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Sample records for interactome analyses identify

  1. Interactome analyses identify ties of PrP and its mammalian paralogs to oligomannosidic N-glycans and endoplasmic reticulum-derived chaperones.

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    Joel C Watts

    2009-10-01

    Full Text Available The physiological environment which hosts the conformational conversion of the cellular prion protein (PrP(C to disease-associated isoforms has remained enigmatic. A quantitative investigation of the PrP(C interactome was conducted in a cell culture model permissive to prion replication. To facilitate recognition of relevant interactors, the study was extended to Doppel (Prnd and Shadoo (Sprn, two mammalian PrP(C paralogs. Interestingly, this work not only established a similar physiological environment for the three prion protein family members in neuroblastoma cells, but also suggested direct interactions amongst them. Furthermore, multiple interactions between PrP(C and the neural cell adhesion molecule, the laminin receptor precursor, Na/K ATPases and protein disulfide isomerases (PDI were confirmed, thereby reconciling previously separate findings. Subsequent validation experiments established that interactions of PrP(C with PDIs may extend beyond the endoplasmic reticulum and may play a hitherto unrecognized role in the accumulation of PrP(Sc. A simple hypothesis is presented which accounts for the majority of interactions observed in uninfected cells and suggests that PrP(C organizes its molecular environment on account of its ability to bind to adhesion molecules harboring immunoglobulin-like domains, which in turn recognize oligomannose-bearing membrane proteins.

  2. Interactome analyses identify ties of PrP and its mammalian paralogs to oligomannosidic N-glycans and endoplasmic reticulum-derived chaperones.

    Science.gov (United States)

    Watts, Joel C; Huo, Hairu; Bai, Yu; Ehsani, Sepehr; Jeon, Amy Hye Won; Won, Amy Hye; Shi, Tujin; Daude, Nathalie; Lau, Agnes; Young, Rebecca; Xu, Lei; Carlson, George A; Williams, David; Westaway, David; Schmitt-Ulms, Gerold

    2009-10-01

    The physiological environment which hosts the conformational conversion of the cellular prion protein (PrP(C)) to disease-associated isoforms has remained enigmatic. A quantitative investigation of the PrP(C) interactome was conducted in a cell culture model permissive to prion replication. To facilitate recognition of relevant interactors, the study was extended to Doppel (Prnd) and Shadoo (Sprn), two mammalian PrP(C) paralogs. Interestingly, this work not only established a similar physiological environment for the three prion protein family members in neuroblastoma cells, but also suggested direct interactions amongst them. Furthermore, multiple interactions between PrP(C) and the neural cell adhesion molecule, the laminin receptor precursor, Na/K ATPases and protein disulfide isomerases (PDI) were confirmed, thereby reconciling previously separate findings. Subsequent validation experiments established that interactions of PrP(C) with PDIs may extend beyond the endoplasmic reticulum and may play a hitherto unrecognized role in the accumulation of PrP(Sc). A simple hypothesis is presented which accounts for the majority of interactions observed in uninfected cells and suggests that PrP(C) organizes its molecular environment on account of its ability to bind to adhesion molecules harboring immunoglobulin-like domains, which in turn recognize oligomannose-bearing membrane proteins.

  3. A predicted protein interactome identifies conserved global networks and disease resistance subnetworks in maize.

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    Matt eGeisler

    2015-06-01

    Full Text Available Interactomes are genome-wide roadmaps of protein-protein interactions. They have been produced for humans, yeast, the fruit fly, and Arabidopsis thaliana and have become invaluable tools for generating and testing hypotheses. A predicted interactome for Zea mays (PiZeaM is presented here as an aid to the research community for this valuable crop species. PiZeaM was built using a proven method of interologs (interacting orthologs that were identified using both one-to-one and many-to-many orthology between genomes of maize and reference species. Where both maize orthologs occurred for an experimentally determined interaction in the reference species, we predicted a likely interaction in maize. A total of 49,026 unique interactions for 6,004 maize proteins were predicted. These interactions are enriched for processes that are evolutionarily conserved, but include many otherwise poorly annotated proteins in maize. The predicted maize interactions were further analyzed by comparing annotation of interacting proteins, including different layers of ontology. A map of pairwise gene co-expression was also generated and compared to predicted interactions. Two global subnetworks were constructed for highly conserved interactions. These subnetworks showed clear clustering of proteins by function. Another subnetwork was created for disease response using a bait and prey strategy to capture interacting partners for proteins that respond to other organisms. Closer examination of this subnetwork revealed the connectivity between biotic and abiotic hormone stress pathways. We believe PiZeaM will provide a useful tool for the prediction of protein function and analysis of pathways for Z. mays researchers and is presented in this paper as a reference tool for the exploration of protein interactions in maize.

  4. An affinity pull-down approach to identify the plant cyclic nucleotide interactome

    KAUST Repository

    Donaldson, Lara Elizabeth; Meier, Stuart Kurt

    2013-01-01

    Cyclic nucleotides (CNs) are intracellular second messengers that play an important role in mediating physiological responses to environmental and developmental signals, in species ranging from bacteria to humans. In response to these signals, CNs are synthesized by nucleotidyl cyclases and then act by binding to and altering the activity of downstream target proteins known as cyclic nucleotide-binding proteins (CNBPs). A number of CNBPs have been identified across kingdoms including transcription factors, protein kinases, phosphodiesterases, and channels, all of which harbor conserved CN-binding domains. In plants however, few CNBPs have been identified as homology searches fail to return plant sequences with significant matches to known CNBPs. Recently, affinity pull-down techniques have been successfully used to identify CNBPs in animals and have provided new insights into CN signaling. The application of these techniques to plants has not yet been extensively explored and offers an alternative approach toward the unbiased discovery of novel CNBP candidates in plants. Here, an affinity pull-down technique for the identification of the plant CN interactome is presented. In summary, the method involves an extraction of plant proteins which is incubated with a CN-bait, followed by a series of increasingly stringent elutions that eliminates proteins in a sequential manner according to their affinity to the bait. The eluted and bait-bound proteins are separated by one-dimensional gel electrophoresis, excised, and digested with trypsin after which the resultant peptides are identified by mass spectrometry - techniques that are commonplace in proteomics experiments. The discovery of plant CNBPs promises to provide valuable insight into the mechanism of CN signal transduction in plants. © Springer Science+Business Media New York 2013.

  5. An affinity pull-down approach to identify the plant cyclic nucleotide interactome

    KAUST Repository

    Donaldson, Lara Elizabeth

    2013-09-03

    Cyclic nucleotides (CNs) are intracellular second messengers that play an important role in mediating physiological responses to environmental and developmental signals, in species ranging from bacteria to humans. In response to these signals, CNs are synthesized by nucleotidyl cyclases and then act by binding to and altering the activity of downstream target proteins known as cyclic nucleotide-binding proteins (CNBPs). A number of CNBPs have been identified across kingdoms including transcription factors, protein kinases, phosphodiesterases, and channels, all of which harbor conserved CN-binding domains. In plants however, few CNBPs have been identified as homology searches fail to return plant sequences with significant matches to known CNBPs. Recently, affinity pull-down techniques have been successfully used to identify CNBPs in animals and have provided new insights into CN signaling. The application of these techniques to plants has not yet been extensively explored and offers an alternative approach toward the unbiased discovery of novel CNBP candidates in plants. Here, an affinity pull-down technique for the identification of the plant CN interactome is presented. In summary, the method involves an extraction of plant proteins which is incubated with a CN-bait, followed by a series of increasingly stringent elutions that eliminates proteins in a sequential manner according to their affinity to the bait. The eluted and bait-bound proteins are separated by one-dimensional gel electrophoresis, excised, and digested with trypsin after which the resultant peptides are identified by mass spectrometry - techniques that are commonplace in proteomics experiments. The discovery of plant CNBPs promises to provide valuable insight into the mechanism of CN signal transduction in plants. © Springer Science+Business Media New York 2013.

  6. A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors

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    Mohamed Lamine Hafirassou

    2017-12-01

    Full Text Available Dengue virus (DENV infections cause the most prevalent mosquito-borne viral disease worldwide, for which no therapies are available. DENV encodes seven non-structural (NS proteins that co-assemble and recruit poorly characterized host factors to form the DENV replication complex essential for viral infection. Here, we provide a global proteomic analysis of the human host factors that interact with the DENV NS1 protein. Combined with a functional RNAi screen, this study reveals a comprehensive network of host cellular processes involved in DENV infection and identifies DENV host restriction and dependency factors. We highlight an important role of RACK1 and the chaperonin TRiC (CCT and oligosaccharyltransferase (OST complexes during DENV replication. We further show that the OST complex mediates NS1 and NS4B glycosylation, and pharmacological inhibition of its N-glycosylation function strongly impairs DENV infection. In conclusion, our study provides a global interactome of the DENV NS1 and identifies host factors targetable for antiviral therapies.

  7. Identifying candidate agents for lung adenocarcinoma by walking the human interactome

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    Sun Y

    2016-09-01

    Full Text Available Yajiao Sun,1 Ranran Zhang,2 Zhe Jiang,1 Rongyao Xia,1 Jingwen Zhang,1 Jing Liu,1 Fuhui Chen1 1Department of Respiratory, The Second Affiliated Hospital of Harbin Medical University, 2Department of Respiratory, Harbin First Hospital, Harbin, People’s Republic of China Abstract: Despite recent advances in therapeutic strategies for lung cancer, mortality is still increasing. Therefore, there is an urgent need to identify effective novel drugs. In the present study, we implement drug repositioning for lung adenocarcinoma (LUAD by a bioinformatics method followed by experimental validation. We first identified differentially expressed genes between LUAD tissues and nontumor tissues from RNA sequencing data obtained from The Cancer Genome Atlas database. Then, candidate small molecular drugs were ranked according to the effect of their targets on differentially expressed genes of LUAD by a random walk with restart algorithm in protein–protein interaction networks. Our method identified some potentially novel agents for LUAD besides those that had been previously reported (eg, hesperidin. Finally, we experimentally verified that atracurium, one of the potential agents, could induce A549 cells death in non-small-cell lung cancer-derived A549 cells by an MTT assay, acridine orange and ethidium bromide staining, and electron microscopy. Furthermore, Western blot assays demonstrated that atracurium upregulated the proapoptotic Bad and Bax proteins, downregulated the antiapoptotic p-Bad and Bcl-2 proteins, and enhanced caspase-3 activity. It could also reduce the expression of p53 and p21Cip1/Waf1 in A549 cells. In brief, the candidate agents identified by our approach may provide greater insights into improving the therapeutic status of LUAD. Keywords: lung adenocarcinoma, drug repositioning, bioinformatics, protein–protein interaction network, atracurium

  8. System-level insights into the cellular interactome of a non-model organism: inferring, modelling and analysing functional gene network of soybean (Glycine max.

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    Yungang Xu

    Full Text Available Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN, a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max, due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs, in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional

  9. RNA/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage.

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    Cristini, Agnese; Groh, Matthias; Kristiansen, Maiken S; Gromak, Natalia

    2018-05-08

    R-loops comprise an RNA/DNA hybrid and displaced single-stranded DNA. They play important biological roles and are implicated in pathology. Even so, proteins recognizing these structures are largely undefined. Using affinity purification with the S9.6 antibody coupled to mass spectrometry, we defined the RNA/DNA hybrid interactome in HeLa cells. This consists of known R-loop-associated factors SRSF1, FACT, and Top1, and yet uncharacterized interactors, including helicases, RNA processing, DNA repair, and chromatin factors. We validate specific examples of these interactors and characterize their involvement in R-loop biology. A top candidate DHX9 helicase promotes R-loop suppression and transcriptional termination. DHX9 interacts with PARP1, and both proteins prevent R-loop-associated DNA damage. DHX9 and other interactome helicases are overexpressed in cancer, linking R-loop-mediated DNA damage and disease. Our RNA/DNA hybrid interactome provides a powerful resource to study R-loop biology in health and disease. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Information flow analysis of interactome networks.

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    Patrycja Vasilyev Missiuro

    2009-04-01

    Full Text Available Recent studies of cellular networks have revealed modular organizations of genes and proteins. For example, in interactome networks, a module refers to a group of interacting proteins that form molecular complexes and/or biochemical pathways and together mediate a biological process. However, it is still poorly understood how biological information is transmitted between different modules. We have developed information flow analysis, a new computational approach that identifies proteins central to the transmission of biological information throughout the network. In the information flow analysis, we represent an interactome network as an electrical circuit, where interactions are modeled as resistors and proteins as interconnecting junctions. Construing the propagation of biological signals as flow of electrical current, our method calculates an information flow score for every protein. Unlike previous metrics of network centrality such as degree or betweenness that only consider topological features, our approach incorporates confidence scores of protein-protein interactions and automatically considers all possible paths in a network when evaluating the importance of each protein. We apply our method to the interactome networks of Saccharomyces cerevisiae and Caenorhabditis elegans. We find that the likelihood of observing lethality and pleiotropy when a protein is eliminated is positively correlated with the protein's information flow score. Even among proteins of low degree or low betweenness, high information scores serve as a strong predictor of loss-of-function lethality or pleiotropy. The correlation between information flow scores and phenotypes supports our hypothesis that the proteins of high information flow reside in central positions in interactome networks. We also show that the ranks of information flow scores are more consistent than that of betweenness when a large amount of noisy data is added to an interactome. Finally, we

  11. Inferring modules from human protein interactome classes

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    Chaurasia Gautam

    2010-07-01

    Full Text Available Abstract Background The integration of protein-protein interaction networks derived from high-throughput screening approaches and complementary sources is a key topic in systems biology. Although integration of protein interaction data is conventionally performed, the effects of this procedure on the result of network analyses has not been examined yet. In particular, in order to optimize the fusion of heterogeneous interaction datasets, it is crucial to consider not only their degree of coverage and accuracy, but also their mutual dependencies and additional salient features. Results We examined this issue based on the analysis of modules detected by network clustering methods applied to both integrated and individual (disaggregated data sources, which we call interactome classes. Due to class diversity, we deal with variable dependencies of data features arising from structural specificities and biases, but also from possible overlaps. Since highly connected regions of the human interactome may point to potential protein complexes, we have focused on the concept of modularity, and elucidated the detection power of module extraction algorithms by independent validations based on GO, MIPS and KEGG. From the combination of protein interactions with gene expressions, a confidence scoring scheme has been proposed before proceeding via GO with further classification in permanent and transient modules. Conclusions Disaggregated interactomes are shown to be informative for inferring modularity, thus contributing to perform an effective integrative analysis. Validation of the extracted modules by multiple annotation allows for the assessment of confidence measures assigned to the modules in a protein pathway context. Notably, the proposed multilayer confidence scheme can be used for network calibration by enabling a transition from unweighted to weighted interactomes based on biological evidence.

  12. Interactome Screening Identifies the ER Luminal Chaperone Hsp47 as a Regulator of the Unfolded Protein Response Transducer IRE1α.

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    Sepulveda, Denisse; Rojas-Rivera, Diego; Rodríguez, Diego A; Groenendyk, Jody; Köhler, Andres; Lebeaupin, Cynthia; Ito, Shinya; Urra, Hery; Carreras-Sureda, Amado; Hazari, Younis; Vasseur-Cognet, Mireille; Ali, Maruf M U; Chevet, Eric; Campos, Gisela; Godoy, Patricio; Vaisar, Tomas; Bailly-Maitre, Béatrice; Nagata, Kazuhiro; Michalak, Marek; Sierralta, Jimena; Hetz, Claudio

    2018-01-18

    Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). IRE1α is a major UPR transducer, determining cell fate under ER stress. We used an interactome screening to unveil several regulators of the UPR, highlighting the ER chaperone Hsp47 as the major hit. Cellular and biochemical analysis indicated that Hsp47 instigates IRE1α signaling through a physical interaction. Hsp47 directly binds to the ER luminal domain of IRE1α with high affinity, displacing the negative regulator BiP from the complex to facilitate IRE1α oligomerization. The regulation of IRE1α signaling by Hsp47 is evolutionarily conserved as validated using fly and mouse models of ER stress. Hsp47 deficiency sensitized cells and animals to experimental ER stress, revealing the significance of Hsp47 to global proteostasis maintenance. We conclude that Hsp47 adjusts IRE1α signaling by fine-tuning the threshold to engage an adaptive UPR. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Anti-schistosomal intervention targets identified by lifecycle transcriptomic analyses.

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    Jennifer M Fitzpatrick

    2009-11-01

    Full Text Available Novel methods to identify anthelmintic drug and vaccine targets are urgently needed, especially for those parasite species currently being controlled by singular, often limited strategies. A clearer understanding of the transcriptional components underpinning helminth development will enable identification of exploitable molecules essential for successful parasite/host interactions. Towards this end, we present a combinatorial, bioinformatics-led approach, employing both statistical and network analyses of transcriptomic data, for identifying new immunoprophylactic and therapeutic lead targets to combat schistosomiasis.Utilisation of a Schistosoma mansoni oligonucleotide DNA microarray consisting of 37,632 elements enabled gene expression profiling from 15 distinct parasite lifecycle stages, spanning three unique ecological niches. Statistical approaches of data analysis revealed differential expression of 973 gene products that minimally describe the three major characteristics of schistosome development: asexual processes within intermediate snail hosts, sexual maturation within definitive vertebrate hosts and sexual dimorphism amongst adult male and female worms. Furthermore, we identified a group of 338 constitutively expressed schistosome gene products (including 41 transcripts sharing no sequence similarity outside the Platyhelminthes, which are likely to be essential for schistosome lifecycle progression. While highly informative, statistics-led bioinformatics mining of the transcriptional dataset has limitations, including the inability to identify higher order relationships between differentially expressed transcripts and lifecycle stages. Network analysis, coupled to Gene Ontology enrichment investigations, facilitated a re-examination of the dataset and identified 387 clusters (containing 12,132 gene products displaying novel examples of developmentally regulated classes (including 294 schistosomula and/or adult transcripts with no

  14. Cell Interactomics and Carcinogenetic Mechanisms

    CERN Document Server

    Baianu, IC; Report to the Institute of Genomics

    2004-01-01

    Single cell interactomics in simpler organisms, as well as somatic cell interactomics in multicellular organisms, involve biomolecular interactions in complex signalling pathways that were recently represented in modular terms by quantum automata with ‘reversible behavior’ representing normal cell cycling and division. Other implications of such quantum automata, modular modeling of signaling pathways and cell differentiation during development are in the fields of neural plasticity and brain development leading to quantum-weave dynamic patterns and specific molecular processes underlying extensive memory, learning, anticipation mechanisms and the emergence of human consciousness during the early brain development in children. Cell interactomics is here represented for the first time as a mixture of ‘classical’ states that determine molecular dynamics subject to Boltzmann statistics and ‘steady-state’, metabolic (multi-stable) manifolds, together with ‘configuration’ spaces of metastable quant...

  15. A critical and Integrated View of the Yeast Interactome

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    Stephen G. Oliver

    2006-04-01

    Full Text Available Global studies of protein–protein interactions are crucial to both elucidating gene function and producing an integrated view of the workings of living cells. High-throughput studies of the yeast interactome have been performed using both genetic and biochemical screens. Despite their size, the overlap between these experimental datasets is very limited. This could be due to each approach sampling only a small fraction of the total interactome. Alternatively, a large proportion of the data from these screens may represent false-positive interactions. We have used the Genome Information Management System (GIMS to integrate interactome datasets with transcriptome and protein annotation data and have found significant evidence that the proportion of false-positive results is high. Not all high-throughput datasets are similarly contaminated, and the tandem affinity purification (TAP approach appears to yield a high proportion of reliable interactions for which corroborating evidence is available. From our integrative analyses, we have generated a set of verified interactome data for yeast.

  16. The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

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    de Chassey, Benoît; Aublin-Gex, Anne; Ruggieri, Alessia; Meyniel-Schicklin, Laurène; Pradezynski, Fabrine; Davoust, Nathalie; Chantier, Thibault; Tafforeau, Lionel; Mangeot, Philippe-Emmanuel; Ciancia, Claire; Perrin-Cocon, Laure; Bartenschlager, Ralf; André, Patrice; Lotteau, Vincent

    2013-01-01

    Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

  17. The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

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    Benoît de Chassey

    Full Text Available Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1 appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

  18. Identifying null meta-analyses that are ripe for updating

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    Fang Manchun

    2003-07-01

    Full Text Available Abstract Background As an increasingly large number of meta-analyses are published, quantitative methods are needed to help clinicians and systematic review teams determine when meta-analyses are not up to date. Methods We propose new methods for determining when non-significant meta-analytic results might be overturned, based on a prediction of the number of participants required in new studies. To guide decision making, we introduce the "new participant ratio", the ratio of the actual number of participants in new studies to the predicted number required to obtain statistical significance. A simulation study was conducted to study the performance of our methods and a real meta-analysis provides further evidence. Results In our three simulation configurations, our diagnostic test for determining whether a meta-analysis is out of date had sensitivity of 55%, 62%, and 49% with corresponding specificity of 85%, 80%, and 90% respectively. Conclusions Simulations suggest that our methods are able to detect out-of-date meta-analyses. These quick and approximate methods show promise for use by systematic review teams to help decide whether to commit the considerable resources required to update a meta-analysis. Further investigation and evaluation of the methods is required before they can be recommended for general use.

  19. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-03

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  20. Serial interactome capture of the human cell nucleus.

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    Conrad, Thomas; Albrecht, Anne-Susann; de Melo Costa, Veronica Rodrigues; Sauer, Sascha; Meierhofer, David; Ørom, Ulf Andersson

    2016-04-04

    Novel RNA-guided cellular functions are paralleled by an increasing number of RNA-binding proteins (RBPs). Here we present 'serial RNA interactome capture' (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)-RNA-protein complexes that enables global RBP detection with high specificity. We apply serIC to the nuclei of proliferating K562 cells to obtain the first human nuclear RNA interactome. The domain composition of the 382 identified nuclear RBPs markedly differs from previous IC experiments, including few factors without known RNA-binding domains that are in good agreement with computationally predicted RNA binding. serIC extends the number of DNA-RNA-binding proteins (DRBPs), and reveals a network of RBPs involved in p53 signalling and double-strand break repair. serIC is an effective tool to couple global RBP capture with additional selection or labelling steps for specific detection of highly purified RBPs.

  1. Organization of physical interactomes as uncovered by network schemas.

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    Banks, Eric; Nabieva, Elena; Chazelle, Bernard; Singh, Mona

    2008-10-01

    Large-scale protein-protein interaction networks provide new opportunities for understanding cellular organization and functioning. We introduce network schemas to elucidate shared mechanisms within interactomes. Network schemas specify descriptions of proteins and the topology of interactions among them. We develop algorithms for systematically uncovering recurring, over-represented schemas in physical interaction networks. We apply our methods to the S. cerevisiae interactome, focusing on schemas consisting of proteins described via sequence motifs and molecular function annotations and interacting with one another in one of four basic network topologies. We identify hundreds of recurring and over-represented network schemas of various complexity, and demonstrate via graph-theoretic representations how more complex schemas are organized in terms of their lower-order constituents. The uncovered schemas span a wide range of cellular activities, with many signaling and transport related higher-order schemas. We establish the functional importance of the schemas by showing that they correspond to functionally cohesive sets of proteins, are enriched in the frequency with which they have instances in the H. sapiens interactome, and are useful for predicting protein function. Our findings suggest that network schemas are a powerful paradigm for organizing, interrogating, and annotating cellular networks.

  2. RNA-Binding Proteins Revisited – The Emerging Arabidopsis mRNA Interactome

    KAUST Repository

    Kö ster, Tino; Marondedze, Claudius; Meyer, Katja; Staiger, Dorothee

    2017-01-01

    RNA–protein interaction is an important checkpoint to tune gene expression at the RNA level. Global identification of proteins binding in vivo to mRNA has been possible through interactome capture – where proteins are fixed to target RNAs by UV crosslinking and purified through affinity capture of polyadenylated RNA. In Arabidopsis over 500 RNA-binding proteins (RBPs) enriched in UV-crosslinked samples have been identified. As in mammals and yeast, the mRNA interactomes came with a few surprises. For example, a plethora of the proteins caught on RNA had not previously been linked to RNA-mediated processes, for example proteins of intermediary metabolism. Thus, the studies provide unprecedented insights into the composition of the mRNA interactome, highlighting the complexity of RNA-mediated processes.

  3. RNA-Binding Proteins Revisited – The Emerging Arabidopsis mRNA Interactome

    KAUST Repository

    Köster, Tino

    2017-04-13

    RNA–protein interaction is an important checkpoint to tune gene expression at the RNA level. Global identification of proteins binding in vivo to mRNA has been possible through interactome capture – where proteins are fixed to target RNAs by UV crosslinking and purified through affinity capture of polyadenylated RNA. In Arabidopsis over 500 RNA-binding proteins (RBPs) enriched in UV-crosslinked samples have been identified. As in mammals and yeast, the mRNA interactomes came with a few surprises. For example, a plethora of the proteins caught on RNA had not previously been linked to RNA-mediated processes, for example proteins of intermediary metabolism. Thus, the studies provide unprecedented insights into the composition of the mRNA interactome, highlighting the complexity of RNA-mediated processes.

  4. A highly efficient approach to protein interactome mapping based on collaborative filtering framework.

    Science.gov (United States)

    Luo, Xin; You, Zhuhong; Zhou, Mengchu; Li, Shuai; Leung, Hareton; Xia, Yunni; Zhu, Qingsheng

    2015-01-09

    The comprehensive mapping of protein-protein interactions (PPIs) is highly desired for one to gain deep insights into both fundamental cell biology processes and the pathology of diseases. Finely-set small-scale experiments are not only very expensive but also inefficient to identify numerous interactomes despite their high accuracy. High-throughput screening techniques enable efficient identification of PPIs; yet the desire to further extract useful knowledge from these data leads to the problem of binary interactome mapping. Network topology-based approaches prove to be highly efficient in addressing this problem; however, their performance deteriorates significantly on sparse putative PPI networks. Motivated by the success of collaborative filtering (CF)-based approaches to the problem of personalized-recommendation on large, sparse rating matrices, this work aims at implementing a highly efficient CF-based approach to binary interactome mapping. To achieve this, we first propose a CF framework for it. Under this framework, we model the given data into an interactome weight matrix, where the feature-vectors of involved proteins are extracted. With them, we design the rescaled cosine coefficient to model the inter-neighborhood similarity among involved proteins, for taking the mapping process. Experimental results on three large, sparse datasets demonstrate that the proposed approach outperforms several sophisticated topology-based approaches significantly.

  5. New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals

    DEFF Research Database (Denmark)

    Kraja, Aldi T.; Cook, James P.; Warren, Helen R.

    2017-01-01

    Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data...

  6. Serum Amyloid P Component (SAP) Interactome in Human Plasma Containing Physiological Calcium Levels.

    Science.gov (United States)

    Poulsen, Ebbe Toftgaard; Pedersen, Kata Wolff; Marzeda, Anna Maria; Enghild, Jan J

    2017-02-14

    The pentraxin serum amyloid P component (SAP) is secreted by the liver and found in plasma at a concentration of approximately 30 mg/L. SAP is a 25 kDa homopentamer known to bind both protein and nonprotein ligands, all in a calcium-dependent manner. The function of SAP is unclear but likely involves the humoral innate immune system spanning the complement system, inflammation, and coagulation. Also, SAP is known to bind to the generic structure of amyloid deposits and possibly to protect them against proteolysis. In this study, we have characterized the SAP interactome in human plasma containing the physiological Ca 2+ concentration using SAP affinity pull-down and co-immunoprecipitation experiments followed by mass spectrometry analyses. The analyses resulted in the identification of 33 proteins, of which 24 were direct or indirect interaction partners not previously reported. The SAP interactome can be divided into categories that include apolipoproteins, the complement system, coagulation, and proteolytic regulation.

  7. In vitro nuclear interactome of the HIV-1 Tat protein.

    LENUS (Irish Health Repository)

    Gautier, Virginie W

    2009-01-01

    BACKGROUND: One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86-101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry. RESULTS: Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied in silico analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture. CONCLUSION: We have completed the in vitro Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will

  8. Structural identifiability analyses of candidate models for in vitro Pitavastatin hepatic uptake.

    Science.gov (United States)

    Grandjean, Thomas R B; Chappell, Michael J; Yates, James W T; Evans, Neil D

    2014-05-01

    In this paper a review of the application of four different techniques (a version of the similarity transformation approach for autonomous uncontrolled systems, a non-differential input/output observable normal form approach, the characteristic set differential algebra and a recent algebraic input/output relationship approach) to determine the structural identifiability of certain in vitro nonlinear pharmacokinetic models is provided. The Organic Anion Transporting Polypeptide (OATP) substrate, Pitavastatin, is used as a probe on freshly isolated animal and human hepatocytes. Candidate pharmacokinetic non-linear compartmental models have been derived to characterise the uptake process of Pitavastatin. As a prerequisite to parameter estimation, structural identifiability analyses are performed to establish that all unknown parameters can be identified from the experimental observations available. Copyright © 2013. Published by Elsevier Ireland Ltd.

  9. The arabidopsis cyclic nucleotide interactome

    KAUST Repository

    Donaldson, Lara Elizabeth

    2016-05-11

    Background Cyclic nucleotides have been shown to play important signaling roles in many physiological processes in plants including photosynthesis and defence. Despite this, little is known about cyclic nucleotide-dependent signaling mechanisms in plants since the downstream target proteins remain unknown. This is largely due to the fact that bioinformatics searches fail to identify plant homologs of protein kinases and phosphodiesterases that are the main targets of cyclic nucleotides in animals. Methods An affinity purification technique was used to identify cyclic nucleotide binding proteins in Arabidopsis thaliana. The identified proteins were subjected to a computational analysis that included a sequence, transcriptional co-expression and functional annotation analysis in order to assess their potential role in plant cyclic nucleotide signaling. Results A total of twelve cyclic nucleotide binding proteins were identified experimentally including key enzymes in the Calvin cycle and photorespiration pathway. Importantly, eight of the twelve proteins were shown to contain putative cyclic nucleotide binding domains. Moreover, the identified proteins are post-translationally modified by nitric oxide, transcriptionally co-expressed and annotated to function in hydrogen peroxide signaling and the defence response. The activity of one of these proteins, GLYGOLATE OXIDASE 1, a photorespiratory enzyme that produces hydrogen peroxide in response to Pseudomonas, was shown to be repressed by a combination of cGMP and nitric oxide treatment. Conclusions We propose that the identified proteins function together as points of cross-talk between cyclic nucleotide, nitric oxide and reactive oxygen species signaling during the defence response.

  10. Curating the innate immunity interactome.

    LENUS (Irish Health Repository)

    Lynn, David J

    2010-01-01

    The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http:\\/\\/www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity.

  11. Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia.

    Science.gov (United States)

    Rampino, Antonio; Walker, Rosie May; Torrance, Helen Scott; Anderson, Susan Maguire; Fazio, Leonardo; Di Giorgio, Annabella; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Ursini, Gianluca; Caforio, Grazia; Blasi, Giuseppe; Millar, J Kirsty; Porteous, David John; Thomson, Pippa Ann; Bertolino, Alessandro; Evans, Kathryn Louise

    2014-01-01

    Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1), a leading candidate gene for schizophrenia and related psychiatric conditions, in cognitive function. Altered expression of DISC1 and DISC1-interactors has been identified in schizophrenia. Dysregulated expression of DISC1-interactome genes might, therefore, contribute to schizophrenia susceptibility via disruption of molecular systems required for normal cognitive function. Here, the blood RNA expression levels of DISC1 and DISC1-interacting proteins were measured in 63 control subjects. Cognitive function was assessed using neuropsychiatric tests and functional magnetic resonance imaging was used to assess the activity of prefrontal cortical regions during the N-back working memory task, which is abnormal in schizophrenia. Pairwise correlations between gene expression levels and the relationship between gene expression levels and cognitive function and N-back-elicited brain activity were assessed. Finally, the expression levels of DISC1, AKAP9, FEZ1, NDEL1 and PCM1 were compared between 63 controls and 69 schizophrenic subjects. We found that DISC1-interactome genes showed correlated expression in the blood of healthy individuals. The expression levels of several interactome members were correlated with cognitive performance and N-back-elicited activity in the prefrontal cortex. In addition, DISC1 and NDEL1 showed decreased expression in schizophrenic subjects compared to healthy controls. Our findings highlight the importance of the coordinated expression of DISC1-interactome genes for normal cognitive function and suggest that dysregulated DISC1 and NDEL1 expression might, in part, contribute to susceptibility for schizophrenia via disruption of prefrontal cortex-dependent cognitive functions.

  12. Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia.

    Directory of Open Access Journals (Sweden)

    Antonio Rampino

    Full Text Available Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1, a leading candidate gene for schizophrenia and related psychiatric conditions, in cognitive function. Altered expression of DISC1 and DISC1-interactors has been identified in schizophrenia. Dysregulated expression of DISC1-interactome genes might, therefore, contribute to schizophrenia susceptibility via disruption of molecular systems required for normal cognitive function. Here, the blood RNA expression levels of DISC1 and DISC1-interacting proteins were measured in 63 control subjects. Cognitive function was assessed using neuropsychiatric tests and functional magnetic resonance imaging was used to assess the activity of prefrontal cortical regions during the N-back working memory task, which is abnormal in schizophrenia. Pairwise correlations between gene expression levels and the relationship between gene expression levels and cognitive function and N-back-elicited brain activity were assessed. Finally, the expression levels of DISC1, AKAP9, FEZ1, NDEL1 and PCM1 were compared between 63 controls and 69 schizophrenic subjects. We found that DISC1-interactome genes showed correlated expression in the blood of healthy individuals. The expression levels of several interactome members were correlated with cognitive performance and N-back-elicited activity in the prefrontal cortex. In addition, DISC1 and NDEL1 showed decreased expression in schizophrenic subjects compared to healthy controls. Our findings highlight the importance of the coordinated expression of DISC1-interactome genes for normal cognitive function and suggest that dysregulated DISC1 and NDEL1 expression might, in part, contribute to susceptibility for schizophrenia via disruption of prefrontal cortex-dependent cognitive functions.

  13. Mining protein interactomes to improve their reliability and support the advancement of network medicine

    KAUST Repository

    Alanis Lobato, Gregorio

    2015-09-23

    High-throughput detection of protein interactions has had a major impact in our understanding of the intricate molecular machinery underlying the living cell, and has permitted the construction of very large protein interactomes. The protein networks that are currently available are incomplete and a significant percentage of their interactions are false positives. Fortunately, the structural properties observed in good quality social or technological networks are also present in biological systems. This has encouraged the development of tools, to improve the reliability of protein networks and predict new interactions based merely on the topological characteristics of their components. Since diseases are rarely caused by the malfunction of a single protein, having a more complete and reliable interactome is crucial in order to identify groups of inter-related proteins involved in disease etiology. These system components can then be targeted with minimal collateral damage. In this article, an important number of network mining tools is reviewed, together with resources from which reliable protein interactomes can be constructed. In addition to the review, a few representative examples of how molecular and clinical data can be integrated to deepen our understanding of pathogenesis are discussed.

  14. Mining protein interactomes to improve their reliability and support the advancement of network medicine

    Directory of Open Access Journals (Sweden)

    Gregorio eAlanis-Lobato

    2015-09-01

    Full Text Available High-throughput detection of protein interactions has had a major impact in our understanding of the intricate molecular machinery underlying the living cell, and has permitted the construction of very large protein interactomes. The protein networks that are currently available are incomplete and a significant percentage of their interactions are false positives. Fortunately, the structural properties observed in good quality social or technological networks are also present in biological systems. This has encouraged the development of tools, to improve the reliability of protein networks and predict new interactions based merely on the topological characteristics of their components. Since diseases are rarely caused by the malfunction of a single protein, having a more complete and reliable interactome is crucial in order to identify groups of inter-related proteins involved in disease aetiology. These system components can then be targeted with minimal collateral damage. In this article, an important number of network mining tools is reviewed, together with resources from which reliable protein interactomes can be constructed. In addition to the review, a few representative examples of how molecular and clinical data can be integrated to deepen our understanding of pathogenesis are discussed.

  15. Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Kleijnen, J.P.C.; Helton, J.C.

    1999-04-01

    The robustness of procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses is investigated. These procedures are based on attempts to detect increasingly complex patterns in the scatterplots under consideration and involve the identification of (1) linear relationships with correlation coefficients, (2) monotonic relationships with rank correlation coefficients, (3) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (4) trends in variability as defined by variances and interquartile ranges, and (5) deviations from randomness as defined by the chi-square statistic. The following two topics related to the robustness of these procedures are considered for a sequence of example analyses with a large model for two-phase fluid flow: the presence of Type I and Type II errors, and the stability of results obtained with independent Latin hypercube samples. Observations from analysis include: (1) Type I errors are unavoidable, (2) Type II errors can occur when inappropriate analysis procedures are used, (3) physical explanations should always be sought for why statistical procedures identify variables as being important, and (4) the identification of important variables tends to be stable for independent Latin hypercube samples.

  16. Poplar Interactome: Project Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Jaiswal, Pankaj [Oregon State Univ., Corvallis, OR (United States)

    2018-03-21

    The feedstock plant Poplar has many advantages over traditional crop plants. Not only Poplar needs low energy input and off season storage as compared to feedstocks such as corn, in the winter season Poplar biomass is stored on the stem/trunk, and Poplar plantations serve as large carbon sink. A key constraint to the expansion of cellulosic bioenergy sources such as in Poplar however, is the negative consequence of converting land use from food crops to energy crops. Therefore in order for Poplar to become a viable energy crop it needs to be grown mostly on marginal land unsuitable agricultural crops. For this we need a better understanding of abiotic stress and adaptation response in poplar. In the process we expected to find new and existing poplar genes and their function that respond to sustain abiotic stress. We carried out an extensive gene expression study on the control untreated and stress (drought, salinity, cold and heat) treated poplar plants. The samples were collected from the stem, leaf and root tissues. The RNA of protein coding genes and regulatory smallRNA genes were sequenced generating more than a billion reads. This is the first such known study in Poplar plants. These were used for quantification and genomic analysis to identify stress responsive genes in poplar. Based on the quantification and genomic analysis, a select set of genes were studied for gene-gene interactions to find their association to stress response. The data was also used to find novel stress responsive genes in poplar that were previously not identified in the Poplar reference genome. The data is made available to the public through the national and international genomic data archives.

  17. Molecular characterization and interactome analysis of Trypanosoma cruzi tryparedoxin II.

    Science.gov (United States)

    Arias, Diego G; Piñeyro, María Dolores; Iglesias, Alberto A; Guerrero, Sergio A; Robello, Carlos

    2015-04-29

    Trypanosoma cruzi, the causative agent of Chagas disease, possesses two tryparedoxins (TcTXNI and TcTXNII), belonging to the thioredoxin superfamily. TXNs are oxidoreductases which mediate electron transfer between trypanothione and peroxiredoxins. This constitutes a difference with the host cells, in which these activities are mediated by thioredoxins. These differences make TXNs an attractive target for drug development. In a previous work we characterized TcTXNI, including the redox interactome. In this work we extend the study to TcTXNII. We demonstrate that TcTXNII is a transmembrane protein anchored to the surface of the mitochondria and endoplasmic reticulum, with a cytoplasmatic orientation of the redox domain. It would be expressed during the metacyclogenesis process. In order to continue with the characterization of the redox interactome of T. cruzi, we designed an active site mutant TcTXNII lacking the resolving cysteine, and through the expression of this mutant protein and incubation with T. cruzi proteins, heterodisulfide complexes were isolated by affinity chromatography and identified by mass spectrometry. This allowed us to identify sixteen TcTXNII interacting proteins, which are involved in a wide range of cellular processes, indicating the relevance of TcTXNII, and contributing to our understanding of the redox interactome of T. cruzi. T. cruzi, the causative agent of Chagas disease, constitutes a major sanitary problem in Latin America. The number of estimated infected persons is ca. 8 million, 28 million people are at risk of infection and ~20,000 deaths occur per year in endemic regions. No vaccines are available at present, and most drugs currently in use were developed decades ago and show variable efficacy with undesirable side effects. The parasite is able to live and prolipherate inside macrophage phagosomes, where it is exposed to cytotoxic reactive oxygen and nitrogen species, derived from macrophage activation. Therefore, T. cruzi

  18. Phosphinothricin Acetyltransferases Identified Using In Vivo, In Vitro, and Bioinformatic Analyses

    Science.gov (United States)

    VanDrisse, Chelsey M.; Hentchel, Kristy L.

    2016-01-01

    ABSTRACT Acetylation of small molecules is widespread in nature, and in some cases, cells use this process to detoxify harmful chemicals. Streptomyces species utilize a Gcn5 N-acetyltransferase (GNAT), known as Bar, to acetylate and detoxify a self-produced toxin, phosphinothricin (PPT), a glutamate analogue. Bar homologues, such as MddA from Salmonella enterica, acetylate methionine analogues such as methionine sulfoximine (MSX) and methionine sulfone (MSO), but not PPT, even though Bar homologues are annotated as PPT acetyltransferases. S. enterica was used as a heterologous host to determine whether or not putative PPT acetyltransferases from various sources could acetylate PPT, MSX, and MSO. In vitro and in vivo analyses identified substrates acetylated by putative PPT acetyltransferases from Deinococcus radiodurans (DR_1057 and DR_1182) and Geobacillus kaustophilus (GK0593 and GK2920). In vivo, synthesis of DR_1182, GK0593, and GK2920 blocked the inhibitory effects of PPT, MSX, and MSO. In contrast, DR_1057 did not detoxify any of the above substrates. Results of in vitro studies were consistent with the in vivo results. In addition, phylogenetic analyses were used to predict the functionality of annotated PPT acetyltransferases in Burkholderia xenovorans, Bacillus subtilis, Staphylococcus aureus, Acinetobacter baylyi, and Escherichia coli. IMPORTANCE The work reported here provides an example of the use of a heterologous system for the identification of enzyme function. Many members of this superfamily of proteins do not have a known function, or it has been annotated solely on the basis of sequence homology to previously characterized enzymes. The critical role of Gcn5 N-acetyltransferases (GNATs) in the modulation of central metabolic processes, and in controlling metabolic stress, necessitates approaches that can reveal their physiological role. The combination of in vivo, in vitro, and bioinformatics approaches reported here identified GNATs that can

  19. A side-effect free method for identifying cancer drug targets.

    Science.gov (United States)

    Ashraf, Md Izhar; Ong, Seng-Kai; Mujawar, Shama; Pawar, Shrikant; More, Pallavi; Paul, Somnath; Lahiri, Chandrajit

    2018-04-27

    Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

  20. Two novel antimicrobial defensins from rice identified by gene coexpression network analyses.

    Science.gov (United States)

    Tantong, Supaluk; Pringsulaka, Onanong; Weerawanich, Kamonwan; Meeprasert, Arthitaya; Rungrotmongkol, Thanyada; Sarnthima, Rakrudee; Roytrakul, Sittiruk; Sirikantaramas, Supaart

    2016-10-01

    Defensins form an antimicrobial peptides (AMP) family, and have been widely studied in various plants because of their considerable inhibitory functions. However, their roles in rice (Oryza sativa L.) have not been characterized, even though rice is one of the most important staple crops that is susceptible to damaging infections. Additionally, a previous study identified 598 rice genes encoding cysteine-rich peptides, suggesting there are several uncharacterized AMPs in rice. We performed in silico gene expression and coexpression network analyses of all genes encoding defensin and defensin-like peptides, and determined that OsDEF7 and OsDEF8 are coexpressed with pathogen-responsive genes. Recombinant OsDEF7 and OsDEF8 could form homodimers. They inhibited the growth of the bacteria Xanthomonas oryzae pv. oryzae, X. oryzae pv. oryzicola, and Erwinia carotovora subsp. atroseptica with minimum inhibitory concentration (MIC) ranging from 0.6 to 63μg/mL. However, these OsDEFs are weakly active against the phytopathogenic fungi Helminthosporium oryzae and Fusarium oxysporum f.sp. cubense. This study describes a useful method for identifying potential plant AMPs with biological activities. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Attribute analyses of gpr data for detecting and identifying heavy minerals

    Science.gov (United States)

    Catakli, Aycan

    Attribute analyses have been used successfully in seismic applications for many years. In this study, the application of the attribute analyses to Ground Penetrating Radar (GPR) data has been proposed to detect and identify heavy minerals within the Moon soil (regolith). Lunar samples are mostly composed of heavy minerals such as ilmenite, plagioclase, olivine and pyroxene, a characteristic that makes lunar soil a source for elements such as titanium, oxygen and iron. The main goal of this study is to demonstrate the use of GPR method for detecting and mapping heavy minerals concentrations. The attribute analyses used in this study are Attenuation Analysis (AA), Complex Trace Analysis (CTA), Texture Analysis (TA) and Center Frequency Destitution (CFD). Attribute analysis was applied to both synthetic models and prototype laboratory measurements to study its application to GPR data. The results indicate that the attribute analyses of GPR data can be useful to provide valuable subsurface information. The findings of AA show that attenuation values are function of mineralogy of the subsurface. This could be applicable to Moon and Mars in addition to Earth environment to explore their near-surface soils. CTA can successfully estimate the location of heavy mineral samples embedded inside host medium through the variation of reflected energy around buried sample and sharpen the reflecting interface. Results indicate that as the amount of the buried heavy minerals increases, the value of CTA parameters (Normal distribution of amplitude spectra `NDoAS' and tau-parameter) proportionally increase. TA measures combined can be used as an enhanced interpretation tool. The texture results show that heavy mineral concentrations can be identified by the high contrast, entropy, autocorrelation, correlation, cluster, dissimilarity, standard deviation, variance and low energy, maximum probability, and homogeneity. The measures also help in highlighting the edge of the buried samples

  2. The Topology of the Growing Human Interactome Data

    Directory of Open Access Journals (Sweden)

    Janjić Vuk

    2014-06-01

    Full Text Available We have long moved past the one-gene-one-function concept originally proposed by Beadle and Tatum back in 1941; but the full understanding of genotype-phenotype relations still largely relies on the analysis of static, snapshot-like, interaction data sets. Here, we look at what global patterns can be uncovered if we simply trace back the human interactome network over the last decade of protein-protein interaction (PPI screening. We take a purely topological approach and find that as the human interactome is getting denser, it is not only gaining in structure (in terms of now being better fit by structured network models than before, but also there are patterns in the way in which it is growing: (a newly added proteins tend to get linked to existing proteins in the interactome that are not know to interact; and (b new proteins tend to link to already well connected proteins. Moreover, the alignment between human and yeast interactomes spanning over 40% of yeast’s proteins - that are involved in regulation of transcription, RNA splicing and other cellcycle- related processes-suggests the existence of a part of the interactome which remains topologically and functionally unaffected through evolution. Furthermore, we find a small sub-network, specific to the “core” of the human interactome and involved in regulation of transcription and cancer development, whose wiring has not changed within the human interactome over the last 10 years of interacome data acquisition. Finally, we introduce a generalisation of the clustering coefficient of a network as a new measure called the cycle coefficient, and use it to show that PPI networks of human and model organisms are wired in a tight way which forbids the occurrence large cycles.

  3. Multiple gene analyses identify distinct “bois noir” phytoplasma genotypes in the Republic of Macedonia

    Directory of Open Access Journals (Sweden)

    Emilija KOSTADINOVSKA

    2015-01-01

    Full Text Available “Bois noir” (BN is a grapevine yellows disease, associated with phytoplasma strains related to ‘Candidatus Phytoplasma solani’, that causes severe losses to viticulture in the Euro-Mediterranean basin. Due to the complex ecological cycle of its etiological agent, BN epidemiology is only partially known, and no effective control strategies have been developed. Numerous studies have focused on molecular characterization of BN phytoplasma strains, to identify molecular markers useful to accurately describe their genetic diversity, geographic distribution and host range. In the present study, a multiple gene analysess were carried out on 16S rRNA, tuf, vmp1, and stamp genes to study the genetic variability among 18 BN phytoplasma strains detected in diverse regions of the Republic of Macedonia. Restriction fragment length polymorphism (RFLP assays showed the presence of one 16S rRNA (16SrXII-A, two tuf (tuf-type a, tuf-type b, five vmp1 (V2-TA, V3, V4, V14, V18, and three stamp (S1, S2, S3 gene patterns among the examined strains. Based on the collective RFLP patterns, seven genotypes (Mac1 to Mac7 were described as evidence for genetic heterogeneity, and highlighting their prevalence and distribution in the investigated regions. Phylogenetic analyses on vmp1 and stamp genes underlined the affiliation of Macedonian BN phytoplasma strains to clusters associated with distinct ecologies.

  4. Genome-wide meta-analyses identify multiple loci associated with smoking behavior.

    LENUS (Irish Health Repository)

    2010-05-01

    Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], beta = 1.03, standard error (s.e.) = 0.053, P = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], beta = 0.367, s.e. = 0.059, P = 5.7 x 10(-10); and rs1028936[A], beta = 0.446, s.e. = 0.074, P = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], beta = 0.333, s.e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.

  5. Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae.

    Science.gov (United States)

    Uthe, Henriette; Vanselow, Jens T; Schlosser, Andreas

    2017-02-27

    Here we present the most comprehensive analysis of the yeast Mediator complex interactome to date. Particularly gentle cell lysis and co-immunopurification conditions allowed us to preserve even transient protein-protein interactions and to comprehensively probe the molecular environment of the Mediator complex in the cell. Metabolic 15 N-labeling thereby enabled stringent discrimination between bona fide interaction partners and nonspecifically captured proteins. Our data indicates a functional role for Mediator beyond transcription initiation. We identified a large number of Mediator-interacting proteins and protein complexes, such as RNA polymerase II, general transcription factors, a large number of transcriptional activators, the SAGA complex, chromatin remodeling complexes, histone chaperones, highly acetylated histones, as well as proteins playing a role in co-transcriptional processes, such as splicing, mRNA decapping and mRNA decay. Moreover, our data provides clear evidence, that the Mediator complex interacts not only with RNA polymerase II, but also with RNA polymerases I and III, and indicates a functional role of the Mediator complex in rRNA processing and ribosome biogenesis.

  6. Quantum Interactomics and Cancer Molecular Mechanisms: I. Report Outline

    CERN Document Server

    Baianu, I C

    2004-01-01

    Single cell interactomics in simpler organisms, as well as somatic cell interactomics in multicellular organisms, involve biomolecular interactions in complex signalling pathways that were recently represented in modular terms by quantum automata with ‘reversible behavior’ representing normal cell cycling and division. Other implications of such quantum automata, modular modeling of signaling pathways and cell differentiation during development are in the fields of neural plasticity and brain development leading to quantum-weave dynamic patterns and specific molecular processes underlying extensive memory, learning, anticipation mechanisms and the emergence of human consciousness during the early brain development in children. Cell interactomics is here represented for the first time as a mixture of ‘classical’ states that determine molecular dynamics subject to Boltzmann statistics and ‘steady-state’, metabolic (multi-stable) manifolds, together with ‘configuration’ spaces of metastable quant...

  7. "Fuzziness" in the celular interactome: a historical perspective.

    Science.gov (United States)

    Welch, G Rickey

    2012-01-01

    Some historical background is given for appreciating the impact of the empirical construct known as the cellular protein-protein interactome, which is a seemingly de novo entity that has arisen of late within the context of postgenomic systems biology. The approach here builds on a generalized principle of "fuzziness" in protein behavior, proposed by Tompa and Fuxreiter.(1) Recent controversies in the analysis and interpretation of the interactome studies are rationalized historically under the auspices of this concept. There is an extensive literature on protein-protein interactions, dating to the mid-1900s, which may help clarify the "fuzziness" in the interactome picture and, also, provide a basis for understanding the physiological importance of protein-protein interactions in vivo.

  8. Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity*

    Science.gov (United States)

    Chen, Ying; Yang, Li-Na; Cheng, Li; Tu, Shun; Guo, Shu-Juan; Le, Huang-Ying; Xiong, Qian; Mo, Ran; Li, Chong-Yang; Jeong, Jun-Seop; Jiang, Lizhi; Blackshaw, Seth; Bi, Li-Jun; Zhu, Heng; Tao, Sheng-Ce; Ge, Feng

    2013-01-01

    Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach. PMID:23824909

  9. Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry

    Directory of Open Access Journals (Sweden)

    Isabelle Maxim

    2010-04-01

    Full Text Available Abstract Background Poly(ADP-ribose polymerases (PARPs catalyze the formation of poly(ADP-ribose (pADPr, a post-translational modification involved in several important biological processes, namely surveillance of genome integrity, cell cycle progression, initiation of the DNA damage response, apoptosis, and regulation of transcription. Poly(ADP-ribose glycohydrolase (PARG, on the other hand, catabolizes pADPr and thereby accounts for the transient nature of poly(ADP-ribosylation. Our investigation of the interactomes of PARP-1, PARP-2, and PARG by affinity-purification mass spectrometry (AP-MS aimed, on the one hand, to confirm current knowledge on these interactomes and, on the other hand, to discover new protein partners which could offer insights into PARPs and PARG functions. Results PARP-1, PARP-2, and PARG were immunoprecipitated from human cells, and pulled-down proteins were separated by gel electrophoresis prior to in-gel trypsin digestion. Peptides were identified by tandem mass spectrometry. Our AP-MS experiments resulted in the identifications of 179 interactions, 139 of which are novel interactions. Gene Ontology analysis of the identified protein interactors points to five biological processes in which PARP-1, PARP-2 and PARG may be involved: RNA metabolism for PARP-1, PARP-2 and PARG; DNA repair and apoptosis for PARP-1 and PARP-2; and glycolysis and cell cycle for PARP-1. Conclusions This study reveals several novel protein partners for PARP-1, PARP-2 and PARG. It provides a global view of the interactomes of these proteins as well as a roadmap to establish the systems biology of poly(ADP-ribose metabolism.

  10. Genome-wide meta-analyses identify multiple loci associated with smoking behavior

    NARCIS (Netherlands)

    H. Furberg (Helena); Y. Kim (Yunjung); J. Dackor (Jennifer); E.A. Boerwinkle (Eric); N. Franceschini (Nora); D. Ardissino (Diego); L. Bernardinelli (Luisa); P.M. Mannucci (Pier); F. Mauri (Francesco); P.A. Merlini (Piera); D. Absher (Devin); T.L. Assimes (Themistocles); S.P. Fortmann (Stephen); C. Iribarren (Carlos); J.W. Knowles (Joshua); T. Quertermous (Thomas); L. Ferrucci (Luigi); T. Tanaka (Toshiko); J.C. Bis (Joshua); T. Haritunians (Talin); B. McKnight (Barbara); B.M. Psaty (Bruce); K.D. Taylor (Kent); E.L. Thacker (Evan); P. Almgren (Peter); L. Groop (Leif); C. Ladenvall (Claes); M. Boehnke (Michael); A.U. Jackson (Anne); K.L. Mohlke (Karen); H.M. Stringham (Heather); J. Tuomilehto (Jaakko); E.J. Benjamin (Emelia); S.J. Hwang; D. Levy (Daniel); S.R. Preis; R.S. Vasan (Ramachandran Srini); J. Duan (Jubao); P.V. Gejman (Pablo); D.F. Levinson (Douglas); A.R. Sanders (Alan); J. Shi (Jianxin); E.H. Lips (Esther); J.D. McKay (James); A. Agudo (Antonio); L. Barzan (Luigi); V. Bencko (Vladimir); S. Benhamou (Simone); X. Castellsagué (Xavier); C. Canova (Cristina); D.I. Conway (David); E. Fabianova (Eleonora); L. Foretova (Lenka); V. Janout (Vladimir); C.M. Healy (Claire); I. Holcátová (Ivana); K. Kjaerheim (Kristina); P. Lagiou; J. Lissowska (Jolanta); R. Lowry (Ray); T.V. MacFarlane (Tatiana); D. Mates (Dana); L. Richiardi (Lorenzo); P. Rudnai (Peter); N. Szeszenia-Dabrowska (Neonilia); D. Zaridze; A. Znaor (Ariana); M. Lathrop (Mark); P. Brennan (Paul); S. Bandinelli (Stefania); T.M. Frayling (Timothy); J.M. Guralnik (Jack); Y. Milaneschi (Yuri); J.R.B. Perry (John); D. Altshuler (David); R. Elosua (Roberto); S. Kathiresan (Sekar); G. Lucas (Gavin); O. Melander (Olle); V. Salomaa (Veikko); S.M. Schwartz (Stephen); B.F. Voight (Benjamin); B.W.J.H. Penninx (Brenda); J.H. Smit (Johannes); N. Vogelzangs (Nicole); D.I. Boomsma (Dorret); E.J.C. de Geus (Eco); J.M. Vink (Jacqueline); G.A.H.M. Willemsen (Gonneke); S.J. Chanock (Stephen); F. Gu (Fangyi); S.E. Hankinson (Susan); D. Hunter (David); A. Hofman (Albert); H.W. Tiemeier (Henning); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); S. Walter (Stefan); D.I. Chasman (Daniel); B.M. Everett (Brendan); G. Pare (Guillaume); P.M. Ridker (Paul); M.D. Li (Ming); H.H. Maes (Hermine); J. Audrain-Mcgovern (Janet); D. Posthuma (Danielle); L.M. Thornton (Laura); C. Lerman (Caryn); J. Kaprio (Jaakko); J.E. Rose (Jed); J.P.A. Ioannidis (John); P. Kraft (Peter); D.Y. Lin (Dan); P.F. Sullivan (Patrick); C.J. O'Donnell (Christopher)

    2010-01-01

    textabstractConsistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology

  11. The L1TD1 Protein Interactome Reveals the Importance of Post-transcriptional Regulation in Human Pluripotency

    Directory of Open Access Journals (Sweden)

    Maheswara Reddy Emani

    2015-03-01

    Full Text Available The RNA-binding protein L1TD1 is one of the most specific and abundant proteins in pluripotent stem cells and is essential for the maintenance of pluripotency in human cells. Here, we identify the protein interaction network of L1TD1 in human embryonic stem cells (hESCs and provide insights into the interactome network constructed in human pluripotent cells. Our data reveal that L1TD1 has an important role in RNA splicing, translation, protein traffic, and degradation. L1TD1 interacts with multiple stem-cell-specific proteins, many of which are still uncharacterized in the context of development. Further, we show that L1TD1 is a part of the pluripotency interactome network of OCT4, SOX2, and NANOG, bridging nuclear and cytoplasmic regulation and highlighting the importance of RNA biology in pluripotency.

  12. Attempts to identify and analyse prospects and challenges of tourism marketing in Bangladesh.

    OpenAIRE

    Redwan, Md

    2017-01-01

    Master's thesis in International hotel and tourism management The research has been done to analyse the tourism position of the country Bangladesh. Bangladesh is country of huge potential and the country can do well its present assets related to the tourism. The natural resources of the country and the foreign exchange inflow in the country can make the country economically sound. The research aims to understand the present scenario of the tourism industry of Bangladesh and the challenges ...

  13. Sequential Elution Interactome Analysis of the Mind Bomb 1 Ubiquitin Ligase Reveals a Novel Role in Dendritic Spine Outgrowth*

    Science.gov (United States)

    Mertz, Joseph; Tan, Haiyan; Pagala, Vishwajeeth; Bai, Bing; Chen, Ping-Chung; Li, Yuxin; Cho, Ji-Hoon; Shaw, Timothy; Wang, Xusheng; Peng, Junmin

    2015-01-01

    The mind bomb 1 (Mib1) ubiquitin ligase is essential for controlling metazoan development by Notch signaling and possibly the Wnt pathway. It is also expressed in postmitotic neurons and regulates neuronal morphogenesis and synaptic activity by mechanisms that are largely unknown. We sought to comprehensively characterize the Mib1 interactome and study its potential function in neuron development utilizing a novel sequential elution strategy for affinity purification, in which Mib1 binding proteins were eluted under different stringency and then quantified by the isobaric labeling method. The strategy identified the Mib1 interactome with both deep coverage and the ability to distinguish high-affinity partners from low-affinity partners. A total of 817 proteins were identified during the Mib1 affinity purification, including 56 high-affinity partners and 335 low-affinity partners, whereas the remaining 426 proteins are likely copurified contaminants or extremely weak binding proteins. The analysis detected all previously known Mib1-interacting proteins and revealed a large number of novel components involved in Notch and Wnt pathways, endocytosis and vesicle transport, the ubiquitin-proteasome system, cellular morphogenesis, and synaptic activities. Immunofluorescence studies further showed colocalization of Mib1 with five selected proteins: the Usp9x (FAM) deubiquitinating enzyme, alpha-, beta-, and delta-catenins, and CDKL5. Mutations of CDKL5 are associated with early infantile epileptic encephalopathy-2 (EIEE2), a severe form of mental retardation. We found that the expression of Mib1 down-regulated the protein level of CDKL5 by ubiquitination, and antagonized CDKL5 function during the formation of dendritic spines. Thus, the sequential elution strategy enables biochemical characterization of protein interactomes; and Mib1 analysis provides a comprehensive interactome for investigating its role in signaling networks and neuronal development. PMID:25931508

  14. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

    NARCIS (Netherlands)

    Nicolas, Aude; Kenna, Kevin P.; Renton, Alan E.; Ticozzi, Nicola; Faghri, Faraz; Chia, Ruth; Dominov, Janice A.; Kenna, Brendan J.; Nalls, Mike A.; Keagle, Pamela; Rivera, Alberto M.; van Rheenen, Wouter; Murphy, Natalie A.; van Vugt, Joke J.F.A.; Geiger, Joshua T.; van der Spek, Rick; Pliner, Hannah A.; Smith, Bradley N.; Marangi, Giuseppe; Topp, Simon D.; Abramzon, Yevgeniya; Gkazi, Athina Soragia; Eicher, John D.; Kenna, Aoife; Logullo, Francesco O.; Simone, Isabella L.; Logroscino, Giancarlo; Salvi, Fabrizio; Bartolomei, Ilaria; Borghero, Giuseppe; Murru, Maria Rita; Costantino, Emanuela; Pani, Carla; Puddu, Roberta; Caredda, Carla; Piras, Valeria; Tranquilli, Stefania; Cuccu, Stefania; Corongiu, Daniela; Melis, Maurizio; Milia, Antonio; Marrosu, Francesco; Marrosu, Maria Giovanna; Floris, Gianluca; Cannas, Antonino; Capasso, Margherita; Caponnetto, Claudia; Mancardi, Gianluigi; Origone, Paola; Mandich, Paola; Conforti, Francesca L.; Cavallaro, Sebastiano; Mora, Gabriele; Marinou, Kalliopi; Sideri, Riccardo; Penco, Silvana; Mosca, Lorena; Lunetta, Christian; Pinter, Giuseppe Lauria; Corbo, Massimo; Riva, Nilo; Carrera, Paola; Volanti, Paolo; Mandrioli, Jessica; Fini, Nicola; Fasano, Antonio; Tremolizzo, Lucio; Arosio, Alessandro; Ferrarese, Carlo; Trojsi, Francesca; Tedeschi, Gioacchino; Monsurrò, Maria Rosaria; Piccirillo, Giovanni; Femiano, Cinzia; Ticca, Anna; Ortu, Enzo; La Bella, Vincenzo; Spataro, Rossella; Colletti, Tiziana; Sabatelli, Mario; Zollino, Marcella; Conte, Amelia; Luigetti, Marco; Lattante, Serena; Marangi, Giuseppe; Santarelli, Marialuisa; Petrucci, Antonio; Pugliatti, Maura; Pirisi, Angelo; Parish, Leslie D.; Occhineri, Patrizia; Giannini, Fabio; Battistini, Stefania; Ricci, Claudia; Benigni, Michele; Cau, Tea B.; Loi, Daniela; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Barberis, Marco; Restagno, Gabriella; Casale, Federico; Marrali, Giuseppe; Fuda, Giuseppe; Ossola, Irene; Cammarosano, Stefania; Canosa, Antonio; Ilardi, Antonio; Manera, Umberto; Grassano, Maurizio; Tanel, Raffaella; Pisano, Fabrizio; Mora, Gabriele; Calvo, Andrea; Mazzini, Letizia; Riva, Nilo; Mandrioli, Jessica; Caponnetto, Claudia; Battistini, Stefania; Volanti, Paolo; La Bella, Vincenzo; Conforti, Francesca L.; Borghero, Giuseppe; Messina, Sonia; Simone, Isabella L.; Trojsi, Francesca; Salvi, Fabrizio; Logullo, Francesco O.; D'Alfonso, Sandra; Corrado, Lucia; Capasso, Margherita; Ferrucci, Luigi; Harms, Matthew B.; Goldstein, David B.; Shneider, Neil A.; Goutman, Stephen A.; Simmons, Zachary; Miller, Timothy M.; Chandran, Siddharthan; Pal, Suvankar; Manousakis, George; Appel, Stanley H.; Simpson, Ericka; Wang, Leo; Baloh, Robert H.; Gibson, Summer B.; Bedlack, Richard; Lacomis, David; Sareen, Dhruv; Sherman, Alexander; Bruijn, Lucie; Penny, Michelle; Moreno, Cristiane de Araujo Martins; Kamalakaran, Sitharthan; Goldstein, David B.; Allen, Andrew S.; Appel, Stanley; Baloh, Robert H.; Bedlack, Richard S.; Boone, Braden E.; Brown, Robert; Carulli, John P.; Chesi, Alessandra; Chung, Wendy K.; Cirulli, Elizabeth T.; Cooper, Gregory M.; Couthouis, Julien; Day-Williams, Aaron G.; Dion, Patrick A.; Gibson, Summer B.; Gitler, Aaron D.; Glass, Jonathan D.; Goldstein, David B.; Han, Yujun; Harms, Matthew B.; Harris, Tim; Hayes, Sebastian D.; Jones, Angela L.; Keebler, Jonathan; Krueger, Brian J.; Lasseigne, Brittany N.; Levy, Shawn E.; Lu, Yi Fan; Maniatis, Tom; McKenna-Yasek, Diane; Miller, Timothy M.; Myers, Richard M.; Petrovski, Slavé; Pulst, Stefan M.; Raphael, Alya R.; Ravits, John M.; Ren, Zhong; Rouleau, Guy A.; Sapp, Peter C.; Shneider, Neil A.; Simpson, Ericka; Sims, Katherine B.; Staropoli, John F.; Waite, Lindsay L.; Wang, Quanli; Wimbish, Jack R.; Xin, Winnie W.; Gitler, Aaron D.; Harris, Tim; Myers, Richard M.; Phatnani, Hemali; Kwan, Justin; Sareen, Dhruv; Broach, James R.; Simmons, Zachary; Arcila-Londono, Ximena; Lee, Edward B.; Van Deerlin, Vivianna M.; Shneider, Neil A.; Fraenkel, Ernest; Ostrow, Lyle W.; Baas, Frank; Zaitlen, Noah; Berry, James D.; Malaspina, Andrea; Fratta, Pietro; Cox, Gregory A.; Thompson, Leslie M.; Finkbeiner, Steve; Dardiotis, Efthimios; Miller, Timothy M.; Chandran, Siddharthan; Pal, Suvankar; Hornstein, Eran; MacGowan, Daniel J.L.; Heiman-Patterson, Terry D.; Hammell, Molly G.; Patsopoulos, Nikolaos A.; Dubnau, Joshua; Nath, Avindra; Phatnani, Hemali; Musunuri, Rajeeva Lochan; Evani, Uday Shankar; Abhyankar, Avinash; Zody, Michael C.; Kaye, Julia; Finkbeiner, Steven; Wyman, Stacia K.; LeNail, Alexander; Lima, Leandro; Fraenkel, Ernest; Rothstein, Jeffrey D.; Svendsen, Clive N.; Thompson, Leslie M.; Van Eyk, Jenny; Maragakis, Nicholas J.; Berry, James D.; Glass, Jonathan D.; Miller, Timothy M.; Kolb, Stephen J.; Baloh, Robert H.; Cudkowicz, Merit; Baxi, Emily; Kaye, Julia; Finkbeiner, Steven; Wyman, Stacia K.; Finkbeiner, Steven; LeNail, Alex; Lima, Leandro; Fraenkel, Ernest; Fraenkel, Ernest; Svendsen, Clive N.; Svendsen, Clive N.; Thompson, Leslie M.; Thompson, Leslie M.; Van Eyk, Jennifer E.; Berry, James D.; Berry, James D.; Miller, Timothy M.; Kolb, Stephen J.; Cudkowicz, Merit; Cudkowicz, Merit; Baxi, Emily; Benatar, Michael; Taylor, J. Paul; Wu, Gang; Rampersaud, Evadnie; Wuu, Joanne; Rademakers, Rosa; Züchner, Stephan; Schule, Rebecca; McCauley, Jacob; Hussain, Sumaira; Cooley, Anne; Wallace, Marielle; Clayman, Christine; Barohn, Richard; Statland, Jeffrey; Ravits, John M.; Swenson, Andrea; Jackson, Carlayne; Trivedi, Jaya; Khan, Shaida; Katz, Jonathan; Jenkins, Liberty; Burns, Ted; Gwathmey, Kelly; Caress, James; McMillan, Corey; Elman, Lauren; Pioro, Erik P.; Heckmann, Jeannine; So, Yuen; Walk, David; Maiser, Samuel; Zhang, Jinghui; Benatar, Michael; Taylor, J. Paul; Taylor, J. Paul; Rampersaud, Evadnie; Wu, Gang; Wuu, Joanne; Silani, Vincenzo; Ticozzi, Nicola; Gellera, Cinzia; Ratti, Antonia; Taroni, Franco; Lauria, Giuseppe; Verde, Federico; Fogh, Isabella; Tiloca, Cinzia; Comi, Giacomo P.; Sorarù, Gianni; Cereda, Cristina; D'Alfonso, Sandra; Corrado, Lucia; De Marchi, Fabiola; Corti, Stefania; Ceroni, Mauro; Mazzini, Letizia; Siciliano, Gabriele; Filosto, Massimiliano; Inghilleri, Maurizio; Peverelli, Silvia; Colombrita, Claudia; Poletti, Barbara; Maderna, Luca; Del Bo, Roberto; Gagliardi, Stella; Querin, Giorgia; Bertolin, Cinzia; Pensato, Viviana; Castellotti, Barbara; Lauria, Giuseppe; Verde, Federico; Fogh, Isabella; Tiloca, Cinzia; Fogh, Isabella; Comi, Giacomo P.; Sorarù, Gianni; Cereda, Cristina; Camu, William; Mouzat, Kevin; Lumbroso, Serge; Corcia, Philippe; Meininger, Vincent; Besson, Gérard; Lagrange, Emmeline; Clavelou, Pierre; Guy, Nathalie; Couratier, Philippe; Vourch, Patrick; Danel, Véronique; Bernard, Emilien; Lemasson, Gwendal; Corcia, Philippe; Laaksovirta, Hannu; Myllykangas, Liisa; Jansson, Lilja; Valori, Miko; Ealing, John; Hamdalla, Hisham; Rollinson, Sara; Pickering-Brown, Stuart; Orrell, Richard W.; Sidle, Katie C.; Malaspina, Andrea; Hardy, John; Singleton, Andrew B.; Johnson, Janel O.; Arepalli, Sampath; Sapp, Peter C.; McKenna-Yasek, Diane; Polak, Meraida; Asress, Seneshaw; Al-Sarraj, Safa; King, Andrew; Troakes, Claire; Vance, Caroline; de Belleroche, Jacqueline; Baas, Frank; ten Asbroek, Anneloor L.M.A.; Muñoz-Blanco, José Luis; Hernandez, Dena G.; Ding, Jinhui; Gibbs, J. Raphael; Scholz, Sonja W.; Scholz, Sonja W.; Floeter, Mary Kay; Campbell, Roy H.; Landi, Francesco; Bowser, Robert; Pulst, Stefan M.; Ravits, John M.; MacGowan, Daniel J.L.; Kirby, Janine; Pioro, Erik P.; Pamphlett, Roger; Broach, James; Gerhard, Glenn; Dunckley, Travis L.; Brady, Christopher B.; Brady, Christopher B.; Kowall, Neil W.; Troncoso, Juan C.; Le Ber, Isabelle; Mouzat, Kevin; Lumbroso, Serge; Mouzat, Kevin; Lumbroso, Serge; Heiman-Patterson, Terry D.; Heiman-Patterson, Terry D.; Kamel, Freya; Van Den Bosch, Ludo; Van Den Bosch, Ludo; Baloh, Robert H.; Strom, Tim M.; Meitinger, Thomas; Strom, Tim M.; Shatunov, Aleksey; Van Eijk, Kristel R.; de Carvalho, Mamede; de Carvalho, Mamede; Kooyman, Maarten; Middelkoop, Bas; Moisse, Matthieu; McLaughlin, Russell; Van Es, Michael A.; Weber, Markus; Boylan, Kevin B.; Van Blitterswijk, Marka; Rademakers, Rosa; Morrison, Karen; Basak, A. Nazli; Mora, Jesús S.; Drory, Vivian; Shaw, Pamela; Turner, Martin R.; Talbot, Kevin; Hardiman, Orla; Williams, Kelly L.; Fifita, Jennifer A.; Nicholson, Garth A.; Blair, Ian P.; Nicholson, Garth A.; Rouleau, Guy A.; Esteban-Pérez, Jesús; García-Redondo, Alberto; Al-Chalabi, Ammar; Al Kheifat, Ahmad; Al-Chalabi, Ammar; Andersen, Peter M.; Basak, A. Nazli; Blair, Ian P.; Chio, Adriano; Cooper-Knock, Jonathan; Corcia, Philippe; Couratier, Philippe; de Carvalho, Mamede; Dekker, Annelot; Drory, Vivian; Redondo, Alberto Garcia; Gotkine, Marc; Hardiman, Orla; Hide, Winston; Iacoangeli, Alfredo; Glass, Jonathan D.; Kenna, Kevin P.; Kiernan, Matthew; Kooyman, Maarten; Landers, John E.; McLaughlin, Russell; Middelkoop, Bas; Mill, Jonathan; Neto, Miguel Mitne; Moisse, Matthieu; Pardina, Jesus Mora; Morrison, Karen; Newhouse, Stephen; Pinto, Susana; Pulit, Sara; Robberecht, Wim; Shatunov, Aleksey; Shaw, Pamela; Shaw, Chris; Silani, Vincenzo; Sproviero, William; Tazelaar, Gijs; Ticozzi, Nicola; Van Damme, Philip; van den Berg, Leonard; van der Spek, Rick; Van Eijk, Kristel R.; Van Es, Michael A.; van Rheenen, Wouter; van Vugt, Joke J.F.A.; Veldink, Jan H.; Weber, Markus; Williams, Kelly L.; Van Damme, Philip; Robberecht, Wim; Zatz, Mayana; Robberecht, Wim; Bauer, Denis C.; Twine, Natalie A.; Rogaeva, Ekaterina; Zinman, Lorne; Ostrow, Lyle W.; Maragakis, Nicholas J.; Rothstein, Jeffrey D.; Simmons, Zachary; Cooper-Knock, Johnathan; Brice, Alexis; Goutman, Stephen A.; Feldman, Eva L.; Gibson, Summer B.; Taroni, Franco; Ratti, Antonia; Ratti, Antonia; Gellera, Cinzia; Van Damme, Philip; Robberecht, Wim; Fratta, Pietro; Sabatelli, Mario; Lunetta, Christian; Ludolph, Albert C.; Andersen, Peter M.; Weishaupt, Jochen H.; Camu, William; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Brown, Robert H.; van den Berg, Leonard; Veldink, Jan H.; Harms, Matthew B.; Glass, Jonathan D.; Stone, David J.; Tienari, Pentti; Silani, Vincenzo; Silani, Vincenzo; Chiò, Adriano; Shaw, Christopher E.; Chiò, Adriano; Traynor, Bryan J.; Landers, John E.; Traynor, Bryan J.

