. The aim of the present work is the obtention of a structural integrity analysis procedure for a steam turbine rotor, taking into account the above-mentioned parameters. In this procedure, a stress thermal analysis by finite elements is performed initially, in order to obtain the temperature and stress distribution for a subsequent analysis by fracture mechanics. The risk of a fast fracture due to flaws in the central zone of the rotor is analyzed. The procedure is applied to an operating turbine: the main steam turbine of the Atucha I nuclear power utility. (author)

  14. A taxonomy of integral reaction path analysis

    Energy Technology Data Exchange (ETDEWEB)

    Grcar, Joseph F.; Day, Marcus S.; Bell, John B.

    2004-12-23

    W. C. Gardiner observed that achieving understanding through combustion modeling is limited by the ability to recognize the implications of what has been computed and to draw conclusions about the elementary steps underlying the reaction mechanism. This difficulty can be overcome in part by making better use of reaction path analysis in the context of multidimensional flame simulations. Following a survey of current practice, an integral reaction flux is formulated in terms of conserved scalars that can be calculated in a fully automated way. Conditional analyses are then introduced, and a taxonomy for bidirectional path analysis is explored. Many examples illustrate the resulting path analysis and uncover some new results about nonpremixed methane-air laminar jets.

  15. The ASDEX integrated data analysis system AIDA

    International Nuclear Information System (INIS)

    Grassie, K.; Gruber, O.; Kardaun, O.; Kaufmann, M.; Lackner, K.; Martin, P.; Mast, K.F.; McCarthy, P.J.; Mertens, V.; Pohl, D.; Rang, U.; Wunderlich, R.

    1989-11-01

    Since about two years, the ASDEX integrated data analysis system (AIDA), which combines the database (DABA) and the statistical analysis system (SAS), is successfully in operation. Besides a considerable, but meaningful, reduction of the 'raw' shot data, it offers the advantage of carefully selected and precisely defined datasets, which are easily accessible for informative tabular data overviews (DABA), and multi-shot analysis (SAS). Even rather complicated, statistical analyses can be performed efficiently within this system. In this report, we want to summarise AIDA's main features, give some details on its set-up and on the physical models which have been used for the derivation of the processed data. We also give short introduction how to use DABA and SAS. (orig.)

  16. Using answer set programming to integrate RNA expression with signalling pathway information to infer how mutations affect ageing.

    Science.gov (United States)

    Papatheodorou, Irene; Ziehm, Matthias; Wieser, Daniela; Alic, Nazif; Partridge, Linda; Thornton, Janet M

    2012-01-01

    A challenge of systems biology is to integrate incomplete knowledge on pathways with existing experimental data sets and relate these to measured phenotypes. Research on ageing often generates such incomplete data, creating difficulties in integrating RNA expression with information about biological processes and the phenotypes of ageing, including longevity. Here, we develop a logic-based method that employs Answer Set Programming, and use it to infer signalling effects of genetic perturbations, based on a model of the insulin signalling pathway. We apply our method to RNA expression data from Drosophila mutants in the insulin pathway that alter lifespan, in a foxo dependent fashion. We use this information to deduce how the pathway influences lifespan in the mutant animals. We also develop a method for inferring the largest common sub-paths within each of our signalling predictions. Our comparisons reveal consistent homeostatic mechanisms across both long- and short-lived mutants. The transcriptional changes observed in each mutation usually provide negative feedback to signalling predicted for that mutation. We also identify an S6K-mediated feedback in two long-lived mutants that suggests a crosstalk between these pathways in mutants of the insulin pathway, in vivo. By formulating the problem as a logic-based theory in a qualitative fashion, we are able to use the efficient search facilities of Answer Set Programming, allowing us to explore larger pathways, combine molecular changes with pathways and phenotype and infer effects on signalling in in vivo, whole-organism, mutants, where direct signalling stimulation assays are difficult to perform. Our methods are available in the web-service NetEffects: http://www.ebi.ac.uk/thornton-srv/software/NetEffects.

  17. PathNet: a tool for pathway analysis using topological information

    Directory of Open Access Journals (Sweden)

    Dutta Bhaskar

    2012-09-01

    Full Text Available Abstract Background Identification of canonical pathways through enrichment of differentially expressed genes in a given pathway is a widely used method for interpreting gene lists generated from high-throughput experimental studies. However, most algorithms treat pathways as sets of genes, disregarding any inter- and intra-pathway connectivity information, and do not provide insights beyond identifying lists of pathways. Results We developed an algorithm (PathNet that utilizes the connectivity information in canonical pathway descriptions to help identify study-relevant pathways and characterize non-obvious dependencies and connections among pathways using gene expression data. PathNet considers both the differential expression of genes and their pathway neighbors to strengthen the evidence that a pathway is implicated in the biological conditions characterizing the experiment. As an adjunct to this analysis, PathNet uses the connectivity of the differentially expressed genes among all pathways to score pathway contextual associations and statistically identify biological relations among pathways. In this study, we used PathNet to identify biologically relevant results in two Alzheimer’s disease microarray datasets, and compared its performance with existing methods. Importantly, PathNet identified de-regulation of the ubiquitin-mediated proteolysis pathway as an important component in Alzheimer’s disease progression, despite the absence of this pathway in the standard enrichment analyses. Conclusions PathNet is a novel method for identifying enrichment and association between canonical pathways in the context of gene expression data. It takes into account topological information present in pathways to reveal biological information. PathNet is available as an R workspace image from http://www.bhsai.org/downloads/pathnet/.

  18. Analysis of Stomatal Patterning in Selected Mutants of MAPK Pathways

    KAUST Repository

    Felemban, Abrar

    2016-01-01

    -activated protein kinase (MAPK) signalling pathway, which modulates a variety of other processes, including cell proliferation, regulation of cytokinesis, programed cell death, and response to abiotic and biotic stress. The environment also plays a role in stomatal

  19. [The Alliance Programme: an integrated care pathway for patients with schizophrenia].

    Science.gov (United States)

    Nielsen, Bent; Sigsgaard, Anne; Gregersen, Jane; Meilvang, Bente; Halldorsson, Lene Leth; Christensen, Anders; Kirk, Else; Hansen, Vagn

    2008-11-10

    Experiences and results of implementation of an integrated care pathway (ICP) for patients with schizophrenia are described. The participants of the ICP were the hospital psychiatry unit, the community mental health team and the social psychiatry unit. The article reviews the collaboration in connection with patient hospitalization and discharge. The study includes 224 patients, who fulfill the ICD 10 criteria for schizophrenia or schizo-affective disorder. The patients were interviewed at admission to and discharge from the Psychiatric Department. During hospitalization, the staff filled in a check list establishing whether the established procedures were complied with in each individual case. The Outpatient Section filled in a similar check list. In addition, information from the local registry concerning the hospitalization pattern during the first 12 months after discharge was obtained. As a result of the ICP, collaboration was stimulated. During the first year disagreement between sectors with regard to the degree of compliance with the introduced procedures during hospitalization was observed (p > 0.05). Disagreement concerning the degree of compliance with procedures at admission was observed throughout the observation period (p > 0.05). Neither frequency of re-hospitalization nor inpatient bed costs were significantly reduced. ICP required considerable resource allocation, and the results of the effort were minimal. The ineffective initiatives were subsequently phased out.

  20. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    International Nuclear Information System (INIS)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben A

    2008-01-01

    Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent studies. Besides classification of outcome, these global expression patterns may reflect biological mechanisms involved in metastasis of breast cancer. Our purpose has been to investigate pathways and transcription factors involved in metastasis by use of gene expression data sets. We have analyzed 8 publicly available gene expression data sets. A global approach, 'gene set enrichment analysis' as well as an approach focusing on a subset of significantly differently regulated genes, GenMAPP, has been applied to rank pathway gene sets according to differential regulation in metastasizing tumors compared to non-metastasizing tumors. Meta-analysis has been used to determine overrepresentation of pathways and transcription factors targets, concordant deregulated in metastasizing breast tumors, in several data sets. The major findings are up-regulation of cell cycle pathways and a metabolic shift towards glucose metabolism reflected in several pathways in metastasizing tumors. Growth factor pathways seem to play dual roles; EGF and PDGF pathways are decreased, while VEGF and sex-hormone pathways are increased in tumors that metastasize. Furthermore, migration, proteasome, immune system, angiogenesis, DNA repair and several signal transduction pathways are associated to metastasis. Finally several transcription factors e.g. E2F, NFY, and YY1 are identified as being involved in metastasis. By pathway meta-analysis many biological mechanisms beyond major characteristics such as proliferation are identified. Transcription factor analysis identifies a number of key factors that support central pathways. Several previously proposed treatment targets are identified and several new pathways that may

  1. Accelerator physics analysis with an integrated toolkit

    International Nuclear Information System (INIS)

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

    1992-08-01

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

  2. The Integral A Crux for Analysis

    CERN Document Server

    Krantz, Steven G

    2011-01-01

    This book treats all of the most commonly used theories of the integral. After motivating the idea of integral, we devote a full chapter to the Riemann integral and the next to the Lebesgue integral. Another chapter compares and contrasts the two theories. The concluding chapter offers brief introductions to the Henstock integral, the Daniell integral, the Stieltjes integral, and other commonly used integrals. The purpose of this book is to provide a quick but accurate (and detailed) introduction to all aspects of modern integration theory. It should be accessible to any student who has had ca

  3. Mechanisms and mediation in survival analysis: towards an integrated analytical framework.

    LENUS (Irish Health Repository)

    Haase, Trutz

    2016-02-29

    A wide-ranging debate has taken place in recent years on mediation analysis and causal modelling, raising profound theoretical, philosophical and methodological questions. The authors build on the results of these discussions to work towards an integrated approach to the analysis of research questions that situate survival outcomes in relation to complex causal pathways with multiple mediators. The background to this contribution is the increasingly urgent need for policy-relevant research on the nature of inequalities in health and healthcare.

  4. A Review of Pathway-Based Analysis Tools That Visualize Genetic Variants

    Directory of Open Access Journals (Sweden)

    Elisa Cirillo

    2017-11-01

    Full Text Available Pathway analysis is a powerful method for data analysis in genomics, most often applied to gene expression analysis. It is also promising for single-nucleotide polymorphism (SNP data analysis, such as genome-wide association study data, because it allows the interpretation of variants with respect to the biological processes in which the affected genes and proteins are involved. Such analyses support an interactive evaluation of the possible effects of variations on function, regulation or interaction of gene products. Current pathway analysis software often does not support data visualization of variants in pathways as an alternate method to interpret genetic association results, and specific statistical methods for pathway analysis of SNP data are not combined with these visualization features. In this review, we first describe the visualization options of the tools that were identified by a literature review, in order to provide insight for improvements in this developing field. Tool evaluation was performed using a computational epistatic dataset of gene–gene interactions for obesity risk. Next, we report the necessity to include in these tools statistical methods designed for the pathway-based analysis with SNP data, expressly aiming to define features for more comprehensive pathway-based analysis tools. We conclude by recognizing that pathway analysis of genetic variations data requires a sophisticated combination of the most useful and informative visual aspects of the various tools evaluated.

  5. From elementary flux modes to elementary flux vectors: Metabolic pathway analysis with arbitrary linear flux constraints

    Science.gov (United States)

    Klamt, Steffen; Gerstl, Matthias P.; Jungreuthmayer, Christian; Mahadevan, Radhakrishnan; Müller, Stefan

    2017-01-01

    Elementary flux modes (EFMs) emerged as a formal concept to describe metabolic pathways and have become an established tool for constraint-based modeling and metabolic network analysis. EFMs are characteristic (support-minimal) vectors of the flux cone that contains all feasible steady-state flux vectors of a given metabolic network. EFMs account for (homogeneous) linear constraints arising from reaction irreversibilities and the assumption of steady state; however, other (inhomogeneous) linear constraints, such as minimal and maximal reaction rates frequently used by other constraint-based techniques (such as flux balance analysis [FBA]), cannot be directly integrated. These additional constraints further restrict the space of feasible flux vectors and turn the flux cone into a general flux polyhedron in which the concept of EFMs is not directly applicable anymore. For this reason, there has been a conceptual gap between EFM-based (pathway) analysis methods and linear optimization (FBA) techniques, as they operate on different geometric objects. One approach to overcome these limitations was proposed ten years ago and is based on the concept of elementary flux vectors (EFVs). Only recently has the community started to recognize the potential of EFVs for metabolic network analysis. In fact, EFVs exactly represent the conceptual development required to generalize the idea of EFMs from flux cones to flux polyhedra. This work aims to present a concise theoretical and practical introduction to EFVs that is accessible to a broad audience. We highlight the close relationship between EFMs and EFVs and demonstrate that almost all applications of EFMs (in flux cones) are possible for EFVs (in flux polyhedra) as well. In fact, certain properties can only be studied with EFVs. Thus, we conclude that EFVs provide a powerful and unifying framework for constraint-based modeling of metabolic networks. PMID:28406903

  6. Parallel processing of structural integrity analysis codes

    International Nuclear Information System (INIS)

    Swami Prasad, P.; Dutta, B.K.; Kushwaha, H.S.

    1996-01-01

    Structural integrity analysis forms an important role in assessing and demonstrating the safety of nuclear reactor components. This analysis is performed using analytical tools such as Finite Element Method (FEM) with the help of digital computers. The complexity of the problems involved in nuclear engineering demands high speed computation facilities to obtain solutions in reasonable amount of time. Parallel processing systems such as ANUPAM provide an efficient platform for realising the high speed computation. The development and implementation of software on parallel processing systems is an interesting and challenging task. The data and algorithm structure of the codes plays an important role in exploiting the parallel processing system capabilities. Structural analysis codes based on FEM can be divided into two categories with respect to their implementation on parallel processing systems. The first category codes such as those used for harmonic analysis, mechanistic fuel performance codes need not require the parallelisation of individual modules of the codes. The second category of codes such as conventional FEM codes require parallelisation of individual modules. In this category, parallelisation of equation solution module poses major difficulties. Different solution schemes such as domain decomposition method (DDM), parallel active column solver and substructuring method are currently used on parallel processing systems. Two codes, FAIR and TABS belonging to each of these categories have been implemented on ANUPAM. The implementation details of these codes and the performance of different equation solvers are highlighted. (author). 5 refs., 12 figs., 1 tab

  7. Modelling and performance analysis of clinical pathways using the stochastic process algebra PEPA.

    Science.gov (United States)

    Yang, Xian; Han, Rui; Guo, Yike; Bradley, Jeremy; Cox, Benita; Dickinson, Robert; Kitney, Richard

    2012-01-01

    Hospitals nowadays have to serve numerous patients with limited medical staff and equipment while maintaining healthcare quality. Clinical pathway informatics is regarded as an efficient way to solve a series of hospital challenges. To date, conventional research lacks a mathematical model to describe clinical pathways. Existing vague descriptions cannot fully capture the complexities accurately in clinical pathways and hinders the effective management and further optimization of clinical pathways. Given this motivation, this paper presents a clinical pathway management platform, the Imperial Clinical Pathway Analyzer (ICPA). By extending the stochastic model performance evaluation process algebra (PEPA), ICPA introduces a clinical-pathway-specific model: clinical pathway PEPA (CPP). ICPA can simulate stochastic behaviours of a clinical pathway by extracting information from public clinical databases and other related documents using CPP. Thus, the performance of this clinical pathway, including its throughput, resource utilisation and passage time can be quantitatively analysed. A typical clinical pathway on stroke extracted from a UK hospital is used to illustrate the effectiveness of ICPA. Three application scenarios are tested using ICPA: 1) redundant resources are identified and removed, thus the number of patients being served is maintained with less cost; 2) the patient passage time is estimated, providing the likelihood that patients can leave hospital within a specific period; 3) the maximum number of input patients are found, helping hospitals to decide whether they can serve more patients with the existing resource allocation. ICPA is an effective platform for clinical pathway management: 1) ICPA can describe a variety of components (state, activity, resource and constraints) in a clinical pathway, thus facilitating the proper understanding of complexities involved in it; 2) ICPA supports the performance analysis of clinical pathway, thereby assisting

  8. Analysis of Chlorogenic Acid Oxidation Pathway in Simulated ...

    African Journals Online (AJOL)

    Purpose: To investigate the pathways involved in the oxidation of chlorogenic acid (CA) and phenol metabolism in honeysuckle buds. Methods: A model that mimics CA oxidation by honeysuckle polyphenol oxidase (PPO) by controlling the reaction temperature or reaction duration was employed, and the resulting products ...

  9. Pathway analysis for identification of potential biomarkers in severe ...

    African Journals Online (AJOL)

    It was found by geneMANIA database search that majority of these genes were coexpressed yielding 84.63 % co-expression. It was found that ten genes were in Physical interactions comprising almost 14.33 %. There were < 1 % pathway and genetic interactions with values of 0.97 and 0.06 %, respectively. Final analyses ...

  10. Analysis of Chlorogenic Acid Oxidation Pathway in Simulated ...

    African Journals Online (AJOL)

    Keywords: Honeysuckle, Chlorogenic acid, Enzymatic browning, Mimic system, Oxidation pathway, ... enzymatic oxidation of CA is the major cause of ..... to the concentration of catechol, o-quinone and current at PPO-modified microcylinder biosensor for diffusion- kinetic model. J Electroanal Chem 2011; 660: 200-208.

  11. Pan-cancer analysis of TCGA data reveals notable signaling pathways

    International Nuclear Information System (INIS)

    Neapolitan, Richard; Horvath, Curt M.; Jiang, Xia

    2015-01-01

    A signal transduction pathway (STP) is a network of intercellular information flow initiated when extracellular signaling molecules bind to cell-surface receptors. Many aberrant STPs have been associated with various cancers. To develop optimal treatments for cancer patients, it is important to discover which STPs are implicated in a cancer or cancer-subtype. The Cancer Genome Atlas (TCGA) makes available gene expression level data on cases and controls in ten different types of cancer including breast cancer, colon adenocarcinoma, glioblastoma, kidney renal papillary cell carcinoma, low grade glioma, lung adenocarcinoma, lung squamous cell carcinoma, ovarian carcinoma, rectum adenocarcinoma, and uterine corpus endometriod carcinoma. Signaling Pathway Impact Analysis (SPIA) is a software package that analyzes gene expression data to identify whether a pathway is relevant in a given condition. We present the results of a study that uses SPIA to investigate all 157 signaling pathways in the KEGG PATHWAY database. We analyzed each of the ten cancer types mentioned above separately, and we perform a pan-cancer analysis by grouping the data for all the cancer types. In each analysis several pathways were found to be markedly more significant than all the other pathways. We call them notable. Research has already established a connection between many of these pathways and the corresponding cancer type. However, some of our discovered pathways appear to be new findings. Altogether there were 37 notable findings in the separate analyses, 26 of them occurred in 7 pathways. These 7 pathways included the 4 notable pathways discovered in the pan-cancer analysis. So, our results suggest that these 7 pathways account for much of the mechanisms of cancer. Furthermore, by looking at the overlap among pathways, we identified possible regions on the pathways where the aberrant activity is occurring. We obtained 37 notable findings concerning 18 pathways. Some of them appear to be

  12. Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway

    DEFF Research Database (Denmark)

    Oka, Yasuyoshi; Bekker-Jensen, Simon; Mailand, Niels

    2015-01-01

    in promoting the function of the Fanconi anemia (FA) pathway for repair of DNA interstrand crosslinks (ICLs), mediated by a specific interaction with the central FA pathway component FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI protein stability, defective FANCI function...

  13. Office of Integrated Assessment and Policy Analysis

    International Nuclear Information System (INIS)

    Parzyck, D.C.

    1980-01-01

    The mission of the Office of Integrated Assessments and Policy Analysis (OIAPA) is to examine current and future policies related to the development and use of energy technologies. The principal ongoing research activity to date has focused on the impacts of several energy sources, including coal, oil shale, solar, and geothermal, from the standpoint of the Resource Conservation and Recovery Act. An additional project has recently been initiated on an evaluation of impacts associated with the implementation of the Toxic Substances Control Act. The impacts of the Resource Conservation and Recovery Act and the Toxic Substances Control Act on energy supply constitute the principal research focus of OIAPA for the near term. From these studies a research approach will be developed to identify certain common elements in the regulatory evaluation cycle as a means of evaluating subsequent environmental, health, and socioeconomic impact. It is planned that an integrated assessment team examine studies completed or underway on the following aspects of major regulations: health, risk assessment, testing protocols, environment control cost/benefits, institutional structures, and facility siting. This examination would assess the methodologies used, determine the general applicability of such studies, and present in a logical form information that appears to have broad general application. A suggested action plan for the State of Tennessee on radioactive and hazardous waste management is outlined

  14. A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions.

    Science.gov (United States)

    Roy, Raktim; Shilpa, P Phani; Bagh, Sangram

    2016-09-01

    Bacteria are important organisms for space missions due to their increased pathogenesis in microgravity that poses risks to the health of astronauts and for projected synthetic biology applications at the space station. We understand little about the effect, at the molecular systems level, of microgravity on bacteria, despite their significant incidence. In this study, we proposed a systems biology pipeline and performed an analysis on published gene expression data sets from multiple seminal studies on Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium under spaceflight and simulated microgravity conditions. By applying gene set enrichment analysis on the global gene expression data, we directly identified a large number of new, statistically significant cellular and metabolic pathways involved in response to microgravity. Alteration of metabolic pathways in microgravity has rarely been reported before, whereas in this analysis metabolic pathways are prevalent. Several of those pathways were found to be common across studies and species, indicating a common cellular response in microgravity. We clustered genes based on their expression patterns using consensus non-negative matrix factorization. The genes from different mathematically stable clusters showed protein-protein association networks with distinct biological functions, suggesting the plausible functional or regulatory network motifs in response to microgravity. The newly identified pathways and networks showed connection with increased survival of pathogens within macrophages, virulence, and antibiotic resistance in microgravity. Our work establishes a systems biology pipeline and provides an integrated insight into the effect of microgravity at the molecular systems level. Systems biology-Microgravity-Pathways and networks-Bacteria. Astrobiology 16, 677-689.

  15. Integrating Data Transformation in Principal Components Analysis

    KAUST Repository

    Maadooliat, Mehdi

    2015-01-02

    Principal component analysis (PCA) is a popular dimension reduction method to reduce the complexity and obtain the informative aspects of high-dimensional datasets. When the data distribution is skewed, data transformation is commonly used prior to applying PCA. Such transformation is usually obtained from previous studies, prior knowledge, or trial-and-error. In this work, we develop a model-based method that integrates data transformation in PCA and finds an appropriate data transformation using the maximum profile likelihood. Extensions of the method to handle functional data and missing values are also developed. Several numerical algorithms are provided for efficient computation. The proposed method is illustrated using simulated and real-world data examples.

  16. Compromised Integrity of Central Visual Pathways in Patients With Macular Degeneration.

    Science.gov (United States)

    Malania, Maka; Konrad, Julia; Jägle, Herbert; Werner, John S; Greenlee, Mark W

    2017-06-01

    Macular degeneration (MD) affects the central retina and leads to gradual loss of foveal vision. Although, photoreceptors are primarily affected in MD, the retinal nerve fiber layer (RNFL) and central visual pathways may also be altered subsequent to photoreceptor degeneration. Here we investigate whether retinal damage caused by MD alters microstructural properties of visual pathways using diffusion-weighted magnetic resonance imaging. Six MD patients and six healthy control subjects participated in the study. Retinal images were obtained by spectral-domain optical coherence tomography (SD-OCT). Diffusion tensor images (DTI) and high-resolution T1-weighted structural images were collected for each subject. We used diffusion-based tensor modeling and probabilistic fiber tractography to identify the optic tract (OT) and optic radiations (OR), as well as nonvisual pathways (corticospinal tract and anterior fibers of corpus callosum). Fractional anisotropy (FA) and axial and radial diffusivity values (AD, RD) were calculated along the nonvisual and visual pathways. Measurement of RNFL thickness reveals that the temporal circumpapillary retinal nerve fiber layer was significantly thinner in eyes with macular degeneration than normal. While we did not find significant differences in diffusion properties in nonvisual pathways, patients showed significant changes in diffusion scalars (FA, RD, and AD) both in OT and OR. The results indicate that the RNFL and the white matter of the visual pathways are significantly altered in MD patients. Damage to the photoreceptors in MD leads to atrophy of the ganglion cell axons and to corresponding changes in microstructural properties of central visual pathways.

  17. EarthConnections: Integrating Community Science and Geoscience Education Pathways for More Resilient Communities.

    Science.gov (United States)

    Manduca, C. A.

    2017-12-01

    To develop a diverse geoscience workforce, the EarthConnections collective impact alliance is developing regionally focused, Earth education pathways. These pathways support and guide students from engagement in relevant, Earth-related science at an early age through the many steps and transitions to geoscience-related careers. Rooted in existing regional activities, pathways are developed using a process that engages regional stakeholders and community members with EarthConnections partners. Together they connect, sequence, and create multiple learning opportunities that link geoscience education and community service to address one or more local geoscience issues. Three initial pilots are demonstrating different starting points and strategies for creating pathways that serve community needs while supporting geoscience education. The San Bernardino pilot is leveraging existing academic relationships and programs; the Atlanta pilot is building into existing community activities; and the Oklahoma Tribal Nations pilot is co-constructing a pathway focus and approach. The project is using pathway mapping and a collective impact framework to support and monitor progress. The goal is to develop processes and activities that can help other communities develop similar community-based geoscience pathways. By intertwining Earth education with local community service we aspire to increase the resilience of communities in the face of environmental hazards and limited Earth resources.

  18. Qualitative Analysis of Integration Adapter Modeling

    OpenAIRE

    Ritter, Daniel; Holzleitner, Manuel

    2015-01-01

    Integration Adapters are a fundamental part of an integration system, since they provide (business) applications access to its messaging channel. However, their modeling and configuration remain under-represented. In previous work, the integration control and data flow syntax and semantics have been expressed in the Business Process Model and Notation (BPMN) as a semantic model for message-based integration, while adapter and the related quality of service modeling were left for further studi...

  19. PHIDIAS- Pathogen Host Interaction Data Integration and Analysis

    Indian Academy of Sciences (India)

    PHIDIAS- Pathogen Host Interaction Data Integration and Analysis- allows searching of integrated genome sequences, conserved domains and gene expressions data related to pathogen host interactions in high priority agents for public health and security ...

  20. An Integrative data mining approach to identifying Adverse Outcome Pathway (AOP) Signatures

    Science.gov (United States)

    The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or populatio...

  1. Integrated QSAR study for inhibitors of Hedgehog Signal Pathway against multiple cell lines:a collaborative filtering method.

    Science.gov (United States)

    Gao, Jun; Che, Dongsheng; Zheng, Vincent W; Zhu, Ruixin; Liu, Qi

    2012-07-31

    The Hedgehog Signaling Pathway is one of signaling pathways that are very important to embryonic development. The participation of inhibitors in the Hedgehog Signal Pathway can control cell growth and death, and searching novel inhibitors to the functioning of the pathway are in a great demand. As the matter of fact, effective inhibitors could provide efficient therapies for a wide range of malignancies, and targeting such pathway in cells represents a promising new paradigm for cell growth and death control. Current research mainly focuses on the syntheses of the inhibitors of cyclopamine derivatives, which bind specifically to the Smo protein, and can be used for cancer therapy. While quantitatively structure-activity relationship (QSAR) studies have been performed for these compounds among different cell lines, none of them have achieved acceptable results in the prediction of activity values of new compounds. In this study, we proposed a novel collaborative QSAR model for inhibitors of the Hedgehog Signaling Pathway by integration the information from multiple cell lines. Such a model is expected to substantially improve the QSAR ability from single cell lines, and provide useful clues in developing clinically effective inhibitors and modifications of parent lead compounds for target on the Hedgehog Signaling Pathway. In this study, we have presented: (1) a collaborative QSAR model, which is used to integrate information among multiple cell lines to boost the QSAR results, rather than only a single cell line QSAR modeling. Our experiments have shown that the performance of our model is significantly better than single cell line QSAR methods; and (2) an efficient feature selection strategy under such collaborative environment, which can derive the commonly important features related to the entire given cell lines, while simultaneously showing their specific contributions to a specific cell-line. Based on feature selection results, we have proposed several

  2. Obsessive-compulsive disorder, which genes? Which functions? Which pathways? An integrated holistic view regarding OCD and its complex genetic etiology.

    Science.gov (United States)

    Bozorgmehr, Ali; Ghadirivasfi, Mohammad; Shahsavand Ananloo, Esmaeil

    2017-09-01

    Obsessive-compulsive disorder (OCD) is characterized by recurrent obtrusive and repetitive acts typically occurred following anxiety. In the last two decades, studies done on the gene sequences, large-scale and point mutations and gene-gene, gene-environment and gene-drug interactions have led to the discovery of hundreds of genes associated with OCD. Although each gene in turn is a part of the etiology of this disorder; however, OCD, like other mental disorders is complex and a comprehensive and integrated view is necessary to understand its genetic basis. In this study, through an extensive review of existing published studies, all genes associated with OCD were found. Then, in order to integrate the results, all the interactions between these genes were explored and the achievement was represented as an interactive genetic network. Furthermore, the reconstructed network was analyzed. It was found that GRIN2A, GRIN2B and GRIA2 are the most central nodes in the network. Functional and pathway enrichment analysis showed that glutamate-related pathways are the main deficient systems in patients with OCD. By studying genes shared between OCD and other diseases, it was cleared that OCD, epilepsy and some types of cancer have the most number of shared genes. The results of this study, in addition to reviewing the available results as a comprehensive and integrated manner, provide new hypotheses for future studies.

  3. Integrating Biological Perspectives:. a Quantum Leap for Microarray Expression Analysis

    Science.gov (United States)

    Wanke, Dierk; Kilian, Joachim; Bloss, Ulrich; Mangelsen, Elke; Supper, Jochen; Harter, Klaus; Berendzen, Kenneth W.

    2009-02-01

    Biologists and bioinformatic scientists cope with the analysis of transcript abundance and the extraction of meaningful information from microarray expression data. By exploiting biological information accessible in public databases, we try to extend our current knowledge over the plant model organism Arabidopsis thaliana. Here, we give two examples of increasing the quality of information gained from large scale expression experiments by the integration of microarray-unrelated biological information: First, we utilize Arabidopsis microarray data to demonstrate that expression profiles are usually conserved between orthologous genes of different organisms. In an initial step of the analysis, orthology has to be inferred unambiguously, which then allows comparison of expression profiles between orthologs. We make use of the publicly available microarray expression data of Arabidopsis and barley, Hordeum vulgare. We found a generally positive correlation in expression trajectories between true orthologs although both organisms are only distantly related in evolutionary time scale. Second, extracting clusters of co-regulated genes implies similarities in transcriptional regulation via similar cis-regulatory elements (CREs). Vice versa approaches, where co-regulated gene clusters are found by investigating on CREs were not successful in general. Nonetheless, in some cases the presence of CREs in a defined position, orientation or CRE-combinations is positively correlated with co-regulated gene clusters. Here, we make use of genes involved in the phenylpropanoid biosynthetic pathway, to give one positive example for this approach.

  4. Linked Analysis of East Asia Emission Reduction Pathways

    Science.gov (United States)

    Kim, Y.; Woo, J. H.; Bu, C.; Lee, Y.; Kim, J.; Jang, Y.; Park, M.

    2017-12-01

    Air pollution and its impacts over the Northeast Asia are very severe because of the massive pollutant emissions and high population. Korea has been trying to improve air quality with the enhanced environmental legislation. The air quality over Korea, however, does not entirely dependent on its local emissions. Transboundary air pollution from China highly affects Korean atmosphere. The purpose of this research is to understand role of local and transbounday efforts to improve air quality changes over Korea. In this research, we have tried to set up the multiple emission scenario pathways for Korea and China using IIASA's GAINS (Greenhouse gas - Air pollution Interactions aNd Synergies) modeling framework. More up-to-date growth factors and control policy packets were made using regional socio-economic data and control policy information from local governments and international statistics. Four major scenario pathways, 1) Base (Baseline: current legislation), 2) OTB/OTB(On the book/On the way : existing control measure/planed control measure), 3) BOTW_GHG(Beyond on the way : OTW with GHG reduction plan), 4) BOTW_NH3 (OTW with additional NH3 reduction measure) were developed to represent air quality improvement pathways in consideration of both Korean and Chinese efforts. Strict ambient PM2.5 standards from Seoul metropolitan Air quality Improvement Plan(SAIP) seems too enthusiastic without linking air quality control efforts of China. Step-by-step emission controls and following air quality, control cost, health impact from each scenario will be presented at the conference. This subject is supported by Korea Ministry of Environment as "Climate Change Correspondence Program". And This work was supported under the framework of national strategy project on fine particulate matters by Ministry of Science, ICT and Future Planning.

  5. Gene prediction validation and functional analysis of redundant pathways

    DEFF Research Database (Denmark)

    Sønderkær, Mads

    2011-01-01

    have employed a large mRNA-seq data set to improve and validate ab initio predicted gene models. This direct experimental evidence also provides reliable determinations of UTR regions and polyadenylation sites, which are not easily predicted in plants. Furthermore, once an annotated genome sequence...... is available, gene expression by mRNA-Seq enables acquisition of a more complete overview of gene isoform usage in complex enzymatic pathways enabling the identification of key genes. Metabolism in potatoes This information is useful e.g. for crop improvement based on manipulation of agronomically important...

  6. Migration in Deltas: An Integrated Analysis

    Science.gov (United States)

    Nicholls, Robert J.; Hutton, Craig W.; Lazar, Attila; Adger, W. Neil; Allan, Andrew; Arto, Inaki; Vincent, Katharine; Rahman, Munsur; Salehin, Mashfiqus; Sugata, Hazra; Ghosh, Tuhin; Codjoe, Sam; Appeaning-Addo, Kwasi

    2017-04-01

    Deltas and low-lying coastal regions have long been perceived as vulnerable to global sea-level rise, with the potential for mass displacement of exposed populations. The assumption of mass displacement of populations in deltas requires a comprehensive reassessment in the light of present and future migration in deltas, including the potential role of adaptation to influence these decisions. At present, deltas are subject to multiple drivers of environmental change and often have high population densities as they are accessible and productive ecosystems. Climate change, catchment management, subsidence and land cover change drive environmental change across all deltas. Populations in deltas are also highly mobile, with significant urbanization trends and the growth of large cities and mega-cities within or adjacent to deltas across Asia and Africa. Such migration is driven primarily by economic opportunity, yet environmental change in general, and climate change in particular, are likely to play an increasing direct and indirect role in future migration trends. The policy challenges centre on the role of migration within regional adaptation strategies to climate change; the protection of vulnerable populations; and the future of urban settlements within deltas. This paper reviews current knowledge on migration and adaptation to environmental change to discern specific issues pertinent to delta regions. It develops a new integrated methodology to assess present and future migration in deltas using the Volta delta in Ghana, Mahanadi delta in India and Ganges-Brahmaputra-Meghna delta across India and Bangladesh. The integrated method focuses on: biophysical changes and spatial distribution of vulnerability; demographic changes and migration decision-making using multiple methods and data; macro-economic trends and scenarios in the deltas; and the policies and governance structures that constrain and enable adaptation. The analysis is facilitated by a range of

  7. Functional Module Analysis for Gene Coexpression Networks with Network Integration.

    Science.gov (United States)

    Zhang, Shuqin; Zhao, Hongyu; Ng, Michael K

    2015-01-01

    Network has been a general tool for studying the complex interactions between different genes, proteins, and other small molecules. Module as a fundamental property of many biological networks has been widely studied and many computational methods have been proposed to identify the modules in an individual network. However, in many cases, a single network is insufficient for module analysis due to the noise in the data or the tuning of parameters when building the biological network. The availability of a large amount of biological networks makes network integration study possible. By integrating such networks, more informative modules for some specific disease can be derived from the networks constructed from different tissues, and consistent factors for different diseases can be inferred. In this paper, we have developed an effective method for module identification from multiple networks under different conditions. The problem is formulated as an optimization model, which combines the module identification in each individual network and alignment of the modules from different networks together. An approximation algorithm based on eigenvector computation is proposed. Our method outperforms the existing methods, especially when the underlying modules in multiple networks are different in simulation studies. We also applied our method to two groups of gene coexpression networks for humans, which include one for three different cancers, and one for three tissues from the morbidly obese patients. We identified 13 modules with three complete subgraphs, and 11 modules with two complete subgraphs, respectively. The modules were validated through Gene Ontology enrichment and KEGG pathway enrichment analysis. We also showed that the main functions of most modules for the corresponding disease have been addressed by other researchers, which may provide the theoretical basis for further studying the modules experimentally.

  8. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes

    Directory of Open Access Journals (Sweden)

    Qingzhu Hua

    2016-09-01

    Full Text Available Red dragon fruit or red pitaya (Hylocereus polyrhizus is the only edible fruit that contains betalains. The color of betalains ranges from red and violet to yellow in plants. Betalains may also serve as an important component of health-promoting and disease-preventing functional food. Currently, the biosynthetic and regulatory pathways for betalain production remain to be fully deciphered. In this study, isobaric tags for relative and absolute quantitation (iTRAQ-based proteomic analyses were used to reveal the molecular mechanism of betalain biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively. A total of 1946 proteins were identified as the differentially expressed between the two samples, and 936 of them were significantly highly expressed at the red pulp stage of H. polyrhizus. RNA-seq and iTRAQ analyses showed that some transcripts and proteins were positively correlated; they belonged to “phenylpropanoid biosynthesis”, “tyrosine metabolism”, “flavonoid biosynthesis”, “ascorbate and aldarate metabolism”, “betalains biosynthesis” and “anthocyanin biosynthesis”. In betalains biosynthesis pathway, several proteins/enzymes such as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA dioxygenase extradiol-like protein were identified. The present study provides a new insight into the molecular mechanism of the betalain biosynthesis at the posttranscriptional level.

  9. Integration of risk analysis, land use planning, and cost analysis

    International Nuclear Information System (INIS)

    Rajen, G.; Sanchez, G.

    1994-01-01

    The Department of Energy (DOE) and the Pueblo of San Ildefonso (Pueblo), which is a sovereign Indian tribe, have often been involved in adversarial situations regarding the Los Alamos National Laboratory (LANL). The Pueblo shares a common boundary with the LANL. This paper describes an on-going project that could alter the DOE and the Pueblo's relationship to one of cooperation; and unite the DOE and the Pueblo in a Pollution Prevention/Waste Minimization, and Integrated Risk Analysis and Land Use Planning effort

  10. Critical Radionuclide and Pathway Analysis for the Savannah River Site, 2016 Update

    Energy Technology Data Exchange (ETDEWEB)

    Jannik, Tim [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hartman, Larry [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-09-08

    During the operational history of Savannah River Site, many different radionuclides have been released from site facilities. However, as shown in this analysis, only a relatively small number of the released radionuclides have been significant contributors to doses to the offsite public. This report is an update to the 2011 analysis, Critical Radionuclide and Pathway Analysis for the Savannah River Site. SRS-based Performance Assessments for E-Area, Saltstone, F-Tank Farm, H-Tank Farm, and a Comprehensive SRS Composite Analysis have been completed. The critical radionuclides and pathways identified in those extensive reports are also detailed and included in this analysis.

  11. A cross-study gene set enrichment analysis identifies critical pathways in endometriosis

    Directory of Open Access Journals (Sweden)

    Bai Chunyan

    2009-09-01

    Full Text Available Abstract Background Endometriosis is an enigmatic disease. Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Some of the observed pathways are more inconsistent between the studies, and these candidate pathways presumably only represent a fraction of the pathways involved in endometriosis. Methods We applied a standardised microarray preprocessing and gene set enrichment analysis to six independent studies, and demonstrated increased concordance between these gene datasets. Results We find 16 up-regulated and 19 down-regulated pathways common in ovarian endometriosis data sets, 22 up-regulated and one down-regulated pathway common in peritoneal endometriosis data sets. Among them, 12 up-regulated and 1 down-regulated were found consistent between ovarian and peritoneal endometriosis. The main canonical pathways identified are related to immunological and inflammatory disease. Early secretory phase has the most over-represented pathways in the three uterine cycle phases. There are no overlapping significant pathways between the dataset from human endometrial endothelial cells and the datasets from ovarian endometriosis which used whole tissues. Conclusion The study of complex diseases through pathway analysis is able to highlight genes weakly connected to the phenotype which may be difficult to detect by using classical univariate statistics. By standardised microarray preprocessing and GSEA, we have increased the concordance in identifying many biological mechanisms involved in endometriosis. The identified gene pathways will shed light on the understanding of endometriosis and promote the development of novel therapies.

  12. Activation of the cell wall integrity pathway promotes escape from G2 in the fungus Ustilago maydis.

    Directory of Open Access Journals (Sweden)

    Natalia Carbó

    2010-07-01

    Full Text Available It is widely accepted that MAPK activation in budding and fission yeasts is often associated with negative effects on cell cycle progression, resulting in delay or arrest at a specific stage in the cell cycle, thereby enabling cells to adapt to changing environmental conditions. For instance, activation of the Cell Wall Integrity (CWI pathway in the budding yeast Saccharomyces cerevisiae signals an increase in CDK inhibitory phosphorylation, which leads cells to remain in the G2 phase. Here we characterized the CWI pathway of Ustilago maydis, a fungus evolutionarily distant from budding and fission yeasts, and show that activation of the CWI pathway forces cells to escape from G2 phase. In spite of these disparate cell cycle responses in S. cerevisiae and U. maydis, the CWI pathway in both organisms appears to respond to the same class cell wall stressors. To understand the basis of such a difference, we studied the mechanism behind the U. maydis response. We found that activation of CWI pathway in U. maydis results in a decrease in CDK inhibitory phosphorylation, which depends on the mitotic phosphatase Cdc25. Moreover, in response to activation of the CWI pathway, Cdc25 accumulates in the nucleus, providing a likely explanation for the increase in the unphosphorylated form of CDK. We also found that the extended N-terminal domain of Cdc25, which is dispensable under normal growth conditions, is required for this G2 escape as well as for resistance to cell wall stressors. We propose that the process of cell cycle adaptation to cell stress evolved differently in these two divergent organisms so that each can move towards a cell cycle phase most appropriate for responding to the environmental signals encountered.

  13. Representative Agricultural Pathways and Scenarios for Regional Integrated Assessment of Climate Change Impacts, Vulnerability, and Adaptation. 5; Chapter

    Science.gov (United States)

    Valdivia, Roberto O.; Antle, John M.; Rosenzweig, Cynthia; Ruane, Alexander C.; Vervoort, Joost; Ashfaq, Muhammad; Hathie, Ibrahima; Tui, Sabine Homann-Kee; Mulwa, Richard; Nhemachena, Charles; hide

    2015-01-01

    The global change research community has recognized that new pathway and scenario concepts are needed to implement impact and vulnerability assessment where precise prediction is not possible, and also that these scenarios need to be logically consistent across local, regional, and global scales. For global climate models, representative concentration pathways (RCPs) have been developed that provide a range of time-series of atmospheric greenhouse-gas concentrations into the future. For impact and vulnerability assessment, new socio-economic pathway and scenario concepts have also been developed, with leadership from the Integrated Assessment Modeling Consortium (IAMC).This chapter presents concepts and methods for development of regional representative agricultural pathways (RAOs) and scenarios that can be used for agricultural model intercomparison, improvement, and impact assessment in a manner consistent with the new global pathways and scenarios. The development of agriculture-specific pathways and scenarios is motivated by the need for a protocol-based approach to climate impact, vulnerability, and adaptation assessment. Until now, the various global and regional models used for agricultural-impact assessment have been implemented with individualized scenarios using various data and model structures, often without transparent documentation, public availability, and consistency across disciplines. These practices have reduced the credibility of assessments, and also hampered the advancement of the science through model intercomparison, improvement, and synthesis of model results across studies. The recognition of the need for better coordination among the agricultural modeling community, including the development of standard reference scenarios with adequate agriculture-specific detail led to the creation of the Agricultural Model Intercomparison and Improvement Project (AgMIP) in 2010. The development of RAPs is one of the cross-cutting themes in AgMIP's work

  14. IMP: Integrated method for power analysis

    Energy Technology Data Exchange (ETDEWEB)

    1989-03-01

    An integrated, easy to use, economical package of microcomputer programs has been developed which can be used by small hydro developers to evaluate potential sites for small scale hydroelectric plants in British Columbia. The programs enable evaluation of sites located far from the nearest stream gauging station, for which streamflow data are not available. For each of the province's 6 hydrologic regions, a streamflow record for one small watershed is provided in the data base. The program can then be used to generate synthetic streamflow records and to compare results obtained by the modelling procedure with the actual data. The program can also be used to explore the significance of modelling parameters and to develop a detailed appreciation for the accuracy which can be obtained under various circumstances. The components of the program are an atmospheric model of precipitation; a watershed model that will generate a continuous series of streamflow data, based on information from the atmospheric model; a flood frequency analysis system that uses site-specific topographic data plus information from the atmospheric model to generate a flood frequency curve; a hydroelectric power simulation program which determines daily energy output for a run-of-river or reservoir storage site based on selected generation facilities and the time series generated in the watershed model; and a graphic analysis package that provides direct visualization of data and modelling results. This report contains a description of the programs, a user guide, the theory behind the model, the modelling methodology, and results from a workshop that reviewed the program package. 32 refs., 16 figs., 18 tabs.

  15. Elucidating novel dysfunctional pathways in Alzheimer's disease by integrating loci identified in genetic and epigenetic studies

    Directory of Open Access Journals (Sweden)

    Adam R. Smith

    2016-06-01

    Full Text Available Alzheimer's disease is a complex neurodegenerative disorder. A large number of genome-wide association studies have been performed, which have been supplemented more recently by the first epigenome-wide association studies, leading to the identification of a number of novel loci altered in disease. Twin studies have shown monozygotic twin discordance for Alzheimer's disease (Gatz et al., 2006, leading to the conclusion that a combination of genetic and epigenetic mechanisms is likely to be involved in disease etiology (Lunnon & Mill, 2013. This review focuses on identifying overlapping pathways between published genome-wide association studies and epigenome-wide association studies, highlighting dysfunctional synaptic, lipid metabolism, plasma membrane/cytoskeleton, mitochondrial, and immune cell activation pathways. Identifying common pathways altered in genetic and epigenetic studies will aid our understanding of disease mechanisms and identify potential novel targets for pharmacological intervention.

  16. K West integrated water treatment system subproject safety analysis document

    International Nuclear Information System (INIS)

    SEMMENS, L.S.

    1999-01-01

    This Accident Analysis evaluates unmitigated accident scenarios, and identifies Safety Significant and Safety Class structures, systems, and components for the K West Integrated Water Treatment System

  17. K West integrated water treatment system subproject safety analysis document

    Energy Technology Data Exchange (ETDEWEB)

    SEMMENS, L.S.

    1999-02-24

    This Accident Analysis evaluates unmitigated accident scenarios, and identifies Safety Significant and Safety Class structures, systems, and components for the K West Integrated Water Treatment System.

  18. A method for integrating and ranking the evidence for biochemical pathways by mining reactions from text

    Science.gov (United States)

    Miwa, Makoto; Ohta, Tomoko; Rak, Rafal; Rowley, Andrew; Kell, Douglas B.; Pyysalo, Sampo; Ananiadou, Sophia

    2013-01-01

    Motivation: To create, verify and maintain pathway models, curators must discover and assess knowledge distributed over the vast body of biological literature. Methods supporting these tasks must understand both the pathway model representations and the natural language in the literature. These methods should identify and order documents by relevance to any given pathway reaction. No existing system has addressed all aspects of this challenge. Method: We present novel methods for associating pathway model reactions with relevant publications. Our approach extracts the reactions directly from the models and then turns them into queries for three text mining-based MEDLINE literature search systems. These queries are executed, and the resulting documents are combined and ranked according to their relevance to the reactions of interest. We manually annotate document-reaction pairs with the relevance of the document to the reaction and use this annotation to study several ranking methods, using various heuristic and machine-learning approaches. Results: Our evaluation shows that the annotated document-reaction pairs can be used to create a rule-based document ranking system, and that machine learning can be used to rank documents by their relevance to pathway reactions. We find that a Support Vector Machine-based system outperforms several baselines and matches the performance of the rule-based system. The success of the query extraction and ranking methods are used to update our existing pathway search system, PathText. Availability: An online demonstration of PathText 2 and the annotated corpus are available for research purposes at http://www.nactem.ac.uk/pathtext2/. Contact: makoto.miwa@manchester.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23813008

  19. Integrating health and environmental impact analysis.

    Science.gov (United States)

    Reis, S; Morris, G; Fleming, L E; Beck, S; Taylor, T; White, M; Depledge, M H; Steinle, S; Sabel, C E; Cowie, H; Hurley, F; Dick, J McP; Smith, R I; Austen, M

    2015-10-01

    Scientific investigations have progressively refined our understanding of the influence of the environment on human health, and the many adverse impacts that human activities exert on the environment, from the local to the planetary level. Nonetheless, throughout the modern public health era, health has been pursued as though our lives and lifestyles are disconnected from ecosystems and their component organisms. The inadequacy of the societal and public health response to obesity, health inequities, and especially global environmental and climate change now calls for an ecological approach which addresses human activity in all its social, economic and cultural complexity. The new approach must be integral to, and interactive, with the natural environment. We see the continuing failure to truly integrate human health and environmental impact analysis as deeply damaging, and we propose a new conceptual model, the ecosystems-enriched Drivers, Pressures, State, Exposure, Effects, Actions or 'eDPSEEA' model, to address this shortcoming. The model recognizes convergence between the concept of ecosystems services which provides a human health and well-being slant to the value of ecosystems while equally emphasizing the health of the environment, and the growing calls for 'ecological public health' as a response to global environmental concerns now suffusing the discourse in public health. More revolution than evolution, ecological public health will demand new perspectives regarding the interconnections among society, the economy, the environment and our health and well-being. Success must be built on collaborations between the disparate scientific communities of the environmental sciences and public health as well as interactions with social scientists, economists and the legal profession. It will require outreach to political and other stakeholders including a currently largely disengaged general public. The need for an effective and robust science-policy interface has

  20. Noise analysis of switched integrator preamplifiers

    International Nuclear Information System (INIS)

    Sun Hongbo; Li Yulan; Zhu Weibin

    2004-01-01

    The main noise sources of switched integrator preamplifiers are discussed, and their noise performance are given combined PSpice simulation and experiments on them. Then, some practical methods on how to reduce noise of preamplifiers in two different integrator modes are provided. (authors)

  1. Social Ecological Model Analysis for ICT Integration

    Science.gov (United States)

    Zagami, Jason

    2013-01-01

    ICT integration of teacher preparation programmes was undertaken by the Australian Teaching Teachers for the Future (TTF) project in all 39 Australian teacher education institutions and highlighted the need for guidelines to inform systemic ICT integration approaches. A Social Ecological Model (SEM) was used to positively inform integration…

  2. Triple phase boundary specific pathway analysis for quantitative characterization of solid oxide cell electrode microstructure

    DEFF Research Database (Denmark)

    Jørgensen, Peter Stanley; Ebbehøj, Søren Lyng; Hauch, Anne

    2015-01-01

    of the pathways through which they can be reached. New methods for performing TPB specific pathway analysis on 3D image data are introduced, analyzing the pathway properties of each TPB site in the electrode structure. The methods seek to provide additional information beyond whether the TPB sites are percolating......The density and percolation of Triple phase boundary sites are important quantities in analyzing microstructures of solid oxide fuel cell electrodes from tomography data. However, these measures do not provide descriptions of the quality of the TPB sites in terms of the length and radius...... or not by also analyzing the pathway length to the TPB sites and the bottleneck radius of the pathway. We show how these methods can be utilized in quantifying and relating the TPB specific results to cell test data of an electrode reduction protocol study for Ni/Scandia-and-Yttria-doped-Zirconia (Ni...

  3. Chicken hepatic response to chronic heat stress using integrated transcriptome and metabolome analysis.

    Directory of Open Access Journals (Sweden)

    Sara F Jastrebski

    Full Text Available The liver plays a central role in metabolism and is important in maintaining homeostasis throughout the body. This study integrated transcriptomic and metabolomic data to understand how the liver responds under chronic heat stress. Chickens from a rapidly growing broiler line were heat stressed for 8 hours per day for one week and liver samples were collected at 28 days post hatch. Transcriptome analysis reveals changes in genes responsible for cell cycle regulation, DNA replication, and DNA repair along with immune function. Integrating the metabolome and transcriptome data highlighted multiple pathways affected by heat stress including glucose, amino acid, and lipid metabolism along with glutathione production and beta-oxidation.

  4. Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway.

    Science.gov (United States)

    Oka, Yasuyoshi; Bekker-Jensen, Simon; Mailand, Niels

    2015-05-12

    Ubiquitin and ubiquitin-like proteins (UBLs) function in a wide array of cellular processes. UBL5 is an atypical UBL that does not form covalent conjugates with cellular proteins and which has a known role in modulating pre-mRNA splicing. Here, we report an unexpected involvement of human UBL5 in promoting the function of the Fanconi anemia (FA) pathway for repair of DNA interstrand crosslinks (ICLs), mediated by a specific interaction with the central FA pathway component FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI protein stability, defective FANCI function in response to DNA damage and hypersensitivity to ICLs. By mapping the sequence determinants underlying UBL5-FANCI binding, we generated separation-of-function mutants to demonstrate that key aspects of FA pathway function, including FANCI-FANCD2 heterodimerization, FANCD2 and FANCI monoubiquitylation and maintenance of chromosome stability after ICLs, are compromised when the UBL5-FANCI interaction is selectively inhibited by mutations in either protein. Together, our findings establish UBL5 as a factor that promotes the functionality of the FA DNA repair pathway. © 2015 The Authors.

  5. An Institutional Three-Stage Framework: Elevating Academic Writing and Integrity Standards of International Pathway Students

    Science.gov (United States)

    Velliaris, Donna M.; Breen, Paul

    2016-01-01

    In this paper, the authors explore a holistic three-stage framework currently used by the Eynesbury Institute of Business and Technology (EIBT), focused on academic staff identification and remediation processes for the prevention of (un)intentional student plagiarism. As a pre-university pathway provider--whose student body is 98%…

  6. Uncovering transcription factor and microRNA risk regulatory pathways associated with osteoarthritis by network analysis.

    Science.gov (United States)

    Song, Zhenhua; Zhang, Chi; He, Lingxiao; Sui, Yanfang; Lin, Xiafei; Pan, Jingjing

    2018-05-01

    Osteoarthritis (OA) is the most common form of joint disease. The development of inflammation have been considered to play a key role during the progression of OA. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, deciphering these risk regulatory pathways is critical for elucidating the mechanisms underlying OA. We constructed an OA-specific regulatory network by integrating comprehensive curated transcription and post-transcriptional resource involving transcription factor (TF) and microRNA (miRNA). To deepen our understanding of underlying molecular mechanisms of OA, we developed an integrated systems approach to identify OA-specific risk regulatory pathways. In this study, we identified 89 significantly differentially expressed genes between normal and inflamed areas of OA patients. We found the OA-specific regulatory network was a standard scale-free network with small-world properties. It significant enriched many immune response-related functions including leukocyte differentiation, myeloid differentiation and T cell activation. Finally, 141 risk regulatory pathways were identified based on OA-specific regulatory network, which contains some known regulator of OA. The risk regulatory pathways may provide clues for the etiology of OA and be a potential resource for the discovery of novel OA-associated disease genes. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. CFD Analysis for Advanced Integrated Head Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Won Ho; Kang, Tae Kyo; Cho, Yeon Ho; Kim, Hyun Min [KEPCO Engineering and Construction Co., Daejeon (Korea, Republic of)

    2016-10-15

    The Integrated Head Assembly (IHA) is permanently installed on the reactor vessel closure head during the normal plant operation and refueling operation. It consists of a number of systems and components such as the head lifting system, seismic support system, Control Element Drive Mechanism (CEDM) cooling system, cable support system, cooling shroud assemblies. With the operating experiences of the IHA, the needs for the design change to the current APR1400 IHA arouse to improve the seismic resistance and to accommodate the convenient maintenance. In this paper, the effects of the design changes were rigorously studied for the various sizes of the inlet openings to assure the proper cooling of the CEDMs. And the system pressure differentials and required flow rate for the CEDM cooling fan were analyzed regarding the various operating conditions for determining the capacity of the fan. As a part of the design process of the AIHA, the number of air inlets and baffle regions are reduced by simplifying the design of the APR1400 IHA. The design change of the baffle regions has been made such that the maximum possible space are occupied inside the IHA cooling shroud shell while avoiding the interference with CEDMs. So, only the air inlet opening was studied for the design change to supply a sufficient cooling air flow for each CEDM. The size and location of the air inlets in middle cooling shroud assembly were determined by the CFD analyses of the AIHA. And the case CFD analyses were performed depending on the ambient air temperature and fan operating conditions. The size of the air inlet openings is increased by comparison with the initial AIHA design, and it is confirmed that the cooling air flow rate for each CEDM meet the design requirement of 800 SCFM ± 10% with the increased air inlets. At the initial analysis, the fan outlet flow rate was assumed as 48.3 lbm/s, but the result revealed that the less outflow rate at the fan is enough to meet the design requirement

  8. Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma.