    2018-01-01

    To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494

  15. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

    NARCIS (Netherlands)

    Kottgen, A.; Albrecht, E.; Teumer, A.; Vitart, V.; Krumsiek, J.; Hundertmark, C.; Pistis, G.; Ruggiero, D.; O'Seaghdha, C.M.; Haller, T.; Yang, Q.; Johnson, A.D.; Kutalik, Z.; Smith, A.V.; Shi, J.L.; Struchalin, M.; Middelberg, R.P.S.; Brown, M.J.; Gaffo, A.L.; Pirastu, N.; Li, G.; Hayward, C.; Zemunik, T.; Huffman, J.; Yengo, L.; Zhao, J.H.; Demirkan, A.; Feitosa, M.F.; Liu, X.; Malerba, G.; Lopez, L.M.; van der Harst, P.; Li, X.Z.; Kleber, M.E.; Hicks, A.A.; Nolte, I.M.; Johansson, A.; Murgia, F.; Wild, S.H.; Bakker, S.J.L.; Peden, J.F.; Dehghan, A.; Steri, M.; Tenesa, A.; Lagou, V.; Salo, P.; Mangino, M.; Rose, L.M.; Lehtimaki, T.; Woodward, O.M.; Okada, Y.; Tin, A.; Muller, C.; Oldmeadow, C.; Putku, M.; Czamara, D.; Kraft, P.; Frogheri, L.; Thun, G.A.; Grotevendt, A.; Gislason, G.K.; Harris, T.B.; Launer, L.J.; McArdle, P.; Shuldiner, A.R.; Boerwinkle, E.; Coresh, J.; Schmidt, H.; Schallert, M.; Martin, N.G.; Montgomery, G.W.; Kubo, M.; Nakamura, Y.; Tanaka, T.; Munroe, P.B.; Samani, N.J.; Jacobs, D.R.; Liu, K.; d'Adamo, P.; Ulivi, S.; Rotter, J.I.; Psaty, B.M.; Vollenweider, P.; Waeber, G.; Campbell, S.; Devuyst, O.; Navarro, P.; Kolcic, I.; Hastie, N.; Balkau, B.; Froguel, P.; Esko, T.; Salumets, A.; Khaw, K.T.; Langenberg, C.; Wareham, N.J.; Isaacs, A.; Kraja, A.; Zhang, Q.Y.; Penninx, B.W.J.H.; Smit, J.H.; Bochud, M.; Gieger, C.

    2013-01-01

    Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with

  16. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

    NARCIS (Netherlands)

    Köttgen, Anna; Albrecht, Eva; Teumer, Alexander; Vitart, Veronique; Krumsiek, Jan; Hundertmark, Claudia; Pistis, Giorgio; Ruggiero, Daniela; O'Seaghdha, Conall M; Haller, Toomas; Yang, Qiong; Tanaka, Toshiko; Johnson, Andrew D; Kutalik, Zoltán; Smith, Albert V; Shi, Julia; Struchalin, Maksim; Middelberg, Rita P S; Brown, Morris J; Gaffo, Angelo L; Pirastu, Nicola; Li, Guo; Hayward, Caroline; Zemunik, Tatijana; Huffman, Jennifer; Yengo, Loic; Zhao, Jing Hua; Demirkan, Ayse; Feitosa, Mary F; Liu, Xuan; Malerba, Giovanni; Lopez, Lorna M; van der Harst, Pim; Li, Xinzhong; Kleber, Marcus E; Hicks, Andrew A; Nolte, Ilja M; Johansson, Asa; Murgia, Federico; Bakker, Stephan J L; Lagou, Vasiliki; Bruinenberg, Marcel; Stolk, Ronald P; Penninx, Brenda W; Mateo Leach, Irene; van Gilst, Wiek H; Hillege, Hans L; Wolffenbuttel, Bruce H R; Snieder, Harold; Navis, Gerjan

    Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with

  17. Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation

    DEFF Research Database (Denmark)

    Sinner, Moritz F; Tucker, Nathan R; Lunetta, Kathryn L

    2014-01-01

    BACKGROUND: Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. METHODS AND RESULTS: To identify new AF-re...

  18. Dynamic zebrafish interactome reveals transcriptional mechanisms of dioxin toxicity.

    Directory of Open Access Journals (Sweden)

    Andrey Alexeyenko

    2010-05-01

    Full Text Available In order to generate hypotheses regarding the mechanisms by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin causes toxicity, we analyzed global gene expression changes in developing zebrafish embryos exposed to this potent toxicant in the context of a dynamic gene network. For this purpose, we also computationally inferred a zebrafish (Danio rerio interactome based on orthologs and interaction data from other eukaryotes.Using novel computational tools to analyze this interactome, we distinguished between dioxin-dependent and dioxin-independent interactions between proteins, and tracked the temporal propagation of dioxin-dependent transcriptional changes from a few genes that were altered initially, to large groups of biologically coherent genes at later times. The most notable processes altered at later developmental stages were calcium and iron metabolism, embryonic morphogenesis including neuronal and retinal development, a variety of mitochondria-related functions, and generalized stress response (not including induction of antioxidant genes. Within the interactome, many of these responses were connected to cytochrome P4501A (cyp1a as well as other genes that were dioxin-regulated one day after exposure. This suggests that cyp1a may play a key role initiating the toxic dysregulation of those processes, rather than serving simply as a passive marker of dioxin exposure, as suggested by earlier research.Thus, a powerful microarray experiment coupled with a flexible interactome and multi-pronged interactome tools (which are now made publicly available for microarray analysis and related work suggest the hypothesis that dioxin, best known in fish as a potent cardioteratogen, has many other targets. Many of these types of toxicity have been observed in mammalian species and are potentially caused by alterations to cyp1a.

  19. Comparative analyses identified species-specific functional roles in oral microbial genomes

    Science.gov (United States)

    Chen, Tsute; Gajare, Prasad; Olsen, Ingar; Dewhirst, Floyd E.

    2017-01-01

    ABSTRACT The advent of next generation sequencing is producing more genomic sequences for various strains of many human oral microbial species and allows for insightful functional comparisons at both intra- and inter-species levels. This study performed in-silico functional comparisons for currently available genomic sequences of major species associated with periodontitis including Aggregatibacter actinomycetemcomitans (AA), Porphyromonas gingivalis (PG), Treponema denticola (TD), and Tannerella forsythia (TF), as well as several cariogenic and commensal streptococcal species. Complete or draft sequences were annotated with the RAST to infer structured functional subsystems for each genome. The subsystems profiles were clustered to groups of functions with similar patterns. Functional enrichment and depletion were evaluated based on hypergeometric distribution to identify subsystems that are unique or missing between two groups of genomes. Unique or missing metabolic pathways and biological functions were identified in different species. For example, components involved in flagellar motility were found only in the motile species TD, as expected, with few exceptions scattered in several streptococcal species, likely associated with chemotaxis. Transposable elements were only found in the two Bacteroidales species PG and TF, and half of the AA genomes. Genes involved in CRISPR were prevalent in most oral species. Furthermore, prophage related subsystems were also commonly found in most species except for PG and Streptococcus mutans, in which very few genomes contain prophage components. Comparisons between pathogenic (P) and nonpathogenic (NP) genomes also identified genes potentially important for virulence. Two such comparisons were performed between AA (P) and several A. aphrophilus (NP) strains, and between S. mutans + S. sobrinus (P) and other oral streptococcal species (NP). This comparative genomics approach can be readily used to identify functions unique to

  20. Identifying Breeding Priorities for Blueberry Flavor Using Biochemical, Sensory, and Genotype by Environment Analyses

    Science.gov (United States)

    Gilbert, Jessica L.; Guthart, Matthew J.; Gezan, Salvador A.; Pisaroglo de Carvalho, Melissa; Schwieterman, Michael L.; Colquhoun, Thomas A.; Bartoshuk, Linda M.; Sims, Charles A.; Clark, David G.; Olmstead, James W.

    2015-01-01

    Breeding for a subjective goal such as flavor is challenging, as many blueberry cultivars are grown worldwide, and identifying breeding targets relating to blueberry flavor biochemistry that have a high degree of genetic control and low environmental variability are priorities. A variety of biochemical compounds and physical characters induce the sensory responses of taste, olfaction, and somatosensation, all of which interact to create what is perceived flavor. The goal of this study was to identify the flavor compounds with a larger genetic versus environmental component regulating their expression over an array of cultivars, locations, and years. Over the course of three years, consumer panelists rated overall liking, texture, sweetness, sourness, and flavor intensity of 19 southern highbush blueberry (Vaccinium corymbosum hybrids) genotypes in 30 sensory panels. Significant positive correlations to overall liking of blueberry fruit (Panalysis was used to identify sugars, acids, and volatile compounds contributing to liking and sensory intensities, and revealed strong effects of fructose, pH, and several volatile compounds upon all sensory parameters measured. To assess the feasibility of breeding for flavor components, a three year study was conducted to compare genetic and environmental influences on flavor biochemistry. Panelists could discern genotypic variation in blueberry sensory components, and many of the compounds affecting consumer favor of blueberries, such as fructose, pH, β-caryophyllene oxide and 2-heptanone, were sufficiently genetically controlled that allocating resources for their breeding is worthwhile. PMID:26378911

  1. Dissection of protein interactomics highlights microRNA synergy.

    Science.gov (United States)

    Zhu, Wenliang; Zhao, Yilei; Xu, Yingqi; Sun, Yong; Wang, Zhe; Yuan, Wei; Du, Zhimin

    2013-01-01

    Despite a large amount of microRNAs (miRNAs) have been validated to play crucial roles in human biology and disease, there is little systematic insight into the nature and scale of the potential synergistic interactions executed by miRNAs themselves. Here we established an integrated parameter synergy score to determine miRNA synergy, by combining the two mechanisms for miRNA-miRNA interactions, miRNA-mediated gene co-regulation and functional association between target gene products, into one single parameter. Receiver operating characteristic (ROC) analysis indicated that synergy score accurately identified the gene ontology-defined miRNA synergy (AUC = 0.9415, psynergy, implying poor expectancy of widespread synergy. However, targeting more key genes made two miRNAs more likely to act synergistically. Compared to other miRNAs, miR-21 was a highly exceptional case due to frequent appearance in the top synergistic miRNA pairs. This result highlighted its essential role in coordinating or strengthening physiological and pathological functions of other miRNAs. The synergistic effect of miR-21 and miR-1 were functionally validated for their significant influences on myocardial apoptosis, cardiac hypertrophy and fibrosis. The novel approach established in this study enables easy and effective identification of condition-restricted potent miRNA synergy simply by concentrating the available protein interactomics and miRNA-target interaction data into a single parameter synergy score. Our results may be important for understanding synergistic gene regulation by miRNAs and may have significant implications for miRNA combination therapy of cardiovascular disease.

  2. Identifying Breeding Priorities for Blueberry Flavor Using Biochemical, Sensory, and Genotype by Environment Analyses.

    Directory of Open Access Journals (Sweden)

    Jessica L Gilbert

    Full Text Available Breeding for a subjective goal such as flavor is challenging, as many blueberry cultivars are grown worldwide, and identifying breeding targets relating to blueberry flavor biochemistry that have a high degree of genetic control and low environmental variability are priorities. A variety of biochemical compounds and physical characters induce the sensory responses of taste, olfaction, and somatosensation, all of which interact to create what is perceived flavor. The goal of this study was to identify the flavor compounds with a larger genetic versus environmental component regulating their expression over an array of cultivars, locations, and years. Over the course of three years, consumer panelists rated overall liking, texture, sweetness, sourness, and flavor intensity of 19 southern highbush blueberry (Vaccinium corymbosum hybrids genotypes in 30 sensory panels. Significant positive correlations to overall liking of blueberry fruit (P<0.001 were found with sweetness (R2 = 0.70, texture (R2 = 0.68, and flavor (R2 = 0.63. Sourness had a significantly negative relationship with overall liking (R2 = 0.55. The relationship between flavor and texture liking was also linear (R2 = 0.73, P<0.0001 demonstrating interaction between olfaction and somatosensation. Partial least squares analysis was used to identify sugars, acids, and volatile compounds contributing to liking and sensory intensities, and revealed strong effects of fructose, pH, and several volatile compounds upon all sensory parameters measured. To assess the feasibility of breeding for flavor components, a three year study was conducted to compare genetic and environmental influences on flavor biochemistry. Panelists could discern genotypic variation in blueberry sensory components, and many of the compounds affecting consumer favor of blueberries, such as fructose, pH, β-caryophyllene oxide and 2-heptanone, were sufficiently genetically controlled that allocating resources for their

  3. Differential proteomic and tissue expression analyses identify valuable diagnostic biomarkers of hepatocellular differentiation and hepatoid adenocarcinomas.

    Science.gov (United States)

    Reis, Henning; Padden, Juliet; Ahrens, Maike; Pütter, Carolin; Bertram, Stefanie; Pott, Leona L; Reis, Anna-Carinna; Weber, Frank; Juntermanns, Benjamin; Hoffmann, Andreas-C; Eisenacher, Martin; Schlaak, Joörg F; Canbay, Ali; Meyer, Helmut E; Sitek, Barbara; Baba, Hideo A

    2015-10-01

    The exact discrimination of lesions with true hepatocellular differentiation from secondary tumours and neoplasms with hepatocellular histomorphology like hepatoid adenocarcinomas (HAC) is crucial. Therefore, we aimed to identify ancillary protein biomarkers by using complementary proteomic techniques (2D-DIGE, label-free MS). The identified candidates were immunohistochemically validated in 14 paired samples of hepatocellular carcinoma (HCC) and non-tumourous liver tissue (NT). The candidates and HepPar1/Arginase1 were afterwards tested for consistency in a large cohort of hepatocellular lesions and NT (n = 290), non-hepatocellular malignancies (n = 383) and HAC (n = 13). Eight non-redundant, differentially expressed proteins were suitable for further immunohistochemical validation and four (ABAT, BHMT, FABP1, HAOX1) for further evaluation. Sensitivity and specificity rates for HCC/HAC were as follows: HepPar1 80.2%, 94.3% / 80.2%, 46.2%; Arginase1 82%, 99.4% / 82%, 69.2%; BHMT 61.4%, 93.8% / 61.4%, 100%; ABAT 84.4%, 33.7% / 84.4%, 30.8%; FABP1 87.2%, 95% / 87.2%, 69.2%; HAOX1 95.5%, 36.3% / 95.5%, 46.2%. The best 2×/3× biomarker panels for the diagnosis of HCC consisted of Arginase1/HAOX1 and BHMT/Arginase1/HAOX1 and for HAC consisted of Arginase1/FABP1 and BHMT/Arginase1/FABP1. In summary, we successfully identified, validated and benchmarked protein biomarker candidates of hepatocellular differentiation. BHMT in particular exhibited superior diagnostic characteristics in hepatocellular lesions and specifically in HAC. BHMT is therefore a promising (panel based) biomarker candidate in the differential diagnostic process of lesions with hepatocellular aspect.

  4. Comparative analyses of Legionella species identifies genetic features of strains causing Legionnaires' disease.

    Science.gov (United States)

    Gomez-Valero, Laura; Rusniok, Christophe; Rolando, Monica; Neou, Mario; Dervins-Ravault, Delphine; Demirtas, Jasmin; Rouy, Zoe; Moore, Robert J; Chen, Honglei; Petty, Nicola K; Jarraud, Sophie; Etienne, Jerome; Steinert, Michael; Heuner, Klaus; Gribaldo, Simonetta; Médigue, Claudine; Glöckner, Gernot; Hartland, Elizabeth L; Buchrieser, Carmen

    2014-01-01

    The genus Legionella comprises over 60 species. However, L. pneumophila and L. longbeachae alone cause over 95% of Legionnaires’ disease. To identify the genetic bases underlying the different capacities to cause disease we sequenced and compared the genomes of L. micdadei, L. hackeliae and L. fallonii (LLAP10), which are all rarely isolated from humans. We show that these Legionella species possess different virulence capacities in amoeba and macrophages, correlating with their occurrence in humans. Our comparative analysis of 11 Legionella genomes belonging to five species reveals highly heterogeneous genome content with over 60% representing species-specific genes; these comprise a complete prophage in L. micdadei, the first ever identified in a Legionella genome. Mobile elements are abundant in Legionella genomes; many encode type IV secretion systems for conjugative transfer, pointing to their importance for adaptation of the genus. The Dot/Icm secretion system is conserved, although the core set of substrates is small, as only 24 out of over 300 described Dot/Icm effector genes are present in all Legionella species. We also identified new eukaryotic motifs including thaumatin, synaptobrevin or clathrin/coatomer adaptine like domains. Legionella genomes are highly dynamic due to a large mobilome mainly comprising type IV secretion systems, while a minority of core substrates is shared among the diverse species. Eukaryotic like proteins and motifs remain a hallmark of the genus Legionella. Key factors such as proteins involved in oxygen binding, iron storage, host membrane transport and certain Dot/Icm substrates are specific features of disease-related strains.

  5. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.

    Science.gov (United States)

    Nicolas, Aude; Kenna, Kevin P; Renton, Alan E; Ticozzi, Nicola; Faghri, Faraz; Chia, Ruth; Dominov, Janice A; Kenna, Brendan J; Nalls, Mike A; Keagle, Pamela; Rivera, Alberto M; van Rheenen, Wouter; Murphy, Natalie A; van Vugt, Joke J F A; Geiger, Joshua T; Van der Spek, Rick A; Pliner, Hannah A; Shankaracharya; Smith, Bradley N; Marangi, Giuseppe; Topp, Simon D; Abramzon, Yevgeniya; Gkazi, Athina Soragia; Eicher, John D; Kenna, Aoife; Mora, Gabriele; Calvo, Andrea; Mazzini, Letizia; Riva, Nilo; Mandrioli, Jessica; Caponnetto, Claudia; Battistini, Stefania; Volanti, Paolo; La Bella, Vincenzo; Conforti, Francesca L; Borghero, Giuseppe; Messina, Sonia; Simone, Isabella L; Trojsi, Francesca; Salvi, Fabrizio; Logullo, Francesco O; D'Alfonso, Sandra; Corrado, Lucia; Capasso, Margherita; Ferrucci, Luigi; Moreno, Cristiane de Araujo Martins; Kamalakaran, Sitharthan; Goldstein, David B; Gitler, Aaron D; Harris, Tim; Myers, Richard M; Phatnani, Hemali; Musunuri, Rajeeva Lochan; Evani, Uday Shankar; Abhyankar, Avinash; Zody, Michael C; Kaye, Julia; Finkbeiner, Steven; Wyman, Stacia K; LeNail, Alex; Lima, Leandro; Fraenkel, Ernest; Svendsen, Clive N; Thompson, Leslie M; Van Eyk, Jennifer E; Berry, James D; Miller, Timothy M; Kolb, Stephen J; Cudkowicz, Merit; Baxi, Emily; Benatar, Michael; Taylor, J Paul; Rampersaud, Evadnie; Wu, Gang; Wuu, Joanne; Lauria, Giuseppe; Verde, Federico; Fogh, Isabella; Tiloca, Cinzia; Comi, Giacomo P; Sorarù, Gianni; Cereda, Cristina; Corcia, Philippe; Laaksovirta, Hannu; Myllykangas, Liisa; Jansson, Lilja; Valori, Miko; Ealing, John; Hamdalla, Hisham; Rollinson, Sara; Pickering-Brown, Stuart; Orrell, Richard W; Sidle, Katie C; Malaspina, Andrea; Hardy, John; Singleton, Andrew B; Johnson, Janel O; Arepalli, Sampath; Sapp, Peter C; McKenna-Yasek, Diane; Polak, Meraida; Asress, Seneshaw; Al-Sarraj, Safa; King, Andrew; Troakes, Claire; Vance, Caroline; de Belleroche, Jacqueline; Baas, Frank; Ten Asbroek, Anneloor L M A; Muñoz-Blanco, José Luis; Hernandez, Dena G; Ding, Jinhui; Gibbs, J Raphael; Scholz, Sonja W; Floeter, Mary Kay; Campbell, Roy H; Landi, Francesco; Bowser, Robert; Pulst, Stefan M; Ravits, John M; MacGowan, Daniel J L; Kirby, Janine; Pioro, Erik P; Pamphlett, Roger; Broach, James; Gerhard, Glenn; Dunckley, Travis L; Brady, Christopher B; Kowall, Neil W; Troncoso, Juan C; Le Ber, Isabelle; Mouzat, Kevin; Lumbroso, Serge; Heiman-Patterson, Terry D; Kamel, Freya; Van Den Bosch, Ludo; Baloh, Robert H; Strom, Tim M; Meitinger, Thomas; Shatunov, Aleksey; Van Eijk, Kristel R; de Carvalho, Mamede; Kooyman, Maarten; Middelkoop, Bas; Moisse, Matthieu; McLaughlin, Russell L; Van Es, Michael A; Weber, Markus; Boylan, Kevin B; Van Blitterswijk, Marka; Rademakers, Rosa; Morrison, Karen E; Basak, A Nazli; Mora, Jesús S; Drory, Vivian E; Shaw, Pamela J; Turner, Martin R; Talbot, Kevin; Hardiman, Orla; Williams, Kelly L; Fifita, Jennifer A; Nicholson, Garth A; Blair, Ian P; Rouleau, Guy A; Esteban-Pérez, Jesús; García-Redondo, Alberto; Al-Chalabi, Ammar; Rogaeva, Ekaterina; Zinman, Lorne; Ostrow, Lyle W; Maragakis, Nicholas J; Rothstein, Jeffrey D; Simmons, Zachary; Cooper-Knock, Johnathan; Brice, Alexis; Goutman, Stephen A; Feldman, Eva L; Gibson, Summer B; Taroni, Franco; Ratti, Antonia; Gellera, Cinzia; Van Damme, Philip; Robberecht, Wim; Fratta, Pietro; Sabatelli, Mario; Lunetta, Christian; Ludolph, Albert C; Andersen, Peter M; Weishaupt, Jochen H; Camu, William; Trojanowski, John Q; Van Deerlin, Vivianna M; Brown, Robert H; van den Berg, Leonard H; Veldink, Jan H; Harms, Matthew B; Glass, Jonathan D; Stone, David J; Tienari, Pentti; Silani, Vincenzo; Chiò, Adriano; Shaw, Christopher E; Traynor, Bryan J; Landers, John E

    2018-03-21

    To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Identifying Breeding Priorities for Blueberry Flavor Using Biochemical, Sensory, and Genotype by Environment Analyses.

    Science.gov (United States)

    Gilbert, Jessica L; Guthart, Matthew J; Gezan, Salvador A; Pisaroglo de Carvalho, Melissa; Schwieterman, Michael L; Colquhoun, Thomas A; Bartoshuk, Linda M; Sims, Charles A; Clark, David G; Olmstead, James W

    2015-01-01

    Breeding for a subjective goal such as flavor is challenging, as many blueberry cultivars are grown worldwide, and identifying breeding targets relating to blueberry flavor biochemistry that have a high degree of genetic control and low environmental variability are priorities. A variety of biochemical compounds and physical characters induce the sensory responses of taste, olfaction, and somatosensation, all of which interact to create what is perceived flavor. The goal of this study was to identify the flavor compounds with a larger genetic versus environmental component regulating their expression over an array of cultivars, locations, and years. Over the course of three years, consumer panelists rated overall liking, texture, sweetness, sourness, and flavor intensity of 19 southern highbush blueberry (Vaccinium corymbosum hybrids) genotypes in 30 sensory panels. Significant positive correlations to overall liking of blueberry fruit (Pblueberry sensory components, and many of the compounds affecting consumer favor of blueberries, such as fructose, pH, β-caryophyllene oxide and 2-heptanone, were sufficiently genetically controlled that allocating resources for their breeding is worthwhile.

  7. Single-cell analyses identify bioengineered niches for enhanced maintenance of hematopoietic stem cells.

    Science.gov (United States)

    Roch, Aline; Giger, Sonja; Girotra, Mukul; Campos, Vasco; Vannini, Nicola; Naveiras, Olaia; Gobaa, Samy; Lutolf, Matthias P

    2017-08-09

    The in vitro expansion of long-term hematopoietic stem cells (HSCs) remains a substantial challenge, largely because of our limited understanding of the mechanisms that control HSC fate choices. Using single-cell multigene expression analysis and time-lapse microscopy, here we define gene expression signatures and cell cycle hallmarks of murine HSCs and the earliest multipotent progenitors (MPPs), and analyze systematically single HSC fate choices in culture. Our analysis revealed twelve differentially expressed genes marking the quiescent HSC state, including four genes encoding cell-cell interaction signals in the niche. Under basal culture conditions, most HSCs rapidly commit to become early MPPs. In contrast, when we present ligands of the identified niche components such as JamC or Esam within artificial niches, HSC cycling is reduced and long-term multipotency in vivo is maintained. Our approach to bioengineer artificial niches should be useful in other stem cell systems.Haematopoietic stem cell (HSC) self-renewal is not sufficiently understood to recapitulate in vitro. Here, the authors generate gene signature and cell cycle hallmarks of single murine HSCs, and use identified endothelial receptors Esam and JamC as substrates to enhance HSC growth in engineered niches.

  8. Stable isotope analyses of feather amino acids identify penguin migration strategies at ocean basin scales.

    Science.gov (United States)

    Polito, Michael J; Hinke, Jefferson T; Hart, Tom; Santos, Mercedes; Houghton, Leah A; Thorrold, Simon R

    2017-08-01

    Identifying the at-sea distribution of wide-ranging marine predators is critical to understanding their ecology. Advances in electronic tracking devices and intrinsic biogeochemical markers have greatly improved our ability to track animal movements on ocean-wide scales. Here, we show that, in combination with direct tracking, stable carbon isotope analysis of essential amino acids in tail feathers provides the ability to track the movement patterns of two, wide-ranging penguin species over ocean basin scales. In addition, we use this isotopic approach across multiple breeding colonies in the Scotia Arc to evaluate migration trends at a regional scale that would be logistically challenging using direct tracking alone. © 2017 The Author(s).

  9. Comprehensive analyses of ventricular myocyte models identify targets exhibiting favorable rate dependence.

    Directory of Open Access Journals (Sweden)

    Megan A Cummins

    2014-03-01

    Full Text Available Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP. The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz and fast (2 Hz rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of

  10. Arabidopsis G-protein interactome reveals connections to cell wall carbohydrates and morphogenesis.

    Science.gov (United States)

    Klopffleisch, Karsten; Phan, Nguyen; Augustin, Kelsey; Bayne, Robert S; Booker, Katherine S; Botella, Jose R; Carpita, Nicholas C; Carr, Tyrell; Chen, Jin-Gui; Cooke, Thomas Ryan; Frick-Cheng, Arwen; Friedman, Erin J; Fulk, Brandon; Hahn, Michael G; Jiang, Kun; Jorda, Lucia; Kruppe, Lydia; Liu, Chenggang; Lorek, Justine; McCann, Maureen C; Molina, Antonio; Moriyama, Etsuko N; Mukhtar, M Shahid; Mudgil, Yashwanti; Pattathil, Sivakumar; Schwarz, John; Seta, Steven; Tan, Matthew; Temp, Ulrike; Trusov, Yuri; Urano, Daisuke; Welter, Bastian; Yang, Jing; Panstruga, Ralph; Uhrig, Joachim F; Jones, Alan M

    2011-09-27

    The heterotrimeric G-protein complex is minimally composed of Gα, Gβ, and Gγ subunits. In the classic scenario, the G-protein complex is the nexus in signaling from the plasma membrane, where the heterotrimeric G-protein associates with heptahelical G-protein-coupled receptors (GPCRs), to cytoplasmic target proteins called effectors. Although a number of effectors are known in metazoans and fungi, none of these are predicted to exist in their canonical forms in plants. To identify ab initio plant G-protein effectors and scaffold proteins, we screened a set of proteins from the G-protein complex using two-hybrid complementation in yeast. After deep and exhaustive interrogation, we detected 544 interactions between 434 proteins, of which 68 highly interconnected proteins form the core G-protein interactome. Within this core, over half of the interactions comprising two-thirds of the nodes were retested and validated as genuine in planta. Co-expression analysis in combination with phenotyping of loss-of-function mutations in a set of core interactome genes revealed a novel role for G-proteins in regulating cell wall modification.

  11. Interactomic approach for evaluating nucleophosmin-binding proteins as biomarkers for Ewing's sarcoma.

    Science.gov (United States)

    Haga, Ayako; Ogawara, Yoko; Kubota, Daisuke; Kitabayashi, Issay; Murakami, Yasufumi; Kondo, Tadashi

    2013-06-01

    Nucleophosmin (NPM) is a novel prognostic biomarker for Ewing's sarcoma. To evaluate the prognostic utility of NPM, we conducted an interactomic approach to characterize the NPM protein complex in Ewing's sarcoma cells. A gene suppression assay revealed that NPM promoted cell proliferation and the invasive properties of Ewing's sarcoma cells. FLAG-tag-based affinity purification coupled with liquid chromatography-tandem mass spectrometry identified 106 proteins in the NPM protein complex. The functional classification suggested that the NPM complex participates in critical biological events, including ribosome biogenesis, regulation of transcription and translation, and protein folding, that are mediated by these proteins. In addition to JAK1, a candidate prognostic biomarker for Ewing's sarcoma, the NPM complex, includes 11 proteins known as prognostic biomarkers for other malignancies. Meta-analysis of gene expression profiles of 32 patients with Ewing's sarcoma revealed that 6 of 106 were significantly and independently associated with survival period. These observations suggest a functional role as well as prognostic value of these NPM complex proteins in Ewing's sarcoma. Further, our study suggests the potential applications of interactomics in conjunction with meta-analysis for biomarker discovery. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Comparative and bioinformatics analyses of pathogenic bacterial secretomes identified by mass spectrometry in Burkholderia species.

    Science.gov (United States)

    Nguyen, Thao Thi; Chon, Tae-Soo; Kim, Jaehan; Seo, Young-Su; Heo, Muyoung

    2017-07-01

    Secreted proteins (secretomes) play crucial roles during bacterial pathogenesis in both plant and human hosts. The identification and characterization of secretomes in the two plant pathogens Burkholderia glumae BGR1 and B. gladioli BSR3, which cause diseases in rice such as seedling blight, panicle blight, and grain rot, are important steps to not only understand the disease-causing mechanisms but also find remedies for the diseases. Here, we identified two datasets of secretomes in B. glumae BGR1 and B. gladioli BSR3, which consist of 118 and 111 proteins, respectively, using mass spectrometry approach and literature curation. Next, we characterized the functional properties, potential secretion pathways and sequence information properties of secretomes of two plant pathogens in a comparative analysis by various computational approaches. The ratio of potential non-classically secreted proteins (NCSPs) to classically secreted proteins (CSPs) in B. glumae BGR1 was greater than that in B. gladioli BSR3. For CSPs, the putative hydrophobic regions (PHRs) which are essential for secretion process of CSPs were screened in detail at their N-terminal sequences using hidden Markov model (HMM)-based method. Total 31 pairs of homologous proteins in two bacterial secretomes were indicated based on the global alignment (identity ≥ 70%). Our results may facilitate the understanding of the species-specific features of secretomes in two plant pathogenic Burkholderia species.

  13. Statistical analyses of scatterplots to identify important factors in large-scale simulations, 1: Review and comparison of techniques

    International Nuclear Information System (INIS)

    Kleijnen, J.P.C.; Helton, J.C.

    1999-01-01

    Procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses are described and illustrated. These procedures attempt to detect increasingly complex patterns in scatterplots and involve the identification of (i) linear relationships with correlation coefficients, (ii) monotonic relationships with rank correlation coefficients, (iii) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (iv) trends in variability as defined by variances and interquartile ranges, and (v) deviations from randomness as defined by the chi-square statistic. A sequence of example analyses with a large model for two-phase fluid flow illustrates how the individual procedures can differ in the variables that they identify as having effects on particular model outcomes. The example analyses indicate that the use of a sequence of procedures is a good analysis strategy and provides some assurance that an important effect is not overlooked

  14. Mapping the Small Molecule Interactome by Mass Spectrometry.

    Science.gov (United States)

    Flaxman, Hope A; Woo, Christina M

    2018-01-16

    Mapping small molecule interactions throughout the proteome provides the critical structural basis for functional analysis of their impact on biochemistry. However, translation of mass spectrometry-based proteomics methods to directly profile the interaction between a small molecule and the whole proteome is challenging because of the substoichiometric nature of many interactions, the diversity of covalent and noncovalent interactions involved, and the subsequent computational complexity associated with their spectral assignment. Recent advances in chemical proteomics have begun fill this gap to provide a structural basis for the breadth of small molecule-protein interactions in the whole proteome. Innovations enabling direct characterization of the small molecule interactome include faster, more sensitive instrumentation coupled to chemical conjugation, enrichment, and labeling methods that facilitate detection and assignment. These methods have started to measure molecular interaction hotspots due to inherent differences in local amino acid reactivity and binding affinity throughout the proteome. Measurement of the small molecule interactome is producing structural insights and methods for probing and engineering protein biochemistry. Direct structural characterization of the small molecule interactome is a rapidly emerging area pushing new frontiers in biochemistry at the interface of small molecules and the proteome.

  15. Identification of human disease genes from interactome network using graphlet interaction.

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Wang

    Full Text Available Identifying genes related to human diseases, such as cancer and cardiovascular disease, etc., is an important task in biomedical research because of its applications in disease diagnosis and treatment. Interactome networks, especially protein-protein interaction networks, had been used to disease genes identification based on the hypothesis that strong candidate genes tend to closely relate to each other in some kinds of measure on the network. We proposed a new measure to analyze the relationship between network nodes which was called graphlet interaction. The graphlet interaction contained 28 different isomers. The results showed that the numbers of the graphlet interaction isomers between disease genes in interactome networks were significantly larger than random picked genes, while graphlet signatures were not. Then, we designed a new type of score, based on the network properties, to identify disease genes using graphlet interaction. The genes with higher scores were more likely to be disease genes, and all candidate genes were ranked according to their scores. Then the approach was evaluated by leave-one-out cross-validation. The precision of the current approach achieved 90% at about 10% recall, which was apparently higher than the previous three predominant algorithms, random walk, Endeavour and neighborhood based method. Finally, the approach was applied to predict new disease genes related to 4 common diseases, most of which were identified by other independent experimental researches. In conclusion, we demonstrate that the graphlet interaction is an effective tool to analyze the network properties of disease genes, and the scores calculated by graphlet interaction is more precise in identifying disease genes.

  16. Identification of Human Disease Genes from Interactome Network Using Graphlet Interaction

    Science.gov (United States)

    Yang, Lun; Wei, Dong-Qing; Qi, Ying-Xin; Jiang, Zong-Lai

    2014-01-01

    Identifying genes related to human diseases, such as cancer and cardiovascular disease, etc., is an important task in biomedical research because of its applications in disease diagnosis and treatment. Interactome networks, especially protein-protein interaction networks, had been used to disease genes identification based on the hypothesis that strong candidate genes tend to closely relate to each other in some kinds of measure on the network. We proposed a new measure to analyze the relationship between network nodes which was called graphlet interaction. The graphlet interaction contained 28 different isomers. The results showed that the numbers of the graphlet interaction isomers between disease genes in interactome networks were significantly larger than random picked genes, while graphlet signatures were not. Then, we designed a new type of score, based on the network properties, to identify disease genes using graphlet interaction. The genes with higher scores were more likely to be disease genes, and all candidate genes were ranked according to their scores. Then the approach was evaluated by leave-one-out cross-validation. The precision of the current approach achieved 90% at about 10% recall, which was apparently higher than the previous three predominant algorithms, random walk, Endeavour and neighborhood based method. Finally, the approach was applied to predict new disease genes related to 4 common diseases, most of which were identified by other independent experimental researches. In conclusion, we demonstrate that the graphlet interaction is an effective tool to analyze the network properties of disease genes, and the scores calculated by graphlet interaction is more precise in identifying disease genes. PMID:24465923

  17. Interactome of the hepatitis C virus: Literature mining with ANDSystem.

    Science.gov (United States)

    Saik, Olga V; Ivanisenko, Timofey V; Demenkov, Pavel S; Ivanisenko, Vladimir A

    2016-06-15

    A study of the molecular genetics mechanisms of host-pathogen interactions is of paramount importance in developing drugs against viral diseases. Currently, the literature contains a huge amount of information that describes interactions between HCV and human proteins. In addition, there are many factual databases that contain experimentally verified data on HCV-host interactions. The sources of such data are the original data along with the data manually extracted from the literature. However, the manual analysis of scientific publications is time consuming and, because of this, databases created with such an approach often do not have complete information. One of the most promising methods to provide actualisation and completeness of information is text mining. Here, with the use of a previously developed method by the authors using ANDSystem, an automated extraction of information on the interactions between HCV and human proteins was conducted. As a data source for the text mining approach, PubMed abstracts and full text articles were used. Additionally, external factual databases were analyzed. On the basis of this analysis, a special version of ANDSystem, extended with the HCV interactome, was created. The HCV interactome contains information about the interactions between 969 human and 11 HCV proteins. Among the 969 proteins, 153 'new' proteins were found not previously referred to in any external databases of protein-protein interactions for HCV-host interactions. Thus, the extended ANDSystem possesses a more comprehensive detailing of HCV-host interactions versus other existing databases. It was interesting that HCV proteins more preferably interact with human proteins that were already involved in a large number of protein-protein interactions as well as those associated with many diseases. Among human proteins of the HCV interactome, there were a large number of proteins regulated by microRNAs. It turned out that the results obtained for protein

  18. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    Science.gov (United States)

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian’an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O’Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tönu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control. PMID:22885924

  19. Genetic variants associated with subjective well-being, depressive symptoms and neuroticism identified through genome-wide analyses

    Science.gov (United States)

    Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; Davies, Gail; Furlotte, Nicholas A; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J; Miller, Michael B; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis O; van der Most, Peter J; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Thorleifsson, Gudmar; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Bergmann, Sven; Bjornsdottir, Gyda; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas J; Gieger, Christian; Gupta, Richa; Harris, Tamara B; Harris, Juliette M; Holliday, Elizabeth G; Hottenga, Jouke-Jan; De Jager, Philip L; Kaakinen, Marika A; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J; Franke, Lude; Li-Gao, Ruifang; Liewald, David C; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W; Mosing, Miriam A; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J; Smith, Jennifer A; Sutin, Angelina R; Trzaskowski, Maciej; Vinkhuyzen, Anna E; Yu, Lei; Zabaneh, Delilah; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J; van Duijn, Cornelia M; Eriksson, Johan G; Bültmann, Ute; de Geus, Eco J C; Groenen, Patrick J F; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A; Haworth, Claire M A; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Hyppönen, Elina; Iacono, William G; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Keltikangas-Järvinen, Liisa; Kraft, Peter; Kubzansky, Laura D; Lehtimäki, Terho; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J; Pasterkamp, Gerard; Pedersen, Nancy L; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S; Rosendaal, Frits R; den Ruijter, Hester M; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z; Sørensen, Thorkild I A; Spector, Tim D; Starr, John M; Stefansson, Kari; Steptoe, Andrew; Terracciano, Antonio; Thorsteinsdottir, Unnur; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Uitterlinden, André G; Vollenweider, Peter; Wagner, Gert G; Weir, David R; Yang, Jian; Conley, Dalton C; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Pickrell, Joseph K; Esko, Tõnu; Krueger, Robert F; Beauchamp, Jonathan P; Koellinger, Philipp D; Benjamin, Daniel J; Bartels, Meike; Cesarini, David

    2016-01-01

    We conducted genome-wide association studies of three phenotypes: subjective well-being (N = 298,420), depressive symptoms (N = 161,460), and neuroticism (N = 170,910). We identified three variants associated with subjective well-being, two with depressive symptoms, and eleven with neuroticism, including two inversion polymorphisms. The two depressive symptoms loci replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings, and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal/pancreas tissues are strongly enriched for association. PMID:27089181

  20. Statistical analyses of scatterplots to identify important factors in large-scale simulations, 2: robustness of techniques

    International Nuclear Information System (INIS)

    Kleijnen, J.P.C.; Helton, J.C.

    1999-01-01

    The robustness of procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses is investigated. These procedures are based on attempts to detect increasingly complex patterns in the scatterplots under consideration and involve the identification of (i) linear relationships with correlation coefficients, (ii) monotonic relationships with rank correlation coefficients, (iii) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (iv) trends in variability as defined by variances and interquartile ranges, and (v) deviations from randomness as defined by the chi-square statistic. The following two topics related to the robustness of these procedures are considered for a sequence of example analyses with a large model for two-phase fluid flow: the presence of Type I and Type II errors, and the stability of results obtained with independent Latin hypercube samples. Observations from analysis include: (i) Type I errors are unavoidable, (ii) Type II errors can occur when inappropriate analysis procedures are used, (iii) physical explanations should always be sought for why statistical procedures identify variables as being important, and (iv) the identification of important variables tends to be stable for independent Latin hypercube samples

  1. Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii.

    Science.gov (United States)

    Maifiah, Mohd Hafidz Mahamad; Cheah, Soon-Ee; Johnson, Matthew D; Han, Mei-Ling; Boyce, John D; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S; Hertzog, Paul; Purcell, Anthony W; Song, Jiangning; Velkov, Tony; Creek, Darren J; Li, Jian

    2016-02-29

    Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03-149.1 (polymyxin-susceptible) and 03-149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.

  2. Using multivariate analyses and GIS to identify pollutants and their spatial patterns in urban soils in Galway, Ireland

    International Nuclear Information System (INIS)

    Zhang Chaosheng

    2006-01-01

    Galway is a small but rapidly growing tourism city in western Ireland. To evaluate its environmental quality, a total of 166 surface soil samples (0-10 cm depth) were collected from parks and grasslands at the density of 1 sample per 0.25 km 2 at the end of 2004. All samples were analysed using ICP-AES for the near-total concentrations of 26 chemical elements. Multivariate statistics and GIS techniques were applied to classify the elements and to identify elements influenced by human activities. Cluster analysis (Canada) and principal component analysis (PCA) classified the elements into two groups: the first group predominantly derived from natural sources, the second being influenced by human activities. GIS mapping is a powerful tool in identifying the possible sources of pollutants. Relatively high concentrations of Cu, Pb and Zn were found in the city centre, old residential areas, and along major traffic routes, showing significant effects of traffic pollution. The element As is enriched in soils of the old built-up areas, which can be attributed to coal and peat combustion for home heating. Such significant spatial patterns of pollutants displayed by urban soils may imply potential health threat to residents of the contaminated areas of the city. - Multivariate statistics and GIS are useful tools to identify pollutants in urban soils

  3. Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria.

    Directory of Open Access Journals (Sweden)

    Hong Liu

    Full Text Available As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH had remained unclear until recently when ABCB6 was reported as a causative gene of DUH.We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation.Genome-wide linkage (assuming autosomal dominant inheritance mode and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them.Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.

  4. Comprehensively Characterizing the Thioredoxin Interactome In Vivo Highlights the Central Role Played by This Ubiquitous Oxidoreductase in Redox Control*

    Science.gov (United States)

    Arts, Isabelle S.; Vertommen, Didier; Baldin, Francesca; Laloux, Géraldine; Collet, Jean-François

    2016-01-01

    Thioredoxin (Trx) is a ubiquitous oxidoreductase maintaining protein-bound cysteine residues in the reduced thiol state. Here, we combined a well-established method to trap Trx substrates with the power of bacterial genetics to comprehensively characterize the in vivo Trx redox interactome in the model bacterium Escherichia coli. Using strains engineered to optimize trapping, we report the identification of a total 268 Trx substrates, including 201 that had never been reported to depend on Trx for reduction. The newly identified Trx substrates are involved in a variety of cellular processes, ranging from energy metabolism to amino acid synthesis and transcription. The interaction between Trx and two of its newly identified substrates, a protein required for the import of most carbohydrates, PtsI, and the bacterial actin homolog MreB was studied in detail. We provide direct evidence that PtsI and MreB contain cysteine residues that are susceptible to oxidation and that participate in the formation of an intermolecular disulfide with Trx. By considerably expanding the number of Trx targets, our work highlights the role played by this major oxidoreductase in a variety of cellular processes. Moreover, as the dependence on Trx for reduction is often conserved across species, it also provides insightful information on the interactome of Trx in organisms other than E. coli. PMID:27081212

  5. Evaluation of bentonite alteration due to interactions with iron. Sensitivity analyses to identify the important factors for the bentonite alteration

    International Nuclear Information System (INIS)

    Sasamoto, Hiroshi; Wilson, James; Sato, Tsutomu

    2013-01-01

    Performance assessment of geological disposal systems for high-level radioactive waste requires a consideration of long-term systems behaviour. It is possible that the alteration of swelling clay present in bentonite buffers might have an impact on buffer functions. In the present study, iron (as a candidate overpack material)-bentonite (I-B) interactions were evaluated as the main buffer alteration scenario. Existing knowledge on alteration of bentonite during I-B interactions was first reviewed, then the evaluation methodology was developed considering modeling techniques previously used overseas. A conceptual model for smectite alteration during I-B interactions was produced. The following reactions and processes were selected: 1) release of Fe 2+ due to overpack corrosion; 2) diffusion of Fe 2+ in compacted bentonite; 3) sorption of Fe 2+ on smectite edge and ion exchange in interlayers; 4) dissolution of primary phases and formation of alteration products. Sensitivity analyses were performed to identify the most important factors for the alteration of bentonite by I-B interactions. (author)

  6. Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci.

    Directory of Open Access Journals (Sweden)

    Samuel E Jones

    2016-08-01

    Full Text Available Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8, including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12 and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10. The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8. For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16 and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9. Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05; undersleeping and BMI (rG = 0.147, P = 1x10-5 and oversleeping and BMI (rG = 0.097, P = 0.04, Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and

  7. Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

    Directory of Open Access Journals (Sweden)

    Guan-Feng Wang

    2015-02-01

    Full Text Available Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR. Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC, a nucleotide binding (NB-ARC and a leucine rich repeat (LRR domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

  8. Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

    Science.gov (United States)

    Wang, Guan-Feng; Ji, Jiabing; El-Kasmi, Farid; Dangl, Jeffery L; Johal, Guri; Balint-Kurti, Peter J

    2015-02-01

    Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR) proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR). Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC), a nucleotide binding (NB-ARC) and a leucine rich repeat (LRR) domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

  9. Identifying the Research Process to Analyse the Adoption of the International Baccalaureate's Diploma Programme in England

    Science.gov (United States)

    Outhwaite, Deborah

    2018-01-01

    This article analyses the flow-line around the methodology used inside an educational research process that was originally established to examine the expansion of the International Baccalaureate's Diploma Programme (IBDP) in England. This article analyses the research question, then assesses the research focus, aims and objectives. The article…

  10. Comprehensive RNA Polymerase II Interactomes Reveal Distinct and Varied Roles for Each Phospho-CTD Residue

    Directory of Open Access Journals (Sweden)

    Kevin M. Harlen

    2016-06-01

    Full Text Available Transcription controls splicing and other gene regulatory processes, yet mechanisms remain obscure due to our fragmented knowledge of the molecular connections between the dynamically phosphorylated RNA polymerase II (Pol II C-terminal domain (CTD and regulatory factors. By systematically isolating phosphorylation states of the CTD heptapeptide repeat (Y1S2P3T4S5P6S7, we identify hundreds of protein factors that are differentially enriched, revealing unappreciated connections between the Pol II CTD and co-transcriptional processes. These data uncover a role for threonine-4 in 3′ end processing through control of the transition between cleavage and termination. Furthermore, serine-5 phosphorylation seeds spliceosomal assembly immediately downstream of 3′ splice sites through a direct interaction with spliceosomal subcomplex U1. Strikingly, threonine-4 phosphorylation also impacts splicing by serving as a mark of co-transcriptional spliceosome release and ensuring efficient post-transcriptional splicing genome-wide. Thus, comprehensive Pol II interactomes identify the complex and functional connections between transcription machinery and other gene regulatory complexes.

  11. Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90.

    Directory of Open Access Journals (Sweden)

    Feng Hong

    Full Text Available Up to 10% of cytosolic proteins are dependent on the mammalian heat shock protein 90 (HSP90 for folding. However, the interactors of its endoplasmic reticulum (ER paralogue (gp96, Grp94 and HSP90b1 has not been systematically identified. By combining genetic and biochemical approaches, we have comprehensively mapped the interactome of gp96 in macrophages and B cells. A total of 511 proteins were reduced in gp96 knockdown cells, compared to levels observed in wild type cells. By immunoprecipitation, we found that 201 proteins associated with gp96. Gene Ontology analysis indicated that these proteins are involved in metabolism, transport, translation, protein folding, development, localization, response to stress and cellular component biogenesis. While known gp96 clients such as integrins, Toll-like receptors (TLRs and Wnt co-receptor LRP6, were confirmed, cell surface HSP receptor CD91, TLR4 pathway protein CD180, WDR1, GANAB and CAPZB were identified as potentially novel substrates of gp96. Taken together, our study establishes gp96 as a critical chaperone to integrate innate immunity, Wnt signaling and organ development.

  12. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

    NARCIS (Netherlands)

    Verhoeven, Virginie J. M.; Hysi, Pirro G.; Wojciechowski, Robert; Fan, Qiao; Guggenheim, Jeremy A.; Höhn, René; Macgregor, Stuart; Hewitt, Alex W.; Nag, Abhishek; Cheng, Ching-Yu; Yonova-Doing, Ekaterina; Zhou, Xin; Ikram, M. Kamran; Buitendijk, Gabriëlle H. S.; McMahon, George; Kemp, John P.; Pourcain, Beate St; Simpson, Claire L.; Mäkelä, Kari-Matti; Lehtimäki, Terho; Kähönen, Mika; Paterson, Andrew D.; Hosseini, S. Mohsen; Wong, Hoi Suen; Xu, Liang; Jonas, Jost B.; Pärssinen, Olavi; Wedenoja, Juho; Yip, Shea Ping; Ho, Daniel W. H.; Pang, Chi Pui; Chen, Li Jia; Burdon, Kathryn P.; Craig, Jamie E.; Klein, Barbara E. K.; Klein, Ronald; Haller, Toomas; Metspalu, Andres; Khor, Chiea-Chuen; Tai, E.-Shyong; Aung, Tin; Vithana, Eranga; Tay, Wan-Ting; Barathi, Veluchamy A.; Chen, Peng; Li, Ruoying; Liao, Jiemin; Zheng, Yingfeng; Bergen, Arthur A. B.; Chen, Wei

    2013-01-01

    Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and

  13. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    DEFF Research Database (Denmark)

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes...

  14. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    NARCIS (Netherlands)

    Scott, Robert A.; Lagou, Vasiliki; Welch, Ryan P.; Wheeler, Eleanor; Montasser, May E.; Luan, Jian'an; Mägi, Reedik; Strawbridge, Rona J.; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J.; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C. D.; Jukema, J. Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V.; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J.; Evans, David M.; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S.; Hui, Jennie; Bielak, Lawrence F.; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R.; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tõnu; Mihailov, Evelin; Fraser, Ross M.; Fall, Tove; Voight, Benjamin F.; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M.; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S.; Willems, Sara M.; Chines, Peter S.; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Song, Kijoung; Tanaka, Toshiko; Peden, John F.; Goel, Anuj; Hicks, Andrew A.; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J.; Bruinenberg, Marcel; Pankow, James S.; North, Kari E.; Forouhi, Nita G.; Loos, Ruth J. F.; Edkins, Sarah; Varga, Tibor V.; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J. L.; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B.; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Palmer, Colin N. A.; Doney, Alex S. F.; Willemsen, Gonneke; Smit, Johannes H.; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L.; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L.; Fowkes, Gerard R.; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H.; Basart, Hanneke V.; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E.; Boehm, Bernhard O.; Peters, Annette; Pramstaller, Peter P.; Province, Michael A.; Borecki, Ingrid B.; Hastie, Nicholas D.; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M.; Bergman, Richard N.; Collins, Francis S.; Tuomilehto, Jaakko; Watanabe, Richard M.; de Geus, Eco J. C.; Penninx, Brenda W.; Hofman, Albert; Oostra, Ben A.; Psaty, Bruce M.; Vollenweider, Peter; Wilson, James F.; Wright, Alan F.; Hovingh, G. Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K. E.; Kyvik, Kirsten O.; Kaprio, Jaakko; Price, Jackie F.; Dedoussis, George V.; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R.; van Duijn, Cornelia M.; Morris, Andrew D.; Toenjes, Anke; Peyser, Patricia A.; Beilby, John P.; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R.; Schwarz, Peter E. H.; Lakka, Timo A.; Rauramaa, Rainer; Adair, Linda S.; Smith, George Davey; Spector, Tim D.; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Boomsma, Dorret I.; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L.; Sattar, Naveed; Harris, Tamara B.; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L.; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J.; Bouatia-Naji, Nabila; McCarthy, Mark I.; Franks, Paul W.; Meigs, James B.; Teslovich, Tanya M.; Florez, Jose C.; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes

  15. Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

    Science.gov (United States)

    Hitomi, Yuki; Tokunaga, Katsushi

    2017-01-01

    Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

  16. Efficient Prediction of Progesterone Receptor Interactome Using a Support Vector Machine Model

    Directory of Open Access Journals (Sweden)

    Ji-Long Liu

    2015-03-01

    Full Text Available Protein-protein interaction (PPI is essential for almost all cellular processes and identification of PPI is a crucial task for biomedical researchers. So far, most computational studies of PPI are intended for pair-wise prediction. Theoretically, predicting protein partners for a single protein is likely a simpler problem. Given enough data for a particular protein, the results can be more accurate than general PPI predictors. In the present study, we assessed the potential of using the support vector machine (SVM model with selected features centered on a particular protein for PPI prediction. As a proof-of-concept study, we applied this method to identify the interactome of progesterone receptor (PR, a protein which is essential for coordinating female reproduction in mammals by mediating the actions of ovarian progesterone. We achieved an accuracy of 91.9%, sensitivity of 92.8% and specificity of 91.2%. Our method is generally applicable to any other proteins and therefore may be of help in guiding biomedical experiments.

  17. Characterization of hampin/MSL1 as a node in the nuclear interactome

    International Nuclear Information System (INIS)

    Dmitriev, Ruslan I.; Korneenko, Tatyana V.; Bessonov, Alexander A.; Shakhparonov, Mikhail I.; Modyanov, Nikolai N.; Pestov, Nikolay B.

    2007-01-01

    Hampin, homolog of Drosophila MSL1, is a partner of histone acetyltransferase MYST1/MOF. Functions of these proteins remain poorly understood beyond their participation in chromatin remodeling complex MSL. In order to identify new proteins interacting with hampin, we screened a mouse cDNA library in yeast two-hybrid system with mouse hampin as bait and found five high-confidence interactors: MYST1, TPR proteins TTC4 and KIAA0103, NOP17 (homolog of a yeast nucleolar protein), and transcription factor GC BP. Subsequently, all these proteins were used as baits in library screenings and more new interactions were found: tumor suppressor RASSF1C and spliceosome component PRP3 for KIAA0103, ring finger RNF10 for RASSF1C, and RNA polymerase II regulator NELF-C for MYST1. The majority of the observed interactions was confirmed in vitro by pull-down of bacterially expressed proteins. Reconstruction of a fragment of mammalian interactome suggests that hampin may be linked to diverse regulatory processes in the nucleus

  18. Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity

    DEFF Research Database (Denmark)

    Larsen, Lesli H; Echwald, Søren Morgenthaler; Sørensen, Thorkild I A

    2005-01-01

    )) for mutations in MC4R. A total of 14 different mutations were identified of which two, Ala219Val and Leu325Phe, were novel variants. The variant receptor, Leu325Phe, was unable to bind [Nle4,d-Phe7]-alphaMSH, whereas the Ala219Val variant showed a significantly impaired melanotan II induction of cAMP, compared...

  19. Root Cause Analyses of Suicides of Mental Health Clients: Identifying Systematic Processes and Service-Level Prevention Strategies.

    Science.gov (United States)

    Gillies, Donna; Chicop, David; O'Halloran, Paul

    2015-01-01

    The ability to predict imminent risk of suicide is limited, particularly among mental health clients. Root cause analysis (RCA) can be used by health services to identify service-wide approaches to suicide prevention. To (a) develop a standardized taxonomy for RCAs; (b) to quantitate service-related factors associated with suicides; and (c) to identify service-related suicide prevention strategies. The RCAs of all people who died by suicide within 1 week of contact with the mental health service over 5 years were thematically analyzed using a data collection tool. Data were derived from RCAs of all 64 people who died by suicide between 2008 and 2012. Major themes were categorized as individual, situational, and care-related factors. The most common factor was that clients had recently denied suicidality. Reliance on carers, recent changes in medication, communication problems, and problems in follow-through were also commonly identified. Given the difficulty in predicting suicide in people whose expressions of suicidal ideation change so rapidly, services may consider the use of strategies aimed at improving the individual, stressor, support, and care factors identified in this study.

  20. Identifying consumer segments in health services markets: an application of conjoint and cluster analyses to the ambulatory care pharmacy market.

    Science.gov (United States)

    Carrol, N V; Gagon, J P

    1983-01-01

    Because of increasing competition, it is becoming more important that health care providers pursue consumer-based market segmentation strategies. This paper presents a methodology for identifying and describing consumer segments in health service markets, and demonstrates the use of the methodology by presenting a study of consumer segments in the ambulatory care pharmacy market.

  1. High-resolution linkage analyses to identify genes that influence Varroa sensitive hygiene behavior in honey bees.

    Science.gov (United States)

    Tsuruda, Jennifer M; Harris, Jeffrey W; Bourgeois, Lanie; Danka, Robert G; Hunt, Greg J

    2012-01-01

    Varroa mites (V. destructor) are a major threat to honey bees (Apis melilfera) and beekeeping worldwide and likely lead to colony decline if colonies are not treated. Most treatments involve chemical control of the mites; however, Varroa has evolved resistance to many of these miticides, leaving beekeepers with a limited number of alternatives. A non-chemical control method is highly desirable for numerous reasons including lack of chemical residues and decreased likelihood of resistance. Varroa sensitive hygiene behavior is one of two behaviors identified that are most important for controlling the growth of Varroa populations in bee hives. To identify genes influencing this trait, a study was conducted to map quantitative trait loci (QTL). Individual workers of a backcross family were observed and evaluated for their VSH behavior in a mite-infested observation hive. Bees that uncapped or removed pupae were identified. The genotypes for 1,340 informative single nucleotide polymorphisms were used to construct a high-resolution genetic map and interval mapping was used to analyze the association of the genotypes with the performance of Varroa sensitive hygiene. We identified one major QTL on chromosome 9 (LOD score = 3.21) and a suggestive QTL on chromosome 1 (LOD = 1.95). The QTL confidence interval on chromosome 9 contains the gene 'no receptor potential A' and a dopamine receptor. 'No receptor potential A' is involved in vision and olfaction in Drosophila, and dopamine signaling has been previously shown to be required for aversive olfactory learning in honey bees, which is probably necessary for identifying mites within brood cells. Further studies on these candidate genes may allow for breeding bees with this trait using marker-assisted selection.

  2. High-resolution linkage analyses to identify genes that influence Varroa sensitive hygiene behavior in honey bees.

    Directory of Open Access Journals (Sweden)

    Jennifer M Tsuruda

    Full Text Available Varroa mites (V. destructor are a major threat to honey bees (Apis melilfera and beekeeping worldwide and likely lead to colony decline if colonies are not treated. Most treatments involve chemical control of the mites; however, Varroa has evolved resistance to many of these miticides, leaving beekeepers with a limited number of alternatives. A non-chemical control method is highly desirable for numerous reasons including lack of chemical residues and decreased likelihood of resistance. Varroa sensitive hygiene behavior is one of two behaviors identified that are most important for controlling the growth of Varroa populations in bee hives. To identify genes influencing this trait, a study was conducted to map quantitative trait loci (QTL. Individual workers of a backcross family were observed and evaluated for their VSH behavior in a mite-infested observation hive. Bees that uncapped or removed pupae were identified. The genotypes for 1,340 informative single nucleotide polymorphisms were used to construct a high-resolution genetic map and interval mapping was used to analyze the association of the genotypes with the performance of Varroa sensitive hygiene. We identified one major QTL on chromosome 9 (LOD score = 3.21 and a suggestive QTL on chromosome 1 (LOD = 1.95. The QTL confidence interval on chromosome 9 contains the gene 'no receptor potential A' and a dopamine receptor. 'No receptor potential A' is involved in vision and olfaction in Drosophila, and dopamine signaling has been previously shown to be required for aversive olfactory learning in honey bees, which is probably necessary for identifying mites within brood cells. Further studies on these candidate genes may allow for breeding bees with this trait using marker-assisted selection.

  3. Characterization of the CLASP2 Protein Interaction Network Identifies SOGA1 as a Microtubule-Associated Protein

    DEFF Research Database (Denmark)

    Sørensen, Rikke Kruse; Krantz, James; Barker, Natalie

    2017-01-01

    . The GTPase-activating proteins AGAP1 and AGAP3 were also enriched in the CLASP2 interactome, although subsequent AGAP3 and CLIP2 interactome analysis suggests a preference of AGAP3 for CLIP2. Follow-up MARK2 interactome analysis confirmed reciprocal co-IP of CLASP2 and also revealed MARK2 can co-IP SOGA1......, glycogen synthase, and glycogenin. Investigating the SOGA1 interactome confirmed SOGA1 can reciprocal co-IP both CLASP2 and MARK2 as well as glycogen synthase and glycogenin. SOGA1 was confirmed to colocalize with CLASP2 and also with tubulin, which identifies SOGA1 as a new microtubule-associated protein....... These results introduce the metabolic function of these proposed novel protein networks and their relationship with microtubules as new fields of cytoskeleton-associated protein biology....

  4. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    OpenAIRE

    Okbay, Aysu; Baselmans, B.M.L. (Bart M.L.); Neve, Jan-Emmanuel; Turley, Patrick; Nivard, Michel; Fontana, M.A. (Mark Alan); Meddens, S.F.W. (S. Fleur W.); Linnér, R.K. (Richard Karlsson); Rietveld, C.A. (Cornelius A); Derringer, J.; Gratten, Jacob; Lee, James J.; Liu, J.Z. (Jimmy Z); Vlaming, Ronald; SAhluwalia, T. (Tarunveer)

    2016-01-01

    textabstractVery few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associ...