    Science.gov (United States)

    McGuire, Mary F; Sriram Iyengar, M; Mercer, David W

    2012-04-01

    Although trauma is the leading cause of death for those below 45years of age, there is a dearth of information about the temporal behavior of the underlying biological mechanisms in those who survive the initial trauma only to later suffer from syndromes such as multiple organ failure. Levels of serum cytokines potentially affect the clinical outcomes of trauma; understanding how cytokine levels modulate intra-cellular signaling pathways can yield insights into molecular mechanisms of disease progression and help to identify targeted therapies. However, developing such analyses is challenging since it necessitates the integration and interpretation of large amounts of heterogeneous, quantitative and qualitative data. Here we present the Pathway Semantics Algorithm (PSA), an algebraic process of node and edge analyses of evoked biological pathways over time for in silico discovery of biomedical hypotheses, using data from a prospective controlled clinical study of the role of cytokines in multiple organ failure (MOF) at a major US trauma center. A matrix algebra approach was used in both the PSA node and PSA edge analyses with different matrix configurations and computations based on the biomedical questions to be examined. In the edge analysis, a percentage measure of crosstalk called XTALK was also developed to assess cross-pathway interference. In the node/molecular analysis of the first 24h from trauma, PSA uncovered seven molecules evoked computationally that differentiated outcomes of MOF or non-MOF (NMOF), of which three molecules had not been previously associated with any shock/trauma syndrome. In the edge/molecular interaction analysis, PSA examined four categories of functional molecular interaction relationships--activation, expression, inhibition, and transcription--and found that the interaction patterns and crosstalk changed over time and outcome. The PSA edge analysis suggests that a diagnosis, prognosis or therapy based on molecular interaction

  9. Sensitivity Analysis for Design Optimization Integrated Software Tools, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of this proposed project is to provide a new set of sensitivity analysis theory and codes, the Sensitivity Analysis for Design Optimization Integrated...

  10. Effects of clinical pathways in the joint replacement: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Faggiano F

    2009-07-01

    Full Text Available Abstract Background A meta-analysis was performed to evaluate the use of clinical pathways for hip and knee joint replacements when compared with standard medical care. The impact of clinical pathways was evaluated assessing the major outcomes of in-hospital hip and knee joint replacement processes: postoperative complications, number of patients discharged at home, length of in-hospital stay and direct costs. Methods Medline, Cinahl, Embase and the Cochrane Central Register of Controlled Trials were searched. The search was performed from 1975 to 2007. Each study was assessed independently by two reviewers. The assessment of methodological quality of the included studies was based on the Jadad methodological approach and on the New Castle Ottawa Scale. Data analysis abided by the guidelines set out by The Cochrane Collaboration regarding statistical methods. Meta-analyses were performed using RevMan software, version 4.2. Results Twenty-two studies met the study inclusion criteria and were included in the meta-analysis for a total sample of 6,316 patients. The aggregate overall results showed significantly fewer patients suffering postoperative complications in the clinical pathways group when compared with the standard care group. A shorter length of stay in the clinical pathway group was also observed and lower costs during hospital stay were associated with the use of the clinical pathways. No significant differences were found in the rates of discharge to home. Conclusion The results of this meta-analysis show that clinical pathways can significantly improve the quality of care even if it is not possible to conclude that the implementation of clinical pathways is a cost-effective process, because none of the included studies analysed the cost of the development and implementation of the pathways. Based on the results we assume that pathways have impact on the organisation of care if the care process is structured in a standardised way

  11. Game analysis of product-service integration

    Directory of Open Access Journals (Sweden)

    Heping Zhong

    2014-10-01

    Full Text Available Purpose: This paper aims at defining the value creation mechanism and income distribution strategies of product-service integration in order to promote product-service integration of a firm.Design/methodology/approach: This paper conducts researches quantitatively on the coordination mechanism of product-service integration by using game theory, and uses the methods of Shapley value and Equal growth rate to further discuss income distribution strategies of product-service integration.Findings: Product-service integration increases the total income of a firm and the added value of the income decreases as the unit price demand variation coefficient of products and services increases, while decreases as the marginal cost of products increases, decreases as the marginal cost of services increases. Moreover, the findings suggest that both income distribution strategies of product-service integration based on Shapley value method and Equal growth rate method can make the product department and service department of a firm win-win and realize the pareto improvement. The choice of what kind of distribution strategy to coordinate the actions between departments depends on the department playing dominant role in the firm. Generally speaking, for a firm at the center of market, when the product department is the main contributor to firm income, the service department will choose the income distribution strategy of product-service integration based on Shapley value method; when the service department is the main contributor to firm income, the service department will choose the income distribution strategy of product-service integration based on Equal growth rate method.Research limitations/implications: This paper makes some strict assumptions such as complete information, risk neutral, linear cost function and so on and the discussion is limited to the simple relationship between product department and service department.Practical implications: Product

  12. atBioNet– an integrated network analysis tool for genomics and biomarker discovery

    Directory of Open Access Journals (Sweden)

    Ding Yijun

    2012-07-01

    Full Text Available Abstract Background Large amounts of mammalian protein-protein interaction (PPI data have been generated and are available for public use. From a systems biology perspective, Proteins/genes interactions encode the key mechanisms distinguishing disease and health, and such mechanisms can be uncovered through network analysis. An effective network analysis tool should integrate different content-specific PPI databases into a comprehensive network format with a user-friendly platform to identify key functional modules/pathways and the underlying mechanisms of disease and toxicity. Results atBioNet integrates seven publicly available PPI databases into a network-specific knowledge base. Knowledge expansion is achieved by expanding a user supplied proteins/genes list with interactions from its integrated PPI network. The statistically significant functional modules are determined by applying a fast network-clustering algorithm (SCAN: a Structural Clustering Algorithm for Networks. The functional modules can be visualized either separately or together in the context of the whole network. Integration of pathway information enables enrichment analysis and assessment of the biological function of modules. Three case studies are presented using publicly available disease gene signatures as a basis to discover new biomarkers for acute leukemia, systemic lupus erythematosus, and breast cancer. The results demonstrated that atBioNet can not only identify functional modules and pathways related to the studied diseases, but this information can also be used to hypothesize novel biomarkers for future analysis. Conclusion atBioNet is a free web-based network analysis tool that provides a systematic insight into proteins/genes interactions through examining significant functional modules. The identified functional modules are useful for determining underlying mechanisms of disease and biomarker discovery. It can be accessed at: http

  13. atBioNet--an integrated network analysis tool for genomics and biomarker discovery.

    Science.gov (United States)

    Ding, Yijun; Chen, Minjun; Liu, Zhichao; Ding, Don; Ye, Yanbin; Zhang, Min; Kelly, Reagan; Guo, Li; Su, Zhenqiang; Harris, Stephen C; Qian, Feng; Ge, Weigong; Fang, Hong; Xu, Xiaowei; Tong, Weida

    2012-07-20

    Large amounts of mammalian protein-protein interaction (PPI) data have been generated and are available for public use. From a systems biology perspective, Proteins/genes interactions encode the key mechanisms distinguishing disease and health, and such mechanisms can be uncovered through network analysis. An effective network analysis tool should integrate different content-specific PPI databases into a comprehensive network format with a user-friendly platform to identify key functional modules/pathways and the underlying mechanisms of disease and toxicity. atBioNet integrates seven publicly available PPI databases into a network-specific knowledge base. Knowledge expansion is achieved by expanding a user supplied proteins/genes list with interactions from its integrated PPI network. The statistically significant functional modules are determined by applying a fast network-clustering algorithm (SCAN: a Structural Clustering Algorithm for Networks). The functional modules can be visualized either separately or together in the context of the whole network. Integration of pathway information enables enrichment analysis and assessment of the biological function of modules. Three case studies are presented using publicly available disease gene signatures as a basis to discover new biomarkers for acute leukemia, systemic lupus erythematosus, and breast cancer. The results demonstrated that atBioNet can not only identify functional modules and pathways related to the studied diseases, but this information can also be used to hypothesize novel biomarkers for future analysis. atBioNet is a free web-based network analysis tool that provides a systematic insight into proteins/genes interactions through examining significant functional modules. The identified functional modules are useful for determining underlying mechanisms of disease and biomarker discovery. It can be accessed at: http://www.fda.gov/ScienceResearch/BioinformaticsTools/ucm285284.htm.

  14. A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

    Science.gov (United States)

    Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

    2017-09-01

    The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

  15. Advanced Concept Architecture Design and Integrated Analysis (ACADIA)

    Science.gov (United States)

    2017-11-03

    1 Advanced Concept Architecture Design and Integrated Analysis (ACADIA) Submitted to the National Institute of Aerospace (NIA) on...Research Report 20161001 - 20161030 Advanced Concept Architecture Design and Integrated Analysis (ACADIA) W911NF-16-2-0229 8504Cedric Justin, Youngjun

  16. Integrating fire management analysis into land management planning

    Science.gov (United States)

    Thomas J. Mills

    1983-01-01

    The analysis of alternative fire management programs should be integrated into the land and resource management planning process, but a single fire management analysis model cannot meet all planning needs. Therefore, a set of simulation models that are analytically separate from integrated land management planning models are required. The design of four levels of fire...

  17. Ties that bind: the integration of plastid signalling pathways in plant cell metabolism.

    Science.gov (United States)

    Brunkard, Jacob O; Burch-Smith, Tessa M

    2018-04-13

    Plastids are critical organelles in plant cells that perform diverse functions and are central to many metabolic pathways. Beyond their major roles in primary metabolism, of which their role in photosynthesis is perhaps best known, plastids contribute to the biosynthesis of phytohormones and other secondary metabolites, store critical biomolecules, and sense a range of environmental stresses. Accordingly, plastid-derived signals coordinate a host of physiological and developmental processes, often by emitting signalling molecules that regulate the expression of nuclear genes. Several excellent recent reviews have provided broad perspectives on plastid signalling pathways. In this review, we will highlight recent advances in our understanding of chloroplast signalling pathways. Our discussion focuses on new discoveries illuminating how chloroplasts determine life and death decisions in cells and on studies elucidating tetrapyrrole biosynthesis signal transduction networks. We will also examine the role of a plastid RNA helicase, ISE2, in chloroplast signalling, and scrutinize intriguing results investigating the potential role of stromules in conducting signals from the chloroplast to other cellular locations. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  18. Well-to-wheels analysis of fast pyrolysis pathways with the GREET model.

    Energy Technology Data Exchange (ETDEWEB)

    Han, J.; Elgowainy, A.; Palou-Rivera, I.; Dunn, J.B.; Wang, M.Q. (Energy Systems)

    2011-12-01

    The pyrolysis of biomass can help produce liquid transportation fuels with properties similar to those of petroleum gasoline and diesel fuel. Argonne National Laboratory conducted a life-cycle (i.e., well-to-wheels [WTW]) analysis of various pyrolysis pathways by expanding and employing the Greenhouse Gases, Regulated Emissions, and Energy Use in Transportation (GREET) model. The WTW energy use and greenhouse gas (GHG) emissions from the pyrolysis pathways were compared with those from the baseline petroleum gasoline and diesel pathways. Various pyrolysis pathway scenarios with a wide variety of possible hydrogen sources, liquid fuel yields, and co-product application and treatment methods were considered. At one extreme, when hydrogen is produced from natural gas and when bio-char is used for process energy needs, the pyrolysis-based liquid fuel yield is high (32% of the dry mass of biomass input). The reductions in WTW fossil energy use and GHG emissions relative to those that occur when baseline petroleum fuels are used, however, is modest, at 50% and 51%, respectively, on a per unit of fuel energy basis. At the other extreme, when hydrogen is produced internally via reforming of pyrolysis oil and when bio-char is sequestered in soil applications, the pyrolysis-based liquid fuel yield is low (15% of the dry mass of biomass input), but the reductions in WTW fossil energy use and GHG emissions are large, at 79% and 96%, respectively, relative to those that occur when baseline petroleum fuels are used. The petroleum energy use in all scenarios was restricted to biomass collection and transportation activities, which resulted in a reduction in WTW petroleum energy use of 92-95% relative to that found when baseline petroleum fuels are used. Internal hydrogen production (i.e., via reforming of pyrolysis oil) significantly reduces fossil fuel use and GHG emissions because the hydrogen from fuel gas or pyrolysis oil (renewable sources) displaces that from fossil fuel

  19. A Pathway-Centered Analysis of Pig Domestication and Breeding in Eurasia

    Directory of Open Access Journals (Sweden)

    Jordi Leno-Colorado

    2017-07-01

    Full Text Available Ascertaining the molecular and physiological basis of domestication and breeding is an active area of research. Due to the current wide distribution of its wild ancestor, the wild boar, the pig (Sus scrofa is an excellent model to study these processes, which occurred independently in East Asia and Europe ca. 9000 yr ago. Analyzing genome variability patterns in terms of metabolic pathways is attractive since it considers the impact of interrelated functions of genes, in contrast to genome-wide scans that treat genes or genome windows in isolation. To that end, we studied 40 wild boars and 123 domestic pig genomes from Asia and Europe when metabolic pathway was the unit of analysis. We computed statistical significance for differentiation (Fst and linkage disequilibrium (nSL statistics at the pathway level. In terms of Fst, we found 21 and 12 pathways significantly differentiated at a q-value 10 significant pathways (in terms of Fst, comprising genes involved in the transduction of a large number of signals, like phospholipase PCLB1, which is expressed in the brain, or ITPR3, which has an important role in taste transduction. In terms of nSL, significant pathways were mainly related to reproductive performance (ovarian steroidogenesis, a similarly important target trait during domestication and modern animal breeding. Different levels of recombination cannot explain these results, since we found no correlation between Fst and recombination rate. However, we did find an increased ratio of deleterious mutations in domestic vs. wild populations, suggesting a relaxed functional constraint associated with the domestication and breeding processes. Purifying selection was, nevertheless, stronger in significantly differentiated pathways than in random pathways, mainly in Europe. We conclude that pathway analysis facilitates the biological interpretation of genome-wide studies. Notably, in the case of pig, behavior played an important role, among other

  20. A Pathway-Centered Analysis of Pig Domestication and Breeding in Eurasia.

    Science.gov (United States)

    Leno-Colorado, Jordi; Hudson, Nick J; Reverter, Antonio; Pérez-Enciso, Miguel

    2017-07-05

    Ascertaining the molecular and physiological basis of domestication and breeding is an active area of research. Due to the current wide distribution of its wild ancestor, the wild boar, the pig ( Sus scrofa ) is an excellent model to study these processes, which occurred independently in East Asia and Europe ca. 9000 yr ago. Analyzing genome variability patterns in terms of metabolic pathways is attractive since it considers the impact of interrelated functions of genes, in contrast to genome-wide scans that treat genes or genome windows in isolation. To that end, we studied 40 wild boars and 123 domestic pig genomes from Asia and Europe when metabolic pathway was the unit of analysis. We computed statistical significance for differentiation (Fst) and linkage disequilibrium (nSL) statistics at the pathway level. In terms of Fst, we found 21 and 12 pathways significantly differentiated at a q -value 10 significant pathways (in terms of Fst), comprising genes involved in the transduction of a large number of signals, like phospholipase PCLB1, which is expressed in the brain, or ITPR3, which has an important role in taste transduction. In terms of nSL, significant pathways were mainly related to reproductive performance (ovarian steroidogenesis), a similarly important target trait during domestication and modern animal breeding. Different levels of recombination cannot explain these results, since we found no correlation between Fst and recombination rate. However, we did find an increased ratio of deleterious mutations in domestic vs. wild populations, suggesting a relaxed functional constraint associated with the domestication and breeding processes. Purifying selection was, nevertheless, stronger in significantly differentiated pathways than in random pathways, mainly in Europe. We conclude that pathway analysis facilitates the biological interpretation of genome-wide studies. Notably, in the case of pig, behavior played an important role, among other physiological

  1. Integrated marketing communications:pathway for enhancing client-costomer relationships

    OpenAIRE

    Kehinde Oladele Joseph

    2010-01-01

    The strategic coordination of marketing communication tools is vital and highly crucial for every result driven organization today. Companies must be able to deliver the right message to their target audience in order to elicit the right results. The objectives of this paper amongst others are to: (i) ascertain whether proper implementation of Integrated Marketing Communications can help reduce the cost of marketing communication or promotional budget. (ii) Establish whether the use of integr...

  2. A functional genomics approach using metabolomics and in silico pathway analysis

    DEFF Research Database (Denmark)

    Förster, Jochen; Gombert, Andreas Karoly; Nielsen, Jens

    2002-01-01

    analysis techniques and changes in the genotype will in many cases lead to different metabolite profiles. Here, a theoretical framework that may be applied to identify the function of orphan genes is presented. The approach is based on a combination of metabolome analysis combined with in silico pathway...

  3. Metabolic pathway analysis using a nash equilibrium approach

    NARCIS (Netherlands)

    Lucia, Angelo; DiMaggio, Peter A.; Alonso-Martinez, Diego

    2018-01-01

    A novel approach to metabolic network analysis using a Nash Equilibrium (NE) formulation is proposed in which enzymes are considered players in a multi-player game. Each player has its own payoff function with the objective of minimizing the Gibbs free energy associated with the biochemical

  4. Pathways to Medical Home Recognition: A Qualitative Comparative Analysis of the PCMH Transformation Process.

    Science.gov (United States)

    Mendel, Peter; Chen, Emily K; Green, Harold D; Armstrong, Courtney; Timbie, Justin W; Kress, Amii M; Friedberg, Mark W; Kahn, Katherine L

    2017-12-15

    To understand the process of practice transformation by identifying pathways for attaining patient-centered medical home (PCMH) recognition. The CMS Federally Qualified Health Center (FQHC) Advanced Primary Care Practice Demonstration was designed to help FQHCs achieve NCQA Level 3 PCMH recognition and improve patient outcomes. We used a stratified random sample of 20 (out of 503) participating sites for this analysis. We developed a conceptual model of structural, cultural, and implementation factors affecting PCMH transformation based on literature and initial qualitative interview themes. We then used conventional cross-case analysis, followed by qualitative comparative analysis (QCA), a cross-case method based on Boolean logic algorithms, to systematically identify pathways (i.e., combinations of factors) associated with attaining-or not attaining-Level 3 recognition. Site-level indicators were derived from semistructured interviews with site leaders at two points in time (mid- and late-implementation) and administrative data collected prior to and during the demonstration period. The QCA results identified five distinct pathways to attaining PCMH recognition and four distinct pathways to not attaining recognition by the end of the demonstration. Across these pathways, one condition (change leader capacity) was common to all pathways for attaining recognition, and another (previous improvement or recognition experience) was absent in all pathways for not attaining recognition. In general, sites could compensate for deficiencies in one factor with capacity in others, but they needed a threshold of strengths in cultural and implementation factors to attain PCMH recognition. Future efforts at primary care transformation should take into account multiple pathways sites may pursue. Sites should be assessed on key cultural and implementation factors, in addition to structural components, in order to differentiate interventions and technical assistance. © Health

  5. Proteomics-based network analysis characterizes biological processes and pathways activated by preconditioned mesenchymal stem cells in cardiac repair mechanisms.

    Science.gov (United States)

    Di Silvestre, Dario; Brambilla, Francesca; Scardoni, Giovanni; Brunetti, Pietro; Motta, Sara; Matteucci, Marco; Laudanna, Carlo; Recchia, Fabio A; Lionetti, Vincenzo; Mauri, Pierluigi

    2017-05-01

    We have demonstrated that intramyocardial delivery of human mesenchymal stem cells preconditioned with a hyaluronan mixed ester of butyric and retinoic acid (MSCp + ) is more effective in preventing the decay of regional myocardial contractility in a swine model of myocardial infarction (MI). However, the understanding of the role of MSCp + in proteomic remodeling of cardiac infarcted tissue is not complete. We therefore sought to perform a comprehensive analysis of the proteome of infarct remote (RZ) and border zone (BZ) of pigs treated with MSCp + or unconditioned stem cells. Heart tissues were analyzed by MudPIT and differentially expressed proteins were selected by a label-free approach based on spectral counting. Protein profiles were evaluated by using PPI networks and their topological analysis. The proteomic remodeling was largely prevented in MSCp + group. Extracellular proteins involved in fibrosis were down-regulated, while energetic pathways were globally up-regulated. Cardioprotectant pathways involved in the production of keto acid metabolites were also activated. Additionally, we found that new hub proteins support the cardioprotective phenotype characterizing the left ventricular BZ treated with MSCp + . In fact, the up-regulation of angiogenic proteins NCL and RAC1 can be explained by the increase of capillary density induced by MSCp + . Our results show that angiogenic pathways appear to be uniquely positioned to integrate signaling with energetic pathways involving cardiac repair. Our findings prompt the use of proteomics-based network analysis to optimize new approaches preventing the post-ischemic proteomic remodeling that may underlie the limited self-repair ability of adult heart. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Real analysis measure theory, integration, and Hilbert spaces

    CERN Document Server

    Stein, Elias M

    2005-01-01

    Real Analysis is the third volume in the Princeton Lectures in Analysis, a series of four textbooks that aim to present, in an integrated manner, the core areas of analysis. Here the focus is on the development of measure and integration theory, differentiation and integration, Hilbert spaces, and Hausdorff measure and fractals. This book reflects the objective of the series as a whole: to make plain the organic unity that exists between the various parts of the subject, and to illustrate the wide applicability of ideas of analysis to other fields of mathematics and science. After

  7. 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.

  8. Bridging arctic pathways: Integrating hydrology, geomorphology and remote sensing in the north

    Science.gov (United States)

    Trochim, Erin D.

    This work presents improved approaches for integrating patterns and processes within hydrology, geomorphology, ecology and permafrost on Arctic landscapes. Emphasis was placed on addressing fundamental interdisciplinary questions using robust, repeatable methods. Water tracks were examined in the foothills of the Brooks Range to ascertain their role within the range of features that transport water in Arctic regions. Classes of water tracks were developed using multiple factor analysis based on their geomorphic, soil and vegetation characteristics. These classes were validated to verify that they were repeatable. Water tracks represented a broad spectrum of patterns and processes primarily driven by surficial geology. This research demonstrated a new approach to better understanding regional hydrological patterns. The locations of the water track classes were mapped using a combination method where intermediate processing of spectral classifications, texture and topography were fed into random forests to identify the water track classes. Overall, the water track classes were best visualized where they were the most discrete from the background landscape in terms of both shape and content. Issues with overlapping and imbalances between water track classes were the biggest challenges. Resolving the spatial locations of different water tracks represents a significant step forward for understanding periglacial landscape dynamics. Leaf area index (LAI) calculations using the gap-method were optimized using normalized difference vegetation index (NDVI) as input for both WorldView-2 and Landsat-7 imagery. The study design used groups to separate the effects of surficial drainage networks and the relative magnitude of change in NDVI over time. LAI values were higher for the WorldView-2 data and for each sensor and group combination the distribution of LAI values was unique. This study indicated that there are tradeoffs between increased spatial resolution and the ability

  9. Integrated risk analysis of global climate change

    International Nuclear Information System (INIS)

    Shlyakhter, Alexander; Wilson, Richard; Valverde A, L.J. Jr.

    1995-01-01

    This paper discusses several factors that should be considered in integrated risk analyses of global climate change. We begin by describing how the problem of global climate change can be subdivided into largely independent parts that can be linked together in an analytically tractable fashion. Uncertainty plays a central role in integrated risk analyses of global climate change. Accordingly, we consider various aspects of uncertainty as they relate to the climate change problem. We also consider the impacts of these uncertainties on various risk management issues, such as sequential decision strategies, value of information, and problems of interregional and intergenerational equity. (author)

  10. Updates to the Corn Ethanol Pathway and Development of an Integrated Corn and Corn Stover Ethanol Pathway in the GREET™ Model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhichao [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division; Dunn, Jennifer B. [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division; Wang, Michael Q. [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division

    2014-09-01

    Corn ethanol, a first-generation biofuel, is the predominant biofuel in the United States. In 2013, the total U.S. ethanol fuel production was 13.3 billion gallons, over 95% of which was produced from corn (RFA, 2014). The 2013 total renewable fuel mandate was 16.6 billion gallons according to the Energy Independence and Security Act (EISA) (U.S. Congress, 2007). Furthermore, until 2020, corn ethanol will make up a large portion of the renewable fuel volume mandated by Renewable Fuels Standard (RFS2). For the GREET1_2014 release, the corn ethanol pathway was subject to updates reflecting changes in corn agriculture and at corn ethanol plants. In the latter case, we especially focused on the incorporation of corn oil as a corn ethanol plant co-product. Section 2 covers these updates. In addition, GREET now includes options to integrate corn grain and corn stover ethanol production on the field and at the biorefinery. These changes are the focus of Section 3.

  11. Integrated Assessment of Shallow-Aquifer Vulnerability to Multiple Contaminants and Drinking-Water Exposure Pathways in Holliston, Massachusetts

    Directory of Open Access Journals (Sweden)

    Birgit Claus Henn

    2017-12-01

    Full Text Available Half of U.S. drinking water comes from aquifers, and very shallow ones (<20 feet to water table are especially vulnerable to anthropogenic contamination. We present the case of Holliston, a Boston, Massachusetts suburb that draws its drinking water from very shallow aquifers, and where metals and solvents have been reported in groundwater. Community concerns focus on water discolored by naturally occurring manganese (Mn, despite reports stating regulatory aesthetic compliance. Epidemiologic studies suggest Mn is a potentially toxic element (PTE for children exposed by the drinking-water pathway at levels near the regulatory aesthetic level. We designed an integrated, community-based project: five sites were profiled for contaminant releases; service areas for wells were modeled; and the capture zone for one vulnerable well was estimated. Manganese, mercury, and trichloroethylene are among 20 contaminants of interest. Findings show that past and/or current exposures to multiple contaminants in drinking water are plausible, satisfying the criteria for complete exposure pathways. This case questions the adequacy of aquifer protection and monitoring regulations, and highlights the need for integrated assessment of multiple contaminants, associated exposures and health risks. It posits that community-researcher partnerships are essential for understanding and solving complex problems.

  12. PyPathway: Python Package for Biological Network Analysis and Visualization.

    Science.gov (United States)

    Xu, Yang; Luo, Xiao-Chun

    2018-05-01

    Life science studies represent one of the biggest generators of large data sets, mainly because of rapid sequencing technological advances. Biological networks including interactive networks and human curated pathways are essential to understand these high-throughput data sets. Biological network analysis offers a method to explore systematically not only the molecular complexity of a particular disease but also the molecular relationships among apparently distinct phenotypes. Currently, several packages for Python community have been developed, such as BioPython and Goatools. However, tools to perform comprehensive network analysis and visualization are still needed. Here, we have developed PyPathway, an extensible free and open source Python package for functional enrichment analysis, network modeling, and network visualization. The network process module supports various interaction network and pathway databases such as Reactome, WikiPathway, STRING, and BioGRID. The network analysis module implements overrepresentation analysis, gene set enrichment analysis, network-based enrichment, and de novo network modeling. Finally, the visualization and data publishing modules enable users to share their analysis by using an easy web application. For package availability, see the first Reference.

  13. Integrated watershed analysis: adapting to changing times

    Science.gov (United States)

    Gordon H. Reeves

    2013-01-01

    Resource managers are increasingly required to conduct integrated analyses of aquatic and terrestrial ecosystems before undertaking any activities. Th ere are a number of research studies on the impacts of management actions on these ecosystems, as well as a growing body of knowledge about ecological processes that aff ect them, particularly aquatic ecosystems, which...

  14. Relay Feedback Analysis for Double Integral Plants

    Directory of Open Access Journals (Sweden)

    Zhen Ye

    2011-01-01

    Full Text Available Double integral plants under relay feedback are studied. Complete results on the uniqueness of solutions, existence, and stability of the limit cycles are established using the point transformation method. Analytical expressions are also given for determining the amplitude and period of a limit cycle from the plant parameters.