  5. Signature of Nonstationarity in Precipitation Extremes over Urbanizing Regions in India Identified through a Multivariate Frequency Analyses

    Science.gov (United States)

    Singh, Jitendra; Hari, Vittal; Sharma, Tarul; Karmakar, Subhankar; Ghosh, Subimal

    2016-04-01

    The statistical assumption of stationarity in hydrologic extreme time/event series has been relied heavily in frequency analysis. However, due to the analytically perceivable impacts of climate change, urbanization and concomitant land use pattern, assumption of stationarity in hydrologic time series will draw erroneous results, which in turn may affect the policy and decision-making. Past studies provided sufficient evidences on changes in the characteristics of Indian monsoon precipitation extremes and further it has been attributed to climate change and urbanization, which shows need of nonstationary analysis on the Indian monsoon extremes. Therefore, a comprehensive multivariate nonstationary frequency analysis has been conducted for the entire India to identify the precipitation characteristics (intensity, duration and depth) responsible for significant nonstationarity in the Indian monsoon. We use 1o resolution of precipitation data for a period of 1901-2004, in a Generalized Additive Model for Location, Scale and Shape (GAMLSS) framework. A cluster of GAMLSS models has been developed by considering nonstationarity in different combinations of distribution parameters through different regression techniques, and the best-fit model is further applied for bivariate analysis. A population density data has been utilized to identify the urban, urbanizing and rural regions. The results showed significant differences in the stationary and nonstationary bivariate return periods for the urbanizing grids, when compared to urbanized and rural grids. A comprehensive multivariate analysis has also been conducted to identify the precipitation characteristics particularly responsible for imprinting signature of nonstationarity.

  6. A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis

    DEFF Research Database (Denmark)

    Mechelli, Rosella; Umeton, Renato; Policano, Claudia

    2013-01-01

    of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge......, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate...... immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated...

  7. Synaptic Interactome Mining Reveals p140Cap as a New Hub for PSD Proteins Involved in Psychiatric and Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Annalisa Alfieri

    2017-06-01

    Full Text Available Altered synaptic function has been associated with neurological and psychiatric conditions including intellectual disability, schizophrenia and autism spectrum disorder (ASD. Amongst the recently discovered synaptic proteins is p140Cap, an adaptor that localizes at dendritic spines and regulates their maturation and physiology. We recently showed that p140Cap knockout mice have cognitive deficits, impaired long-term potentiation (LTP and long-term depression (LTD, and immature, filopodia-like dendritic spines. Only a few p140Cap interacting proteins have been identified in the brain and the molecular complexes and pathways underlying p140Cap synaptic function are largely unknown. Here, we isolated and characterized the p140Cap synaptic interactome by co-immunoprecipitation from crude mouse synaptosomes, followed by mass spectrometry-based proteomics. We identified 351 p140Cap interactors and found that they cluster to sub complexes mostly located in the postsynaptic density (PSD. p140Cap interactors converge on key synaptic processes, including transmission across chemical synapses, actin cytoskeleton remodeling and cell-cell junction organization. Gene co-expression data further support convergent functions: the p140Cap interactors are tightly co-expressed with each other and with p140Cap. Importantly, the p140Cap interactome and its co-expression network show strong enrichment in genes associated with schizophrenia, autism, bipolar disorder, intellectual disability and epilepsy, supporting synaptic dysfunction as a shared biological feature in brain diseases. Overall, our data provide novel insights into the molecular organization of the synapse and indicate that p140Cap acts as a hub for postsynaptic complexes relevant to psychiatric and neurological disorders.

  8. Genome-Wide Search Identifies 1.9 Mb from the Polar Bear Y Chromosome for Evolutionary Analyses.

    Science.gov (United States)

    Bidon, Tobias; Schreck, Nancy; Hailer, Frank; Nilsson, Maria A; Janke, Axel

    2015-05-27

    The male-inherited Y chromosome is the major haploid fraction of the mammalian genome, rendering Y-linked sequences an indispensable resource for evolutionary research. However, despite recent large-scale genome sequencing approaches, only a handful of Y chromosome sequences have been characterized to date, mainly in model organisms. Using polar bear (Ursus maritimus) genomes, we compare two different in silico approaches to identify Y-linked sequences: 1) Similarity to known Y-linked genes and 2) difference in the average read depth of autosomal versus sex chromosomal scaffolds. Specifically, we mapped available genomic sequencing short reads from a male and a female polar bear against the reference genome and identify 112 Y-chromosomal scaffolds with a combined length of 1.9 Mb. We verified the in silico findings for the longer polar bear scaffolds by male-specific in vitro amplification, demonstrating the reliability of the average read depth approach. The obtained Y chromosome sequences contain protein-coding sequences, single nucleotide polymorphisms, microsatellites, and transposable elements that are useful for evolutionary studies. A high-resolution phylogeny of the polar bear patriline shows two highly divergent Y chromosome lineages, obtained from analysis of the identified Y scaffolds in 12 previously published male polar bear genomes. Moreover, we find evidence of gene conversion among ZFX and ZFY sequences in the giant panda lineage and in the ancestor of ursine and tremarctine bears. Thus, the identification of Y-linked scaffold sequences from unordered genome sequences yields valuable data to infer phylogenomic and population-genomic patterns in bears. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Genome-Wide Search Identifies 1.9 Mb from the Polar Bear Y Chromosome for Evolutionary Analyses

    Science.gov (United States)

    Bidon, Tobias; Schreck, Nancy; Hailer, Frank; Nilsson, Maria A.; Janke, Axel

    2015-01-01

    The male-inherited Y chromosome is the major haploid fraction of the mammalian genome, rendering Y-linked sequences an indispensable resource for evolutionary research. However, despite recent large-scale genome sequencing approaches, only a handful of Y chromosome sequences have been characterized to date, mainly in model organisms. Using polar bear (Ursus maritimus) genomes, we compare two different in silico approaches to identify Y-linked sequences: 1) Similarity to known Y-linked genes and 2) difference in the average read depth of autosomal versus sex chromosomal scaffolds. Specifically, we mapped available genomic sequencing short reads from a male and a female polar bear against the reference genome and identify 112 Y-chromosomal scaffolds with a combined length of 1.9 Mb. We verified the in silico findings for the longer polar bear scaffolds by male-specific in vitro amplification, demonstrating the reliability of the average read depth approach. The obtained Y chromosome sequences contain protein-coding sequences, single nucleotide polymorphisms, microsatellites, and transposable elements that are useful for evolutionary studies. A high-resolution phylogeny of the polar bear patriline shows two highly divergent Y chromosome lineages, obtained from analysis of the identified Y scaffolds in 12 previously published male polar bear genomes. Moreover, we find evidence of gene conversion among ZFX and ZFY sequences in the giant panda lineage and in the ancestor of ursine and tremarctine bears. Thus, the identification of Y-linked scaffold sequences from unordered genome sequences yields valuable data to infer phylogenomic and population-genomic patterns in bears. PMID:26019166

  10. RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord.

    Directory of Open Access Journals (Sweden)

    David G Brohawn

    Full Text Available ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned >50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR for identification of differentially expressed genes (DEG's. Ingenuity Pathways Analysis (IPA and Weighted Gene Co-expression Network Analysis (WGCNA identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF found to be a major pathway regulator (IPA and TNFα-induced protein 2 (TNFAIP2 as a major network "hub" gene (WGCNA. Using the oPOSSUM algorithm, we analyzed transcription factors (TF controlling expression of the nine DEG/hub genes in the ALS samples and identified TF's involved in inflammation (NFkB, REL, NFkB1 and macrophage function (NR1H2::RXRA heterodimer. Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be

  11. Transcriptome analyses identify five transcription factors differentially expressed in the hypothalamus of post- versus prepubertal Brahman heifers.

    Science.gov (United States)

    Fortes, M R S; Nguyen, L T; Weller, M M D C A; Cánovas, A; Islas-Trejo, A; Porto-Neto, L R; Reverter, A; Lehnert, S A; Boe-Hansen, G B; Thomas, M G; Medrano, J F; Moore, S S

    2016-09-01

    Puberty onset is a developmental process influenced by genetic determinants, environment, and nutrition. Mutations and regulatory gene networks constitute the molecular basis for the genetic determinants of puberty onset. The emerging knowledge of these genetic determinants presents opportunities for innovation in the breeding of early pubertal cattle. This paper presents new data on hypothalamic gene expression related to puberty in (Brahman) in age- and weight-matched heifers. Six postpubertal heifers were compared with 6 prepubertal heifers using whole-genome RNA sequencing methodology for quantification of global gene expression in the hypothalamus. Five transcription factors (TF) with potential regulatory roles in the hypothalamus were identified in this experiment: , , , , and . These TF genes were significantly differentially expressed in the hypothalamus of postpubertal versus prepubertal heifers and were also identified as significant according to the applied regulatory impact factor metric ( cancer and developmental processes. Mutations in were associated with puberty in humans. Mutations in these TF, together with other genetic determinants previously discovered, could be used in genomic selection to predict the genetic merit of cattle (i.e., the likelihood of the offspring presenting earlier than average puberty for Brahman). Knowledge of key mutations involved in genetic traits is an advantage for genomic prediction because it can increase its accuracy.

  12. Identifying Virulence-Associated Genes Using Transcriptomic and Proteomic Association Analyses of the Plant Parasitic Nematode Bursaphelenchus mucronatus

    Directory of Open Access Journals (Sweden)

    Lifeng Zhou

    2016-09-01

    Full Text Available Bursaphelenchus mucronatus (B. mucronatus isolates that originate from different regions may vary in their virulence, but their virulence-associated genes and proteins are poorly understood. Thus, we conducted an integrated study coupling RNA-Seq and isobaric tags for relative and absolute quantitation (iTRAQ to analyse transcriptomic and proteomic data of highly and weakly virulent B. mucronatus isolates during the pathogenic processes. Approximately 40,000 annotated unigenes and 5000 proteins were gained from the isolates. When we matched all of the proteins with their detected transcripts, a low correlation coefficient of r = 0.138 was found, indicating probable post-transcriptional gene regulation involved in the pathogenic processes. A functional analysis showed that five differentially expressed proteins which were all highly expressed in the highly virulent isolate were involved in the pathogenic processes of nematodes. Peroxiredoxin, fatty acid- and retinol-binding protein, and glutathione peroxidase relate to resistance against plant defence responses, while β-1,4-endoglucanase and expansin are associated with the breakdown of plant cell walls. Thus, the pathogenesis of B. mucronatus depends on its successful survival in host plants. Our work adds to the understanding of B. mucronatus’ pathogenesis, and will aid in controlling B. mucronatus and other pinewood nematode species complexes in the future.

  13. The Interactomic Analysis Reveals Pathogenic Protein Networks in Phomopsis longicolla Underlying Seed Decay of Soybean

    Directory of Open Access Journals (Sweden)

    Shuxian Li

    2018-04-01

    Full Text Available Phomopsis longicolla T. W. Hobbs (syn. Diaporthe longicolla is the primary cause of Phomopsis seed decay (PSD in soybean, Glycine max (L. Merrill. This disease results in poor seed quality and is one of the most economically important seed diseases in soybean. The objectives of this study were to infer protein–protein interactions (PPI and to identify conserved global networks and pathogenicity subnetworks in P. longicolla including orthologous pathways for cell signaling and pathogenesis. The interlog method used in the study identified 215,255 unique PPIs among 3,868 proteins. There were 1,414 pathogenicity related genes in P. longicolla identified using the pathogen host interaction (PHI database. Additionally, 149 plant cell wall degrading enzymes (PCWDE were detected. The network captured five different classes of carbohydrate degrading enzymes, including the auxiliary activities, carbohydrate esterases, glycoside hydrolases, glycosyl transferases, and carbohydrate binding molecules. From the PPI analysis, novel interacting partners were determined for each of the PCWDE classes. The most predominant class of PCWDE was a group of 60 glycoside hydrolases proteins. The glycoside hydrolase subnetwork was found to be interacting with 1,442 proteins within the network and was among the largest clusters. The orthologous proteins FUS3, HOG, CYP1, SGE1, and the g5566t.1 gene identified in this study could play an important role in pathogenicity. Therefore, the P. longicolla protein interactome (PiPhom generated in this study can lead to a better understanding of PPIs in soybean pathogens. Furthermore, the PPI may aid in targeting of genes and proteins for further studies of the pathogenicity mechanisms.

  14. Deep sequencing of cardiac microRNA-mRNA interactomes in clinical and experimental cardiomyopathy.

    Science.gov (United States)

    Matkovich, Scot J; Dorn, Gerald W

    2015-01-01

    MicroRNAs are a family of short (~21 nucleotide) noncoding RNAs that serve key roles in cellular growth and differentiation and the response of the heart to stress stimuli. As the sequence-specific recognition element of RNA-induced silencing complexes (RISCs), microRNAs bind mRNAs and prevent their translation via mechanisms that may include transcript degradation and/or prevention of ribosome binding. Short microRNA sequences and the ability of microRNAs to bind to mRNA sites having only partial/imperfect sequence complementarity complicate purely computational analyses of microRNA-mRNA interactomes. Furthermore, computational microRNA target prediction programs typically ignore biological context, and therefore the principal determinants of microRNA-mRNA binding: the presence and quantity of each. To address these deficiencies we describe an empirical method, developed via studies of stressed and failing hearts, to determine disease-induced changes in microRNAs, mRNAs, and the mRNAs targeted to the RISC, without cross-linking mRNAs to RISC proteins. Deep sequencing methods are used to determine RNA abundances, delivering unbiased, quantitative RNA data limited only by their annotation in the genome of interest. We describe the laboratory bench steps required to perform these experiments, experimental design strategies to achieve an appropriate number of sequencing reads per biological replicate, and computer-based processing tools and procedures to convert large raw sequencing data files into gene expression measures useful for differential expression analyses.

  15. Multivariate Analyses and Classification of Inertial Sensor Data to Identify Aging Effects on the Timed-Up-and-Go Test.

    Directory of Open Access Journals (Sweden)

    Danique Vervoort

    Full Text Available Many tests can crudely quantify age-related mobility decrease but instrumented versions of mobility tests could increase their specificity and sensitivity. The Timed-up-and-Go (TUG test includes several elements that people use in daily life. The test has different transition phases: rise from a chair, walk, 180° turn, walk back, turn, and sit-down on a chair. For this reason the TUG is an often used test to evaluate in a standardized way possible decline in balance and walking ability due to age and or pathology. Using inertial sensors, qualitative information about the performance of the sub-phases can provide more specific information about a decline in balance and walking ability. The first aim of our study was to identify variables extracted from the instrumented timed-up-and-go (iTUG that most effectively distinguished performance differences across age (age 18-75. Second, we determined the discriminative ability of those identified variables to classify a younger (age 18-45 and older age group (age 46-75. From healthy adults (n = 59, trunk accelerations and angular velocities were recorded during iTUG performance. iTUG phases were detected with wavelet-analysis. Using a Partial Least Square (PLS model, from the 72-iTUG variables calculated across phases, those that explained most of the covariance between variables and age were extracted. Subsequently, a PLS-discriminant analysis (DA assessed classification power of the identified iTUG variables to discriminate the age groups. 27 variables, related to turning, walking and the stand-to-sit movement explained 71% of the variation in age. The PLS-DA with these 27 variables showed a sensitivity and specificity of 90% and 85%. Based on this model, the iTUG can accurately distinguish young and older adults. Such data can serve as a reference for pathological aging with respect to a widely used mobility test. Mobility tests like the TUG supplemented with smart technology could be used in

  16. Interactome of Obesity: Obesidome : Genetic Obesity, Stress Induced Obesity, Pathogenic Obesity Interaction.

    Science.gov (United States)

    Geronikolou, Styliani A; Pavlopoulou, Athanasia; Cokkinos, Dennis; Chrousos, George

    2017-01-01

    Obesity is a chronic disease of increasing prevalence reaching epidemic proportions. Genetic defects as well as epigenetic effects contribute to the obesity phenotype. Investigating gene (e.g. MC4R defects)-environment (behavior, infectious agents, stress) interactions is a relative new field of great research interest. In this study, we have made an effort to create an interactome (henceforth referred to as "obesidome"), where extrinsic stressors response, intrinsic predisposition, immunity response to inflammation and autonomous nervous system implications are integrated. These pathways are presented in one interactome network for the first time. In our study, obesity-related genes/gene products were found to form a complex interactions network.

  17. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.

    Science.gov (United States)

    Wray, Naomi R; Ripke, Stephan; Mattheisen, Manuel; Trzaskowski, Maciej; Byrne, Enda M; Abdellaoui, Abdel; Adams, Mark J; Agerbo, Esben; Air, Tracy M; Andlauer, Till M F; Bacanu, Silviu-Alin; Bækvad-Hansen, Marie; Beekman, Aartjan F T; Bigdeli, Tim B; Binder, Elisabeth B; Blackwood, Douglas R H; Bryois, Julien; Buttenschøn, Henriette N; Bybjerg-Grauholm, Jonas; Cai, Na; Castelao, Enrique; Christensen, Jane Hvarregaard; Clarke, Toni-Kim; Coleman, Jonathan I R; Colodro-Conde, Lucía; Couvy-Duchesne, Baptiste; Craddock, Nick; Crawford, Gregory E; Crowley, Cheynna A; Dashti, Hassan S; Davies, Gail; Deary, Ian J; Degenhardt, Franziska; Derks, Eske M; Direk, Nese; Dolan, Conor V; Dunn, Erin C; Eley, Thalia C; Eriksson, Nicholas; Escott-Price, Valentina; Kiadeh, Farnush Hassan Farhadi; Finucane, Hilary K; Forstner, Andreas J; Frank, Josef; Gaspar, Héléna A; Gill, Michael; Giusti-Rodríguez, Paola; Goes, Fernando S; Gordon, Scott D; Grove, Jakob; Hall, Lynsey S; Hannon, Eilis; Hansen, Christine Søholm; Hansen, Thomas F; Herms, Stefan; Hickie, Ian B; Hoffmann, Per; Homuth, Georg; Horn, Carsten; Hottenga, Jouke-Jan; Hougaard, David M; Hu, Ming; Hyde, Craig L; Ising, Marcus; Jansen, Rick; Jin, Fulai; Jorgenson, Eric; Knowles, James A; Kohane, Isaac S; Kraft, Julia; Kretzschmar, Warren W; Krogh, Jesper; Kutalik, Zoltán; Lane, Jacqueline M; Li, Yihan; Li, Yun; Lind, Penelope A; Liu, Xiaoxiao; Lu, Leina; MacIntyre, Donald J; MacKinnon, Dean F; Maier, Robert M; Maier, Wolfgang; Marchini, Jonathan; Mbarek, Hamdi; McGrath, Patrick; McGuffin, Peter; Medland, Sarah E; Mehta, Divya; Middeldorp, Christel M; Mihailov, Evelin; Milaneschi, Yuri; Milani, Lili; Mill, Jonathan; Mondimore, Francis M; Montgomery, Grant W; Mostafavi, Sara; Mullins, Niamh; Nauck, Matthias; Ng, Bernard; Nivard, Michel G; Nyholt, Dale R; O'Reilly, Paul F; Oskarsson, Hogni; Owen, Michael J; Painter, Jodie N; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Peterson, Roseann E; Pettersson, Erik; Peyrot, Wouter J; Pistis, Giorgio; Posthuma, Danielle; Purcell, Shaun M; Quiroz, Jorge A; Qvist, Per; Rice, John P; Riley, Brien P; Rivera, Margarita; Saeed Mirza, Saira; Saxena, Richa; Schoevers, Robert; Schulte, Eva C; Shen, Ling; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Sinnamon, Grant B C; Smit, Johannes H; Smith, Daniel J; Stefansson, Hreinn; Steinberg, Stacy; Stockmeier, Craig A; Streit, Fabian; Strohmaier, Jana; Tansey, Katherine E; Teismann, Henning; Teumer, Alexander; Thompson, Wesley; Thomson, Pippa A; Thorgeirsson, Thorgeir E; Tian, Chao; Traylor, Matthew; Treutlein, Jens; Trubetskoy, Vassily; Uitterlinden, André G; Umbricht, Daniel; Van der Auwera, Sandra; van Hemert, Albert M; Viktorin, Alexander; Visscher, Peter M; Wang, Yunpeng; Webb, Bradley T; Weinsheimer, Shantel Marie; Wellmann, Jürgen; Willemsen, Gonneke; Witt, Stephanie H; Wu, Yang; Xi, Hualin S; Yang, Jian; Zhang, Futao; Arolt, Volker; Baune, Bernhard T; Berger, Klaus; Boomsma, Dorret I; Cichon, Sven; Dannlowski, Udo; de Geus, E C J; DePaulo, J Raymond; Domenici, Enrico; Domschke, Katharina; Esko, Tõnu; Grabe, Hans J; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Kendler, Kenneth S; Kloiber, Stefan; Lewis, Glyn; Li, Qingqin S; Lucae, Susanne; Madden, Pamela F A; Magnusson, Patrik K; Martin, Nicholas G; McIntosh, Andrew M; Metspalu, Andres; Mors, Ole; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Nordentoft, Merete; Nöthen, Markus M; O'Donovan, Michael C; Paciga, Sara A; Pedersen, Nancy L; Penninx, Brenda W J H; Perlis, Roy H; Porteous, David J; Potash, James B; Preisig, Martin; Rietschel, Marcella; Schaefer, Catherine; Schulze, Thomas G; Smoller, Jordan W; Stefansson, Kari; Tiemeier, Henning; Uher, Rudolf; Völzke, Henry; Weissman, Myrna M; Werge, Thomas; Winslow, Ashley R; Lewis, Cathryn M; Levinson, Douglas F; Breen, Gerome; Børglum, Anders D; Sullivan, Patrick F

    2018-05-01

    Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

  18. Using Watershed Models and Human Behavioral Analyses to identify Management Options to Reduce Lake Erie's Harmful Algal Blooms

    Science.gov (United States)

    Martin, J.; Wilson, R. S.; Aloysius, N.; Kalcic, M. M.; Roe, B.; Howard, G.; Irwin, E.; Zhang, W.; Liu, H.

    2017-12-01

    In early 2016, the United States and Canada formally agreed to reduce phosphorus inputs to Lake Erie by 40% to reduce the severity of annual Harmful Algal Blooms (HABs). These blooms have become more severe, with record events occurring in 2011 and 2015, and have compromised public safety, shut down drinking water supplies, and negatively impacted the economy of the western Lake Erie basin. Now, a key question is what management options should be pursued to reach the 40% reduction. This presentation will highlight interdisciplinary research to compare the amount and types of practices needed for this reduction to the current and projected levels of adoption. Multiple models of the Maumee watershed identified management plans and adoption rates needed to reach the reduction targets. For example, one successful scenario estimated necessary adoption rates of 50% for subsurface application of fertilizer on row crops, 58% for cover crops, and 78% for buffer strips. Current adoption is below these levels, but future projections based on farmer surveys shows these levels are possible. This information was then used to guide another round of watershed modeling analysis to evaluate scenarios that represented more realistic scenarios based on potential levels of management adoption. In general, these results show that accelerated adoption of management plans is needed compared to past adoption rates, and that some of these greater adoption levels are possible based on likely adoption rates. Increasing the perceived efficacy of the practices is one method that will support greater voluntary rates of adoption.

  19. Combining the Power of Statistical Analyses and Community Interviews to Identify Adoption Barriers for Stormwater Best-Management Practices

    Science.gov (United States)

    Hoover, F. A.; Bowling, L. C.; Prokopy, L. S.

    2015-12-01

    Urban stormwater is an on-going management concern in municipalities of all sizes. In both combined or separated sewer systems, pollutants from stormwater runoff enter the natural waterway system during heavy rain events. Urban flooding during frequent and more intense storms are also a growing concern. Therefore, stormwater best-management practices (BMPs) are being implemented in efforts to reduce and manage stormwater pollution and overflow. The majority of BMP water quality studies focus on the small-scale, individual effects of the BMP, and the change in water quality directly from the runoff of these infrastructures. At the watershed scale, it is difficult to establish statistically whether or not these BMPs are making a difference in water quality, given that watershed scale monitoring is often costly and time consuming, relying on significant sources of funds, which a city may not have. Hence, there is a need to quantify the level of sampling needed to detect the water quality impact of BMPs at the watershed scale. In this study, a power analysis was performed on data from an urban watershed in Lafayette, Indiana, to determine the frequency of sampling required to detect a significant change in water quality measurements. Using the R platform, results indicate that detecting a significant change in watershed level water quality would require hundreds of weekly measurements, even when improvement is present. The second part of this study investigates whether the difficulty in demonstrating water quality change represents a barrier to adoption of stormwater BMPs. Semi-structured interviews of community residents and organizations in Chicago, IL are being used to investigate residents understanding of water quality and best management practices and identify their attitudes and perceptions towards stormwater BMPs. Second round interviews will examine how information on uncertainty in water quality improvements influences their BMP attitudes and perceptions.

  20. The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine.

    Science.gov (United States)

    Cortese-Krott, Miriam M; Koning, Anne; Kuhnle, Gunter G C; Nagy, Peter; Bianco, Christopher L; Pasch, Andreas; Wink, David A; Fukuto, Jon M; Jackson, Alan A; van Goor, Harry; Olson, Kenneth R; Feelisch, Martin

    2017-10-01

    Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level. To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses. Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 00, 000-000.

  1. Construction and application of a protein and genetic interaction network (yeast interactome).

    Science.gov (United States)

    Stuart, Gregory R; Copeland, William C; Strand, Micheline K

    2009-04-01

    Cytoscape is a bioinformatic data analysis and visualization platform that is well-suited to the analysis of gene expression data. To facilitate the analysis of yeast microarray data using Cytoscape, we constructed an interaction network (interactome) using the curated interaction data available from the Saccharomyces Genome Database (www.yeastgenome.org) and the database of yeast transcription factors at YEASTRACT (www.yeastract.com). These data were formatted and imported into Cytoscape using semi-automated methods, including Linux-based scripts, that simplified the process while minimizing the introduction of processing errors. The methods described for the construction of this yeast interactome are generally applicable to the construction of any interactome. Using Cytoscape, we illustrate the use of this interactome through the analysis of expression data from a recent yeast diauxic shift experiment. We also report and briefly describe the complex associations among transcription factors that result in the regulation of thousands of genes through coordinated changes in expression of dozens of transcription factors. These cells are thus able to sensitively regulate cellular metabolism in response to changes in genetic or environmental conditions through relatively small changes in the expression of large numbers of genes, affecting the entire yeast metabolome.

  2. Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

    Directory of Open Access Journals (Sweden)

    Jingjing Liang

    2017-05-01

    Full Text Available Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8 for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4 and multiple-trait analyses identified one novel locus (FRMD3 for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

  3. Can hospital audit teams identify case management problems, analyse their causes, identify and implement improvements? A cross-sectional process evaluation of obstetric near-miss case reviews in Benin

    Directory of Open Access Journals (Sweden)

    Borchert Matthias

    2012-10-01

    Full Text Available Abstract Background Obstetric near-miss case reviews are being promoted as a quality assurance intervention suitable for hospitals in low income countries. We introduced such reviews in five district, regional and national hospitals in Benin, West Africa. In a cross-sectional study we analysed the extent to which the hospital audit teams were able to identify case management problems (CMPs, analyse their causes, agree on solutions and put these solutions into practice. Methods We analysed case summaries, women’s interview transcripts and audit minutes produced by the audit teams for 67 meetings concerning one woman with near-miss complications each. We compared the proportion of CMPs identified by an external assessment team to the number found by the audit teams. For the latter, we described the CMP causes identified, solutions proposed and implemented by the audit teams. Results Audit meetings were conducted regularly and were well attended. Audit teams identified half of the 714 CMPs; they were more likely to find managerial ones (71% than the ones relating to treatment (30%. Most identified CMPs were valid. Almost all causes of CMPs were plausible, but often too superficial to be of great value for directing remedial action. Audit teams suggested solutions, most of them promising ones, for 38% of the CMPs they had identified, but recorded their implementation only for a minority (8.5%. Conclusions The importance of following-up and documenting the implementation of solutions should be stressed in future audit interventions. Tools facilitating the follow-up should be made available. Near-miss case reviews hold promise, but their effectiveness to improve the quality of care sustainably and on a large scale still needs to be established.

  4. Can hospital audit teams identify case management problems, analyse their causes, identify and implement improvements? A cross-sectional process evaluation of obstetric near-miss case reviews in Benin

    Science.gov (United States)

    2012-01-01

    Background Obstetric near-miss case reviews are being promoted as a quality assurance intervention suitable for hospitals in low income countries. We introduced such reviews in five district, regional and national hospitals in Benin, West Africa. In a cross-sectional study we analysed the extent to which the hospital audit teams were able to identify case management problems (CMPs), analyse their causes, agree on solutions and put these solutions into practice. Methods We analysed case summaries, women’s interview transcripts and audit minutes produced by the audit teams for 67 meetings concerning one woman with near-miss complications each. We compared the proportion of CMPs identified by an external assessment team to the number found by the audit teams. For the latter, we described the CMP causes identified, solutions proposed and implemented by the audit teams. Results Audit meetings were conducted regularly and were well attended. Audit teams identified half of the 714 CMPs; they were more likely to find managerial ones (71%) than the ones relating to treatment (30%). Most identified CMPs were valid. Almost all causes of CMPs were plausible, but often too superficial to be of great value for directing remedial action. Audit teams suggested solutions, most of them promising ones, for 38% of the CMPs they had identified, but recorded their implementation only for a minority (8.5%). Conclusions The importance of following-up and documenting the implementation of solutions should be stressed in future audit interventions. Tools facilitating the follow-up should be made available. Near-miss case reviews hold promise, but their effectiveness to improve the quality of care sustainably and on a large scale still needs to be established. PMID:23057707

  5. Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations

    OpenAIRE

    Liang, Jingjing; Le, Thu H.; Edwards, Digna R. Velez; Tayo, Bamidele O.; Gaulton, Kyle J.; Smith, Jennifer A.; Lu, Yingchang; Jensen, Richard A.; Chen, Guanjie; Yanek, Lisa R.; Schwander, Karen; Tajuddin, Salman M.; Sofer, Tamar; Kim, Wonji; Kayima, James

    2017-01-01

    © 2017 Public Library of Science. All Rights Reserved. Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genom...

  6. Integration of multiple biological features yields high confidence human protein interactome.

    Science.gov (United States)

    Karagoz, Kubra; Sevimoglu, Tuba; Arga, Kazim Yalcin

    2016-08-21

    The biological function of a protein is usually determined by its physical interaction with other proteins. Protein-protein interactions (PPIs) are identified through various experimental methods and are stored in curated databases. The noisiness of the existing PPI data is evident, and it is essential that a more reliable data is generated. Furthermore, the selection of a set of PPIs at different confidence levels might be necessary for many studies. Although different methodologies were introduced to evaluate the confidence scores for binary interactions, a highly reliable, almost complete PPI network of Homo sapiens is not proposed yet. The quality and coverage of human protein interactome need to be improved to be used in various disciplines, especially in biomedicine. In the present work, we propose an unsupervised statistical approach to assign confidence scores to PPIs of H. sapiens. To achieve this goal PPI data from six different databases were collected and a total of 295,288 non-redundant interactions between 15,950 proteins were acquired. The present scoring system included the context information that was assigned to PPIs derived from eight biological attributes. A high confidence network, which included 147,923 binary interactions between 13,213 proteins, had scores greater than the cutoff value of 0.80, for which sensitivity, specificity, and coverage were 94.5%, 80.9%, and 82.8%, respectively. We compared the present scoring method with others for evaluation. Reducing the noise inherent in experimental PPIs via our scoring scheme increased the accuracy significantly. As it was demonstrated through the assessment of process and cancer subnetworks, this study allows researchers to construct and analyze context-specific networks via valid PPI sets and one can easily achieve subnetworks around proteins of interest at a specified confidence level. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Building and analyzing protein interactome networks by cross-species comparisons

    Directory of Open Access Journals (Sweden)

    Blackman Barron

    2010-03-01

    Full Text Available Abstract Background A genomic catalogue of protein-protein interactions is a rich source of information, particularly for exploring the relationships between proteins. Numerous systems-wide and small-scale experiments have been conducted to identify interactions; however, our knowledge of all interactions for any one species is incomplete, and alternative means to expand these network maps is needed. We therefore took a comparative biology approach to predict protein-protein interactions across five species (human, mouse, fly, worm, and yeast and developed InterologFinder for research biologists to easily navigate this data. We also developed a confidence score for interactions based on available experimental evidence and conservation across species. Results The connectivity of the resultant networks was determined to have scale-free distribution, small-world properties, and increased local modularity, indicating that the added interactions do not disrupt our current understanding of protein network structures. We show examples of how these improved interactomes can be used to analyze a genome-scale dataset (RNAi screen and to assign new function to proteins. Predicted interactions within this dataset were tested by co-immunoprecipitation, resulting in a high rate of validation, suggesting the high quality of networks produced. Conclusions Protein-protein interactions were predicted in five species, based on orthology. An InteroScore, a score accounting for homology, number of orthologues with evidence of interactions, and number of unique observations of interactions, is given to each known and predicted interaction. Our website http://www.interologfinder.org provides research biologists intuitive access to this data.

  8. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

    DEFF Research Database (Denmark)

    Day, Felix R; Thompson, Deborah J; Helgason, Hannes

    2017-01-01

    The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P ... pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare...... variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women...

  9. Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

    DEFF Research Database (Denmark)

    Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J

    2017-01-01

    We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D...... and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity...... and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates...

  10. Characterization of the Arabidopsis thaliana 2-Cys peroxiredoxin interactome.

    Science.gov (United States)

    Cerveau, Delphine; Kraut, Alexandra; Stotz, Henrik U; Mueller, Martin J; Couté, Yohann; Rey, Pascal

    2016-11-01

    Peroxiredoxins are ubiquitous thiol-dependent peroxidases for which chaperone and signaling roles have been reported in various types of organisms in recent years. In plants, the peroxidase function of the two typical plastidial 2-Cys peroxiredoxins (2-Cys PRX A and B) has been highlighted while the other functions, particularly in ROS-dependent signaling pathways, are still elusive notably due to the lack of knowledge of interacting partners. Using an ex vivo approach based on co-immunoprecipitation of leaf extracts from Arabidopsis thaliana wild-type and mutant plants lacking 2-Cys PRX expression followed by mass spectrometry-based proteomics, 158 proteins were found associated with 2-Cys PRXs. Already known partners like thioredoxin-related electron donors (Chloroplastic Drought-induced Stress Protein of 32kDa, Atypical Cysteine Histidine-rich Thioredoxin 2) and enzymes involved in chlorophyll synthesis (Protochlorophyllide OxidoReductase B) or carbon metabolism (Fructose-1,6-BisPhosphatase) were identified, validating the relevance of the approach. Bioinformatic and bibliographic analyses allowed the functional classification of the identified proteins and revealed that more than 40% are localized in plastids. The possible roles of plant 2-Cys PRXs in redox signaling pathways are discussed in relation with the functions of the potential partners notably those involved in redox homeostasis, carbon and amino acid metabolisms as well as chlorophyll biosynthesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Genome-Wide Association Meta-Analyses to Identify Common Genetic Variants Associated with Hallux Valgus in Caucasian and African Americans

    Science.gov (United States)

    Hsu, Yi-Hsiang; Liu, Youfang; Hannan, Marian T.; Maixner, William; Smith, Shad B.; Diatchenko, Luda; Golightly, Yvonne M.; Menz, Hylton B.; Kraus, Virginia B.; Doherty, Michael; Wilson, A.G.; Jordan, Joanne M.

    2016-01-01

    Objective Hallux valgus (HV) affects ~36% of Caucasian adults. Although considered highly heritable, the underlying genetic determinants are unclear. We conducted the first genome-wide association study (GWAS) aimed to identify genetic variants associated with HV. Methods HV was assessed in 3 Caucasian cohorts (n=2,263, n=915, and n=1,231 participants, respectively). In each cohort, a GWAS was conducted using 2.5M imputed single nucleotide polymorphisms (SNPs). Mixed-effect regression with the additive genetic model adjusted for age, sex, weight and within-family correlations was used for both sex-specific and combined analyses. To combine GWAS results across cohorts, fixed-effect inverse-variance meta-analyses were used. Following meta-analyses, top-associated findings were also examined in an African American cohort (n=327). Results The proportion of HV variance explained by genome-wide genotyped SNPs was 50% in men and 48% in women. A higher proportion of genetic determinants of HV was sex-specific. The most significantly associated SNP in men was rs9675316 located on chr17q23-a24 near the AXIN2 gene (p=5.46×10−7); the most significantly associated SNP in women was rs7996797 located on chr13q14.1-q14.2 near the ESD gene (p=7.21×10−7). Genome-wide significant SNP-by-sex interaction was found for SNP rs1563374 located on chr11p15.1 near the MRGPRX3 gene (interaction p-value =4.1×10−9). The association signals diminished when combining men and women. Conclusion Findings suggest that the potential pathophysiological mechanisms of HV are complex and strongly underlined by sex-specific interactions. The identified genetic variants imply contribution of biological pathways observed in osteoarthritis as well as new pathways, influencing skeletal development and inflammation. PMID:26337638

  12. Next Generation Protein Interactomes for Plant Systems Biology and Biomass Feedstock Research

    Energy Technology Data Exchange (ETDEWEB)

    Ecker, Joseph Robert [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Trigg, Shelly [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Univ. of California, San Diego, CA (United States). Biological Sciences Dept.; Garza, Renee [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Song, Haili [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; MacWilliams, Andrew [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Nery, Joseph [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Reina, Joaquin [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Bartlett, Anna [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Castanon, Rosa [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Goubil, Adeline [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Feeney, Joseph [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; O' Malley, Ronan [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Huang, Shao-shan Carol [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Zhang, Zhuzhu [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.; Galli, Mary [The Salk Inst. for Biological Studies, La Jolla, CA (United States). Genome Analysis and Plant Biology Lab.

    2016-11-30

    Biofuel crop cultivation is a necessary step in heading towards a sustainable future, making their genomic studies a priority. While technology platforms that currently exist for studying non-model crop species, like switch-grass or sorghum, have yielded large quantities of genomic and expression data, still a large gap exists between molecular mechanism and phenotype. The aspect of molecular activity at the level of protein-protein interactions has recently begun to bridge this gap, providing a more global perspective. Interactome analysis has defined more specific functional roles of proteins based on their interaction partners, neighborhoods, and other network features, making it possible to distinguish unique modules of immune response to different plant pathogens(Jiang, Dong, and Zhang 2016). As we work towards cultivating heartier biofuel crops, interactome data will lead to uncovering crop-specific defense and development networks. However, the collection of protein interaction data has been limited to expensive, time-consuming, hard-to-scale assays that mostly require cloned ORF collections. For these reasons, we have successfully developed a highly scalable, economical, and sensitive yeast two-hybrid assay, ProCREate, that can be universally applied to generate proteome-wide primary interactome data. ProCREate enables en masse pooling and massively paralleled sequencing for the identification of interacting proteins by exploiting Cre-lox recombination. ProCREate can be used to screen ORF/cDNA libraries from feedstock plant tissues. The interactome data generated will yield deeper insight into many molecular processes and pathways that can be used to guide improvement of feedstock productivity and sustainability.

  13. Frontotemporal dysregulation of the SNARE protein interactome is associated with faster cognitive decline in old age.

    Science.gov (United States)

    Ramos-Miguel, Alfredo; Jones, Andrea A; Sawada, Ken; Barr, Alasdair M; Bayer, Thomas A; Falkai, Peter; Leurgans, Sue E; Schneider, Julie A; Bennett, David A; Honer, William G

    2018-06-01

    The molecular underpinnings associated with cognitive reserve remain poorly understood. Because animal models fail to fully recapitulate the complexity of human brain aging, postmortem studies from well-designed cohorts are crucial to unmask mechanisms conferring cognitive resistance against cumulative neuropathologies. We tested the hypothesis that functionality of the SNARE protein interactome might be an important resilience factor preserving cognitive abilities in old age. Cognition was assessed annually in participants from the Rush "Memory and Aging Project" (MAP), a community-dwelling cohort representative of the overall aging population. Associations between cognition and postmortem neurochemical data were evaluated in functional assays quantifying various species of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) machinery in samples from the inferior temporal (IT, n = 154) and middle-frontal (MF, n = 174) gyri. Using blue-native gel electrophoresis, we isolated and quantified several types of complexes containing the three SNARE proteins (syntaxin-1, SNAP25, VAMP), as well as the GABAergic/glutamatergic selectively expressed complexins-I/II (CPLX1/2), in brain tissue homogenates and reconstitution assays with recombinant proteins. Multivariate analyses revealed significant associations between IT and MF neurochemical data (SNARE proteins and/or complexes), and multiple age-related neuropathologies, as well as with multiple cognitive domains of MAP participants. Controlling for demographic variables, neuropathologic indices and total synapse density, we found that temporal 150-kDa SNARE species (representative of pan-synaptic functionality) and frontal CPLX1/CPLX2 ratio of 500-kDa heteromeric species (representative of inhibitory/excitatory input functionality) were, among all the immunocharacterized complexes, the strongest predictors of cognitive function nearest death. Interestingly, these two neurochemical

  14. Structures and short linear motif of disordered transcription factor regions provide clues to the interactome of the cellular hub radical-induced cell death1

    DEFF Research Database (Denmark)

    O'Shea, Charlotte; Staby, Lasse; Bendsen, Sidsel Krogh

    2017-01-01

    Intrinsically disordered protein regions (IDRs) lack a well-defined three-dimensional structure, but often facilitate key protein functions. Some interactions between IDRs and folded protein domains rely on short linear motifs (SLiMs). These motifs are challenging to identify, but once found can...... point to larger networks of interactions, such as with proteins that serve as hubs for essential cellular functions. The stress-associated plant protein Radical-Induced Cell Death1 (RCD1) is one such hub, interacting with many transcription factors via their flexible IDRs. To identify the SLiM bound......046 formed different structures or were fuzzy in the complexes. These findings allow us to present a model of the stress-associated RCD1-transcription factor interactome and to contribute to the emerging understanding of the interactions between folded hubs and their intrinsically disordered partners....

  15. HPLC-MS and GC-MS analyses combined with orthogonal partial least squares to identify cytotoxic constituents from turmeric (Curcuma longa L.).

    Science.gov (United States)

    Jiang, Jianlan; Zhang, Huan; Li, Zidan; Zhang, Xiaohang; Su, Xin; Li, Yan; Qiao, Bin; Yuan, Yingjin

    2013-08-01

    We investigated the fingerprints of 48 batches of turmeric total extracts (TTE) by HPLC-MS-MS and GC-MS analyses and 43 characteristic peaks (22 constituents from HPLC-MS-MS; 21 from GC-MS) were analyzed qualitatively and quantitatively. An MTT {3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide} assay was implemented to measure the cytotoxicity of the TTE against HeLa cells. Then we utilized orthogonal partial least squares analysis, which correlated the chemical composition of the TTE to its cytotoxic activity, to identify potential cytotoxic constituents from turmeric. The result showed that 19 constituents contributed significantly to the cytotoxicity. The obtained result was verified by canonical correlation analysis. Comparison with previous reports also indicated some interaction between the curcuminoids and sesquiterpenoids in turmeric.

  16. Analyses of Tissue Culture Adaptation of Human Herpesvirus-6A by Whole Genome Deep Sequencing Redefines the Reference Sequence and Identifies Virus Entry Complex Changes.

    Science.gov (United States)

    Tweedy, Joshua G; Escriva, Eric; Topf, Maya; Gompels, Ursula A

    2017-12-31

    Tissue-culture adaptation of viruses can modulate infection. Laboratory passage and bacterial artificial chromosome (BAC)mid cloning of human cytomegalovirus, HCMV, resulted in genomic deletions and rearrangements altering genes encoding the virus entry complex, which affected cellular tropism, virulence, and vaccine development. Here, we analyse these effects on the reference genome for related betaherpesviruses, Roseolovirus, human herpesvirus 6A (HHV-6A) strain U1102. This virus is also naturally "cloned" by germline subtelomeric chromosomal-integration in approximately 1% of human populations, and accurate references are key to understanding pathological relationships between exogenous and endogenous virus. Using whole genome next-generation deep-sequencing Illumina-based methods, we compared the original isolate to tissue-culture passaged and the BACmid-cloned virus. This re-defined the reference genome showing 32 corrections and 5 polymorphisms. Furthermore, minor variant analyses of passaged and BACmid virus identified emerging populations of a further 32 single nucleotide polymorphisms (SNPs) in 10 loci, half non-synonymous indicating cell-culture selection. Analyses of the BAC-virus genome showed deletion of the BAC cassette via loxP recombination removing green fluorescent protein (GFP)-based selection. As shown for HCMV culture effects, select HHV-6A SNPs mapped to genes encoding mediators of virus cellular entry, including virus envelope glycoprotein genes gB and the gH/gL complex. Comparative models suggest stabilisation of the post-fusion conformation. These SNPs are essential to consider in vaccine-design, antimicrobial-resistance, and pathogenesis.

  17. 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

  18. 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.

  19. Comprehensive Protein Interactome Analysis of a Key RNA Helicase: Detection of Novel Stress Granule Proteins

    Directory of Open Access Journals (Sweden)

    Rebecca Bish

    2015-07-01

    Full Text Available DDX6 (p54/RCK is a human RNA helicase with central roles in mRNA decay and translation repression. To help our understanding of how DDX6 performs these multiple functions, we conducted the first unbiased, large-scale study to map the DDX6-centric protein-protein interactome using immunoprecipitation and mass spectrometry. Using DDX6 as bait, we identify a high-confidence and high-quality set of protein interaction partners which are enriched for functions in RNA metabolism and ribosomal proteins. The screen is highly specific, maximizing the number of true positives, as demonstrated by the validation of 81% (47/58 of the RNA-independent interactors through known functions and interactions. Importantly, we minimize the number of indirect interaction partners through use of a nuclease-based digestion to eliminate RNA. We describe eleven new interactors, including proteins involved in splicing which is an as-yet unknown role for DDX6. We validated and characterized in more detail the interaction of DDX6 with Nuclear fragile X mental retardation-interacting protein 2 (NUFIP2 and with two previously uncharacterized proteins, FAM195A and FAM195B (here referred to as granulin-1 and granulin-2, or GRAN1 and GRAN2. We show that NUFIP2, GRAN1, and GRAN2 are not P-body components, but re-localize to stress granules upon exposure to stress, suggesting a function in translation repression in the cellular stress response. Using a complementary analysis that resolved DDX6’s multiple complex memberships, we further validated these interaction partners and the presence of splicing factors. As DDX6 also interacts with the E3 SUMO ligase TIF1β, we tested for and observed a significant enrichment of sumoylation amongst DDX6’s interaction partners. Our results represent the most comprehensive screen for direct interaction partners of a key regulator of RNA life cycle and localization, highlighting new stress granule components and possible DDX6 functions

  20. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk.

    Science.gov (United States)

    Day, Felix R; Thompson, Deborah J; Helgason, Hannes; Chasman, Daniel I; Finucane, Hilary; Sulem, Patrick; Ruth, Katherine S; Whalen, Sean; Sarkar, Abhishek K; Albrecht, Eva; Altmaier, Elisabeth; Amini, Marzyeh; Barbieri, Caterina M; Boutin, Thibaud; Campbell, Archie; Demerath, Ellen; Giri, Ayush; He, Chunyan; Hottenga, Jouke J; Karlsson, Robert; Kolcic, Ivana; Loh, Po-Ru; Lunetta, Kathryn L; Mangino, Massimo; Marco, Brumat; McMahon, George; Medland, Sarah E; Nolte, Ilja M; Noordam, Raymond; Nutile, Teresa; Paternoster, Lavinia; Perjakova, Natalia; Porcu, Eleonora; Rose, Lynda M; Schraut, Katharina E; Segrè, Ayellet V; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Andrulis, Irene L; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Bergmann, Sven; Bochud, Murielle; Boerwinkle, Eric; Bojesen, Stig E; Bolla, Manjeet K; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Broer, Linda; Brüning, Thomas; Buring, Julie E; Campbell, Harry; Catamo, Eulalia; Chanock, Stephen; Chenevix-Trench, Georgia; Corre, Tanguy; Couch, Fergus J; Cousminer, Diana L; Cox, Angela; Crisponi, Laura; Czene, Kamila; Davey Smith, George; de Geus, Eco J C N; de Mutsert, Renée; De Vivo, Immaculata; Dennis, Joe; Devilee, Peter; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eriksson, Johan G; Fasching, Peter A; Fernández-Rhodes, Lindsay; Ferrucci, Luigi; Flesch-Janys, Dieter; Franke, Lude; Gabrielson, Marike; Gandin, Ilaria; Giles, Graham G; Grallert, Harald; Gudbjartsson, Daniel F; Guénel, Pascal; Hall, Per; Hallberg, Emily; Hamann, Ute; Harris, Tamara B; Hartman, Catharina A; Heiss, Gerardo; Hooning, Maartje J; Hopper, John L; Hu, Frank; Hunter, David J; Ikram, M Arfan; Im, Hae Kyung; Järvelin, Marjo-Riitta; Joshi, Peter K; Karasik, David; Kellis, Manolis; Kutalik, Zoltan; LaChance, Genevieve; Lambrechts, Diether; Langenberg, Claudia; Launer, Lenore J; Laven, Joop S E; Lenarduzzi, Stefania; Li, Jingmei; Lind, Penelope A; Lindstrom, Sara; Liu, YongMei; Luan, Jian'an; Mägi, Reedik; Mannermaa, Arto; Mbarek, Hamdi; McCarthy, Mark I; Meisinger, Christa; Meitinger, Thomas; Menni, Cristina; Metspalu, Andres; Michailidou, Kyriaki; Milani, Lili; Milne, Roger L; Montgomery, Grant W; Mulligan, Anna M; Nalls, Mike A; Navarro, Pau; Nevanlinna, Heli; Nyholt, Dale R; Oldehinkel, Albertine J; O'Mara, Tracy A; Padmanabhan, Sandosh; Palotie, Aarno; Pedersen, Nancy; Peters, Annette; Peto, Julian; Pharoah, Paul D P; Pouta, Anneli; Radice, Paolo; Rahman, Iffat; Ring, Susan M; Robino, Antonietta; Rosendaal, Frits R; Rudan, Igor; Rueedi, Rico; Ruggiero, Daniela; Sala, Cinzia F; Schmidt, Marjanka K; Scott, Robert A; Shah, Mitul; Sorice, Rossella; Southey, Melissa C; Sovio, Ulla; Stampfer, Meir; Steri, Maristella; Strauch, Konstantin; Tanaka, Toshiko; Tikkanen, Emmi; Timpson, Nicholas J; Traglia, Michela; Truong, Thérèse; Tyrer, Jonathan P; Uitterlinden, André G; Edwards, Digna R Velez; Vitart, Veronique; Völker, Uwe; Vollenweider, Peter; Wang, Qin; Widen, Elisabeth; van Dijk, Ko Willems; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce H R; Zhao, Jing Hua; Zoledziewska, Magdalena; Zygmunt, Marek; Alizadeh, Behrooz Z; Boomsma, Dorret I; Ciullo, Marina; Cucca, Francesco; Esko, Tõnu; Franceschini, Nora; Gieger, Christian; Gudnason, Vilmundur; Hayward, Caroline; Kraft, Peter; Lawlor, Debbie A; Magnusson, Patrik K E; Martin, Nicholas G; Mook-Kanamori, Dennis O; Nohr, Ellen A; Polasek, Ozren; Porteous, David; Price, Alkes L; Ridker, Paul M; Snieder, Harold; Spector, Tim D; Stöckl, Doris; Toniolo, Daniela; Ulivi, Sheila; Visser, Jenny A; Völzke, Henry; Wareham, Nicholas J; Wilson, James F; Spurdle, Amanda B; Thorsteindottir, Unnur; Pollard, Katherine S; Easton, Douglas F; Tung, Joyce Y; Chang-Claude, Jenny; Hinds, David; Murray, Anna; Murabito, Joanne M; Stefansson, Kari; Ong, Ken K; Perry, John R B

    2017-06-01

    The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10 -8 ) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.

  1. A comprehensive protein-protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1.

    Science.gov (United States)

    DeMille, Desiree; Bikman, Benjamin T; Mathis, Andrew D; Prince, John T; Mackay, Jordan T; Sowa, Steven W; Hall, Tacie D; Grose, Julianne H

    2014-07-15

    Per-Arnt-Sim (PAS) kinase is a sensory protein kinase required for glucose homeostasis in yeast, mice, and humans, yet little is known about the molecular mechanisms of its function. Using both yeast two-hybrid and copurification approaches, we identified the protein-protein interactome for yeast PAS kinase 1 (Psk1), revealing 93 novel putative protein binding partners. Several of the Psk1 binding partners expand the role of PAS kinase in glucose homeostasis, including new pathways involved in mitochondrial metabolism. In addition, the interactome suggests novel roles for PAS kinase in cell growth (gene/protein expression, replication/cell division, and protein modification and degradation), vacuole function, and stress tolerance. In vitro kinase studies using a subset of 25 of these binding partners identified Mot3, Zds1, Utr1, and Cbf1 as substrates. Further evidence is provided for the in vivo phosphorylation of Cbf1 at T211/T212 and for the subsequent inhibition of respiration. This respiratory role of PAS kinase is consistent with the reported hypermetabolism of PAS kinase-deficient mice, identifying a possible molecular mechanism and solidifying the evolutionary importance of PAS kinase in the regulation of glucose homeostasis. © 2014 DeMille et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  2. Searching for cellular partners of hantaviral nonstructural protein NSs: Y2H screening of mouse cDNA library and analysis of cellular interactome.

    Science.gov (United States)

    Rönnberg, Tuomas; Jääskeläinen, Kirsi; Blot, Guillaume; Parviainen, Ville; Vaheri, Antti; Renkonen, Risto; Bouloy, Michele; Plyusnin, Alexander

    2012-01-01

    Hantaviruses (Bunyaviridae) are negative-strand RNA viruses with a tripartite genome. The small (S) segment encodes the nucleocapsid protein and, in some hantaviruses, also the nonstructural protein (NSs). The aim of this study was to find potential cellular partners for the hantaviral NSs protein. Toward this aim, yeast two-hybrid (Y2H) screening of mouse cDNA library was performed followed by a search for potential NSs protein counterparts via analyzing a cellular interactome. The resulting interaction network was shown to form logical, clustered structures. Furthermore, several potential binding partners for the NSs protein, for instance ACBD3, were identified and, to prove the principle, interaction between NSs and ACBD3 proteins was demonstrated biochemically.

  3. Quantitative in vivo analyses reveal calcium-dependent phosphorylation sites and identifies a novel component of the Toxoplasma invasion motor complex.

    Directory of Open Access Journals (Sweden)

    Thomas Nebl

    2011-09-01

    Full Text Available Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca²⁺-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of ³²[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca²⁺-dependent phosphorylation patterns on three of its components--GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component.

  4. Comprehensive multi-stage linkage analyses identify a locus for adult height on chromosome 3p in a healthy Caucasian population.

    Science.gov (United States)

    Ellis, Justine A; Scurrah, Katrina J; Duncan, Anna E; Lamantia, Angela; Byrnes, Graham B; Harrap, Stephen B

    2007-04-01

    There have been a number of genome-wide linkage studies for adult height in recent years. These studies have yielded few well-replicated loci, and none have been further confirmed by the identification of associated gene variants. The inconsistent results may be attributable to the fact that few studies have combined accurate phenotype measures with informative statistical modelling in healthy populations. We have performed a multi-stage genome-wide linkage analysis for height in 275 adult sibling pairs drawn randomly from the Victorian Family Heart Study (VFHS), a healthy population-based Caucasian cohort. Height was carefully measured in a standardised fashion on regularly calibrated equipment. Following genome-wide identification of a peak Z-score of 3.14 on chromosome 3 at 69 cM, we performed a fine-mapping analysis of this region in an extended sample of 392 two-generation families. We used a number of variance components models that incorporated assortative mating and shared environment effects, and we observed a peak LOD score of approximately 3.5 at 78 cM in four of the five models tested. We also demonstrated that the most prevalent model in the literature gave the worst fit, and the lowest LOD score (2.9) demonstrating the importance of appropriate modelling. The region identified in this study replicates the results of other genome-wide scans of height and bone-related phenotypes, strongly suggesting the presence of a gene important in bone growth on chromosome 3p. Association analyses of relevant candidate genes should identify the genetic variants responsible for the chromosome 3p linkage signal in our population.

  5. Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types

    Science.gov (United States)

    Kar, Siddhartha P.; Beesley, Jonathan; Al Olama, Ali Amin; Michailidou, Kyriaki; Tyrer, Jonathan; Kote-Jarai, ZSofia; Lawrenson, Kate; Lindstrom, Sara; Ramus, Susan J.; Thompson, Deborah J.; Kibel, Adam S.; Dansonka-Mieszkowska, Agnieszka; Michael, Agnieszka; Dieffenbach, Aida K.; Gentry-Maharaj, Aleksandra; Whittemore, Alice S.; Wolk, Alicja; Monteiro, Alvaro; Peixoto, Ana; Kierzek, Andrzej; Cox, Angela; Rudolph, Anja; Gonzalez-Neira, Anna; Wu, Anna H.; Lindblom, Annika; Swerdlow, Anthony; Ziogas, Argyrios; Ekici, Arif B.; Burwinkel, Barbara; Karlan, Beth Y.; Nordestgaard, Børge G.; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B.; Høgdall, Claus K.; Teerlink, Craig C.; Kang, Daehee; Tessier, Daniel C.; Schaid, Daniel J.; Stram, Daniel O.; Cramer, Daniel W.; Neal, David E.; Eccles, Diana; Flesch-Janys, Dieter; Velez Edwards, Digna R.; Wokozorczyk, Dominika; Levine, Douglas A.; Yannoukakos, Drakoulis; Sawyer, Elinor J.; Bandera, Elisa V.; Poole, Elizabeth M.; Goode, Ellen L.; Khusnutdinova, Elza; Høgdall, Estrid; Song, Fengju; Bruinsma, Fiona; Heitz, Florian; Modugno, Francesmary; Hamdy, Freddie C.; Wiklund, Fredrik; Giles, Graham G.; Olsson, Håkan; Wildiers, Hans; Ulmer, Hans-Ulrich; Pandha, Hardev; Risch, Harvey A.; Darabi, Hatef; Salvesen, Helga B.; Nevanlinna, Heli; Gronberg, Henrik; Brenner, Hermann; Brauch, Hiltrud; Anton-Culver, Hoda; Song, Honglin; Lim, Hui-Yi; McNeish, Iain; Campbell, Ian; Vergote, Ignace; Gronwald, Jacek; Lubiński, Jan; Stanford, Janet L.; Benítez, Javier; Doherty, Jennifer A.; Permuth, Jennifer B.; Chang-Claude, Jenny; Donovan, Jenny L.; Dennis, Joe; Schildkraut, Joellen M.; Schleutker, Johanna; Hopper, John L.; Kupryjanczyk, Jolanta; Park, Jong Y.; Figueroa, Jonine; Clements, Judith A.; Knight, Julia A.; Peto, Julian; Cunningham, Julie M.; Pow-Sang, Julio; Batra, Jyotsna; Czene, Kamila; Lu, Karen H.; Herkommer, Kathleen; Khaw, Kay-Tee; Matsuo, Keitaro; Muir, Kenneth; Offitt, Kenneth; Chen, Kexin; Moysich, Kirsten B.; Aittomäki, Kristiina; Odunsi, Kunle; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Fitzgerald, Liesel M.; Cook, Linda S.; Cannon-Albright, Lisa; Hooning, Maartje J.; Pike, Malcolm C.; Bolla, Manjeet K.; Luedeke, Manuel; Teixeira, Manuel R.; Goodman, Marc T.; Schmidt, Marjanka K.; Riggan, Marjorie; Aly, Markus; Rossing, Mary Anne; Beckmann, Matthias W.; Moisse, Matthieu; Sanderson, Maureen; Southey, Melissa C.; Jones, Michael; Lush, Michael; Hildebrandt, Michelle A. T.; Hou, Ming-Feng; Schoemaker, Minouk J.; Garcia-Closas, Montserrat; Bogdanova, Natalia; Rahman, Nazneen; Le, Nhu D.; Orr, Nick; Wentzensen, Nicolas; Pashayan, Nora; Peterlongo, Paolo; Guénel, Pascal; Brennan, Paul; Paulo, Paula; Webb, Penelope M.; Broberg, Per; Fasching, Peter A.; Devilee, Peter; Wang, Qin; Cai, Qiuyin; Li, Qiyuan; Kaneva, Radka; Butzow, Ralf; Kopperud, Reidun Kristin; Schmutzler, Rita K.; Stephenson, Robert A.; MacInnis, Robert J.; Hoover, Robert N.; Winqvist, Robert; Ness, Roberta; Milne, Roger L.; Travis, Ruth C.; Benlloch, Sara; Olson, Sara H.; McDonnell, Shannon K.; Tworoger, Shelley S.; Maia, Sofia; Berndt, Sonja; Lee, Soo Chin; Teo, Soo-Hwang; Thibodeau, Stephen N.; Bojesen, Stig E.; Gapstur, Susan M.; Kjær, Susanne Krüger; Pejovic, Tanja; Tammela, Teuvo L.J.; Dörk, Thilo; Brüning, Thomas; Wahlfors, Tiina; Key, Tim J.; Edwards, Todd L.; Menon, Usha; Hamann, Ute; Mitev, Vanio; Kosma, Veli-Matti; Setiawan, Veronica Wendy; Kristensen, Vessela; Arndt, Volker; Vogel, Walther; Zheng, Wei; Sieh, Weiva; Blot, William J.; Kluzniak, Wojciech; Shu, Xiao-Ou; Gao, Yu-Tang; Schumacher, Fredrick; Freedman, Matthew L.; Berchuck, Andrew; Dunning, Alison M.; Simard, Jacques; Haiman, Christopher A.; Spurdle, Amanda; Sellers, Thomas A.; Hunter, David J.; Henderson, Brian E.; Kraft, Peter; Chanock, Stephen J.; Couch, Fergus J.; Hall, Per; Gayther, Simon A.; Easton, Douglas F.; Chenevix-Trench, Georgia; Eeles, Rosalind; Pharoah, Paul D.P.; Lambrechts, Diether

    2016-01-01

    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P cancer meta-analysis. PMID:27432226

  6. The use of sterol distributions combined with compound specific isotope analyses as a tool to identify the origin of fecal contamination in rivers.

    Science.gov (United States)

    Biache, Coralie; Philp, R Paul

    2013-03-01

    The sterol distributions of 9 sediment samples from the Illinois River Basin (OK and AR, USA) were examined in order to identify the source of fecal contamination. The samples were extracted with organic solvent using sonication and the fractions containing the sterols were isolated and analyzed by gas chromatography-mass spectrometry. The sterol distributions of the Illinois River samples were dominated by phytosterols. They were compared to those of different animal feces and manures using a principal component analysis and correspondence appeared between the sediments and one group of chicken feces samples. Gas chromatography-isotope ratio mass spectrometry analyses were also performed to determine the δ(13)C values for the phytosterols and to get an indication of their origin based on the C(3)/C(4) plant signatures. The δ(13)C values obtained ranged from -30.6 ‰ to -17.4 ‰ (VPDB) corresponding to a mixed signature between C(3) and C(4) plants, indicating a C(4) plant contribution to the C(3) plant natural background. These observations indicate that a proportion of the phytosterols originated from chicken feces. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Protein Inference from the Integration of Tandem MS Data and Interactome Networks.

    Science.gov (United States)

    Zhong, Jiancheng; Wang, Jianxing; Ding, Xiaojun; Zhang, Zhen; Li, Min; Wu, Fang-Xiang; Pan, Yi

    2017-01-01

    Since proteins are digested into a mixture of peptides in the preprocessing step of tandem mass spectrometry (MS), it is difficult to determine which specific protein a shared peptide belongs to. In recent studies, besides tandem MS data and peptide identification information, some other information is exploited to infer proteins. Different from the methods which first use only tandem MS data to infer proteins and then use network information to refine them, this study proposes a protein inference method named TMSIN, which uses interactome networks directly. As two interacting proteins should co-exist, it is reasonable to assume that if one of the interacting proteins is confidently inferred in a sample, its interacting partners should have a high probability in the same sample, too. Therefore, we can use the neighborhood information of a protein in an interactome network to adjust the probability that the shared peptide belongs to the protein. In TMSIN, a multi-weighted graph is constructed by incorporating the bipartite graph with interactome network information, where the bipartite graph is built with the peptide identification information. Based on multi-weighted graphs, TMSIN adopts an iterative workflow to infer proteins. At each iterative step, the probability that a shared peptide belongs to a specific protein is calculated by using the Bayes' law based on the neighbor protein support scores of each protein which are mapped by the shared peptides. We carried out experiments on yeast data and human data to evaluate the performance of TMSIN in terms of ROC, q-value, and accuracy. The experimental results show that AUC scores yielded by TMSIN are 0.742 and 0.874 in yeast dataset and human dataset, respectively, and TMSIN yields the maximum number of true positives when q-value less than or equal to 0.05. The overlap analysis shows that TMSIN is an effective complementary approach for protein inference.

  8. The chicken B-cell line DT40 proteome, beadome and interactomes

    Directory of Open Access Journals (Sweden)

    Johanna S. Rees

    2015-06-01

    Full Text Available In developing a new quantitative AP-MS method for exploring interactomes in the chicken B-cell line DT40, we also surveyed the most abundant proteins in this organism and explored the likely contaminants that bind to a variety of affinity resins that would later be confirmed quantitatively [1]. We present the ‘Top 150 abundant DT40 proteins list’, the DT40 beadomes as well as protein interaction lists for the Phosphatidyl inositol 5-phosphate 4-kinase 2β and Fanconi anaemia protein complexes.

  9. Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation

    DEFF Research Database (Denmark)

    Kieffer-Kwon, Kyong-Rim; Tang, Zhonghui; Mathe, Ewy

    2013-01-01

    IA-PET technologies to map the promoter-enhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this feature extends to broadly transcribed genes, including Myc and Pim1 cell-cycle regulators, which...... associate with an entirely different set of enhancers in ES and B cells. By means of high-resolution CpG methylomes, genome editing, and digital footprinting, we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the turning on and off of enhancers during...

  10. Supplementary Material for: The arabidopsis cyclic nucleotide interactome

    KAUST Repository

    Donaldson, Lara; Meier, Stuart; Gehring, Christoph A

    2016-01-01

    Abstract Background Cyclic nucleotides have been shown to play important signaling roles in many physiological processes in plants including photosynthesis and defence. Despite this, little is known about cyclic nucleotide-dependent signaling mechanisms in plants since the downstream target proteins remain unknown. This is largely due to the fact that bioinformatics searches fail to identify plant homologs of protein kinases and phosphodiesterases that are the main targets of cyclic nucleotides in animals. Methods An affinity purification technique was used to identify cyclic nucleotide binding proteins in Arabidopsis thaliana. The identified proteins were subjected to a computational analysis that included a sequence, transcriptional co-expression and functional annotation analysis in order to assess their potential role in plant cyclic nucleotide signaling. Results A total of twelve cyclic nucleotide binding proteins were identified experimentally including key enzymes in the Calvin cycle and photorespiration pathway. Importantly, eight of the twelve proteins were shown to contain putative cyclic nucleotide binding domains. Moreover, the identified proteins are post-translationally modified by nitric oxide, transcriptionally co-expressed and annotated to function in hydrogen peroxide signaling and the defence response. The activity of one of these proteins, GLYGOLATE OXIDASE 1, a photorespiratory enzyme that produces hydrogen peroxide in response to Pseudomonas, was shown to be repressed by a combination of cGMP and nitric oxide treatment. Conclusions We propose that the identified proteins function together as points of cross-talk between cyclic nucleotide, nitric oxide and reactive oxygen species signaling during the defence response.

  11. An Interactome-Centered Protein Discovery Approach Reveals Novel Components Involved in Mitosome Function and Homeostasis in Giardia lamblia.

    Directory of Open Access Journals (Sweden)

    Samuel Rout

    2016-12-01

    Full Text Available Protozoan parasites of the genus Giardia are highly prevalent globally, and infect a wide range of vertebrate hosts including humans, with proliferation and pathology restricted to the small intestine. This narrow ecological specialization entailed extensive structural and functional adaptations during host-parasite co-evolution. An example is the streamlined mitosomal proteome with iron-sulphur protein maturation as the only biochemical pathway clearly associated with this organelle. Here, we applied techniques in microscopy and protein biochemistry to investigate the mitosomal membrane proteome in association to mitosome homeostasis. Live cell imaging revealed a highly immobilized array of 30-40 physically distinct mitosome organelles in trophozoites. We provide direct evidence for the single giardial dynamin-related protein as a contributor to mitosomal morphogenesis and homeostasis. To overcome inherent limitations that have hitherto severely hampered the characterization of these unique organelles we applied a novel interaction-based proteome discovery strategy using forward and reverse protein co-immunoprecipitation. This allowed generation of organelle proteome data strictly in a protein-protein interaction context. We built an initial Tom40-centered outer membrane interactome by co-immunoprecipitation experiments, identifying small GTPases, factors with dual mitosome and endoplasmic reticulum (ER distribution, as well as novel matrix proteins. Through iterative expansion of this protein-protein interaction network, we were able to i significantly extend this interaction-based mitosomal proteome to include other membrane-associated proteins with possible roles in mitosome morphogenesis and connection to other subcellular compartments, and ii identify novel matrix proteins which may shed light on mitosome-associated metabolic functions other than Fe-S cluster biogenesis. Functional analysis also revealed conceptual conservation of protein

  12. Identifying the sources of nitrate contamination of groundwater in an agricultural area (Haean basin, Korea) using isotope and microbial community analyses

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Heejung [School of Earth and Environmental Sciences (BK21 SEES), Seoul National University, Seoul 151–747 (Korea, Republic of); Kaown, Dugin, E-mail: dugin1@snu.ac.kr [School of Earth and Environmental Sciences (BK21 SEES), Seoul National University, Seoul 151–747 (Korea, Republic of); Mayer, Bernhard [Department of Geoscience, University of Calgary, 2500 University Drive NW, Calgary T2N 1N4, Alberta (Canada); Lee, Jin-Yong [Department of Geology, Kangwon National University, Chuncheon 200–701 (Korea, Republic of); Hyun, Yunjung [Planning and Management Group, Korea Environment Institute, Sejong 339-007 (Korea, Republic of); Lee, Kang-Kun [School of Earth and Environmental Sciences (BK21 SEES), Seoul National University, Seoul 151–747 (Korea, Republic of)

    2015-11-15

    } and SO{sub 4}{sup 2−} in groundwater in areas with intensive agricultural land use. - Highlights: • Dual isotope analyses identified contaminant sources. • Aquifer contamination was affected by land use. • Microbial community in groundwater reflects land use. • Approach is promising for managing water quality in agricultural areas.