  15. Screening key candidate genes and pathways involved in insulinoma by microarray analysis.

    Science.gov (United States)

    Zhou, Wuhua; Gong, Li; Li, Xuefeng; Wan, Yunyan; Wang, Xiangfei; Li, Huili; Jiang, Bin

    2018-06-01

    Insulinoma is a rare type tumor and its genetic features remain largely unknown. This study aimed to search for potential key genes and relevant enriched pathways of insulinoma.The gene expression data from GSE73338 were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified between insulinoma tissues and normal pancreas tissues, followed by pathway enrichment analysis, protein-protein interaction (PPI) network construction, and module analysis. The expressions of candidate key genes were validated by quantitative real-time polymerase chain reaction (RT-PCR) in insulinoma tissues.A total of 1632 DEGs were obtained, including 1117 upregulated genes and 514 downregulated genes. Pathway enrichment results showed that upregulated DEGs were significantly implicated in insulin secretion, and downregulated DEGs were mainly enriched in pancreatic secretion. PPI network analysis revealed 7 hub genes with degrees more than 10, including GCG (glucagon), GCGR (glucagon receptor), PLCB1 (phospholipase C, beta 1), CASR (calcium sensing receptor), F2R (coagulation factor II thrombin receptor), GRM1 (glutamate metabotropic receptor 1), and GRM5 (glutamate metabotropic receptor 5). DEGs involved in the significant modules were enriched in calcium signaling pathway, protein ubiquitination, and platelet degranulation. Quantitative RT-PCR data confirmed that the expression trends of these hub genes were similar to the results of bioinformatic analysis.The present study demonstrated that candidate DEGs and enriched pathways were the potential critical molecule events involved in the development of insulinoma, and these findings were useful for better understanding of insulinoma genesis.

  16. Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yingrong Chen

    2015-01-01

    Full Text Available Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer.

  17. Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways

    Directory of Open Access Journals (Sweden)

    Salcedo Mauricio

    2007-09-01

    Full Text Available Abstract Background Cervical carcinoma (CC is a leading cause of death among women worldwide. Human papilloma virus (HPV is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways. Results We found 2,067 genes significantly up or down-modulated (at least 2-fold in tumor clinical samples compared to normal tissues, representing ~3.7% of analyzed genes. Cervical carcinoma was associated with an important up-regulation of Wnt signaling pathway, which was validated by in situ hybridization in clinical samples. Other up-regulated pathways were those of calcium signaling and MAPK signaling, as well as cell cycle-related genes. There was down-regulation of focal adhesion, TGF-β signaling, among other metabolic pathways. Conclusion This analysis of HPV 16 tumors transcriptome could be useful for the identification of genes and molecular pathways involved in the pathogenesis of cervical carcinoma. Understanding the possible role of these proteins in the pathogenesis of CC deserves further studies.

  18. Energy pathway analysis - a hydrogen fuel cycle framework for system studies

    International Nuclear Information System (INIS)

    Badin, J.S.; Tagore, S.

    1997-01-01

    An analytical framework has been developed that can be used to estimate a range of life-cycle costs and impacts that result from the incremental production, storage, transport, and use of different fuels or energy carriers, such as hydrogen, electricity, natural gas, and gasoline. This information is used in a comparative analysis of energy pathways. The pathways provide the U.S. Department of Energy (DOE) with an indication of near-, mid-, and long-term technologies that have the greatest potential for advancement and can meet the cost goals. The methodology and conceptual issues are discussed. Also presented are results for selected pathways from the E3 (Energy, Economics, Emissions) Pathway Analysis Model. This model will be expanded to consider networks of pathways and to be compatible with a linear programming optimization processor. Scenarios and sets of constraints (energy demands, sources, emissions) will be defined so the effects on energy transformation activities included in the solution and on the total optimized system cost can be investigated. This evaluation will be used as a guide to eliminate technically feasible pathways if they are not cost effective or do not meet the threshold requirements for the market acceptance. (Author)

  19. Endocrine-disrupting Chemicals: Review of Toxicological Mechanisms Using Molecular Pathway Analysis

    Science.gov (United States)

    Yang, Oneyeol; Kim, Hye Lim; Weon, Jong-Il; Seo, Young Rok

    2015-01-01

    Endocrine disruptors are known to cause harmful effects to human through various exposure routes. These chemicals mainly appear to interfere with the endocrine or hormone systems. As importantly, numerous studies have demonstrated that the accumulation of endocrine disruptors can induce fatal disorders including obesity and cancer. Using diverse biological tools, the potential molecular mechanisms related with these diseases by exposure of endocrine disruptors. Recently, pathway analysis, a bioinformatics tool, is being widely used to predict the potential mechanism or biological network of certain chemicals. In this review, we initially summarize the major molecular mechanisms involved in the induction of the above mentioned diseases by endocrine disruptors. Additionally, we provide the potential markers and signaling mechanisms discovered via pathway analysis under exposure to representative endocrine disruptors, bisphenol, diethylhexylphthalate, and nonylphenol. The review emphasizes the importance of pathway analysis using bioinformatics to finding the specific mechanisms of toxic chemicals, including endocrine disruptors. PMID:25853100

  20. Static analysis of a Model of the LDL degradation pathway

    DEFF Research Database (Denmark)

    Pilegaard, Henrik; Nielson, Flemming; Nielson, Hanne Riis

    2005-01-01

    BioAmbients is a derivative of mobile ambients that has shown promise of describing interesting features of the behaviour of biological systems. As for other ambient calculi static program analysis can be used to compute safe approximations of the behavior of modelled systems. We use these tools ...... to model and analyse the production of cholesterol in living cells and show that we are able to pinpoint the difference in behaviour between models of healthy systems and models of mutated systems giving rise to known diseases....

  1. Genomic analysis and selected molecular pathways in rare cancers

    International Nuclear Information System (INIS)

    Liu, Stephen V; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Demeure, Michael J; Ramanathan, Ramesh K; Von Hoff, Daniel D; Barrett, Michael T; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Eng, Cathy

    2012-01-01

    It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer. (paper)

  2. A techno-economic analysis of EU renewable electricity policy pathways in 2030

    International Nuclear Information System (INIS)

    Río, Pablo del; Resch, Gustav; Ortner, Andre; Liebmann, Lukas; Busch, Sebastian; Panzer, Christian

    2017-01-01

    The aim of this paper is to assess several pathways of a harmonised European policy framework for supporting renewable electricity (RES-E) in a 2030 horizon according to different criteria. The pathways combine two main dimensions: degrees of harmonisation and instruments and design elements. A quantitative model-based analysis with the Green-X model is provided. The results of the simulations show that there are small differences between the evaluated cases regarding effectiveness. All the policy pathways score similarly with respect to RES-E deployment, i.e., with different degrees of harmonisation and whether using a feed-in tariff, a feed-in premium, a quota system with banding or a quota without banding scheme. In contrast, the policy costs clearly differ across the pathways, but the differences can mostly be attributed to the instruments rather than to the degrees of harmonisation. This is also the case with other criteria (static and dynamic efficiency and the socioeconomic and environmental benefits in terms of CO2 emissions and fossil fuels avoided). Both the degree of harmonisation and the choice of instrument influence the distribution of support costs across countries. Finally, our findings suggest that keeping strengthened national support leads to similar results to other policy pathways. - Highlights: • Pathways of a harmonised European policy framework for renewable electricity in 2030. • Two main dimensions: degrees of harmonisation and instruments. • A quantitative model-based analysis based on the Green-X model. • Small differences between the pathways regarding the effectiveness criterion. • Important differences between pathways regarding other assessment criteria.

  3. Pathway analysis of systemic transcriptome responses to injected polystyrene particles in zebrafish larvae.

    Science.gov (United States)

    Veneman, Wouter J; Spaink, Herman P; Brun, Nadja R; Bosker, Thijs; Vijver, Martina G

    2017-09-01

    Microplastics are a contaminant of emergent concern in the environment, however, to date there is a limited understanding on their movement within organisms and the response of organisms. In the current study zebrafish embryos at different development stages were exposed to 700nm fluorescent polystyrene (PS) particles and the response pathway after exposure was investigated using imaging and transcriptomics. Our results show limited spreading of particles within the larvae after injection during the blastula stage. This is in contrast to injection of PS particles in the yolk of 2-day old embryos, which resulted in redistribution of the PS particles throughout the bloodstream, and accumulation in the heart region. Although injection was local, the transcriptome profiling showed strong responses of zebrafish embryos exposed to PS particle, indicating a systemic response. We found several biological pathways activated which are related to an immune response in the PS exposed zebrafish larvae. Most notably the complement system was enriched as indicated by upregulation of genes in the alternative complement pathway (e.g. cfhl3, cfhl4, cfb and c9). The fact that complement pathway is activated indicates that plastic microparticles are integrated in immunological recognition processes. This was supported by fluorescence microscopy results, in which we observed co-localisation of neutrophils and macrophages around the PS particles. Identifying these key events can be a first building block to the development of an adverse outcome pathway (AOP). These data subsequently can be used within ecological and human risk assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Global analysis of the sporulation pathway of Clostridium difficile.

    Science.gov (United States)

    Fimlaid, Kelly A; Bond, Jeffrey P; Schutz, Kristin C; Putnam, Emily E; Leung, Jacqueline M; Lawley, Trevor D; Shen, Aimee

    2013-01-01

    The Gram-positive, spore-forming pathogen Clostridium difficile is the leading definable cause of healthcare-associated diarrhea worldwide. C. difficile infections are difficult to treat because of their frequent recurrence, which can cause life-threatening complications such as pseudomembranous colitis. The spores of C. difficile are responsible for these high rates of recurrence, since they are the major transmissive form of the organism and resistant to antibiotics and many disinfectants. Despite the importance of spores to the pathogenesis of C. difficile, little is known about their composition or formation. Based on studies in Bacillus subtilis and other Clostridium spp., the sigma factors σ(F), σ(E), σ(G), and σ(K) are predicted to control the transcription of genes required for sporulation, although their specific functions vary depending on the organism. In order to determine the roles of σ(F), σ(E), σ(G), and σ(K) in regulating C. difficile sporulation, we generated loss-of-function mutations in genes encoding these sporulation sigma factors and performed RNA-Sequencing to identify specific sigma factor-dependent genes. This analysis identified 224 genes whose expression was collectively activated by sporulation sigma factors: 183 were σ(F)-dependent, 169 were σ(E)-dependent, 34 were σ(G)-dependent, and 31 were σ(K)-dependent. In contrast with B. subtilis, C. difficile σ(E) was dispensable for σ(G) activation, σ(G) was dispensable for σ(K) activation, and σ(F) was required for post-translationally activating σ(G). Collectively, these results provide the first genome-wide transcriptional analysis of genes induced by specific sporulation sigma factors in the Clostridia and highlight that diverse mechanisms regulate sporulation sigma factor activity in the Firmicutes.

  5. Integration of video and radiation analysis data

    International Nuclear Information System (INIS)

    Menlove, H.O.; Howell, J.A.; Rodriguez, C.A.; Eccleston, G.W.; Beddingfield, D.; Smith, J.E.; Baumgart, C.W.

    1995-01-01

    For the past several years, the integration of containment and surveillance (C/S) with nondestructive assay (NDA) sensors for monitoring the movement of nuclear material has focused on the hardware and communications protocols in the transmission network. Little progress has been made in methods to utilize the combined C/S and NDA data for safeguards and to reduce the inspector time spent in nuclear facilities. One of the fundamental problems in the integration of the combined data is that the two methods operate in different dimensions. The C/S video data is spatial in nature; whereas, the NDA sensors provide radiation levels versus time data. The authors have introduced a new method to integrate spatial (digital video) with time (radiation monitoring) information. This technology is based on pattern recognition by neural networks, provides significant capability to analyze complex data, and has the ability to learn and adapt to changing situations. This technique has the potential of significantly reducing the frequency of inspection visits to key facilities without a loss of safeguards effectiveness

  6. The Single Market and Synchronized Mechanisms for the Exercise of Administrative Functions: Converging Pathways or New Pathways for Integration? The Case of the European Banking Union

    Directory of Open Access Journals (Sweden)

    Giglioni Fabio

    2017-11-01

    Full Text Available The EBU represents a clear investment in administrative integration with clear implications for the constitutional features of the EU. This paper aims to give an analysis of the administrative arrangements, through which the functions of supervision and resolution are affecting the single financial market. This case study is very interesting because these functions represent a genuine novelty in the history of financial integration since they are pre-ordained to a specific public interest: financial stability. Particularly, they cause a shift in the decision gradient from the technical to the political, as market integrity is less and less the key interest compared to financial stability. However, this wider discretionary power is not adequately counteracted by checks and balances in favour of accountability. As a result, the EBU makes a new contribution to the well-known ‘fragmentation of the executive power’ of the EU by introducing a new governance tool positioned between the Communitarian and Intergovernmental Method, but its development is still full of uncertainties given that constitutional equilibrium is far from being definitively reached.

  7. Environmental-pathways analysis for evaluation of a low-level waste disposal site

    International Nuclear Information System (INIS)

    Lee, D.W.; Ketelle, R.H.; Pin, F.G.; Hill, G.S.

    1983-01-01

    The suitability of a site for the shallow land burial of low-level waste is evaluated by an environmental-pathways analysis. The environmental-pathways analysis considers the probable paths for the transport of contamination to man and models the long-term transport of contamination to determine the resulting dose-to-man. The model of the long-term transport of contamination is developed for a proposed site using data obtained from a comprehensive laboratory and field investigation. The proposed site is located at the US Department of Energy Portsmouth Reservation, Piketon, Ohio and is planned to accept low-level radioactive waste generated by the enrichment of uranium. Laboratory studies were performed to characterize the waste and determine the wastes' leaching and retardation characteristics with site soils and groundwater. Comprehensive drilling, sampling and laboratory investigations were performed to provide the necessary information for interpreting the site's geology and hydrology. Field tests were performed to further quantify the site's hydrology. The pathway of greatest concern is the migration of contaminated groundwater and subsequent consumption by man. This pathway was modeled using a numerical simulation of the long-term transport of contamination. Conservative scenarios were developed for leachate generation and migration through the geohydrologic system. The dose-to-man determined from the pathways analysis formed the basis for evaluating site acceptability and providing recommendations for site design and development

  8. Life Cycle Greenhouse Gas Analysis of Multiple Vehicle Fuel Pathways in China

    Directory of Open Access Journals (Sweden)

    Tianduo Peng

    2017-11-01

    Full Text Available The Tsinghua University Life Cycle Analysis Model (TLCAM is applied to calculate the life cycle fossil energy consumption and greenhouse gas (GHG emissions for more than 20 vehicle fuel pathways in China. In addition to conventional gasoline and diesel, these include coal- and gas-based vehicle fuels, and electric vehicle (EV pathways. The results indicate the following. (1 China’s current dependence on coal and relative low-efficiency processes limits the potential for most alternative fuel pathways to decrease energy consumption and emissions; (2 Future low-carbon electricity pathways offer more obvious advantages, with coal-based pathways needing to adopt carbon dioxide capture and storage technology to compete; (3 A well-to-wheels analysis of the fossil energy consumption of vehicles fueled by compressed natural gas and liquefied natural gas (LNG showed that they are comparable to conventional gasoline vehicles. However, importing rather than domestically producing LNG for vehicle use can decrease domestic GHG emissions by 35% and 31% compared with those of conventional gasoline and diesel vehicles, respectively; (4 The manufacturing and recovery of battery and vehicle in the EV analysis has significant impact on the overall ability of EVs to decrease fossil energy consumption and GHG emissions from ICEVs.

  9. Constraint-based modeling and kinetic analysis of the Smad dependent TGF-beta signaling pathway.

    Directory of Open Access Journals (Sweden)

    Zhike Zi

    Full Text Available BACKGROUND: Investigation of dynamics and regulation of the TGF-beta signaling pathway is central to the understanding of complex cellular processes such as growth, apoptosis, and differentiation. In this study, we aim at using systems biology approach to provide dynamic analysis on this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We proposed a constraint-based modeling method to build a comprehensive mathematical model for the Smad dependent TGF-beta signaling pathway by fitting the experimental data and incorporating the qualitative constraints from the experimental analysis. The performance of the model generated by constraint-based modeling method is significantly improved compared to the model obtained by only fitting the quantitative data. The model agrees well with the experimental analysis of TGF-beta pathway, such as the time course of nuclear phosphorylated Smad, the subcellular location of Smad and signal response of Smad phosphorylation to different doses of TGF-beta. CONCLUSIONS/SIGNIFICANCE: The simulation results indicate that the signal response to TGF-beta is regulated by the balance between clathrin dependent endocytosis and non-clathrin mediated endocytosis. This model is useful to be built upon as new precise experimental data are emerging. The constraint-based modeling method can also be applied to quantitative modeling of other signaling pathways.

  10. Environmental pathways analysis for evaluation of a low-level waste disposal site

    International Nuclear Information System (INIS)

    Lee, D.W.; Ketelle, R.H.; Pin, F.G.; Hill, G.S.

    1984-01-01

    The suitability of a site for the shallow land burial of low-level waste is evaluated by an environmental pathways analysis. The environmental pathways analysis considers the probable paths for the transport of contamination to man and models the long-term transport of contamination to determine the resulting dose to man. The model of the long-term transport of contamination is developed for a proposed site using data obtained from a comprehensive laboratory and field investigation. The proposed site is located at the US Department of Energy Portsmouth Reservation, Piketon, Ohio, and is planned to accept low-level radioactive waste generated by the enrichment of uranium. Laboratory studies were performed to characterize the waste and determine the wastes' leaching and retardation characteristics with site soils and groundwater. Comprehensive drilling, sampling and laboratory investigations were performed to provide the necessary information for interpreting the site's geology and hydrology. Field tests were performed to further quantify the site's hydrology. The pathway of greatest concern is the migration of contaminated groundwater and subsequent consumption by man. This pathway was modelled using a numerical simulation of the long-term transport of contamination. Conservative scenarios were developed for leachate generation and migration through the geohydrologic system. The dose to man determined from the pathways analysis formed the basis for evaluating site acceptability and providing recommendations for site design and development. (author)

  11. Large-scale transcriptome analysis reveals arabidopsis metabolic pathways are frequently influenced by different pathogens.

    Science.gov (United States)

    Jiang, Zhenhong; He, Fei; Zhang, Ziding

    2017-07-01

    Through large-scale transcriptional data analyses, we highlighted the importance of plant metabolism in plant immunity and identified 26 metabolic pathways that were frequently influenced by the infection of 14 different pathogens. Reprogramming of plant metabolism is a common phenomenon in plant defense responses. Currently, a large number of transcriptional profiles of infected tissues in Arabidopsis (Arabidopsis thaliana) have been deposited in public databases, which provides a great opportunity to understand the expression patterns of metabolic pathways during plant defense responses at the systems level. Here, we performed a large-scale transcriptome analysis based on 135 previously published expression samples, including 14 different pathogens, to explore the expression pattern of Arabidopsis metabolic pathways. Overall, metabolic genes are significantly changed in expression during plant defense responses. Upregulated metabolic genes are enriched on defense responses, and downregulated genes are enriched on photosynthesis, fatty acid and lipid metabolic processes. Gene set enrichment analysis (GSEA) identifies 26 frequently differentially expressed metabolic pathways (FreDE_Paths) that are differentially expressed in more than 60% of infected samples. These pathways are involved in the generation of energy, fatty acid and lipid metabolism as well as secondary metabolite biosynthesis. Clustering analysis based on the expression levels of these 26 metabolic pathways clearly distinguishes infected and control samples, further suggesting the importance of these metabolic pathways in plant defense responses. By comparing with FreDE_Paths from abiotic stresses, we find that the expression patterns of 26 FreDE_Paths from biotic stresses are more consistent across different infected samples. By investigating the expression correlation between transcriptional factors (TFs) and FreDE_Paths, we identify several notable relationships. Collectively, the current study

  12. Integration of Design and Control through Model Analysis

    DEFF Research Database (Denmark)

    Russel, Boris Mariboe; Henriksen, Jens Peter; Jørgensen, Sten Bay

    2002-01-01

    A systematic computer aided analysis of the process model is proposed as a pre-solution step for integration of design and control problems. The process model equations are classified in terms of balance equations, constitutive equations and conditional equations. Analysis of the phenomena models...... (structure selection) issues for the integrated problems are considered. (C) 2002 Elsevier Science Ltd. All rights reserved....... representing the constitutive equations identify the relationships between the important process and design variables, which help to understand, define and address some of the issues related to integration of design and control. Furthermore, the analysis is able to identify a set of process (control) variables...

  13. Integration of deep geothermal energy and woody biomass conversion pathways in urban systems

    OpenAIRE

    Moret, Stefano; Peduzzi, Emanuela; Gerber, Léda; Maréchal, François

    2016-01-01

    Urban systems account for about two-thirds of global primary energy consumption and energy-related greenhouse gas emissions, with a projected increasing trend. Deep geothermal energy and woody biomass can be used for the production of heat, electricity and biofuels, thus constituting a renewable alternative to fossil fuels for all end-uses in cities: heating, cooling, electricity and mobility. This paper presents a methodology to assess the potential for integrating deep geothermal energy and...

  14. Parallel imaging of Drosophila embryos for quantitative analysis of genetic perturbations of the Ras pathway

    Directory of Open Access Journals (Sweden)

    Yogesh Goyal

    2017-07-01

    Full Text Available The Ras pathway patterns the poles of the Drosophila embryo by downregulating the levels and activity of a DNA-binding transcriptional repressor Capicua (Cic. We demonstrate that the spatiotemporal pattern of Cic during this signaling event can be harnessed for functional studies of mutations in the Ras pathway in human diseases. Our approach relies on a new microfluidic device that enables parallel imaging of Cic dynamics in dozens of live embryos. We found that although the pattern of Cic in early embryos is complex, it can be accurately approximated by a product of one spatial profile and one time-dependent amplitude. Analysis of these functions of space and time alone reveals the differential effects of mutations within the Ras pathway. Given the highly conserved nature of Ras-dependent control of Cic, our approach provides new opportunities for functional analysis of multiple sequence variants from developmental abnormalities and cancers.

  15. A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility

    DEFF Research Database (Denmark)

    Damotte, V; Guillot-Noel, L; Patsopoulos, N A

    2014-01-01

    adhesion molecule (CAMs) biological pathway using Cytoscape software. This network is a strong candidate, as it is involved in the crossing of the blood-brain barrier by the T cells, an early event in MS pathophysiology, and is used as an efficient therapeutic target. We drew up a list of 76 genes...... in interaction with other genes as a group. Pathway analysis is an alternative way to highlight such group of genes. Using SNP association P-values from eight multiple sclerosis (MS) GWAS data sets, we performed a candidate pathway analysis for MS susceptibility by considering genes interacting in the cell...... belonging to the CAM network. We highlighted 64 networks enriched with CAM genes with low P-values. Filtering by a percentage of CAM genes up to 50% and rejecting enriched signals mainly driven by transcription factors, we highlighted five networks associated with MS susceptibility. One of them, constituted...

  16. TEGS-CN: A Statistical Method for Pathway Analysis of Genome-wide Copy Number Profile.

    Science.gov (United States)

    Huang, Yen-Tsung; Hsu, Thomas; Christiani, David C

    2014-01-01

    The effects of copy number alterations make up a significant part of the tumor genome profile, but pathway analyses of these alterations are still not well established. We proposed a novel method to analyze multiple copy numbers of genes within a pathway, termed Test for the Effect of a Gene Set with Copy Number data (TEGS-CN). TEGS-CN was adapted from TEGS, a method that we previously developed for gene expression data using a variance component score test. With additional development, we extend the method to analyze DNA copy number data, accounting for different sizes and thus various numbers of copy number probes in genes. The test statistic follows a mixture of X (2) distributions that can be obtained using permutation with scaled X (2) approximation. We conducted simulation studies to evaluate the size and the power of TEGS-CN and to compare its performance with TEGS. We analyzed a genome-wide copy number data from 264 patients of non-small-cell lung cancer. With the Molecular Signatures Database (MSigDB) pathway database, the genome-wide copy number data can be classified into 1814 biological pathways or gene sets. We investigated associations of the copy number profile of the 1814 gene sets with pack-years of cigarette smoking. Our analysis revealed five pathways with significant P values after Bonferroni adjustment (number data, and causal mechanisms of the five pathways require further study.

  17. Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation

    Energy Technology Data Exchange (ETDEWEB)

    Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands); Pronk, Tessa E. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Brandhof, Evert-Jan van den [Centre for Environmental Quality, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Ven, Leo T.M. van der [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Piersma, Aldert H. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands)

    2013-10-01

    The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol and saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomics was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.

  18. In Silico Analysis of Putrefaction Pathways in Bacteria and Its Implication in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Harrisham Kaur

    2017-11-01

    Full Text Available Fermentation of undigested proteins in human gastrointestinal tract (gut by the resident microbiota, a process called bacterial putrefaction, can sometimes disrupt the gut homeostasis. In this process, essential amino acids (e.g., histidine, tryptophan, etc. that are required by the host may be utilized by the gut microbes. In addition, some of the products of putrefaction, like ammonia, putrescine, cresol, indole, phenol, etc., have been implicated in the disease pathogenesis of colorectal cancer (CRC. We have investigated bacterial putrefaction pathways that are known to be associated with such metabolites. Results of the comprehensive in silico analysis of the selected putrefaction pathways across bacterial genomes revealed presence of these pathways in limited bacterial groups. Majority of these bacteria are commonly found in human gut. These include Bacillus, Clostridium, Enterobacter, Escherichia, Fusobacterium, Salmonella, etc. Interestingly, while pathogens utilize almost all the analyzed pathways, commensals prefer putrescine and H2S production pathways for metabolizing the undigested proteins. Further, comparison of the putrefaction pathways in the gut microbiomes of healthy, carcinoma and adenoma datasets indicate higher abundances of putrefying bacteria in the carcinoma stage of CRC. The insights obtained from the present study indicate utilization of possible microbiome-based therapies to minimize the adverse effects of gut microbiome in enteric diseases.

  19. Analysis of Optimal Operation of an Energy Integrated Distillation Plant

    DEFF Research Database (Denmark)

    Li, Hong Wen; Hansen, C.A.; Gani, Rafiqul

    2003-01-01

    The efficiency of manufacturing systems can be significantly increased through diligent application of control based on mathematical models thereby enabling more tight integration of decision making with systems operation. In the present paper analysis of optimal operation of an energy integrated...

  20. Integrated program of using of Probabilistic Safety Analysis in Spain

    International Nuclear Information System (INIS)

    1998-01-01

    Since 25 June 1986, when the CSN (Nuclear Safety Conseil) approve the Integrated Program of Probabilistic Safety Analysis, this program has articulated the main activities of CSN. This document summarize the activities developed during these years and reviews the Integrated programme

  1. Analysis of integrated video and radiation data

    International Nuclear Information System (INIS)

    Howell, J.A.; Menlove, H.O.; Rodriguez, C.A.; Beddingfield, D.; Vasil, A.

    1995-01-01

    We have developed prototype software for a facility-monitoring application that will detect anomalous activity in a nuclear facility. The software, which forms the basis of a simple model, automatically reviews and analyzes integrated safeguards data from continuous unattended monitoring systems. This technology, based on pattern recognition by neural networks, provides significant capability to analyze complex data and has the ability to learn and adapt to changing situations. It is well suited for large automated facilities, reactors, spent-fuel storage facilities, reprocessing plants, and nuclear material storage vaults

  2. Signal integrity analysis on discontinuous microstrip line

    International Nuclear Information System (INIS)

    Qiao, Qingyang; Dai, Yawen; Chen, Zipeng

    2013-01-01

    In high speed PCB design, microstirp lines were used to control the impedance, however, the discontinuous microstrip line can cause signal integrity problems. In this paper, we use the transmission line theory to study the characteristics of microstrip lines. Research results indicate that the discontinuity such as truncation, gap and size change result in the problems such as radiation, reflection, delay and ground bounce. We change the discontinuities to distributed parameter circuits, analysed the steady-state response and transient response and the phase delay. The transient response cause radiation and voltage jump.

  3. Advantages of Integrative Data Analysis for Developmental Research

    Science.gov (United States)

    Bainter, Sierra A.; Curran, Patrick J.

    2015-01-01

    Amid recent progress in cognitive development research, high-quality data resources are accumulating, and data sharing and secondary data analysis are becoming increasingly valuable tools. Integrative data analysis (IDA) is an exciting analytical framework that can enhance secondary data analysis in powerful ways. IDA pools item-level data across…

  4. Integrated care: a comprehensive bibliometric analysis and literature review

    Directory of Open Access Journals (Sweden)

    Xiaowei Sun

    2014-06-01

    Full Text Available Introduction: Integrated care could not only fix up fragmented health care but also improve the continuity of care and the quality of life. Despite the volume and variety of publications, little is known about how ‘integrated care’ has developed. There is a need for a systematic bibliometric analysis on studying the important features of the integrated care literature.Aim: To investigate the growth pattern, core journals and jurisdictions and identify the key research domains of integrated care.Methods: We searched Medline/PubMed using the search strategy ‘(delivery of health care, integrated [MeSH Terms] OR integrated care [Title/Abstract]’ without time and language limits. Second, we extracted the publishing year, journals, jurisdictions and keywords of the retrieved articles. Finally, descriptive statistical analysis by the Bibliographic Item Co-occurrence Matrix Builder and hierarchical clustering by SPSS were used.Results: As many as 9090 articles were retrieved. Results included: (1 the cumulative numbers of the publications on integrated care rose perpendicularly after 1993; (2 all documents were recorded by 1646 kinds of journals. There were 28 core journals; (3 the USA is the predominant publishing country; and (4 there are six key domains including: the definition/models of integrated care, interdisciplinary patient care team, disease management for chronically ill patients, types of health care organizations and policy, information system integration and legislation/jurisprudence.Discussion and conclusion: Integrated care literature has been most evident in developed countries. International Journal of Integrated Care is highly recommended in this research area. The bibliometric analysis and identification of publication hotspots provides researchers and practitioners with core target journals, as well as an overview of the field for further research in integrated care.