  13. Identifying the sources of nitrate contamination of groundwater in an agricultural area (Haean basin, Korea) using isotope and microbial community analyses

    International Nuclear Information System (INIS)

    Kim, Heejung; Kaown, Dugin; Mayer, Bernhard; Lee, Jin-Yong; Hyun, Yunjung; Lee, Kang-Kun

    2015-01-01

    An integrated study based on hydrogeochemical, microbiological and dual isotopic approaches for nitrate and sulfate was conducted to elucidate sources and biogeochemical reactions governing groundwater contaminants in different seasons and under different land use in a basin of Korea. The land use in the study area is comprised of forests (58.0%), vegetable fields (27.6%), rice paddy fields (11.4%) and others (3.0%). The concentrations of NO 3 –N and SO 4 2− in groundwater in vegetable fields were highest with 4.2–15.2 mg L −1 and 1.6–19.7 mg L −1 respectively, whereas under paddy fields NO 3 –N concentrations ranged from 0 to 10.7 mg L −1 and sulfate concentrations were ~ 15 mg L −1 . Groundwater with high NO 3 –N concentrations of > 10 mg L −1 had δ 15 N–NO 3 − values ranging from 5.2 to 5.9‰ and δ 18 O values of nitrate between 2.7 and 4.6‰ suggesting that the nitrate was mineralized from soil organic matter that was amended by fertilizer additions. Elevated concentrations of SO 4 2− with δ 34 S–SO 4 2− values between 1 and 6‰ in aquifers in vegetable fields indicated that a mixture of sulfate from atmospheric deposition, mineralization of soil organic matter and from synthetic fertilizers is the source of groundwater sulfate. Elevated δ 18 O–NO 3 − and δ 18 O–SO 4 2− values in samples collected from the paddy fields indicated that denitrification and bacterial sulfate reduction are actively occurring removing sulfate and nitrate from the groundwater. This was supported by high occurrences of denitrifying and sulfate reducing bacteria in groundwater of the paddy fields as evidenced by 16S rRNA pyrosequencing analysis. This study shows that dual isotope techniques combined with microbial data can be a powerful tool for identification of sources and microbial processes affecting NO 3 − and SO 4 2− in groundwater in areas with intensive agricultural land use. - Highlights: • Dual isotope analyses identified

  14. Foxtail millet NF-Y families: genome-wide survey and evolution analyses identified two functional genes important in abiotic stresses

    Directory of Open Access Journals (Sweden)

    Zhi-Juan eFeng

    2015-12-01

    Full Text Available It was reported that Nuclear Factor Y (NF-Y genes were involved in abiotic stress in plants. Foxtail millet (Setaria italica, an elite stress tolerant crop, provided an impetus for the investigation of the NF-Y families in abiotic responses. In the present study, a total of 39 NF-Y genes were identified in foxtail millet. Synteny analyses suggested that foxtail millet NF-Y genes had experienced rapid expansion and strong purifying selection during the process of plant evolution. De novo transcriptome assembly of foxtail millet revealed 11 drought up-regulated NF-Y genes. SiNF-YA1 and SiNF-YB8 were highly activated in leaves and/or roots by drought and salt stresses. Abscisic acid (ABA and H2O2 played positive roles in the induction of SiNF-YA1 and SiNF-YB8 under stress treatments. Transient luciferase (LUC expression assays revealed that SiNF-YA1 and SiNF-YB8 could activate the LUC gene driven by the tobacco (Nicotiana tobacam NtERD10, NtLEA5, NtCAT, NtSOD or NtPOD promoter under normal or stress conditions. Overexpression of SiNF-YA1 enhanced drought and salt tolerance by activating stress-related genes NtERD10 and NtCAT1 and by maintaining relatively stable relative water content (RWC and contents of chlorophyll, superoxide dismutase (SOD, peroxidase (POD, catalase (CAT and malondialdehyde (MDA in transgenic lines under stresses. SiNF-YB8 regulated expression of NtSOD, NtPOD, NtLEA5 and NtERD10 and conferred relatively high RWC and chlorophyll contents and low MDA content, resulting in drought and osmotic tolerance in transgenic lines under stresses. Therefore, SiNF-YA1 and SiNF-YB8 could activate stress-related genes and improve physiological traits, resulting in tolerance to abiotic stresses in plants. All these results will facilitate functional characterization of foxtail millet NF-Ys in future studies.

  15. Crowd Sourcing a New Paradigm for Interactome Driven Drug Target Identification in Mycobacterium tuberculosis

    Science.gov (United States)

    Rohira, Harsha; Bhat, Ashwini G.; Passi, Anurag; Mukherjee, Keya; Choudhary, Kumari Sonal; Kumar, Vikas; Arora, Anshula; Munusamy, Prabhakaran; Subramanian, Ahalyaa; Venkatachalam, Aparna; S, Gayathri; Raj, Sweety; Chitra, Vijaya; Verma, Kaveri; Zaheer, Salman; J, Balaganesh; Gurusamy, Malarvizhi; Razeeth, Mohammed; Raja, Ilamathi; Thandapani, Madhumohan; Mevada, Vishal; Soni, Raviraj; Rana, Shruti; Ramanna, Girish Muthagadhalli; Raghavan, Swetha; Subramanya, Sunil N.; Kholia, Trupti; Patel, Rajesh; Bhavnani, Varsha; Chiranjeevi, Lakavath; Sengupta, Soumi; Singh, Pankaj Kumar; Atray, Naresh; Gandhi, Swati; Avasthi, Tiruvayipati Suma; Nisthar, Shefin; Anurag, Meenakshi; Sharma, Pratibha; Hasija, Yasha; Dash, Debasis; Sharma, Arun; Scaria, Vinod; Thomas, Zakir; Chandra, Nagasuma; Brahmachari, Samir K.; Bhardwaj, Anshu

    2012-01-01

    A decade since the availability of Mycobacterium tuberculosis (Mtb) genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative ‘Connect to Decode’ (C2D) to generate the first and largest manually curated interactome of Mtb termed ‘interactome pathway’ (IPW), encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach. PMID:22808064

  16. Crowd sourcing a new paradigm for interactome driven drug target identification in Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Rohit Vashisht

    Full Text Available A decade since the availability of Mycobacterium tuberculosis (Mtb genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative 'Connect to Decode' (C2D to generate the first and largest manually curated interactome of Mtb termed 'interactome pathway' (IPW, encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach.

  17. Embryonic stem cell interactomics: the beginning of a long road to biological function.

    Science.gov (United States)

    Yousefi, Maram; Hajihoseini, Vahid; Jung, Woojin; Hosseinpour, Batol; Rassouli, Hassan; Lee, Bonghee; Baharvand, Hossein; Lee, KiYoung; Salekdeh, Ghasem Hosseini

    2012-12-01

    Embryonic stem cells (ESCs) are capable of unlimited self-renewal while maintaining pluripotency. They are of great interest in regenerative medicine due to their ability to differentiate into all cell types of the three embryonic germ layers. Recently, induced pluripotent stem cells (iPSCs) have shown similarities to ESCs and thus promise great therapeutic potential in regenerative medicine. Despite progress in stem cell biology, our understanding of the exact mechanisms by which pluripotency and self-renewal are established and maintained is largely unknown. A better understanding of these processes may lead to discovery of alternative ways for reprogramming, differentiation and more reliable applications of stem cells in therapies. It has become evident that proteins generally function as members of large complexes that are part of a more complex network. Therefore, the identification of protein-protein interactions (PPI) is an efficient strategy for understanding protein function and regulation. Systematic genome-wide and pathway-specific PPI analysis of ESCs has generated a network of ESC proteins, including major transcription factors. These PPI networks of ESCs may contribute to a mechanistic understanding of self-renewal and pluripotency. In this review we describe different experimental approaches for the identification of PPIs along with various databases. We discuss biological findings and technical challenges encountered with interactome studies of pluripotent stem cells, and provide insight into how interactomics is likely to develop.

  18. Functional interactome of Aquaporin 1 sub-family reveals new physiological functions in Arabidopsis Thaliana

    Directory of Open Access Journals (Sweden)

    Mohamed Ragab Abdel Gawwad

    2013-09-01

    Full Text Available Aquaporins are channel proteins found in plasma membranes and intercellular membranes of different cellular compartments, facilitate the water flux, solutes and gases across the cellular plasma membranes. The present study highlights the sub-family plasma membrane intrinsic protein (PIP predicting the 3-D structure and analyzing the functional interactome of it homologs. PIP1 homologs integrate with many proteins with different plant physiological roles in Arabidopsis thaliana including; PIP1A and PIP1B: facilitate the transport of water, diffusion of amino acids and/or peptides from the vacuolar compartment to the cytoplasm, play a role in the control of cell turgor and cell expansion and involved in root water uptake respectively. In addition we found that PIP1B plays a defensive role against Pseudomonas syringae infection through the interaction with the plasma membrane Rps2 protein. Another substantial function of PIP1C via the interaction with PIP2E is the response to nematode infection. Generally, PIP1 sub-family interactome controlling many physiological processes in plant cell like; osmoregulation in plants under high osmotic stress such as under a high salt, response to nematode, facilitate the transport of water across cell membrane and regulation of floral initiation in Arabidopsis thaliana.

  19. Interactomes, manufacturomes and relational biology: analogies between systems biology and manufacturing systems

    Science.gov (United States)

    2011-01-01

    Background We review and extend the work of Rosen and Casti who discuss category theory with regards to systems biology and manufacturing systems, respectively. Results We describe anticipatory systems, or long-range feed-forward chemical reaction chains, and compare them to open-loop manufacturing processes. We then close the loop by discussing metabolism-repair systems and describe the rationality of the self-referential equation f = f (f). This relationship is derived from some boundary conditions that, in molecular systems biology, can be stated as the cardinality of the following molecular sets must be about equal: metabolome, genome, proteome. We show that this conjecture is not likely correct so the problem of self-referential mappings for describing the boundary between living and nonliving systems remains an open question. We calculate a lower and upper bound for the number of edges in the molecular interaction network (the interactome) for two cellular organisms and for two manufacturomes for CMOS integrated circuit manufacturing. Conclusions We show that the relevant mapping relations may not be Abelian, and that these problems cannot yet be resolved because the interactomes and manufacturomes are incomplete. PMID:21689427

  20. Improved microarray-based decision support with graph encoded interactome data.

    Directory of Open Access Journals (Sweden)

    Anneleen Daemen

    Full Text Available In the past, microarray studies have been criticized due to noise and the limited overlap between gene signatures. Prior biological knowledge should therefore be incorporated as side information in models based on gene expression data to improve the accuracy of diagnosis and prognosis in cancer. As prior knowledge, we investigated interaction and pathway information from the human interactome on different aspects of biological systems. By exploiting the properties of kernel methods, relations between genes with similar functions but active in alternative pathways could be incorporated in a support vector machine classifier based on spectral graph theory. Using 10 microarray data sets, we first reduced the number of data sources relevant for multiple cancer types and outcomes. Three sources on metabolic pathway information (KEGG, protein-protein interactions (OPHID and miRNA-gene targeting (microRNA.org outperformed the other sources with regard to the considered class of models. Both fixed and adaptive approaches were subsequently considered to combine the three corresponding classifiers. Averaging the predictions of these classifiers performed best and was significantly better than the model based on microarray data only. These results were confirmed on 6 validation microarray sets, with a significantly improved performance in 4 of them. Integrating interactome data thus improves classification of cancer outcome for the investigated microarray technologies and cancer types. Moreover, this strategy can be incorporated in any kernel method or non-linear version of a non-kernel method.

  1. Grouping annotations on the subcellular layered interactome demonstrates enhanced autophagy activity in a recurrent experimental autoimmune uveitis T cell line.

    Directory of Open Access Journals (Sweden)

    Xiuzhi Jia

    Full Text Available Human uveitis is a type of T cell-mediated autoimmune disease that often shows relapse-remitting courses affecting multiple biological processes. As a cytoplasmic process, autophagy has been seen as an adaptive response to cell death and survival, yet the link between autophagy and T cell-mediated autoimmunity is not certain. In this study, based on the differentially expressed genes (GSE19652 between the recurrent versus monophasic T cell lines, whose adoptive transfer to susceptible animals may result in respective recurrent or monophasic uveitis, we proposed grouping annotations on a subcellular layered interactome framework to analyze the specific bioprocesses that are linked to the recurrence of T cell autoimmunity. That is, the subcellular layered interactome was established by the Cytoscape and Cerebral plugin based on differential expression, global interactome, and subcellular localization information. Then, the layered interactomes were grouping annotated by the ClueGO plugin based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The analysis showed that significant bioprocesses with autophagy were orchestrated in the cytoplasmic layered interactome and that mTOR may have a regulatory role in it. Furthermore, by setting up recurrent and monophasic uveitis in Lewis rats, we confirmed by transmission electron microscopy that, in comparison to the monophasic disease, recurrent uveitis in vivo showed significantly increased autophagy activity and extended lymphocyte infiltration to the affected retina. In summary, our framework methodology is a useful tool to disclose specific bioprocesses and molecular targets that can be attributed to a certain disease. Our results indicated that targeted inhibition of autophagy pathways may perturb the recurrence of uveitis.

  2. Crosstalk between apoptosis and autophagy within the Beclin 1 interactome.

    Science.gov (United States)

    Maiuri, Maria Chiara; Criollo, Alfredo; Kroemer, Guido

    2010-02-03

    Although the essential genes for autophagy (Atg) have been identified, the molecular mechanisms through which Atg proteins control 'self eating' in mammalian cells remain elusive. Beclin 1 (Bec1), the mammalian orthologue of yeast Atg6, is part of the class III phosphatidylinositol 3-kinase (PI3K) complex that induces autophagy. The first among an increasing number of Bec1-interacting proteins that has been identified is the anti-apoptotic protein Bcl-2. The dissociation of Bec1 from Bcl-2 is essential for its autophagic activity, and Bcl-2 only inhibits autophagy when it is present in the endoplasmic reticulum (ER). A paper in this issue of the EMBO Journal has identified a novel protein, NAF-1 (nutrient-deprivation autophagy factor-1), that binds Bcl-2 at the ER. NAF-1 is a component of the inositol-1,4,5 trisphosphate (IP3) receptor complex, which contributes to the interaction of Bcl-2 with Bec1 and is required for Bcl-2 to functionally antagonize Bec1-mediated autophagy. This work provides mechanistic insights into how autophagy- and apoptosis-regulatory molecules crosstalk at the ER.

  3. Expanding the substantial interactome of NEMO using protein microarrays.

    LENUS (Irish Health Repository)

    Fenner, Beau J

    2010-01-01

    Signal transduction by the NF-kappaB pathway is a key regulator of a host of cellular responses to extracellular and intracellular messages. The NEMO adaptor protein lies at the top of this pathway and serves as a molecular conduit, connecting signals transmitted from upstream sensors to the downstream NF-kappaB transcription factor and subsequent gene activation. The position of NEMO within this pathway makes it an attractive target from which to search for new proteins that link NF-kappaB signaling to additional pathways and upstream effectors. In this work, we have used protein microarrays to identify novel NEMO interactors. A total of 112 protein interactors were identified, with the most statistically significant hit being the canonical NEMO interactor IKKbeta, with IKKalpha also being identified. Of the novel interactors, more than 30% were kinases, while at least 25% were involved in signal transduction. Binding of NEMO to several interactors, including CALB1, CDK2, SAG, SENP2 and SYT1, was confirmed using GST pulldown assays and coimmunoprecipitation, validating the initial screening approach. Overexpression of CALB1, CDK2 and SAG was found to stimulate transcriptional activation by NF-kappaB, while SYT1 overexpression repressed TNFalpha-dependent NF-kappaB transcriptional activation in human embryonic kidney cells. Corresponding with this finding, RNA silencing of CDK2, SAG and SENP2 reduced NF-kappaB transcriptional activation, supporting a positive role for these proteins in the NF-kappaB pathway. The identification of a host of new NEMO interactors opens up new research opportunities to improve understanding of this essential cell signaling pathway.

  4. Exploring off-targets and off-systems for adverse drug reactions via chemical-protein interactome--clozapine-induced agranulocytosis as a case study.

    Directory of Open Access Journals (Sweden)

    Lun Yang

    2011-03-01

    Full Text Available In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI, which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs.

  5. Lukasiewicz-Topos Models of Neural Networks, Cell Genome and Interactome Nonlinear Dynamic Models

    CERN Document Server

    Baianu, I C

    2004-01-01

    A categorical and Lukasiewicz-Topos framework for Lukasiewicz Algebraic Logic models of nonlinear dynamics in complex functional systems such as neural networks, genomes and cell interactomes is proposed. Lukasiewicz Algebraic Logic models of genetic networks and signaling pathways in cells are formulated in terms of nonlinear dynamic systems with n-state components that allow for the generalization of previous logical models of both genetic activities and neural networks. An algebraic formulation of variable 'next-state functions' is extended to a Lukasiewicz Topos with an n-valued Lukasiewicz Algebraic Logic subobject classifier description that represents non-random and nonlinear network activities as well as their transformations in developmental processes and carcinogenesis.

  6. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

    NARCIS (Netherlands)

    Day, Felix R; Thompson, Deborah J; Helgason, Hannes; Chasman, Daniel I; Finucane, Hilary; Sulem, Patrick; Ruth, Katherine S; Whalen, Sean; Sarkar, Abhishek K; Albrecht, Eva; Altmaier, Elisabeth; Amini, Marzyeh; Barbieri, Caterina M; Boutin, Thibaud; Campbell, Archie; Demerath, Ellen; Giri, Ayush; He, Chunyan; Hottenga, Jouke J; Karlsson, Robert; Kolcic, Ivana; Loh, Po-Ru; Lunetta, Kathryn L; Mangino, Massimo; Marco, Brumat; McMahon, George; Medland, Sarah E; Nolte, Ilja M; Noordam, Raymond; Nutile, Teresa; Paternoster, Lavinia; Perjakova, Natalia; Porcu, Eleonora; Rose, Lynda M; Schraut, Katharina E; Segrè, Ayellet V; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Andrulis, Irene L; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Bergmann, Sven; Bochud, Murielle; de Geus, Eco J C N; Mbarek, Hamdi; Willemsen, Gonneke; Boomsma, Dorret I; Visser, Jenny A

    2017-01-01

    The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10(-8)) for age at menarche, a milestone in female

  7. Gene Expression Responses to FUS, EWS, and TAF15 Reduction and Stress Granule Sequestration Analyses Identifies FET-Protein Non-Redundant Functions

    DEFF Research Database (Denmark)

    Blechingberg, Jenny; Luo, Yonglun; Bolund, Lars

    2012-01-01

    The FET family of proteins is composed of FUS/TLS, EWS/EWSR1, and TAF15 and possesses RNA- and DNA-binding capacities. The FET-proteins are involved in transcriptional regulation and RNA processing, and FET-gene deregulation is associated with development of cancer and protein granule formations...... in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and trinucleotide repeat expansion diseases. We here describe a comparative characterization of FET-protein localization and gene regulatory functions. We show that FUS and TAF15 locate to cellular stress granules to a larger extend than EWS....... FET-proteins have no major importance for stress granule formation and cellular stress responses, indicating that FET-protein stress granule association most likely is a downstream response to cellular stress. Gene expression analyses showed that the cellular response towards FUS and TAF15 reduction...

  8. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

    DEFF Research Database (Denmark)

    Kar, Siddhartha P; Beesley, Jonathan; Amin Al Olama, Ali

    2016-01-01

    UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112...... (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell......-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P cancer meta-analysis. SIGNIFICANCE...

  9. Integrated genomic analyses identify KDM1A's role in cell proliferation via modulating E2F signaling activity and associate with poor clinical outcome in oral cancer.

    Science.gov (United States)

    Narayanan, Sathiya Pandi; Singh, Smriti; Gupta, Amit; Yadav, Sandhya; Singh, Shree Ram; Shukla, Sanjeev

    2015-10-28

    The histone demethylase KDM1A specifically demethylates lysine residues and its deregulation has been implicated in the initiation and progression of various cancers. However, KDM1A's molecular role and its pathological consequences, and prognostic significance in oral cancer remain less understood. In the present study, we sought to investigate the expression of KDM1A and its downstream role in oral cancer pathogenesis. By comparing mRNA expression profiles, we identified an elevated KDM1A expression in oral tumors when compared to normal oral tissues. In silico pathway prediction identified the association between KDM1A and E2F1 signaling in oral cancer. Pathway scanning, functional annotation analysis and In vitro assays showed the KDM1A's involvement in oral cancer cell proliferation and the cell cycle. Moreover, real time PCR and luciferase assays confirmed KDM1A's role in regulation of E2F1 signaling activity in oral cancer. Elevated KDM1A expression is associated with poor clinical outcome in oral cancer. Our data indicate that deregulated KDM1A expression is positively associated with proliferative phenotype of oral cancer and confers poor clinical outcome. These cumulative data suggest that KDM1A might be a potential diagnostic and therapeutic target for oral cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Reduced Representation Libraries from DNA Pools Analysed with Next Generation Semiconductor Based-Sequencing to Identify SNPs in Extreme and Divergent Pigs for Back Fat Thickness

    Directory of Open Access Journals (Sweden)

    Samuele Bovo

    2015-01-01

    Full Text Available The aim of this study was to identify single nucleotide polymorphisms (SNPs that could be associated with back fat thickness (BFT in pigs. To achieve this goal, we evaluated the potential and limits of an experimental design that combined several methodologies. DNA samples from two groups of Italian Large White pigs with divergent estimating breeding value (EBV for BFT were separately pooled and sequenced, after preparation of reduced representation libraries (RRLs, on the Ion Torrent technology. Taking advantage from SNAPE for SNPs calling in sequenced DNA pools, 39,165 SNPs were identified; 1/4 of them were novel variants not reported in dbSNP. Combining sequencing data with Illumina PorcineSNP60 BeadChip genotyping results on the same animals, 661 genomic positions overlapped with a good approximation of minor allele frequency estimation. A total of 54 SNPs showing enriched alleles in one or in the other RRLs might be potential markers associated with BFT. Some of these SNPs were close to genes involved in obesity related phenotypes.

  11. Comparative proteomic analysis of normal and collagen IX null mouse cartilage reveals altered extracellular matrix composition and novel components of the collagen IX interactome.

    Science.gov (United States)

    Brachvogel, Bent; Zaucke, Frank; Dave, Keyur; Norris, Emma L; Stermann, Jacek; Dayakli, Münire; Koch, Manuel; Gorman, Jeffrey J; Bateman, John F; Wilson, Richard

    2013-05-10

    Collagen IX is an integral cartilage extracellular matrix component important in skeletal development and joint function. Proteomic analysis and validation studies revealed novel alterations in collagen IX null cartilage. Matrilin-4, collagen XII, thrombospondin-4, fibronectin, βig-h3, and epiphycan are components of the in vivo collagen IX interactome. We applied a proteomics approach to advance our understanding of collagen IX ablation in cartilage. The cartilage extracellular matrix is essential for endochondral bone development and joint function. In addition to the major aggrecan/collagen II framework, the interacting complex of collagen IX, matrilin-3, and cartilage oligomeric matrix protein (COMP) is essential for cartilage matrix stability, as mutations in Col9a1, Col9a2, Col9a3, Comp, and Matn3 genes cause multiple epiphyseal dysplasia, in which patients develop early onset osteoarthritis. In mice, collagen IX ablation results in severely disturbed growth plate organization, hypocellular regions, and abnormal chondrocyte shape. This abnormal differentiation is likely to involve altered cell-matrix interactions but the mechanism is not known. To investigate the molecular basis of the collagen IX null phenotype we analyzed global differences in protein abundance between wild-type and knock-out femoral head cartilage by capillary HPLC tandem mass spectrometry. We identified 297 proteins in 3-day cartilage and 397 proteins in 21-day cartilage. Components that were differentially abundant between wild-type and collagen IX-deficient cartilage included 15 extracellular matrix proteins. Collagen IX ablation was associated with dramatically reduced COMP and matrilin-3, consistent with known interactions. Matrilin-1, matrilin-4, epiphycan, and thrombospondin-4 levels were reduced in collagen IX null cartilage, providing the first in vivo evidence for these proteins belonging to the collagen IX interactome. Thrombospondin-4 expression was reduced at the mRNA level

  12. Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks.

    Science.gov (United States)

    Fischer, Martin; Grossmann, Patrick; Padi, Megha; DeCaprio, James A

    2016-07-27

    Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Quantitative and mixed analyses to identify factors that affect cervical cancer screening uptake among lesbian and bisexual women and transgender men.

    Science.gov (United States)

    Johnson, Michael J; Mueller, Martina; Eliason, Michele J; Stuart, Gail; Nemeth, Lynne S

    2016-12-01

    The purposes of this study were to measure the prevalence of, and identify factors associated with, cervical cancer screening among a sample of lesbian, bisexual and queer women, and transgender men. Past research has found that lesbian, bisexual and queer women underuse cervical screening service. Because deficient screening remains the most significant risk factor for cervical cancer, it is essential to understand the differences between routine and nonroutine screeners. A convergent-parallel mixed methods design. A convenience sample of 21- to 65-year-old lesbian and bisexual women and transgender men were recruited in the USA from August-December 2014. Quantitative data were collected via a 48-item Internet questionnaire (N = 226), and qualitative data were collected through in-depth telephone interviews (N = 20) and open-ended questions on the Internet questionnaire. Seventy-three per cent of the sample was routine cervical screeners. The results showed that a constellation of factors influence the use of cervical cancer screening among lesbian, bisexual and queer women. Some of those factors overlap with the general female population, whereas others are specific to the lesbian, bisexual or queer identity. Routine screeners reported feeling more welcome in the health care setting, while nonroutine screeners reported more discrimination related to their sexual orientation and gender expression. Routine screeners were also more likely to 'out' to their provider. The quantitative and qualitative factors were also compared and contrasted. Many of the factors identified in this study to influence cervical cancer screening relate to the health care environment and to interactions between the patient and provider. Nurses should be involved with creating welcoming environments for lesbian, bisexual and queer women and their partners. Moreover, nurses play a large role in patient education and should promote self-care behaviours among lesbian women and transgender

  14. Analyses of expressed sequence tags from the maize foliar pathogen Cercospora zeae-maydis identify novel genes expressed during vegetative, infectious, and reproductive growth

    Directory of Open Access Journals (Sweden)

    Kema Gert HJ

    2008-11-01

    Full Text Available Abstract Background The ascomycete fungus Cercospora zeae-maydis is an aggressive foliar pathogen of maize that causes substantial losses annually throughout the Western Hemisphere. Despite its impact on maize production, little is known about the regulation of pathogenesis in C. zeae-maydis at the molecular level. The objectives of this study were to generate a collection of expressed sequence tags (ESTs from C. zeae-maydis and evaluate their expression during vegetative, infectious, and reproductive growth. Results A total of 27,551 ESTs was obtained from five cDNA libraries constructed from vegetative and sporulating cultures of C. zeae-maydis. The ESTs, grouped into 4088 clusters and 531 singlets, represented 4619 putative unique genes. Of these, 36% encoded proteins similar (E value ≤ 10-05 to characterized or annotated proteins from the NCBI non-redundant database representing diverse molecular functions and biological processes based on Gene Ontology (GO classification. We identified numerous, previously undescribed genes with potential roles in photoreception, pathogenesis, and the regulation of development as well as Zephyr, a novel, actively transcribed transposable element. Differential expression of selected genes was demonstrated by real-time PCR, supporting their proposed roles in vegetative, infectious, and reproductive growth. Conclusion Novel genes that are potentially involved in regulating growth, development, and pathogenesis were identified in C. zeae-maydis, providing specific targets for characterization by molecular genetics and functional genomics. The EST data establish a foundation for future studies in evolutionary and comparative genomics among species of Cercospora and other groups of plant pathogenic fungi.

  15. Giant Galápagos tortoises; molecular genetic analyses identify a trans-island hybrid in a repatriation program of an endangered taxon

    Directory of Open Access Journals (Sweden)

    Caccone Adalgisa

    2007-02-01

    Full Text Available Abstract Background Giant Galápagos tortoises on the island of Española have been the focus of an intensive captive breeding-repatriation programme for over 35 years that saved the taxon from extinction. However, analysis of 118 samples from released individuals indicated that the bias sex ratio and large variance in reproductive success among the 15 breeders has severely reduced the effective population size (Ne. Results We report here that an analysis of an additional 473 captive-bred tortoises released back to the island reveals an individual (E1465 that exhibits nuclear microsatellite alleles not found in any of the 15 breeders. Statistical analyses incorporating genotypes of 304 field-sampled individuals from all populations on the major islands indicate that E1465 is most probably a hybrid between an Española female tortoise and a male from the island of Pinzón, likely present on Española due to human transport. Conclusion Removal of E1465 as well as its father and possible (half-siblings is warranted to prevent further contamination within this taxon of particular conservation significance. Despite this detected single contamination, it is highly noteworthy to emphasize the success of this repatriation program conducted over nearly 40 years and involving release of over 2000 captive-bred tortoises that now reproduce in situ. The incorporation of molecular genetic analysis of the program is providing guidance that will aid in monitoring the genetic integrity of this ambitious effort to restore a unique linage of a spectacular animal.

  16. Post-genome wide association studies and functional analyses identify association of MPP7 gene variants with site-specific bone mineral density.

    Science.gov (United States)

    Xiao, Su-Mei; Kung, Annie Wai Chee; Gao, Yi; Lau, Kam-Shing; Ma, Alvin; Zhang, Zhen-Lin; Liu, Jian-Min; Xia, Wiebo; He, Jin-Wei; Zhao, Lin; Nie, Min; Fu, Wei-Zhen; Zhang, Min-Jia; Sun, Jing; Kwan, Johnny S H; Tso, Gloria Hoi Wan; Dai, Zhi-Jie; Cheung, Ching-Lung; Bow, Cora H; Leung, Anskar Yu Hung; Tan, Kathryn Choon Beng; Sham, Pak Chung

    2012-04-01

    Our previous genome-wide association study (GWAS) in a Hong Kong Southern Chinese population with extreme bone mineral density (BMD) scores revealed suggestive association with MPP7, which ranked second after JAG1 as a candidate gene for BMD. To follow-up this suggestive signal, we replicated the top single-nucleotide polymorphism rs4317882 of MPP7 in three additional independent Asian-descent samples (n= 2684). The association of rs4317882 reached the genome-wide significance in the meta-analysis of all available subjects (P(meta)= 4.58 × 10(-8), n= 4204). Site heterogeneity was observed, with a larger effect on spine than hip BMD. Further functional studies in a zebrafish model revealed that vertebral bone mass was lower in an mpp7 knock-down model compared with the wide-type (P= 9.64 × 10(-4), n= 21). In addition, MPP7 was found to have constitutive expression in human bone-derived cells during osteogenesis. Immunostaining of murine MC3T3-E1 cells revealed that the Mpp7 protein is localized in the plasma membrane and intracytoplasmic compartment of osteoblasts. In an assessment of the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of transcriptional factor GATA2 to the risk allele 'A' but not the 'G' allele of rs4317882. An mRNA expression study in human peripheral blood mononuclear cells confirmed that the low BMD-related allele 'A' of rs4317882 was associated with lower MPP7 expression (P= 9.07 × 10(-3), n= 135). Our data suggest a genetic and functional association of MPP7 with BMD variation.

  17. Striatal Transcriptome and Interactome Analysis of Shank3-overexpressing Mice Reveals the Connectivity between Shank3 and mTORC1 Signaling

    Directory of Open Access Journals (Sweden)

    Yeunkum Lee

    2017-06-01

    Full Text Available Mania causes symptoms of hyperactivity, impulsivity, elevated mood, reduced anxiety and decreased need for sleep, which suggests that the dysfunction of the striatum, a critical component of the brain motor and reward system, can be causally associated with mania. However, detailed molecular pathophysiology underlying the striatal dysfunction in mania remains largely unknown. In this study, we aimed to identify the molecular pathways showing alterations in the striatum of SH3 and multiple ankyrin repeat domains 3 (Shank3-overexpressing transgenic (TG mice that display manic-like behaviors. The results of transcriptome analysis suggested that mammalian target of rapamycin complex 1 (mTORC1 signaling may be the primary molecular signature altered in the Shank3 TG striatum. Indeed, we found that striatal mTORC1 activity, as measured by mTOR S2448 phosphorylation, was significantly decreased in the Shank3 TG mice compared to wild-type (WT mice. To elucidate the potential underlying mechanism, we re-analyzed previously reported protein interactomes, and detected a high connectivity between Shank3 and several upstream regulators of mTORC1, such as tuberous sclerosis 1 (TSC1, TSC2 and Ras homolog enriched in striatum (Rhes, via 94 common interactors that we denominated “Shank3-mTORC1 interactome”. We noticed that, among the 94 common interactors, 11 proteins were related to actin filaments, the level of which was increased in the dorsal striatum of Shank3 TG mice. Furthermore, we could co-immunoprecipitate Shank3, Rhes and Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1 proteins from the striatal lysate of Shank3 TG mice. By comparing with the gene sets of psychiatric disorders, we also observed that the 94 proteins of Shank3-mTORC1 interactome were significantly associated with bipolar disorder (BD. Altogether, our results suggest a protein interaction-mediated connectivity between Shank3 and certain upstream

  18. A rapid and accurate approach for prediction of interactomes from co-elution data (PrInCE).

    Science.gov (United States)

    Stacey, R Greg; Skinnider, Michael A; Scott, Nichollas E; Foster, Leonard J

    2017-10-23

    An organism's protein interactome, or complete network of protein-protein interactions, defines the protein complexes that drive cellular processes. Techniques for studying protein complexes have traditionally applied targeted strategies such as yeast two-hybrid or affinity purification-mass spectrometry to assess protein interactions. However, given the vast number of protein complexes, more scalable methods are necessary to accelerate interaction discovery and to construct whole interactomes. We recently developed a complementary technique based on the use of protein correlation profiling (PCP) and stable isotope labeling in amino acids in cell culture (SILAC) to assess chromatographic co-elution as evidence of interacting proteins. Importantly, PCP-SILAC is also capable of measuring protein interactions simultaneously under multiple biological conditions, allowing the detection of treatment-specific changes to an interactome. Given the uniqueness and high dimensionality of co-elution data, new tools are needed to compare protein elution profiles, control false discovery rates, and construct an accurate interactome. Here we describe a freely available bioinformatics pipeline, PrInCE, for the analysis of co-elution data. PrInCE is a modular, open-source library that is computationally inexpensive, able to use label and label-free data, and capable of detecting tens of thousands of protein-protein interactions. Using a machine learning approach, PrInCE offers greatly reduced run time, more predicted interactions at the same stringency, prediction of protein complexes, and greater ease of use over previous bioinformatics tools for co-elution data. PrInCE is implemented in Matlab (version R2017a). Source code and standalone executable programs for Windows and Mac OSX are available at https://github.com/fosterlab/PrInCE , where usage instructions can be found. An example dataset and output are also provided for testing purposes. PrInCE is the first fast and easy

  19. Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

    International Nuclear Information System (INIS)

    Park, Sung-Dong; Cheon, So Yeong; Park, Tae-Yoon; Shin, Bo-Young; Oh, Hyunju; Ghosh, Sankar; Koo, Bon-Nyeo; Lee, Sang-Kyou

    2015-01-01

    Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. - Highlights: • The nt-p65-TMD is intra-nuclear interactomic inhibitor of endogenous p65. • The nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines. • The excellent therapeutic potential of nt-p65-TMD was confirmed in sepsis model

  20. Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung-Dong [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Cheon, So Yeong [Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Park, Tae-Yoon; Shin, Bo-Young [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Oh, Hyunju; Ghosh, Sankar [Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Koo, Bon-Nyeo, E-mail: koobn@yuhs.ac [Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Sang-Kyou, E-mail: sjrlee@yonsei.ac.kr [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2015-08-28

    Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. - Highlights: • The nt-p65-TMD is intra-nuclear interactomic inhibitor of endogenous p65. • The nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines. • The excellent therapeutic potential of nt-p65-TMD was confirmed in sepsis model.

  1. Exploitation of complex network topology for link prediction in biological interactomes

    KAUST Repository

    Alanis Lobato, Gregorio

    2014-06-01

    The network representation of the interactions between proteins and genes allows for a holistic perspective of the complex machinery underlying the living cell. However, the large number of interacting entities within the cell makes network construction a daunting and arduous task, prone to errors and missing information. Fortunately, the structure of biological networks is not different from that of other complex systems, such as social networks, the world-wide web or power grids, for which growth models have been proposed to better understand their structure and function. This means that we can design tools based on these models in order to exploit the topology of biological interactomes with the aim to construct more complete and reliable maps of the cell. In this work, we propose three novel and powerful approaches for the prediction of interactions in biological networks and conclude that it is possible to mine the topology of these complex system representations and produce reliable and biologically meaningful information that enriches the datasets to which we have access today.

  2. Characterization and interactome study of white spot syndrome virus envelope protein VP11.

    Directory of Open Access Journals (Sweden)

    Wang-Jing Liu

    Full Text Available White spot syndrome virus (WSSV is a large enveloped virus. The WSSV viral particle consists of three structural layers that surround its core DNA: an outer envelope, a tegument and a nucleocapsid. Here we characterize the WSSV structural protein VP11 (WSSV394, GenBank accession number AF440570, and use an interactome approach to analyze the possible associations between this protein and an array of other WSSV and host proteins. Temporal transcription analysis showed that vp11 is an early gene. Western blot hybridization of the intact viral particles and fractionation of the viral components, and immunoelectron microscopy showed that VP11 is an envelope protein. Membrane topology software predicted VP11 to be a type of transmembrane protein with a highly hydrophobic transmembrane domain at its N-terminal. Based on an immunofluorescence assay performed on VP11-transfected Sf9 cells and a trypsin digestion analysis of the virion, we conclude that, contrary to topology software prediction, the C-terminal of this protein is in fact inside the virion. Yeast two-hybrid screening combined with co-immunoprecipitation assays found that VP11 directly interacted with at least 12 other WSSV structural proteins as well as itself. An oligomerization assay further showed that VP11 could form dimers. VP11 is also the first reported WSSV structural protein to interact with the major nucleocapsid protein VP664.

  3. Making connections for life: an in vivo map of the yeast interactome.

    Science.gov (United States)

    Kast, Juergen

    2008-10-01

    Proteins are the true workhorses of any cell. To carry out specific tasks, they frequently bind other molecules in their surroundings. Due to their structural complexity and flexibility, the most diverse array of interactions is seen with other proteins. The different geometries and affinities available for such interactions typically bestow specific functions on proteins. Having available a map of protein-protein interactions is therefore of enormous importance for any researcher interested in gaining insight into biological systems at the level of cells and organisms. In a recent report, a novel approach has been employed that relies on the spontaneous folding of complementary enzyme fragments fused to two different proteins to test whether these interact in their actual cellular context [Tarassov et al., Science 320, 1465-1470 (2008)]. Genome-wide application of this protein-fragment complementation assay has resulted in the first map of the in vivo interactome of Saccharomyces cerevisiae. The current data show striking similarities but also significant differences to those obtained using other large-scale approaches for the same task. This warrants a general discussion of the current state of affairs of protein-protein interaction studies and foreseeable future trends, highlighting their significance for a variety of applications and their potential to revolutionize our understanding of the architecture and dynamics of biological systems.

  4. Interactomes to Biological Phase Space: a call to begin thinking at a new level in computational biology.

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, George S.; Brown, William Michael

    2007-09-01

    Techniques for high throughput determinations of interactomes, together with high resolution protein collocalizations maps within organelles and through membranes will soon create a vast resource. With these data, biological descriptions, akin to the high dimensional phase spaces familiar to physicists, will become possible. These descriptions will capture sufficient information to make possible realistic, system-level models of cells. The descriptions and the computational models they enable will require powerful computing techniques. This report is offered as a call to the computational biology community to begin thinking at this scale and as a challenge to develop the required algorithms and codes to make use of the new data.3

  5. IIS--Integrated Interactome System: a web-based platform for the annotation, analysis and visualization of protein-metabolite-gene-drug interactions by integrating a variety of data sources and tools.

    Science.gov (United States)

    Carazzolle, Marcelo Falsarella; de Carvalho, Lucas Miguel; Slepicka, Hugo Henrique; Vidal, Ramon Oliveira; Pereira, Gonçalo Amarante Guimarães; Kobarg, Jörg; Meirelles, Gabriela Vaz

    2014-01-01

    High-throughput screening of physical, genetic and chemical-genetic interactions brings important perspectives in the Systems Biology field, as the analysis of these interactions provides new insights into protein/gene function, cellular metabolic variations and the validation of therapeutic targets and drug design. However, such analysis depends on a pipeline connecting different tools that can automatically integrate data from diverse sources and result in a more comprehensive dataset that can be properly interpreted. We describe here the Integrated Interactome System (IIS), an integrative platform with a web-based interface for the annotation, analysis and visualization of the interaction profiles of proteins/genes, metabolites and drugs of interest. IIS works in four connected modules: (i) Submission module, which receives raw data derived from Sanger sequencing (e.g. two-hybrid system); (ii) Search module, which enables the user to search for the processed reads to be assembled into contigs/singlets, or for lists of proteins/genes, metabolites and drugs of interest, and add them to the project; (iii) Annotation module, which assigns annotations from several databases for the contigs/singlets or lists of proteins/genes, generating tables with automatic annotation that can be manually curated; and (iv) Interactome module, which maps the contigs/singlets or the uploaded lists to entries in our integrated database, building networks that gather novel identified interactions, protein and metabolite expression/concentration levels, subcellular localization and computed topological metrics, GO biological processes and KEGG pathways enrichment. This module generates a XGMML file that can be imported into Cytoscape or be visualized directly on the web. We have developed IIS by the integration of diverse databases following the need of appropriate tools for a systematic analysis of physical, genetic and chemical-genetic interactions. IIS was validated with yeast two

  6. Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants

    Science.gov (United States)

    Juran, Brian D.; Hirschfield, Gideon M.; Invernizzi, Pietro; Atkinson, Elizabeth J.; Li, Yafang; Xie, Gang; Kosoy, Roman; Ransom, Michael; Sun, Ye; Bianchi, Ilaria; Schlicht, Erik M.; Lleo, Ana; Coltescu, Catalina; Bernuzzi, Francesca; Podda, Mauro; Lammert, Craig; Shigeta, Russell; Chan, Landon L.; Balschun, Tobias; Marconi, Maurizio; Cusi, Daniele; Heathcote, E. Jenny; Mason, Andrew L.; Myers, Robert P.; Milkiewicz, Piotr; Odin, Joseph A.; Luketic, Velimir A.; Bacon, Bruce R.; Bodenheimer, Henry C.; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Franke, Andre; Gregersen, Peter K.; Bossa, Fabrizio; Gershwin, M. Eric; deAndrade, Mariza; Amos, Christopher I.; Lazaridis, Konstantinos N.; Seldin, Michael F.; Siminovitch, Katherine A.

    2012-01-01

    To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies. PMID:22936693

  7. Evidence That a Psychopathology Interactome Has Diagnostic Value, Predicting Clinical Needs: An Experience Sampling Study

    Science.gov (United States)

    van Os, Jim; Lataster, Tineke; Delespaul, Philippe; Wichers, Marieke; Myin-Germeys, Inez

    2014-01-01

    measures of psychopathology, similarly moderated by momentary interactions with emotions and context. Conclusion The results suggest that psychopathology, represented as an interactome at the momentary level of temporal resolution, is informative in diagnosing clinical needs, over and above traditional symptom measures. PMID:24466189

  8. Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

    Directory of Open Access Journals (Sweden)

    C. J. Carter

    2013-01-01

    Full Text Available Toxoplasma gondii is not only implicated in schizophrenia and related disorders, but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's disease, schizophrenia, bipolar disorder, depression, childhood obesity, Parkinson's disease, attention deficit hyperactivity disorder (multiple sclerosis, and autism (, but not anorexia or chronic fatigue are highly enriched in the human arm of this interactome and 18 (ADHD to 33% (MS of the susceptibility genes relate to it. The signalling pathways involved in the susceptibility gene/interactome overlaps are relatively specific and relevant to each disease suggesting a means whereby susceptibility genes could orient the attentions of a single pathogen towards disruption of the specific pathways that together contribute (positively or negatively to the endophenotypes of different diseases. Conditional protein knockdown, orchestrated by T. gondii proteins or antibodies binding to those of the host (pathogen derived autoimmunity and metabolite exchange, may contribute to this disruption. Susceptibility genes may thus be related to the causes and influencers of disease, rather than (and as well as to the disease itself.

  9. Analysis of the robustness of network-based disease-gene prioritization methods reveals redundancy in the human interactome and functional diversity of disease-genes.

    Directory of Open Access Journals (Sweden)

    Emre Guney

    Full Text Available Complex biological systems usually pose a trade-off between robustness and fragility where a small number of perturbations can substantially disrupt the system. Although biological systems are robust against changes in many external and internal conditions, even a single mutation can perturb the system substantially, giving rise to a pathophenotype. Recent advances in identifying and analyzing the sequential variations beneath human disorders help to comprehend a systemic view of the mechanisms underlying various disease phenotypes. Network-based disease-gene prioritization methods rank the relevance of genes in a disease under the hypothesis that genes whose proteins interact with each other tend to exhibit similar phenotypes. In this study, we have tested the robustness of several network-based disease-gene prioritization methods with respect to the perturbations of the system using various disease phenotypes from the Online Mendelian Inheritance in Man database. These perturbations have been introduced either in the protein-protein interaction network or in the set of known disease-gene associations. As the network-based disease-gene prioritization methods are based on the connectivity between known disease-gene associations, we have further used these methods to categorize the pathophenotypes with respect to the recoverability of hidden disease-genes. Our results have suggested that, in general, disease-genes are connected through multiple paths in the human interactome. Moreover, even when these paths are disturbed, network-based prioritization can reveal hidden disease-gene associations in some pathophenotypes such as breast cancer, cardiomyopathy, diabetes, leukemia, parkinson disease and obesity to a greater extend compared to the rest of the pathophenotypes tested in this study. Gene Ontology (GO analysis highlighted the role of functional diversity for such diseases.

  10. sCLIP-an integrated platform to study RNA-protein interactomes in biomedical research: identification of CSTF2tau in alternative processing of small nuclear RNAs.

    Science.gov (United States)

    Kargapolova, Yulia; Levin, Michal; Lackner, Karl; Danckwardt, Sven

    2017-06-02

    RNA-binding proteins (RBPs) are central for gene expression by controlling the RNA fate from birth to decay. Various disorders arising from perturbations of RNA-protein interactions document their critical function. However, deciphering their function is complex, limiting the general functional elucidation of this growing class of proteins and their contribution to (patho)physiology. Here, we present sCLIP, a simplified and robust platform for genome-wide interrogation of RNA-protein interactomes based on crosslinking-immunoprecipitation and high-throughput sequencing. sCLIP exploits linear amplification of the immunoprecipitated RNA improving the complexity of the sequencing-library despite significantly reducing the amount of input material and omitting several purification steps. Additionally, it permits a radiolabel-free visualization of immunoprecipitated RNA. In a proof of concept, we identify that CSTF2tau binds many previously not recognized RNAs including histone, snoRNA and snRNAs. CSTF2tau-binding is associated with internal oligoadenylation resulting in shortened snRNA isoforms subjected to rapid degradation. We provide evidence for a new mechanism whereby CSTF2tau controls the abundance of snRNAs resulting in alternative splicing of several RNAs including ANK2 with critical roles in tumorigenesis and cardiac function. Combined with a bioinformatic pipeline sCLIP thus uncovers new functions for established RBPs and fosters the illumination of RBP-protein interaction landscapes in health and disease. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Characterization of protein interactomes of DNA damages: application to oxidation injuries

    International Nuclear Information System (INIS)

    Pietras-Barbier, Ewa

    2013-01-01

    Cyclo-nucleosides are complex DNA damages implying both bases and sugar residues. They are generated by free radicals, in particular by the effect of ionizing radiations, and are not easily covered by cellular mechanisms. Using a protein trapping technique on probes containing these injuries, the negative influence of cyclo-nucleosides on the recognition of its target sequence by a DREF transcription factor and on the interactions of PARP1 with DNA have been identified. Interactions between Fpg bacterial glycosylase and cyclo-nucleosides have been analysed and it has been found that this enzyme has an affinity for them, without excision activity. Finally, a Thermococcus gammatolerans radiation resistant archae has been studied: the formation of simple and complex oxidation injuries at strong radiation doses has been measured and the action mechanism of two new glycosylases has been explained. (author) [fr

  12. Systematic differences in signal emitting and receiving revealed by PageRank analysis of a human protein interactome.

    Directory of Open Access Journals (Sweden)

    Donglei Du

    Full Text Available Most protein PageRank studies do not use signal flow direction information in protein interactions because this information was not readily available in large protein databases until recently. Therefore, four questions have yet to be answered: A What is the general difference between signal emitting and receiving in a protein interactome? B Which proteins are among the top ranked in directional ranking? C Are high ranked proteins more evolutionarily conserved than low ranked ones? D Do proteins with similar ranking tend to have similar subcellular locations? In this study, we address these questions using the forward, reverse, and non-directional PageRank approaches to rank an information-directional network of human proteins and study their evolutionary conservation. The forward ranking gives credit to information receivers, reverse ranking to information emitters, and non-directional ranking mainly to the number of interactions. The protein lists generated by the forward and non-directional rankings are highly correlated, but those by the reverse and non-directional rankings are not. The results suggest that the signal emitting/receiving system is characterized by key-emittings and relatively even receivings in the human protein interactome. Signaling pathway proteins are frequent in top ranked ones. Eight proteins are both informational top emitters and top receivers. Top ranked proteins, except a few species-related novel-function ones, are evolutionarily well conserved. Protein-subunit ranking position reflects subunit function. These results demonstrate the usefulness of different PageRank approaches in characterizing protein networks and provide insights to protein interaction in the cell.

  13. Systematic differences in signal emitting and receiving revealed by PageRank analysis of a human protein interactome.

    Science.gov (United States)

    Du, Donglei; Lee, Connie F; Li, Xiu-Qing

    2012-01-01

    Most protein PageRank studies do not use signal flow direction information in protein interactions because this information was not readily available in large protein databases until recently. Therefore, four questions have yet to be answered: A) What is the general difference between signal emitting and receiving in a protein interactome? B) Which proteins are among the top ranked in directional ranking? C) Are high ranked proteins more evolutionarily conserved than low ranked ones? D) Do proteins with similar ranking tend to have similar subcellular locations? In this study, we address these questions using the forward, reverse, and non-directional PageRank approaches to rank an information-directional network of human proteins and study their evolutionary conservation. The forward ranking gives credit to information receivers, reverse ranking to information emitters, and non-directional ranking mainly to the number of interactions. The protein lists generated by the forward and non-directional rankings are highly correlated, but those by the reverse and non-directional rankings are not. The results suggest that the signal emitting/receiving system is characterized by key-emittings and relatively even receivings in the human protein interactome. Signaling pathway proteins are frequent in top ranked ones. Eight proteins are both informational top emitters and top receivers. Top ranked proteins, except a few species-related novel-function ones, are evolutionarily well conserved. Protein-subunit ranking position reflects subunit function. These results demonstrate the usefulness of different PageRank approaches in characterizing protein networks and provide insights to protein interaction in the cell.

  14. Interactome analysis of transcriptional coactivator multiprotein bridging factor 1 unveils a yeast AP-1-like transcription factor involved in oxidation tolerance of mycopathogen Beauveria bassiana.

    Science.gov (United States)

    Chu, Xin-Ling; Dong, Wei-Xia; Ding, Jin-Li; Feng, Ming-Guang; Ying, Sheng-Hua

    2018-02-01

    Oxidation tolerance is an important determinant to predict the virulence and biocontrol potential of Beauveria bassiana, a well-known entomopathogenic fungus. As a transcriptional coactivator, multiprotein bridging factor 1 mediates the activity of transcription factor in diverse physiological processes, and its homolog in B. bassiana (BbMBF1) contributes to fungal oxidation tolerance. In this study, the BbMBF1-interactomes under oxidative stress and normal growth condition were deciphered by mass spectrometry integrated with the immunoprecipitation. BbMBF1p factor has a broad interaction with proteins that are involved in various cellular processes, and this interaction is dynamically regulated by oxidative stress. Importantly, a B. bassiana homolog of yeast AP-1-like transcription factor (BbAP-1) was specifically associated with the BbMBF1-interactome under oxidation and significantly contributed to fungal oxidation tolerance. In addition, qPCR analysis revealed that several antioxidant genes are jointly controlled by BbAP-1 and BbMBF1. Conclusively, it is proposed that BbMBF1p protein mediates BbAP-1p factor to transcribe the downstream antioxidant genes in B. bassiana under oxidative stress. This study demonstrates for the first time a proteomic view of the MBF1-interactome in fungi, and presents an initial framework to probe the transcriptional mechanism involved in fungal response to oxidation, which will provide a new strategy to improve the biocontrol efficacy of B. bassiana.

  15. Analysis of the Protein Kinase A-Regulated Proteome of Cryptococcus neoformans Identifies a Role for the Ubiquitin-Proteasome Pathway in Capsule Formation

    Directory of Open Access Journals (Sweden)

    J. M. H. Geddes

    2016-01-01

    Full Text Available The opportunistic fungal pathogen Cryptococcus neoformans causes life-threatening meningitis in immunocompromised individuals. The expression of virulence factors, including capsule and melanin, is in part regulated by the cyclic-AMP/protein kinase A (cAMP/PKA signal transduction pathway. In this study, we investigated the influence of PKA on the composition of the intracellular proteome to obtain a comprehensive understanding of the regulation that underpins virulence. Through quantitative proteomics, enrichment and bioinformatic analyses, and an interactome study, we uncovered a pattern of PKA regulation for proteins associated with translation, the proteasome, metabolism, amino acid biosynthesis, and virulence-related functions. PKA regulation of the ubiquitin-proteasome pathway in C. neoformans showed a striking parallel with connections between PKA and protein degradation in chronic neurodegenerative disorders and other human diseases. Further investigation of proteasome function with the inhibitor bortezomib revealed an impact on capsule production as well as hypersusceptibility for strains with altered expression or activity of PKA. Parallel studies with tunicamycin also linked endoplasmic reticulum stress with capsule production and PKA. Taken together, the data suggest a model whereby expression of PKA regulatory and catalytic subunits and the activation of PKA influence proteostasis and the function of the endoplasmic reticulum to control the elaboration of the polysaccharide capsule. Overall, this study revealed both broad and conserved influences of the cAMP/PKA pathway on the proteome and identified proteostasis as a potential therapeutic target for the treatment of cryptococcosis.

  16. Sequence- and interactome-based prediction of viral protein hotspots targeting host proteins: a case study for HIV Nef.

    Directory of Open Access Journals (Sweden)

    Mahdi Sarmady

    Full Text Available Virus proteins alter protein pathways of the host toward the synthesis of viral particles by breaking and making edges via binding to host proteins. In this study, we developed a computational approach to predict viral sequence hotspots for binding to host proteins based on sequences of viral and host proteins and literature-curated virus-host protein interactome data. We use a motif discovery algorithm repeatedly on collections of sequences of viral proteins and immediate binding partners of their host targets and choose only those motifs that are conserved on viral sequences and highly statistically enriched among binding partners of virus protein targeted host proteins. Our results match experimental data on binding sites of Nef to host proteins such as MAPK1, VAV1, LCK, HCK, HLA-A, CD4, FYN, and GNB2L1 with high statistical significance but is a poor predictor of Nef binding sites on highly flexible, hoop-like regions. Predicted hotspots recapture CD8 cell epitopes of HIV Nef highlighting their importance in modulating virus-host interactions. Host proteins potentially targeted or outcompeted by Nef appear crowding the T cell receptor, natural killer cell mediated cytotoxicity, and neurotrophin signaling pathways. Scanning of HIV Nef motifs on multiple alignments of hepatitis C protein NS5A produces results consistent with literature, indicating the potential value of the hotspot discovery in advancing our understanding of virus-host crosstalk.

  17. MitProNet: A knowledgebase and analysis platform of proteome, interactome and diseases for mammalian mitochondria.

    Directory of Open Access Journals (Sweden)

    Jiabin Wang

    Full Text Available Mitochondrion plays a central role in diverse biological processes in most eukaryotes, and its dysfunctions are critically involved in a large number of diseases and the aging process. A systematic identification of mitochondrial proteomes and characterization of functional linkages among mitochondrial proteins are fundamental in understanding the mechanisms underlying biological functions and human diseases associated with mitochondria. Here we present a database MitProNet which provides a comprehensive knowledgebase for mitochondrial proteome, interactome and human diseases. First an inventory of mammalian mitochondrial proteins was compiled by widely collecting proteomic datasets, and the proteins were classified by machine learning to achieve a high-confidence list of mitochondrial proteins. The current version of MitProNet covers 1124 high-confidence proteins, and the remainders were further classified as middle- or low-confidence. An organelle-specific network of functional linkages among mitochondrial proteins was then generated by integrating genomic features encoded by a wide range of datasets including genomic context, gene expression profiles, protein-protein interactions, functional similarity and metabolic pathways. The functional-linkage network should be a valuable resource for the study of biological functions of mitochondrial proteins and human mitochondrial diseases. Furthermore, we utilized the network to predict candidate genes for mitochondrial diseases using prioritization algorithms. All proteins, functional linkages and disease candidate genes in MitProNet were annotated according to the information collected from their original sources including GO, GEO, OMIM, KEGG, MIPS, HPRD and so on. MitProNet features a user-friendly graphic visualization interface to present functional analysis of linkage networks. As an up-to-date database and analysis platform, MitProNet should be particularly helpful in comprehensive studies of

  18. Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis.

    Directory of Open Access Journals (Sweden)

    Feixiong Cheng

    2016-09-01

    Full Text Available Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase. Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline that may be potential for antiviral indication (e.g. anti-Ebola. In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics.

  19. Proton NMR-based metabolite analyses of archived serial paired serum and urine samples from myeloma patients at different stages of disease activity identifies acetylcarnitine as a novel marker of active disease.

    Directory of Open Access Journals (Sweden)

    Alessia Lodi

    Full Text Available BACKGROUND: Biomarker identification is becoming increasingly important for the development of personalized or stratified therapies. Metabolomics yields biomarkers indicative of phenotype that can be used to characterize transitions between health and disease, disease progression and therapeutic responses. The desire to reproducibly detect ever greater numbers of metabolites at ever diminishing levels has naturally nurtured advances in best practice for sample procurement, storage and analysis. Reciprocally, since many of the available extensive clinical archives were established prior to the metabolomics era and were not processed in such an 'ideal' fashion, considerable scepticism has arisen as to their value for metabolomic analysis. Here we have challenged that paradigm. METHODS: We performed proton nuclear magnetic resonance spectroscopy-based metabolomics on blood serum and urine samples from 32 patients representative of a total cohort of 1970 multiple myeloma patients entered into the United Kingdom Medical Research Council Myeloma IX trial. FINDINGS: Using serial paired blood and urine samples we detected metabolite profiles that associated with diagnosis, post-treatment remission and disease progression. These studies identified carnitine and acetylcarnitine as novel potential biomarkers of active disease both at diagnosis and relapse and as a mediator of disease associated pathologies. CONCLUSIONS: These findings show that samples conventionally processed and archived can provide useful metabolomic information that has important implications for understanding the biology of myeloma, discovering new therapies and identifying biomarkers potentially useful in deciding the choice and application of therapy.

  20. Vitiligo blood transcriptomics provides new insights into disease mechanisms and identifies potential novel therapeutic targets.

    Science.gov (United States)

    Dey-Rao, Rama; Sinha, Animesh A

    2017-01-28

    Significant gaps remain regarding the pathomechanisms underlying the autoimmune response in vitiligo (VL), where the loss of self-tolerance leads to the targeted killing of melanocytes. Specifically, there is incomplete information regarding alterations in the systemic environment that are relevant to the disease state. We undertook a genome-wide profiling approach to examine gene expression in the peripheral blood of VL patients and healthy controls in the context of our previously published VL-skin gene expression profile. We used several in silico bioinformatics-based analyses to provide new insights into disease mechanisms and suggest novel targets for future therapy. Unsupervised clustering methods of the VL-blood dataset demonstrate a "disease-state"-specific set of co-expressed genes. Ontology enrichment analysis of 99 differentially expressed genes (DEGs) uncovers a down-regulated immune/inflammatory response, B-Cell antigen receptor (BCR) pathways, apoptosis and catabolic processes in VL-blood. There is evidence for both type I and II interferon (IFN) playing a role in VL pathogenesis. We used interactome analysis to identify several key blood associated transcriptional factors (TFs) from within (STAT1, STAT6 and NF-kB), as well as "hidden" (CREB1, MYC, IRF4, IRF1, and TP53) from the dataset that potentially affect disease pathogenesis. The TFs overlap with our reported lesional-skin transcriptional circuitry, underscoring their potential importance to the disease. We also identify a shared VL-blood and -skin transcriptional "hot spot" that maps to chromosome 6, and includes three VL-blood dysregulated genes (PSMB8, PSMB9 and TAP1) described as potential VL-associated genetic susceptibility loci. Finally, we provide bioinformatics-based support for prioritizing dysregulated genes in VL-blood or skin as potential therapeutic targets. We examined the VL-blood transcriptome in context with our (previously published) VL-skin transcriptional profile to address

  1. A human phenome-interactome network of protein complexes implicated in genetic disorders

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Karlberg, Erik, Olof, Linnart; Størling, Zenia, Marian

    2007-01-01

    the known disease-causing protein as the top candidate, and in 870 intervals with no identified disease-causing gene, provides novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type...

  2. Laser Beam Focus Analyser

    DEFF Research Database (Denmark)

    Nielsen, Peter Carøe; Hansen, Hans Nørgaard; Olsen, Flemming Ove

    2007-01-01

    the obtainable features in direct laser machining as well as heat affected zones in welding processes. This paper describes the development of a measuring unit capable of analysing beam shape and diameter of lasers to be used in manufacturing processes. The analyser is based on the principle of a rotating......The quantitative and qualitative description of laser beam characteristics is important for process implementation and optimisation. In particular, a need for quantitative characterisation of beam diameter was identified when using fibre lasers for micro manufacturing. Here the beam diameter limits...... mechanical wire being swept through the laser beam at varying Z-heights. The reflected signal is analysed and the resulting beam profile determined. The development comprised the design of a flexible fixture capable of providing both rotation and Z-axis movement, control software including data capture...

  3. Identifying carbon sources and trophic position of coral reef fishes using diet and stable isotope (δ15N and δ13C) analyses in two contrasted bays in Moorea, French Polynesia

    Science.gov (United States)

    Letourneur, Y.; Lison de Loma, T.; Richard, P.; Harmelin-Vivien, M. L.; Cresson, P.; Banaru, D.; Fontaine, M.-F.; Gref, T.; Planes, S.

    2013-12-01

    Stable isotope ratios (δ15N and δ13C) and diet of three fish species, Stegastes nigricans, Chaetodon citrinellus and Epinephelus merra, were analyzed on the fringing coral reefs of two bays that are differentially exposed to river runoff on Moorea Island, French Polynesia. S. nigricans and C. citrinellus relied mostly on turf algae and presented similar trophic levels and δ15N values, whereas E. merra fed on large invertebrates (crabs and shrimps) and had higher trophic levels and δ15N values. Discrepancies existed between stomach content and stable isotope analyses for the relative importance of food items. Bayesian mixing models indicated that sedimented organic matter was also an important additional food for S. nigricans and C. citrinellus, and fishes for E. merra. The main sources of organic matter involved in the food webs ending with these species were algal turfs and surface sediments, while water particulate organic matter was barely used. Significant spatial differences in C and N isotopic ratios for sources and fishes were found within and between bays. Lower 13C and higher 15N values were observed for various compartments of the studied trophic network at the end of each bay than at the entrance. Differences were observed between bays, with organic sources and consumers being, on average, slightly more 13C-depleted and 15N-enriched in Cook's Bay than in Opunohu Bay, linked with a higher mean annual flow of the river at Cook's Bay. Our results suggest that rivers bring continental material into these two bays, which is partly incorporated into the food webs of fringing coral reefs at least close to river mouths. Thus, continental inputs can influence the transfer of organic matter within coral reef food webs depending on the diet of organisms.

  4. Heterozygous deletion at the RLN1 locus in a family with testicular germ cell cancer identified by integrating copy number variation data with phenome and interactome information

    DEFF Research Database (Denmark)

    Edsgärd, D; Scheel, M; Hansen, N T

    2011-01-01

    -associated genes among loci targeted by CNVs. The top-ranked candidate, RLN1, encoding a Relaxin-H1 peptide, although only detected in one of the families, was selected for further investigations. Validation of the CNV at the RLN1 locus was performed as an association study using qPCR with 106 sporadic testicular...... GCT patients and 200 healthy controls. Observed CNV frequencies of 1.9% among cases and 1.5% amongst controls were not significantly different and this was further confirmed by CNV data extracted from a genome-wide analysis of 189 cases and 380 controls, where similar frequencies of 2.2% were observed....... Collectively, the findings show that a heterozygous loss at the RLN1 locus is not a genetic factor mediating high population-wide risk for testicular germ cell tumour, but do not exclude a contribution of this aberration in some cases of cancer. The preliminary expression data suggest a possible role...

  5. Heterozygous deletion at the RLN1 locus in a family with testicular germ cell cancer identified by integrating copy number variation data with phenome and interactome information

    DEFF Research Database (Denmark)

    Edsgard, Stefan Daniel; Scheel, M.; Hansen, Niclas Tue

    2011-01-01

    ‐associated genes among loci targeted by CNVs. The top‐ranked candidate, RLN1, encoding a Relaxin‐H1 peptide, although only detected in one of the families, was selected for further investigations. Validation of the CNV at the RLN1 locus was performed as an association study using qPCR with 106 sporadic testicular...... GCT patients and 200 healthy controls. Observed CNV frequencies of 1.9% among cases and 1.5% amongst controls were not significantly different and this was further confirmed by CNV data extracted from a genome‐wide analysis of 189 cases and 380 controls, where similar frequencies of 2.2% were observed...... and spermatids. Collectively, the findings show that a heterozygous loss at the RLN1 locus is not a genetic factor mediating high population‐wide risk for testicular germ cell tumour, but do not exclude a contribution of this aberration in some cases of cancer. The preliminary expression data suggest a possible...

  6. New Targets for Zika Virus Determined by Human-Viral Interactomic: A Bioinformatics Approach

    Directory of Open Access Journals (Sweden)

    Eduardo Esteves

    2017-01-01

    Full Text Available Identifying ZIKV factors interfering with human host pathways represents a major challenge in understanding ZIKV tropism and pathogenesis. The integration of proteomic, gene expression and Protein-Protein Interactions (PPIs established between ZIKV and human host proteins predicted by the OralInt algorithm identified 1898 interactions with medium or high score (≥0.7. Targets implicated in vesicular traffic and docking were identified. New receptors involved in endocytosis pathways as ZIKV entry targets, using both clathrin-dependent (17 receptors and independent (10 receptors pathways, are described. New targets used by the ZIKV to undermine the host’s antiviral immune response are proposed based on predicted interactions established between the virus and host cell receptors and/or proteins with an effector or signaling role in the immune response such as IFN receptors and TLR. Complement and cytokines are proposed as extracellular potential interacting partners of the secreted form of NS1 ZIKV protein. Altogether, in this article, 18 new human targets for structural and nonstructural ZIKV proteins are proposed. These results are of great relevance for the understanding of viral pathogenesis and consequently the development of preventive (vaccines and therapeutic targets for ZIKV infection management.

  7. Proteomic-coupled-network analysis of T877A-androgen receptor interactomes can predict clinical prostate cancer outcomes between White (non-Hispanic and African-American groups.