  5. An operator expansion technique for path integral analysis

    International Nuclear Information System (INIS)

    Tsvetkov, I.V.

    1995-01-01

    A new method of path integral analysis in the framework of a power series technique is presented. The method is based on the operator expansion of an exponential. A regular procedure to calculate the correction terms is found. (orig.)

  6. Analysis of Price Variation and Market Integration of Prosopis ...

    African Journals Online (AJOL)

    Analysis of Price Variation and Market Integration of Prosopis Africana (guill. ... select five markets based on the presence of traders selling the commodity in the markets ... T- test result showed that Prosopis africana seed trade is profitable and ...

  7. Metabolic-flux analysis of hydrogen production pathway in Citrobacter amalonaticus Y19

    Energy Technology Data Exchange (ETDEWEB)

    Oh, You-Kwan; Kim, Mi-Sun [Bioenergy Research Center, Korea Institute of Energy Research, Daejeon 305-343 (Korea); Kim, Heung-Joo; Park, Sunghoon [Department of Chemical and Biochemical Engineering and Institute for Environmental Technology and Industry, Pusan National University, Busan 609-735 (Korea); Ryu, Dewey D.Y. [Biochemical Engineering Program, Department of Chemical Engineering and Material Science, University of California, Davis, CA 95616 (United States)

    2008-03-15

    For the newly isolated chemoheterotrophic bacterium Citrobacter amalonaticus Y19, anaerobic glucose metabolism and hydrogen (H{sub 2}) production pathway were studied using batch cultivation and an in silico metabolic-flux analysis. Batch cultivation was conducted under varying initial glucose concentration between 1.5 and 9.5 g/L with quantitative measurement of major metabolites to obtain accurate carbon material balance. The metabolic flux of Y19 was analyzed using a metabolic-pathway model which was constructed from 81 biochemical reactions. The linear optimization program MetaFluxNet was employed for the analysis. When the specific growth rate of cells was chosen as an objective function, the model described the batch culture characteristics of Ci. amalonaticus Y19 reasonably well. When the specific H{sub 2} production rate was selected as an objective function, on the other hand, the achievable maximal H{sub 2} production yield (8.7molH{sub 2}/mol glucose) and the metabolic pathway enabling the high H{sub 2} yield were identified. The pathway involved non-native NAD(P)-linked hydrogenase and H{sub 2} production from NAD(P)H which were supplied at a high rate from glucose degradation through the pentose phosphate pathway. (author)

  8. Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia

    International Nuclear Information System (INIS)

    Raponi, Mitch; Belly, Robert T; Karp, Judith E; Lancet, Jeffrey E; Atkins, David; Wang, Yixin

    2004-01-01

    Farnesyl protein transferase inhibitors (FTIs) were originally developed to inhibit oncogenic ras, however it is now clear that there are several other potential targets for this drug class. The FTI tipifarnib (ZARNESTRA™, R115777) has recently demonstrated clinical responses in adults with refractory and relapsed acute leukemias. This study was conducted to identify genetic markers and pathways that are regulated by tipifarnib in acute myeloid leukemia (AML). Tipifarnib-mediated gene expression changes in 3 AML cell lines and bone marrow samples from two patients with AML were analyzed on a cDNA microarray containing approximately 7000 human genes. Pathways associated with these expression changes were identified using the Ingenuity Pathway Analysis tool. The expression analysis identified a common set of genes that were regulated by tipifarnib in three leukemic cell lines and in leukemic blast cells isolated from two patients who had been treated with tipifarnib. Association of modulated genes with biological functional groups identified several pathways affected by tipifarnib including cell signaling, cytoskeletal organization, immunity, and apoptosis. Gene expression changes were verified in a subset of genes using real time RT-PCR. Additionally, regulation of apoptotic genes was found to correlate with increased Annexin V staining in the THP-1 cell line but not in the HL-60 cell line. The genetic networks derived from these studies illuminate some of the biological pathways affected by FTI treatment while providing a proof of principle for identifying candidate genes that might be used as surrogate biomarkers of drug activity

  9. Integrating Data Transformation in Principal Components Analysis

    KAUST Repository

    Maadooliat, Mehdi; Huang, Jianhua Z.; Hu, Jianhua

    2015-01-01

    Principal component analysis (PCA) is a popular dimension reduction method to reduce the complexity and obtain the informative aspects of high-dimensional datasets. When the data distribution is skewed, data transformation is commonly used prior

  10. Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

    Science.gov (United States)

    van Uitert, Miranda; Moerland, Perry D; Enquobahrie, Daniel A; Laivuori, Hannele; van der Post, Joris A M; Ris-Stalpers, Carrie; Afink, Gijs B

    2015-01-01

    Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and protein-protein associations (STRING). This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300) and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.

  11. Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Miranda van Uitert

    Full Text Available Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite and protein-protein associations (STRING. This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome. The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300 and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.

  12. Genome-wide analysis of a Wnt1-regulated transcriptional network implicates neurodegenerative pathways.

    Science.gov (United States)

    Wexler, Eric M; Rosen, Ezra; Lu, Daning; Osborn, Gregory E; Martin, Elizabeth; Raybould, Helen; Geschwind, Daniel H

    2011-10-04

    Wnt proteins are critical to mammalian brain development and function. The canonical Wnt signaling pathway involves the stabilization and nuclear translocation of β-catenin; however, Wnt also signals through alternative, noncanonical pathways. To gain a systems-level, genome-wide view of Wnt signaling, we analyzed Wnt1-stimulated changes in gene expression by transcriptional microarray analysis in cultured human neural progenitor (hNP) cells at multiple time points over a 72-hour time course. We observed a widespread oscillatory-like pattern of changes in gene expression, involving components of both the canonical and the noncanonical Wnt signaling pathways. A higher-order, systems-level analysis that combined independent component analysis, waveform analysis, and mutual information-based network construction revealed effects on pathways related to cell death and neurodegenerative disease. Wnt effectors were tightly clustered with presenilin1 (PSEN1) and granulin (GRN), which cause dominantly inherited forms of Alzheimer's disease and frontotemporal dementia (FTD), respectively. We further explored a potential link between Wnt1 and GRN and found that Wnt1 decreased GRN expression by hNPs. Conversely, GRN knockdown increased WNT1 expression, demonstrating that Wnt and GRN reciprocally regulate each other. Finally, we provided in vivo validation of the in vitro findings by analyzing gene expression data from individuals with FTD. These unbiased and genome-wide analyses provide evidence for a connection between Wnt signaling and the transcriptional regulation of neurodegenerative disease genes.

  13. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben

    2008-01-01

    ABSTRACT: BACKGROUND: Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent stud...

  14. SNP-based pathway enrichment analysis for genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Potkin Steven G

    2011-04-01

    Full Text Available Abstract Background Recently we have witnessed a surge of interest in using genome-wide association studies (GWAS to discover the genetic basis of complex diseases. Many genetic variations, mostly in the form of single nucleotide polymorphisms (SNPs, have been identified in a wide spectrum of diseases, including diabetes, cancer, and psychiatric diseases. A common theme arising from these studies is that the genetic variations discovered by GWAS can only explain a small fraction of the genetic risks associated with the complex diseases. New strategies and statistical approaches are needed to address this lack of explanation. One such approach is the pathway analysis, which considers the genetic variations underlying a biological pathway, rather than separately as in the traditional GWAS studies. A critical challenge in the pathway analysis is how to combine evidences of association over multiple SNPs within a gene and multiple genes within a pathway. Most current methods choose the most significant SNP from each gene as a representative, ignoring the joint action of multiple SNPs within a gene. This approach leads to preferential identification of genes with a greater number of SNPs. Results We describe a SNP-based pathway enrichment method for GWAS studies. The method consists of the following two main steps: 1 for a given pathway, using an adaptive truncated product statistic to identify all representative (potentially more than one SNPs of each gene, calculating the average number of representative SNPs for the genes, then re-selecting the representative SNPs of genes in the pathway based on this number; and 2 ranking all selected SNPs by the significance of their statistical association with a trait of interest, and testing if the set of SNPs from a particular pathway is significantly enriched with high ranks using a weighted Kolmogorov-Smirnov test. We applied our method to two large genetically distinct GWAS data sets of schizophrenia, one

  15. The strategy role of transitional care units to support Integrated Care and Personalised pathways for frail persons

    OpenAIRE

    Morando, Verdiana; Tozzi, Valeria D.

    2017-01-01

    The paper presents a comparative analysis of three models of transitional care units that have been set up in Italy in the last three years within the processes of Regional Healthcare Services and healthcare organisations’ reforms. The comparative analysis is worth of providing interesting insights and generalizable lessons learnt from integrated care in practice. The three cases of transitional care units belong to a similar background wherein greater needs for care coordination across the s...

  16. Sparse multivariate factor analysis regression models and its applications to integrative genomics analysis.

    Science.gov (United States)

    Zhou, Yan; Wang, Pei; Wang, Xianlong; Zhu, Ji; Song, Peter X-K

    2017-01-01

    The multivariate regression model is a useful tool to explore complex associations between two kinds of molecular markers, which enables the understanding of the biological pathways underlying disease etiology. For a set of correlated response variables, accounting for such dependency can increase statistical power. Motivated by integrative genomic data analyses, we propose a new methodology-sparse multivariate factor analysis regression model (smFARM), in which correlations of response variables are assumed to follow a factor analysis model with latent factors. This proposed method not only allows us to address the challenge that the number of association parameters is larger than the sample size, but also to adjust for unobserved genetic and/or nongenetic factors that potentially conceal the underlying response-predictor associations. The proposed smFARM is implemented by the EM algorithm and the blockwise coordinate descent algorithm. The proposed methodology is evaluated and compared to the existing methods through extensive simulation studies. Our results show that accounting for latent factors through the proposed smFARM can improve sensitivity of signal detection and accuracy of sparse association map estimation. We illustrate smFARM by two integrative genomics analysis examples, a breast cancer dataset, and an ovarian cancer dataset, to assess the relationship between DNA copy numbers and gene expression arrays to understand genetic regulatory patterns relevant to the disease. We identify two trans-hub regions: one in cytoband 17q12 whose amplification influences the RNA expression levels of important breast cancer genes, and the other in cytoband 9q21.32-33, which is associated with chemoresistance in ovarian cancer. © 2016 WILEY PERIODICALS, INC.

  17. Prevention and diagnosis of invasive fungal disease in high-risk patients within an integrative care pathway.

    Science.gov (United States)

    Barnes, Rosemary A; Stocking, Kate; Bowden, Sarah; Poynton, Matthew H; White, P Lewis

    2013-09-01

    The aim of this study was to assess the clinical utility of enhanced diagnostics on the management of invasive fungal disease in high risk patients within an integrated care pathway and to audit compliance and efficacy of antifungal prophylaxis. A cohort of 549 high risk haematology and stem-cell transplant recipients was followed over a 5 year period. The routine standard of care involved the use of antimould prophylaxis and a neutropenic care pathway utilizing twice weekly antigen and PCR testing. Prophylaxis with itraconazole was poorly tolerated and therapeutic levels could not be maintained. Antigen testing and PCR showed good clinical utility in the management of invasive aspergilosis with high sensitivity (98%) and negative predictive value (99.6%) when both tests were used together, allowing a diagnosis IA to be excluded and obviating the need for empirical antifungal agents. When used serially, multiple positive PCR and antigen test results enabled accurate diagnosis of IA with a specificity of 95% and a positive likelihood ratio of 11. Biomarkers preceded clinical signs in 85% of proven and probable invasive disease. The combination of both tests showed optimum clinical utility for the diagnosis and management of IA in this high risk group. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  18. Impairments of Multisensory Integration and Cross-Sensory Learning as Pathways to Dyslexia

    Science.gov (United States)

    Hahn, Noemi; Foxe, John J.; Molholm, Sophie

    2014-01-01

    Two sensory systems are intrinsic to learning to read. Written words enter the brain through the visual system and associated sounds through the auditory system. The task before the beginning reader is quite basic. She must learn correspondences between orthographic tokens and phonemic utterances, and she must do this to the point that there is seamless automatic ‘connection’ between these sensorially distinct units of language. It is self-evident then that learning to read requires formation of cross-sensory associations to the point that deeply encoded multisensory representations are attained. While the majority of individuals manage this task to a high degree of expertise, some struggle to attain even rudimentary capabilities. Why do dyslexic individuals, who learn well in myriad other domains, fail at this particular task? Here, we examine the literature as it pertains to multisensory processing in dyslexia. We find substantial support for multisensory deficits in dyslexia, and make the case that to fully understand its neurological basis, it will be necessary to thoroughly probe the integrity of auditory-visual integration mechanisms. PMID:25265514

  19. Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

    Science.gov (United States)

    Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

    2016-05-01

    Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights

  20. In silico analysis of phytohormone metabolism and communication pathways in citrus transcriptome

    Directory of Open Access Journals (Sweden)

    Vera Quecini

    2007-01-01

    Full Text Available Plant hormones play a crucial role in integrating endogenous and exogenous signals and in determining developmental responses to form the plant body throughout its life cycle. In citrus species, several economically important processes are controlled by phytohormones, including seed germination, secondary growth, fruit abscission and ripening. Integrative genomics is a powerful tool for linking newly researched organisms, such as tropical woody species, to functional studies already carried out on established model organisms. Based on gene orthology analyses and expression patterns, we searched the Citrus Genome Sequencing Consortium (CitEST database for Expressed Sequence Tags (EST consensus sequences sharing similarity to known components of hormone metabolism and signaling pathways in model species. More than 600 homologs of functionally characterized hormone metabolism and signal transduction members from model species were identified in citrus, allowing us to propose a framework for phytohormone signaling mechanisms in citrus. A number of components from hormone-related metabolic pathways were absent in citrus, suggesting the presence of distinct metabolic pathways. Our results demonstrated the power of comparative genomics between model systems and economically important crop species to elucidate several aspects of plant physiology and metabolism.

  1. The Spalt transcription factors regulate cell proliferation, survival and epithelial integrity downstream of the Decapentaplegic signalling pathway

    Directory of Open Access Journals (Sweden)

    María F. Organista

    2012-10-01

    The expression of the spalt genes is regulated by the Decapentaplegic signalling pathway in the Drosophila wing. These genes participate in the patterning of the longitudinal wing veins by regulating the expression of vein-specific genes, and in the establishment of cellular affinities in the central region of the wing blade epithelium. The Spalt proteins act as transcription factors, most likely regulating gene expression by repression, but the identity of their target genes in the wing is still unknown. As a preliminary step to unravel the genetic hierarchy controlled by the Spalt proteins, we have analysed their requirements during wing development, and addressed to what extent they mediate all the functions of the Decapentaplegic pathway in this developmental system. We identify additional functions for Spalt in cell division, survival, and maintenance of epithelial integrity. Thus, Spalt activity is required to promote cell proliferation, acting in the G2/M transition of the cell cycle. The contribution of Spalt to cell division is limited to the central region of the wing blade, as they do not mediate the extra growth triggered by Decapentaplegic signalling in the peripheral regions of the wing disc. In addition, Spalt function is required to maintain cell viability in cells exposed to high levels of Decapentaplegic signalling. This aspect of Spalt function is related to the repression of JNK signalling in the spalt domain of expression. Finally, we further characterise the requirements of Spalt to maintain epithelial integrity by regulating cellular affinities between cells located in the central wing region. Our results indicate that Spalt function mediates most of the requirements identified for Decapentaplegic signalling, contributing to establish the cellular qualities that differentiate central versus peripheral territories in the wing blade.

  2. A Gene Module-Based eQTL Analysis Prioritizing Disease Genes and Pathways in Kidney Cancer

    Directory of Open Access Journals (Sweden)

    Mary Qu Yang

    Full Text Available Clear cell renal cell carcinoma (ccRCC is the most common and most aggressive form of renal cell cancer (RCC. The incidence of RCC has increased steadily in recent years. The pathogenesis of renal cell cancer remains poorly understood. Many of the tumor suppressor genes, oncogenes, and dysregulated pathways in ccRCC need to be revealed for improvement of the overall clinical outlook of the disease. Here, we developed a systems biology approach to prioritize the somatic mutated genes that lead to dysregulation of pathways in ccRCC. The method integrated multi-layer information to infer causative mutations and disease genes. First, we identified differential gene modules in ccRCC by coupling transcriptome and protein-protein interactions. Each of these modules consisted of interacting genes that were involved in similar biological processes and their combined expression alterations were significantly associated with disease type. Then, subsequent gene module-based eQTL analysis revealed somatic mutated genes that had driven the expression alterations of differential gene modules. Our study yielded a list of candidate disease genes, including several known ccRCC causative genes such as BAP1 and PBRM1, as well as novel genes such as NOD2, RRM1, CSRNP1, SLC4A2, TTLL1 and CNTN1. The differential gene modules and their driver genes revealed by our study provided a new perspective for understanding the molecular mechanisms underlying the disease. Moreover, we validated the results in independent ccRCC patient datasets. Our study provided a new method for prioritizing disease genes and pathways. Keywords: ccRCC, Causative mutation, Pathways, Protein-protein interaction, Gene module, eQTL

  3. Different corticostriatal integration in spiny projection neurons from direct and indirect pathways

    Directory of Open Access Journals (Sweden)

    Edén Flores-Barrera

    2010-06-01

    Full Text Available The striatum is the principal input structure of the basal ganglia (BG. Major glutamatergic afferents to the striatum come from the cerebral cortex and make monosynaptic contacts with medium spiny projection neurons (MSNs and interneurons. Despite differences in axonal projections, dopamine receptors expression and differences in excitability between MSNs from “direct” and “indirect” BG pathways, these neuronal classes have been thought as electrophysiologically very similar. Based on work with BAC transgenic mice, here it is shown that corticostriatal responses in D1- and D2-receptor expressing MSNs (D1- and D2-MSNs are radically different so as to establish an electrophysiological footprint that readily differentiates between them. Experiments in BAC mice allowed us to predict, with high probability (P>0.9, in rats or non-BAC mice, whether a recorded neuron, from rat or mouse, was going to be substance P or enkephalin immunoreactive. Responses are more prolonged and evoke more action potentials in D1-MSNs, while they are briefer and exhibit intrinsic autoregenerative responses in D2-MSNs. A main cause for these differences was the interaction of intrinsic properties with the inhibitory contribution in each response Inhibition always depressed corticostriatal depolarization in D2-MSNs, while it helped in sustaining prolonged depolarizations in D1-MSNs, in spite of depressing early discharge. Corticostriatal responses changed dramatically after striatal DA-depletion in 6-hydroxy-dopamine (6-OHDA lesioned animals: a response reduction was seen in SP+ MSNs whereas an enhanced response was seen in ENK+ MSNs. The end result was that differences in the responses were greatly diminished after DA depletion.

  4. Broadening Pathways to Geosciences with an Integrated Program at The University of Michigan

    Science.gov (United States)

    Dick, G.; Munson, J.

    2017-12-01

    Low participation of under-represented minorities (URM) in the geosciences is an acute issue at the University of Michigan (U-M), where the number of undergraduate URM students majoring in the Department of Earth and Environmental Sciences (EES) is typically 5% of total majors. The goal of our project is to substantially increase the number and success rate of underrepresented minorities majoring in EES at U-M. We are pursuing this goal with five primary objectives: (i) inspire and recruit high schools seniors to pursue geoscience at U-M, especially through hands-on experiences including field trips; (ii) establish infrastructure to support students interested in geosciences through the critical juncture between high school and college; (iii) increase the number of URM students transferring from community college; (iv) develop student interest in geosciences through research and field experiences; (v) expose students to career opportunities in the geosciences. To accomplish these objectives we are leveraging existing programs, including Earth Camp, Foundations for Undergraduate Teaching: Uniting Research and Education (FUTURE), M-Sci, and college academic advisors. Throughout our interactions with students from high-school through college, we expose them to career opportunities in the geosciences, including private industry, academia, and government agencies. Evaluation of the program revealed three main conclusions: (i) the program increased student interest in pursuing an earth science degree; (ii) participating students showed a marked increase in awareness about the various opportunities that are available with an earth science degree including pathways to graduate school and earth science careers; (iii) field trips were the most effective route for achieving outcomes (i) and (ii).

  5. Cost benefit analysis of power plant database integration

    International Nuclear Information System (INIS)

    Wilber, B.E.; Cimento, A.; Stuart, R.

    1988-01-01

    A cost benefit analysis of plant wide data integration allows utility management to evaluate integration and automation benefits from an economic perspective. With this evaluation, the utility can determine both the quantitative and qualitative savings that can be expected from data integration. The cost benefit analysis is then a planning tool which helps the utility to develop a focused long term implementation strategy that will yield significant near term benefits. This paper presents a flexible cost benefit analysis methodology which is both simple to use and yields accurate, verifiable results. Included in this paper is a list of parameters to consider, a procedure for performing the cost savings analysis, and samples of this procedure when applied to a utility. A case study is presented involving a specific utility where this procedure was applied. Their uses of the cost-benefit analysis are also described

  6. Development of data analysis tool for combat system integration

    Directory of Open Access Journals (Sweden)

    Seung-Chun Shin

    2013-03-01

    Full Text Available System integration is an important element for the construction of naval combat ships. In particular, because impeccable combat system integration together with the sensors and weapons can ensure the combat capability and survivability of the ship, the integrated performance of the combat system should be verified and validated whether or not it fulfills the requirements of the end user. In order to conduct systematic verification and validation, a data analysis tool is requisite. This paper suggests the Data Extraction, Recording and Analysis Tool (DERAT for the data analysis of the integrated performance of the combat system, including the functional definition, architecture and effectiveness of the DERAT by presenting the test results.

  7. Metabolome Integrated Analysis of High-Temperature Response in Pinus radiata

    Directory of Open Access Journals (Sweden)

    Mónica Escandón

    2018-04-01

    Full Text Available The integrative omics approach is crucial to identify the molecular mechanisms underlying high-temperature response in non-model species. Based on future scenarios of heat increase, Pinus radiata plants were exposed to a temperature of 40°C for a period of 5 days, including recovered plants (30 days after last exposure to 40°C in the analysis. The analysis of the metabolome using complementary mass spectrometry techniques (GC-MS and LC-Orbitrap-MS allowed the reliable quantification of 2,287 metabolites. The analysis of identified metabolites and highlighter metabolic pathways across heat time exposure reveal the dynamism of the metabolome in relation to high-temperature response in P. radiata, identifying the existence of a turning point (on day 3 at which P. radiata plants changed from an initial stress response program (shorter-term response to an acclimation one (longer-term response. Furthermore, the integration of metabolome and physiological measurements, which cover from the photosynthetic state to hormonal profile, suggests a complex metabolic pathway interaction network related to heat-stress response. Cytokinins (CKs, fatty acid metabolism and flavonoid and terpenoid biosynthesis were revealed as the most important pathways involved in heat-stress response in P. radiata, with zeatin riboside (ZR and isopentenyl adenosine (iPA as the key hormones coordinating these multiple and complex interactions. On the other hand, the integrative approach allowed elucidation of crucial metabolic mechanisms involved in heat response in P. radiata, as well as the identification of thermotolerance metabolic biomarkers (L-phenylalanine, hexadecanoic acid, and dihydromyricetin, crucial metabolites which can reschedule the metabolic strategy to adapt to high temperature.

  8. Transcriptome Analysis of Manganese-deficient Chlamydomonas reinhardtii Provides Insight on the Chlorophyll Biosynthesis Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lockhart, Ainsley; Zvenigorodsky, Natasha; Pedraza, Mary Ann; Lindquist, Erika

    2011-08-11

    The biosynthesis of chlorophyll and other tetrapyrroles is a vital but poorly understood process. Recent genomic advances with the unicellular green algae Chlamydomonas reinhardtii have created opportunity to more closely examine the mechanisms of the chlorophyll biosynthesis pathway via transcriptome analysis. Manganese is a nutrient of interest for complex reactions because of its multiple stable oxidation states and role in molecular oxygen coordination. C. reinhardtii was cultured in Manganese-deplete Tris-acetate-phosphate (TAP) media for 24 hours and used to create cDNA libraries for sequencing using Illumina TruSeq technology. Transcriptome analysis provided intriguing insight on possible regulatory mechanisms in the pathway. Evidence supports similarities of GTR (Glutamyl-tRNA synthase) to its Chlorella vulgaris homolog in terms of Mn requirements. Data was also suggestive of Mn-related compensatory up-regulation for pathway proteins CHLH1 (Manganese Chelatase), GUN4 (Magnesium chelatase activating protein), and POR1 (Light-dependent protochlorophyllide reductase). Intriguingly, data suggests possible reciprocal expression of oxygen dependent CPX1 (coproporphyrinogen III oxidase) and oxygen independent CPX2. Further analysis using RT-PCR could provide compelling evidence for several novel regulatory mechanisms in the chlorophyll biosynthesis pathway.

  9. Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity

    Directory of Open Access Journals (Sweden)

    Kelsey H. Collins

    2018-02-01

    Full Text Available Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS. Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK complications (i.e., muscle, bone, tendon, and joints that result from obesity-associated metabolic disturbances are less frequently interrogated. As musculoskeletal diseases can lead to the worsening of MetS, this underscores the imminent need to understand the cause and effect relations between the two, and the convergence between inflammatory pathways that contribute to MSK damage. Muscle mass is a key predictor of longevity in older adults, and obesity-induced sarcopenia is a significant risk factor for adverse health outcomes. Muscle is highly plastic, undergoes regular remodeling, and is responsible for the majority of total body glucose utilization, which when impaired leads to insulin resistance. Furthermore, impaired muscle integrity, defined as persistent muscle loss, intramuscular lipid accumulation, or connective tissue deposition, is a hallmark of metabolic dysfunction. In fact, many common inflammatory pathways have been implicated in the pathogenesis of the interrelated tissues of the musculoskeletal system (e.g., tendinopathy, osteoporosis, and osteoarthritis. Despite these similarities, these diseases are rarely evaluated in a comprehensive manner. The aim of this review is to summarize the common pathways that lead to musculoskeletal damage and disease that result from and contribute to MetS. We propose the overarching

  10. Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity.

    Science.gov (United States)

    Collins, Kelsey H; Herzog, Walter; MacDonald, Graham Z; Reimer, Raylene A; Rios, Jaqueline L; Smith, Ian C; Zernicke, Ronald F; Hart, David A

    2018-01-01

    Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i.e., muscle, bone, tendon, and joints) that result from obesity-associated metabolic disturbances are less frequently interrogated. As musculoskeletal diseases can lead to the worsening of MetS, this underscores the imminent need to understand the cause and effect relations between the two, and the convergence between inflammatory pathways that contribute to MSK damage. Muscle mass is a key predictor of longevity in older adults, and obesity-induced sarcopenia is a significant risk factor for adverse health outcomes. Muscle is highly plastic, undergoes regular remodeling, and is responsible for the majority of total body glucose utilization, which when impaired leads to insulin resistance. Furthermore, impaired muscle integrity, defined as persistent muscle loss, intramuscular lipid accumulation, or connective tissue deposition, is a hallmark of metabolic dysfunction. In fact, many common inflammatory pathways have been implicated in the pathogenesis of the interrelated tissues of the musculoskeletal system (e.g., tendinopathy, osteoporosis, and osteoarthritis). Despite these similarities, these diseases are rarely evaluated in a comprehensive manner. The aim of this review is to summarize the common pathways that lead to musculoskeletal damage and disease that result from and contribute to MetS. We propose the overarching hypothesis that there

  11. 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.

  12. Integrated systems analysis of the PIUS reactor

    Energy Technology Data Exchange (ETDEWEB)

    Fullwood, F.; Kroeger, P.; Higgins, J. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1993-11-01

    Results are presented of a systems failure analysis of the PIUS plant systems that are used during normal reactor operation and postulated accidents. This study was performed to provide the NRC with an understanding of the behavior of the plant. The study applied two diverse failure identification methods, Failure Modes Effects & Criticality Analysis (FMECA) and Hazards & Operability (HAZOP) to the plant systems, supported by several deterministic analyses. Conventional PRA methods were also used along with a scheme for classifying events by initiator frequency and combinations of failures. Principal results of this study are: (a) an extensive listing of potential event sequences, grouped in categories that can be used by the NRC, (b) identification of support systems that are important to safety, and (c) identification of key operator actions.

  13. Integrated systems analysis of the PIUS reactor

    International Nuclear Information System (INIS)

    Fullwood, F.; Kroeger, P.; Higgins, J.

    1993-11-01

    Results are presented of a systems failure analysis of the PIUS plant systems that are used during normal reactor operation and postulated accidents. This study was performed to provide the NRC with an understanding of the behavior of the plant. The study applied two diverse failure identification methods, Failure Modes Effects ampersand Criticality Analysis (FMECA) and Hazards ampersand Operability (HAZOP) to the plant systems, supported by several deterministic analyses. Conventional PRA methods were also used along with a scheme for classifying events by initiator frequency and combinations of failures. Principal results of this study are: (a) an extensive listing of potential event sequences, grouped in categories that can be used by the NRC, (b) identification of support systems that are important to safety, and (c) identification of key operator actions

  14. Integrative data analysis of male reproductive disorders

    DEFF Research Database (Denmark)

    Edsgard, Stefan Daniel

    of such data in conjunction with data from publicly available repositories. This thesis presents an introduction to disease genetics and molecular systems biology, followed by four studies that each provide detailed clues to the etiology of male reproductive disorders. Finally, a fifth study illustrates......-wide association data with respect to copy number variation and show that the aggregated effect of rare variants can influence the risk for testicular cancer. Paper V provides an example of the application of RNA-Seq for expression analysis of a species with an unsequenced genome. We analysed the plant...... of this thesis is the identification of the molecular basis of male reproductive disorders, with a special focus on testicular cancer. To this end, clinical samples were characterized by microarraybased transcription and genomic variation assays and molecular entities were identified by computational analysis...

  15. Evaluating the effect of clinical care pathways on quality of cancer care: analysis of breast, colon and rectal cancer pathways.

    Science.gov (United States)

    Bao, Han; Yang, Fengjuan; Su, Shaofei; Wang, Xinyu; Zhang, Meiqi; Xiao, Yaming; Jiang, Hao; Wang, Jiaying; Liu, Meina

    2016-05-01

    Substantial gaps exist between clinical practice and evidence-based cancer care, potentially leading to adverse clinical outcomes and decreased quality of life for cancer patients. This study aimed to evaluate the usefulness of clinical pathways as a tool for improving quality of cancer care, using breast, colon, and rectal cancer pathways as demonstrations. Newly diagnosed patients with invasive breast, colon, and rectal cancer were enrolled as pre-pathway groups, while patients with the same diagnoses treated according to clinical pathways were recruited for post-pathway groups. Compliance with preoperative core biopsy or fine-needle aspiration, utilization of sentinel lymph node biopsy, and proportion of patients whose tumor hormone receptor status was stated in pathology report were significantly increased after implementation of clinical pathway for breast cancer. For colon cancer, compliance with two care processes was significantly improved: surgical resection with anastomosis and resection of at least 12 lymph nodes. Regarding rectal cancer, there was a significant increase in compliance with preoperative evaluation of depth of tumor invasion, total mesorectal excision treatment of middle- or low-position rectal cancer, and proportion of patients who had undergone rectal cancer surgery whose pathology report included margin status. Moreover, total length of hospital stay was decreased remarkably for all three cancer types, and postoperative complications remained unchanged following implementation of the clinical pathways. Clinical pathways can improve compliance with standard care by implementing evidence-based quality indicators in daily practice, which could serve as a useful tool for narrowing the gap between clinical practice and evidence-based care.

  16. Cloning and Expression Analysis of MEP Pathway Enzyme-encoding Genes in Osmanthus fragrans

    Directory of Open Access Journals (Sweden)

    Chen Xu

    2016-09-01

    Full Text Available The 2-C-methyl-d-erythritol 4-phosphate (MEP pathway is responsible for the biosynthesis of many crucial secondary metabolites, such as carotenoids, monoterpenes, plastoquinone, and tocopherols. In this study, we isolated and identified 10 MEP pathway genes in the important aromatic plant sweet osmanthus (Osmanthus fragrans. Multiple sequence alignments revealed that 10 MEP pathway genes shared high identities with other reported proteins. The genes showed distinctive expression profiles in various tissues, or at different flower stages and diel time points. The qRT-PCR results demonstrated that these genes were highly expressed in inflorescences, which suggested a tissue-specific transcript pattern. Our results also showed that OfDXS1, OfDXS2, and OfHDR1 had a clear diurnal oscillation pattern. The isolation and expression analysis provides a strong foundation for further research on the MEP pathway involved in gene function and molecular evolution, and improves our understanding of the molecular mechanism underlying this pathway in plants.

  17. Ensemble Modeling for Robustness Analysis in engineering non-native metabolic pathways.

    Science.gov (United States)

    Lee, Yun; Lafontaine Rivera, Jimmy G; Liao, James C

    2014-09-01

    Metabolic pathways in cells must be sufficiently robust to tolerate fluctuations in expression levels and changes in environmental conditions. Perturbations in expression levels may lead to system failure due to the disappearance of a stable steady state. Increasing evidence has suggested that biological networks have evolved such that they are intrinsically robust in their network structure. In this article, we presented Ensemble Modeling for Robustness Analysis (EMRA), which combines a continuation method with the Ensemble Modeling approach, for investigating the robustness issue of non-native pathways. EMRA investigates a large ensemble of reference models with different parameters, and determines the effects of parameter drifting until a bifurcation point, beyond which a stable steady state disappears and system failure occurs. A pathway is considered to have high bifurcational robustness if the probability of system failure is low in the ensemble. To demonstrate the utility of EMRA, we investigate the bifurcational robustness of two synthetic central metabolic pathways that achieve carbon conservation: non-oxidative glycolysis and reverse glyoxylate cycle. With EMRA, we determined the probability of system failure of each design and demonstrated that alternative designs of these pathways indeed display varying degrees of bifurcational robustness. Furthermore, we demonstrated that target selection for flux improvement should consider the trade-offs between robustness and performance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Meta-analysis of global transcriptomics reveals conserved genetic pathways of Quercetin and Tannic acid mediated longevity in C. elegans

    Directory of Open Access Journals (Sweden)

    Kerstin ePietsch

    2012-04-01

    Full Text Available Recent research has highlighted that the polyphenols Quercetin and Tannic acid are capable of extending the lifespan of C. elegans. To gain a deep understanding of the underlying molecular genetics, we analyzed the global transcriptional patterns of nematodes exposed to Quercetin or Tannic acid concentrations that are non-effective (in lifespan extension, lifespan extending or toxic. By means of an intricate meta-analysis it was possible to compare the transcriptomes of polyphenol exposure to recently published data sets derived from i longevity mutants or ii infection. This detailed comparative in silico analysis facilitated the identification of compound specific and overlapping transcriptional profiles and allowed the formulation of mechanistic models of Quercetin and Tannic acid mediated longevity. Lifespan extension due to Quercetin was predominantly driven by the metabolome, TGF-beta signaling, Insulin-like signaling and the p38 MAPK pathway and Tannic acid’s impact involved, in part, the amino acid metabolism and was modulated by the TGF-beta and the p38 MAPK pathways. DAF-12, which integrates TGF-beta and Insulin-like downstream signaling, therefore seems to be a crucial regulator for both polyphenols.

  19. Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Paolo Cossu-Rocca

    Full Text Available Triple Negative Breast Cancer (TNBC accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20-40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data.PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components.PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC.Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

  20. Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Orrù, Sandra; Muroni, Maria Rosaria; Sanges, Francesca; Sotgiu, Giovanni; Ena, Sara; Pira, Giovanna; Murgia, Luciano; Manca, Alessandra; Uras, Maria Gabriela; Sarobba, Maria Giuseppina; Urru, Silvana; De Miglio, Maria Rosaria

    2015-01-01

    Triple Negative Breast Cancer (TNBC) accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20-40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data. PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components. PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC. Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

  1. Integrated analysis of the molecular action of Vorinostat identifies epi-sensitised targets for combination therapy.

    Science.gov (United States)

    Hay, Jodie F; Lappin, Katrina; Liberante, Fabio; Kettyle, Laura M; Matchett, Kyle B; Thompson, Alexander; Mills, Ken I

    2017-09-15

    Several histone deacetylase inhibitors including Vorinostat have received FDA approval for the treatment of haematological malignancies. However, data from these trials indicate that Vorinostat has limited efficacy as a monotherapy, prompting the need for rational design of combination therapies. A number of epi-sensitised pathways, including sonic hedgehog (SHH), were identified in AML cells by integration of global patterns of histone H3 lysine 9 (H3K9) acetylation with transcriptomic analysis following Vorinostat-treatment. Direct targeting of the SHH pathway with SANT-1, following Vorinostat induced epi-sensitisation, resulted in synergistic cell death of AML cells. In addition, xenograft studies demonstrated that combination therapy induced a marked reduction in leukemic burden compared to control or single agents. Together, the data supports epi-sensitisation as a potential component of the strategy for the rational development of combination therapies in AML.

  2. An integrated platform for biomolecule interaction analysis

    Science.gov (United States)

    Jan, Chia-Ming; Tsai, Pei-I.; Chou, Shin-Ting; Lee, Shu-Sheng; Lee, Chih-Kung

    2013-02-01

    We developed a new metrology platform which can detect real-time changes in both a phase-interrogation mode and intensity mode of a SPR (surface plasmon resonance). We integrated a SPR and ellipsometer to a biosensor chip platform to create a new biomolecular interaction measurement mechanism. We adopted a conductive ITO (indium-tinoxide) film to the bio-sensor platform chip to expand the dynamic range and improve measurement accuracy. The thickness of the conductive film and the suitable voltage constants were found to enhance performance. A circularly polarized ellipsometry configuration was incorporated into the newly developed platform to measure the label-free interactions of recombinant human C-reactive protein (CRP) with immobilized biomolecule target monoclonal human CRP antibody at various concentrations. CRP was chosen as it is a cardiovascular risk biomarker and is an acute phase reactant as well as a specific prognostic indicator for inflammation. We found that the sensitivity of a phaseinterrogation SPR is predominantly dependent on the optimization of the sample incidence angle. The effect of the ITO layer effective index under DC and AC effects as well as an optimal modulation were experimentally performed and discussed. Our experimental results showed that the modulated dynamic range for phase detection was 10E-2 RIU based on a current effect and 10E-4 RIU based on a potential effect of which a 0.55 (°/RIU) measurement was found by angular-interrogation. The performance of our newly developed metrology platform was characterized to have a higher sensitivity and less dynamic range when compared to a traditional full-field measurement system.

  3. An analysis of 3D particle path integration algorithms

    International Nuclear Information System (INIS)

    Darmofal, D.L.; Haimes, R.

    1996-01-01

    Several techniques for the numerical integration of particle paths in steady and unsteady vector (velocity) fields are analyzed. Most of the analysis applies to unsteady vector fields, however, some results apply to steady vector field integration. Multistep, multistage, and some hybrid schemes are considered. It is shown that due to initialization errors, many unsteady particle path integration schemes are limited to third-order accuracy in time. Multistage schemes require at least three times more internal data storage than multistep schemes of equal order. However, for timesteps within the stability bounds, multistage schemes are generally more accurate. A linearized analysis shows that the stability of these integration algorithms are determined by the eigenvalues of the local velocity tensor. Thus, the accuracy and stability of the methods are interpreted with concepts typically used in critical point theory. This paper shows how integration schemes can lead to erroneous classification of critical points when the timestep is finite and fixed. For steady velocity fields, we demonstrate that timesteps outside of the relative stability region can lead to similar integration errors. From this analysis, guidelines for accurate timestep sizing are suggested for both steady and unsteady flows. In particular, using simulation data for the unsteady flow around a tapered cylinder, we show that accurate particle path integration requires timesteps which are at most on the order of the physical timescale of the flow

  4. Building Integrated Photovoltaics: A Concise Description of the Current State of the Art and Possible Research Pathways

    Directory of Open Access Journals (Sweden)

    Bjørn Petter Jelle

    2015-12-01

    Full Text Available Building integrated photovoltaics (BIPV offer an aesthetical, economical and technical solution to integrate solar cells harvesting solar radiation to produce electricity within the climate envelopes of buildings. Photovoltaic (PV cells may be mounted above or onto the existing or traditional roofing or wall systems. However, BIPV systems replace the outer building envelope skin, i.e., the climate screen, hence serving simultanously as both a climate screen and a power source generating electricity. Thus, BIPV may provide savings in materials and labor, in addition to reducing the electricity costs. Hence, for the BIPV products, in addition to specific requirements put on the solar cell technology, it is of major importance to have satisfactory or strict requirements of rain tightness and durability, where building physical issues like e.g., heat and moisture transport in the building envelope also have to be considered and accounted for. This work, from both a technological and scientific point of view, summarizes briefly the current state-of-the-art of BIPV, including both BIPV foil, tiles, modules and solar cell glazing products, and addresses possible research pathways for BIPV in the years to come.

  5. Field-to-Fuel Performance Testing of Lignocellulosic Feedstocks: An Integrated Study of the Fast Pyrolysis/Hydrotreating Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Howe, Daniel T.; Westover, Tyler; Carpenter, Daniel; Santosa, Daniel M.; Emerson, Rachel; Deutch, Steve; Starace, Anne; Kutnyakov, Igor V.; Lukins, Craig D.

    2015-05-21

    Feedstock composition can affect final fuel yields and quality for the fast pyrolysis and hydrotreatment upgrading pathway. However, previous studies have focused on individual unit operations rather than the integrated system. In this study, a suite of six pure lignocellulosic feedstocks (clean pine, whole pine, tulip poplar, hybrid poplar, switchgrass, and corn stover) and two blends (equal weight percentages whole pine/tulip poplar/switchgrass and whole pine/clean pine/hybrid poplar) were prepared and characterized at Idaho National Laboratory. These blends then underwent fast pyrolysis at the National Renewable Energy Laboratory and hydrotreatment at Pacific Northwest National Laboratory. Although some feedstocks showed a high fast pyrolysis bio-oil yield such as tulip poplar at 57%, high yields in the hydrotreater were not always observed. Results showed overall fuel yields of 15% (switchgrass), 18% (corn stover), 23% (tulip poplar, Blend 1, Blend 2), 24% (whole pine, hybrid poplar) and 27% (clean pine). Simulated distillation of the upgraded oils indicated that the gasoline fraction varied from 39% (clean pine) to 51% (corn stover), while the diesel fraction ranged from 40% (corn stover) to 46% (tulip poplar). Little variation was seen in the jet fuel fraction at 11 to 12%. Hydrogen consumption during hydrotreating, a major factor in the economic feasibility of the integrated process, ranged from 0.051 g/g dry feed (tulip poplar) to 0.070 g/g dry feed (clean pine).

  6. Defective chromatic and achromatic visual pathways in developmental dyslexia: Cues for an integrated intervention programme.

    Science.gov (United States)

    Bonfiglio, Luca; Bocci, Tommaso; Minichilli, Fabrizio; Crecchi, Alessandra; Barloscio, Davide; Spina, Donata Maria; Rossi, Bruno; Sartucci, Ferdinando

    2017-01-01

    As well as obtaining confirmation of the magnocellular system involvement in developmental dyslexia (DD); the aim was primarily to search for a possible involvement of the parvocellular system; and, furthermore, to complete the assessment of the visual chromatic axis by also analysing the koniocellular system. Visual evoked potentials (VEPs) in response to achromatic stimuli with low luminance contrast and low spatial frequency, and isoluminant red/green and blue/yellow stimuli with high spatial frequency were recorded in 10 dyslexic children and 10 age- and sex-matched, healthy subjects. Dyslexic children showed delayed VEPs to both achromatic stimuli (magnocellular-dorsal stream) and isoluminant red/green and blue/yellow stimuli (parvocellular-ventral and koniocellular streams). To our knowledge, this is the first time that a dysfunction of colour vision has been brought to light in an objective way (i.e., by means of electrophysiological methods) in children with DD. These results give rise to speculation concerning the need for a putative approach for promoting both learning how to read and/or improving existing reading skills of children with or at risk of DD. The working hypothesis would be to combine two integrated interventions in a single programme aimed at fostering the function of both the magnocellular and the parvocellular streams.

  7. Development of computationally predicted Adverse Outcome Pathway (AOP) networks through data mining and integration of publicly available in vivo, in vitro, phenotype, and biological pathway data

    Science.gov (United States)

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

  8. Generation of computationally predicted Adverse Outcome Pathway networks through integration of publicly available in vivo, in vitro, phenotype, and biological pathway data.

    Science.gov (United States)

    The Adverse Outcome Pathway (AOP) framework is becoming a widely used tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse ecological and human health outcomes. However, the conventional process...

  9. Integrating human factors into process hazard analysis

    International Nuclear Information System (INIS)

    Kariuki, S.G.; Loewe, K.

    2007-01-01

    A comprehensive process hazard analysis (PHA) needs to address human factors. This paper describes an approach that systematically identifies human error in process design and the human factors that influence its production and propagation. It is deductive in nature and therefore considers human error as a top event. The combinations of different factors that may lead to this top event are analysed. It is qualitative in nature and is used in combination with other PHA methods. The method has an advantage because it does not look at the operator error as the sole contributor to the human failure within a system but a combination of all underlying factors

  10. Integrative Genomic Analysis of Complex traits

    DEFF Research Database (Denmark)

    Ehsani, Ali Reza

    In the last decade rapid development in biotechnologies has made it possible to extract extensive information about practically all levels of biological organization. An ever-increasing number of studies are reporting miltilayered datasets on the entire DNA sequence, transceroption, protein...... expression, and metabolite abundance of more and more populations in a multitude of invironments. However, a solid model for including all of this complex information in one analysis, to disentangle genetic variation and the underlying genetic architecture of complex traits and diseases, has not yet been...

  11. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles.

    Science.gov (United States)

    Zaya, Renee M; Amini, Zakariya; Whitaker, Ashley S; Ide, Charles F

    2011-08-01

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 μg/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 μg/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 μg/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 μg/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p=0.07) increases in peroxisome proliferator-activated receptor β (PPAR-β) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid β-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-β, an energy homeostasis regulatory molecule, also

  12. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles

    International Nuclear Information System (INIS)

    Zaya, Renee M.; Amini, Zakariya; Whitaker, Ashley S.; Ide, Charles F.

    2011-01-01

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 μg/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 μg/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 μg/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 μg/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p = 0.07) increases in peroxisome proliferator-activated receptor β (PPAR-β) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid β-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-β, an energy homeostasis regulatory molecule

  13. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles

    Energy Technology Data Exchange (ETDEWEB)

    Zaya, Renee M., E-mail: renee.zaya@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Amini, Zakariya, E-mail: zakariya.amini@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Whitaker, Ashley S., E-mail: ashley.s.whitaker@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Ide, Charles F., E-mail: charles.ide@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States)

    2011-08-15

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 {mu}g/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 {mu}g/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 {mu}g/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 {mu}g/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p = 0.07) increases in peroxisome proliferator-activated receptor {beta} (PPAR-{beta}) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid {beta}-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-{beta}, an energy

  14. KeyPathwayMinerWeb

    DEFF Research Database (Denmark)

    List, Markus; Alcaraz, Nicolas; Dissing-Hansen, Martin

    2016-01-01

    , for instance), KeyPathwayMiner extracts connected sub-networks containing a high number of active or differentially regulated genes (proteins, metabolites) in the molecular profiles. The web interface at (http://keypathwayminer.compbio.sdu.dk) implements all core functionalities of the KeyPathwayMiner tool set......We present KeyPathwayMinerWeb, the first online platform for de novo pathway enrichment analysis directly in the browser. Given a biological interaction network (e.g. protein-protein interactions) and a series of molecular profiles derived from one or multiple OMICS studies (gene expression...... such as data integration, input of background knowledge, batch runs for parameter optimization and visualization of extracted pathways. In addition to an intuitive web interface, we also implemented a RESTful API that now enables other online developers to integrate network enrichment as a web service...

  15. Monetary valuation with impact pathway analysis: Benefits of reducing nitrate leaching in European Catchments

    DEFF Research Database (Denmark)

    Andersen, Mikael Skou; Hansen, Morten Søes; Carstensen, Jacob

    2011-01-01

    Integrated assessment frameworks which can account comprehensively for the benefits related to water quality improvements have not yet been established. The main challenge is to link economic valuation with hydrological data in an appropriate way.We here explore the so-called ‘impact pathway...... approach’ as a novel analytical method in the area ofwater management. It can identify site- and catchment-specific benefits associated with management measures by linking economic and hydrological data through consecutive modelling stages, allowing for monetization of specific end point effects...

  16. [Establishment and testing practice of an integrative medical pathway for clinical management of acute myocardial infarction].

    Science.gov (United States)

    Wang, Lei; Zhang, Min-zhou; Zhang, Jun

    2011-01-01

    To establish an integrative medical approach (IMA) for clinical management of acute myocardial infarction (AMI), and to test its efficacy. IMA was preliminarily established according to the guidelines and based on the Chinese medical therapy of benefiting vital qi and promoting blood circulation. And adopting non-synchronous queue design, AMI patients were assigned to the IMA group (71 cases) and the non-IMA group (70 cases), they were managed following or didn't follow the established IMA respectively. The total hospitalization time (THT), the ICU indwelling time (ICUD) and the total medical expenditure (TME) of patients were compared between groups. Moreover, for patients received primary PCI, the time for door-to-balloon (DTB) was compared in addition. Comparisons between groups showed that THT in the IMA group was shorter than that in the non-IMA group (9.80 +/- 5.62 days vs. 12.01 +/- 7. 35 days , P < 0.05); but the difference of TME between groups was insignificant. For those received PCT, the DTB in the IMA group was shorter than that in the non-IMA group in terms of DTB time (82.56 +/- 17.36 min vs. 119.19 +/- 30.88 min, P < 0.01), THT (9.69 +/- 5.59 vs. 13.34 +/- 7.49 days, P < 0.01) and TME. Practicing IMA for AMI, which was established based on Chinese medical therapy of benefiting vital qi and promoting blood circulation, could shorten the hospitalization time of patients, reduce the DTB time and TME in patients receiving primary PCI; fully displays its significance in hospital administration and quality control on AMI.

  17. Proliferation Resistance: Acquisition/Diversion Pathway Analysis for the DUPIC Fuel Cycle

    International Nuclear Information System (INIS)

    Ko, Won Il; Chang, Hong Lae; Song, Dae Yong; Lee, Ho Hee; Kwon, Eun Ha; Jeong, Chang Joon; Kim, Ho Dong

    2009-07-01

    Within the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO), a methodology for evaluating proliferation resistance (INPRO PR methodology) has been developed. However, it remains to develop the methodology to evaluate User Requirements (UR) 4 regarding multiplicity and robustness of barriers against proliferation - innovative nuclear energy systems should incorporate multiple proliferation resistance features and measures. Since this requires an acquisition/diversion pathway analysis, this report describes a systematic approach developed for the identification and analysis of pathways for the acquisition of weapons-usable nuclear material using the DUPIC fuel cycle system. At the first step, the objectives of the proliferation were identified, including the quality and quantity of the material, the time required to acquire the material for the proliferation, thr capability of the potential proliferant country, etc. At the second step, the possible strategies, which the potential proliferant country could adopt, were identified: undeclared removal of nuclear material from the fuel cycle facilities; and further treatment of the diverted nuclear materials needed to acquire weapons-usable materials. At the final step, a systematic approach to select the plausible pathways for the acquisition/diversion of nuclear material during the whole fuel cycle has been developed. The coarse material diversion pathways for the DUPIC fuel cycle and the approach developed was reviewed and discussed at the experts meeting at the IAEA for its appropriateness and comprehensiveness

  18. Project analysis and integration economic analyses summary

    Science.gov (United States)

    Macomber, H. L.

    1986-01-01

    An economic-analysis summary was presented for the manufacture of crystalline-silicon modules involving silicon ingot/sheet, growth, slicing, cell manufacture, and module assembly. Economic analyses provided: useful quantitative aspects for complex decision-making to the Flat-plate Solar Array (FSA) Project; yardsticks for design and performance to industry; and demonstration of how to evaluate and understand the worth of research and development both to JPL and other government agencies and programs. It was concluded that future research and development funds for photovoltaics must be provided by the Federal Government because the solar industry today does not reap enough profits from its present-day sales of photovoltaic equipment.

  19. Integrative analysis of metabolomics and transcriptomics data

    DEFF Research Database (Denmark)

    Brink-Jensen, Kasper; Bak, Søren; Jørgensen, Kirsten

    2013-01-01

    ) measurements from the same samples, to identify genes controlling the production of metabolites. Due to the high dimensionality of both LC-MS and DNA microarray data, dimension reduction and variable selection are key elements of the analysis. Our proposed approach starts by identifying the basis functions......The abundance of high-dimensional measurements in the form of gene expression and mass spectroscopy calls for models to elucidate the underlying biological system. For widely studied organisms like yeast, it is possible to incorporate prior knowledge from a variety of databases, an approach used...... ("building blocks") that constitute the output from a mass spectrometry experiment. Subsequently, the weights of these basis functions are related to the observations from the corresponding gene expression data in order to identify which genes are associated with specific patterns seen in the metabolite data...

  20. CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures.

    Science.gov (United States)

    Chovancova, Eva; Pavelka, Antonin; Benes, Petr; Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri

    2012-01-01

    Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz.

  1. CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures.

    Directory of Open Access Journals (Sweden)

    Eva Chovancova

    Full Text Available Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz.

  2. CAVER 3.0: A Tool for the Analysis of Transport Pathways in Dynamic Protein Structures

    Science.gov (United States)

    Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri

    2012-01-01

    Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz. PMID:23093919

  3. Estimating environmental co-benefits of U.S. low-carbon pathways using an integrated assessment model with state-level resolution.

    Science.gov (United States)

    Ou, Yang; Shi, Wenjing; Smith, Steven J; Ledna, Catherine M; West, J Jason; Nolte, Christopher G; Loughlin, Daniel H

    2018-04-15

    There are many technological pathways that can lead to reduced carbon dioxide emissions. However, these pathways can have substantially different impacts on other environmental endpoints, such as air quality and energy-related water demand. This study uses an integrated assessment model with state-level resolution of the energy system to compare environmental impacts of alternative low-carbon pathways for the United States. One set of pathways emphasizes nuclear energy and carbon capture and storage, while another set emphasizes renewable energy, including wind, solar, geothermal power, and bioenergy. These are compared with pathways in which all technologies are available. Air pollutant emissions, mortality costs attributable to particulate matter smaller than 2.5 μm in diameter, and energy-related water demands are evaluated for 50% and 80% carbon dioxide reduction targets in 2050. The renewable low-carbon pathways require less water withdrawal and consumption than the nuclear and carbon capture pathways. However, the renewable low-carbon pathways modeled in this study produce higher particulate matter-related mortality costs due to greater use of biomass in residential heating. Environmental co-benefits differ among states because of factors such as existing technology stock, resource availability, and environmental and energy policies.

  4. Vertically Integrated Seismological Analysis II : Inference

    Science.gov (United States)

    Arora, N. S.; Russell, S.; Sudderth, E.