    Directory of Open Access Journals (Sweden)

    Naif Zaman

    Full Text Available The androgen receptor (AR remains an important contributor to the neoplastic evolution of prostate cancer (CaP. CaP progression is linked to several somatic AR mutational changes that endow upon the AR dramatic gain-of-function properties. One of the most common somatic mutations identified is Thr877-to-Ala (T877A, located in the ligand-binding domain, that results in a receptor capable of promiscuous binding and activation by a variety of steroid hormones and ligands including estrogens, progestins, glucocorticoids, and several anti-androgens. In an attempt to further define somatic mutated AR gain-of-function properties, as a consequence of its promiscuous ligand binding, we undertook a proteomic/network analysis approach to characterize the protein interactome of the mutant T877A-AR in LNCaP cells under eight different ligand-specific treatments (dihydrotestosterone, mibolerone, R1881, testosterone, estradiol, progesterone, dexamethasone, and cyproterone acetate. In extending the analysis of our multi-ligand complexes of the mutant T877A-AR we observed significant enrichment of specific complexes between normal and primary prostatic tumors, which were furthermore correlated with known clinical outcomes. Further analysis of certain mutant T877A-AR complexes showed specific population preferences distinguishing primary prostatic disease between white (non-Hispanic vs. African-American males. Moreover, these cancer-related AR-protein complexes demonstrated predictive survival outcomes specific to CaP, and not for breast, lung, lymphoma or medulloblastoma cancers. Our study, by coupling data generated by our proteomics to network analysis of clinical samples, has helped to define real and novel biological pathways in complicated gain-of-function AR complex systems.

  8. Designing Dietary Recommendations Using System Level Interactomics Analysis and Network-Based Inference

    Directory of Open Access Journals (Sweden)

    Tingting Zheng

    2017-09-01

    Full Text Available Background: A range of computational methods that rely on the analysis of genome-wide expression datasets have been developed and successfully used for drug repositioning. The success of these methods is based on the hypothesis that introducing a factor (in this case, a drug molecule that could reverse the disease gene expression signature will lead to a therapeutic effect. However, it has also been shown that globally reversing the disease expression signature is not a prerequisite for drug activity. On the other hand, the basic idea of significant anti-correlation in expression profiles could have great value for establishing diet-disease associations and could provide new insights into the role of dietary interventions in disease.Methods: We performed an integrated analysis of publicly available gene expression profiles for foods, diseases and drugs, by calculating pairwise similarity scores for diet and disease gene expression signatures and characterizing their topological features in protein-protein interaction networks.Results: We identified 485 diet-disease pairs where diet could positively influence disease development and 472 pairs where specific diets should be avoided in a disease state. Multiple evidence suggests that orange, whey and coconut fat could be beneficial for psoriasis, lung adenocarcinoma and macular degeneration, respectively. On the other hand, fructose-rich diet should be restricted in patients with chronic intermittent hypoxia and ovarian cancer. Since humans normally do not consume foods in isolation, we also applied different algorithms to predict synergism; as a result, 58 food pairs were predicted. Interestingly, the diets identified as anti-correlated with diseases showed a topological proximity to the disease proteins similar to that of the corresponding drugs.Conclusions: In conclusion, we provide a computational framework for establishing diet-disease associations and additional information on the role of

  9. Conserved salt-bridge competition triggered by phosphorylation regulates the protein interactome

    KAUST Repository

    Skinner, John J.

    2017-12-05

    Phosphorylation is a major regulator of protein interactions; however, the mechanisms by which regulation occurs are not well understood. Here we identify a salt-bridge competition or “theft” mechanism that enables a phospho-triggered swap of protein partners by Raf Kinase Inhibitory Protein (RKIP). RKIP transitions from inhibiting Raf-1 to inhibiting G-protein–coupled receptor kinase 2 upon phosphorylation, thereby bridging MAP kinase and G-Protein–Coupled Receptor signaling. NMR and crystallography indicate that a phosphoserine, but not a phosphomimetic, competes for a lysine from a preexisting salt bridge, initiating a partial unfolding event and promoting new protein interactions. Structural elements underlying the theft occurred early in evolution and are found in 10% of homo-oligomers and 30% of hetero-oligomers including Bax, Troponin C, and Early Endosome Antigen 1. In contrast to a direct recognition of phosphorylated residues by binding partners, the salt-bridge theft mechanism represents a facile strategy for promoting or disrupting protein interactions using solvent-accessible residues, and it can provide additional specificity at protein interfaces through local unfolding or conformational change.

  10. A high-resolution map of the three-dimensional chromatin interactome in human cells.

    Science.gov (United States)

    Jin, Fulai; Li, Yan; Dixon, Jesse R; Selvaraj, Siddarth; Ye, Zhen; Lee, Ah Young; Yen, Chia-An; Schmitt, Anthony D; Espinoza, Celso A; Ren, Bing

    2013-11-14

    A large number of cis-regulatory sequences have been annotated in the human genome, but defining their target genes remains a challenge. One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C)-based techniques. However, previous studies lack either the resolution or coverage to permit a whole-genome, unbiased view of chromatin interactions. Here we report a comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C). We determined over one million long-range chromatin interactions at 5-10-kb resolution, and uncovered general principles of chromatin organization at different types of genomic features. We also characterized the dynamics of promoter-enhancer contacts after TNF-α signalling in these cells. Unexpectedly, we found that TNF-α-responsive enhancers are already in contact with their target promoters before signalling. Such pre-existing chromatin looping, which also exists in other cell types with different extracellular signalling, is a strong predictor of gene induction. Our observations suggest that the three-dimensional chromatin landscape, once established in a particular cell type, is relatively stable and could influence the selection or activation of target genes by a ubiquitous transcription activator in a cell-specific manner.

  11. Conserved salt-bridge competition triggered by phosphorylation regulates the protein interactome

    KAUST Repository

    Skinner, John J.; Wang, Sheng; Lee, Jiyoung; Ong, Colin; Sommese, Ruth; Sivaramakrishnan, Sivaraj; Koelmel, Wolfgang; Hirschbeck, Maria; Schindelin, Hermann; Kisker, Caroline; Lorenz, Kristina; Sosnick, Tobin R.; Rosner, Marsha Rich

    2017-01-01

    Phosphorylation is a major regulator of protein interactions; however, the mechanisms by which regulation occurs are not well understood. Here we identify a salt-bridge competition or “theft” mechanism that enables a phospho-triggered swap of protein partners by Raf Kinase Inhibitory Protein (RKIP). RKIP transitions from inhibiting Raf-1 to inhibiting G-protein–coupled receptor kinase 2 upon phosphorylation, thereby bridging MAP kinase and G-Protein–Coupled Receptor signaling. NMR and crystallography indicate that a phosphoserine, but not a phosphomimetic, competes for a lysine from a preexisting salt bridge, initiating a partial unfolding event and promoting new protein interactions. Structural elements underlying the theft occurred early in evolution and are found in 10% of homo-oligomers and 30% of hetero-oligomers including Bax, Troponin C, and Early Endosome Antigen 1. In contrast to a direct recognition of phosphorylated residues by binding partners, the salt-bridge theft mechanism represents a facile strategy for promoting or disrupting protein interactions using solvent-accessible residues, and it can provide additional specificity at protein interfaces through local unfolding or conformational change.

  12. The comprehensive native interactome of a fully functional tagged prion protein.

    Directory of Open Access Journals (Sweden)

    Dorothea Rutishauser

    Full Text Available The enumeration of the interaction partners of the cellular prion protein, PrP(C, may help clarifying its elusive molecular function. Here we added a carboxy proximal myc epitope tag to PrP(C. When expressed in transgenic mice, PrP(myc carried a GPI anchor, was targeted to lipid rafts, and was glycosylated similarly to PrP(C. PrP(myc antagonized the toxicity of truncated PrP, restored prion infectibility of PrP(C-deficient mice, and was physically incorporated into PrP(Sc aggregates, indicating that it possessed all functional characteristics of genuine PrP(C. We then immunopurified myc epitope-containing protein complexes from PrP(myc transgenic mouse brains. Gentle differential elution with epitope-mimetic decapeptides, or a scrambled version thereof, yielded 96 specifically released proteins. Quantitative mass spectrometry with isotope-coded tags identified seven proteins which co-eluted equimolarly with PrP(C and may represent component of a multiprotein complex. Selected PrP(C interactors were validated using independent methods. Several of these proteins appear to exert functions in axomyelinic maintenance.

  13. Bayesian modeling of the yeast SH3 domain interactome predicts spatiotemporal dynamics of endocytosis proteins.

    Directory of Open Access Journals (Sweden)

    Raffi Tonikian

    2009-10-01

    Full Text Available SH3 domains are peptide recognition modules that mediate the assembly of diverse biological complexes. We scanned billions of phage-displayed peptides to map the binding specificities of the SH3 domain family in the budding yeast, Saccharomyces cerevisiae. Although most of the SH3 domains fall into the canonical classes I and II, each domain utilizes distinct features of its cognate ligands to achieve binding selectivity. Furthermore, we uncovered several SH3 domains with specificity profiles that clearly deviate from the two canonical classes. In conjunction with phage display, we used yeast two-hybrid and peptide array screening to independently identify SH3 domain binding partners. The results from the three complementary techniques were integrated using a Bayesian algorithm to generate a high-confidence yeast SH3 domain interaction map. The interaction map was enriched for proteins involved in endocytosis, revealing a set of SH3-mediated interactions that underlie formation of protein complexes essential to this biological pathway. We used the SH3 domain interaction network to predict the dynamic localization of several previously uncharacterized endocytic proteins, and our analysis suggests a novel role for the SH3 domains of Lsb3p and Lsb4p as hubs that recruit and assemble several endocytic complexes.

  14. Angiogenesis interactome and time course microarray data reveal the distinct activation patterns in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Liang-Hui Chu

    Full Text Available Angiogenesis involves stimulation of endothelial cells (EC by various cytokines and growth factors, but the signaling mechanisms are not completely understood. Combining dynamic gene expression time-course data for stimulated EC with protein-protein interactions associated with angiogenesis (the "angiome" could reveal how different stimuli result in different patterns of network activation and could implicate signaling intermediates as points for control or intervention. We constructed the protein-protein interaction networks of positive and negative regulation of angiogenesis comprising 367 and 245 proteins, respectively. We used five published gene expression datasets derived from in vitro assays using different types of blood endothelial cells stimulated by VEGFA (vascular endothelial growth factor A. We used the Short Time-series Expression Miner (STEM to identify significant temporal gene expression profiles. The statistically significant patterns between 2D fibronectin and 3D type I collagen substrates for telomerase-immortalized EC (TIME show that different substrates could influence the temporal gene activation patterns in the same cell line. We investigated the different activation patterns among 18 transmembrane tyrosine kinase receptors, and experimentally measured the protein level of the tyrosine-kinase receptors VEGFR1, VEGFR2 and VEGFR3 in human umbilical vein EC (HUVEC and human microvascular EC (MEC. The results show that VEGFR1-VEGFR2 levels are more closely coupled than VEGFR1-VEGFR3 or VEGFR2-VEGFR3 in HUVEC and MEC. This computational methodology can be extended to investigate other molecules or biological processes such as cell cycle.

  15. The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors.

    Directory of Open Access Journals (Sweden)

    Susanne Pfefferle

    2011-10-01

    Full Text Available Coronaviruses (CoVs are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS in 2002/2003 has demonstrated human vulnerability to (Coronavirus CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B as interaction partners of the CoV non-structural protein 1 (Nsp1. These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock.

  16. Fly-DPI: database of protein interactomes for D. melanogaster in the approach of systems biology

    Directory of Open Access Journals (Sweden)

    Lin Chieh-Hua

    2006-12-01

    the reliability of protein interaction. First, the hybrid model statistically estimates both experimental and predicted protein interaction relationships. Second, the biological information for filtering and annotation itself is a strong indicator for the reliability of protein-protein interaction. The space-temporal or stage-specific expression patterns of genes are also critical for identifying proteins involved in a particular situation.

  17. The Type 1 Diabetes - HLA Susceptibility Interactome - Identification of HLA Genotype-Specific Disease Genes for Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, C.; Hansen, Niclas Tue; Bergholdt, R.

    2010-01-01

    Background: The individual contribution of genes in the HLA region to the risk of developing type 1 diabetes (T1D) is confounded by the high linkage disequilibrium (LD) in this region. Using a novel approach we have combined genetic association data with information on functional protein......-protein interactions to elucidate risk independent of LD and to place the genetic association into a functional context. Methodology/Principal Findings: Genetic association data from 2300 single nucleotide polymorphisms (SNPs) in the HLA region was analysed in 2200 T1D family trios divided into six risk groups based...... on HLA-DRB1 genotypes. The best SNP signal in each gene was mapped to proteins in a human protein interaction network and their significance of clustering in functional network modules was evaluated. The significant network modules identified through this approach differed between the six HLA risk groups...

  18. EEG analyses with SOBI.

    Energy Technology Data Exchange (ETDEWEB)

    Glickman, Matthew R.; Tang, Akaysha (University of New Mexico, Albuquerque, NM)

    2009-02-01

    The motivating vision behind Sandia's MENTOR/PAL LDRD project has been that of systems which use real-time psychophysiological data to support and enhance human performance, both individually and of groups. Relevant and significant psychophysiological data being a necessary prerequisite to such systems, this LDRD has focused on identifying and refining such signals. The project has focused in particular on EEG (electroencephalogram) data as a promising candidate signal because it (potentially) provides a broad window on brain activity with relatively low cost and logistical constraints. We report here on two analyses performed on EEG data collected in this project using the SOBI (Second Order Blind Identification) algorithm to identify two independent sources of brain activity: one in the frontal lobe and one in the occipital. The first study looks at directional influences between the two components, while the second study looks at inferring gender based upon the frontal component.

  19. A systems immunology approach identifies the collective impact of 5 miRs in Th2 inflammation.

    Science.gov (United States)

    Kılıç, Ayşe; Santolini, Marc; Nakano, Taiji; Schiller, Matthias; Teranishi, Mizue; Gellert, Pascal; Ponomareva, Yuliya; Braun, Thomas; Uchida, Shizuka; Weiss, Scott T; Sharma, Amitabh; Renz, Harald

    2018-06-07

    Allergic asthma is a chronic inflammatory disease dominated by a CD4+ T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including microRNAs (miRs), are pivotal in maintaining immune homeostasis. Since an altered expression of various miRs has been associated with T cell-driven diseases, including asthma, we hypothesized that miRs control mechanisms ensuring Th2 stability and maintenance in the lung. We isolated murine CD4+ Th2 cells from allergic inflamed lungs and profiled gene and miR expression. Instead of focusing on the magnitude of miR differential expression, here we addressed the secondary consequences for the set of molecular interactions in the cell, the interactome. We developed the Impact of Differential Expression Across Layers, a network-based algorithm to prioritize disease-relevant miRs based on the central role of their targets in the molecular interactome. This method identified 5 Th2-related miRs (mir27b, mir206, mir106b, mir203, and mir23b) whose antagonization led to a sharp reduction of the Th2 phenotype. Overall, a systems biology tool was developed and validated, highlighting the role of miRs in Th2-driven immune response. This result offers potentially novel approaches for therapeutic interventions.

  20. Analysing Access Control Specifications

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, René Rydhof

    2009-01-01

    When prosecuting crimes, the main question to answer is often who had a motive and the possibility to commit the crime. When investigating cyber crimes, the question of possibility is often hard to answer, as in a networked system almost any location can be accessed from almost anywhere. The most...... common tool to answer this question, analysis of log files, faces the problem that the amount of logged data may be overwhelming. This problems gets even worse in the case of insider attacks, where the attacker’s actions usually will be logged as permissible, standard actions—if they are logged at all....... Recent events have revealed intimate knowledge of surveillance and control systems on the side of the attacker, making it often impossible to deduce the identity of an inside attacker from logged data. In this work we present an approach that analyses the access control configuration to identify the set...

  1. Identifying co-targets to fight drug resistance based on a random walk model

    Directory of Open Access Journals (Sweden)

    Chen Liang-Chun

    2012-01-01

    Full Text Available Abstract Background Drug resistance has now posed more severe and emergent threats to human health and infectious disease treatment. However, wet-lab approaches alone to counter drug resistance have so far still achieved limited success due to less knowledge about the underlying mechanisms of drug resistance. Our approach apply a heuristic search algorithm in order to extract active network under drug treatment and use a random walk model to identify potential co-targets for effective antibacterial drugs. Results We use interactome network of Mycobacterium tuberculosis and gene expression data which are treated with two kinds of antibiotic, Isoniazid and Ethionamide as our test data. Our analysis shows that the active drug-treated networks are associated with the trigger of fatty acid metabolism and synthesis and nicotinamide adenine dinucleotide (NADH-related processes and those results are consistent with the recent experimental findings. Efflux pumps processes appear to be the major mechanisms of resistance but SOS response is significantly up-regulation under Isoniazid treatment. We also successfully identify the potential co-targets with literature confirmed evidences which are related to the glycine-rich membrane, adenosine triphosphate energy and cell wall processes. Conclusions With gene expression and interactome data supported, our study points out possible pathways leading to the emergence of drug resistance under drug treatment. We develop a computational workflow for giving new insights to bacterial drug resistance which can be gained by a systematic and global analysis of the bacterial regulation network. Our study also discovers the potential co-targets with good properties in biological and graph theory aspects to overcome the problem of drug resistance.

  2. Uncertainty Analyses and Strategy

    International Nuclear Information System (INIS)

    Kevin Coppersmith

    2001-01-01

    The DOE identified a variety of uncertainties, arising from different sources, during its assessment of the performance of a potential geologic repository at the Yucca Mountain site. In general, the number and detail of process models developed for the Yucca Mountain site, and the complex coupling among those models, make the direct incorporation of all uncertainties difficult. The DOE has addressed these issues in a number of ways using an approach to uncertainties that is focused on producing a defensible evaluation of the performance of a potential repository. The treatment of uncertainties oriented toward defensible assessments has led to analyses and models with so-called ''conservative'' assumptions and parameter bounds, where conservative implies lower performance than might be demonstrated with a more realistic representation. The varying maturity of the analyses and models, and uneven level of data availability, result in total system level analyses with a mix of realistic and conservative estimates (for both probabilistic representations and single values). That is, some inputs have realistically represented uncertainties, and others are conservatively estimated or bounded. However, this approach is consistent with the ''reasonable assurance'' approach to compliance demonstration, which was called for in the U.S. Nuclear Regulatory Commission's (NRC) proposed 10 CFR Part 63 regulation (64 FR 8640 [DIRS 101680]). A risk analysis that includes conservatism in the inputs will result in conservative risk estimates. Therefore, the approach taken for the Total System Performance Assessment for the Site Recommendation (TSPA-SR) provides a reasonable representation of processes and conservatism for purposes of site recommendation. However, mixing unknown degrees of conservatism in models and parameter representations reduces the transparency of the analysis and makes the development of coherent and consistent probability statements about projected repository

  3. 3D structure prediction of histone acetyltransferase (HAC proteins of the p300/CBP family and their interactome in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Amar Cemanovic

    2014-09-01

    Full Text Available Histone acetylation is an important posttranslational modification correlated with gene activation. In Arabidopsis thaliana the histone acetyltransferase (HAC proteins of the CBP family are homologous to animal p300/CREB (cAMP-responsive element-binding proteins, which are important histone acetyltransferases participating in many physiological processes, including proliferation, differentiation, and apoptosis. In this study the 3-D structure of all HAC protein subunits in Arabidopsis thaliana: HAC1, HAC2, HAC4, HAC5 and HAC12 is predicted by homology modeling and confirmed by Ramachandran plot analysis. The amino acid sequences HAC family members are highly similar to the sequences of the homologous human p300/CREB protein. Conservation of p300/CBP domains among the HAC proteins was examined further by sequence alignment and pattern search. The domains of p300/CBP required for the HAC function, such as PHD, TAZ and ZZ domains, are conserved in all HAC proteins. Interactome analysis revealed that HAC1, HAC5 and HAC12 proteins interact with S-adenosylmethionine-dependent methyltransferase domaincontaining protein that shows methyltransferase activity, suggesting an additional function of the HAC proteins. Additionally, HAC5 has a strong interaction value for the putative c-myb-like transcription factor MYB3R-4, which suggests that it also may have a function in regulation of DNA replication.

  4. The ultra-sensitive Nodewalk technique identifies stochastic from virtual, population-based enhancer hubs regulating MYC in 3D: Implications for the fitness of cancer cells

    KAUST Repository

    Sumida, Noriyuki

    2018-03-27

    The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood due to poor sensitivity and/or resolution of current chromatin structure-based assays. Consequently, it is not well established if enhancers operate individually and/or in clusters to coordinate gene transcription. In the current study, we introduce Nodewalk, which uniquely combines high sensitivity with high resolution to enable the analysis of chromatin networks in minute input material. The >10,000-fold increase in sensitivity over other many-to-all competing methods uncovered that active chromatin hubs identified in large input material, corresponding to 10 000 cells, flanking the MYC locus are primarily virtual. Thus, the close agreement between chromatin interactomes generated from aliquots corresponding to less than 10 cells with randomly re-sampled interactomes, we find that numerous distal enhancers positioned within flanking topologically associating domains (TADs) converge on MYC in largely mutually exclusive manners. Moreover, when comparing with several enhancer baits, the assignment of the MYC locus as the node with the highest dynamic importance index, indicates that it is MYC targeting its enhancers, rather than vice versa. Dynamic changes in the configuration of the boundary between TADs flanking MYC underlie numerous stochastic encounters with a diverse set of enhancers to depict the plasticity of its transcriptional regulation. Such an arrangement might increase the fitness of the cancer cell by increasing the probability of MYC transcription in response to a wide range of environmental cues encountered by the cell during the neoplastic process.

  5. The ultra-sensitive Nodewalk technique identifies stochastic from virtual, population-based enhancer hubs regulating MYC in 3D: Implications for the fitness of cancer cells

    KAUST Repository

    Sumida, Noriyuki; Sifakis, Emmanouil; Scholz, Barbara A; Fernandez Woodbridge, Alejandro; Kiani, Narsis A.; Gomez-Cabrero, David; Svensson, J Peter; Tegner, Jesper; Gondor, Anita; Ohlsson, Rolf

    2018-01-01

    The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood due to poor sensitivity and/or resolution of current chromatin structure-based assays. Consequently, it is not well established if enhancers operate individually and/or in clusters to coordinate gene transcription. In the current study, we introduce Nodewalk, which uniquely combines high sensitivity with high resolution to enable the analysis of chromatin networks in minute input material. The >10,000-fold increase in sensitivity over other many-to-all competing methods uncovered that active chromatin hubs identified in large input material, corresponding to 10 000 cells, flanking the MYC locus are primarily virtual. Thus, the close agreement between chromatin interactomes generated from aliquots corresponding to less than 10 cells with randomly re-sampled interactomes, we find that numerous distal enhancers positioned within flanking topologically associating domains (TADs) converge on MYC in largely mutually exclusive manners. Moreover, when comparing with several enhancer baits, the assignment of the MYC locus as the node with the highest dynamic importance index, indicates that it is MYC targeting its enhancers, rather than vice versa. Dynamic changes in the configuration of the boundary between TADs flanking MYC underlie numerous stochastic encounters with a diverse set of enhancers to depict the plasticity of its transcriptional regulation. Such an arrangement might increase the fitness of the cancer cell by increasing the probability of MYC transcription in response to a wide range of environmental cues encountered by the cell during the neoplastic process.

  6. Anthocyanin analyses of Vaccinium fruit dietary supplements

    Science.gov (United States)

    Vaccinium fruit ingredients within dietary supplements were identified by comparisons with anthocyanin analyses of known Vaccinium profiles (demonstration of anthocyanin fingerprinting). Available Vaccinium supplements were purchased and analyzed; their anthocyanin profiles (based on HPLC separation...

  7. Contesting Citizenship: Comparative Analyses

    DEFF Research Database (Denmark)

    Siim, Birte; Squires, Judith

    2007-01-01

    importance of particularized experiences and multiple ineequality agendas). These developments shape the way citizenship is both practiced and analysed. Mapping neat citizenship modles onto distinct nation-states and evaluating these in relation to formal equality is no longer an adequate approach....... Comparative citizenship analyses need to be considered in relation to multipleinequalities and their intersections and to multiple governance and trans-national organisinf. This, in turn, suggests that comparative citizenship analysis needs to consider new spaces in which struggles for equal citizenship occur...

  8. Diffany: an ontology-driven framework to infer, visualise and analyse differential molecular networks.

    Science.gov (United States)

    Van Landeghem, Sofie; Van Parys, Thomas; Dubois, Marieke; Inzé, Dirk; Van de Peer, Yves

    2016-01-05

    Differential networks have recently been introduced as a powerful way to study the dynamic rewiring capabilities of an interactome in response to changing environmental conditions or stimuli. Currently, such differential networks are generated and visualised using ad hoc methods, and are often limited to the analysis of only one condition-specific response or one interaction type at a time. In this work, we present a generic, ontology-driven framework to infer, visualise and analyse an arbitrary set of condition-specific responses against one reference network. To this end, we have implemented novel ontology-based algorithms that can process highly heterogeneous networks, accounting for both physical interactions and regulatory associations, symmetric and directed edges, edge weights and negation. We propose this integrative framework as a standardised methodology that allows a unified view on differential networks and promotes comparability between differential network studies. As an illustrative application, we demonstrate its usefulness on a plant abiotic stress study and we experimentally confirmed a predicted regulator. Diffany is freely available as open-source java library and Cytoscape plugin from http://bioinformatics.psb.ugent.be/supplementary_data/solan/diffany/.

  9. Workload analyse of assembling process

    Science.gov (United States)

    Ghenghea, L. D.

    2015-11-01

    The workload is the most important indicator for managers responsible of industrial technological processes no matter if these are automated, mechanized or simply manual in each case, machines or workers will be in the focus of workload measurements. The paper deals with workload analyses made to a most part manual assembling technology for roller bearings assembling process, executed in a big company, with integrated bearings manufacturing processes. In this analyses the delay sample technique have been used to identify and divide all bearing assemblers activities, to get information about time parts from 480 minutes day work time that workers allow to each activity. The developed study shows some ways to increase the process productivity without supplementary investments and also indicated the process automation could be the solution to gain maximum productivity.

  10. Random error in cardiovascular meta-analyses

    DEFF Research Database (Denmark)

    Albalawi, Zaina; McAlister, Finlay A; Thorlund, Kristian

    2013-01-01

    BACKGROUND: Cochrane reviews are viewed as the gold standard in meta-analyses given their efforts to identify and limit systematic error which could cause spurious conclusions. The potential for random error to cause spurious conclusions in meta-analyses is less well appreciated. METHODS: We exam...

  11. Risico-analyse brandstofpontons

    NARCIS (Netherlands)

    Uijt de Haag P; Post J; LSO

    2001-01-01

    Voor het bepalen van de risico's van brandstofpontons in een jachthaven is een generieke risico-analyse uitgevoerd. Er is een referentiesysteem gedefinieerd, bestaande uit een betonnen brandstofponton met een relatief grote inhoud en doorzet. Aangenomen is dat de ponton gelegen is in een

  12. Fast multichannel analyser

    Energy Technology Data Exchange (ETDEWEB)

    Berry, A; Przybylski, M M; Sumner, I [Science Research Council, Daresbury (UK). Daresbury Lab.

    1982-10-01

    A fast multichannel analyser (MCA) capable of sampling at a rate of 10/sup 7/ s/sup -1/ has been developed. The instrument is based on an 8 bit parallel encoding analogue to digital converter (ADC) reading into a fast histogramming random access memory (RAM) system, giving 256 channels of 64 k count capacity. The prototype unit is in CAMAC format.

  13. A fast multichannel analyser

    International Nuclear Information System (INIS)

    Berry, A.; Przybylski, M.M.; Sumner, I.

    1982-01-01

    A fast multichannel analyser (MCA) capable of sampling at a rate of 10 7 s -1 has been developed. The instrument is based on an 8 bit parallel encoding analogue to digital converter (ADC) reading into a fast histogramming random access memory (RAM) system, giving 256 channels of 64 k count capacity. The prototype unit is in CAMAC format. (orig.)

  14. Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

    Directory of Open Access Journals (Sweden)

    Erik Corona

    Full Text Available Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS, providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

  15. Targeting EphA2-Sam and Its Interactome: Design and Evaluation of Helical Peptides Enriched in Charged Residues.

    Science.gov (United States)

    Mercurio, Flavia A; Marasco, Daniela; Di Natale, Concetta; Pirone, Luciano; Costantini, Susan; Pedone, Emilia M; Leone, Marilisa

    2016-11-17

    The EphA2 receptor controls diverse physiological and pathological conditions and its levels are often upregulated in cancer. Targeting receptor overexpression, through modulation of endocytosis and consequent degradation, appears to be an appealing strategy for attacking tumor malignancy. In this scenario, the Sam domain of EphA2 plays a pivotal role because it is the site where protein regulators of endocytosis and stability are recruited by means of heterotypic Sam-Sam interactions. Because EphA2-Sam heterotypic complexes are largely based on electrostatic contacts, we have investigated the possibility of attacking these interactions with helical peptides enriched in charged residues. Several peptide sequences with high predicted helical propensities were designed, and detailed conformational analyses were conducted by diverse techniques including NMR, CD, and molecular dynamics (MD) simulations. Interaction studies were also performed by NMR, surface plasmon resonance (SPR), and microscale thermophoresis (MST) and led to the identification of two peptides capable of binding to the first Sam domain of Odin. These molecules represent early candidates for the generation of efficient Sam domain binders and antagonists of Sam-Sam interactions involving EphA2. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Possible future HERA analyses

    International Nuclear Information System (INIS)

    Geiser, Achim

    2015-12-01

    A variety of possible future analyses of HERA data in the context of the HERA data preservation programme is collected, motivated, and commented. The focus is placed on possible future analyses of the existing ep collider data and their physics scope. Comparisons to the original scope of the HERA pro- gramme are made, and cross references to topics also covered by other participants of the workshop are given. This includes topics on QCD, proton structure, diffraction, jets, hadronic final states, heavy flavours, electroweak physics, and the application of related theory and phenomenology topics like NNLO QCD calculations, low-x related models, nonperturbative QCD aspects, and electroweak radiative corrections. Synergies with other collider programmes are also addressed. In summary, the range of physics topics which can still be uniquely covered using the existing data is very broad and of considerable physics interest, often matching the interest of results from colliders currently in operation. Due to well-established data and MC sets, calibrations, and analysis procedures the manpower and expertise needed for a particular analysis is often very much smaller than that needed for an ongoing experiment. Since centrally funded manpower to carry out such analyses is not available any longer, this contribution not only targets experienced self-funded experimentalists, but also theorists and master-level students who might wish to carry out such an analysis.

  17. Biomass feedstock analyses

    Energy Technology Data Exchange (ETDEWEB)

    Wilen, C.; Moilanen, A.; Kurkela, E. [VTT Energy, Espoo (Finland). Energy Production Technologies

    1996-12-31

    The overall objectives of the project `Feasibility of electricity production from biomass by pressurized gasification systems` within the EC Research Programme JOULE II were to evaluate the potential of advanced power production systems based on biomass gasification and to study the technical and economic feasibility of these new processes with different type of biomass feed stocks. This report was prepared as part of this R and D project. The objectives of this task were to perform fuel analyses of potential woody and herbaceous biomasses with specific regard to the gasification properties of the selected feed stocks. The analyses of 15 Scandinavian and European biomass feed stock included density, proximate and ultimate analyses, trace compounds, ash composition and fusion behaviour in oxidizing and reducing atmospheres. The wood-derived fuels, such as whole-tree chips, forest residues, bark and to some extent willow, can be expected to have good gasification properties. Difficulties caused by ash fusion and sintering in straw combustion and gasification are generally known. The ash and alkali metal contents of the European biomasses harvested in Italy resembled those of the Nordic straws, and it is expected that they behave to a great extent as straw in gasification. Any direct relation between the ash fusion behavior (determined according to the standard method) and, for instance, the alkali metal content was not found in the laboratory determinations. A more profound characterisation of the fuels would require gasification experiments in a thermobalance and a PDU (Process development Unit) rig. (orig.) (10 refs.)

  18. Data set of interactomes and metabolic pathways of proteins differentially expressed in brains with Alzheimer׳s disease

    Directory of Open Access Journals (Sweden)

    Benito Minjarez

    2016-06-01

    Full Text Available Alzheimer׳s disease is one of the main causes of dementia in the elderly and its frequency is on the rise worldwide. It is considered the result of complex interactions between genetic and environmental factors, being many of them unknown. Therefore, there is a dire necessity for the identification of novel molecular players for the understanding of this disease. In this data article we determined the protein expression profiles of whole protein extracts from cortex regions of brains from patients with Alzheimer׳s disease in comparison to a normal brain. We identified 721 iTRAQ-labeled polypeptides with more than 95% in confidence. We analyzed all proteins that changed in their expression level and located them in the KEGG metabolic pathways, as well as in the mitochondrial complexes of the electron transport chain and ATP synthase. In addition, we analyzed the over- and sub-expressed polypeptides through IPA software, specifically Core I and Biomarkers I modules. Data in this article is related to the research article “Identification of proteins that are differentially expressed in brains with Alzheimer’s disease using iTRAQ labeling and tandem mass spectrometry” (Minjarez et al., 2016 [1].

  19. Proteins analysed as virtual knots

    Science.gov (United States)

    Alexander, Keith; Taylor, Alexander J.; Dennis, Mark R.

    2017-02-01

    Long, flexible physical filaments are naturally tangled and knotted, from macroscopic string down to long-chain molecules. The existence of knotting in a filament naturally affects its configuration and properties, and may be very stable or disappear rapidly under manipulation and interaction. Knotting has been previously identified in protein backbone chains, for which these mechanical constraints are of fundamental importance to their molecular functionality, despite their being open curves in which the knots are not mathematically well defined; knotting can only be identified by closing the termini of the chain somehow. We introduce a new method for resolving knotting in open curves using virtual knots, which are a wider class of topological objects that do not require a classical closure and so naturally capture the topological ambiguity inherent in open curves. We describe the results of analysing proteins in the Protein Data Bank by this new scheme, recovering and extending previous knotting results, and identifying topological interest in some new cases. The statistics of virtual knots in protein chains are compared with those of open random walks and Hamiltonian subchains on cubic lattices, identifying a regime of open curves in which the virtual knotting description is likely to be important.

  20. Dengue-2 Structural Proteins Associate with Human Proteins to Produce a Coagulation and Innate Immune Response Biased Interactome

    Directory of Open Access Journals (Sweden)

    Soares Luis RB

    2011-01-01

    Full Text Available Abstract Background Dengue virus infection is a public health threat to hundreds of millions of individuals in the tropical regions of the globe. Although Dengue infection usually manifests itself in its mildest, though often debilitating clinical form, dengue fever, life-threatening complications commonly arise in the form of hemorrhagic shock and encephalitis. The etiological basis for the virus-induced pathology in general, and the different clinical manifestations in particular, are not well understood. We reasoned that a detailed knowledge of the global biological processes affected by virus entry into a cell might help shed new light on this long-standing problem. Methods A bacterial two-hybrid screen using DENV2 structural proteins as bait was performed, and the results were used to feed a manually curated, global dengue-human protein interaction network. Gene ontology and pathway enrichment, along with network topology and microarray meta-analysis, were used to generate hypothesis regarding dengue disease biology. Results Combining bioinformatic tools with two-hybrid technology, we screened human cDNA libraries to catalogue proteins physically interacting with the DENV2 virus structural proteins, Env, cap and PrM. We identified 31 interacting human proteins representing distinct biological processes that are closely related to the major clinical diagnostic feature of dengue infection: haemostatic imbalance. In addition, we found dengue-binding human proteins involved with additional key aspects, previously described as fundamental for virus entry into cells and the innate immune response to infection. Construction of a DENV2-human global protein interaction network revealed interesting biological properties suggested by simple network topology analysis. Conclusions Our experimental strategy revealed that dengue structural proteins interact with human protein targets involved in the maintenance of blood coagulation and innate anti

  1. AMS analyses at ANSTO

    Energy Technology Data Exchange (ETDEWEB)

    Lawson, E.M. [Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW (Australia). Physics Division

    1998-03-01

    The major use of ANTARES is Accelerator Mass Spectrometry (AMS) with {sup 14}C being the most commonly analysed radioisotope - presently about 35 % of the available beam time on ANTARES is used for {sup 14}C measurements. The accelerator measurements are supported by, and dependent on, a strong sample preparation section. The ANTARES AMS facility supports a wide range of investigations into fields such as global climate change, ice cores, oceanography, dendrochronology, anthropology, and classical and Australian archaeology. Described here are some examples of the ways in which AMS has been applied to support research into the archaeology, prehistory and culture of this continent`s indigenous Aboriginal peoples. (author)

  2. AMS analyses at ANSTO

    International Nuclear Information System (INIS)

    Lawson, E.M.

    1998-01-01

    The major use of ANTARES is Accelerator Mass Spectrometry (AMS) with 14 C being the most commonly analysed radioisotope - presently about 35 % of the available beam time on ANTARES is used for 14 C measurements. The accelerator measurements are supported by, and dependent on, a strong sample preparation section. The ANTARES AMS facility supports a wide range of investigations into fields such as global climate change, ice cores, oceanography, dendrochronology, anthropology, and classical and Australian archaeology. Described here are some examples of the ways in which AMS has been applied to support research into the archaeology, prehistory and culture of this continent's indigenous Aboriginal peoples. (author)

  3. Analyses of MHD instabilities

    International Nuclear Information System (INIS)

    Takeda, Tatsuoki

    1985-01-01

    In this article analyses of the MHD stabilities which govern the global behavior of a fusion plasma are described from the viewpoint of the numerical computation. First, we describe the high accuracy calculation of the MHD equilibrium and then the analysis of the linear MHD instability. The former is the basis of the stability analysis and the latter is closely related to the limiting beta value which is a very important theoretical issue of the tokamak research. To attain a stable tokamak plasma with good confinement property it is necessary to control or suppress disruptive instabilities. We, next, describe the nonlinear MHD instabilities which relate with the disruption phenomena. Lastly, we describe vectorization of the MHD codes. The above MHD codes for fusion plasma analyses are relatively simple though very time-consuming and parts of the codes which need a lot of CPU time concentrate on a small portion of the codes, moreover, the codes are usually used by the developers of the codes themselves, which make it comparatively easy to attain a high performance ratio on the vector processor. (author)

  4. A simple beam analyser

    International Nuclear Information System (INIS)

    Lemarchand, G.

    1977-01-01

    (ee'p) experiments allow to measure the missing energy distribution as well as the momentum distribution of the extracted proton in the nucleus versus the missing energy. Such experiments are presently conducted on SACLAY's A.L.S. 300 Linac. Electrons and protons are respectively analysed by two spectrometers and detected in their focal planes. Counting rates are usually low and include time coincidences and accidentals. Signal-to-noise ratio is dependent on the physics of the experiment and the resolution of the coincidence, therefore it is mandatory to get a beam current distribution as flat as possible. Using new technologies has allowed to monitor in real time the behavior of the beam pulse and determine when the duty cycle can be considered as being good with respect to a numerical basis

  5. Pathway-based analyses.

    Science.gov (United States)

    Kent, Jack W

    2016-02-03

    New technologies for acquisition of genomic data, while offering unprecedented opportunities for genetic discovery, also impose severe burdens of interpretation and penalties for multiple testing. The Pathway-based Analyses Group of the Genetic Analysis Workshop 19 (GAW19) sought reduction of multiple-testing burden through various approaches to aggregation of highdimensional data in pathways informed by prior biological knowledge. Experimental methods testedincluded the use of "synthetic pathways" (random sets of genes) to estimate power and false-positive error rate of methods applied to simulated data; data reduction via independent components analysis, single-nucleotide polymorphism (SNP)-SNP interaction, and use of gene sets to estimate genetic similarity; and general assessment of the efficacy of prior biological knowledge to reduce the dimensionality of complex genomic data. The work of this group explored several promising approaches to managing high-dimensional data, with the caveat that these methods are necessarily constrained by the quality of external bioinformatic annotation.

  6. Network class superposition analyses.

    Directory of Open Access Journals (Sweden)

    Carl A B Pearson

    Full Text Available Networks are often used to understand a whole system by modeling the interactions among its pieces. Examples include biomolecules in a cell interacting to provide some primary function, or species in an environment forming a stable community. However, these interactions are often unknown; instead, the pieces' dynamic states are known, and network structure must be inferred. Because observed function may be explained by many different networks (e.g., ≈ 10(30 for the yeast cell cycle process, considering dynamics beyond this primary function means picking a single network or suitable sample: measuring over all networks exhibiting the primary function is computationally infeasible. We circumvent that obstacle by calculating the network class ensemble. We represent the ensemble by a stochastic matrix T, which is a transition-by-transition superposition of the system dynamics for each member of the class. We present concrete results for T derived from boolean time series dynamics on networks obeying the Strong Inhibition rule, by applying T to several traditional questions about network dynamics. We show that the distribution of the number of point attractors can be accurately estimated with T. We show how to generate Derrida plots based on T. We show that T-based Shannon entropy outperforms other methods at selecting experiments to further narrow the network structure. We also outline an experimental test of predictions based on T. We motivate all of these results in terms of a popular molecular biology boolean network model for the yeast cell cycle, but the methods and analyses we introduce are general. We conclude with open questions for T, for example, application to other models, computational considerations when scaling up to larger systems, and other potential analyses.

  7. Seismic fragility analyses

    International Nuclear Information System (INIS)

    Kostov, Marin

    2000-01-01

    In the last two decades there is increasing number of probabilistic seismic risk assessments performed. The basic ideas of the procedure for performing a Probabilistic Safety Analysis (PSA) of critical structures (NUREG/CR-2300, 1983) could be used also for normal industrial and residential buildings, dams or other structures. The general formulation of the risk assessment procedure applied in this investigation is presented in Franzini, et al., 1984. The probability of failure of a structure for an expected lifetime (for example 50 years) can be obtained from the annual frequency of failure, β E determined by the relation: β E ∫[d[β(x)]/dx]P(flx)dx. β(x) is the annual frequency of exceedance of load level x (for example, the variable x may be peak ground acceleration), P(fI x) is the conditional probability of structure failure at a given seismic load level x. The problem leads to the assessment of the seismic hazard β(x) and the fragility P(fl x). The seismic hazard curves are obtained by the probabilistic seismic hazard analysis. The fragility curves are obtained after the response of the structure is defined as probabilistic and its capacity and the associated uncertainties are assessed. Finally the fragility curves are combined with the seismic loading to estimate the frequency of failure for each critical scenario. The frequency of failure due to seismic event is presented by the scenario with the highest frequency. The tools usually applied for probabilistic safety analyses of critical structures could relatively easily be adopted to ordinary structures. The key problems are the seismic hazard definitions and the fragility analyses. The fragility could be derived either based on scaling procedures or on the base of generation. Both approaches have been presented in the paper. After the seismic risk (in terms of failure probability) is assessed there are several approaches for risk reduction. Generally the methods could be classified in two groups. The

  8. Theorising and Analysing Academic Labour

    Directory of Open Access Journals (Sweden)

    Thomas Allmer

    2018-01-01

    Full Text Available The aim of this article is to contextualise universities historically within capitalism and to analyse academic labour and the deployment of digital media theoretically and critically. It argues that the post-war expansion of the university can be considered as medium and outcome of informational capitalism and as a dialectical development of social achievement and advanced commodification. The article strives to identify the class position of academic workers, introduces the distinction between academic work and labour, discusses the connection between academic, information and cultural work, and suggests a broad definition of university labour. It presents a theoretical model of working conditions that helps to systematically analyse the academic labour process and to provide an overview of working conditions at universities. The paper furthermore argues for the need to consider the development of education technologies as a dialectics of continuity and discontinuity, discusses the changing nature of the forces and relations of production, and the impact on the working conditions of academics in the digital university. Based on Erik Olin Wright’s inclusive approach of social transformation, the article concludes with the need to bring together anarchist, social democratic and revolutionary strategies for establishing a socialist university in a commons-based information society.

  9. Website-analyse

    DEFF Research Database (Denmark)

    Thorlacius, Lisbeth

    2009-01-01

    eller blindgyder, når han/hun besøger sitet. Studier i design og analyse af de visuelle og æstetiske aspekter i planlægning og brug af websites har imidlertid kun i et begrænset omfang været under reflektorisk behandling. Det er baggrunden for dette kapitel, som indleder med en gennemgang af æstetikkens......Websitet er i stigende grad det foretrukne medie inden for informationssøgning,virksomhedspræsentation, e-handel, underholdning, undervisning og social kontakt. I takt med denne voksende mangfoldighed af kommunikationsaktiviteter på nettet, er der kommet mere fokus på at optimere design og...... planlægning af de funktionelle og indholdsmæssige aspekter ved websites. Der findes en stor mængde teori- og metodebøger, som har specialiseret sig i de tekniske problemstillinger i forbindelse med interaktion og navigation, samt det sproglige indhold på websites. Den danske HCI (Human Computer Interaction...

  10. A channel profile analyser

    International Nuclear Information System (INIS)

    Gobbur, S.G.

    1983-01-01

    It is well understood that due to the wide band noise present in a nuclear analog-to-digital converter, events at the boundaries of adjacent channels are shared. It is a difficult and laborious process to exactly find out the shape of the channels at the boundaries. A simple scheme has been developed for the direct display of channel shape of any type of ADC on a cathode ray oscilliscope display. This has been accomplished by sequentially incrementing the reference voltage of a precision pulse generator by a fraction of a channel and storing ADC data in alternative memory locations of a multichannel pulse height analyser. Alternative channels are needed due to the sharing at the boundaries of channels. In the flat region of the profile alternate memory locations are channels with zero counts and channels with the full scale counts. At the boundaries all memory locations will have counts. The shape of this is a direct display of the channel boundaries. (orig.)

  11. The Breast Cancer DNA Interactome

    Science.gov (United States)

    2014-12-01

    an antisense orientation compared with the IGF1R gene, and it is expressed exclusively from the paternal allele, with the maternal allele being...orientation compared with the IGF1R gene, and it is expressed exclusively from the paternal allele, with the maternal allele being silenced...progression and metastasis is not yet fully understood. Our major goal has been to characterize physical interactions among selected breast cancer gene loci

  12. The arabidopsis cyclic nucleotide interactome

    KAUST Repository

    Donaldson, Lara Elizabeth; Meier, Stuart Kurt; Gehring, Christoph A

    2016-01-01

    Cyclic nucleotides have been shown to play important signaling roles in many physiological processes in plants including photosynthesis and defence. Despite this, little is known about cyclic nucleotide-dependent signaling mechanisms

  13. Supporting analyses and assessments

    Energy Technology Data Exchange (ETDEWEB)

    Ohi, J. [National Renewable Energy Lab., Golden, CO (United States)

    1995-09-01

    Supporting analysis and assessments can provide a sound analytic foundation and focus for program planning, evaluation, and coordination, particularly if issues of hydrogen production, distribution, storage, safety, and infrastructure can be analyzed in a comprehensive and systematic manner. The overall purpose of this activity is to coordinate all key analytic tasks-such as technology and market status, opportunities, and trends; environmental costs and benefits; and regulatory constraints and opportunities-within a long-term and systematic analytic foundation for program planning and evaluation. Within this context, the purpose of the project is to help develop and evaluate programmatic pathway options that incorporate near and mid-term strategies to achieve the long-term goals of the Hydrogen Program. In FY 95, NREL will develop a comprehensive effort with industry, state and local agencies, and other federal agencies to identify and evaluate programmatic pathway options to achieve the long-term goals of the Program. Activity to date is reported.

  14. NOAA's National Snow Analyses

    Science.gov (United States)

    Carroll, T. R.; Cline, D. W.; Olheiser, C. M.; Rost, A. A.; Nilsson, A. O.; Fall, G. M.; Li, L.; Bovitz, C. T.

    2005-12-01

    NOAA's National Operational Hydrologic Remote Sensing Center (NOHRSC) routinely ingests all of the electronically available, real-time, ground-based, snow data; airborne snow water equivalent data; satellite areal extent of snow cover information; and numerical weather prediction (NWP) model forcings for the coterminous U.S. The NWP model forcings are physically downscaled from their native 13 km2 spatial resolution to a 1 km2 resolution for the CONUS. The downscaled NWP forcings drive an energy-and-mass-balance snow accumulation and ablation model at a 1 km2 spatial resolution and at a 1 hour temporal resolution for the country. The ground-based, airborne, and satellite snow observations are assimilated into the snow model's simulated state variables using a Newtonian nudging technique. The principle advantages of the assimilation technique are: (1) approximate balance is maintained in the snow model, (2) physical processes are easily accommodated in the model, and (3) asynoptic data are incorporated at the appropriate times. The snow model is reinitialized with the assimilated snow observations to generate a variety of snow products that combine to form NOAA's NOHRSC National Snow Analyses (NSA). The NOHRSC NSA incorporate all of the available information necessary and available to produce a "best estimate" of real-time snow cover conditions at 1 km2 spatial resolution and 1 hour temporal resolution for the country. The NOHRSC NSA consist of a variety of daily, operational, products that characterize real-time snowpack conditions including: snow water equivalent, snow depth, surface and internal snowpack temperatures, surface and blowing snow sublimation, and snowmelt for the CONUS. The products are generated and distributed in a variety of formats including: interactive maps, time-series, alphanumeric products (e.g., mean areal snow water equivalent on a hydrologic basin-by-basin basis), text and map discussions, map animations, and quantitative gridded products

  15. Thoughts on identifiers

    CERN Multimedia

    CERN. Geneva

    2005-01-01

    As business processes and information transactions have become an inextricably intertwined with the Web, the importance of assignment, registration, discovery, and maintenance of identifiers has increased. In spite of this, integrated frameworks for managing identifiers have been slow to emerge. Instead, identification systems arise (quite naturally) from immediate business needs without consideration for how they fit into larger information architectures. In addition, many legacy identifier systems further complicate the landscape, making it difficult for content managers to select and deploy identifier systems that meet both the business case and long term information management objectives. This presentation will outline a model for evaluating identifier applications and the functional requirements of the systems necessary to support them. The model is based on a layered analysis of the characteristics of identifier systems, including: * Functional characteristics * Technology * Policy * Business * Social T...

  16. Identifiability in stochastic models

    CERN Document Server

    1992-01-01

    The problem of identifiability is basic to all statistical methods and data analysis, occurring in such diverse areas as Reliability Theory, Survival Analysis, and Econometrics, where stochastic modeling is widely used. Mathematics dealing with identifiability per se is closely related to the so-called branch of ""characterization problems"" in Probability Theory. This book brings together relevant material on identifiability as it occurs in these diverse fields.

  17. Erosion of the Alps: use of Rb-Sr isotopic data from molassic sediments to identify the ages of the metamorphism recorded by the eroded rocks; Erosion des Alpes: histoire metamorphique des roches erodees par l`analyse du couple Rb-Sr des sediments molassiques

    Energy Technology Data Exchange (ETDEWEB)

    Henry, P; Deloule, E [Centre National de la Recherche Scientifique (CNRS), 54 - Nancy (France). Centre de Recherches Petrographiques et Geochimiques; Michard, A [Aix-Marseille-3 Univ., 13 - Marseille (France)

    1994-06-01

    Rb-Sr isotopic data from Oligocene and Miocene peri-alpine molassic sediments allow us to identify the different periods for which the eroded rocks have or have not recorded an alpine metamorphism. The Chattian and the Burdigalian sediments result from the erosion of rocks for which the latest metamorphic event was variscan, while the Stampian, Aquitanian and ``Helvetian`` sediments show evidence for the erosion of rocks which have recorded alpine metamorphic events. The application of this method to old detrital sediments could permit determination of the ages of the tectonic events which occurred in the sediment source regions. (authors). 18 refs., 6 figs.

  18. Identifying Strategic Scientific Opportunities

    Science.gov (United States)

    As NCI's central scientific strategy office, CRS collaborates with the institute's divisions, offices, and centers to identify research opportunities to advance NCI's vision for the future of cancer research.

  19. Identifying Breast Cancer Oncogenes

    Science.gov (United States)

    2011-10-01

    cells we observed that it promoted transformation of HMLE cells, suggesting a tumor suppressive role of Merlin in breast cancer (Figure 4B). A...08-1-0767 TITLE: Identifying Breast Cancer Oncogenes PRINCIPAL INVESTIGATOR: Yashaswi Shrestha...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 W81XWH-08-1-0767 Identifying Breast Cancer Oncogenes Yashaswi Shrestha Dana-Farber

  20. Complex Systems Analysis of Cell Cycling Models in Carcinogenesis:II. Cell Genome and Interactome, Neoplastic Non-random Transformation Models in Topoi with Lukasiewicz-Logic and MV Algebras

    CERN Document Server

    Baianu, I C

    2004-01-01

    Quantitative Biology, abstract q-bio.OT/0406045 From: I.C. Baianu Dr. [view email] Date (v1): Thu, 24 Jun 2004 02:45:13 GMT (164kb) Date (revised v2): Fri, 2 Jul 2004 00:58:06 GMT (160kb) Complex Systems Analysis of Cell Cycling Models in Carcinogenesis: II. Authors: I.C. Baianu Comments: 23 pages, 1 Figure Report-no: CC04 Subj-class: Other Carcinogenesis is a complex process that involves dynamically inter-connected modular sub-networks that evolve under the influence of micro-environmentally induced perturbations, in non-random, pseudo-Markov chain processes. An appropriate n-stage model of carcinogenesis involves therefore n-valued Logic treatments of nonlinear dynamic transformations of complex functional genomes and cell interactomes. Lukasiewicz Algebraic Logic models of genetic networks and signaling pathways in cells are formulated in terms of nonlinear dynamic systems with n-state components that allow for the generalization of previous, Boolean or "fuzzy", logic models of genetic activities in vivo....

  1. Identifying Knowledge and Communication

    Directory of Open Access Journals (Sweden)

    Eduardo Coutinho Lourenço de Lima

    2006-12-01

    Full Text Available In this paper, I discuss how the principle of identifying knowledge which Strawson advances in ‘Singular Terms and Predication’ (1961, and in ‘Identifying Reference and Truth-Values’ (1964 turns out to constrain communication. The principle states that a speaker’s use of a referring expression should invoke identifying knowledge on the part of the hearer, if the hearer is to understand what the speaker is saying, and also that, in so referring, speakers are attentive to hearers’ epistemic states. In contrasting it with Russell’s Principle (Evans 1982, as well as with the principle of identifying descriptions (Donnellan 1970, I try to show that the principle of identifying knowledge, ultimately a condition for understanding, makes sense only in a situation of conversation. This allows me to conclude that the cooperative feature of communication (Grice 1975 and reference (Clark andWilkes-Gibbs 1986 holds also at the understanding level. Finally, I discuss where Strawson’s views seem to be unsatisfactory, and suggest how they might be improved.

  2. Identifying and Managing Risk.

    Science.gov (United States)

    Abraham, Janice M.

    1999-01-01

    The role of the college or university chief financial officer in institutional risk management is (1) to identify risk (physical, casualty, fiscal, business, reputational, workplace safety, legal liability, employment practices, general liability), (2) to develop a campus plan to reduce and control risk, (3) to transfer risk, and (4) to track and…

  3. Internally readable identifying tag

    International Nuclear Information System (INIS)

    Jefferts, K.B.; Jefferts, E.R.

    1980-01-01

    A method of identifying non-metallic objects by means of X-ray equipment is described in detail. A small metal pin with a number of grooves cut in a pre-determined equi-spaced pattern is implanted into the non-metallic object and by decoding the groove patterns using X-ray equipment, the object is uniquely identified. A specific example of such an application is in studying the migratory habits of fish. The pin inserted into the snout of the fish is 0.010 inch in diameter, 0.040 inch in length with 8 possible positions for grooves if spaced 0.005 inch apart. With 6 of the groove positions available for data, the capacity is 2 6 or 64 combinations; clearly longer pins would increase the data capacity. This method of identification is a major advance over previous techniques which necessitated destruction of the fish in order to recover the identification tag. (UK)

  4. Identifying Breast Cancer Oncogenes

    Science.gov (United States)

    2010-10-01

    tyrosine kinases with an SH3, SH2 and catalytic domain, it lacks a native myristylation signal shared by most members of this class [14], [38]. The...therapeutics and consequently, improve clinical outcomes. We aim to identify novel drivers of breast oncogenesis. We hypothesize that a kinase gain-of...human mammary epithelial cells. A pBabe-Puro-Myr-Flag kinase open reading frame (ORF) library was screened in immortalized human mammary epithelial

  5. Rock disposal problems identified

    Energy Technology Data Exchange (ETDEWEB)

    Knox, R

    1978-06-01

    Mathematical models are the only way of examining the return of radioactivity from nuclear waste to the environment over long periods of time. Work in Britain has helped identify areas where more basic data is required, but initial results look very promising for final disposal of high level waste in hard rock repositories. A report by the National Radiological Protection Board of a recent study, is examined.

  6. Pawnee Nation Energy Option Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Matlock, M.; Kersey, K.; Riding In, C.

    2009-07-21

    Pawnee Nation of Oklahoma Energy Option Analyses In 2003, the Pawnee Nation leadership identified the need for the tribe to comprehensively address its energy issues. During a strategic energy planning workshop a general framework was laid out and the Pawnee Nation Energy Task Force was created to work toward further development of the tribe’s energy vision. The overarching goals of the “first steps” project were to identify the most appropriate focus for its strategic energy initiatives going forward, and to provide information necessary to take the next steps in pursuit of the “best fit” energy options. Description of Activities Performed The research team reviewed existing data pertaining to the availability of biomass (focusing on woody biomass, agricultural biomass/bio-energy crops, and methane capture), solar, wind and hydropower resources on the Pawnee-owned lands. Using these data, combined with assumptions about costs and revenue streams, the research team performed preliminary feasibility assessments for each resource category. The research team also reviewed available funding resources and made recommendations to Pawnee Nation highlighting those resources with the greatest potential for financially-viable development, both in the near-term and over a longer time horizon. Findings and Recommendations Due to a lack of financial incentives for renewable energy, particularly at the state level, combined mediocre renewable energy resources, renewable energy development opportunities are limited for Pawnee Nation. However, near-term potential exists for development of solar hot water at the gym, and an exterior wood-fired boiler system at the tribe’s main administrative building. Pawnee Nation should also explore options for developing LFGTE resources in collaboration with the City of Pawnee. Significant potential may also exist for development of bio-energy resources within the next decade. Pawnee Nation representatives should closely monitor

  7. Identifying phenomenal consciousness.

    Science.gov (United States)

    Schier, Elizabeth

    2009-03-01

    This paper examines the possibility of finding evidence that phenomenal consciousness is independent of access. The suggestion reviewed is that we should look for isomorphisms between phenomenal and neural activation spaces. It is argued that the fact that phenomenal spaces are mapped via verbal report is no problem for this methodology. The fact that activation and phenomenal space are mapped via different means does not mean that they cannot be identified. The paper finishes by examining how data addressing this theoretical question could be obtained.

  8. Use of phylogenetic and phenotypic analyses to identify nonhemolytic streptococci isolated from bacteremic patients

    DEFF Research Database (Denmark)

    Hoshino, T; Fujivwara, T; Kilian, Mogens

    2005-01-01

    and identification using two commercial kits, Rapid ID 32 STREP and STREPTOGRAM and the associated databases. A phylogenetic tree based on concatenated sequences of the four housekeeping genes allowed unequivocal differentiation of recognized species and was used as the reference. Analysis of single gene sequences...

  9. Methods of Identifying, Collecting and Analysing Accelerants in Arson Fires in the Kingdom of Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Abdulrhman M. Dhabbah

    2015-12-01

    Full Text Available If there is a suspicion of arson, analysis of fire debris and identification of potential accelerants is considered to be one of the most essential examinations of the investigation. The existence of any traces of potential accelerants in a sample taken from the fire scene is crucial in determining whether the fire was started deliberately or not. This study is divided into four parts: the first part describes the most important ignition accelerators which are used in arson fires in Saudi Arabia. The second part is devoted to determining the methods that are used to collect and store trace evidences from fire scenes in Saudi Arabia, if there is a suspicion that accelerants have been used to ignite the fire. The most important techniques used in the extraction and analysis of ignitable liquid residue (ILR in arson cases are presented in the third section. Finally, the fourth part discusses the problems and difficulties which both experts and employees in The General Department of Forensic Evidence in Saudi Arabia face when collecting and sampling traces as well as some recommendations to address these issues. The results obtained from this study indicate that the most common accelerant used to start fires is gasoline, specifically ‘Octane 91’, followed by kerosene, thereafter diesel and finally paint thinner. Experts are also agreed on the difficulty of obtaining evidence from this type of crime scene, especially after the fire has been extinguished and the scene is released for investigation by the Civil Defense. They also agree that the best technique for extracting and analyzing ignitable liquid residue (ILR in the solid phase should be Gas Chromatography coupled with Headspace (GC-Headspace. In liquid samples, either Gas Chromatography coupled with Mass Spectroscopy (GC-MS or Fourier transform infrared (FT- IR can be used.

  10. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

    NARCIS (Netherlands)

    Peifer, Martin; Fernandez-Cuesta, Lynnette; Sos, Martin L.; George, Julie; Seidel, Danila; Kasper, Lawryn H.; Plenker, Dennis; Leenders, Frauke; Sun, Ruping; Zander, Thomas; Menon, Roopika; Koker, Mirjam; Dahmen, Ilona; Mueller, Christian; Di Cerbo, Vincenzo; Schildhaus, Hans-Ulrich; Altmueller, Janine; Baessmann, Ingelore; Becker, Christian; de Wilde, Bram; Vandesompele, Jo; Boehm, Diana; Ansen, Sascha; Gabler, Franziska; Wilkening, Ines; Heynck, Stefanie; Heuckmann, Johannes M.; Lu, Xin; Carter, Scott L.; Cibulskis, Kristian; Banerji, Shantanu; Getz, Gad; Park, Kwon-Sik; Rauh, Daniel; Gruetter, Christian; Fischer, Matthias; Pasqualucci, Laura; Wright, Gavin; Wainer, Zoe; Russell, Prudence; Petersen, Iver; Chen, Yuan; Stoelben, Erich; Ludwig, Corinna; Schnabel, Philipp; Hoffmann, Hans; Muley, Thomas; Brockmann, Michael; Engel-Riedel, Walburga; Muscarella, Lucia A.; Fazio, Vito M.; Groen, Harry; Timens, Wim; Sietsma, Hannie; Thunnissen, Erik; Smit, Egbert; Heideman, Danielle A. M.; Snijders, Peter J. F.; Cappuzzo, Federico; Ligorio, Claudia; Damiani, Stefania; Field, John; Solberg, Steinar; Brustugun, Odd Terje; Lund-Iversen, Marius; Saenger, Joerg; Clement, Joachim H.; Soltermann, Alex; Moch, Holger; Weder, Walter; Solomon, Benjamin; Soria, Jean-Charles; Validire, Pierre; Besse, Benjamin; Brambilla, Elisabeth; Brambilla, Christian; Lantuejoul, Sylvie; Lorimier, Philippe; Schneider, Peter M.; Hallek, Michael; Pao, William; Meyerson, Matthew; Sage, Julien; Shendure, Jay; Schneider, Robert; Buettner, Reinhard; Wolf, Juergen; Nuernberg, Peter; Perner, Sven; Heukamp, Lukas C.; Brindle, Paul K.; Haas, Stefan; Thomas, Roman K.

    2012-01-01

    Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated

  11. Identifying Key Workplace Stressors Affecting Twentieth Air Force: Analyses Conducted from December 2012 Through February 2013

    Science.gov (United States)

    2014-01-01

    24-hour basis include nursing , air traffic control, manufacturing, police service, and fire protection. Many studies have shown that evening, night...of occupational injuries for a variety of jobs, including construction workers, nurses , miners, truck drivers, firefighters, and nuclear power plant...lish a strict schedule of AFS-specific focus group times in advance. We could not reschedule if the times proved inconvenient for participants

  12. Genome-wide association analyses identify variants in developmental genes associated with hypospadias

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Carstensen, Lisbeth

    2014-01-01

    Hypospadias is a common congenital condition in boys in which the urethra opens on the underside of the penis. We performed a genome-wide association study on 1,006 surgery-confirmed hypospadias cases and 5,486 controls from Denmark. After replication genotyping of an additional 1,972 cases and 1...

  13. Spatial analyses identify the geographic source of patients at a National Cancer Institute Comprehensive Cancer Center.

    Science.gov (United States)

    Su, Shu-Chih; Kanarek, Norma; Fox, Michael G; Guseynova, Alla; Crow, Shirley; Piantadosi, Steven

    2010-02-01

    We examined the geographic distribution of patients to better understand the service area of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, a designated National Cancer Institute (NCI) comprehensive cancer center located in an urban center. Like most NCI cancer centers, the Sidney Kimmel Comprehensive Cancer Center serves a population beyond city limits. Urban cancer centers are expected to serve their immediate neighborhoods and to address disparities in access to specialty care. Our purpose was to learn the extent and nature of the cancer center service area. Statistical clustering of patient residence in the continental United States was assessed for all patients and by gender, cancer site, and race using SaTScan. Primary clusters detected for all cases and demographically and tumor-defined subpopulations were centered at Baltimore City and consisted of adjacent counties in Delaware, Pennsylvania, Virginia, West Virginia, New Jersey and New York, and the District of Columbia. Primary clusters varied in size by race, gender, and cancer site. Spatial analysis can provide insights into the populations served by urban cancer centers, assess centers' performance relative to their communities, and aid in developing a cancer center business plan that recognizes strengths, regional utility, and referral patterns. Today, 62 NCI cancer centers serve a quarter of the U.S. population in their immediate communities. From the Baltimore experience, we might project that the population served by these centers is actually more extensive and varies by patient characteristics, cancer site, and probably cancer center services offered.

  14. Use of phylogenetic and phenotypic analyses to identify nonhemolytic streptococci isolated from bacteremic patients.

    Science.gov (United States)

    Hoshino, Tomonori; Fujiwara, Taku; Kilian, Mogens

    2005-12-01

    The aim of this study was to evaluate molecular and phenotypic methods for the identification of nonhemolytic streptococci. A collection of 148 strains consisting of 115 clinical isolates from cases of infective endocarditis, septicemia, and meningitis and 33 reference strains, including type strains of all relevant Streptococcus species, were examined. Identification was performed by phylogenetic analysis of nucleotide sequences of four housekeeping genes, ddl, gdh, rpoB, and sodA; by PCR analysis of the glucosyltransferase (gtf) gene; and by conventional phenotypic characterization and identification using two commercial kits, Rapid ID 32 STREP and STREPTOGRAM and the associated databases. A phylogenetic tree based on concatenated sequences of the four housekeeping genes allowed unequivocal differentiation of recognized species and was used as the reference. Analysis of single gene sequences revealed deviation clustering in eight strains (5.4%) due to homologous recombination with other species. This was particularly evident in S. sanguinis and in members of the anginosus group of streptococci. The rate of correct identification of the strains by both commercial identification kits was below 50% but varied significantly between species. The most significant problems were observed with S. mitis and S. oralis and 11 Streptococcus species described since 1991. Our data indicate that identification based on multilocus sequence analysis is optimal. As a more practical alternative we recommend identification based on sodA sequences with reference to a comprehensive set of sequences that is available for downloading from our server. An analysis of the species distribution of 107 nonhemolytic streptococci from bacteremic patients showed a predominance of S. oralis and S. anginosus with various underlying infections.

  15. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and

  16. The concept of computer software designed to identify and analyse logistics costs in agricultural enterprises

    Directory of Open Access Journals (Sweden)

    Karol Wajszczyk

    2009-01-01

    Full Text Available The study comprised research, development and computer programming works concerning the development of a concept for the IT tool to be used in the identification and analysis of logistics costs in agricultural enterprises in terms of the process-based approach. As a result of research and programming work an overall functional and IT concept of software was developed for the identification and analysis of logistics costs for agricultural enterprises.

  17. Metabolomics analyses identify platelet activating factors and heme breakdown products as Lassa fever biomarkers.

    Directory of Open Access Journals (Sweden)

    Trevor V Gale

    2017-09-01

    Full Text Available Lassa fever afflicts tens of thousands of people in West Africa annually. The rapid progression of patients from febrile illness to fulminant syndrome and death provides incentive for development of clinical prognostic markers that can guide case management. The small molecule profile of serum from febrile patients triaged to the Viral Hemorrhagic Fever Ward at Kenema Government Hospital in Sierra Leone was assessed using untargeted Ultra High Performance Liquid Chromatography Mass Spectrometry. Physiological dysregulation resulting from Lassa virus (LASV infection occurs at the small molecule level. Effects of LASV infection on pathways mediating blood coagulation, and lipid, amino acid, nucleic acid metabolism are manifest in changes in the levels of numerous metabolites in the circulation. Several compounds, including platelet activating factor (PAF, PAF-like molecules and products of heme breakdown emerged as candidates that may prove useful in diagnostic assays to inform better care of Lassa fever patients.

  18. Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3

    Science.gov (United States)

    2012-01-01

    Background Usher syndrome (USH) is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa (RP). We have identified a consanguineous Lebanese family with two affected members displaying progressive hearing loss, RP and cataracts, therefore clinically diagnosed as USH type 3 (USH3). Our study was aimed at the identification of the causative mutation in this USH3-like family. Methods Candidate loci were identified using genomewide SNP-array-based homozygosity mapping followed by targeted enrichment and next-generation sequencing. Results Using a capture array targeting the three identified homozygosity-by-descent regions on chromosomes 1q43-q44, 20p13-p12.2 and 20p11.23-q12, we identified a homozygous nonsense mutation, p.Arg65X, in ABHD12 segregating with the phenotype. Conclusion Mutations of ABHD12, an enzyme hydrolyzing an endocannabinoid lipid transmitter, cause PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract). After the identification of the ABHD12 mutation in this family, one patient underwent neurological examination which revealed ataxia, but no polyneuropathy. ABHD12 is not known to be related to the USH protein interactome. The phenotype of our patient represents a variant of PHARC, an entity that should be taken into account as differential diagnosis for USH3. Our study demonstrates the potential of comprehensive genetic analysis for improving the clinical diagnosis. PMID:22938382

  19. Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3.

    Science.gov (United States)

    Eisenberger, Tobias; Slim, Rima; Mansour, Ahmad; Nauck, Markus; Nürnberg, Gudrun; Nürnberg, Peter; Decker, Christian; Dafinger, Claudia; Ebermann, Inga; Bergmann, Carsten; Bolz, Hanno Jörn

    2012-09-02

    Usher syndrome (USH) is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa (RP). We have identified a consanguineous Lebanese family with two affected members displaying progressive hearing loss, RP and cataracts, therefore clinically diagnosed as USH type 3 (USH3). Our study was aimed at the identification of the causative mutation in this USH3-like family. Candidate loci were identified using genomewide SNP-array-based homozygosity mapping followed by targeted enrichment and next-generation sequencing. Using a capture array targeting the three identified homozygosity-by-descent regions on chromosomes 1q43-q44, 20p13-p12.2 and 20p11.23-q12, we identified a homozygous nonsense mutation, p.Arg65X, in ABHD12 segregating with the phenotype. Mutations of ABHD12, an enzyme hydrolyzing an endocannabinoid lipid transmitter, cause PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract). After the identification of the ABHD12 mutation in this family, one patient underwent neurological examination which revealed ataxia, but no polyneuropathy. ABHD12 is not known to be related to the USH protein interactome. The phenotype of our patient represents a variant of PHARC, an entity that should be taken into account as differential diagnosis for USH3. Our study demonstrates the potential of comprehensive genetic analysis for improving the clinical diagnosis.

  20. Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3

    Directory of Open Access Journals (Sweden)

    Eisenberger Tobias

    2012-09-01

    Full Text Available Abstract Background Usher syndrome (USH is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa (RP. We have identified a consanguineous Lebanese family with two affected members displaying progressive hearing loss, RP and cataracts, therefore clinically diagnosed as USH type 3 (USH3. Our study was aimed at the identification of the causative mutation in this USH3-like family. Methods Candidate loci were identified using genomewide SNP-array-based homozygosity mapping followed by targeted enrichment and next-generation sequencing. Results Using a capture array targeting the three identified homozygosity-by-descent regions on chromosomes 1q43-q44, 20p13-p12.2 and 20p11.23-q12, we identified a homozygous nonsense mutation, p.Arg65X, in ABHD12 segregating with the phenotype. Conclusion Mutations of ABHD12, an enzyme hydrolyzing an endocannabinoid lipid transmitter, cause PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract. After the identification of the ABHD12 mutation in this family, one patient underwent neurological examination which revealed ataxia, but no polyneuropathy. ABHD12 is not known to be related to the USH protein interactome. The phenotype of our patient represents a variant of PHARC, an entity that should be taken into account as differential diagnosis for USH3. Our study demonstrates the potential of comprehensive genetic analysis for improving the clinical diagnosis.

  1. List identifies threatened ecosystems

    Science.gov (United States)

    Showstack, Randy

    2012-09-01

    The International Union for Conservation of Nature (IUCN) announced on 9 September that it will develop a new Red List of Ecosystems that will identify which ecosystems are vulnerable or endangered. The list, which is modeled on the group's Red List of Threatened Species™, could help to guide conservation activities and influence policy processes such as the Convention on Biological Diversity, according to the group. “We will assess the status of marine, terrestrial, freshwater, and subterranean ecosystems at local, regional, and global levels,” stated Jon Paul Rodriguez, leader of IUCN's Ecosystems Red List Thematic Group. “The assessment can then form the basis for concerted implementation action so that we can manage them sustainably if their risk of collapse is low or restore them if they are threatened and then monitor their recovery.”

  2. Global Microbial Identifier

    DEFF Research Database (Denmark)

    Wielinga, Peter; Hendriksen, Rene S.; Aarestrup, Frank Møller

    2017-01-01

    ) will likely also enable a much better understanding of the pathogenesis of the infection and the molecular basis of the host response to infection. But the full potential of these advances will only transpire if the data in this area become transferable and thereby comparable, preferably in open-source...... of microorganisms, for the identification of relevant genes and for the comparison of genomes to detect outbreaks and emerging pathogens. To harness the full potential of WGS, a shared global database of genomes linked to relevant metadata and the necessary software tools needs to be generated, hence the global...... microbial identifier (GMI) initiative. This tool will ideally be used in amongst others in the diagnosis of infectious diseases in humans and animals, in the identification of microorganisms in food and environment, and to track and trace microbial agents in all arenas globally. This will require...

  3. Sample preparation in foodomic analyses.

    Science.gov (United States)

    Martinović, Tamara; Šrajer Gajdošik, Martina; Josić, Djuro

    2018-04-16

    Representative sampling and adequate sample preparation are key factors for successful performance of further steps in foodomic analyses, as well as for correct data interpretation. Incorrect sampling and improper sample preparation can be sources of severe bias in foodomic analyses. It is well known that both wrong sampling and sample treatment cannot be corrected anymore. These, in the past frequently neglected facts, are now taken into consideration, and the progress in sampling and sample preparation in foodomics is reviewed here. We report the use of highly sophisticated instruments for both high-performance and high-throughput analyses, as well as miniaturization and the use of laboratory robotics in metabolomics, proteomics, peptidomics and genomics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Discrete frequency identification using the HP 5451B Fourier analyser

    International Nuclear Information System (INIS)

    Holland, L.; Barry, P.

    1977-01-01

    The frequency analysis by the HP5451B discrete frequency Fourier analyser is studied. The advantages of cross correlation analysis to identify discrete frequencies in a background noise are discussed in conjuction with the elimination of aliasing and wraparound error. Discrete frequency identification is illustrated by a series of graphs giving the results of analysing 'electrical' and 'acoustical' white noise and sinusoidal signals [pt

  5. Descriptive Analyses of Mechanical Systems

    DEFF Research Database (Denmark)

    Andreasen, Mogens Myrup; Hansen, Claus Thorp

    2003-01-01

    Forord Produktanalyse og teknologianalyse kan gennmføres med et bredt socio-teknisk sigte med henblik på at forstå kulturelle, sociologiske, designmæssige, forretningsmæssige og mange andre forhold. Et delområde heri er systemisk analyse og beskrivelse af produkter og systemer. Nærværende kompend...

  6. Analysing and Comparing Encodability Criteria

    Directory of Open Access Journals (Sweden)

    Kirstin Peters

    2015-08-01

    Full Text Available Encodings or the proof of their absence are the main way to compare process calculi. To analyse the quality of encodings and to rule out trivial or meaningless encodings, they are augmented with quality criteria. There exists a bunch of different criteria and different variants of criteria in order to reason in different settings. This leads to incomparable results. Moreover it is not always clear whether the criteria used to obtain a result in a particular setting do indeed fit to this setting. We show how to formally reason about and compare encodability criteria by mapping them on requirements on a relation between source and target terms that is induced by the encoding function. In particular we analyse the common criteria full abstraction, operational correspondence, divergence reflection, success sensitiveness, and respect of barbs; e.g. we analyse the exact nature of the simulation relation (coupled simulation versus bisimulation that is induced by different variants of operational correspondence. This way we reduce the problem of analysing or comparing encodability criteria to the better understood problem of comparing relations on processes.

  7. Analysing Children's Drawings: Applied Imagination

    Science.gov (United States)

    Bland, Derek

    2012-01-01

    This article centres on a research project in which freehand drawings provided a richly creative and colourful data source of children's imagined, ideal learning environments. Issues concerning the analysis of the visual data are discussed, in particular, how imaginative content was analysed and how the analytical process was dependent on an…

  8. Impact analyses after pipe rupture

    International Nuclear Information System (INIS)

    Chun, R.C.; Chuang, T.Y.

    1983-01-01

    Two of the French pipe whip experiments are reproduced with the computer code WIPS. The WIPS results are in good agreement with the experimental data and the French computer code TEDEL. This justifies the use of its pipe element in conjunction with its U-bar element in a simplified method of impact analyses

  9. Millifluidic droplet analyser for microbiology

    NARCIS (Netherlands)

    Baraban, L.; Bertholle, F.; Salverda, M.L.M.; Bremond, N.; Panizza, P.; Baudry, J.; Visser, de J.A.G.M.; Bibette, J.

    2011-01-01

    We present a novel millifluidic droplet analyser (MDA) for precisely monitoring the dynamics of microbial populations over multiple generations in numerous (=103) aqueous emulsion droplets (100 nL). As a first application, we measure the growth rate of a bacterial strain and determine the minimal

  10. Analyser of sweeping electron beam

    International Nuclear Information System (INIS)

    Strasser, A.

    1993-01-01

    The electron beam analyser has an array of conductors that can be positioned in the field of the sweeping beam, an electronic signal treatment system for the analysis of the signals generated in the conductors by the incident electrons and a display for the different characteristics of the electron beam

  11. Radiograph identifying means

    International Nuclear Information System (INIS)

    Sheldon, A.D.

    1983-01-01

    A flexible character-indentable plastics embossing tape is backed by and bonded to a lead strip, not more than 0.025 inches thick, to form a tape suitable for identifying radiographs. The lead strip is itself backed by a relatively thin and flimsy plastics or fabric strip which, when removed, allows the lead plastic tape to be pressure-bonded to the surface to be radiographed. A conventional tape-embossing gun is used to indent the desired characters in succession into the lead-backed tape, without necessarily severing the lead; and then the backing strip is peeled away to expose the layer of adhesive which pressure-bonds the indented tape to the object to be radiographed. X-rays incident on the embossed tape will cause the raised characters to show up dark on the subsequently-developed film, whilst the raised side areas will show up white. Each character will thus stand out on the developed film. (author)

  12. Combining affinity proteomics and network context to identify new phosphatase substrates and adapters in growth pathways.

    Directory of Open Access Journals (Sweden)

    Francesca eSacco

    2014-05-01

    Full Text Available Protein phosphorylation homoeostasis is tightly controlled and pathological conditions are caused by subtle alterations of the cell phosphorylation profile. Altered levels of kinase activities have already been associated to specific diseases. Less is known about the impact of phosphatases, the enzymes that down-regulate phosphorylation by removing the phosphate groups. This is partly due to our poor understanding of the phosphatase-substrate network. Much of phosphatase substrate specificity is not based on intrinsic enzyme specificity with the catalytic pocket recognizing the sequence/structure context of the phosphorylated residue. In addition many phosphatase catalytic subunits do not form a stable complex with their substrates. This makes the inference and validation of phosphatase substrates a non-trivial task. Here, we present a novel approach that builds on the observation that much of phosphatase substrate selection is based on the network of physical interactions linking the phosphatase to the substrate. We first used affinity proteomics coupled to quantitative mass spectrometry to saturate the interactome of eight phosphatases whose down regulations was shown to affect the activation of the RAS-PI#K pathway. By integrating information from functional siRNA with protein interaction information, we develop a strategy that aims at inferring phosphatase physiological substrates. Graph analysis is used to identify protein scaffolds that may link the catalytic subunits to their substrates. By this approach we rediscover several previously described phosphatase substrate interactions and characterize two new protein scaffolds that promote the dephosphorylation of PTPN11 and ERK by DUSP18 and DUSP26 respectively.

  13. Precise Chemical Analyses of Planetary Surfaces

    Science.gov (United States)

    Kring, David; Schweitzer, Jeffrey; Meyer, Charles; Trombka, Jacob; Freund, Friedemann; Economou, Thanasis; Yen, Albert; Kim, Soon Sam; Treiman, Allan H.; Blake, David; hide

    1996-01-01

    We identify the chemical elements and element ratios that should be analyzed to address many of the issues identified by the Committee on Planetary and Lunar Exploration (COMPLEX). We determined that most of these issues require two sensitive instruments to analyze the necessary complement of elements. In addition, it is useful in many cases to use one instrument to analyze the outermost planetary surface (e.g. to determine weathering effects), while a second is used to analyze a subsurface volume of material (e.g., to determine the composition of unaltered planetary surface material). This dual approach to chemical analyses will also facilitate the calibration of orbital and/or Earth-based spectral observations of the planetary body. We determined that in many cases the scientific issues defined by COMPLEX can only be fully addressed with combined packages of instruments that would supplement the chemical data with mineralogic or visual information.

  14. Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma.

    Science.gov (United States)

    Lee, Hyun-Sung; Jang, Hee-Jin; Choi, Jong Min; Zhang, Jun; de Rosen, Veronica Lenge; Wheeler, Thomas M; Lee, Ju-Seog; Tu, Thuydung; Jindra, Peter T; Kerman, Ronald H; Jung, Sung Yun; Kheradmand, Farrah; Sugarbaker, David J; Burt, Bryan M

    2018-04-05

    We generated a comprehensive atlas of the immunologic cellular networks within human malignant pleural mesothelioma (MPM) using mass cytometry. Data-driven analyses of these high-resolution single-cell data identified 2 distinct immunologic subtypes of MPM with vastly different cellular composition, activation states, and immunologic function; mass spectrometry demonstrated differential abundance of MHC-I and -II neopeptides directly identified between these subtypes. The clinical relevance of this immunologic subtyping was investigated with a discriminatory molecular signature derived through comparison of the proteomes and transcriptomes of these 2 immunologic MPM subtypes. This molecular signature, representative of a favorable intratumoral cell network, was independently associated with improved survival in MPM and predicted response to immune checkpoint inhibitors in patients with MPM and melanoma. These data additionally suggest a potentially novel mechanism of response to checkpoint blockade: requirement for high measured abundance of neopeptides in the presence of high expression of MHC proteins specific for these neopeptides.

  15. Mitogenomic analyses from ancient DNA

    DEFF Research Database (Denmark)

    Paijmans, Johanna L. A.; Gilbert, Tom; Hofreiter, Michael

    2013-01-01

    The analysis of ancient DNA is playing an increasingly important role in conservation genetic, phylogenetic and population genetic analyses, as it allows incorporating extinct species into DNA sequence trees and adds time depth to population genetics studies. For many years, these types of DNA...... analyses (whether using modern or ancient DNA) were largely restricted to the analysis of short fragments of the mitochondrial genome. However, due to many technological advances during the past decade, a growing number of studies have explored the power of complete mitochondrial genome sequences...... yielded major progress with regard to both the phylogenetic positions of extinct species, as well as resolving population genetics questions in both extinct and extant species....

  16. Recriticality analyses for CAPRA cores

    International Nuclear Information System (INIS)

    Maschek, W.; Thiem, D.

    1995-01-01

    The first scoping calculation performed show that the energetics levels from recriticalities in CAPRA cores are in the same range as in conventional cores. However, considerable uncertainties exist and further analyses are necessary. Additional investigations are performed for the separation scenarios of fuel/steel/inert and matrix material as a large influence of these processes on possible ramp rates and kinetics parameters was detected in the calculations. (orig./HP)

  17. Recriticality analyses for CAPRA cores

    Energy Technology Data Exchange (ETDEWEB)

    Maschek, W.; Thiem, D.

    1995-08-01

    The first scoping calculation performed show that the energetics levels from recriticalities in CAPRA cores are in the same range as in conventional cores. However, considerable uncertainties exist and further analyses are necessary. Additional investigations are performed for the separation scenarios of fuel/steel/inert and matrix material as a large influence of these processes on possible ramp rates and kinetics parameters was detected in the calculations. (orig./HP)

  18. Technical center for transportation analyses

    International Nuclear Information System (INIS)

    Foley, J.T.

    1978-01-01

    A description is presented of an information search/retrieval/research activity of Sandia Laboratories which provides technical environmental information which may be used in transportation risk analyses, environmental impact statements, development of design and test criteria for packaging of energy materials, and transportation mode research studies. General activities described are: (1) history of center development; (2) environmental information storage/retrieval system; (3) information searches; (4) data needs identification; and (5) field data acquisition system and applications

  19. Methodology of cost benefit analyses

    International Nuclear Information System (INIS)

    Patrik, M.; Babic, P.

    2000-10-01

    The report addresses financial aspects of proposed investments and other steps which are intended to contribute to nuclear safety. The aim is to provide introductory insight into the procedures and potential of cost-benefit analyses as a routine guide when making decisions on costly provisions as one of the tools to assess whether a particular provision is reasonable. The topic is applied to the nuclear power sector. (P.A.)

  20. Resistance to Inhibitors of Cholinesterase 3 (Ric-3 Expression Promotes Selective Protein Associations with the Human α7-Nicotinic Acetylcholine Receptor Interactome.

    Directory of Open Access Journals (Sweden)

    Matthew J Mulcahy

    Full Text Available The α7-nicotinic acetylcholine receptor (α7-nAChR is a ligand-gated ion channel widely expressed in vertebrates and is associated with numerous physiological functions. As transmembrane ion channels, α7-nAChRs need to be expressed on the surface of the plasma membrane to function. The receptor has been reported to associate with proteins involved with receptor biogenesis, modulation of receptor properties, as well as intracellular signaling cascades and some of these associated proteins may affect surface expression of α7-nAChRs. The putative chaperone resistance to inhibitors of cholinesterase 3 (Ric-3 has been reported to interact with, and enhance the surface expression of, α7-nAChRs. In this study, we identified proteins that associate with α7-nAChRs when Ric-3 is expressed. Using α-bungarotoxin (α-bgtx, we isolated and compared α7-nAChR-associated proteins from two stably transfected, human tumor-derived cell lines: SH-EP1-hα7 expressing human α7-nAChRs and the same cell line further transfected to express Ric-3, SH-EP1-hα7-Ric-3. Mass spectrometric analysis of peptides identified thirty-nine proteins that are associated with α7-nAChRs only when Ric-3 was expressed. Significantly, and consistent with reports of Ric-3 function in the literature, several of the identified proteins are involved in biological processes that may affect nAChR surface expression such as post-translational processing of proteins, protein trafficking, and protein transport. Additionally, proteins affecting the cell cycle, the cytoskeleton, stress responses, as well as cyclic AMP- and inositol triphosphate-dependent signaling cascades were identified. These results illuminate how α-bgtx may be used to isolate and identify α7-nAChRs as well as how the expression of chaperones such as Ric-3 can influence proteins associating with α7-nAChRs. These associating proteins may alter activities of α7-nAChRs to expand their functionally-relevant repertoire as

  1. Chapter No.4. Safety analyses

    International Nuclear Information System (INIS)

    2002-01-01

    In 2001 the activity in the field of safety analyses was focused on verification of the safety analyses reports for NPP V-2 Bohunice and NPP Mochovce concerning the new profiled fuel and probabilistic safety assessment study for NPP Mochovce. The calculation safety analyses were performed and expert reviews for the internal UJD needs were elaborated. An important part of work was performed also in solving of scientific and technical tasks appointed within bilateral projects of co-operation between UJD and its international partnership organisations as well as within international projects ordered and financed by the European Commission. All these activities served as an independent support for UJD in its deterministic and probabilistic safety assessment of nuclear installations. A special attention was paid to a review of probabilistic safety assessment study of level 1 for NPP Mochovce. The probabilistic safety analysis of NPP related to the full power operation was elaborated in the study and a contribution of the technical and operational improvements to the risk decreasing was quantified. A core damage frequency of the reactor was calculated and the dominant initiating events and accident sequences with the major contribution to the risk were determined. The target of the review was to determine the acceptance of the sources of input information, assumptions, models, data, analyses and obtained results, so that the probabilistic model could give a real picture of the NPP. The review of the study was performed in co-operation of UJD with the IAEA (IPSART mission) as well as with other external organisations, which were not involved in the elaboration of the reviewed document and probabilistic model of NPP. The review was made in accordance with the IAEA guidelines and methodical documents of UJD and US NRC. In the field of calculation safety analyses the UJD activity was focused on the analysis of an operational event, analyses of the selected accident scenarios

  2. Analysing the Wrongness of Killing

    DEFF Research Database (Denmark)

    Di Nucci, Ezio

    2014-01-01

    This article provides an in-depth analysis of the wrongness of killing by comparing different versions of three influential views: the traditional view that killing is always wrong; the liberal view that killing is wrong if and only if the victim does not want to be killed; and Don Marquis‟ future...... of value account of the wrongness of killing. In particular, I illustrate the advantages that a basic version of the liberal view and a basic version of the future of value account have over competing alternatives. Still, ultimately none of the views analysed here are satisfactory; but the different...

  3. Methodological challenges in carbohydrate analyses

    Directory of Open Access Journals (Sweden)

    Mary Beth Hall

    2007-07-01

    Full Text Available Carbohydrates can provide up to 80% of the dry matter in animal diets, yet their specific evaluation for research and diet formulation is only now becoming a focus in the animal sciences. Partitioning of dietary carbohydrates for nutritional purposes should reflect differences in digestion and fermentation characteristics and effects on animal performance. Key challenges to designating nutritionally important carbohydrate fractions include classifying the carbohydrates in terms of nutritional characteristics, and selecting analytical methods that describe the desired fraction. The relative lack of information on digestion characteristics of various carbohydrates and their interactions with other fractions in diets means that fractions will not soon be perfectly established. Developing a system of carbohydrate analysis that could be used across animal species could enhance the utility of analyses and amount of data we can obtain on dietary effects of carbohydrates. Based on quantities present in diets and apparent effects on animal performance, some nutritionally important classes of carbohydrates that may be valuable to measure include sugars, starch, fructans, insoluble fiber, and soluble fiber. Essential to selection of methods for these fractions is agreement on precisely what carbohydrates should be included in each. Each of these fractions has analyses that could potentially be used to measure them, but most of the available methods have weaknesses that must be evaluated to see if they are fatal and the assay is unusable, or if the assay still may be made workable. Factors we must consider as we seek to analyze carbohydrates to describe diets: Does the assay accurately measure the desired fraction? Is the assay for research, regulatory, or field use (affects considerations of acceptable costs and throughput? What are acceptable accuracy and variability of measures? Is the assay robust (enhances accuracy of values? For some carbohydrates, we

  4. CFD analyses in regulatory practice

    International Nuclear Information System (INIS)

    Bloemeling, F.; Pandazis, P.; Schaffrath, A.

    2012-01-01

    Numerical software is used in nuclear regulatory procedures for many problems in the fields of neutron physics, structural mechanics, thermal hydraulics etc. Among other things, the software is employed in dimensioning and designing systems and components and in simulating transients and accidents. In nuclear technology, analyses of this kind must meet strict requirements. Computational Fluid Dynamics (CFD) codes were developed for computing multidimensional flow processes of the type occurring in reactor cooling systems or in containments. Extensive experience has been accumulated by now in selected single-phase flow phenomena. At the present time, there is a need for development and validation with respect to the simulation of multi-phase and multi-component flows. As insufficient input by the user can lead to faulty results, the validity of the results and an assessment of uncertainties are guaranteed only through consistent application of so-called Best Practice Guidelines. The authors present the possibilities now available to CFD analyses in nuclear regulatory practice. This includes a discussion of the fundamental requirements to be met by numerical software, especially the demands upon computational analysis made by nuclear rules and regulations. In conclusion, 2 examples are presented of applications of CFD analysis to nuclear problems: Determining deboration in the condenser reflux mode of operation, and protection of the reactor pressure vessel (RPV) against brittle failure. (orig.)

  5. Parameter identifiability and redundancy: theoretical considerations.

    Directory of Open Access Journals (Sweden)

    Mark P Little

    Full Text Available BACKGROUND: Models for complex biological systems may involve a large number of parameters. It may well be that some of these parameters cannot be derived from observed data via regression techniques. Such parameters are said to be unidentifiable, the remaining parameters being identifiable. Closely related to this idea is that of redundancy, that a set of parameters can be expressed in terms of some smaller set. Before data is analysed it is critical to determine which model parameters are identifiable or redundant to avoid ill-defined and poorly convergent regression. METHODOLOGY/PRINCIPAL FINDINGS: In this paper we outline general considerations on parameter identifiability, and introduce the notion of weak local identifiability and gradient weak local identifiability. These are based on local properties of the likelihood, in particular the rank of the Hessian matrix. We relate these to the notions of parameter identifiability and redundancy previously introduced by Rothenberg (Econometrica 39 (1971 577-591 and Catchpole and Morgan (Biometrika 84 (1997 187-196. Within the widely used exponential family, parameter irredundancy, local identifiability, gradient weak local identifiability and weak local identifiability are shown to be largely equivalent. We consider applications to a recently developed class of cancer models of Little and Wright (Math Biosciences 183 (2003 111-134 and Little et al. (J Theoret Biol 254 (2008 229-238 that generalize a large number of other recently used quasi-biological cancer models. CONCLUSIONS/SIGNIFICANCE: We have shown that the previously developed concepts of parameter local identifiability and redundancy are closely related to the apparently weaker properties of weak local identifiability and gradient weak local identifiability--within the widely used exponential family these concepts largely coincide.

  6. Comparative interactomics: analysis of arabidopsis 14-3-3 complexes reveals highly conserved 14-3-3 interactions between humans and plants.

    Science.gov (United States)

    Paul, Anna-Lisa; Liu, Li; McClung, Scott; Laughner, Beth; Chen, Sixue; Ferl, Robert J

    2009-04-01

    As a first step in the broad characterization of plant 14-3-3 multiprotein complexes in vivo, stringent and specific antibody affinity purification was used to capture 14-3-3s together with their interacting proteins from extracts of Arabidopsis cell suspension cultures. Approximately 120 proteins were identified as potential in vivo 14-3-3 interacting proteins by mass spectrometry of the recovered complexes. Comparison of the proteins in this data set with the 14-3-3 interacting proteins from a similar study in human embryonic kidney cell cultures revealed eight interacting proteins that likely represent reasonably abundant, fundamental 14-3-3 interaction complexes that are highly conserved across all eukaryotes. The Arabidopsis 14-3-3 interaction data set was also compared to a yeast in vivo 14-3-3 interaction data set. Four 14-3-3 interacting proteins are conserved in yeast, humans, and Arabidopsis. Comparisons of the data sets based on biochemical function revealed many additional similarities in the human and Arabidopsis data sets that represent conserved functional interactions, while also leaving many proteins uniquely identified in either Arabidopsis or human cells. In particular, the Arabidopsis interaction data set is enriched for proteins involved in metabolism.

  7. SPARQL-enabled identifier conversion with Identifiers.org

    Science.gov (United States)

    Wimalaratne, Sarala M.; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

    2015-01-01

    Motivation: On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. Results: We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. Availability and implementation: The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. Contact: sarala@ebi.ac.uk PMID:25638809

  8. SPARQL-enabled identifier conversion with Identifiers.org.

    Science.gov (United States)

    Wimalaratne, Sarala M; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

    2015-06-01

    On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. © The Author 2015. Published by Oxford University Press.

  9. Retorisk analyse af historiske tekster

    DEFF Research Database (Denmark)

    Kock, Christian Erik J

    2014-01-01

    scholars who identify themselves as rhetoricians tend to define and conduct such an analysis. It is argued that while rhetoricians would sympathize with Skinner’s adoption of speech act theory in his reading of historical documents, they would generally extend their rhetorical readings of such documents...... political theory, and it presents its own brief readings of historically significant speeches by H.P. Hanssen and George W. Bush....

  10. Severe accident recriticality analyses (SARA)

    DEFF Research Database (Denmark)

    Frid, W.; Højerup, C.F.; Lindholm, I.

    2001-01-01

    with all three codes. The core initial and boundary conditions prior to recriticality have been studied with the severe accident codes SCDAP/RELAP5, MELCOR and MAAP4. The results of the analyses show that all three codes predict recriticality-both super-prompt power bursts and quasi steady-state power......Recriticality in a BWR during reflooding of an overheated partly degraded core, i.e. with relocated control rods, has been studied for a total loss of electric power accident scenario. In order to assess the impact of recriticality on reactor safety, including accident management strategies......, which results in large energy deposition in the fuel during power burst in some accident scenarios. The highest value, 418 cal g(-1), was obtained with SIMULATE-3K for an Oskarshamn 3 case with reflooding rate of 2000 kg s(-1). In most cases, however, the predicted energy deposition was smaller, below...

  11. Hydrogen Analyses in the EPR

    International Nuclear Information System (INIS)

    Worapittayaporn, S.; Eyink, J.; Movahed, M.

    2008-01-01

    In severe accidents with core melting large amounts of hydrogen may be released into the containment. The EPR provides a combustible gas control system to prevent hydrogen combustion modes with the potential to challenge the containment integrity due to excessive pressure and temperature loads. This paper outlines the approach for the verification of the effectiveness and efficiency of this system. Specifically, the justification is a multi-step approach. It involves the deployment of integral codes, lumped parameter containment codes and CFD codes and the use of the sigma criterion, which provides the link to the broad experimental data base for flame acceleration (FA) and deflagration to detonation transition (DDT). The procedure is illustrated with an example. The performed analyses show that hydrogen combustion at any time does not lead to pressure or temperature loads that threaten the containment integrity of the EPR. (authors)

  12. Uncertainty and Sensitivity Analyses Plan

    International Nuclear Information System (INIS)

    Simpson, J.C.; Ramsdell, J.V. Jr.

    1993-04-01

    Hanford Environmental Dose Reconstruction (HEDR) Project staff are developing mathematical models to be used to estimate the radiation dose that individuals may have received as a result of emissions since 1944 from the US Department of Energy's (DOE) Hanford Site near Richland, Washington. An uncertainty and sensitivity analyses plan is essential to understand and interpret the predictions from these mathematical models. This is especially true in the case of the HEDR models where the values of many parameters are unknown. This plan gives a thorough documentation of the uncertainty and hierarchical sensitivity analysis methods recommended for use on all HEDR mathematical models. The documentation includes both technical definitions and examples. In addition, an extensive demonstration of the uncertainty and sensitivity analysis process is provided using actual results from the Hanford Environmental Dose Reconstruction Integrated Codes (HEDRIC). This demonstration shows how the approaches used in the recommended plan can be adapted for all dose predictions in the HEDR Project

  13. The hemispherical deflector analyser revisited

    Energy Technology Data Exchange (ETDEWEB)

    Benis, E.P. [Institute of Electronic Structure and Laser, P.O. Box 1385, 71110 Heraklion, Crete (Greece)], E-mail: benis@iesl.forth.gr; Zouros, T.J.M. [Institute of Electronic Structure and Laser, P.O. Box 1385, 71110 Heraklion, Crete (Greece); Department of Physics, University of Crete, P.O. Box 2208, 71003 Heraklion, Crete (Greece)

    2008-04-15

    Using the basic spectrometer trajectory equation for motion in an ideal 1/r potential derived in Eq. (101) of part I [T.J.M. Zouros, E.P. Benis, J. Electron Spectrosc. Relat. Phenom. 125 (2002) 221], the operational characteristics of a hemispherical deflector analyser (HDA) such as dispersion, energy resolution, energy calibration, input lens magnification and energy acceptance window are investigated from first principles. These characteristics are studied as a function of the entry point R{sub 0} and the nominal value of the potential V(R{sub 0}) at entry. Electron-optics simulations and actual laboratory measurements are compared to our theoretical results for an ideal biased paracentric HDA using a four-element zoom lens and a two-dimensional position sensitive detector (2D-PSD). These results should be of particular interest to users of modern HDAs utilizing a PSD.

  14. The hemispherical deflector analyser revisited

    International Nuclear Information System (INIS)

    Benis, E.P.; Zouros, T.J.M.

    2008-01-01

    Using the basic spectrometer trajectory equation for motion in an ideal 1/r potential derived in Eq. (101) of part I [T.J.M. Zouros, E.P. Benis, J. Electron Spectrosc. Relat. Phenom. 125 (2002) 221], the operational characteristics of a hemispherical deflector analyser (HDA) such as dispersion, energy resolution, energy calibration, input lens magnification and energy acceptance window are investigated from first principles. These characteristics are studied as a function of the entry point R 0 and the nominal value of the potential V(R 0 ) at entry. Electron-optics simulations and actual laboratory measurements are compared to our theoretical results for an ideal biased paracentric HDA using a four-element zoom lens and a two-dimensional position sensitive detector (2D-PSD). These results should be of particular interest to users of modern HDAs utilizing a PSD

  15. Analysing Protocol Stacks for Services

    DEFF Research Database (Denmark)

    Gao, Han; Nielson, Flemming; Nielson, Hanne Riis

    2011-01-01

    We show an approach, CaPiTo, to model service-oriented applications using process algebras such that, on the one hand, we can achieve a certain level of abstraction without being overwhelmed by the underlying implementation details and, on the other hand, we respect the concrete industrial...... standards used for implementing the service-oriented applications. By doing so, we will be able to not only reason about applications at different levels of abstractions, but also to build a bridge between the views of researchers on formal methods and developers in industry. We apply our approach...... to the financial case study taken from Chapter 0-3. Finally, we develop a static analysis to analyse the security properties as they emerge at the level of concrete industrial protocols....

  16. Analysing performance through value creation

    Directory of Open Access Journals (Sweden)

    Adrian TRIFAN

    2015-12-01

    Full Text Available This paper draws a parallel between measuring financial performance in 2 variants: the first one using data offered by accounting, which lays emphasis on maximizing profit, and the second one which aims to create value. The traditional approach to performance is based on some indicators from accounting data: ROI, ROE, EPS. The traditional management, based on analysing the data from accounting, has shown its limits, and a new approach is needed, based on creating value. The evaluation of value based performance tries to avoid the errors due to accounting data, by using other specific indicators: EVA, MVA, TSR, CVA. The main objective is shifted from maximizing the income to maximizing the value created for shareholders. The theoretical part is accompanied by a practical analysis regarding the creation of value and an analysis of the main indicators which evaluate this concept.

  17. Elucidation of epithelial-mesenchymal transition-related pathways in a triple-negative breast cancer cell line model by multi-omics interactome analysis

    DEFF Research Database (Denmark)

    Pauling, Josch K; Christensen, Anne G; Batra, Richa

    2014-01-01

    exhibiting epithelial-like and mesenchymal-like morphology, respectively. Here we identified altered protein signaling activity in a complex biologically relevant network, related to focal adhesion and migration of breast cancer cells. We found dysregulated functional network modules revealing altered...... obtained from a triple-negative breast cancer cell line model, combining data sets of gene and protein expression as well as protein phosphorylation. We focus on alterations associated with the phenotypical differences arising from epithelial-mesenchymal transition in two breast cancer cell lines...... with generation of biological networks. This allows identification of intrinsic patterns in the data and their linkage to a specific context such as cellular compartments, diseases or functions. Identification of aberrant pathways by traditional approaches is often limited to biological networks based on either...

  18. Structural Identifiability of Dynamic Systems Biology Models.

    Science.gov (United States)

    Villaverde, Alejandro F; Barreiro, Antonio; Papachristodoulou, Antonis

    2016-10-01

    A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areas.

  19. LncSubpathway: a novel approach for identifying dysfunctional subpathways associated with risk lncRNAs by integrating lncRNA and mRNA expression profiles and pathway topologies.

    Science.gov (United States)

    Xu, Yanjun; Li, Feng; Wu, Tan; Xu, Yingqi; Yang, Haixiu; Dong, Qun; Zheng, Meiyu; Shang, Desi; Zhang, Chunlong; Zhang, Yunpeng; Li, Xia

    2017-02-28

    Long non-coding RNAs (lncRNAs) play important roles in various biological processes, including the development of many diseases. Pathway analysis is a valuable aid for understanding the cellular functions of these transcripts. We have developed and characterized LncSubpathway, a novel method that integrates lncRNA and protein coding gene (PCG) expression with interactome data to identify disease risk subpathways that functionally associated with risk lncRNAs. LncSubpathway identifies the most relevance regions which are related with risk lncRNA set and implicated with study conditions through simultaneously considering the dysregulation extent of lncRNAs, PCGs and their correlations. Simulation studies demonstrated that the sensitivity and false positive rates of LncSubpathway were within acceptable ranges, and that LncSubpathway could accurately identify dysregulated regions that related with disease risk lncRNAs within pathways. When LncSubpathway was applied to colorectal carcinoma and breast cancer subtype datasets, it identified cancer type- and breast cancer subtype-related meaningful subpathways. Further, analysis of its robustness and reproducibility indicated that LncSubpathway was a reliable means of identifying subpathways that functionally associated with lncRNAs. LncSubpathway is freely available at http://www.bio-bigdata.com/lncSubpathway/.

  20. The plant design analyser and its applications

    International Nuclear Information System (INIS)

    Whitmarsh-Everiss, M.J.

    1992-01-01

    Consideration is given to the history of computational methods for the non-linear dynamic analysis of plant behaviour. This is traced from analogue to hybrid computers. When these were phased out simulation languages were used in the batch mode and the interactive computational capabilities were lost. These have subsequently been recovered using mainframe computing architecture in the context of small models using the Prototype Plant Design Analyser. Given the development of parallel processing architectures, the restriction on model size can be lifted. This capability and the use of advanced Work Stations and graphics software has enabled an advanced interactive design environment to be developed. This system is generic and can be used, with suitable graphics development, to study the dynamics and control behaviour of any plant or system for minimum cost. Examples of past and possible future uses are identified. (author)

  1. The Clavibacter michiganensis subsp. michiganensis-tomato interactome reveals the perception of pathogen by the host and suggests mechanisms of infection

    Energy Technology Data Exchange (ETDEWEB)

    Savidor, Alon [Tel Aviv University; Teper, [Tel Aviv University; Gartemann, KH [Tel Aviv University; Eichenlaub, R [Tel Aviv University; Chalupowicz, L [Tel Aviv University; Manulis-Sasson, S [Tel Aviv University; Barash, I [Tel Aviv University; Tews, H [Tel Aviv University; Mayer, K [Tel Aviv University; Giannone, Richard J [ORNL; Hettich, Robert {Bob} L [ORNL; Sessa, G [Tel Aviv University

    2012-01-01

    The Gram-positive bacterium Clavibacter michiganensis subsp. michiganensis (Cmm) causes wilt and canker disease of tomato (Solanum lycopersicum). Mechanisms of Cmm pathogenicity and tomato response to Cmm infection are not well understood. To explore the interaction between Cmm and tomato, multidimensional protein identification technology (MudPIT) and tandem mass spectrometry were used to analyze in vitro and in planta generated samples. The results show that during infection Cmm senses the plant environment, transmits signals, induces, and then secretes multiple hydrolytic enzymes, including serine proteases of the Pat-1, Ppa, and Sbt familes, the CelA, XysA, and NagA glycosyl hydrolases, and other cell wall-degrading enzymes. Tomato induction of pathogenesis-related (PR) proteins, LOX1, and other defense-related proteins during infection indicates that the plant senses the invading bacterium and mounts a basal defense response, although partial with some suppressed components including class III peroxidases and a secreted serine peptidase. The tomato ethylene-synthesizing enzyme ACC-oxidase was induced during infection with the wild-type Cmm but not during infection with an endophytic Cmm strain, identifying Cmm-triggered host synthesis of ethylene as an important factor in disease symptom development. The proteomic data were also used to improve Cmm genome annotation, and thousands of Cmm gene models were confirmed or expanded.

  2. Digital image analyser for autoradiography

    International Nuclear Information System (INIS)

    Muth, R.A.; Plotnick, J.

    1985-01-01

    The most critical parameter in quantitative autoradiography for assay of tissue concentrations of tracers is the ability to obtain precise and accurate measurements of optical density of the images. Existing high precision systems for image analysis, rotating drum densitometers, are expensive, suffer from mechanical problems and are slow. More moderately priced and reliable video camera based systems are available, but their outputs generally do not have the uniformity and stability necessary for high resolution quantitative autoradiography. The authors have designed and constructed an image analyser optimized for quantitative single and multiple tracer autoradiography which the authors refer to as a memory-mapped charged-coupled device scanner (MM-CCD). The input is from a linear array of CCD's which is used to optically scan the autoradiograph. Images are digitized into 512 x 512 picture elements with 256 gray levels and the data is stored in buffer video memory in less than two seconds. Images can then be transferred to RAM memory by direct memory-mapping for further processing. Arterial blood curve data and optical density-calibrated standards data can be entered and the optical density images can be converted automatically to tracer concentration or functional images. In double tracer studies, images produced from both exposures can be stored and processed in RAM to yield ''pure'' individual tracer concentration or functional images. Any processed image can be transmitted back to the buffer memory to be viewed on a monitor and processed for region of interest analysis

  3. Systems reliability analyses and risk analyses for the licencing procedure under atomic law

    International Nuclear Information System (INIS)

    Berning, A.; Spindler, H.

    1983-01-01

    For the licencing procedure under atomic law in accordance with Article 7 AtG, the nuclear power plant as a whole needs to be assessed, plus the reliability of systems and plant components that are essential to safety are to be determined with probabilistic methods. This requirement is the consequence of safety criteria for nuclear power plants issued by the Home Department (BMI). Systems reliability studies and risk analyses used in licencing procedures under atomic law are identified. The stress is on licencing decisions, mainly for PWR-type reactors. Reactor Safety Commission (RSK) guidelines, examples of reasoning in legal proceedings and arguments put forth by objectors are also dealt with. Correlations are shown between reliability analyses made by experts and licencing decisions by means of examples. (orig./HP) [de

  4. Socioeconomic issues and analyses for radioactive waste disposal facilities

    International Nuclear Information System (INIS)

    Ulland, L.

    1988-01-01

    Radioactive Waste facility siting and development can raise major social and economic issues in the host area. Initial site screening and analyses have been conducted for both potential high-level and low-level radioactive waste facilities; more detailed characterization and analyses are being planned. Results of these assessments are key to developing community plans that identify and implement measures to mitigate adverse socioeconomic impacts. Preliminary impact analyses conducted at high-level sites in Texas and Nevada, and site screening activities for low-level facilities in Illinois and California have identified a number of common socioeconomic issues and characteristics as well as issues and characteristics that differ between the sites and the type of facilities. Based on these comparisons, implications for selection of an appropriate methodology for impact assessment and elements of impact mitigation are identified

  5. Homozygous disruption of PDZD7 by reciprocal translocation in a consanguineous family: a new member of the Usher syndrome protein interactome causing congenital hearing impairment.

    Science.gov (United States)

    Schneider, Eberhard; Märker, Tina; Daser, Angelika; Frey-Mahn, Gabriele; Beyer, Vera; Farcas, Ruxandra; Schneider-Rätzke, Brigitte; Kohlschmidt, Nicolai; Grossmann, Bärbel; Bauss, Katharina; Napiontek, Ulrike; Keilmann, Annerose; Bartsch, Oliver; Zechner, Ulrich; Wolfrum, Uwe; Haaf, Thomas

    2009-02-15

    A homozygous reciprocal translocation, 46,XY,t(10;11),t(10;11), was detected in a boy with non-syndromic congenital sensorineural hearing impairment. Both parents and their four other children were heterozygous translocation carriers, 46,XX,t(10;11) and 46,XY,t(10;11), respectively. Fluorescence in situ hybridization of region-specific clones to patient chromosomes was used to localize the breakpoints within bacterial artificial chromosome (BAC) RP11-108L7 on chromosome 10q24.3 and within BAC CTD-2527F12 on chromosome 11q23.3. Junction fragments were cloned by vector ligation and sequenced. The chromosome 10 breakpoint was identified within the PDZ domain containing 7 (PDZD7) gene, disrupting the open reading frame of transcript PDZD7-C (without PDZ domain) and the 5'-untranslated region of transcript PDZD7-D (with one PDZ and two prolin-rich domains). The chromosome 11 breakpoint was localized in an intergenic segment. Reverse transcriptase-polymerase chain reaction analysis revealed PDZD7 expression in the human inner ear. A murine Pdzd7 transcript that is most similar in structure to human PDZD7-D is known to be expressed in the adult inner ear and retina. PDZD7 shares sequence homology with the PDZ domain-containing genes, USH1C (harmonin) and DFNB31 (whirlin). Allelic mutations in harmonin and whirlin can cause both Usher syndrome (USH1C and USH2D, respectively) and congenital hearing impairment (DFNB18 and DFNB31, respectively). Protein-protein interaction assays revealed the integration of PDZD7 in the protein network related to the human Usher syndrome. Collectively, our data provide strong evidence that PDZD7 is a new autosomal-recessive deafness-causing gene and also a prime candidate gene for Usher syndrome.

  6. Severe Accident Recriticality Analyses (SARA)

    Energy Technology Data Exchange (ETDEWEB)

    Frid, W. [Swedish Nuclear Power Inspectorate, Stockholm (Sweden); Hoejerup, F. [Risoe National Lab. (Denmark); Lindholm, I.; Miettinen, J.; Puska, E.K. [VTT Energy, Helsinki (Finland); Nilsson, Lars [Studsvik Eco and Safety AB, Nykoeping (Sweden); Sjoevall, H. [Teoliisuuden Voima Oy (Finland)

    1999-11-01

    Recriticality in a BWR has been studied for a total loss of electric power accident scenario. In a BWR, the B{sub 4}C control rods would melt and relocate from the core before the fuel during core uncovery and heat-up. If electric power returns during this time-window unborated water from ECCS systems will start to reflood the partly control rod free core. Recriticality might take place for which the only mitigating mechanisms are the Doppler effect and void formation. In order to assess the impact of recriticality on reactor safety, including accident management measures, the following issues have been investigated in the SARA project: 1. the energy deposition in the fuel during super-prompt power burst, 2. the quasi steady-state reactor power following the initial power burst and 3. containment response to elevated quasi steady-state reactor power. The approach was to use three computer codes and to further develop and adapt them for the task. The codes were SIMULATE-3K, APROS and RECRIT. Recriticality analyses were carried out for a number of selected reflooding transients for the Oskarshamn 3 plant in Sweden with SIMULATE-3K and for the Olkiluoto 1 plant in Finland with all three codes. The core state initial and boundary conditions prior to recriticality have been studied with the severe accident codes SCDAP/RELAP5, MELCOR and MAAP4. The results of the analyses show that all three codes predict recriticality - both superprompt power bursts and quasi steady-state power generation - for the studied range of parameters, i. e. with core uncovery and heat-up to maximum core temperatures around 1800 K and water flow rates of 45 kg/s to 2000 kg/s injected into the downcomer. Since the recriticality takes place in a small fraction of the core the power densities are high which results in large energy deposition in the fuel during power burst in some accident scenarios. The highest value, 418 cal/g, was obtained with SIMULATE-3K for an Oskarshamn 3 case with reflooding

  7. Severe accident recriticality analyses (SARA)

    Energy Technology Data Exchange (ETDEWEB)

    Frid, W. E-mail: wiktor.frid@ski.se; Hoejerup, F.; Lindholm, I.; Miettinen, J.; Nilsson, L.; Puska, E.K.; Sjoevall, H

    2001-11-01

    Recriticality in a BWR during reflooding of an overheated partly degraded core, i.e. with relocated control rods, has been studied for a total loss of electric power accident scenario. In order to assess the impact of recriticality on reactor safety, including accident management strategies, the following issues have been investigated in the SARA project: (1) the energy deposition in the fuel during super-prompt power burst; (2) the quasi steady-state reactor power following the initial power burst; and (3) containment response to elevated quasi steady-state reactor power. The approach was to use three computer codes and to further develop and adapt them for the task. The codes were SIMULATE-3K, APROS and RECRIT. Recriticality analyses were carried out for a number of selected reflooding transients for the Oskarshamn 3 plant in Sweden with SIMULATE-3K and for the Olkiluoto 1 plant in Finland with all three codes. The core initial and boundary conditions prior to recriticality have been studied with the severe accident codes SCDAP/RELAP5, MELCOR and MAAP4. The results of the analyses show that all three codes predict recriticality--both super-prompt power bursts and quasi steady-state power generation--for the range of parameters studied, i.e. with core uncovering and heat-up to maximum core temperatures of approximately 1800 K, and water flow rates of 45-2000 kg s{sup -1} injected into the downcomer. Since recriticality takes place in a small fraction of the core, the power densities are high, which results in large energy deposition in the fuel during power burst in some accident scenarios. The highest value, 418 cal g{sup -1}, was obtained with SIMULATE-3K for an Oskarshamn 3 case with reflooding rate of 2000 kg s{sup -1}. In most cases, however, the predicted energy deposition was smaller, below the regulatory limits for fuel failure, but close to or above recently observed thresholds for fragmentation and dispersion of high burn-up fuel. The highest calculated

  8. Severe accident recriticality analyses (SARA)

    International Nuclear Information System (INIS)

    Frid, W.; Hoejerup, F.; Lindholm, I.; Miettinen, J.; Nilsson, L.; Puska, E.K.; Sjoevall, H.

    2001-01-01

    Recriticality in a BWR during reflooding of an overheated partly degraded core, i.e. with relocated control rods, has been studied for a total loss of electric power accident scenario. In order to assess the impact of recriticality on reactor safety, including accident management strategies, the following issues have been investigated in the SARA project: (1) the energy deposition in the fuel during super-prompt power burst; (2) the quasi steady-state reactor power following the initial power burst; and (3) containment response to elevated quasi steady-state reactor power. The approach was to use three computer codes and to further develop and adapt them for the task. The codes were SIMULATE-3K, APROS and RECRIT. Recriticality analyses were carried out for a number of selected reflooding transients for the Oskarshamn 3 plant in Sweden with SIMULATE-3K and for the Olkiluoto 1 plant in Finland with all three codes. The core initial and boundary conditions prior to recriticality have been studied with the severe accident codes SCDAP/RELAP5, MELCOR and MAAP4. The results of the analyses show that all three codes predict recriticality--both super-prompt power bursts and quasi steady-state power generation--for the range of parameters studied, i.e. with core uncovering and heat-up to maximum core temperatures of approximately 1800 K, and water flow rates of 45-2000 kg s -1 injected into the downcomer. Since recriticality takes place in a small fraction of the core, the power densities are high, which results in large energy deposition in the fuel during power burst in some accident scenarios. The highest value, 418 cal g -1 , was obtained with SIMULATE-3K for an Oskarshamn 3 case with reflooding rate of 2000 kg s -1 . In most cases, however, the predicted energy deposition was smaller, below the regulatory limits for fuel failure, but close to or above recently observed thresholds for fragmentation and dispersion of high burn-up fuel. The highest calculated quasi steady

  9. Severe Accident Recriticality Analyses (SARA)

    International Nuclear Information System (INIS)

    Frid, W.; Hoejerup, F.; Lindholm, I.; Miettinen, J.; Puska, E.K.; Nilsson, Lars; Sjoevall, H.

    1999-11-01

    Recriticality in a BWR has been studied for a total loss of electric power accident scenario. In a BWR, the B 4 C control rods would melt and relocate from the core before the fuel during core uncovery and heat-up. If electric power returns during this time-window unborated water from ECCS systems will start to reflood the partly control rod free core. Recriticality might take place for which the only mitigating mechanisms are the Doppler effect and void formation. In order to assess the impact of recriticality on reactor safety, including accident management measures, the following issues have been investigated in the SARA project: 1. the energy deposition in the fuel during super-prompt power burst, 2. the quasi steady-state reactor power following the initial power burst and 3. containment response to elevated quasi steady-state reactor power. The approach was to use three computer codes and to further develop and adapt them for the task. The codes were SIMULATE-3K, APROS and RECRIT. Recriticality analyses were carried out for a number of selected reflooding transients for the Oskarshamn 3 plant in Sweden with SIMULATE-3K and for the Olkiluoto 1 plant in Finland with all three codes. The core state initial and boundary conditions prior to recriticality have been studied with the severe accident codes SCDAP/RELAP5, MELCOR and MAAP4. The results of the analyses show that all three codes predict recriticality - both superprompt power bursts and quasi steady-state power generation - for the studied range of parameters, i. e. with core uncovery and heat-up to maximum core temperatures around 1800 K and water flow rates of 45 kg/s to 2000 kg/s injected into the downcomer. Since the recriticality takes place in a small fraction of the core the power densities are high which results in large energy deposition in the fuel during power burst in some accident scenarios. The highest value, 418 cal/g, was obtained with SIMULATE-3K for an Oskarshamn 3 case with reflooding

  10. A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex.

    Science.gov (United States)

    Armour, Sean M; Bennett, Eric J; Braun, Craig R; Zhang, Xiao-Yong; McMahon, Steven B; Gygi, Steven P; Harper, J Wade; Sinclair, David A

    2013-04-01

    Although many functions and targets have been attributed to the histone and protein deacetylase SIRT1, a comprehensive analysis of SIRT1 binding proteins yielding a high-confidence interaction map has not been established. Using a comparative statistical analysis of binding partners, we have assembled a high-confidence SIRT1 interactome. Employing this method, we identified the deubiquitinating enzyme ubiquitin-specific protease 22 (USP22), a component of the deubiquitinating module (DUBm) of the SAGA transcriptional coactivating complex, as a SIRT1-interacting partner. We found that this interaction is highly specific, requires the ZnF-UBP domain of USP22, and is disrupted by the inactivating H363Y mutation within SIRT1. Moreover, we show that USP22 is acetylated on multiple lysine residues and that alteration of a single lysine (K129) within the ZnF-UBP domain is sufficient to alter interaction of the DUBm with the core SAGA complex. Furthermore, USP22-mediated recruitment of SIRT1 activity promotes the deacetylation of individual SAGA complex components. Our results indicate an important role of SIRT1-mediated deacetylation in regulating the formation of DUBm subcomplexes within the larger SAGA complex.

  11. A systems wide mass spectrometric based linear motif screen to identify dominant in-vivo interacting proteins for the ubiquitin ligase MDM2.

    Science.gov (United States)

    Nicholson, Judith; Scherl, Alex; Way, Luke; Blackburn, Elizabeth A; Walkinshaw, Malcolm D; Ball, Kathryn L; Hupp, Ted R

    2014-06-01

    Linear motifs mediate protein-protein interactions (PPI) that allow expansion of a target protein interactome at a systems level. This study uses a proteomics approach and linear motif sub-stratifications to expand on PPIs of MDM2. MDM2 is a multi-functional protein with over one hundred known binding partners not stratified by hierarchy or function. A new linear motif based on a MDM2 interaction consensus is used to select novel MDM2 interactors based on Nutlin-3 responsiveness in a cell-based proteomics screen. MDM2 binds a subset of peptide motifs corresponding to real proteins with a range of allosteric responses to MDM2 ligands. We validate cyclophilin B as a novel protein with a consensus MDM2 binding motif that is stabilised by Nutlin-3 in vivo, thus identifying one of the few known interactors of MDM2 that is stabilised by Nutlin-3. These data invoke two modes of peptide binding at the MDM2 N-terminus that rely on a consensus core motif to control the equilibrium between MDM2 binding proteins. This approach stratifies MDM2 interacting proteins based on the linear motif feature and provides a new biomarker assay to define clinically relevant Nutlin-3 responsive MDM2 interactors. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Genome-Wide Bimolecular Fluorescence Complementation-Based Proteomic Analysis of Toxoplasma gondii ROP18’s Human Interactome Shows Its Key Role in Regulation of Cell Immunity and Apoptosis

    Directory of Open Access Journals (Sweden)

    Jing Xia

    2018-02-01

    Full Text Available Toxoplasma gondii rhoptry protein ROP18 (TgROP18 is a key virulence factor secreted into the host cell during invasion, where it modulates the host cell response by interacting with its host targets. However, only a few TgROP18 targets have been identified. In this study, we applied a high-throughput protein–protein interaction (PPI screening in human cells using bimolecular fluorescence complementation (BiFC to identify the targets of Type I strain ROP18 (ROP18I and Type II strain ROP18 (ROP18II. From a pool of more than 18,000 human proteins, 492 and 141 proteins were identified as the targets of ROP18I and ROP18II, respectively. Gene ontology, search tool for the retrieval of interacting genes/proteins PPI network, and Ingenuity pathway analyses revealed that the majority of these proteins were associated with immune response and apoptosis. This indicates a key role of TgROP18 in manipulating host’s immunity and cell apoptosis, which might contribute to the immune escape and successful parasitism of the parasite. Among the proteins identified, the immunity-related proteins N-myc and STAT interactor, IL20RB, IL21, ubiquitin C, and vimentin and the apoptosis-related protein P2RX1 were further verified as ROP18I targets by sensitized emission-fluorescence resonance energy transfer (SE-FRET and co-immunoprecipitation. Our study substantially contributes to the current limited knowledge on human targets of TgROP18 and provides a novel tool to investigate the function of parasite effectors in human cells.

  13. Pawnee Nation Energy Option Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Matlock, M.; Kersey, K.; Riding In, C.

    2009-07-31

    In 2003, the Pawnee Nation leadership identified the need for the tribe to comprehensively address its energy issues. During a strategic energy planning workshop a general framework was laid out and the Pawnee Nation Energy Task Force was created to work toward further development of the tribe’s energy vision. The overarching goals of the “first steps” project were to identify the most appropriate focus for its strategic energy initiatives going forward, and to provide information necessary to take the next steps in pursuit of the “best fit” energy options. Based on the request of Pawnee Nation’s Energy Task Force the research team, consisting Tribal personnel and Summit Blue Consulting, focused on a review of renewable energy resource development potential, funding sources and utility organizational along with energy savings options. Elements of the energy demand forecasting and characterization and demand side options review remained in the scope of work, but were only addressed at a high level. Description of Activities Performed Renewable Energy Resource Development Potential The research team reviewed existing data pertaining to the availability of biomass (focusing on woody biomass, agricultural biomass/bio-energy crops, and methane capture), solar, wind and hydropower resources on the Pawnee-owned lands. Using these data, combined with assumptions about costs and revenue streams, the research team performed preliminary feasibility assessments for each resource category. The research team also reviewed available funding resources and made recommendations to Pawnee Nation highlighting those resources with the greatest potential for financially-viable development, both in the near-term and over a longer time horizon. Energy Efficiency Options While this was not a major focus of the project, the research team highlighted common strategies for reducing energy use in buildings. The team also discussed the benefits of adopting a building energy code and

  14. A study on the re-identifiability of Dutch citizens

    OpenAIRE

    Koot, M.R.; van 't Noordende, G.; de Laat, C.; Serjantov, A.; Troncoso, C.

    2010-01-01

    This paper analyses the re-identifiability of Dutch citizens by various demographics. Our analysis is based on registry office data of 2.7 million Dutch citizens, ~16% of the total population. We provide overall statistics on re-identifiability for a range of quasi-identifiers, and present an in-depth analysis of quasi-identifiers found in two de-identified data sets. We found that 67.0% of the sampled population is unambiguously identifiable by date of birth and four-digit postal code alone,...

  15. Isotropy analyses of the Planck convergence map

    Science.gov (United States)

    Marques, G. A.; Novaes, C. P.; Bernui, A.; Ferreira, I. S.

    2018-01-01

    The presence of matter in the path of relic photons causes distortions in the angular pattern of the cosmic microwave background (CMB) temperature fluctuations, modifying their properties in a slight but measurable way. Recently, the Planck Collaboration released the estimated convergence map, an integrated measure of the large-scale matter distribution that produced the weak gravitational lensing (WL) phenomenon observed in Planck CMB data. We perform exhaustive analyses of this convergence map calculating the variance in small and large regions of the sky, but excluding the area masked due to Galactic contaminations, and compare them with the features expected in the set of simulated convergence maps, also released by the Planck Collaboration. Our goal is to search for sky directions or regions where the WL imprints anomalous signatures to the variance estimator revealed through a χ2 analyses at a statistically significant level. In the local analysis of the Planck convergence map, we identified eight patches of the sky in disagreement, in more than 2σ, with what is observed in the average of the simulations. In contrast, in the large regions analysis we found no statistically significant discrepancies, but, interestingly, the regions with the highest χ2 values are surrounding the ecliptic poles. Thus, our results show a good agreement with the features expected by the Λ cold dark matter concordance model, as given by the simulations. Yet, the outliers regions found here could suggest that the data still contain residual contamination, like noise, due to over- or underestimation of systematic effects in the simulation data set.

  16. Near Identifiability of Dynamical Systems

    Science.gov (United States)

    Hadaegh, F. Y.; Bekey, G. A.

    1987-01-01

    Concepts regarding approximate mathematical models treated rigorously. Paper presents new results in analysis of structural identifiability, equivalence, and near equivalence between mathematical models and physical processes they represent. Helps establish rigorous mathematical basis for concepts related to structural identifiability and equivalence revealing fundamental requirements, tacit assumptions, and sources of error. "Structural identifiability," as used by workers in this field, loosely translates as meaning ability to specify unique mathematical model and set of model parameters that accurately predict behavior of corresponding physical system.

  17. Probing the drug interactome by chemical proteomics

    NARCIS (Netherlands)

    Dadvar, P.

    2009-01-01

    Approved PDE5 inhibitors for the treatment of erectile dysfunction (ED) include sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis), all of which are considered very specific and ‘safe’ drugs. However, even highly selective, FDA approved drugs can have the potential to bind to other

  18. Unraveling the Plant-Soil Interactome

    Science.gov (United States)

    Lipton, M. S.; Hixson, K.; Ahkami, A. H.; HaHandkumbura, P. P.; Hess, N. J.; Fang, Y.; Fortin, D.; Stanfill, B.; Yabusaki, S.; Engbrecht, K. M.; Baker, E.; Renslow, R.; Jansson, C.

    2017-12-01

    Plant photosynthesis is the primary conduit of carbon fixation from the atmosphere to the terrestrial ecosystem. While more is known about plant physiology and biochemistry, the interplay between genetic and environmental factors that govern partitioning of carbon to above- and below ground plant biomass, to microbes, to the soil, and respired to the atmosphere is not well understood holistically. To address this knowledge gap there is a need to define, study, comprehend, and model the plant ecosystem as an integrated system of integrated biotic and abiotic processes and feedbacks. Local rhizosphere conditions are an important control on plant performance but are in turn affected by plant uptake and rhizodeposition processes. C3 and C4 plants have different CO2 fixation strategies and likely have differential metabolic profiles resulting in different carbon sources exuding to the rhizosphere. In this presentation, we report on an integrated capability to better understand plant-soil interactions, including modeling tools that address the spatiotemporal hydrobiogeochemistry in the rhizosphere. Comparing Brachypodium distachyon, (Brachypodium) as our C3 representative and Setaria viridis (Setaria) as our C4 representative, we designed, highly controlled single-plant experimental ecosystems based these model grasses to enable quantitative prediction of ecosystem traits and responses as a function of plant genotype and environmental variables. A metabolomics survey of 30 Brachypodium genotypes grown under control and drought conditions revealed specific metabolites that correlated with biomass production and drought tolerance. A comparison of Brachypodium and Setaria grown with control and a future predicted elevated CO2 level revealed changes in biomass accumulation and metabolite profiles between the C3 and C4 species in both leaves and roots. Finally, we are building an mechanistic modeling capability that will contribute to a better basis for modeling plant water and nutrient cycling in larger scale models.

  19. A draft of the human septin interactome.

    Directory of Open Access Journals (Sweden)

    Marcel Nakahira

    Full Text Available BACKGROUND: Septins belong to the GTPase superclass of proteins and have been functionally implicated in cytokinesis and the maintenance of cellular morphology. They are found in all eukaryotes, except in plants. In mammals, 14 septins have been described that can be divided into four groups. It has been shown that mammalian septins can engage in homo- and heterooligomeric assemblies, in the form of filaments, which have as a basic unit a hetero-trimeric core. In addition, it has been speculated that the septin filaments may serve as scaffolds for the recruitment of additional proteins. METHODOLOGY/PRINCIPAL FINDINGS: Here, we performed yeast two-hybrid screens with human septins 1-10, which include representatives of all four septin groups. Among the interactors detected, we found predominantly other septins, confirming the tendency of septins to engage in the formation of homo- and heteropolymeric filaments. CONCLUSIONS/SIGNIFICANCE: If we take as reference the reported arrangement of the septins 2, 6 and 7 within the heterofilament, (7-6-2-2-6-7, we note that the majority of the observed interactions respect the "group rule", i.e. members of the same group (e.g. 6, 8, 10 and 11 can replace each other in the specific position along the heterofilament. Septins of the SEPT6 group preferentially interacted with septins of the SEPT2 group (p<0.001, SEPT3 group (p<0.001 and SEPT7 group (p<0.001. SEPT2 type septins preferentially interacted with septins of the SEPT6 group (p<0.001 aside from being the only septin group which interacted with members of its own group. Finally, septins of the SEPT3 group interacted preferentially with septins of the SEPT7 group (p<0.001. Furthermore, we found non-septin interactors which can be functionally attributed to a variety of different cellular activities, including: ubiquitin/sumoylation cycles, microtubular transport and motor activities, cell division and the cell cycle, cell motility, protein phosphorylation/signaling, endocytosis, and apoptosis.

  20. Improving word coverage using unsupervised morphological analyser

    Indian Academy of Sciences (India)

    To enable a computer to process information in human languages, ... vised morphological analyser (UMA) would learn how to analyse a language just by looking ... result for English, but they did remarkably worse for Finnish and Turkish.

  1. Techniques for Analysing Problems in Engineering Projects

    DEFF Research Database (Denmark)

    Thorsteinsson, Uffe

    1998-01-01

    Description of how CPM network can be used for analysing complex problems in engineering projects.......Description of how CPM network can be used for analysing complex problems in engineering projects....

  2. Automatic incrementalization of Prolog based static analyses

    DEFF Research Database (Denmark)

    Eichberg, Michael; Kahl, Matthias; Saha, Diptikalyan

    2007-01-01

    Modem development environments integrate various static analyses into the build process. Analyses that analyze the whole project whenever the project changes are impractical in this context. We present an approach to automatic incrementalization of analyses that are specified as tabled logic prog...

  3. Target gene analyses of 39 amelogenesis imperfecta kindreds

    Science.gov (United States)

    Chan, Hui-Chen; Estrella, Ninna M. R. P.; Milkovich, Rachel N.; Kim, Jung-Wook; Simmer, James P.; Hu, Jan C-C.

    2012-01-01

    Previously, mutational analyses identified six disease-causing mutations in 24 amelogenesis imperfecta (AI) kindreds. We have since expanded the number of AI kindreds to 39, and performed mutation analyses covering the coding exons and adjoining intron sequences for the six proven AI candidate genes [amelogenin (AMELX), enamelin (ENAM), family with sequence similarity 83, member H (FAM83H), WD repeat containing domain 72 (WDR72), enamelysin (MMP20), and kallikrein-related peptidase 4 (KLK4)] and for ameloblastin (AMBN) (a suspected candidate gene). All four of the X-linked AI families (100%) had disease-causing mutations in AMELX, suggesting that AMELX is the only gene involved in the aetiology of X-linked AI. Eighteen families showed an autosomal-dominant pattern of inheritance. Disease-causing mutations were identified in 12 (67%): eight in FAM83H, and four in ENAM. No FAM83H coding-region or splice-junction mutations were identified in three probands with autosomal-dominant hypocalcification AI (ADHCAI), suggesting that a second gene may contribute to the aetiology of ADHCAI. Six families showed an autosomal-recessive pattern of inheritance, and disease-causing mutations were identified in three (50%): two in MMP20, and one in WDR72. No disease-causing mutations were found in 11 families with only one affected member. We conclude that mutation analyses of the current candidate genes for AI have about a 50% chance of identifying the disease-causing mutation in a given kindred. PMID:22243262

  4. Reproducibility of neuroimaging analyses across operating systems.

    Science.gov (United States)

    Glatard, Tristan; Lewis, Lindsay B; Ferreira da Silva, Rafael; Adalat, Reza; Beck, Natacha; Lepage, Claude; Rioux, Pierre; Rousseau, Marc-Etienne; Sherif, Tarek; Deelman, Ewa; Khalili-Mahani, Najmeh; Evans, Alan C

    2015-01-01

    Neuroimaging pipelines are known to generate different results depending on the computing platform where they are compiled and executed. We quantify these differences for brain tissue classification, fMRI analysis, and cortical thickness (CT) extraction, using three of the main neuroimaging packages (FSL, Freesurfer and CIVET) and different versions of GNU/Linux. We also identify some causes of these differences using library and system call interception. We find that these packages use mathematical functions based on single-precision floating-point arithmetic whose implementations in operating systems continue to evolve. While these differences have little or no impact on simple analysis pipelines such as brain extraction and cortical tissue classification, their accumulation creates important differences in longer pipelines such as subcortical tissue classification, fMRI analysis, and cortical thickness extraction. With FSL, most Dice coefficients between subcortical classifications obtained on different operating systems remain above 0.9, but values as low as 0.59 are observed. Independent component analyses (ICA) of fMRI data differ between operating systems in one third of the tested subjects, due to differences in motion correction. With Freesurfer and CIVET, in some brain regions we find an effect of build or operating system on cortical thickness. A first step to correct these reproducibility issues would be to use more precise representations of floating-point numbers in the critical sections of the pipelines. The numerical stability of pipelines should also be reviewed.

  5. Statistical analyses of extreme food habits

    International Nuclear Information System (INIS)

    Breuninger, M.; Neuhaeuser-Berthold, M.

    2000-01-01

    This report is a summary of the results of the project ''Statistical analyses of extreme food habits'', which was ordered from the National Office for Radiation Protection as a contribution to the amendment of the ''General Administrative Regulation to paragraph 45 of the Decree on Radiation Protection: determination of the radiation exposition by emission of radioactive substances from facilities of nuclear technology''. Its aim is to show if the calculation of the radiation ingested by 95% of the population by food intake, like it is planned in a provisional draft, overestimates the true exposure. If such an overestimation exists, the dimension of it should be determined. It was possible to prove the existence of this overestimation but its dimension could only roughly be estimated. To identify the real extent of it, it is necessary to include the specific activities of the nuclides, which were not available for this investigation. In addition to this the report shows how the amounts of food consumption of different groups of foods influence each other and which connections between these amounts should be taken into account, in order to estimate the radiation exposition as precise as possible. (orig.) [de

  6. Thermomagnetic Analyses to Test Concrete Stability

    Science.gov (United States)

    Geiss, C. E.; Gourley, J. R.