    2009-12-01

    Methods for automatically associating detected waveform features with hypothesized seismic events, and localizing those events, are a critical component of efforts to verify the Comprehensive Test Ban Treaty (CTBT). As outlined in our companion abstract, we have developed a hierarchical model which views detection, association, and localization as an integrated probabilistic inference problem. In this abstract, we provide more details on the Markov chain Monte Carlo (MCMC) methods used to solve this inference task. MCMC generates samples from a posterior distribution π(x) over possible worlds x by defining a Markov chain whose states are the worlds x, and whose stationary distribution is π(x). In the Metropolis-Hastings (M-H) method, transitions in the Markov chain are constructed in two steps. First, given the current state x, a candidate next state x‧ is generated from a proposal distribution q(x‧ | x), which may be (more or less) arbitrary. Second, the transition to x‧ is not automatic, but occurs with an acceptance probability—α(x‧ | x) = min(1, π(x‧)q(x | x‧)/π(x)q(x‧ | x)). The seismic event model outlined in our companion abstract is quite similar to those used in multitarget tracking, for which MCMC has proved very effective. In this model, each world x is defined by a collection of events, a list of properties characterizing those events (times, locations, magnitudes, and types), and the association of each event to a set of observed detections. The target distribution π(x) = P(x | y), the posterior distribution over worlds x given the observed waveform data y at all stations. Proposal distributions then implement several types of moves between worlds. For example, birth moves create new events; death moves delete existing events; split moves partition the detections for an event into two new events; merge moves combine event pairs; swap moves modify the properties and assocations for pairs of events. Importantly, the rules for

  5. Development of safety analysis technology for integral reactor

    Energy Technology Data Exchange (ETDEWEB)

    Sim, Suk K.; Song, J. H.; Chung, Y. J. and others

    1999-03-01

    Inherent safety features and safety system characteristics of the SMART integral reactor are investigated in this study. Performance and safety of the SMART conceptual design have been evaluated and confirmed through the performance and safety analyses using safety analysis system codes as well as a preliminary performance and safety analysis methodology. SMART design base events and their acceptance criteria are identified to develop a preliminary PIRT for the SMART integral reactor. Using the preliminary PIRT, a set of experimental program for the thermal hydraulic separate effect tests and the integral effect tests was developed for the thermal hydraulic model development and the system code validation. Safety characteristics as well as the safety issues of the integral reactor has been identified during the study, which will be used to resolve the safety issues and guide the regulatory criteria for the integral reactor. The results of the performance and safety analyses performed during the study were used to feedback for the SMART conceptual design. The performance and safety analysis code systems as well as the preliminary safety analysis methodology developed in this study will be validated as the SMART design evolves. The performance and safety analysis technology developed during the study will be utilized for the SMART basic design development. (author)

  6. ASCR Cybersecurity for Scientific Computing Integrity - Research Pathways and Ideas Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Peisert, Sean [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Davis, CA (United States); Potok, Thomas E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jones, Todd [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-06-03

    At the request of the U.S. Department of Energy's (DOE) Office of Science (SC) Advanced Scientific Computing Research (ASCR) program office, a workshop was held June 2-3, 2015, in Gaithersburg, MD, to identify potential long term (10 to +20 year) cybersecurity fundamental basic research and development challenges, strategies and roadmap facing future high performance computing (HPC), networks, data centers, and extreme-scale scientific user facilities. This workshop was a follow-on to the workshop held January 7-9, 2015, in Rockville, MD, that examined higher level ideas about scientific computing integrity specific to the mission of the DOE Office of Science. Issues included research computation and simulation that takes place on ASCR computing facilities and networks, as well as network-connected scientific instruments, such as those run by various DOE Office of Science programs. Workshop participants included researchers and operational staff from DOE national laboratories, as well as academic researchers and industry experts. Participants were selected based on the submission of abstracts relating to the topics discussed in the previous workshop report [1] and also from other ASCR reports, including "Abstract Machine Models and Proxy Architectures for Exascale Computing" [27], the DOE "Preliminary Conceptual Design for an Exascale Computing Initiative" [28], and the January 2015 machine learning workshop [29]. The workshop was also attended by several observers from DOE and other government agencies. The workshop was divided into three topic areas: (1) Trustworthy Supercomputing, (2) Extreme-Scale Data, Knowledge, and Analytics for Understanding and Improving Cybersecurity, and (3) Trust within High-end Networking and Data Centers. Participants were divided into three corresponding teams based on the category of their abstracts. The workshop began with a series of talks from the program manager and workshop chair, followed by the leaders for each of the

  7. Overcoming barriers to integrating economic analysis into risk assessment.

    Science.gov (United States)

    Hoffmann, Sandra

    2011-09-01

    Regulatory risk analysis is designed to provide decisionmakers with a clearer understanding of how policies are likely to affect risk. The systems that produce risk are biological, physical, and social and economic. As a result, risk analysis is an inherently interdisciplinary task. Yet in practice, risk analysis has been interdisciplinary in only limited ways. Risk analysis could provide more accurate assessments of risk if there were better integration of economics and other social sciences into risk assessment itself. This essay examines how discussions about risk analysis policy have influenced the roles of various disciplines in risk analysis. It explores ways in which integrated bio/physical-economic modeling could contribute to more accurate assessments of risk. It reviews examples of the kind of integrated economics-bio/physical modeling that could be used to enhance risk assessment. The essay ends with a discussion of institutional barriers to greater integration of economic modeling into risk assessment and provides suggestions on how these might be overcome. © 2011 Society for Risk Analysis.

  8. A network analysis of leadership theory : the infancy of integration.

    OpenAIRE

    Meuser, J. D.; Gardner, W. L.; Dinh, J. E.; Hu, J.; Liden, R. C.; Lord, R. G.

    2016-01-01

    We investigated the status of leadership theory integration by reviewing 14 years of published research (2000 through 2013) in 10 top journals (864 articles). The authors of these articles examined 49 leadership approaches/theories, and in 293 articles, 3 or more of these leadership approaches were included in their investigations. Focusing on these articles that reflected relatively extensive integration, we applied an inductive approach and used graphic network analysis as a guide for drawi...

  9. Integrated analysis of oxide nuclear fuel sintering

    International Nuclear Information System (INIS)

    Baranov, V.; Kuzmin, R.; Tenishev, A.; Timoshin, I.; Khlunov, A.; Ivanov, A.; Petrov, I.

    2011-01-01

    Dilatometric and thermal-gravimetric investigations have been carried out for the sintering process of oxide nuclear fuel in gaseous Ar - 8% H 2 atmosphere at temperatures up to 1600 0 C. The pressed compacts were fabricated under real production conditions of the OAO MSZ with application of two different technologies, so called 'dry' and 'wet' technologies. Effects of the grain size growth after the heating to different temperatures were observed. In order to investigate the effects produced by rate of heating on properties of sintered fuel pellets, the heating rates were varied from 1 to 8 0 C per minute. Time of isothermal overexposure at maximal temperature (1600 0 C) was about 8 hours. Real production conditions were imitated. The results showed that the sintering process of the fuel pellets produced by two technologies differs. The samples sintered under different heating rates were studied with application of scanning electronic microscopy analysis for determination of mean grain size. A simulation of heating profile for industrial furnaces was performed to reduce the beam cycles and estimate the effects of variation of the isothermal overexposure temperatures. Based on this data, an optimization of the sintering conditions was performed in operations terms of OAO MSZ. (authors)

  10. Momentum integral network method for thermal-hydraulic transient analysis

    International Nuclear Information System (INIS)

    Van Tuyle, G.J.

    1983-01-01

    A new momentum integral network method has been developed, and tested in the MINET computer code. The method was developed in order to facilitate the transient analysis of complex fluid flow and heat transfer networks, such as those found in the balance of plant of power generating facilities. The method employed in the MINET code is a major extension of a momentum integral method reported by Meyer. Meyer integrated the momentum equation over several linked nodes, called a segment, and used a segment average pressure, evaluated from the pressures at both ends. Nodal mass and energy conservation determined nodal flows and enthalpies, accounting for fluid compression and thermal expansion

  11. A novel approach to select differential pathways associated with hypertrophic cardiomyopathy based on gene co‑expression analysis.

    Science.gov (United States)

    Chen, Xiao-Min; Feng, Ming-Jun; Shen, Cai-Jie; He, Bin; Du, Xian-Feng; Yu, Yi-Bo; Liu, Jing; Chu, Hui-Min

    2017-07-01

    The present study was designed to develop a novel method for identifying significant pathways associated with human hypertrophic cardiomyopathy (HCM), based on gene co‑expression analysis. The microarray dataset associated with HCM (E‑GEOD‑36961) was obtained from the European Molecular Biology Laboratory‑European Bioinformatics Institute database. Informative pathways were selected based on the Reactome pathway database and screening treatments. An empirical Bayes method was utilized to construct co‑expression networks for informative pathways, and a weight value was assigned to each pathway. Differential pathways were extracted based on weight threshold, which was calculated using a random model. In order to assess whether the co‑expression method was feasible, it was compared with traditional pathway enrichment analysis of differentially expressed genes, which were identified using the significance analysis of microarrays package. A total of 1,074 informative pathways were screened out for subsequent investigations and their weight values were also obtained. According to the threshold of weight value of 0.01057, 447 differential pathways, including folding of actin by chaperonin containing T‑complex protein 1 (CCT)/T‑complex protein 1 ring complex (TRiC), purine ribonucleoside monophosphate biosynthesis and ubiquinol biosynthesis, were obtained. Compared with traditional pathway enrichment analysis, the number of pathways obtained from the co‑expression approach was increased. The results of the present study demonstrated that this method may be useful to predict marker pathways for HCM. The pathways of folding of actin by CCT/TRiC and purine ribonucleoside monophosphate biosynthesis may provide evidence of the underlying molecular mechanisms of HCM, and offer novel therapeutic directions for HCM.

  12. Study on integrated design and analysis platform of NPP

    International Nuclear Information System (INIS)

    Lu Dongsen; Gao Zuying; Zhou Zhiwei

    2001-01-01

    Many calculation software have been developed to nuclear system's design and safety analysis, such as structure design software, fuel design and manage software, thermal hydraulic analysis software, severe accident simulation software, etc. This study integrates those software to a platform, develops visual modeling tool for Retran, NGFM90. And in this platform, a distribution calculation method is also provided for couple calculation between different software. The study will improve the design and analysis of NPP

  13. Integrated failure probability estimation based on structural integrity analysis and failure data: Natural gas pipeline case

    International Nuclear Information System (INIS)

    Dundulis, Gintautas; Žutautaitė, Inga; Janulionis, Remigijus; Ušpuras, Eugenijus; Rimkevičius, Sigitas; Eid, Mohamed

    2016-01-01

    In this paper, the authors present an approach as an overall framework for the estimation of the failure probability of pipelines based on: the results of the deterministic-probabilistic structural integrity analysis (taking into account loads, material properties, geometry, boundary conditions, crack size, and defected zone thickness), the corrosion rate, the number of defects and failure data (involved into the model via application of Bayesian method). The proposed approach is applied to estimate the failure probability of a selected part of the Lithuanian natural gas transmission network. The presented approach for the estimation of integrated failure probability is a combination of several different analyses allowing us to obtain: the critical crack's length and depth, the failure probability of the defected zone thickness, dependency of the failure probability on the age of the natural gas transmission pipeline. A model's uncertainty analysis and uncertainty propagation analysis are performed, as well. - Highlights: • Degradation mechanisms of natural gas transmission pipelines. • Fracture mechanic analysis of the pipe with crack. • Stress evaluation of the pipe with critical crack. • Deterministic-probabilistic structural integrity analysis of gas pipeline. • Integrated estimation of pipeline failure probability by Bayesian method.

  14. Direct integration multiple collision integral transport analysis method for high energy fusion neutronics

    International Nuclear Information System (INIS)

    Koch, K.R.

    1985-01-01

    A new analysis method specially suited for the inherent difficulties of fusion neutronics was developed to provide detailed studies of the fusion neutron transport physics. These studies should provide a better understanding of the limitations and accuracies of typical fusion neutronics calculations. The new analysis method is based on the direct integration of the integral form of the neutron transport equation and employs a continuous energy formulation with the exact treatment of the energy angle kinematics of the scattering process. In addition, the overall solution is analyzed in terms of uncollided, once-collided, and multi-collided solution components based on a multiple collision treatment. Furthermore, the numerical evaluations of integrals use quadrature schemes that are based on the actual dependencies exhibited in the integrands. The new DITRAN computer code was developed on the Cyber 205 vector supercomputer to implement this direct integration multiple-collision fusion neutronics analysis. Three representative fusion reactor models were devised and the solutions to these problems were studied to provide suitable choices for the numerical quadrature orders as well as the discretized solution grid and to understand the limitations of the new analysis method. As further verification and as a first step in assessing the accuracy of existing fusion-neutronics calculations, solutions obtained using the new analysis method were compared to typical multigroup discrete ordinates calculations

  15. IMG: the integrated microbial genomes database and comparative analysis system

    Science.gov (United States)

    Markowitz, Victor M.; Chen, I-Min A.; Palaniappan, Krishna; Chu, Ken; Szeto, Ernest; Grechkin, Yuri; Ratner, Anna; Jacob, Biju; Huang, Jinghua; Williams, Peter; Huntemann, Marcel; Anderson, Iain; Mavromatis, Konstantinos; Ivanova, Natalia N.; Kyrpides, Nikos C.

    2012-01-01

    The Integrated Microbial Genomes (IMG) system serves as a community resource for comparative analysis of publicly available genomes in a comprehensive integrated context. IMG integrates publicly available draft and complete genomes from all three domains of life with a large number of plasmids and viruses. IMG provides tools and viewers for analyzing and reviewing the annotations of genes and genomes in a comparative context. IMG's data content and analytical capabilities have been continuously extended through regular updates since its first release in March 2005. IMG is available at http://img.jgi.doe.gov. Companion IMG systems provide support for expert review of genome annotations (IMG/ER: http://img.jgi.doe.gov/er), teaching courses and training in microbial genome analysis (IMG/EDU: http://img.jgi.doe.gov/edu) and analysis of genomes related to the Human Microbiome Project (IMG/HMP: http://www.hmpdacc-resources.org/img_hmp). PMID:22194640

  16. Data mining and pathway analysis of glucose-6-phosphate dehydrogenase with natural language processing

    Science.gov (United States)

    Chen, Long; Zhang, Chunhua; Wang, Yanling; Li, Yuqian; Han, Qiaoqiao; Yang, Huixin; Zhu, Yuechun

    2017-01-01

    Human glucose-6-phosphate dehydrogenase (G6PD) is a crucial enzyme in the pentose phosphate pathway, and serves an important role in biosynthesis and the redox balance. G6PD deficiency is a major cause of neonatal jaundice and acute hemolyticanemia, and recently, G6PD has been associated with diseases including inflammation and cancer. The aim of the present study was to conduct a search of the National Center for Biotechnology Information PubMed library for articles discussing G6PD. Genes that were identified to be associated with G6PD were recorded, and the frequency at which each gene appeared was calculated. Gene ontology (GO), pathway and network analyses were then performed. A total of 98 G6PD-associated genes and 33 microRNAs (miRNAs) that potentially regulate G6PD were identified. The 98 G6PD-associated genes were then sub-classified into three functional groups by GO analysis, followed by analysis of function, pathway, network, and disease association. Out of the 47 signaling pathways identified, seven were significantly correlated with G6PD-associated genes. At least two out of four independent programs identified the 33 miRNAs that were predicted to target G6PD. miR-1207-5P, miR-1 and miR-125a-5p were predicted by all four software programs to target G6PD. The results of the present study revealed that dysregulation of G6PD was associated with cancer, autoimmune diseases, and oxidative stress-induced disorders. These results revealed the potential roles of G6PD-regulated signaling and metabolic pathways in the etiology of these diseases. PMID:28627690

  17. The Effectiveness of Integrated Care Pathways for Adults and Children in Health Care Settings: A Systematic Review.

    Science.gov (United States)

    Allen, Davina; Gillen, Elizabeth; Rixson, Laura

    Integrated Care Pathways (ICPs) are management technologies which formalise multi-disciplinary team-working and enable professionals to examine and address how they articulate their respective roles, responsibilities and activities. They map out a patient's journey and aim to have: 'the right people, doing the right things, in the right order, at the right time, in the right place, with the right outcome'. Initially introduced into the health care context in the 1980s in the US, enthusiasm for ICPs now extends across the world. They have been promoted as a means to realise: evidence based practice, clinical governance, continuity of care, patient empowerment, efficiency gains, service re-engineering, role realignment and staff education.While ICPs are now being developed and implemented across international health care arena, evidence to support their use is equivocal and understanding of their 'active ingredients' is poor. Reviews of evidence of ICP effectiveness have focused on their use in specific patient populations. However, ICPs are 'complex interventions' and are increasingly being implemented for a variety of purposes in a range of organisational contexts. Identification of the circumstances in which ICPs are effective is the first step towards developing hypotheses about their active ingredients and the generative mechanisms by which they have their effects.This review was designed to address a slightly different set of questions to those that typify systematic reviews of ICP effectiveness. Rather than simply asking: 'Are ICPs effective?', our concern was to identify the circumstances in which ICPs are effective, for whom and in what contexts. In addition to identifying evidence of ICP effectiveness, the review therefore required attention to the contexts in which ICPs are utilised, the purposes to which they are put and the factors critical to their success. In framing the review in this way we are drawing on the insights afforded by Pawson and Tilley

  18. Extending in silico mechanism-of-action analysis by annotating targets with pathways: application to cellular cytotoxicity readouts.

    Science.gov (United States)

    Liggi, Sonia; Drakakis, Georgios; Koutsoukas, Alexios; Cortes-Ciriano, Isidro; Martínez-Alonso, Patricia; Malliavin, Thérèse E; Velazquez-Campoy, Adrian; Brewerton, Suzanne C; Bodkin, Michael J; Evans, David A; Glen, Robert C; Carrodeguas, José Alberto; Bender, Andreas

    2014-01-01

    An in silico mechanism-of-action analysis protocol was developed, comprising molecule bioactivity profiling, annotation of predicted targets with pathways and calculation of enrichment factors to highlight targets and pathways more likely to be implicated in the studied phenotype. The method was applied to a cytotoxicity phenotypic endpoint, with enriched targets/pathways found to be statistically significant when compared with 100 random datasets. Application on a smaller apoptotic set (10 molecules) did not allowed to obtain statistically relevant results, suggesting that the protocol requires modification such as analysis of the most frequently predicted targets/annotated pathways. Pathway annotations improved the mechanism-of-action information gained by target prediction alone, allowing a better interpretation of the predictions and providing better mapping of targets onto pathways.

  19. Integrative genomic analysis identifies isoleucine and CodY as regulators of Listeria monocytogenes virulence.

    Directory of Open Access Journals (Sweden)

    Lior Lobel

    2012-09-01

    Full Text Available Intracellular bacterial pathogens are metabolically adapted to grow within mammalian cells. While these adaptations are fundamental to the ability to cause disease, we know little about the relationship between the pathogen's metabolism and virulence. Here we used an integrative Metabolic Analysis Tool that combines transcriptome data with genome-scale metabolic models to define the metabolic requirements of Listeria monocytogenes during infection. Twelve metabolic pathways were identified as differentially active during L. monocytogenes growth in macrophage cells. Intracellular replication requires de novo synthesis of histidine, arginine, purine, and branch chain amino acids (BCAAs, as well as catabolism of L-rhamnose and glycerol. The importance of each metabolic pathway during infection was confirmed by generation of gene knockout mutants in the respective pathways. Next, we investigated the association of these metabolic requirements in the regulation of L. monocytogenes virulence. Here we show that limiting BCAA concentrations, primarily isoleucine, results in robust induction of the master virulence activator gene, prfA, and the PrfA-regulated genes. This response was specific and required the nutrient responsive regulator CodY, which is known to bind isoleucine. Further analysis demonstrated that CodY is involved in prfA regulation, playing a role in prfA activation under limiting conditions of BCAAs. This study evidences an additional regulatory mechanism underlying L. monocytogenes virulence, placing CodY at the crossroads of metabolism and virulence.

  20. Enhancement of Nucleoside Production in Hirsutella sinensis Based on Biosynthetic Pathway Analysis

    Science.gov (United States)

    Liu, Zhi-Qiang; Zhang, Bo; Lin, Shan; Baker, Peter James; Chen, Mao-Sheng; Xue, Ya-Ping; Wu, Hui; Xu, Feng; Yuan, Shui-Jin; Teng, Yi; Wu, Ling-Fang

    2017-01-01

    To enhance nucleoside production in Hirsutella sinensis, the biosynthetic pathways of purine and pyrimidine nucleosides were constructed and verified. The differential expression analysis showed that purine nucleoside phosphorylase, inosine monophosphate dehydrogenase, and guanosine monophosphate synthase genes involved in purine nucleotide biosynthesis were significantly upregulated 16.56-fold, 8-fold, and 5.43-fold, respectively. Moreover, dihydroorotate dehydrogenase, uridine nucleosidase, uridine/cytidine monophosphate kinase, and inosine triphosphate pyrophosphatase genes participating in pyrimidine nucleoside biosynthesis were upregulated 4.53-fold, 10.63-fold, 4.26-fold, and 5.98-fold, respectively. To enhance the nucleoside production, precursors for synthesis of nucleosides were added based on the analysis of biosynthetic pathways. Uridine and cytidine contents, respectively, reached 5.04 mg/g and 3.54 mg/g when adding 2 mg/mL of ribose, resulting in an increase of 28.6% and 296% compared with the control, respectively. Meanwhile, uridine and cytidine contents, respectively, reached 10.83 mg/g 2.12 mg/g when adding 0.3 mg/mL of uracil, leading to an increase of 176.3% and 137.1%, respectively. This report indicated that fermentation regulation was an effective way to enhance the nucleoside production in H. sinensis based on biosynthetic pathway analysis. PMID:29333435

  1. Identification of Key Pathways and Genes in Advanced Coronary Atherosclerosis Using Bioinformatics Analysis

    Directory of Open Access Journals (Sweden)

    Xiaowen Tan

    2017-01-01

    Full Text Available Background. Coronary artery atherosclerosis is a chronic inflammatory disease. This study aimed to identify the key changes of gene expression between early and advanced carotid atherosclerotic plaque in human. Methods. Gene expression dataset GSE28829 was downloaded from Gene Expression Omnibus (GEO, including 16 advanced and 13 early stage atherosclerotic plaque samples from human carotid. Differentially expressed genes (DEGs were analyzed. Results. 42,450 genes were obtained from the dataset. Top 100 up- and downregulated DEGs were listed. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG identification were performed. The result of functional and pathway enrichment analysis indicted that the immune system process played a critical role in the progression of carotid atherosclerotic plaque. Protein-protein interaction (PPI networks were performed either. Top 10 hub genes were identified from PPI network and top 6 modules were inferred. These genes were mainly involved in chemokine signaling pathway, cell cycle, B cell receptor signaling pathway, focal adhesion, and regulation of actin cytoskeleton. Conclusion. The present study indicated that analysis of DEGs would make a deeper understanding of the molecular mechanisms of atherosclerosis development and they might be used as molecular targets and diagnostic biomarkers for the treatment of atherosclerosis.

  2. Metabolic pathway analysis and kinetic studies for production of nattokinase in Bacillus subtilis.

    Science.gov (United States)

    Unrean, Pornkamol; Nguyen, Nhung H A

    2013-01-01

    We have constructed a reaction network model of Bacillus subtilis. The model was analyzed using a pathway analysis tool called elementary mode analysis (EMA). The analysis tool was used to study the network capabilities and the possible effects of altered culturing conditions on the production of a fibrinolytic enzyme, nattokinase (NK) by B. subtilis. Based on all existing metabolic pathways, the maximum theoretical yield for NK synthesis in B. subtilis under different substrates and oxygen availability was predicted and the optimal culturing condition for NK production was identified. To confirm model predictions, experiments were conducted by testing these culture conditions for their influence on NK activity. The optimal culturing conditions were then applied to batch fermentation, resulting in high NK activity. The EMA approach was also applied for engineering B. subtilis metabolism towards the most efficient pathway for NK synthesis by identifying target genes for deletion and overexpression that enable the cell to produce NK at the maximum theoretical yield. The consistency between experiments and model predictions proves the feasibility of EMA being used to rationally design culture conditions and genetic manipulations for the efficient production of desired products.

  3. Tolerant industrial yeast Saccharomyces cerevisiae posses a more robust cell wall integrity signaling pathway against 2-furaldehyde and 5-(hydroxymethyl)-2-furaldehyde

    Science.gov (United States)

    Cell wall integrity signaling pathway in Saccharomyces cerevisiae is a conserved function for detecting and responding to cell stress conditions but less understood for industrial yeast. We dissected gene expression dynamics for a tolerant industrial yeast strain NRRL Y-50049 in response to challeng...

  4. A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways

    Science.gov (United States)

    Yang, Yunlai; Arouri, Khaled

    2016-03-01

    A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations.

  5. GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia

    Directory of Open Access Journals (Sweden)

    Naveen S. Khanzada

    2017-02-01

    Full Text Available Bipolar disorder (BPD and schizophrenia (SCH show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes, BPD (290 genes and SCH (560 genes. Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e.g., diseases, tissues or functional pathways. Twenty-three genes were common to all three disorders and mapped to nine biological Superpathways including Circadian entrainment (10 genes, score = 37.0, Amphetamine addiction (five genes, score = 24.2, and Sudden infant death syndrome (six genes, score = 24.1. Brain tissues included the medulla oblongata (11 genes, score = 2.1, thalamus (10 genes, score = 2.0 and hypothalamus (nine genes, score = 2.0 with six common genes (BDNF, DRD2, CHRNA7, HTR2A, SLC6A3, and TPH2. Overlapping genes impacted dopamine and serotonin homeostasis and signal transduction pathways, impacting mood, behavior and physical activity level. Converging effects on pathways governing circadian rhythms support a core etiological relationship between neuropsychiatric illnesses and sleep disruption with hypoxia and central brain stem dysfunction.

  6. A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways.

    Science.gov (United States)

    Yang, Yunlai; Arouri, Khaled

    2016-03-11

    A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations.

  7. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features.

    Directory of Open Access Journals (Sweden)

    Marcel Kool

    Full Text Available BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements in cure rates, prediction of disease outcome remains a major challenge and survivors suffer from serious therapy-related side-effects. Recent data showed that patients with WNT-activated tumors have a favorable prognosis, suggesting that these patients could be treated less intensively, thereby reducing the side-effects. This illustrates the potential benefits of a robust classification of medulloblastoma patients and a detailed knowledge of associated biological mechanisms. METHODS AND FINDINGS: To get a better insight into the molecular biology of medulloblastoma we established mRNA expression profiles of 62 medulloblastomas and analyzed 52 of them also by comparative genomic hybridization (CGH arrays. Five molecular subtypes were identified, characterized by WNT signaling (A; 9 cases, SHH signaling (B; 15 cases, expression of neuronal differentiation genes (C and D; 16 and 11 cases, respectively or photoreceptor genes (D and E; both 11 cases. Mutations in beta-catenin were identified in all 9 type A tumors, but not in any other tumor. PTCH1 mutations were exclusively identified in type B tumors. CGH analysis identified several fully or partly subtype-specific chromosomal aberrations. Monosomy of chromosome 6 occurred only in type A tumors, loss of 9q mostly occurred in type B tumors, whereas chromosome 17 aberrations, most common in medulloblastoma, were strongly associated with type C or D tumors. Loss of the inactivated X-chromosome was highly specific for female cases of type C, D and E tumors. Gene expression levels faithfully reflected the chromosomal copy number changes. Clinicopathological features significantly different between the 5 subtypes included metastatic disease and age at diagnosis and histology. Metastatic disease at diagnosis was significantly associated with subtypes C and D and most strongly with subtype E

  8. Integrative sparse principal component analysis of gene expression data.

    Science.gov (United States)

    Liu, Mengque; Fan, Xinyan; Fang, Kuangnan; Zhang, Qingzhao; Ma, Shuangge

    2017-12-01

    In the analysis of gene expression data, dimension reduction techniques have been extensively adopted. The most popular one is perhaps the PCA (principal component analysis). To generate more reliable and more interpretable results, the SPCA (sparse PCA) technique has been developed. With the "small sample size, high dimensionality" characteristic of gene expression data, the analysis results generated from a single dataset are often unsatisfactory. Under contexts other than dimension reduction, integrative analysis techniques, which jointly analyze the raw data of multiple independent datasets, have been developed and shown to outperform "classic" meta-analysis and other multidatasets techniques and single-dataset analysis. In this study, we conduct integrative analysis by developing the iSPCA (integrative SPCA) method. iSPCA achieves the selection and estimation of sparse loadings using a group penalty. To take advantage of the similarity across datasets and generate more accurate results, we further impose contrasted penalties. Different penalties are proposed to accommodate different data conditions. Extensive simulations show that iSPCA outperforms the alternatives under a wide spectrum of settings. The analysis of breast cancer and pancreatic cancer data further shows iSPCA's satisfactory performance. © 2017 WILEY PERIODICALS, INC.

  9. Gastric Cancer Associated Genes Identified by an Integrative Analysis of Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Bing Jiang

    2017-01-01

    Full Text Available Gastric cancer is one of the most severe complex diseases with high morbidity and mortality in the world. The molecular mechanisms and risk factors for this disease are still not clear since the cancer heterogeneity caused by different genetic and environmental factors. With more and more expression data accumulated nowadays, we can perform integrative analysis for these data to understand the complexity of gastric cancer and to identify consensus players for the heterogeneous cancer. In the present work, we screened the published gene expression data and analyzed them with integrative tool, combined with pathway and gene ontology enrichment investigation. We identified several consensus differentially expressed genes and these genes were further confirmed with literature mining; at last, two genes, that is, immunoglobulin J chain and C-X-C motif chemokine ligand 17, were screened as novel gastric cancer associated genes. Experimental validation is proposed to further confirm this finding.