    2017-12-01

    Over the past decades pyrrhotite-containing aggregate has been used in concrete to build basements and foundations in central Connecticut. The sulphur in the pyrrhotite reacts to several secondary minerals, and associated changes in volume lead to a loss of structural integrity. As a result hundreds of homes have been rendered worthless as remediation costs often exceed the value of the homes and the value of many other homes constructed during the same time period is in question as concrete provenance and potential future structural issues are unknown. While minor abundances of pyrrhotite are difficult to detect or quantify by traditional means, the mineral is easily identified through its magnetic properties. All concrete samples from affected homes show a clear increase in magnetic susceptibility above 220°C due to the γ - transition of Fe9S10 [1] and a clearly defined Curie-temperature near 320°C for Fe7S8. X-ray analyses confirm the presence of pyrrhotite and ettringite in these samples. Synthetic mixtures of commercially available concrete and pyrrhotite show that the method is semiquantitative but needs to be calibrated for specific pyrrhotite mineralogies. 1. Schwarz, E.J., Magnetic properties of pyrrhotite and their use in applied geology and geophysics. 1975, Geological Survey of Canada : Ottawa, ON, Canada: Canada.

  7. The NOAA Dataset Identifier Project

    Science.gov (United States)

    de la Beaujardiere, J.; Mccullough, H.; Casey, K. S.

    2013-12-01

    The US National Oceanic and Atmospheric Administration (NOAA) initiated a project in 2013 to assign persistent identifiers to datasets archived at NOAA and to create informational landing pages about those datasets. The goals of this project are to enable the citation of datasets used in products and results in order to help provide credit to data producers, to support traceability and reproducibility, and to enable tracking of data usage and impact. A secondary goal is to encourage the submission of datasets for long-term preservation, because only archived datasets will be eligible for a NOAA-issued identifier. A team was formed with representatives from the National Geophysical, Oceanographic, and Climatic Data Centers (NGDC, NODC, NCDC) to resolve questions including which identifier scheme to use (answer: Digital Object Identifier - DOI), whether or not to embed semantics in identifiers (no), the level of granularity at which to assign identifiers (as coarsely as reasonable), how to handle ongoing time-series data (do not break into chunks), creation mechanism for the landing page (stylesheet from formal metadata record preferred), and others. Decisions made and implementation experience gained will inform the writing of a Data Citation Procedural Directive to be issued by the Environmental Data Management Committee in 2014. Several identifiers have been issued as of July 2013, with more on the way. NOAA is now reporting the number as a metric to federal Open Government initiatives. This paper will provide further details and status of the project.

  8. Trial sequential analyses of meta-analyses of complications in laparoscopic vs. small-incision cholecystectomy: more randomized patients are needed

    DEFF Research Database (Denmark)

    Keus, Frederik; Wetterslev, Jørn; Gluud, Christian

    2010-01-01

    Conclusions based on meta-analyses of randomized trials carry a status of "truth." Methodological components may identify trials with systematic errors ("bias"). Trial sequential analysis (TSA) evaluates random errors in meta-analysis. We analyzed meta-analyses on laparoscopic vs. small-incision ......Conclusions based on meta-analyses of randomized trials carry a status of "truth." Methodological components may identify trials with systematic errors ("bias"). Trial sequential analysis (TSA) evaluates random errors in meta-analysis. We analyzed meta-analyses on laparoscopic vs. small...

  9. Altools: a user friendly NGS data analyser.

    Science.gov (United States)

    Camiolo, Salvatore; Sablok, Gaurav; Porceddu, Andrea

    2016-02-17

    Genotyping by re-sequencing has become a standard approach to estimate single nucleotide polymorphism (SNP) diversity, haplotype structure and the biodiversity and has been defined as an efficient approach to address geographical population genomics of several model species. To access core SNPs and insertion/deletion polymorphisms (indels), and to infer the phyletic patterns of speciation, most such approaches map short reads to the reference genome. Variant calling is important to establish patterns of genome-wide association studies (GWAS) for quantitative trait loci (QTLs), and to determine the population and haplotype structure based on SNPs, thus allowing content-dependent trait and evolutionary analysis. Several tools have been developed to investigate such polymorphisms as well as more complex genomic rearrangements such as copy number variations, presence/absence variations and large deletions. The programs available for this purpose have different strengths (e.g. accuracy, sensitivity and specificity) and weaknesses (e.g. low computation speed, complex installation procedure and absence of a user-friendly interface). Here we introduce Altools, a software package that is easy to install and use, which allows the precise detection of polymorphisms and structural variations. Altools uses the BWA/SAMtools/VarScan pipeline to call SNPs and indels, and the dnaCopy algorithm to achieve genome segmentation according to local coverage differences in order to identify copy number variations. It also uses insert size information from the alignment of paired-end reads and detects potential large deletions. A double mapping approach (BWA/BLASTn) identifies precise breakpoints while ensuring rapid elaboration. Finally, Altools implements several processes that yield deeper insight into the genes affected by the detected polymorphisms. Altools was used to analyse both simulated and real next-generation sequencing (NGS) data and performed satisfactorily in terms of

  10. RELAP5 analyses and support of Oconee-1 PTS studies

    International Nuclear Information System (INIS)

    Charlton, T.R.

    1983-01-01

    The integrity of a reactor vessel during a severe overcooling transient with primary system pressurization is a current safety concern and has been identified as an Unresolved Safety Issue(USI) A-49 by the US Nuclear Regulatory Commission (NRC). Resolution of USI A-49, denoted as Pressurized Thermal Shock (PTS), is being examined by the US NRC sponsored PTS integration study. In support of this study, the Idaho National Engineering Laboratory (INEL) has performed RELAP5/MOD1.5 thermal-hydraulic analyses of selected overcooling transients. These transient analyses were performed for the Oconee-1 pressurized water reactor (PWR), which is Babcock and Wilcox designed nuclear steam supply system

  11. Identifying tier one key suppliers.

    Science.gov (United States)

    Wicks, Steve

    2013-01-01

    In today's global marketplace, businesses are becoming increasingly reliant on suppliers for the provision of key processes, activities, products and services in support of their strategic business goals. The result is that now, more than ever, the failure of a key supplier has potential to damage reputation, productivity, compliance and financial performance seriously. Yet despite this, there is no recognised standard or guidance for identifying a tier one key supplier base and, up to now, there has been little or no research on how to do so effectively. This paper outlines the key findings of a BCI-sponsored research project to investigate good practice in identifying tier one key suppliers, and suggests a scalable framework process model and risk matrix tool to help businesses effectively identify their tier one key supplier base.

  12. Football refereeing: Identifying innovative methods

    Directory of Open Access Journals (Sweden)

    Reza MohammadKazemi

    2014-08-01

    Full Text Available The aim of the present study is to identify the potentials innovation in football industry. Data were collected from 10 national and international referees, assistant referees and referees’ supervisors in Iran. In this study, technological innovations are identified that assist better refereeing performances. The analysis revealed a significant relationship between using new technologies and referees ‘performance. The results indicate that elite referees, assistant referees and supervisors agreed to use new technological innovations during the game. According to their comments, this kind of technology causes the referees’ performance development.

  13. Fracture analyses of WWER reactor pressure vessels

    International Nuclear Information System (INIS)

    Sievers, J.; Liu, X.

    1997-01-01

    In the paper first the methodology of fracture assessment based on finite element (FE) calculations is described and compared with simplified methods. The FE based methodology was verified by analyses of large scale thermal shock experiments in the framework of the international comparative study FALSIRE (Fracture Analyses of Large Scale Experiments) organized by GRS and ORNL. Furthermore, selected results from fracture analyses of different WWER type RPVs with postulated cracks under different loading transients are presented. 11 refs, 13 figs, 1 tab

  14. Fracture analyses of WWER reactor pressure vessels

    Energy Technology Data Exchange (ETDEWEB)

    Sievers, J; Liu, X [Gesellschaft fuer Anlagen- und Reaktorsicherheit mbH (GRS), Koeln (Germany)

    1997-09-01

    In the paper first the methodology of fracture assessment based on finite element (FE) calculations is described and compared with simplified methods. The FE based methodology was verified by analyses of large scale thermal shock experiments in the framework of the international comparative study FALSIRE (Fracture Analyses of Large Scale Experiments) organized by GRS and ORNL. Furthermore, selected results from fracture analyses of different WWER type RPVs with postulated cracks under different loading transients are presented. 11 refs, 13 figs, 1 tab.

  15. [Anne Arold. Kontrastive Analyse...] / Paul Alvre

    Index Scriptorium Estoniae

    Alvre, Paul, 1921-2008

    2001-01-01

    Arvustus: Arold, Anne. Kontrastive analyse der Wortbildungsmuster im Deutschen und im Estnischen (am Beispiel der Aussehensadjektive). Tartu, 2000. (Dissertationes philologiae germanicae Universitatis Tartuensis)

  16. Database-Driven Analyses of Astronomical Spectra

    Science.gov (United States)

    Cami, Jan

    2012-03-01

    species to the fullerene species C60 and C70 [4]. Given the large number and variety of molecules detected in space, molecular infrared spectroscopy can be used to study pretty much any astrophysical environment that is not too energetic to dissociate the molecules. At the lowest energies, it is interesting to note that molecules such as CN have been used to measure the temperature of the Cosmic Microwave Background (see e.g., Ref. 15). The great diagnostic potential of infrared molecular spectroscopy comes at a price though. Extracting the physical parameters from the observations requires expertise in knowing how various physical processes and instrumental characteristics play together in producing the observed spectra. In addition to the astronomical aspects, this often includes interpreting and understanding the limitations of laboratory data and quantum-chemical calculations; the study of the interaction of matter with radiation at microscopic scales (called radiative transfer, akin to ray tracing) and the effects of observing (e.g., smoothing and resampling) on the resulting spectra and possible instrumental effects (e.g., fringes). All this is not trivial. To make matters worse, observational spectra often contain many components, and might include spectral contributions stemming from very different physical conditions. Fully analyzing such observations is thus a time-consuming task that requires mastery of several techniques. And with ever-increasing rates of observational data acquisition, it seems clear that in the near future, some form of automation is required to handle the data stream. It is thus appealing to consider what part of such analyses could be done without too much human intervention. Two different aspects can be separated: the first step involves simply identifying the molecular species present in the observations. Once the molecular inventory is known, we can try to extract the physical parameters from the observed spectral properties. For both

  17. SOCIODEMOGRAPHIC DATA USED FOR IDENTIFYING ...

    Science.gov (United States)

    Due to unique social and demographic characteristics, various segments of the population may experience exposures different from those of the general population, which, in many cases, may be greater. When risk assessments do not characterize subsets of the general population, the populations that may experience the greatest risk remain unidentified. When such populations are not identified, the social and demographic data relevant to these populations is not considered when preparing exposure estimates, which can underestimate exposure and risk estimates for at-risk populations. Thus, it is necessary for risk or exposure assessors characterizing a diverse population, to first identify and then enumerate certain groups within the general population who are at risk for greater contaminant exposures. The document entitled Sociodemographic Data Used for Identifying Potentially Highly Exposed Populations (also referred to as the Highly Exposed Populations document), assists assessors in identifying and enumerating potentially highly exposed populations. This document presents data relating to factors which potentially impact an individual or group's exposure to environmental contaminants based on activity patterns (how time is spent), microenvironments (locations where time is spent), and other socio-demographic data such as age, gender, race and economic status. Populations potentially more exposed to various chemicals of concern, relative to the general population

  18. SNP interaction pattern identifier (SIPI)

    DEFF Research Database (Denmark)

    Lin, Hui Yi; Chen, Dung Tsa; Huang, Po Yu

    2017-01-01

    Motivation: Testing SNP-SNP interactions is considered as a key for overcoming bottlenecks of genetic association studies. However, related statistical methods for testing SNP-SNP interactions are underdeveloped. Results: We propose the SNP Interaction Pattern Identifier (SIPI), which tests 45...

  19. Identifying the Gifted Child Humorist.

    Science.gov (United States)

    Fern, Tami L.

    1991-01-01

    This study attempted to identify gifted child humorists among 1,204 children in grades 3-6. Final identification of 13 gifted child humorists was determined through application of such criteria as funniness, originality, and exemplary performance or product. The influence of intelligence, development, social factors, sex differences, family…

  20. Identifying high-risk medication

    DEFF Research Database (Denmark)

    Sædder, Eva; Brock, Birgitte; Nielsen, Lars Peter

    2014-01-01

    salicylic acid, and beta-blockers; 30 drugs or drug classes caused 82 % of all serious MEs. The top ten drugs involved in fatal events accounted for 73 % of all drugs identified. CONCLUSION: Increasing focus on seven drugs/drug classes can potentially reduce hospitalizations, extended hospitalizations...

  1. Distributed Persistent Identifiers System Design

    Directory of Open Access Journals (Sweden)

    Pavel Golodoniuc

    2017-06-01

    Full Text Available The need to identify both digital and physical objects is ubiquitous in our society. Past and present persistent identifier (PID systems, of which there is a great variety in terms of technical and social implementation, have evolved with the advent of the Internet, which has allowed for globally unique and globally resolvable identifiers. PID systems have, by in large, catered for identifier uniqueness, integrity, and persistence, regardless of the identifier’s application domain. Trustworthiness of these systems has been measured by the criteria first defined by Bütikofer (2009 and further elaborated by Golodoniuc 'et al'. (2016 and Car 'et al'. (2017. Since many PID systems have been largely conceived and developed by a single organisation they faced challenges for widespread adoption and, most importantly, the ability to survive change of technology. We believe that a cause of PID systems that were once successful fading away is the centralisation of support infrastructure – both organisational and computing and data storage systems. In this paper, we propose a PID system design that implements the pillars of a trustworthy system – ensuring identifiers’ independence of any particular technology or organisation, implementation of core PID system functions, separation from data delivery, and enabling the system to adapt for future change. We propose decentralisation at all levels — persistent identifiers and information objects registration, resolution, and data delivery — using Distributed Hash Tables and traditional peer-to-peer networks with information replication and caching mechanisms, thus eliminating the need for a central PID data store. This will increase overall system fault tolerance thus ensuring its trustworthiness. We also discuss important aspects of the distributed system’s governance, such as the notion of the authoritative source and data integrity

  2. Fourier Transform Mass Spectrometry: The Transformation of Modern Environmental Analyses

    Science.gov (United States)

    Lim, Lucy; Yan, Fangzhi; Bach, Stephen; Pihakari, Katianna; Klein, David

    2016-01-01

    Unknown compounds in environmental samples are difficult to identify using standard mass spectrometric methods. Fourier transform mass spectrometry (FTMS) has revolutionized how environmental analyses are performed. With its unsurpassed mass accuracy, high resolution and sensitivity, researchers now have a tool for difficult and complex environmental analyses. Two features of FTMS are responsible for changing the face of how complex analyses are accomplished. First is the ability to quickly and with high mass accuracy determine the presence of unknown chemical residues in samples. For years, the field has been limited by mass spectrometric methods that were based on knowing what compounds of interest were. Secondly, by utilizing the high resolution capabilities coupled with the low detection limits of FTMS, analysts also could dilute the sample sufficiently to minimize the ionization changes from varied matrices. PMID:26784175

  3. Fourier Transform Mass Spectrometry: The Transformation of Modern Environmental Analyses

    Directory of Open Access Journals (Sweden)

    Lucy Lim

    2016-01-01

    Full Text Available Unknown compounds in environmental samples are difficult to identify using standard mass spectrometric methods. Fourier transform mass spectrometry (FTMS has revolutionized how environmental analyses are performed. With its unsurpassed mass accuracy, high resolution and sensitivity, researchers now have a tool for difficult and complex environmental analyses. Two features of FTMS are responsible for changing the face of how complex analyses are accomplished. First is the ability to quickly and with high mass accuracy determine the presence of unknown chemical residues in samples. For years, the field has been limited by mass spectrometric methods that were based on knowing what compounds of interest were. Secondly, by utilizing the high resolution capabilities coupled with the low detection limits of FTMS, analysts also could dilute the sample sufficiently to minimize the ionization changes from varied matrices.

  4. An MDE Approach for Modular Program Analyses

    NARCIS (Netherlands)

    Yildiz, Bugra Mehmet; Bockisch, Christoph; Aksit, Mehmet; Rensink, Arend

    Program analyses are an important tool to check if a system fulfills its specification. A typical implementation strategy for program analyses is to use an imperative, general-purpose language like Java, and access the program to be analyzed through libraries that offer an API for reading, writing

  5. Diversity of primary care systems analysed.

    NARCIS (Netherlands)

    Kringos, D.; Boerma, W.; Bourgueil, Y.; Cartier, T.; Dedeu, T.; Hasvold, T.; Hutchinson, A.; Lember, M.; Oleszczyk, M.; Pavlick, D.R.

    2015-01-01

    This chapter analyses differences between countries and explains why countries differ regarding the structure and process of primary care. The components of primary care strength that are used in the analyses are health policy-making, workforce development and in the care process itself (see Fig.

  6. Approximate analyses of inelastic effects in pipework

    International Nuclear Information System (INIS)

    Jobson, D.A.

    1983-01-01

    This presentation shows figures concerned with analyses of inelastic effects in pipework as follows: comparison of experimental and calculated simplified analyses results for free end rotation and for circumferential strain; interrupted stress relaxation; regenerated relaxation caused by reversed yield; buckling of straight pipe under combined bending and torsion; results of fatigues test of pipe bend

  7. ORCID: Author Identifiers for Librarians

    Directory of Open Access Journals (Sweden)

    Robyn B. Reed

    2017-10-01

    Full Text Available Generating accurate publication lists by researchers can be challenging when faced with scholars who have common names or who have published under name variations. This article describes ORCID and the goal of generating author identifiers for scholars to connect their research outputs. Included are the reasons for having author identifiers as well as the types of information within individual profiles. This article includes information on how academic libraries are playing a role with ORCID initiatives as well as describing how publishers, institutions, and funders are employing ORCID in their workflows. Highlighted is material on academic institutions in Pennsylvania using ORCID. The purpose of the article is to provide an overview of ORCID and its uses to inform librarians about this important initiative.

  8. Device for identifying fuel assembly

    International Nuclear Information System (INIS)

    Imai, Tetsuo; Miyazawa, Tatsuo.

    1982-01-01

    Purpose: To accurately identify a symbol printed on a hanging tool at the upper part of a fuel assembly. Constitution: Optical fibers are bundled to prepare a detector which is disposed at a predetermined position on a hanging tool. This position is set by a guide. Thus, the light emitted from an illumination lamp arrives at the bottom of a groove printed on the upper surface of the tool, and is divided into a weak light reflected upwardly and a strong light reflected on the surface lower than the groove. When these lights are received by the optical fibers, the fibers corresponding to the grooved position become dark, and the fibers corresponding to the ungrooved position become bright. Since the fuel assembly is identified by the dark and bright of the optical fibers as symbols, different machining can be performed every fuel assembly on the upper surface of the tool. (Yoshihara, H.)

  9. Identifying patient risks during hospitalization

    Directory of Open Access Journals (Sweden)

    Lucélia Ferreira Lima

    2008-12-01

    Full Text Available Objective: To identify the risks reported at a public institution andto know the main patient risks from the nursing staff point of view.Methods: A retrospective, descriptive and exploratory study. Thesurvey was developed at a hospital in the city of Taboão da Serra, SãoPaulo, Brazil. The study included all nurses working in care areas whoagreed to participate in the study. At the same time, sentinel eventsoccurring in the period from July 2006 to July 2007 were identified.Results: There were 440 sentinel events reported, and the main risksincluded patient falls, medication errors and pressure ulcers. Sixty-fivenurses were interviewed. They also reported patient falls, medicationerrors and pressure ulcers as the main risks. Conclusions: Riskassessment and implementation of effective preventive actions arenecessary to ensure patient’s safety. Involvement of a multidisciplinaryteam is one of the steps for a successful process.

  10. Analyses of hypothetical FCI's in a fast reactor

    International Nuclear Information System (INIS)

    Padilla, A. Jr.; Martin, F.J.; Niccoli, L.G.

    1981-01-01

    Parametric analyses using the SIMMER code were performed to evaluate the potential for a severe recriticality from a pressure-driven recompaction caused by an energetic FCI during the transition phase of a hypothetical accident in a fast reactor. For realistic and reasonable estimates for the assumed accident conditions, a severe recriticality was not predicted. The conditions under which a severe recriticality would be obtained or averted were identified. 10 figures, 2 tables

  11. Model-based Recursive Partitioning for Subgroup Analyses

    OpenAIRE

    Seibold, Heidi; Zeileis, Achim; Hothorn, Torsten

    2016-01-01

    The identification of patient subgroups with differential treatment effects is the first step towards individualised treatments. A current draft guideline by the EMA discusses potentials and problems in subgroup analyses and formulated challenges to the development of appropriate statistical procedures for the data-driven identification of patient subgroups. We introduce model-based recursive partitioning as a procedure for the automated detection of patient subgroups that are identifiable by...

  12. Identifying High Performance ERP Projects

    OpenAIRE

    Stensrud, Erik; Myrtveit, Ingunn

    2002-01-01

    Learning from high performance projects is crucial for software process improvement. Therefore, we need to identify outstanding projects that may serve as role models. It is common to measure productivity as an indicator of performance. It is vital that productivity measurements deal correctly with variable returns to scale and multivariate data. Software projects generally exhibit variable returns to scale, and the output from ERP projects is multivariate. We propose to use Data Envelopment ...

  13. Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks.

    Directory of Open Access Journals (Sweden)

    Dimitrios Iliopoulos

    Full Text Available BACKGROUND: Osteoarthritis is a multifactorial disease characterized by destruction of the articular cartilage due to genetic, mechanical and environmental components affecting more than 100 million individuals all over the world. Despite the high prevalence of the disease, the absence of large-scale molecular studies limits our ability to understand the molecular pathobiology of osteoathritis and identify targets for drug development. METHODOLOGY/PRINCIPAL FINDINGS: In this study we integrated genetic, bioinformatic and proteomic approaches in order to identify new genes and their collaborative networks involved in osteoarthritis pathogenesis. MicroRNA profiling of patient-derived osteoarthritic cartilage in comparison to normal cartilage, revealed a 16 microRNA osteoarthritis gene signature. Using reverse-phase protein arrays in the same tissues we detected 76 differentially expressed proteins between osteoarthritic and normal chondrocytes. Proteins such as SOX11, FGF23, KLF6, WWOX and GDF15 not implicated previously in the genesis of osteoarthritis were identified. Integration of microRNA and proteomic data with microRNA gene-target prediction algorithms, generated a potential "interactome" network consisting of 11 microRNAs and 58 proteins linked by 414 potential functional associations. Comparison of the molecular and clinical data, revealed specific microRNAs (miR-22, miR-103 and proteins (PPARA, BMP7, IL1B to be highly correlated with Body Mass Index (BMI. Experimental validation revealed that miR-22 regulated PPARA and BMP7 expression and its inhibition blocked inflammatory and catabolic changes in osteoarthritic chondrocytes. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that obesity and inflammation are related to osteoarthritis, a metabolic disease affected by microRNA deregulation. Gene network approaches provide new insights for elucidating the complexity of diseases such as osteoarthritis. The integration of microRNA, proteomic

  14. Level II Ergonomic Analyses, Dover AFB, DE

    Science.gov (United States)

    1999-02-01

    IERA-RS-BR-TR-1999-0002 UNITED STATES AIR FORCE IERA Level II Ergonomie Analyses, Dover AFB, DE Andrew Marcotte Marilyn Joyce The Joyce...Project (070401881, Washington, DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE 4. TITLE AND SUBTITLE Level II Ergonomie Analyses, Dover...1.0 INTRODUCTION 1-1 1.1 Purpose Of The Level II Ergonomie Analyses : 1-1 1.2 Approach 1-1 1.2.1 Initial Shop Selection and Administration of the

  15. Automatic incrementalization of Prolog based static analyses

    DEFF Research Database (Denmark)

    Eichberg, Michael; Kahl, Matthias; Saha, Diptikalyan

    2007-01-01

    Modem development environments integrate various static analyses into the build process. Analyses that analyze the whole project whenever the project changes are impractical in this context. We present an approach to automatic incrementalization of analyses that are specified as tabled logic...... programs and evaluated using incremental tabled evaluation, a technique for efficiently updating memo tables in response to changes in facts and rules. The approach has been implemented and integrated into the Eclipse IDE. Our measurements show that this technique is effective for automatically...

  16. Cost-Benefit Analyses of Transportation Investments

    DEFF Research Database (Denmark)

    Næss, Petter

    2006-01-01

    This paper discusses the practice of cost-benefit analyses of transportation infrastructure investment projects from the meta-theoretical perspective of critical realism. Such analyses are based on a number of untenable ontological assumptions about social value, human nature and the natural......-to-pay investigations. Accepting the ontological and epistemological assumptions of cost-benefit analysis involves an implicit acceptance of the ethical and political values favoured by these assumptions. Cost-benefit analyses of transportation investment projects tend to neglect long-term environmental consequences...

  17. Use of DNA barcodes to identify flowering plants

    OpenAIRE

    Kress, W. John; Wurdack, Kenneth J.; Zimmer, Elizabeth A.; Weigt, Lee A.; Janzen, Daniel H.

    2005-01-01

    Methods for identifying species by using short orthologous DNA sequences, known as “DNA barcodes,” have been proposed and initiated to facilitate biodiversity studies, identify juveniles, associate sexes, and enhance forensic analyses. The cytochrome c oxidase 1 sequence, which has been found to be widely applicable in animal barcoding, is not appropriate for most species of plants because of a much slower rate of cytochrome c oxidase 1 gene evolution in higher plants than in animals. We ther...

  18. Sparse Linear Identifiable Multivariate Modeling

    DEFF Research Database (Denmark)

    Henao, Ricardo; Winther, Ole

    2011-01-01

    and bench-marked on artificial and real biological data sets. SLIM is closest in spirit to LiNGAM (Shimizu et al., 2006), but differs substantially in inference, Bayesian network structure learning and model comparison. Experimentally, SLIM performs equally well or better than LiNGAM with comparable......In this paper we consider sparse and identifiable linear latent variable (factor) and linear Bayesian network models for parsimonious analysis of multivariate data. We propose a computationally efficient method for joint parameter and model inference, and model comparison. It consists of a fully...

  19. Identifying flares in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Bykerk, Vivian P; Bingham, Clifton O; Choy, Ernest H

    2016-01-01

    to flare, with escalation planned in 61%. CONCLUSIONS: Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with...... Set. METHODS: Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares...

  20. Comparison with Russian analyses of meteor impact

    Energy Technology Data Exchange (ETDEWEB)

    Canavan, G.H.

    1997-06-01

    The inversion model for meteor impacts is used to discuss Russian analyses and compare principal results. For common input parameters, the models produce consistent estimates of impactor parameters. Directions for future research are discussed and prioritized.

  1. 7 CFR 94.102 - Analyses available.

    Science.gov (United States)

    2010-01-01

    ... analyses for total ash, fat by acid hydrolysis, moisture, salt, protein, beta-carotene, catalase... glycol, SLS, and zeolex. There are also be tests for starch, total sugars, sugar profile, whey, standard...

  2. Analyse of Maintenance Cost in ST

    CERN Document Server

    Jenssen, B W

    2001-01-01

    An analyse has been carried out in ST concerning the total costs for the division. Even though the target was the maintenance costs in ST, the global budget over has been analysed. This has been done since there is close relation between investments & consolidation and the required level for maintenance. The purpose of the analyse was to focus on maintenance cost in ST as a ratio of total maintenance costs over the replacement value of the equipment, and to make some comparisons with other industries and laboratories. Families of equipment have been defined and their corresponding ratios calculated. This first approach gives us some "quantitative" measurements. This analyse should be combined with performance indicators (more "qualitative" measurements) that are telling us how well we are performing. This will help us in defending our budget, make better priorities, and we will satisfy the requirements from our external auditors.

  3. A History of Rotorcraft Comprehensive Analyses

    Science.gov (United States)

    Johnson, Wayne

    2013-01-01

    A history of the development of rotorcraft comprehensive analyses is presented. Comprehensive analyses are digital computer programs that calculate the aeromechanical behavior of the rotor and aircraft, bringing together the most advanced models of the geometry, structure, dynamics, and aerodynamics available in rotary wing technology. The development of the major codes of the last five decades from industry, government, and universities is described. A number of common themes observed in this history are discussed.

  4. Safety analyses for reprocessing and waste processing

    International Nuclear Information System (INIS)

    1983-03-01

    Presentation of an incident analysis of process steps of the RP, simplified considerations concerning safety, and safety analyses of the storage and solidification facilities of the RP. A release tree method is developed and tested. An incident analysis of process steps, the evaluation of the SRL-study and safety analyses of the storage and solidification facilities of the RP are performed in particular. (DG) [de

  5. Risk analyses of nuclear power plants

    International Nuclear Information System (INIS)

    Jehee, J.N.T.; Seebregts, A.J.

    1991-02-01

    Probabilistic risk analyses of nuclear power plants are carried out by systematically analyzing the possible consequences of a broad spectrum of causes of accidents. The risk can be expressed in the probabilities for melt down, radioactive releases, or harmful effects for the environment. Following risk policies for chemical installations as expressed in the mandatory nature of External Safety Reports (EVRs) or, e.g., the publication ''How to deal with risks'', probabilistic risk analyses are required for nuclear power plants

  6. Identifying suitable sites for Florida panther reintroduction

    Science.gov (United States)

    Thatcher, Cindy A.; van Manen, Frank T.; Clark, Joseph D.

    2006-01-01

    A major objective of the 1995 Florida Panther (Puma concolor cory) Recovery Plan is the establishment of 2 additional panther populations within the historic range. Our goal was to identify prospective sites for Florida panther reintroduction within the historic range based on quantitative landscape assessments. First, we delineated 86 panther home ranges using telemetry data collected from 1981 to 2001 in south Florida to develop a Mahalanobis distance (D2) habitat model, using 4 anthropogenic variables and 3 landscape variables mapped at a 500-m resolution. From that analysis, we identified 9 potential reintroduction sites of sufficient size to support a panther population. We then developed a similar D2 model at a higher spatial resolution to quantify the area of favorable panther habitat at each site. To address potential for the population to expand, we calculated the amount of favorable habitat adjacent to each prospective reintroduction site within a range of dispersal distances of female panthers. We then added those totals to the contiguous patches to estimate the total amount of effective panther habitat at each site. Finally, we developed an expert-assisted model to rank and incorporate potentially important habitat variables that were not appropriate for our empirical analysis (e.g., area of public lands, livestock density). Anthropogenic factors heavily influenced both the landscape and the expert-assisted models. Of the 9 areas we identified, the Okefenokee National Wildlife Refuge, Ozark National Forest, and Felsenthal National Wildlife Refuge regions had the highest combination of effective habitat area and expert opinion scores. Sensitivity analyses indicated that variability among key model parameters did not affect the high ranking of those sites. Those sites should be considered as starting points for the field evaluation of potential reintroduction sites.

  7. Prevalent Diseases Identified in Semi-Industrial Poultry Farming in ...

    African Journals Online (AJOL)

    This study was conducted in 2003-2007 with the aim of identifying prevalent diseases in modern poultry farming in Mali. It covered 22 modern layer farms located in the suburban areas of Bamako District and of Sikasso and Segou towns. Analyses focused on a total of 536 samples, 260 sera, 254 eggs, 149 organ samples, ...

  8. Human group C rotaviruses identified in Kenya | Mwenda | East ...

    African Journals Online (AJOL)

    Subjects and Methods:Faecal samples were collected from 119 infants and young children with diarrhoea and were analysed by commercial ELISA and polyacrylamide gel electrophoresis (SDS-PAGE) to identify possible non-group A rotaviruses. Extraction of any potential rrotavirus double-stranded RNA from faeces amd ...

  9. A framework for identifying carbon hotspots and forest management drivers

    Science.gov (United States)

    Nilesh Timilsina; Francisco J. Escobedo; Wendell P. Cropper; Amr Abd-Elrahman; Thomas Brandeis; Sonia Delphin; Samuel Lambert

    2013-01-01

    Spatial analyses of ecosystem system services that are directly relevant to both forest management decision making and conservation in the subtropics are rare. Also, frameworks that identify and map carbon stocks and corresponding forest management drivers using available regional, national, and international-level forest inventory datasets could provide insights into...

  10. Persistent Identifiers as Boundary Objects

    Science.gov (United States)

    Parsons, M. A.; Fox, P. A.

    2017-12-01

    In 1989, Leigh Star and Jim Griesemer defined the seminal concept of `boundary objects'. These `objects' are what Latour calls `immutable mobiles' that enable communication and collaboration across difference by helping meaning to be understood in different contexts. As Star notes, they are a sort of arrangement that allow different groups to work together without (a priori) consensus. Part of the idea is to recognize and allow for the `interpretive flexibility' that is central to much of the `constructivist' approach in the sociology of science. Persistent Identifiers (PIDs) can clearly act as boundary objects, but people do not usually assume that they enable interpretive flexibility. After all, they are meant to be unambiguous, machine-interpretable identifiers of defined artifacts. In this paper, we argue that PIDs can fill at least two roles: 1) That of the standardized form, where there is strong agreement on what is being represented and how and 2) that of the idealized type, a more conceptual concept that allows many different representations. We further argue that these seemingly abstract conceptions actually help us implement PIDs more effectively to link data, publications, various other artifacts, and especially people. Considering PIDs as boundary objects can help us address issues such as what level of granularity is necessary for PIDs, what metadata should be directly associated with PIDs, and what purpose is the PID serving (reference, provenance, credit, etc.). In short, sociological theory can improve data sharing standards and their implementation in a way that enables broad interdisciplinary data sharing and reuse. We will illustrate this with several specific examples of Earth science data.

  11. GIS-Mapping and Statistical Analyses to Identify Climate-Vulnerable Communities and Populations Exposed to Superfund Sites

    Science.gov (United States)

    Climate change-related cumulative health risks are expected to be disproportionately greater for overburdened communities, due to differential proximity and exposures to chemical sources and flood zones. Communities and populations vulnerable to climate change-associated impacts ...

  12. Econometric Mediation Analyses: Identifying the Sources of Treatment Effects from Experimentally Estimated Production Technologies with Unmeasured and Mismeasured Inputs.

    Science.gov (United States)

    Heckman, James; Pinto, Rodrigo

    2015-01-01

    This paper presents an econometric mediation analysis. It considers identification of production functions and the sources of output effects (treatment effects) from experimental interventions when some inputs are mismeasured and others are entirely omitted. JEL Code: D24, C21, C43, C38.

  13. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

    NARCIS (Netherlands)

    Liu, Jimmy Z.; van Sommeren, Suzanne; Huang, Hailiang; Ng, Siew C.; Alberts, Rudi; Takahashi, Atsushi; Ripke, Stephan; Lee, James C.; Jostins, Luke; Shah, Tejas; Abedian, Shifteh; Cheon, Jae Hee; Cho, Judy; Daryani, Naser E.; Franke, Lude; Fuyuno, Yuta; Hart, Ailsa; Juyal, Ramesh C.; Juyal, Garima; Kim, Won Ho; Morris, Andrew P.; Poustchi, Hossein; Newman, William G.; Midha, Vandana; Orchard, Timothy R.; Vahedi, Homayon; Sood, Ajit; Sung, Joseph J. Y.; Malekzadeh, Reza; Westra, Harm-Jan; Yamazaki, Keiko; Yang, Suk-Kyun; Barrett, Jeffrey C.; Franke, Andre; Alizadeh, Behrooz Z.; Parkes, Miles; Thelma, B. K.; Daly, Mark J.; Kubo, Michiaki; Anderson, Carl A.; Weersma, Rinse K.

    Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first transancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846

  14. New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8.

    Science.gov (United States)

    Karanjawala, Zarir E; Illei, Peter B; Ashfaq, Raheela; Infante, Jeffrey R; Murphy, Kathleen; Pandey, Akhilesh; Schulick, Richard; Winter, Jordan; Sharma, Rajni; Maitra, Anirban; Goggins, Michael; Hruban, Ralph H

    2008-02-01

    New markers to distinguish benign reactive glands from infiltrating ductal adenocarcinoma of the pancreas are needed. The gene expression patterns of 24 surgically resected primary infiltrating ductal adenocarcinomas of the pancreas were compared with 18 non-neoplastic samples using the Affymetrix U133 Plus 2.0 Arrays and the Gene Logic GeneExpress Software System. Gene fragments from 4 genes (annexin A8, claudin 18, CXCL5, and S100 A2) were selected from the fragments found to be highly expressed in infiltrating adenocarcinomas when compared with normal tissues. The protein expression of these genes was examined using immunohistochemical labeling of tissue microarrays. Claudin 18 labeled infiltrating carcinomas in a membranous pattern. When compared with normal and reactive ducts, claudin 18 was overexpressed, at least focally, in 159 of 166 evaluable carcinomas (96%). Strong and diffuse claudin 18 overexpression was most often seen in well-differentiated carcinomas (P=0.02). Claudin 18 was overexpressed in 51 of 52 cases (98%) of pancreatic intraepithelial neoplasia. Annexin A8 was at least focally overexpressed in 149 of 154 evaluable infiltrating carcinomas (97%). S100 A2 was at least focally overexpressed in 118 of 154 evaluable infiltrating carcinomas (77%). Non-neoplastic glands also frequently expressed S100 A2 diminishing its potential diagnostic utility. Immunolabeling with antibodies directed against CXCL5 did not reveal any significant differences in protein expression between infiltrating adenocarcinomas and normal pancreatic ducts. Claudin 18 and annexin A8 are frequently highly overexpressed in infiltrating ductal adenocarcinomas when compared with normal reactive ducts, suggesting a role for these molecules in pancreatic ductal adenocarcinomas. Furthermore, these may serve as diagnostic markers, as screening tests and as therapeutic targets.

  15. High-Resolution Linkage Analyses to Identify Genes That Influence Varroa Sensitive Hygiene Behavior in Honey Bees.

    Science.gov (United States)

    Varroa mites (V. destructor) are a major threat to honey bees (Apis melilfera) and beekeeping worldwide and likely lead to colony decline if colonies are not treated. Most treatments involve chemical control of the mites; however, Varroa has evolved resistance to many of these miticides, leaving be...

  16. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M; McLaughlin, Russell L; Diekstra, Frank P; Pulit, Sara L; van der Spek, Rick A A; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R; Yang, Jian; Fogh, Isabella; van Doormaal, Perry Tc; Tazelaar, Gijs H P; Koppers, Max; Blokhuis, Anna M; Sproviero, William; Jones, Ashley R; Kenna, Kevin P; van Eijk, Kristel R; Harschnitz, Oliver; Schellevis, Raymond D; Brands, William J; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E; Shaw, Pamela J; Hardy, John; Orrell, Richard W; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A.; Staats, Kim A; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; Van Deerlin, Vivianna M; Trojanowski, John Q; Elman, Lauren; McCluskey, Leo; Basak, A Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A M; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M; van der Kooi, Anneke J; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E; Smith, Bradley N; Pansarasa, Orietta; Cereda, Cristina; Del Bo, Roberto; Comi, Giacomo P; D'Alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P; Fifita, Jennifer A; Nicholson, Garth A; Rowe, Dominic B; Pamphlett, Roger; Kiernan, Matthew C; Grosskreutz, Julian; Witte, Otto W; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A; Leigh, P Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C; Weishaupt, Jochen H; Robberecht, Wim; Van Damme, Philip; Franke, Lude; Pers, Tune H; Brown, Robert H; Glass, Jonathan D; Landers, John E; Hardiman, Orla; Andersen, Peter M; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R; Visscher, Peter M; de Bakker, Paul I W; van Es, Michael A; Pasterkamp, R Jeroen; Lewis, Cathryn M; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H; Veldink, Jan H

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577

  17. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M.; McLaughlin, Russell L.; Diekstra, Frank P.; Pulit, Sara L.; van der Spek, Rick A. A.; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R.; Yang, Jian; Fogh, Isabella; van Doormaal, Perry Tc; Tazelaar, Gijs H. P.; Koppers, Max; Blokhuis, Anna M.; Sproviero, William; Jones, Ashley R.; Kenna, Kevin P.; van Eijk, Kristel R.; Harschnitz, Oliver; Schellevis, Raymond D.; Brands, William J.; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S.; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E.; Shaw, Pamela J.; Hardy, John; Orrell, Richard W.; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A.; Staats, Kim A.; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; van Deerlin, Vivianna M.; Trojanowski, John Q.; Elman, Lauren; McCluskey, Leo; Basak, A. Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R.; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A. M.; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W.; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M.; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G.; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M.; van der Kooi, Anneke J.; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E.; Smith, Bradley N.; Pansarasa, Orietta; Cereda, Cristina; del Bo, Roberto; Comi, Giacomo P.; D'alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P.; Fifita, Jennifer A.; Nicholson, Garth A.; Rowe, Dominic B.; Pamphlett, Roger; Kiernan, Matthew C.; Grosskreutz, Julian; Witte, Otto W.; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A.; Leigh, P. Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C.; Weishaupt, Jochen H.; Robberecht, Wim; van Damme, Philip; Franke, Lude; Pers, Tune H.; Brown, Robert H.; Glass, Jonathan D.; Landers, John E.; Hardiman, Orla; Andersen, Peter M.; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R.; Visscher, Peter M.; de Bakker, Paul I. W.; van Es, Michael A.; Pasterkamp, R. Jeroen; Lewis, Cathryn M.; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H.; Veldink, Jan H.

    2016-01-01

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577

  18. Study of rare neutron induced processes and coincidence analyses to identify and reduce background contributions in the COBRA experiment

    International Nuclear Information System (INIS)

    Timm, Jan Horst Karl

    2015-11-01

    The aim of the COBRA experiment is the observation of neutrinoless double-beta decay, primarily of the isotope 116 Cd. The applied semiconductor detectors of cadmium zinc telluride that are 90% to be enriched enable both the detection and the source of this decay. The half-lives of decays of this kind are expected in the range of more than 10 26 years. Therefore, the reduction of contributions to the background is of decisive importance. The main subjects of this work are, on the one hand, the time synchronization of the data, which provides the basis for coincidence analysis. This analysis method has access not only to identification of contributions to the background, but also to observe decays involving positron annihilation and decays into excited states. In this study, the intrinsic detector contamination of some decay products of 238 U and 232 Th was measured and sensitivities to the half-lives of the decays like 120 Te and 128 Te in each case to the first excited state of daughter products are given. On the other hand, qualitative studies on the importance of neutrons in the COBRA experiment were conducted. These have shown that fast neutrons, thus with energies greater than 10 keV, only result in an insignificant contribution to the background for the detection of neutrinoless double-beta decay of the 116 Cd. Previous studies have also shown that the thermal neutron flux can be in situ determined by coincidence analysis.

  19. Microarray and growth analyses identify differences and similarities of early corn response to weeds, shade, and nitrogen stress

    Science.gov (United States)

    Weed interference with crop growth is often attributed to water, nutrient, or light competition; however, specific physiological responses to these stresses are not well described. This study’s objective was to compare growth, yield, and gene expression responses of corn to nitrogen (N), low light (...

  20. The use of differential item functioning analyses to identify cultural differences in responses to the EORTC QLQ-C30

    NARCIS (Netherlands)

    Scott, N. W.; Fayers, P. M.; Aaronson, N. K.; Bottomley, A.; de Graeff, A.; Groenvold, M.; Koller, M.; Petersen, M. A.; Sprangers, M. A. G.

    2007-01-01

    INTRODUCTION: The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 is a widely used health-related quality of life instrument. The main aim of this study is to investigate whether there are international differences in response to the questionnaire that can be explained by

  1. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    NARCIS (Netherlands)

    A. Okbay (Aysu); Baselmans, B.M.L. (Bart M.L.); J.E. de Neve (Jan-Emmanuel); P. Turley (Patrick); M. Nivard (Michel); Fontana, M.A. (Mark Alan); Meddens, S.F.W. (S. Fleur W.); Linnér, R.K. (Richard Karlsson); Rietveld, C.A. (Cornelius A); J. Derringer; J. Gratten (Jacob); J.J. Lee (James J.); Liu, J.Z. (Jimmy Z); R. de Vlaming (Ronald); SAhluwalia, T. (Tarunveer); Buchwald, J. (Jadwiga); A. Cavadino (Alana); A.C. Frazier-Wood (Alexis C.); Furlotte, N.A. (Nicholas A); Garfield, V. (Victoria); Geisel, M.H. (Marie Henrike); J.R. Gonzalez (Juan R.); Haitjema, S. (Saskia); R. Karlsson (Robert); Der Laan, S.W. (Sander Wvan); K.-H. Ladwig (Karl-Heinz); J. Lahti (Jari); S.J. van der Lee (Sven); P.A. Lind (Penelope); Liu, T. (Tian); Matteson, L. (Lindsay); E. Mihailov (Evelin); M. Miller (Mike); CMinica, C. (Camelia); MNolte, I. (Ilja); D.O. Mook-Kanamori (Dennis); P.J. van der Most (Peter); C. Oldmeadow (Christopher); Y. Qian (Yong); O. Raitakari (Olli); R. Rawal (R.); A. Realo; Rueedi, R. (Rico); Schmidt, B. (Börge); A.V. Smith (Albert Vernon); E. Stergiakouli (Evangelia); T. Tanaka (Toshiko); K.D. Taylor (Kent); Wedenoja, J. (Juho); Wellmann, J. (Juergen); H.J. Westra (Harm-Jan); MWillems, S. (Sara); Zhao, W. (Wei); L.C. Study (LifeLines Cohort); N. Amin (Najaf); Bakshi, A. (Andrew); P.A. Boyle (Patricia); Cherney, S. (Samantha); Cox, S.R. (Simon R); G. Davies (Gail); O.S.P. Davis (Oliver S.); J. Ding (Jun); N. Direk (Nese); Eibich, P. (Peter); R. Emeny (Rebecca); Fatemifar, G. (Ghazaleh); J.D. Faul; L. Ferrucci (Luigi); A.J. Forstner (Andreas); C. Gieger (Christian); Gupta, R. (Richa); T.B. Harris (Tamara); J.M. Harris (Juliette); E.G. Holliday (Elizabeth); J.J. Hottenga (Jouke Jan); P.L. de Jager (Philip); M. Kaakinen (Marika); E. Kajantie (Eero); Karhunen, V. (Ville); I. Kolcic (Ivana); M. Kumari (Meena); L.J. Launer (Lenore); L. Franke (Lude); Li-Gao, R. (Ruifang); Koini, M. (Marisa); A. Loukola (Anu); P. Marques-Vidal; G.W. Montgomery (Grant); M. Mosing (Miriam); L. Paternoster (Lavinia); A. Pattie (Alison); K. Petrovic (Katja); Pulkki-R'back, L. (Laura); L. Quaye (Lydia); R'ikkönen, K. (Katri); I. Rudan (Igor); R. Scott (Rodney); J.A. Smith (Jennifer A); A.R. Sutin; Trzaskowski, M. (Maciej); Vinkhuyze, A.E. (Anna E.); L. Yu (Lei); D. Zabaneh (Delilah); J. Attia (John); D.A. Bennett (David A.); Berger, K. (Klaus); L. Bertram (Lars); D.I. Boomsma (Dorret); H. Snieder (Harold); Chang, S.-C. (Shun-Chiao); F. Cucca (Francesco); I.J. Deary (Ian J.); C.M. van Duijn (Cornelia); K. Hagen (Knut); U. Bültmann (Ute); E.J.C. de Geus (Eco); P.J.F. Groenen (Patrick); V. Gudnason (Vilmundur); T. Hansen (T.); Hartman, C.A. (Catharine A); C.M.A. Haworth (Claire M.); C. Hayward (Caroline); A.C. Heath (Andrew C.); D.A. Hinds (David A.); E. Hypponen (Elina); W.G. Iacono (William); M.-R. Jarvelin (Marjo-Riitta); K.-H. JöCkel (Karl-Heinz); J. Kaprio (Jaakko); S.L.R. Kardia (Sharon); Keltikangas-J'rvinen, L. (Liisa); P. Kraft (Peter); Kubzansky, L.D. (Laura D.); Lehtim'ki, T. (Terho); P.K. Magnusson (Patrik); N.G. Martin (Nicholas); M. McGue (Matt); A. Metspalu (Andres); M. Mills (Melinda); R. de Mutsert (Reneé); A.J. Oldehinkel (Albertine); G. Pasterkamp (Gerard); N.L. Pedersen (Nancy); R. Plomin (Robert); O. Polasek (Ozren); C. Power (Christopher); S.S. Rich (Stephen); F.R. Rosendaal (Frits); H.M. den Ruijter (Hester ); Schlessinger, D. (David); R. Schmidt (Reinhold); R. Svento (Rauli); R. Schmidt (Reinhold); B.Z. Alizadeh (Behrooz); T.I.A. Sørensen (Thorkild); DSpector, T. (Tim); Steptoe, A. (Andrew); A. Terracciano; A.R. Thurik (Roy); N.J. Timpson (Nicholas); H.W. Tiemeier (Henning); A.G. Uitterlinden (André); P. Vollenweider (Peter); Wagner, G.G. (Gert G.); D.R. Weir (David); J. Yang (Joanna); Conley, D.C. (Dalton C.); G.D. Smith; Hofman, A. (Albert); M. Johannesson (Magnus); D. Laibson (David); S.E. Medland (Sarah Elizabeth); M.N. Meyer (Michelle N.); Pickrell, J.K. (Joseph K.); Esko, T. (T'nu); R.F. Krueger; J.P. Beauchamp (Jonathan); Ph.D. Koellinger (Philipp); D.J. Benjamin (Daniel J.); M. Bartels (Meike); D. Cesarini (David)

    2016-01-01

    textabstractVery few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data.

  2. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    NARCIS (Netherlands)

    Okbay, Aysu; Baselmans, Bart M L; De Neve, Jan-Emmanuel; Turley, Patrick; Nivard, Michel G; Fontana, Mark Alan; Meddens, S Fleur W; Linnér, Richard Karlsson; Rietveld, Cornelius A; Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; Furlotte, Nicholas A; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Miller, Michael B; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis; van der Most, Peter J; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davies, Gail; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas; Gieger, Christian; Gupta, Richa; Harris, Tamara B; Harris, Juliette M; Holliday, Elizabeth G; Hottenga, Jouke-Jan; De Jager, Philip L; Kaakinen, Marika A; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J; Franke, Lude; Li-Gao, Ruifang; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W; Mosing, Miriam A; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J; Smith, Jennifer A; Sutin, Angelina R; Trzaskowski, Maciej; Vinkhuyzen, Anna E; Yu, Lei; Zabaneh, Delilah; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J; van Duijn, Cornelia M; Eriksson, Johan G; Bültmann, Ute; de Geus, Eco J C; Groenen, Patrick J F; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A; Haworth, Claire M A; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Hyppönen, Elina; Iacono, William G; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Keltikangas-Järvinen, Liisa; Kraft, Peter; Kubzansky, Laura D; Lehtimäki, Terho; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J; Pasterkamp, Gerard; Pedersen, Nancy L; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S; Rosendaal, Frits R; den Ruijter, Hester M; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z; Sørensen, Thorkild I A; Spector, Tim D; Steptoe, Andrew; Terracciano, Antonio; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Uitterlinden, André G; Vollenweider, Peter; Wagner, Gert G; Weir, David R; Yang, Jian; Conley, Dalton C; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Pickrell, Joseph K; Esko, Tõnu; Krueger, Robert F; Beauchamp, Jonathan P; Koellinger, Philipp D; Benjamin, Daniel J; Bartels, Meike; Cesarini, David

    Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted

  3. Multivariate Analyses and Classification of Inertial Sensor Data to Identify Aging Effects on the Timed-Up-and-Go Test

    NARCIS (Netherlands)

    Vervoort, Danique; Vuillerme, Nicolas; Kosse, Nienke; Hortobágyi, Tibor; Lamoth, Claudine J C

    2016-01-01

    Many tests can crudely quantify age-related mobility decrease but instrumented versions of mobility tests could increase their specificity and sensitivity. The Timed-up-and-Go (TUG) test includes several elements that people use in daily life. The test has different transition phases: rise from a

  4. Corrigendum: Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    NARCIS (Netherlands)

    Okbay, Aysu; Baselmans, Bart M. L.; De Neve, Jan-Emmanuel; Turley, Patrick; Nivard, Michel G.; Fontana, Mark Alan; Meddens, S. Fleur W.; Linner, Richard Karlsson; Rietveld, Cornelius A.; Derringer, Jaime; Gratten, Jacob; Lee, James J.; Liu, Jimmy Z.; de Vlaming, Ronald; Ahluwalia, Tarunveer S.; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C.; Furlotte, Nicholas A.; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R.; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W.; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J.; Lind, Penelope A.; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Miller, Michael B.; Minica, Camelia C.; Nolte, Ilja M.; Mook-Kanamori, Dennis; van der Most, Peter J.; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Borge; Smith, Albert V.; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Thorleifsson, Gudmar; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M.; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Bergmann, Sven; Bjornsdottir, Gyda; Boyle, Patricia A.; Cherney, Samantha; Cox, Simon R.; Davies, Gail; Davis, Oliver S. P.; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T.; Fatemifar, Ghazaleh; Faul, Jessica D.; Ferrucci, Luigi; Forstner, Andreas J.; Gieger, Christian; Gupta, Richa; Harris, Tamara B.; Harris, Juliette M.; Holliday, Elizabeth G.; Hottenga, Jouke-Jan; De Jager, Philip L.; Kaakinen, Marika A.; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J.; Franke, Lude; Li-Gao, Ruifang; Liewald, David C.; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W.; Mosing, Miriam A.; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E.; Pulkki-Raback, Laura; Quaye, Lydia; Raikkonen, Katri; Rudan, Igor; Scott, Rodney J.; Smith, Jennifer A.; Sutin, Angelina R.; Trzaskowski, Maciej; Vinkhuyzen, Anna E.; Yu, Lei; Zabaneh, Delilah; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I.; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J.; van Duijn, Cornelia M.; Eriksson, Johan G.; Bultmann, Ute; de Geus, Eco J. C.; Groenen, Patrick J. F.; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A.; Haworth, Claire M. A.; Hayward, Caroline; Heath, Andrew C.; Hinds, David A.; Hypponen, Elina; Iacono, William G.; Jarvelin, Marjo-Rutta; Jockel, Karl -Heinz; Kaprio, Jaakko; Kardia, Sharon L. R.; Keltikangas-Jarvinen, Liisa; Kraft, Peter; Kubzansky, Laura D.; Lehtimaki, Terho; Magnusson, Patrik K. E.; Martin, Nicholas G.; Mcgue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renee; Oldehinkel, Albertine J.; Pasterkamp, Gerard; Pedersen, Nancy L.; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S.; Rosendaal, Frits R.; den Ruijter, Hester M.; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z.; Sorensen, Thorkild I. A.; Spector, Tim D.; Starr, John M.; Stefansson, Kari; Steptoe, Andrew; Terracciano, Antonio; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Uitterlinden, Andre G.; Vollenweider, Peter; Wagner, Gert G.; Weir, David R.; Yang, Jian; Conley, Dalton C.; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I.; Medland, Sarah E.; Meyer, Michelle N.; Pickrell, Joseph K.; Esko, Tonu; Krueger, Robert F.; Beauchamp, Jonathan P.; Koellinger, Philipp D.; Benjamin, Daniel J.; Bartels, Meike; Cesarini, David

    2016-01-01

    In the version of this article initially published, one of the affiliations listed for author Maciej Trzaskowski, to the Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia, was included in error. The correct affiliation for this author is the Queensland Brain

  5. High-Resolution Linkage Analyses to Identify Genes That Influence Varroa Sensitive Hygiene Behavior in Honey Bees

    OpenAIRE

    Tsuruda, Jennifer M.; Harris, Jeffrey W.; Bourgeois, Lanie; Danka, Robert G.; Hunt, Greg J.

    2012-01-01

    Varroa mites (V. destructor) are a major threat to honey bees (Apis melilfera) and beekeeping worldwide and likely lead to colony decline if colonies are not treated. Most treatments involve chemical control of the mites; however, Varroa has evolved resistance to many of these miticides, leaving beekeepers with a limited number of alternatives. A non-chemical control method is highly desirable for numerous reasons including lack of chemical residues and decreased likelihood of resistance. Var...

  6. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    NARCIS (Netherlands)

    Surendran, Praveen; Drenos, Fotios; Young, Robin; Warren, Helen; Cook, James P; Manning, Alisa K; Grarup, Niels; Sim, Xueling; Barnes, Daniel R; Witkowska, Kate; Staley, James R; Tragante, Vinicius; Tukiainen, Taru; Yaghootkar, Hanieh; Masca, Nicholas; Freitag, Daniel F; Ferreira, Teresa; Giannakopoulou, Olga; Tinker, Andrew; Harakalova, Magdalena; Mihailov, Evelin; Liu, Chunyu; Kraja, Aldi T; Nielsen, Sune Fallgaard; Rasheed, Asif; Samuel, Maria; Zhao, Wei; Bonnycastle, Lori L; Jackson, Anne U; Narisu, Narisu; Swift, Amy J; Southam, Lorraine; Marten, Jonathan; Huyghe, Jeroen R; Stančáková, Alena; Fava, Cristiano; Ohlsson, Therese; Matchan, Angela; Stirrups, Kathleen E; Bork-Jensen, Jette; Gjesing, Anette P; Kontto, Jukka; Perola, Markus; Shaw-Hawkins, Susan; Havulinna, Aki S; Zhang, He; Donnelly, Louise A; Groves, Christopher J; Rayner, N William; Neville, Matt J; Robertson, Neil R; Yiorkas, Andrianos M; Herzig, Karl-Heinz; Kajantie, Eero; Zhang, Weihua; Willems, Sara M; Lannfelt, Lars; Malerba, Giovanni; Soranzo, Nicole; Trabetti, Elisabetta; Verweij, Niek; Evangelou, Evangelos; Moayyeri, Alireza; Vergnaud, Anne-Claire; Nelson, Christopher P; Poveda, Alaitz; Varga, Tibor V; Caslake, Muriel; de Craen, Anton J M; Trompet, Stella; Luan, Jian'an; Scott, Robert A; Harris, Sarah E; Liewald, David C M; Marioni, Riccardo; Menni, Cristina; Farmaki, Aliki-Eleni; Hallmans, Göran; Renström, Frida; Huffman, Jennifer E; Hassinen, Maija; Burgess, Stephen; Vasan, Ramachandran S; Felix, Janine F; Uria-Nickelsen, Maria; Malarstig, Anders; Reilly, Dermot F; Hoek, Maarten; Vogt, Thomas F; Lin, Honghuang; Lieb, Wolfgang; Traylor, Matthew; Markus, Hugh S; Highland, Heather M; Justice, Anne E; Marouli, Eirini; Lindström, Jaana; Uusitupa, Matti; Komulainen, Pirjo; Lakka, Timo A; Rauramaa, Rainer; Polasek, Ozren; Rudan, Igor; Rolandsson, Olov; Franks, Paul W; Dedoussis, George; Spector, Timothy D; Jousilahti, Pekka; Männistö, Satu; Deary, Ian J; Starr, John M; Langenberg, Claudia; Wareham, Nick J; Brown, Morris J; Dominiczak, Anna F; Connell, John M; Jukema, J Wouter; Sattar, Naveed; Ford, Ian; Packard, Chris J; Esko, Tõnu; Mägi, Reedik; Metspalu, Andres; de Boer, Rudolf A; van der Meer, Peter; van der Harst, Pim; Gambaro, Giovanni; Ingelsson, Erik; Lind, Lars; de Bakker, Paul I W; Numans, Mattijs E; Brandslund, Ivan; Christensen, Cramer; Petersen, Eva R B; Korpi-Hyövälti, Eeva; Oksa, Heikki; Chambers, John C; Kooner, Jaspal S; Blakemore, Alexandra I F; Franks, Steve; Jarvelin, Marjo-Riitta; Husemoen, Lise L; Linneberg, Allan; Skaaby, Tea; Thuesen, Betina; Karpe, Fredrik; Tuomilehto, Jaakko; Doney, Alex S F; Morris, Andrew D; Palmer, Colin N A; Holmen, Oddgeir Lingaas; Hveem, Kristian; Willer, Cristen J; Tuomi, Tiinamaija; Groop, Leif; Käräjämäki, AnneMari; Palotie, Aarno; Ripatti, Samuli; Salomaa, Veikko; Alam, Dewan S; Majumder, Abdulla Al Shafi; Di Angelantonio, Emanuele; Chowdhury, Rajiv; McCarthy, Mark I; Poulter, Neil; Stanton, Alice V; Sever, Peter; Amouyel, Philippe; Arveiler, Dominique; Blankenberg, Stefan; Ferrières, Jean; Kee, Frank; Kuulasmaa, Kari; Müller-Nurasyid, Martina; Veronesi, Giovanni; Virtamo, Jarmo; Deloukas, Panos; Elliott, Paul; Zeggini, Eleftheria; Kathiresan, Sekar; Melander, Olle; Kuusisto, Johanna; Laakso, Markku; Padmanabhan, Sandosh; Porteous, David J; Hayward, Caroline; Scotland, Generation; Collins, Francis S; Mohlke, Karen L; Hansen, Torben; Pedersen, Oluf; Boehnke, Michael; Stringham, Heather M; Frossard, Philippe; Newton-Cheh, Christopher; Tobin, Martin D; Nordestgaard, Børge Grønne; Caulfield, Mark J; Mahajan, Anubha; Morris, Andrew P; Tomaszewski, Maciej; Samani, Nilesh J; Saleheen, Danish; Asselbergs, Folkert W; Lindgren, Cecilia M; Danesh, John; Wain, Louise V; Butterworth, Adam S; Howson, Joanna M M; Munroe, Patricia B

    2016-01-01

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to

  7. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    NARCIS (Netherlands)

    Surendran, P. (Praveen); F. Drenos (Fotios); R. Young (Robin); H. Warren (Helen); Cook, J.P. (James P.); A.K. Manning (Alisa); N. Grarup (Niels); X. Sim (Xueling); D. Barnes (Daniel); H.E. Witkowska (Ewa); J.R. Staley (James R.); V. Tragante (Vinicius); T. Tukiainen (Taru); H. Yaghootkar (Hanieh); Masca, N. (Nicholas); C.M. Freitag (Christine); T. Ferreira (Teresa); O. Giannakopoulou (Olga); Tinker, A. (Andrew); M. Harakalova (Magdalena); E. Mihailov (Evelin); Liu, C. (Chunyu); A. Kraja (Aldi); S.F. Nielsen (Sune); A. Rasheed (Asif); M. Samuel (Maria); W. Zhao (Wei); L.L. Bonnycastle (Lori); A.U. Jackson (Anne); N. Narisu (Narisu); A.J. Swift (Amy); L. Southam (Lorraine); J. Marten (Jonathan); J.R. Huyghe (Jeroen R.); A. Stancáková (Alena); C. Fava (Cristiano); Ohlsson, T. (Therese); A. Matchan (Angela); K. Stirrups (Kathy); J. Bork-Jensen (Jette); A.P. Gjesing (Anette); Kontto, J. (Jukka); M. Perola (Markus); S. Shaw-Hawkins (Sue); A.S. Havulinna (Aki); Zhang, H. (He); L.A. Donnelly (Louise); C.J. Groves (Christopher); N.W. Rayner (Nigel William); M.J. Neville (Matthew); N.R. Robertson (Neil); Yiorkas, A.M. (Andrianos M.); K.H. Herzig; E. Kajantie (Eero); W. Zhang (Weihua); S.M. Willems (Sara); L. Lannfelt (Lars); G. Malerba (Giovanni); N. Soranzo (Nicole); E. Trabetti (Elisabetta); N. Verweij (Niek); E. Evangelou (Evangelos); A. Moayyeri (Alireza); Vergnaud, A.-C. (Anne-Claire); C.P. Nelson (Christopher P.); Poveda, A. (Alaitz); T.V. Varga (Tibor V.); M. Caslake (Muriel); A.J.M. De Craen (Anton J. M.); S. Trompet (Stella); J. Luan (Jian'An); R.A. Scott (Robert); S.E. Harris (Sarah); D.C. Liewald (David C.); R.E. Marioni (Riccardo); C. Menni (Cristina); A.-E. Farmaki (Aliki-Eleni); G. Hallmans (Göran); F. Renström (Frida); J.E. Huffman (Jennifer); Hassinen, M. (Maija); S. Burgess (Stephen); Vasan, R.S. (Ramachandran S.); J.F. Felix (Janine); Uria-Nickelsen, M. (Maria); A. Mälarstig (Anders); Reilly, D.F. (Dermot F.); Hoek, M. (Maarten); Vogt, T.F. (Thomas F.); H. Lin (Honghuang); W. Lieb (Wolfgang); M. Traylor (Matthew); H.S. Markus (Hugh); H. Highland (Heather); A.E. Justice (Anne); E. Marouli (Eirini); J. Lindström (Jaana); M. Uusitupa (Matti); P. Komulainen (Pirjo); T.A. Lakka (Timo); R. Rauramaa (Rainer); O. Polasek (Ozren); I. Rudan (Igor); Rolandsson, O. (Olov); P.W. Franks (Paul); G.V. Dedoussis (George); T.D. Spector (Timothy); P. Jousilahti (Pekka); S. Männistö (Satu); I.J. Deary (Ian J.); J.M. Starr (John); C. Langenberg (Claudia); N.J. Wareham (Nick); M.J. Brown (Morris); A. Dominiczak (Anna); Connell, J.M. (John M.); J.W. Jukema (Jan Wouter); N. Sattar (Naveed); I. Ford (Ian); Packard, C.J. (Chris J.); T. Esko (Tõnu); R. Mägi (Reedik); A. Metspalu (Andres); R.A. de Boer (Rudolf); Van Der Meer, P. (Peter); P. van der Harst (Pim); G. Gambaro (Giovanni); Ingelsson, E. (Erik); W.H.L. Kao (Wen); P.I.W. de Bakker (Paul); M.E. Numans (Mattijs); I. Brandslund (Ivan); Christensen, C. (Cramer); Petersen, E.R.B. (Eva R. B.); E. Korpi-Hyövälti (Eeva); H. Oksa (Heikki); J.C. Chambers (John); J.S. Kooner (Jaspal S.); A.I.F. Blakemore (Alexandra); S. Franks (Steve); M.-R. Jarvelin (Marjo-Riitta); L.L.N. Husemoen (Lise Lotte); Linneberg, A. (Allan); T. Skaaby (Tea); Thuesen, B. (Betina); F. Karpe (Fredrik); J. Tuomilehto (Jaakko); A.S.F. Doney (Alex); A.D. Morris (Andrew); C.N.A. Palmer (Colin); O.L. Holmen (Oddgeir); K. Hveem (Kristian); C.J. Willer (Cristen); T. Tuomi (Tiinamaija); L. Groop (Leif); Käräjämäki, A. (Annemari); A. Palotie (Aarno); S. Ripatti (Samuli); V. Salomaa (Veikko); D.S. Alam (Dewan S.); Majumder, A.A.S. (Abdulla Al Shafi); E. di Angelantonio (Emanuele); R. Chowdhury (Rajiv); M.I. McCarthy (Mark); N.R. Poulter (Neil); A. Stanton (Alice); P. Sever (Peter); P. Amouyel (Philippe); D. Arveiler (Dominique); Blankenberg, S. (Stefan); J. Ferrieres (Jean); F. Kee (Frank); K. Kuulasmaa (Kari); M. Müller-Nurasyid (Martina); G. Veronesi (Giovanni); J. Virtamo (Jarmo); P. Deloukas (Panagiotis); P. Elliott (Paul); E. Zeggini (Eleftheria); S. Kathiresan (Sekar); O. Melander (Olle); J. Kuusisto (Johanna); M. Laakso (Markku); S. Padmanabhan (Sandosh); D. Porteous (David); C. Hayward (Caroline); G. Scotland (Generation); F.S. Collins (Francis); K.L. Mohlke (Karen); T. Hansen (T.); O. Pedersen (Oluf); M. Boehnke (Michael); H.M. Stringham (Heather); R. Frossard; C. Newton-Cheh (Christopher); M.D. Tobin (Martin); B.G. Nordestgaard (Børge); M. Caulfield (Mark); A. Mahajan (Anubha); A.P. Morris (Andrew); Tomaszewski, M. (Maciej); N.J. Samani (Nilesh); Saleheen, D. (Danish); F.W. Asselbergs (Folkert); C.M. Lindgren (Cecilia M.); J. Danesh (John); Wain, L.V. (Louise V.); A.S. Butterworth (Adam); Howson, J.M.M. (Joanna M. M.); P. Munroe (Patricia)

    2016-01-01

    textabstractHigh blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants

  8. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.

    NARCIS (Netherlands)

    Okbay, A.; Baselmans, B.M.L.; de Neve, J.E.; Turley, P.; Nivard, M.G.; Fontana, M.A.; Meddens, S.F.W.; Karlsson Linnér, R.; Rietveld, C.A.; Derringer, J.; de Vlaming, R.; Minica, C.C.; Hottenga, J.J.; Vinkhuyzen, A.A.E.; Boomsma, D.I.; de Geus, E.J.C.; Medland, S.E.; Meyer, M.N.; Pickrell, J.K.; Esko, T.; Krueger, R.F.; Beauchamp, J.; Koellinger, P.D.; Benjamin, D.J.; Bartels, M.; Cesarini, D.