  10. Pathways to Energy from Inertial Fusion. An Integrated Approach. Report of a Coordinated Research Project 2006-2010

    International Nuclear Information System (INIS)

    2013-04-01

    The IAEA has continuously demonstrated its commitment to supporting the development of safe and environmentally clean nuclear fusion energy. Statistics show that at the current rate of energy consumption, fusion energy would remain an inexhaustible energy source for humankind for millions of years. Furthermore, some of the existing and foreseen risks - such as nuclear waste disposal and rising greenhouse gas emissions from the use of fossil fuels - can also be reduced. In the quest for fusion energy, two main lines of research and development are currently being pursued worldwide, namely the inertial and the magnetic confinement fusion concepts. For both approaches, the IAEA has conducted coordinated research activities focusing on specific physics and technological issues relevant the establishment of the knowledge base and foundation for the design and construction of fusion power plants. This report describes the recent research and technological developments and challenges in inertial fusion energy within the framework of such a coordinated research effort. The coordinated research project on Pathways to Energy from Inertial Fusion: An Integrated Approach was initiated in 2006 and concluded in 2010. The project involved experts and institutions from 16 Member States, addressing issues relevant to advancing inertial fusion energy research and development in its practical applications. The key topics addressed include: (i) high repetition rate, low cost, high efficiency ignition drivers; (ii) beam-matter/beam-plasma interaction related to inertial fusion target physics; (iii) target fusion chamber coupling and interface; and (iv) integrated inertial fusion power plant design. Participants in this coordinated research project have contributed 17 detailed research and technology progress reports of work performed at national and international levels. This report compiles all these reports while highlighting the various achievements.

  11. Using Ambystoma mexicanum (Mexican axolotl) embryos, chemical genetics, and microarray analysis to identify signaling pathways associated with tissue regeneration.

    Science.gov (United States)

    Ponomareva, Larissa V; Athippozhy, Antony; Thorson, Jon S; Voss, S Randal

    2015-12-01

    Amphibian vertebrates are important models in regenerative biology because they present exceptional regenerative capabilities throughout life. However, it takes considerable effort to rear amphibians to juvenile and adult stages for regeneration studies, and the relatively large sizes that frogs and salamanders achieve during development make them difficult to use in chemical screens. Here, we introduce a new tail regeneration model using late stage Mexican axolotl embryos. We show that axolotl embryos completely regenerate amputated tails in 7days before they exhaust their yolk supply and begin to feed. Further, we show that axolotl embryos can be efficiently reared in microtiter plates to achieve moderate throughput screening of soluble chemicals to investigate toxicity and identify molecules that alter regenerative outcome. As proof of principle, we identified integration 1 / wingless (Wnt), transforming growth factor beta (Tgf-β), and fibroblast growth factor (Fgf) pathway antagonists that completely block tail regeneration and additional chemicals that significantly affected tail outgrowth. Furthermore, we used microarray analysis to show that inhibition of Wnt signaling broadly affects transcription of genes associated with Wnt, Fgf, Tgf-β, epidermal growth factor (Egf), Notch, nerve growth factor (Ngf), homeotic gene (Hox), rat sarcoma/mitogen-activated protein kinase (Ras/Mapk), myelocytomatosis viral oncogene (Myc), tumor protein 53 (p53), and retinoic acid (RA) pathways. Punctuated changes in the expression of genes known to regulate vertebrate development were observed; this suggests the tail regeneration transcriptional program is hierarchically structured and temporally ordered. Our study establishes the axolotl as a chemical screening model to investigate signaling pathways associated with tissue regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Impacts of agricultural land use on biological integrity: A causal analysis

    Science.gov (United States)

    Riseng, C.M.; Wiley, M.J.; Black, R.W.; Munn, M.D.

    2011-01-01

    Agricultural land use has often been linked to nutrient enrichment, habitat degradation, hydrologic alteration, and loss of biotic integrity in streams. The U.S. Geological Survey's National Water Quality Assessment Program sampled 226 stream sites located in eight agriculture-dominated study units across the United States to investigate the geographic variability and causes of agricultural impacts on stream biotic integrity. In this analysis we used structural equation modeling (SEM) to develop a national and set of regional causal models linking agricultural land use to measured instream conditions. We then examined the direct, indirect, and total effects of agriculture on biotic integrity as it acted through multiple water quality and habitat pathways. In our nation-wide model, cropland affected benthic communities by both altering structural habitats and by imposing water quality-related stresses. Regionspecific modeling demonstrated that geographic context altered the relative importance of causal pathways through which agricultural activities affected stream biotic integrity. Cropland had strong negative total effects on the invertebrate community in the national, Midwest, and Western models, but a very weak effect in the Eastern Coastal Plain model. In theWestern Arid and Eastern Coastal Plain study regions, cropland impacts were transmitted primarily through dissolved water quality contaminants, but in the Midwestern region, they were transmitted primarily through particulate components of water quality. Habitat effects were important in the Western Arid model, but negligible in the Midwest and Eastern Coastal Plain models. The relative effects of riparian forested wetlands also varied regionally, having positive effects on biotic integrity in the Eastern Coastal Plain andWestern Arid region models, but no statistically significant effect in the Midwest. These differences in response to cropland and riparian cover suggest that best management practices and

  13. Potential barriers and facilitators for implementation of an integrated care pathway for hearing-impaired persons: an exploratory survey among patients and professionals

    Directory of Open Access Journals (Sweden)

    Verschuure Hans

    2007-04-01

    Full Text Available Abstract Background Because of the increasing costs and anticipated shortage of Ear Nose and Throat (ENT specialists in the care for hearing-impaired persons, an integrated care pathway that includes direct hearing aid provision was developed. While this direct pathway is still under investigation, in a survey we examined expectations and potential barriers and facilitators towards this direct pathway, of patients and professionals involved in the pathway. Methods Two study populations were assessed: members of the health professions involved in the care pathway for hearing-impaired persons (general practitioners (GPs, hearing aid dispensers, ENT-specialists and clinical audiologists and persons with hearing complaints. We developed a comprehensive semi-structured questionnaire for the professionals, regarding expectations, barriers, facilitators and conditions for implementation. We developed two questionnaires for persons with hearing complaints, both regarding evaluations and preferences, and administered them after they had experienced two key elements of the direct pathway: the triage and the hearing aid fitting. Results On average GPs and hearing aid dispensers had positive expectations towards the direct pathway, while ENT-specialists and clinical audiologists had negative expectations. Professionals stated both barriers and facilitators towards the direct pathway. Most professionals either supported implementation of the direct pathway, provided that a number of conditions were satisfied, or did not support implementation, unless roughly the same conditions were satisfied. Professionals generally agreed on which conditions need to be satisfied. Persons with hearing complaints evaluated the present referral pathway and the new direct pathway equally. Many, especially older, participants stated however that they would still visit the GP and ENT-specialist, even when this would not be necessary for reimbursement of the hearing aid, and

  14. Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development

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    Jesús Lascorz

    2011-01-01

    Full Text Available Background: A large number of gene expression profiling (GEP studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis. Materials and Methods: We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9% had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO categories or Kyoto Encyclopedia of Genes and Genomes (KEGG pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration. Results: Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities. Conclusions: We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.

  15. Uncertainty and sensitivity analysis of food pathway results with the MACCS Reactor Accident Consequence Model

    International Nuclear Information System (INIS)

    Helton, J.C.; Johnson, J.D.; Rollstin, J.A.; Shiver, A.W.; Sprung, J.L.

    1995-01-01

    Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis are used in an investigation with the MACCS model of the food pathways associated with a severe accident at a nuclear power station. The primary purpose of this study is to provide guidance on the variables to be considered in future review work to reduce the uncertainty in the important variables used in the calculation of reactor accident consequences. The effects of 87 imprecisely-known input variables on the following reactor accident consequences are studied: crop growing season dose, crop long-term dose, milk growing season dose, total food pathways dose, total ingestion pathways dose, total long-term pathways dose, area dependent cost, crop disposal cost, milk disposal cost, condemnation area, crop disposal area and milk disposal area. When the predicted variables are considered collectively, the following input variables were found to be the dominant contributors to uncertainty: fraction of cesium deposition on grain fields that is retained on plant surfaces and transferred directly to grain, maximum allowable ground concentrations of Cs-137 and Sr-90 for production of crops, ground concentrations of Cs-134, Cs-137 and I-131 at which the disposal of milk will be initiated due to accidents that occur during the growing season, ground concentrations of Cs-134, I-131 and Sr-90 at which the disposal of crops will be initiated due to accidents that occur during the growing season, rate of depletion of Cs-137 and Sr-90 from the root zone, transfer of Sr-90 from soil to legumes, transfer of Cs-137 from soil to pasture, transfer of cesium from animal feed to meat, and the transfer of cesium, iodine and strontium from animal feed to milk

  16. Uncertainty and sensitivity analysis of food pathway results with the MACCS reactor accident consequence model

    International Nuclear Information System (INIS)

    Helton, J.C.; Johnson, J.D.; Rollstin, J.A.; Shiver, A.W.; Sprung, J.L.

    1995-01-01

    Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis are used in an investigation with the MACCS model of the food pathways associated with a severe accident at a nuclear power station. The primary purpose of this study is to provide guidance on the variables to be considered in future review work to reduce the uncertainty in the important variables used in the calculation of reactor accident consequences. The effects of 87 imprecisely-known input variables on the following reactor accident consequences are studied: crop growing-season dose, crop long-term dose, milk growing-season dose, total food pathways dose, total ingestion pathways dose, total long-term pathways dose, area dependent cost, crop disposal cost, milk disposal cost, condemnation area, crop disposal area and milk disposal area. When the predicted variables are considered collectively, the following input variables were found to be the dominant contributors to uncertainty: fraction of cesium deposition on grain fields that is retained on plant surfaces and transferred directly to grain, maximum allowable ground concentrations of Cs-137 and Sr-90 for production of crops, ground concentrations of Cs-134, Cs-137 and I-131 at which the disposal of milk will be initiated due to accidents that occur during the growing season, ground concentrations of Cs-134, I-131 and Sr-90 at which the disposal of crops will be initiated due to accidents that occur during the growing season, rate of depletion of Cs-137 and Sr-90 from the root zone, transfer of Sr-90 from soil to legumes, transfer of Cs-137 from soil to pasture, transfer of cesium from animal feed to meat, and the transfer of cesium, iodine and strontium from animal feed to milk

  17. Phytohormone signaling pathway analysis method for comparing hormone responses in plant-pest interactions

    Directory of Open Access Journals (Sweden)

    Studham Matthew E

    2012-07-01

    Full Text Available Abstract Background Phytohormones mediate plant defense responses to pests and pathogens. In particular, the hormones jasmonic acid, ethylene, salicylic acid, and abscisic acid have been shown to dictate and fine-tune defense responses, and identification of the phytohormone components of a particular defense response is commonly used to characterize it. Identification of phytohormone regulation is particularly important in transcriptome analyses. Currently there is no computational tool to determine the relative activity of these hormones that can be applied to transcriptome analyses in soybean. Findings We developed a pathway analysis method that provides a broad measure of the activation or suppression of individual phytohormone pathways based on changes in transcript expression of pathway-related genes. The magnitude and significance of these changes are used to determine a pathway score for a phytohormone for a given comparison in a microarray experiment. Scores for individual hormones can then be compared to determine the dominant phytohormone in a given defense response. To validate this method, it was applied to publicly available data from previous microarray experiments that studied the response of soybean plants to Asian soybean rust and soybean cyst nematode. The results of the analyses for these experiments agreed with our current understanding of the role of phytohormones in these defense responses. Conclusions This method is useful in providing a broad measure of the relative induction and suppression of soybean phytohormones during a defense response. This method could be used as part of microarray studies that include individual transcript analysis, gene set analysis, and other methods for a comprehensive defense response characterization.

  18. 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.

  19. Differential phosphorylation of Smad1 integrates BMP and neurotrophin pathways through Erk/Dusp in axon development.

    Science.gov (United States)

    Finelli, Mattéa J; Murphy, Kevin J; Chen, Lei; Zou, Hongyan

    2013-05-30

    Sensory axon development requires concerted actions of growth factors for the precise control of axonal outgrowth and target innervation. How developing sensory neurons integrate different cues is poorly understood. We demonstrate here that Smad1 activation is required for neurotrophin-mediated sensory axon growth in vitro and in vivo. Through differential phosphorylation, Smad1 exerts transcriptional selectivity to regulate the expression and activity of Erk1 and Erk2-two key neurotrophin effectors. Specifically, bone morphogenetic proteins (BMPs) signal through carboxy-terminal phosphorylation of Smad1 (pSmad1C) to induce Erk1/2 transcription for enhanced neurotrophin responsiveness. Meanwhile, neurotrophin signaling results in linker phosphorylation of Smad1 (pSmad1L), which in turn upregulates an Erk-specific dual-specificity phosphatase, Dusp6, leading to reduced pErk1/2 and constituting a negative-feedback loop for the prevention of axon overgrowth. Together, the BMP and neurotrophin pathways form a tightly regulated signaling network with a balanced ratio of Erk1/2 and pErk1/2 to direct the precise connections between sensory neurons and peripheral targets. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Following User Pathways: Cross Platform and Mixed Methods Analysis in Social Media Studies

    DEFF Research Database (Denmark)

    Hall, Margeret; Mazarakis, Athanasios; Peters, Isabella

    2016-01-01

    is the mixed method approach (e.g. qualitative and quantitative methods) in order to better understand how users and society interacts online. The workshop 'Following User Pathways' brings together a community of researchers and professionals to address methodological, analytical, conceptual, and technological......Social media and the resulting tidal wave of available data have changed the ways and methods researchers analyze communities at scale. But the full potential for social scientists (and others) is not yet achieved. Despite the popularity of social media analysis in the past decade, few researchers...... challenges and opportunities of cross-platform, mixed method analysis in social media ecosystems....

  1. Hanford Site Composite Analysis Technical Approach Description: Groundwater Pathway Dose Calculation.

    Energy Technology Data Exchange (ETDEWEB)

    Morgans, D. L. [CH2M Hill Plateau Remediation Company, Richland, WA (United States); Lindberg, S. L. [Intera Inc., Austin, TX (United States)

    2017-09-20

    The purpose of this technical approach document (TAD) is to document the assumptions, equations, and methods used to perform the groundwater pathway radiological dose calculations for the revised Hanford Site Composite Analysis (CA). DOE M 435.1-1, states, “The composite analysis results shall be used for planning, radiation protection activities, and future use commitments to minimize the likelihood that current low-level waste disposal activities will result in the need for future corrective or remedial actions to adequately protect the public and the environment.”

  2. Heading in the right direction: thermodynamics-based network analysis and pathway engineering.

    Science.gov (United States)

    Ataman, Meric; Hatzimanikatis, Vassily

    2015-12-01

    Thermodynamics-based network analysis through the introduction of thermodynamic constraints in metabolic models allows a deeper analysis of metabolism and guides pathway engineering. The number and the areas of applications of thermodynamics-based network analysis methods have been increasing in the last ten years. We review recent applications of these methods and we identify the areas that such analysis can contribute significantly, and the needs for future developments. We find that organisms with multiple compartments and extremophiles present challenges for modeling and thermodynamics-based flux analysis. The evolution of current and new methods must also address the issues of the multiple alternatives in flux directionalities and the uncertainties and partial information from analytical methods. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Assembly of inflammation-related genes for pathway-focused genetic analysis.

    Directory of Open Access Journals (Sweden)

    Matthew J Loza

    2007-10-01

    Full Text Available Recent identifications of associations between novel variants in inflammation-related genes and several common diseases emphasize the need for systematic evaluations of these genes in disease susceptibility. Considering that many genes are involved in the complex inflammation responses and many genetic variants in these genes have the potential to alter the functions and expression of these genes, we assembled a list of key inflammation-related genes to facilitate the identification of genetic associations of diseases with an inflammation-related etiology. We first reviewed various phases of inflammation responses, including the development of immune cells, sensing of danger, influx of cells to sites of insult, activation and functional responses of immune and non-immune cells, and resolution of the immune response. Assisted by the Ingenuity Pathway Analysis, we then identified 17 functional sub-pathways that are involved in one or multiple phases. This organization would greatly increase the chance of detecting gene-gene interactions by hierarchical clustering of genes with their functional closeness in a pathway. Finally, as an example application, we have developed tagging single nucleotide polymorphism (tSNP arrays for populations of European and African descent to capture all the common variants of these key inflammation-related genes. Assays of these tSNPs have been designed and assembled into two Affymetrix ParAllele customized chips, one each for European (12,011 SNPs and African (21,542 SNPs populations. These tSNPs have greater coverage for these inflammation-related genes compared to the existing genome-wide arrays, particularly in the African population. These tSNP arrays can facilitate systematic evaluation of inflammation pathways in disease susceptibility. For additional applications, other genotyping platforms could also be employed. For existing genome-wide association data, this list of key inflammation-related genes and

  4. Argentinean integrated small reactor design and scale economy analysis of integrated reactor

    International Nuclear Information System (INIS)

    Florido, P. C.; Bergallo, J. E.; Ishida, M. V.

    2000-01-01

    This paper describes the design of CAREM, which is Argentinean integrated small reactor project and the scale economy analysis results of integrated reactor. CAREM project consists on the development, design and construction of a small nuclear power plant. CAREM is an advanced reactor conceived with new generation design solutions and standing on the large experience accumulated in the safe operation of Light Water Reactors. The CAREM is an indirect cycle reactor with some distinctive and characteristic features that greatly simplify the reactor and also contribute to a highly level of safety: integrated primary cooling system, self pressurized, primary cooling by natural circulation and safety system relying on passive features. For a fully doupled economic evaluation of integrated reactors done by IREP (Integrated Reactor Evaluation Program) code transferred to IAEA, CAREM have been used as a reference point. The results shows that integrated reactors become competitive with power larger than 200MWe with Argentinean cheapest electricity option. Due to reactor pressure vessel construction limit, low pressure drop steam generator are used to reach power output of 200MWe for natural circulation. For forced circulation, 300MWe can be achieved. (author)

  5. Development of Probabilistic Structural Analysis Integrated with Manufacturing Processes

    Science.gov (United States)

    Pai, Shantaram S.; Nagpal, Vinod K.

    2007-01-01

    An effort has been initiated to integrate manufacturing process simulations with probabilistic structural analyses in order to capture the important impacts of manufacturing uncertainties on component stress levels and life. Two physics-based manufacturing process models (one for powdered metal forging and the other for annular deformation resistance welding) have been linked to the NESSUS structural analysis code. This paper describes the methodology developed to perform this integration including several examples. Although this effort is still underway, particularly for full integration of a probabilistic analysis, the progress to date has been encouraging and a software interface that implements the methodology has been developed. The purpose of this paper is to report this preliminary development.

  6. Integration of rocket turbine design and analysis through computer graphics

    Science.gov (United States)

    Hsu, Wayne; Boynton, Jim

    1988-01-01

    An interactive approach with engineering computer graphics is used to integrate the design and analysis processes of a rocket engine turbine into a progressive and iterative design procedure. The processes are interconnected through pre- and postprocessors. The graphics are used to generate the blade profiles, their stacking, finite element generation, and analysis presentation through color graphics. Steps of the design process discussed include pitch-line design, axisymmetric hub-to-tip meridional design, and quasi-three-dimensional analysis. The viscous two- and three-dimensional analysis codes are executed after acceptable designs are achieved and estimates of initial losses are confirmed.

  7. INS integrated motion analysis for autonomous vehicle navigation

    Science.gov (United States)

    Roberts, Barry; Bazakos, Mike

    1991-01-01

    The use of inertial navigation system (INS) measurements to enhance the quality and robustness of motion analysis techniques used for obstacle detection is discussed with particular reference to autonomous vehicle navigation. The approach to obstacle detection used here employs motion analysis of imagery generated by a passive sensor. Motion analysis of imagery obtained during vehicle travel is used to generate range measurements to points within the field of view of the sensor, which can then be used to provide obstacle detection. Results obtained with an INS integrated motion analysis approach are reviewed.

  8. Integrating computer programs for engineering analysis and design

    Science.gov (United States)

    Wilhite, A. W.; Crisp, V. K.; Johnson, S. C.

    1983-01-01

    The design of a third-generation system for integrating computer programs for engineering and design has been developed for the Aerospace Vehicle Interactive Design (AVID) system. This system consists of an engineering data management system, program interface software, a user interface, and a geometry system. A relational information system (ARIS) was developed specifically for the computer-aided engineering system. It is used for a repository of design data that are communicated between analysis programs, for a dictionary that describes these design data, for a directory that describes the analysis programs, and for other system functions. A method is described for interfacing independent analysis programs into a loosely-coupled design system. This method emphasizes an interactive extension of analysis techniques and manipulation of design data. Also, integrity mechanisms exist to maintain database correctness for multidisciplinary design tasks by an individual or a team of specialists. Finally, a prototype user interface program has been developed to aid in system utilization.

  9. Functional pathway analysis of genes associated with response to treatment for chronic hepatitis C.

    Science.gov (United States)

    Birerdinc, A; Afendy, A; Stepanova, M; Younossi, I; Manyam, G; Baranova, A; Younossi, Z M

    2010-10-01

    Chronic hepatitis C (CH-C) is among the most common causes of chronic liver disease. Approximately 50% of patients with CH-C treated with pegylated interferon-α and ribavirin (PEG-IFN-α + RBV) achieve a sustained virological response (SVR). Several factors such as genotype 1, African American (AA) race, obesity and the absence of an early virological response (EVR) are associated with low SVR. This study elucidates molecular pathways deregulated in patients with CH-C with negative predictors of response to antiviral therapy. Sixty-eight patients with CH-C who underwent a full course of treatment with PEG-IFN-α + RBV were included in the study. Pretreatment blood samples were collected in PAXgene™ RNA tubes. EVR, complete EVR (cEVR), and SVR rates were 76%, 57% and 41%, respectively. Total RNA was extracted from pretreatment peripheral blood mononuclear cells, quantified and used for one-step RT-PCR to profile 154 mRNAs. The expression of mRNAs was normalized with six 'housekeeping' genes. Differentially expressed genes were separated into up and downregulated gene lists according to the presence or absence of a risk factor and subjected to KEGG Pathway Painter which allows high-throughput visualization of the pathway-specific changes in expression profiles. The genes were consolidated into the networks associated with known predictors of response. Before treatment, various genes associated with core components of the JAK/STAT pathway were activated in the cohorts least likely to achieve SVR. Genes related to focal adhesion and TGF-β pathways were activated in some patients with negative predictors of response. Pathway-centred analysis of gene expression profiles from treated patients with CH-C points to the Janus kinase-signal transducers and activators of transcription signalling cascade as the major pathogenetic component responsible for not achieving SVR. In addition, focal adhesion and TGF-β pathways are associated with some predictors of response.

  10. Thermodynamics of metabolic pathways for penicillin production: Analysis of thermodynamic feasibility and free energy changes during fed-batch cultivation

    DEFF Research Database (Denmark)

    Pissarra, P.D.; Nielsen, Jens Bredal

    1997-01-01

    This paper describes the thermodynamic analysis of pathways related to penicillin production in Penicillium chrysogenum. First a thermodynamic feasibility analysis is performed of the L-lysine pathway of which one of the precursors for penicillin biosynthesis (alpha-aminoadipic acid......) is an intermediate. It is found that the L-lysine pathway in P. chrysogenum is thermodynamically feasible and that the calculated standard Gibbs free energy values of the two enzymes controlling the pathway flux indicate that they operate far from equilibrium. It is therefore proposed that the regulation of alpha......-aminoadipate reductase by lysine is important to maintain a high concentration of alpha-aminoadipate in order to direct the carbon flux to penicillin production. Secondly the changes in Gibbs free energy in the penicillin biosynthetic pathway during fed-batch cultivation were studied. The analysis showed that all...

  11. Pathway-based Analysis of the Hidden Genetic Heterogeneities in Cancers

    Directory of Open Access Journals (Sweden)

    Xiaolei Zhao

    2014-02-01

    Full Text Available Many cancers apparently showing similar phenotypes are actually distinct at the molecular level, leading to very different responses to the same treatment. It has been recently demonstrated that pathway-based approaches are robust and reliable for genetic analysis of cancers. Nevertheless, it remains unclear whether such function-based approaches are useful in deciphering molecular heterogeneities in cancers. Therefore, we aimed to test this possibility in the present study. First, we used a NCI60 dataset to validate the ability of pathways to correctly partition samples. Next, we applied the proposed method to identify the hidden subtypes in diffuse large B-cell lymphoma (DLBCL. Finally, the clinical significance of the identified subtypes was verified using survival analysis. For the NCI60 dataset, we achieved highly accurate partitions that best fit the clinical cancer phenotypes. Subsequently, for a DLBCL dataset, we identified three hidden subtypes that showed very different 10-year overall survival rates (90%, 46% and 20% and were highly significantly (P = 0.008 correlated with the clinical survival rate. This study demonstrated that the pathway-based approach is promising for unveiling genetic heterogeneities in complex human diseases.

  12. Novel degradation pathway and kinetic analysis for buprofezin removal by newly isolated Bacillus sp.

    Science.gov (United States)

    Wang, Guangli; Xu, Dayong; Xiong, Minghua; Zhang, Hui; Li, Feng; Liu, Yuan

    2016-09-15

    Given the intensive and widespread application of the pesticide, buprofezin, its environmental residues potentially pose a problem; yet little is known about buprofezin's kinetic and metabolic behaviors. In this study, a novel gram-positive strain, designated BF-5, isolated from aerobic activated sludge, was found to be capable of metabolizing buprofezin as its sole energy, carbon, and nitrogen source. Based on its physiological and biochemical characteristics, other aspects of its phenotype, and a phylogenetic analysis, strain BF-5 was identified as Bacillus sp. This study investigated the effect of culture conditions on bacterial growth and substrate degradation, such as pH, temperature, initial concentration, different nitrogen source, and additional nitrogen sources as co-substrates. The degradation rate parameters, qmax, Ks, Ki and Sm were determined to be 0.6918 h(-1), 105.4 mg L(-1), 210.5 mg L(-1), and 148.95 mg L(-1) respectively. The capture of unpublished potential metabolites by gas chromatography-mass spectrometry (GC-MS) analysis has led to the proposal of a novel degradation pathway. Taken together, our results clarify buprofezin's biodegradation pathway(s) and highlight the promising potential of strain BF-5 in bioremediation of buprofezin-contaminated environments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Analysis and Modeling of Integrated Magnetics for LLC resonant Converters

    DEFF Research Database (Denmark)

    Li, Mingxiao; Ouyang, Ziwei; Zhao, Bin

    2017-01-01

    Shunt-inserted transformers are widely used toobtain high leakage inductance. This paper investigates thismethod in depth to make it applicable to integrate resonantinductor for the LLC resonant converters. The analysis andmodel of magnetizing inductance and leakage inductance forshunt...... transformers can provide a significantdifference. The way to obtain the desirable magnetizing andleakage inductance value for LLC resonant converters issimplified by the creation of air gaps together with a magneticshunt. The calculation and relation are validated by finiteelement analysis (FEA) simulations...

  14. Integrated dynamic modeling and management system mission analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, A.K.

    1994-12-28

    This document summarizes the mission analysis performed on the Integrated Dynamic Modeling and Management System (IDMMS). The IDMMS will be developed to provide the modeling and analysis capability required to understand the TWRS system behavior in terms of the identified TWRS performance measures. The IDMMS will be used to demonstrate in a verified and validated manner the satisfactory performance of the TWRS system configuration and assurance that the requirements have been satisfied.

  15. Integrated dynamic modeling and management system mission analysis

    International Nuclear Information System (INIS)

    Lee, A.K.

    1994-01-01

    This document summarizes the mission analysis performed on the Integrated Dynamic Modeling and Management System (IDMMS). The IDMMS will be developed to provide the modeling and analysis capability required to understand the TWRS system behavior in terms of the identified TWRS performance measures. The IDMMS will be used to demonstrate in a verified and validated manner the satisfactory performance of the TWRS system configuration and assurance that the requirements have been satisfied

  16. Heater-Integrated Cantilevers for Nano-Samples Thermogravimetric Analysis

    OpenAIRE

    Toffoli, Valeria; Carrato, Sergio; Lee, Dongkyu; Jeon, Sangmin; Lazzarino, Marco

    2013-01-01

    The design and characteristics of a micro-system for thermogravimetric analysis (TGA) in which heater, temperature sensor and mass sensor are integrated into a single device are presented. The system consists of a suspended cantilever that incorporates a microfabricated resistor, used as both heater and thermometer. A three-dimensional finite element analysis was used to define the structure parameters. TGA sensors were fabricated by standard microlithographic techniques and tested using mill...

  17. On the Integration of Digital Design and Analysis Tools

    DEFF Research Database (Denmark)

    Klitgaard, Jens; Kirkegaard, Poul Henning

    2006-01-01

    The aim of this research is to look into integrated digital design and analysis tools in order to find out if it is suited for use by architects and designers or only by specialists and technicians - and if not, then to look at what can be done to make them more available to architects and design...