    2016-01-01

    Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted

  9. Molecular analyses of the agouti allele in the Japanese house mouse identify a novel variant of the agouti gene.

    Science.gov (United States)

    Iwasa, Masahiro A; Kawamura, Sayaka; Myoshu, Hikari; Suzuki, Taichi A

    2018-03-01

    It has been thought that the Japanese house mouse carries the A w allele at the agouti locus causing light-colored bellies, but they do not always show this coloration. Thus, the presence of the A w allele seems to be doubtful in them. To ascertain whether the A w allele is present, a two-pronged approach was used. First, we compared lengths of DNA fragments obtained from three PCRs conducted on them to the known fragment sizes generated from mouse strains exhibiting homozygosities of either a/a, A/A, or A w /A w . PCR I, PCR II, and PCR III amplify only in the A and A w alleles, the a and A w alleles, and the a allele, respectively, and we detected amplifications in strains with A/A and A w /A w by PCR I, in those with a/a and the Japanese house mouse by PCR II, and in those with a/a by PCR III. Second, we sequenced the exon 1A region of the agouti gene and obtained sequences corresponding to the above strains and the Japanese house mouse, but their sequences were similar to those of the a allele. We concluded that their agouti allele is not identical to the A w allele and seems to be a novel type similar to the a allele.

  10. Deep sequencing and transcriptome analyses to identify genes involved in secoiridoid biosynthesis in Tibetan medicinal plant Sewertia mussotii

    Science.gov (United States)

    Swertia mussotii Franch. is an important traditional Tibetan medicinal plant with pharmacological properties useful for the treatment of various ailments, such as hepatitis. Secoiridoids, including swertiamarin, are the major bioactive compounds in S. mussotii. The development of genomic resources ...

  11. Community-level physiological profiling analyses show potential to identify the copiotrophic bacteria present in soil environments

    Czech Academy of Sciences Publication Activity Database

    Lladó, Salvador; Baldrian, Petr

    2017-01-01

    Roč. 12, č. 2 (2017), s. 1-9, č. článku e0171638. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GP14-09040P; GA MŠk(CZ) LD15086 Institutional support: RVO:61388971 Keywords : SUBSTRATE UTILIZATION PATTERNS * CARBON -SOURCE UTILIZATION * MICROBIAL COMMUNITIES Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.806, year: 2016

  12. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    DEFF Research Database (Denmark)

    Surendran, Praveen; Drenos, Fotios; Young, Robin

    2016-01-01

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ...

  13. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

    NARCIS (Netherlands)

    Surendran, Praveen; Drenos, Fotios; Young, Robin; Warren, Helen; Cook, James P.; Manning, Alisa K.; Grarup, Niels; Sim, Xueling; Barnes, Daniel R.; Witkowska, Kate; Staley, James R.; Tragante, Vinicius; Tukiainen, Taru; Yaghootkar, Hanieh; Masca, Nicholas; Freitag, Daniel F.; Ferreira, Teresa; Giannakopoulou, Olga; Tinker, Andrew; Harakalova, Magdalena; Mihailov, Evelin; Liu, Chunyu; Kraja, Aldi T.; Nielsen, Sune Fallgaard; Rasheed, Asif; Samue, Maria; Zhao, Wei; Bonnycastle, Lori L.; Jackson, Anne U.; Narisu, Narisu; Swift, Amy J.; Southam, Lorraine; Marten, Jonathan; Huyghe, Jeroen R.; Stancakova, Alena; Fava, Cristiano; Ohlsson, Therese; Matchan, Angela; Stirrups, Kathleen E.; Bork-Jensen, Jette; Gjesing, Anette P.; Kontto, Jukka; Perola, Markus; Shaw-Hawkins, Susan; Havulinna, Aki S.; Verweij, Niek; de Boer, Rudolf A.; van der Meer, Peter; van der Harst, Pim; Asselbergs, Folkert W.

    2016-01-01

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low frequency and common genetic variants in up to

  14. Financial relationships in economic analyses of targeted therapies in oncology.

    Science.gov (United States)

    Valachis, Antonis; Polyzos, Nikolaos P; Nearchou, Andreas; Lind, Pehr; Mauri, Davide

    2012-04-20

    A potential financial relationship between investigators and pharmaceutical manufacturers has been associated with an increased likelihood of reporting favorable conclusions about a sponsor's proprietary agent in pharmacoeconomic studies. The purpose of this study is to investigate whether there is an association between financial relationships and outcome in economic analyses of new targeted therapies in oncology. We searched PubMed (last update June 2011) for economic analyses of targeted therapies (including monoclonal antibodies, tyrosine-kinase inhibitors, and mammalian target of rapamycin inhibitors) in oncology. The trials were qualitatively rated regarding the cost assessment as favorable, neutral, or unfavorable on the basis of prespecified criteria. Overall, 81 eligible studies were identified. Economic analyses that were funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates (28 [82%] of 34 v 21 [45%] of 47; P = .003). The presence of an author affiliated with manufacturer was not associated with study outcome. Furthermore, if only studies including a conflict of interest statement were included (66 of 81), studies that reported any financial relationship with manufacturers (author affiliation and/or funding and/or other financial relationship) were more likely to report favorable results of targeted therapies compared with studies without financial relationship (32 [71%] of 45 v nine [43%] of 21; P = .025). Our study reveals a potential threat for industry-related bias in economic analyses of targeted therapies in oncology in favor of analyses with financial relationships between authors and manufacturers. A more balanced funding of economic analyses from other sources may allow greater confidence in the interpretation of their results.

  15. Numerical identifiability of the parameters of induction machines

    Energy Technology Data Exchange (ETDEWEB)

    Corcoles, F.; Pedra, J.; Salichs, M. [Dep. d' Eng. Electrica ETSEIB. UPC, Barcelona (Spain)

    2000-08-01

    This paper analyses the numerical identifiability of the electrical parameters of induction machines. Relations between parameters and the impossibility to estimate all of them - when only external measures are used: voltage, current, speed and torque - are shown. Formulations of the single and double-cage induction machine, with and without core losses in both models, are developed. The proposed solution is the formulation of machine equations by using the minimum number of parameters (which are identifiable parameters). As an application example, the parameters of a double-cage induction machine are identified using steady-state measurements corresponding to different angular speeds. (orig.)

  16. RECOVIR Software for Identifying Viruses

    Science.gov (United States)

    Chakravarty, Sugoto; Fox, George E.; Zhu, Dianhui

    2013-01-01

    Most single-stranded RNA (ssRNA) viruses mutate rapidly to generate a large number of strains with highly divergent capsid sequences. Determining the capsid residues or nucleotides that uniquely characterize these strains is critical in understanding the strain diversity of these viruses. RECOVIR (an acronym for "recognize viruses") software predicts the strains of some ssRNA viruses from their limited sequence data. Novel phylogenetic-tree-based databases of protein or nucleic acid residues that uniquely characterize these virus strains are created. Strains of input virus sequences (partial or complete) are predicted through residue-wise comparisons with the databases. RECOVIR uses unique characterizing residues to identify automatically strains of partial or complete capsid sequences of picorna and caliciviruses, two of the most highly diverse ssRNA virus families. Partition-wise comparisons of the database residues with the corresponding residues of more than 300 complete and partial sequences of these viruses resulted in correct strain identification for all of these sequences. This study shows the feasibility of creating databases of hitherto unknown residues uniquely characterizing the capsid sequences of two of the most highly divergent ssRNA virus families. These databases enable automated strain identification from partial or complete capsid sequences of these human and animal pathogens.

  17. Benchmarking in Identifying Priority Directions of Development of Telecommunication Operators

    Directory of Open Access Journals (Sweden)

    Zaharchenko Lolita A.

    2013-12-01

    Full Text Available The article analyses evolution of development and possibilities of application of benchmarking in the telecommunication sphere. It studies essence of benchmarking on the basis of generalisation of approaches of different scientists to definition of this notion. In order to improve activity of telecommunication operators, the article identifies the benchmarking technology and main factors, that determine success of the operator in the modern market economy, and the mechanism of benchmarking and component stages of carrying out benchmarking by a telecommunication operator. It analyses the telecommunication market and identifies dynamics of its development and tendencies of change of the composition of telecommunication operators and providers. Having generalised the existing experience of benchmarking application, the article identifies main types of benchmarking of telecommunication operators by the following features: by the level of conduct of (branch, inter-branch and international benchmarking; by relation to participation in the conduct (competitive and joint; and with respect to the enterprise environment (internal and external.

  18. Mass separated neutral particle energy analyser

    International Nuclear Information System (INIS)

    Takeuchi, Hiroshi; Matsuda, Toshiaki; Miura, Yukitoshi; Shiho, Makoto; Maeda, Hikosuke; Hashimoto, Kiyoshi; Hayashi, Kazuo.

    1983-09-01

    A mass separated neutral particle energy analyser which could simultaneously measure hydrogen and deuterium atoms emitted from tokamak plasma was constructed. The analyser was calibrated for the energy and mass separation in the energy range from 0.4 keV to 9 keV. In order to investigate the behavior of deuteron and proton in the JFT-2 tokamak plasma heated with ion cyclotron wave and neutral beam injection, this analyser was installed in JFT-2 tokamak. It was found that the energy spectrum could be determined with sufficient accuracy. The obtained ion temperature and ratio of deuteron and proton density from the energy spectrum were in good agreement with the value deduced from Doppler broadening of TiXIV line and the line intensities of H sub(α) and D sub(α) respectively. (author)

  19. Advanced toroidal facility vaccuum vessel stress analyses

    International Nuclear Information System (INIS)

    Hammonds, C.J.; Mayhall, J.A.

    1987-01-01

    The complex geometry of the Advance Toroidal Facility (ATF) vacuum vessel required special analysis techniques in investigating the structural behavior of the design. The response of a large-scale finite element model was found for transportation and operational loading. Several computer codes and systems, including the National Magnetic Fusion Energy Computer Center Cray machines, were implemented in accomplishing these analyses. The work combined complex methods that taxed the limits of both the codes and the computer systems involved. Using MSC/NASTRAN cyclic-symmetry solutions permitted using only 1/12 of the vessel geometry to mathematically analyze the entire vessel. This allowed the greater detail and accuracy demanded by the complex geometry of the vessel. Critical buckling-pressure analyses were performed with the same model. The development, results, and problems encountered in performing these analyses are described. 5 refs., 3 figs

  20. Thermal and stress analyses with ANSYS program

    International Nuclear Information System (INIS)

    Kanoo, Iwao; Kawaguchi, Osamu; Asakura, Junichi.

    1975-03-01

    Some analyses of the heat conduction and elastic/inelastic stresses, carried out in Power Reactor and Nuclear Fuel Development Corporation (PNC) in fiscal 1973 using ANSYS (Engineering Analysis System) program, are summarized. In chapter I, the present state of structural analysis programs available for a FBR (fast breeder reactor) in PNC is explained. Chapter II is a brief description of the ANSYS current status. In chapter III are presented 8 examples of the steady-state and transient thermal analyses for fast-reactor plant components, and in chapter IV 5 examples of the inelastic structural analysis. With the advance in the field of finite element method, its applications in design study should extend progressively in the future. The present report, it is hoped, will contribute as references in similar analyses and at the same time help to understand the deformation and strain behaviors of structures. (Mori, K.)

  1. Periodic safety analyses; Les essais periodiques

    Energy Technology Data Exchange (ETDEWEB)

    Gouffon, A; Zermizoglou, R

    1990-12-01

    The IAEA Safety Guide 50-SG-S8 devoted to 'Safety Aspects of Foundations of Nuclear Power Plants' indicates that operator of a NPP should establish a program for inspection of safe operation during construction, start-up and service life of the plant for obtaining data needed for estimating the life time of structures and components. At the same time the program should ensure that the safety margins are appropriate. Periodic safety analysis are an important part of the safety inspection program. Periodic safety reports is a method for testing the whole system or a part of the safety system following the precise criteria. Periodic safety analyses are not meant for qualification of the plant components. Separate analyses are devoted to: start-up, qualification of components and materials, and aging. All these analyses are described in this presentation. The last chapter describes the experience obtained for PWR-900 and PWR-1300 units from 1986-1989.

  2. A Simple, Reliable Precision Time Analyser

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, B. V.; Nargundkar, V. R.; Subbarao, K.; Kamath, M. S.; Eligar, S. K. [Atomic Energy Establishment Trombay, Bombay (India)

    1966-06-15

    A 30-channel time analyser is described. The time analyser was designed and built for pulsed neutron research but can be applied to other uses. Most of the logic is performed by means of ferrite memory core and transistor switching circuits. This leads to great versatility, low power consumption, extreme reliability and low cost. The analyser described provides channel Widths from 10 {mu}s to 10 ms; arbitrarily wider channels are easily obtainable. It can handle counting rates up to 2000 counts/min in each channel with less than 1% dead time loss. There is a provision for an initial delay equal to 100 channel widths. An input pulse de-randomizer unit using tunnel diodes ensures exactly equal channel widths. A brief description of the principles involved in core switching circuitry is given. The core-transistor transfer loop is compared with the usual core-diode loops and is shown to be more versatile and better adapted to the making of a time analyser. The circuits derived from the basic loop are described. These include the scale of ten, the frequency dividers and the delay generator. The current drivers developed for driving the cores are described. The crystal-controlled clock which controls the width of the time channels and synchronizes the operation of the various circuits is described. The detector pulse derandomizer unit using tunnel diodes is described. The scheme of the time analyser is then described showing how the various circuits can be integrated together to form a versatile time analyser. (author)

  3. Identifying ELIXIR Core Data Resources.

    Science.gov (United States)

    Durinx, Christine; McEntyre, Jo; Appel, Ron; Apweiler, Rolf; Barlow, Mary; Blomberg, Niklas; Cook, Chuck; Gasteiger, Elisabeth; Kim, Jee-Hyub; Lopez, Rodrigo; Redaschi, Nicole; Stockinger, Heinz; Teixeira, Daniel; Valencia, Alfonso

    2016-01-01

    The core mission of ELIXIR is to build a stable and sustainable infrastructure for biological information across Europe. At the heart of this are the data resources, tools and services that ELIXIR offers to the life-sciences community, providing stable and sustainable access to biological data. ELIXIR aims to ensure that these resources are available long-term and that the life-cycles of these resources are managed such that they support the scientific needs of the life-sciences, including biological research. ELIXIR Core Data Resources are defined as a set of European data resources that are of fundamental importance to the wider life-science community and the long-term preservation of biological data. They are complete collections of generic value to life-science, are considered an authority in their field with respect to one or more characteristics, and show high levels of scientific quality and service. Thus, ELIXIR Core Data Resources are of wide applicability and usage. This paper describes the structures, governance and processes that support the identification and evaluation of ELIXIR Core Data Resources. It identifies key indicators which reflect the essence of the definition of an ELIXIR Core Data Resource and support the promotion of excellence in resource development and operation. It describes the specific indicators in more detail and explains their application within ELIXIR's sustainability strategy and science policy actions, and in capacity building, life-cycle management and technical actions. The identification process is currently being implemented and tested for the first time. The findings and outcome will be evaluated by the ELIXIR Scientific Advisory Board in March 2017. Establishing the portfolio of ELIXIR Core Data Resources and ELIXIR Services is a key priority for ELIXIR and publicly marks the transition towards a cohesive infrastructure.

  4. DIA-datasnooping and identifiability

    Science.gov (United States)

    Zaminpardaz, S.; Teunissen, P. J. G.

    2018-04-01

    In this contribution, we present and analyze datasnooping in the context of the DIA method. As the DIA method for the detection, identification and adaptation of mismodelling errors is concerned with estimation and testing, it is the combination of both that needs to be considered. This combination is rigorously captured by the DIA estimator. We discuss and analyze the DIA-datasnooping decision probabilities and the construction of the corresponding partitioning of misclosure space. We also investigate the circumstances under which two or more hypotheses are nonseparable in the identification step. By means of a theorem on the equivalence between the nonseparability of hypotheses and the inestimability of parameters, we demonstrate that one can forget about adapting the parameter vector for hypotheses that are nonseparable. However, as this concerns the complete vector and not necessarily functions of it, we also show that parameter functions may exist for which adaptation is still possible. It is shown how this adaptation looks like and how it changes the structure of the DIA estimator. To demonstrate the performance of the various elements of DIA-datasnooping, we apply the theory to some selected examples. We analyze how geometry changes in the measurement setup affect the testing procedure, by studying their partitioning of misclosure space, the decision probabilities and the minimal detectable and identifiable biases. The difference between these two minimal biases is highlighted by showing the difference between their corresponding contributing factors. We also show that if two alternative hypotheses, say Hi and Hj , are nonseparable, the testing procedure may have different levels of sensitivity to Hi -biases compared to the same Hj -biases.

  5. Fundamental data analyses for measurement control

    International Nuclear Information System (INIS)

    Campbell, K.; Barlich, G.L.; Fazal, B.; Strittmatter, R.B.

    1987-02-01

    A set of measurment control data analyses was selected for use by analysts responsible for maintaining measurement quality of nuclear materials accounting instrumentation. The analyses consist of control charts for bias and precision and statistical tests used as analytic supplements to the control charts. They provide the desired detection sensitivity and yet can be interpreted locally, quickly, and easily. The control charts provide for visual inspection of data and enable an alert reviewer to spot problems possibly before statistical tests detect them. The statistical tests are useful for automating the detection of departures from the controlled state or from the underlying assumptions (such as normality). 8 refs., 3 figs., 5 tabs

  6. A theoretical framework for analysing preschool teaching

    DEFF Research Database (Denmark)

    Chaiklin, Seth

    2014-01-01

    This article introduces a theoretical framework for analysing preschool teaching as a historically-grounded societal practice. The aim is to present a unified framework that can be used to analyse and compare both historical and contemporary examples of preschool teaching practice within and across...... national traditions. The framework has two main components, an analysis of preschool teaching as a practice, formed in relation to societal needs, and an analysis of the categorical relations which necessarily must be addressed in preschool teaching activity. The framework is introduced and illustrated...

  7. Power System Oscillatory Behaviors: Sources, Characteristics, & Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Follum, James D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Tuffner, Francis K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Dosiek, Luke A. [Union College, Schenectady, NY (United States); Pierre, John W. [Univ. of Wyoming, Laramie, WY (United States)

    2017-05-17

    This document is intended to provide a broad overview of the sources, characteristics, and analyses of natural and forced oscillatory behaviors in power systems. These aspects are necessarily linked. Oscillations appear in measurements with distinguishing characteristics derived from the oscillation’s source. These characteristics determine which analysis methods can be appropriately applied, and the results from these analyses can only be interpreted correctly with an understanding of the oscillation’s origin. To describe oscillations both at their source within a physical power system and within measurements, a perspective from the boundary between power system and signal processing theory has been adopted.

  8. Neoliberalism in education: Five images of critical analyses

    Directory of Open Access Journals (Sweden)

    Branislav Pupala

    2011-03-01

    Full Text Available The survey study brings information about the way that educational researchcopes with neoliberalism as a generalized form of social government in the currentwestern culture. It shows that neoliberalism is considered as a universal scope of otherchanges in the basic segments of education and those theoretical and critical analyses ofthis phenomenon represent an important part of production in the area of educationalresearch. It emphasizes the contribution of formation and development of the socalledgovernmental studies for comprehension of mechanisms and consequences ofneoliberal government of the society and shows how way the methodology of thesestudies helps to identify neoliberal strategies used in the regulation of social subjectsby education. There are five selected segments of critical analyses elaborated (fromthe concept of a lifelong learning, through preschool and university education to theeducation of teachers and PISA project that obviously show ideological and theoreticalcohesiveness of the education analysis through the scope of neoliberal governmentality.

  9. The moral economy of austerity: analysing UK welfare reform.

    Science.gov (United States)

    Morris, Lydia

    2016-03-01

    This paper notes the contemporary emergence of 'morality' in both sociological argument and political rhetoric, and analyses its significance in relation to ongoing UK welfare reforms. It revisits the idea of 'moral economy' and identifies two strands in its contemporary application; that all economies depend on an internal moral schema, and that some external moral evaluation is desirable. UK welfare reform is analysed as an example of the former, with reference to three distinct orientations advanced in the work of Freeden (1996), Laclau (2014), and Lockwood (1996). In this light, the paper then considers challenges to the reform agenda, drawn from third sector and other public sources. It outlines the forms of argument present in these challenges, based respectively on rationality, legality, and morality, which together provide a basis for evaluation of the welfare reforms and for an alternative 'moral economy'. © London School of Economics and Political Science 2016.

  10. 10 CFR 61.13 - Technical analyses.

    Science.gov (United States)

    2010-01-01

    ... air, soil, groundwater, surface water, plant uptake, and exhumation by burrowing animals. The analyses... processes such as erosion, mass wasting, slope failure, settlement of wastes and backfill, infiltration through covers over disposal areas and adjacent soils, and surface drainage of the disposal site. The...

  11. Analysing Simple Electric Motors in the Classroom

    Science.gov (United States)

    Yap, Jeff; MacIsaac, Dan

    2006-01-01

    Electromagnetic phenomena and devices such as motors are typically unfamiliar to both teachers and students. To better visualize and illustrate the abstract concepts (such as magnetic fields) underlying electricity and magnetism, we suggest that students construct and analyse the operation of a simply constructed Johnson electric motor. In this…

  12. En kvantitativ metode til analyse af radio

    Directory of Open Access Journals (Sweden)

    Christine Lejre

    2014-06-01

    Full Text Available I den danske såvel som den internationale radiolitteratur er bud på metoder til analyse af radiomediet sparsomme. Det skyldes formentlig, at radiomediet er svært at analysere, fordi det er et medie, der ikke er visualiseret i form af billeder eller understøttet af printet tekst. Denne artikel har til formål at beskrive en ny kvantitativ metode til analyse af radio, der tager særligt hensyn til radiomediets modalitet – lyd struktureret som et lineært forløb i tid. Metoden understøtter dermed både radiomediet som et medie i tid og som et blindt medie. Metoden er udviklet i forbindelse med en komparativ analyse af kulturprogrammer på P1 og Radio24syv lavet for Danmarks Radio. Artiklen peger på, at metoden er velegnet til analyse af ikke kun radio, men også andre medieplatforme samt forskellige journalistiske stofområder.

  13. Analysing User Lifetime in Voluntary Online Collaboration

    DEFF Research Database (Denmark)

    McHugh, Ronan; Larsen, Birger

    2010-01-01

    This paper analyses persuasion in online collaboration projects. It introduces a set of heuristics that can be applied to such projects and combines these with a quantitative analysis of user activity over time. Two example sites are studies, Open Street Map and The Pirate Bay. Results show that ...

  14. Analyses of hydraulic performance of velocity caps

    DEFF Research Database (Denmark)

    Christensen, Erik Damgaard; Degn Eskesen, Mark Chr.; Buhrkall, Jeppe

    2014-01-01

    The hydraulic performance of a velocity cap has been investigated. Velocity caps are often used in connection with offshore intakes. CFD (computational fluid dynamics) examined the flow through the cap openings and further down into the intake pipes. This was combined with dimension analyses...

  15. Quantitative analyses of shrinkage characteristics of neem ...

    African Journals Online (AJOL)

    Quantitative analyses of shrinkage characteristics of neem (Azadirachta indica A. Juss.) wood were carried out. Forty five wood specimens were prepared from the three ecological zones of north eastern Nigeria, viz: sahel savanna, sudan savanna and guinea savanna for the research. The results indicated that the wood ...

  16. UMTS signal measurements with digital spectrum analysers

    International Nuclear Information System (INIS)

    Licitra, G.; Palazzuoli, D.; Ricci, A. S.; Silvi, A. M.

    2004-01-01

    The launch of the Universal Mobile Telecommunications System (UNITS), the most recent mobile telecommunications standard has imposed the requirement of updating measurement instrumentation and methodologies. In order to define the most reliable measurement procedure, which is aimed at assessing the exposure to electromagnetic fields, modern spectrum analysers' features for correct signal characterisation has been reviewed. (authors)

  17. Hybrid Logical Analyses of the Ambient Calculus

    DEFF Research Database (Denmark)

    Bolander, Thomas; Hansen, Rene Rydhof

    2010-01-01

    In this paper, hybrid logic is used to formulate three control flow analyses for Mobile Ambients, a process calculus designed for modelling mobility. We show that hybrid logic is very well-suited to express the semantic structure of the ambient calculus and how features of hybrid logic can...

  18. Micromechanical photothermal analyser of microfluidic samples

    DEFF Research Database (Denmark)

    2014-01-01

    The present invention relates to a micromechanical photothermal analyser of microfluidic samples comprising an oblong micro-channel extending longitudinally from a support element, the micro-channel is made from at least two materials with different thermal expansion coefficients, wherein...

  19. Systematic review and meta-analyses

    DEFF Research Database (Denmark)

    Dreier, Julie Werenberg; Andersen, Anne-Marie Nybo; Berg-Beckhoff, Gabriele

    2014-01-01

    1990 were excluded. RESULTS: The available literature supported an increased risk of adverse offspring health in association with fever during pregnancy. The strongest evidence was available for neural tube defects, congenital heart defects, and oral clefts, in which meta-analyses suggested between a 1...

  20. Secundaire analyses organisatiebeleid psychosociale arbeidsbelasting (PSA)

    NARCIS (Netherlands)

    Kraan, K.O.; Houtman, I.L.D.

    2016-01-01

    Hoe het organisatiebeleid rond psychosociale arbeidsbelasting (PSA) eruit ziet anno 2014 en welke samenhang er is met ander beleid en uitkomstmaten, zijn de centrale vragen in dit onderzoek. De resultaten van deze verdiepende analyses kunnen ten goede komen aan de lopende campagne ‘Check je

  1. Exergoeconomic and environmental analyses of CO

    NARCIS (Netherlands)

    Mosaffa, A. H.; Garousi Farshi, L; Infante Ferreira, C.A.; Rosen, M. A.

    2016-01-01

    Exergoeconomic and environmental analyses are presented for two CO2/NH3 cascade refrigeration systems equipped with (1) two flash tanks and (2) a flash tank along with a flash intercooler with indirect subcooler. A comparative study is performed for the proposed systems, and

  2. Meta-analyses on viral hepatitis

    DEFF Research Database (Denmark)

    Gluud, Lise L; Gluud, Christian

    2009-01-01

    This article summarizes the meta-analyses of interventions for viral hepatitis A, B, and C. Some of the interventions assessed are described in small trials with unclear bias control. Other interventions are supported by large, high-quality trials. Although attempts have been made to adjust...

  3. Multivariate differential analyses of adolescents' experiences of ...

    African Journals Online (AJOL)

    Aggression is reasoned to be dependent on aspects such as self-concept, moral reasoning, communication, frustration tolerance and family relationships. To analyse the data from questionnaires of 101 families (95 adolescents, 95 mothers and 91 fathers) Cronbach Alpha, various consecutive first and second order factor ...

  4. Chromosomal evolution and phylogenetic analyses in Tayassu ...

    Indian Academy of Sciences (India)

    Chromosome preparation and karyotype description. The material analysed consists of chromosome preparations of the tayassuid species T. pecari (three individuals) and. P. tajacu (four individuals) and were made from short-term lymphocyte cultures of whole blood samples using standard protocols (Chaves et al. 2002).

  5. Indexing molecules with chemical graph identifiers.

    Science.gov (United States)

    Gregori-Puigjané, Elisabet; Garriga-Sust, Rut; Mestres, Jordi

    2011-09-01

    Fast and robust algorithms for indexing molecules have been historically considered strategic tools for the management and storage of large chemical libraries. This work introduces a modified and further extended version of the molecular equivalence number naming adaptation of the Morgan algorithm (J Chem Inf Comput Sci 2001, 41, 181-185) for the generation of a chemical graph identifier (CGI). This new version corrects for the collisions recognized in the original adaptation and includes the ability to deal with graph canonicalization, ensembles (salts), and isomerism (tautomerism, regioisomerism, optical isomerism, and geometrical isomerism) in a flexible manner. Validation of the current CGI implementation was performed on the open NCI database and the drug-like subset of the ZINC database containing 260,071 and 5,348,089 structures, respectively. The results were compared with those obtained with some of the most widely used indexing codes, such as the CACTVS hash code and the new InChIKey. The analyses emphasize the fact that compound management activities, like duplicate analysis of chemical libraries, are sensitive to the exact definition of compound uniqueness and thus still depend, to a minor extent, on the type and flexibility of the molecular index being used. Copyright © 2011 Wiley Periodicals, Inc.

  6. Identifying a new particle with jet substructures

    International Nuclear Information System (INIS)

    Han, Chengcheng; Kim, Doojin; Kim, Minho; Postech, Pohang

    2017-01-01

    Here, we investigate a potential of determining properties of a new heavy resonance of mass O(1)TeV which decays to collimated jets via heavy Standard Model intermediary states, exploiting jet substructure techniques. Employing the Z gauge boson as a concrete example for the intermediary state, we utilize a "merged jet" defined by a large jet size to capture the two quarks from its decay. The use of the merged jet bene ts the identification of a Z-induced jet as a single, reconstructed object without any combinatorial ambiguity. We also find that jet substructure procedures may enhance features in some kinematic observables formed with subjet four-momenta extracted from a merged jet. This observation motivates us to feed subjet momenta into the matrix elements associated with plausible hypotheses on the nature of the heavy resonance, which are further processed to construct a matrix element method (MEM)-based observable. For both moderately and highly boosted Z bosons, we demonstrate that the MEM in combination with jet substructure techniques can be a very powerful tool for identifying its physical properties. Finally, we discuss effects from choosing different jet sizes for merged jets and jet-grooming parameters upon the MEM analyses.

  7. Identifying hearing loss by means of iridology.

    Science.gov (United States)

    Stearn, Natalie; Swanepoel, De Wet

    2006-11-13

    Isolated reports of hearing loss presenting as markings on the iris exist, but to date the effectiveness of iridology to identify hearing loss has not been investigated. This study therefore aimed to determine the efficacy of iridological analysis in the identification of moderate to profound sensorineural hearing loss in adolescents. A controlled trial was conducted with an iridologist, blind to the actual hearing status of participants, analyzing the irises of participants with and without hearing loss. Fifty hearing impaired and fifty normal hearing subjects, between the ages of 15 and 19 years, controlled for gender, participated in the study. An experienced iridologist analyzed the randomised set of participants' irises. A 70% correct identification of hearing status was obtained by iridological analyses with a false negative rate of 41% compared to a 19% false positive rate. The respective sensitivity and specificity rates therefore came to 59% and 81%. Iridological analysis of hearing status indicated a statistically significant relationship to actual hearing status (P iridology were not comparable to those of traditional audiological screening procedures.

  8. Identifying User Profiles from Statistical Grouping Methods

    Directory of Open Access Journals (Sweden)

    Francisco Kelsen de Oliveira

    2018-02-01

    Full Text Available This research aimed to group users into subgroups according to their levels of knowledge about technology. Statistical hierarchical and non-hierarchical clustering methods were studied, compared and used in the creations of the subgroups from the similarities of the skill levels with these users’ technology. The research sample consisted of teachers who answered online questionnaires about their skills with the use of software and hardware with educational bias. The statistical methods of grouping were performed and showed the possibilities of groupings of the users. The analyses of these groups allowed to identify the common characteristics among the individuals of each subgroup. Therefore, it was possible to define two subgroups of users, one with skill in technology and another with skill with technology, so that the partial results of the research showed two main algorithms for grouping with 92% similarity in the formation of groups of users with skill with technology and the other with little skill, confirming the accuracy of the techniques of discrimination against individuals.

  9. Grey literature in meta-analyses.

    Science.gov (United States)

    Conn, Vicki S; Valentine, Jeffrey C; Cooper, Harris M; Rantz, Marilyn J

    2003-01-01

    In meta-analysis, researchers combine the results of individual studies to arrive at cumulative conclusions. Meta-analysts sometimes include "grey literature" in their evidential base, which includes unpublished studies and studies published outside widely available journals. Because grey literature is a source of data that might not employ peer review, critics have questioned the validity of its data and the results of meta-analyses that include it. To examine evidence regarding whether grey literature should be included in meta-analyses and strategies to manage grey literature in quantitative synthesis. This article reviews evidence on whether the results of studies published in peer-reviewed journals are representative of results from broader samplings of research on a topic as a rationale for inclusion of grey literature. Strategies to enhance access to grey literature are addressed. The most consistent and robust difference between published and grey literature is that published research is more likely to contain results that are statistically significant. Effect size estimates of published research are about one-third larger than those of unpublished studies. Unfunded and small sample studies are less likely to be published. Yet, importantly, methodological rigor does not differ between published and grey literature. Meta-analyses that exclude grey literature likely (a) over-represent studies with statistically significant findings, (b) inflate effect size estimates, and (c) provide less precise effect size estimates than meta-analyses including grey literature. Meta-analyses should include grey literature to fully reflect the existing evidential base and should assess the impact of methodological variations through moderator analysis.

  10. Masonry structures built with fictile tubules: Experimental and numerical analyses

    Science.gov (United States)

    Tiberti, Simone; Scuro, Carmelo; Codispoti, Rosamaria; Olivito, Renato S.; Milani, Gabriele

    2017-11-01

    Masonry structures with fictile tubules were a distinctive building technique of the Mediterranean area. This technique dates back to Roman and early Christian times, used to build vaulted constructions and domes with various geometrical forms by virtue of their modular structure. In the present work, experimental tests were carried out to identify the mechanical properties of hollow clay fictile tubules and a possible reinforcing technique for existing buildings employing such elements. The experimental results were then validated by devising and analyzing numerical models with the FE software Abaqus, also aimed at investigating the structural behavior of an arch via linear and nonlinear static analyses.

  11. Gamma spectrometric analyses of environmental samples at PINSTECH

    International Nuclear Information System (INIS)

    Faruq, M.U.; Parveen, N.; Ahmed, B.; Aziz, A.

    1979-01-01

    Gamma spectrometric analyses of air and other environmental samples from PINSTECH were carried out. Air particulate samples were analyzed by a Ge(Li) detector on a computer-based multichannel analyzer. Other environmental samples were analyzed by a Na(T1) scintillation detector spectrometer and a multichannel analyzer with manual analysis. Concentration of radionuclides in the media was determined and the sources of their production were identified. Age of the fall out was estimated from the ratios of the fission products. (authors)

  12. Thermal analyses. Information on the expected baking process; Thermische analyses. Informatie over een te verwachten bakgedrag

    Energy Technology Data Exchange (ETDEWEB)

    Van Wijck, H. [Stichting Technisch Centrum voor de Keramische Industrie TCKI, Velp (Netherlands)

    2009-09-01

    The design process and the drying process for architectural ceramics and pottery partly determine the characteristics of the final product, but the largest changes occur during the baking process. An overview is provided of the different thermal analyses and how the information from these analyses can predict the process in practice. (mk) [Dutch] Het vormgevingsproces en het droogproces voor bouwkeramische producten en aardewerk bepalen voor een deel de eigenschappen van de eindproducten, maar de grootste veranderingen treden op bij het bakproces. Een overzicht wordt gegeven van de verschillende thermische analyses en hoe de informatie uit deze analyses het in de praktijk te verwachten gedrag kan voorspellen.

  13. Pigment and terracotta analyses of Hellenistic figurines in Crete

    International Nuclear Information System (INIS)

    Maravelaki-Kalaitzaki, P.; Kallithrakas-Kontos, N.

    2003-01-01

    The results of the analyses performed on blue, black, brown, orange, white and purple pigments decorating Hellenistic figurines, excavated in a rock-cut tomb in the archaeological zone of Chania, Crete, Greece, are presented. Different spectroscopic techniques, such as Fourier transform infrared spectroscopy and energy dispersive X-ray fluorescence identified the compounds present in the chromatic layers. X-ray diffraction analysis gave complementary information and further support to the spectral assignments. Optical microscopy revealed the nature and sequence of the pigmented layer on the terracotta. Several precious pigments, such as Egyptian blue for the bluish areas, Tyrian purple for the purple ones, and the rare huntite for the white-pigmented areas were identified among the studied pigmented areas. The pigment analysis provides information on the technical aspects related to terracotta manufacture and preservation, and promotes historical indications on cultural and commercial changes among the Mediterranean civilisations

  14. Analyses and characterization of double shell tank

    Energy Technology Data Exchange (ETDEWEB)

    1994-10-04

    Evaporator candidate feed from tank 241-AP-108 (108-AP) was sampled under prescribed protocol. Physical, inorganic, and radiochemical analyses were performed on tank 108-AP. Characterization of evaporator feed tank waste is needed primarily for an evaluation of its suitability to be safely processed through the evaporator. Such analyses should provide sufficient information regarding the waste composition to confidently determine whether constituent concentrations are within not only safe operating limits, but should also be relevant to functional limits for operation of the evaporator. Characterization of tank constituent concentrations should provide data which enable a prediction of where the types and amounts of environmentally hazardous waste are likely to occur in the evaporator product streams.

  15. DCH analyses using the CONTAIN code

    International Nuclear Information System (INIS)

    Hong, Sung Wan; Kim, Hee Dong

    1996-08-01

    This report describes CONTAIN analyses performed during participation in the project of 'DCH issue resolution for ice condenser plants' which is sponsored by NRC at SNL. Even though the calculations were performed for the Ice Condenser plant, CONTAIN code has been used for analyses of many phenomena in the PWR containment and the DCH module can be commonly applied to any plant types. The present ice condenser issue resolution effort intended to provide guidance as to what might be needed to resolve DCH for ice condenser plants. It includes both a screening analysis and a scoping study if the screening analysis cannot provide an complete resolution. The followings are the results concerning DCH loads in descending order. 1. Availability of ignition sources prior to vessel breach 2. availability and effectiveness of ice in the ice condenser 3. Loads modeling uncertainties related to co-ejected RPV water 4. Other loads modeling uncertainties 10 tabs., 3 figs., 14 refs. (Author)

  16. DCH analyses using the CONTAIN code

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Sung Wan; Kim, Hee Dong [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1996-08-01

    This report describes CONTAIN analyses performed during participation in the project of `DCH issue resolution for ice condenser plants` which is sponsored by NRC at SNL. Even though the calculations were performed for the Ice Condenser plant, CONTAIN code has been used for analyses of many phenomena in the PWR containment and the DCH module can be commonly applied to any plant types. The present ice condenser issue resolution effort intended to provide guidance as to what might be needed to resolve DCH for ice condenser plants. It includes both a screening analysis and a scoping study if the screening analysis cannot provide an complete resolution. The followings are the results concerning DCH loads in descending order. 1. Availability of ignition sources prior to vessel breach 2. availability and effectiveness of ice in the ice condenser 3. Loads modeling uncertainties related to co-ejected RPV water 4. Other loads modeling uncertainties 10 tabs., 3 figs., 14 refs. (Author).

  17. Analyses and characterization of double shell tank

    International Nuclear Information System (INIS)

    1994-01-01

    Evaporator candidate feed from tank 241-AP-108 (108-AP) was sampled under prescribed protocol. Physical, inorganic, and radiochemical analyses were performed on tank 108-AP. Characterization of evaporator feed tank waste is needed primarily for an evaluation of its suitability to be safely processed through the evaporator. Such analyses should provide sufficient information regarding the waste composition to confidently determine whether constituent concentrations are within not only safe operating limits, but should also be relevant to functional limits for operation of the evaporator. Characterization of tank constituent concentrations should provide data which enable a prediction of where the types and amounts of environmentally hazardous waste are likely to occur in the evaporator product streams

  18. Soil analyses by ICP-MS (Review)

    International Nuclear Information System (INIS)

    Yamasaki, Shin-ichi

    2000-01-01

    Soil analyses by inductively coupled plasma mass spectrometry (ICP-MS) are reviewed. The first half of the paper is devoted to the development of techniques applicable to soil analyses, where diverse analytical parameters are carefully evaluated. However, the choice of soil samples is somewhat arbitrary, and only a limited number of samples (mostly reference materials) are examined. In the second half, efforts are mostly concentrated on the introduction of reports, where a large number of samples and/or very precious samples have been analyzed. Although the analytical techniques used in these reports are not necessarily novel, valuable information concerning such topics as background levels of elements in soils, chemical forms of elements in soils and behavior of elements in soil ecosystems and the environment can be obtained. The major topics discussed are total elemental analysis, analysis of radionuclides with long half-lives, speciation, leaching techniques, and isotope ratio measurements. (author)

  19. Sorption analyses in materials science: selected oxides

    International Nuclear Information System (INIS)

    Fuller, E.L. Jr.; Condon, J.B.; Eager, M.H.; Jones, L.L.

    1981-01-01

    Physical adsorption studies have been shown to be extremely valuable in studying the chemistry and structure of dispersed materials. Many processes rely on the access to the large amount of surface made available by the high degree of dispersion. Conversely, there are many applications where consolidation of the dispersed solids is required. Several systems (silica gel, alumina catalysts, mineralogic alumino-silicates, and yttrium oxide plasters) have been studied to show the type and amount of chemical and structural information that can be obtained. Some review of current theories is given and additional concepts are developed based on statistical and thermodynamic arguments. The results are applied to sorption data to show that detailed sorption analyses are extremely useful and can provide valuable information that is difficult to obtain by any other means. Considerable emphasis has been placed on data analyses and interpretation of a nonclassical nature to show the potential of such studies that is often not recognized nor utilized

  20. Standardized analyses of nuclear shipping containers

    International Nuclear Information System (INIS)

    Parks, C.V.; Hermann, O.W.; Petrie, L.M.; Hoffman, T.J.; Tang, J.S.; Landers, N.F.; Turner, W.D.

    1983-01-01

    This paper describes improved capabilities for analyses of nuclear fuel shipping containers within SCALE -- a modular code system for Standardized Computer Analyses for Licensing Evaluation. Criticality analysis improvements include the new KENO V, a code which contains an enhanced geometry package and a new control module which uses KENO V and allows a criticality search on optimum pitch (maximum k-effective) to be performed. The SAS2 sequence is a new shielding analysis module which couples fuel burnup, source term generation, and radial cask shielding. The SAS5 shielding sequence allows a multidimensional Monte Carlo analysis of a shipping cask with code generated biasing of the particle histories. The thermal analysis sequence (HTAS1) provides an easy-to-use tool for evaluating a shipping cask response to the accident capability of the SCALE system to provide the cask designer or evaluator with a computational system that provides the automated procedures and easy-to-understand input that leads to standarization

  1. Quantitative Analyse und Visualisierung der Herzfunktionen

    Science.gov (United States)

    Sauer, Anne; Schwarz, Tobias; Engel, Nicole; Seitel, Mathias; Kenngott, Hannes; Mohrhardt, Carsten; Loßnitzer, Dirk; Giannitsis, Evangelos; Katus, Hugo A.; Meinzer, Hans-Peter

    Die computergestützte bildbasierte Analyse der Herzfunktionen ist mittlerweile Standard in der Kardiologie. Die verfügbaren Produkte erfordern meist ein hohes Maß an Benutzerinteraktion und somit einen erhöhten Zeitaufwand. In dieser Arbeit wird ein Ansatz vorgestellt, der dem Kardiologen eine größtenteils automatische Analyse der Herzfunktionen mittels MRT-Bilddaten ermöglicht und damit Zeitersparnis schafft. Hierbei werden alle relevanten herzphysiologsichen Parameter berechnet und mithilfe von Diagrammen und Graphen visualisiert. Diese Berechnungen werden evaluiert, indem die ermittelten Werte mit manuell vermessenen verglichen werden. Der hierbei berechnete mittlere Fehler liegt mit 2,85 mm für die Wanddicke und 1,61 mm für die Wanddickenzunahme immer noch im Bereich einer Pixelgrösse der verwendeten Bilder.

  2. Exergetic and thermoeconomic analyses of power plants

    International Nuclear Information System (INIS)

    Kwak, H.-Y.; Kim, D.-J.; Jeon, J.-S.

    2003-01-01

    Exergetic and thermoeconomic analyses were performed for a 500-MW combined cycle plant. In these analyses, mass and energy conservation laws were applied to each component of the system. Quantitative balances of the exergy and exergetic cost for each component, and for the whole system was carefully considered. The exergoeconomic model, which represented the productive structure of the system considered, was used to visualize the cost formation process and the productive interaction between components. The computer program developed in this study can determine the production costs of power plants, such as gas- and steam-turbines plants and gas-turbine cogeneration plants. The program can be also be used to study plant characteristics, namely, thermodynamic performance and sensitivity to changes in process and/or component design variables

  3. Pratique de l'analyse fonctionelle

    CERN Document Server

    Tassinari, Robert

    1997-01-01

    Mettre au point un produit ou un service qui soit parfaitement adapté aux besoins et aux exigences du client est indispensable pour l'entreprise. Pour ne rien laisser au hasard, il s'agit de suivre une méthodologie rigoureuse : celle de l'analyse fonctionnelle. Cet ouvrage définit précisément cette méthode ainsi que ses champs d'application. Il décrit les méthodes les plus performantes en termes de conception de produit et de recherche de qualité et introduit la notion d'analyse fonctionnelle interne. Un ouvrage clé pour optimiser les processus de conception de produit dans son entreprise. -- Idées clés, par Business Digest

  4. Kinetic stability analyses in a bumpy cylinder

    International Nuclear Information System (INIS)

    Dominguez, R.R.; Berk, H.L.

    1981-01-01

    Recent interest in the ELMO Bumpy Torus (EBT) has prompted a number of stability analyses of both the hot electron rings and the toroidal plasma. Typically these works employ the local approximation, neglecting radial eigenmode structure and ballooning effects to perform the stability analysis. In the present work we develop a fully kinetic formalism for performing nonlocal stability analyses in a bumpy cylinder. We show that the Vlasov-Maxwell integral equations (with one ignorable coordinate) are self-adjoint and hence amenable to analysis using numerical techniques developed for self-adjoint systems of equations. The representation we obtain for the kernel of the Vlasov-Maxwell equations is a differential operator of arbitrarily high order. This form leads to a manifestly self-adjoint system of differential equations for long wavelength modes

  5. Sectorial Group for Incident Analyses (GSAI)

    International Nuclear Information System (INIS)

    Galles, Q.; Gamo, J. M.; Jorda, M.; Sanchez-Garrido, P.; Lopez, F.; Asensio, L.; Reig, J.

    2013-01-01

    In 2008, the UNESA Nuclear Energy Committee (CEN) proposed the creation of a working group formed by experts from all Spanish NPPs with the purpose of jointly analyze relevant incidents occurred in each one of the plants. This initiative was a response to a historical situation in which the exchange of information on incidents between the Spanish NPP's was below the desired level. In june 2009, UNESA's Guide CEN-29 established the performance criteria for the so called Sectorial Group for Incident Analyses (GSAI), whose activity would be coordinated by the UNESA's Group for Incident Analyses (GSAI), whose activity would be coordinated by the UNESA's Group of Operating Experience, under the Operations Commission (COP). (Author)

  6. Analyses of cavitation instabilities in ductile metals

    DEFF Research Database (Denmark)

    Tvergaard, Viggo

    2007-01-01

    Cavitation instabilities have been predicted for a single void in a ductile metal stressed under high triaxiality conditions. In experiments for a ceramic reinforced by metal particles a single dominant void has been observed on the fracture surface of some of the metal particles bridging a crack......, and also tests for a thin ductile metal layer bonding two ceramic blocks have indicated rapid void growth. Analyses for these material configurations are discussed here. When the void radius is very small, a nonlocal plasticity model is needed to account for observed size-effects, and recent analyses......, while the surrounding voids are represented by a porous ductile material model in terms of a field quantity that specifies the variation of the void volume fraction in the surrounding metal....

  7. Analysing organic transistors based on interface approximation

    International Nuclear Information System (INIS)

    Akiyama, Yuto; Mori, Takehiko

    2014-01-01

    Temperature-dependent characteristics of organic transistors are analysed thoroughly using interface approximation. In contrast to amorphous silicon transistors, it is characteristic of organic transistors that the accumulation layer is concentrated on the first monolayer, and it is appropriate to consider interface charge rather than band bending. On the basis of this model, observed characteristics of hexamethylenetetrathiafulvalene (HMTTF) and dibenzotetrathiafulvalene (DBTTF) transistors with various surface treatments are analysed, and the trap distribution is extracted. In turn, starting from a simple exponential distribution, we can reproduce the temperature-dependent transistor characteristics as well as the gate voltage dependence of the activation energy, so we can investigate various aspects of organic transistors self-consistently under the interface approximation. Small deviation from such an ideal transistor operation is discussed assuming the presence of an energetically discrete trap level, which leads to a hump in the transfer characteristics. The contact resistance is estimated by measuring the transfer characteristics up to the linear region

  8. New environmental metabarcodes for analysing soil DNA

    DEFF Research Database (Denmark)

    Epp, Laura S.; Boessenkool, Sanne; Bellemain, Eva P.

    2012-01-01

    was systematically evaluated by (i) in silico PCRs using all standard sequences in the EMBL public database as templates, (ii) in vitro PCRs of DNA extracts from surface soil samples from a site in Varanger, northern Norway and (iii) in vitro PCRs of DNA extracts from permanently frozen sediment samples of late......Metabarcoding approaches use total and typically degraded DNA from environmental samples to analyse biotic assemblages and can potentially be carried out for any kinds of organisms in an ecosystem. These analyses rely on specific markers, here called metabarcodes, which should be optimized...... for taxonomic resolution, minimal bias in amplification of the target organism group and short sequence length. Using bioinformatic tools, we developed metabarcodes for several groups of organisms: fungi, bryophytes, enchytraeids, beetles and birds. The ability of these metabarcodes to amplify the target groups...

  9. The Quality of Cost-Utility Analyses in Orthopedic Trauma.

    Science.gov (United States)

    Nwachukwu, Benedict U; Schairer, William W; O'Dea, Evan; McCormick, Frank; Lane, Joseph M

    2015-08-01

    As health care in the United States transitions toward a value-based model, there is increasing interest in applying cost-effectiveness analysis within orthopedic surgery. Orthopedic trauma care has traditionally underemphasized economic analysis. The goals of this review were to identify US-based cost-utility analysis in orthopedic trauma, to assess the quality of the available evidence, and to identify cost-effective strategies within orthopedic trauma. Based on a review of 971 abstracts, 8 US-based cost-utility analyses evaluating operative strategies in orthopedic trauma were identified. Study findings were recorded, and the Quality of Health Economic Studies (QHES) instrument was used to grade the overall quality. Of the 8 studies included in this review, 4 studies evaluated hip and femur fractures, 3 studies analyzed upper extremity fractures, and 1 study assessed open tibial fracture management. Cost-effective interventions identified in this review include total hip arthroplasty (over hemiarthroplasty) for femoral neck fractures in the active elderly, open reduction and internal fixation (over nonoperative management) for distal radius and scaphoid fractures, limb salvage (over amputation) for complex open tibial fractures, and systems-based interventions to prevent delay in hip fracture surgery. The mean QHES score of the studies was 79.25 (range, 67-89). Overall, there is a paucity of cost-utility analyses in orthopedic trauma; however, the available evidence suggests that certain operative interventions can be cost-effective. The quality of these studies, however, is fair, based on QHES grading. More attention should be paid to evaluating the cost-effectiveness of operative intervention in orthopedic trauma. Copyright 2015, SLACK Incorporated.

  10. Visuelle Analyse von E-mail-Verkehr

    OpenAIRE

    Mansmann, Florian

    2003-01-01

    Diese Arbeit beschreibt Methoden zur visuellen geographischen Analyse von E-mail Verkehr.Aus dem Header einer E-mail können Hostadressen und IP-Adressen herausgefiltert werden. Anhand einer Datenbank werden diesen Host- und IP-Adressen geographische Koordinaten zugeordnet.Durch eine Visualisierung werden in übersichtlicher Art und Weise mehrere tausend E-mail Routen dargestellt. Zusätzlich dazu wurden interktive Manipulationsmöglichkeiten vorgestellt, welche eine visuelle Exploration der Date...

  11. BWR core melt progression phenomena: Experimental analyses

    International Nuclear Information System (INIS)

    Ott, L.J.

    1992-01-01

    In the BWR Core Melt in Progression Phenomena Program, experimental results concerning severe fuel damage and core melt progression in BWR core geometry are used to evaluate existing models of the governing phenomena. These include control blade eutectic liquefaction and the subsequent relocation and attack on the channel box structure; oxidation heating and hydrogen generation; Zircaloy melting and relocation; and the continuing oxidation of zirconium with metallic blockage formation. Integral data have been obtained from the BWR DF-4 experiment in the ACRR and from BWR tests in the German CORA exreactor fuel-damage test facility. Additional integral data will be obtained from new CORA BWR test, the full-length FLHT-6 BWR test in the NRU test reactor, and the new program of exreactor experiments at Sandia National Laboratories (SNL) on metallic melt relocation and blockage formation. an essential part of this activity is interpretation and use of the results of the BWR tests. The Oak Ridge National Laboratory (ORNL) has developed experiment-specific models for analysis of the BWR experiments; to date, these models have permitted far more precise analyses of the conditions in these experiments than has previously been available. These analyses have provided a basis for more accurate interpretation of the phenomena that the experiments are intended to investigate. The results of posttest analyses of BWR experiments are discussed and significant findings from these analyses are explained. The ORNL control blade/canister models with materials interaction, relocation and blockage models are currently being implemented in SCDAP/RELAP5 as an optional structural component

  12. En Billig GPS Data Analyse Platform

    DEFF Research Database (Denmark)

    Andersen, Ove; Christiansen, Nick; Larsen, Niels T.

    2011-01-01

    Denne artikel præsenterer en komplet software platform til analyse af GPS data. Platformen er bygget udelukkende vha. open-source komponenter. De enkelte komponenter i platformen beskrives i detaljer. Fordele og ulemper ved at bruge open-source diskuteres herunder hvilke IT politiske tiltage, der...... organisationer med et digitalt vejkort og GPS data begynde at lave trafikanalyser på disse data. Det er et krav, at der er passende IT kompetencer tilstede i organisationen....

  13. Neuronal network analyses: premises, promises and uncertainties

    OpenAIRE

    Parker, David

    2010-01-01

    Neuronal networks assemble the cellular components needed for sensory, motor and cognitive functions. Any rational intervention in the nervous system will thus require an understanding of network function. Obtaining this understanding is widely considered to be one of the major tasks facing neuroscience today. Network analyses have been performed for some years in relatively simple systems. In addition to the direct insights these systems have provided, they also illustrate some of the diffic...

  14. Modelling and analysing oriented fibrous structures

    International Nuclear Information System (INIS)

    Rantala, M; Lassas, M; Siltanen, S; Sampo, J; Takalo, J; Timonen, J

    2014-01-01

    A mathematical model for fibrous structures using a direction dependent scaling law is presented. The orientation of fibrous nets (e.g. paper) is analysed with a method based on the curvelet transform. The curvelet-based orientation analysis has been tested successfully on real data from paper samples: the major directions of fibrefibre orientation can apparently be recovered. Similar results are achieved in tests on data simulated by the new model, allowing a comparison with ground truth

  15. Kinematic gait analyses in healthy Golden Retrievers

    OpenAIRE

    Silva, Gabriela C.A.; Cardoso, Mariana Trés; Gaiad, Thais P.; Brolio, Marina P.; Oliveira, Vanessa C.; Assis Neto, Antonio; Martins, Daniele S.; Ambrósio, Carlos E.

    2014-01-01

    Kinematic analysis relates to the relative movement between rigid bodies and finds application in gait analysis and other body movements, interpretation of their data when there is change, determines the choice of treatment to be instituted. The objective of this study was to standardize the march of Dog Golden Retriever Healthy to assist in the diagnosis and treatment of musculoskeletal disorders. We used a kinematic analysis system to analyse the gait of seven dogs Golden Retriever, female,...

  16. Evaluation of periodic safety status analyses

    International Nuclear Information System (INIS)

    Faber, C.; Staub, G.

    1997-01-01

    In order to carry out the evaluation of safety status analyses by the safety assessor within the periodical safety reviews of nuclear power plants safety goal oriented requirements have been formulated together with complementary evaluation criteria. Their application in an inter-disciplinary coopertion covering the subject areas involved facilitates a complete safety goal oriented assessment of the plant status. The procedure is outlined briefly by an example for the safety goal 'reactivity control' for BWRs. (orig.) [de

  17. Application of RUNTA code in flood analyses

    International Nuclear Information System (INIS)

    Perez Martin, F.; Benitez Fonzalez, F.

    1994-01-01

    Flood probability analyses carried out to date indicate the need to evaluate a large number of flood scenarios. This necessity is due to a variety of reasons, the most important of which include: - Large number of potential flood sources - Wide variety of characteristics of flood sources - Large possibility of flood-affected areas becoming inter linked, depending on the location of the potential flood sources - Diversity of flood flows from one flood source, depending on the size of the rupture and mode of operation - Isolation times applicable - Uncertainties in respect of the structural resistance of doors, penetration seals and floors - Applicable degrees of obstruction of floor drainage system Consequently, a tool which carries out the large number of calculations usually required in flood analyses, with speed and flexibility, is considered necessary. The RUNTA Code enables the range of possible scenarios to be calculated numerically, in accordance with all those parameters which, as a result of previous flood analyses, it is necessary to take into account in order to cover all the possible floods associated with each flood area

  18. An analyser for power plant operations

    International Nuclear Information System (INIS)

    Rogers, A.E.; Wulff, W.

    1990-01-01

    Safe and reliable operation of power plants is essential. Power plant operators need a forecast of what the plant will do when its current state is disturbed. The in-line plant analyser provides precisely this information at relatively low cost. The plant analyser scheme uses a mathematical model of the dynamic behaviour of the plant to establish a numerical simulation. Over a period of time, the simulation is calibrated with measurements from the particular plant in which it is used. The analyser then provides a reference against which to evaluate the plant's current behaviour. It can be used to alert the operator to any atypical excursions or combinations of readings that indicate malfunction or off-normal conditions that, as the Three Mile Island event suggests, are not easily recognised by operators. In a look-ahead mode, it can forecast the behaviour resulting from an intended change in settings or operating conditions. Then, when such changes are made, the plant's behaviour can be tracked against the forecast in order to assure that the plant is behaving as expected. It can be used to investigate malfunctions that have occurred and test possible adjustments in operating procedures. Finally, it can be used to consider how far from the limits of performance the elements of the plant are operating. Then by adjusting settings, the required power can be generated with as little stress as possible on the equipment. (6 figures) (Author)

  19. Proteomic analyses of host and pathogen responses during bovine mastitis.

    Science.gov (United States)

    Boehmer, Jamie L

    2011-12-01

    The pursuit of biomarkers for use as clinical screening tools, measures for early detection, disease monitoring, and as a means for assessing therapeutic responses has steadily evolved in human and veterinary medicine over the past two decades. Concurrently, advances in mass spectrometry have markedly expanded proteomic capabilities for biomarker discovery. While initial mass spectrometric biomarker discovery endeavors focused primarily on the detection of modulated proteins in human tissues and fluids, recent efforts have shifted to include proteomic analyses of biological samples from food animal species. Mastitis continues to garner attention in veterinary research due mainly to affiliated financial losses and food safety concerns over antimicrobial use, but also because there are only a limited number of efficacious mastitis treatment options. Accordingly, comparative proteomic analyses of bovine milk have emerged in recent years. Efforts to prevent agricultural-related food-borne illness have likewise fueled an interest in the proteomic evaluation of several prominent strains of bacteria, including common mastitis pathogens. The interest in establishing biomarkers of the host and pathogen responses during bovine mastitis stems largely from the need to better characterize mechanisms of the disease, to identify reliable biomarkers for use as measures of early detection and drug efficacy, and to uncover potentially novel targets for the development of alternative therapeutics. The following review focuses primarily on comparative proteomic analyses conducted on healthy versus mastitic bovine milk. However, a comparison of the host defense proteome of human and bovine milk and the proteomic analysis of common veterinary pathogens are likewise introduced.

  20. Analysing the Improper Pronunciation of Diphthongs by Iraqi EFL learners

    Directory of Open Access Journals (Sweden)

    Mukhalad Malik Almutalabi

    2018-04-01

    Full Text Available The current study aims at analysing the improper pronunciation of Iraqi EFL learners concerning the pronunciation of diphthongs in words of various syllables. It describes and identifies thoroughly the mispronunciations of such important sounds in English language. The study attempts at analysing such mispronunciations by clarifying and assigning the phonetic deviations of Iraqi EFL learners when they pronounce diphthongs. So the main objective of the study is to analyse the errors committed by Iraqi learners in the pronunciation of diphthongs grouping each error into its specific category. To verify the objective of the paper, 25 Iraqi EFL learners from the department of English at Cihan University/ Slemani are chosen to be the main participants of the study. The test which was conducted in the laboratory of the Department of English contained 10 words comprising various diphthongs. The results clearly revealed that mispronouncing English diphthongs by Iraqi EFL were mostly observed by replacing the required diphthong with another improper one and they also tended to use simple vowels instead of the correct required diphthongs.

  1. ALBEDO PATTERN RECOGNITION AND TIME-SERIES ANALYSES IN MALAYSIA

    Directory of Open Access Journals (Sweden)

    S. A. Salleh

    2012-07-01

    Full Text Available Pattern recognition and time-series analyses will enable one to evaluate and generate predictions of specific phenomena. The albedo pattern and time-series analyses are very much useful especially in relation to climate condition monitoring. This study is conducted to seek for Malaysia albedo pattern changes. The pattern recognition and changes will be useful for variety of environmental and climate monitoring researches such as carbon budgeting and aerosol mapping. The 10 years (2000–2009 MODIS satellite images were used for the analyses and interpretation. These images were being processed using ERDAS Imagine remote sensing software, ArcGIS 9.3, the 6S code for atmospherical calibration and several MODIS tools (MRT, HDF2GIS, Albedo tools. There are several methods for time-series analyses were explored, this paper demonstrates trends and seasonal time-series analyses using converted HDF format MODIS MCD43A3 albedo land product. The results revealed significance changes of albedo percentages over the past 10 years and the pattern with regards to Malaysia's nebulosity index (NI and aerosol optical depth (AOD. There is noticeable trend can be identified with regards to its maximum and minimum value of the albedo. The rise and fall of the line graph show a similar trend with regards to its daily observation. The different can be identified in term of the value or percentage of rises and falls of albedo. Thus, it can be concludes that the temporal behavior of land surface albedo in Malaysia have a uniform behaviours and effects with regards to the local monsoons. However, although the average albedo shows linear trend with nebulosity index, the pattern changes of albedo with respects to the nebulosity index indicates that there are external factors that implicates the albedo values, as the sky conditions and its diffusion plotted does not have uniform trend over the years, especially when the trend of 5 years interval is examined, 2000 shows high

  2. Visualizing Confidence in Cluster-Based Ensemble Weather Forecast Analyses.

    Science.gov (United States)

    Kumpf, Alexander; Tost, Bianca; Baumgart, Marlene; Riemer, Michael; Westermann, Rudiger; Rautenhaus, Marc

    2018-01-01

    In meteorology, cluster analysis is frequently used to determine representative trends in ensemble weather predictions in a selected spatio-temporal region, e.g., to reduce a set of ensemble members to simplify and improve their analysis. Identified clusters (i.e., groups of similar members), however, can be very sensitive to small changes of the selected region, so that clustering results can be misleading and bias subsequent analyses. In this article, we - a team of visualization scientists and meteorologists-deliver visual analytics solutions to analyze the sensitivity of clustering results with respect to changes of a selected region. We propose an interactive visual interface that enables simultaneous visualization of a) the variation in composition of identified clusters (i.e., their robustness), b) the variability in cluster membership for individual ensemble members, and c) the uncertainty in the spatial locations of identified trends. We demonstrate that our solution shows meteorologists how representative a clustering result is, and with respect to which changes in the selected region it becomes unstable. Furthermore, our solution helps to identify those ensemble members which stably belong to a given cluster and can thus be considered similar. In a real-world application case we show how our approach is used to analyze the clustering behavior of different regions in a forecast of "Tropical Cyclone Karl", guiding the user towards the cluster robustness information required for subsequent ensemble analysis.

  3. A novel stroke locus identified in a northern Sweden pedigree

    DEFF Research Database (Denmark)

    Janunger, T.; Nilsson-Ardnor, S.; Wiklund, P.-G.

    2009-01-01

    OBJECTIVES: The population of northern Sweden is characterized by reduced genetic diversity and a high incidence of stroke. We sought to reduce genetic variation further, using genealogic analysis in a set of nuclear families affected by stroke, and we subsequently performed a genome-wide scan...... to identify novel stroke susceptibility loci. METHODS: Through genealogy, 7 nuclear families with a common ancestor, connected over 8 generations, were identified. A genome-wide scan using 449 microsatellite markers was performed with subsequent haplotype analyses. RESULTS: A maximum allele-sharing lod score...... of 4.81 on chromosome 9q31-q33 was detected. Haplotype analysis identified a common 2.2-megabase interval in the chromosomal region in 4 of the nuclear families, where an overrepresentation of intracerebral hemorrhage was observed. CONCLUSIONS: We have identified a novel susceptibility locus for stroke...

  4. Conserved regulators of nucleolar size revealed by global phenotypic analyses.

    Science.gov (United States)

    Neumüller, Ralph A; Gross, Thomas; Samsonova, Anastasia A; Vinayagam, Arunachalam; Buckner, Michael; Founk, Karen; Hu, Yanhui; Sharifpoor, Sara; Rosebrock, Adam P; Andrews, Brenda; Winston, Fred; Perrimon, Norbert

    2013-08-20

    Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I-mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I-mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry-based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules.

  5. Conserved Regulators of Nucleolar Size Revealed by Global Phenotypic Analyses

    Science.gov (United States)

    Neumüller, Ralph A.; Gross, Thomas; Samsonova, Anastasia A.; Vinayagam, Arunachalam; Buckner, Michael; Founk, Karen; Hu, Yanhui; Sharifpoor, Sara; Rosebrock, Adam P.; Andrews, Brenda; Winston, Fred; Perrimon, Norbert

    2014-01-01

    Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I–mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I–mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry–based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules. PMID:23962978

  6. Fungi identify the geographic origin of dust samples.

    Directory of Open Access Journals (Sweden)

    Neal S Grantham

    Full Text Available There is a long history of archaeologists and forensic scientists using pollen found in a dust sample to identify its geographic origin or history. Such palynological approaches have important limitations as they require time-consuming identification of pollen grains, a priori knowledge of plant species distributions, and a sufficient diversity of pollen types to permit spatial or temporal identification. We demonstrate an alternative approach based on DNA sequencing analyses of the fungal diversity found in dust samples. Using nearly 1,000 dust samples collected from across the continental U.S., our analyses identify up to 40,000 fungal taxa from these samples, many of which exhibit a high degree of geographic endemism. We develop a statistical learning algorithm via discriminant analysis that exploits this geographic endemicity in the fungal diversity to correctly identify samples to within a few hundred kilometers of their geographic origin with high probability. In addition, our statistical approach provides a measure of certainty for each prediction, in contrast with current palynology methods that are almost always based on expert opinion and devoid of statistical inference. Fungal taxa found in dust samples can therefore be used to identify the origin of that dust and, more importantly, we can quantify our degree of certainty that a sample originated in a particular place. This work opens up a new approach to forensic biology that could be used by scientists to identify the origin of dust or soil samples found on objects, clothing, or archaeological artifacts.

  7. Plasma proteomics to identify biomarkers - Application to cardiovascular diseases

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Overgaard, Martin; Melholt Rasmussen, Lars

    2015-01-01

    There is an unmet need for new cardiovascular biomarkers. Despite this only few biomarkers for the diagnosis or screening of cardiovascular diseases have been implemented in the clinic. Thousands of proteins can be analysed in plasma by mass spectrometry-based proteomics technologies. Therefore......, this technology may therefore identify new biomarkers that previously have not been associated with cardiovascular diseases. In this review, we summarize the key challenges and considerations, including strategies, recent discoveries and clinical applications in cardiovascular proteomics that may lead...

  8. Identifying tectonic parameters that influence tsunamigenesis

    Science.gov (United States)

    van Zelst, Iris; Brizzi, Silvia; van Dinther, Ylona; Heuret, Arnauld; Funiciello, Francesca

    2017-04-01

    The role of tectonics in tsunami generation is at present poorly understood. However, the fact that some regions produce more tsunamis than others indicates that tectonics could influence tsunamigenesis. Here, we complement a global earthquake database that contains geometrical, mechanical, and seismicity parameters of subduction zones with tsunami data. We statistically analyse the database to identify the tectonic parameters that affect tsunamigenesis. The Pearson's product-moment correlation coefficients reveal high positive correlations of 0.65 between, amongst others, the maximum water height of tsunamis and the seismic coupling in a subduction zone. However, these correlations are mainly caused by outliers. The Spearman's rank correlation coefficient results in more robust correlations of 0.60 between the number of tsunamis in a subduction zone and subduction velocity (positive correlation) and the sediment thickness at the trench (negative correlation). Interestingly, there is a positive correlation between the latter and tsunami magnitude. In an effort towards multivariate statistics, a binary decision tree analysis is conducted with one variable. However, this shows that the amount of data is too scarce. To complement this limi