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Sample records for large-scale genetic studies

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. Discovering Genetic Interactions in Large-Scale Association Studies by Stage-wise Likelihood Ratio Tests.

    PubMed

    Frånberg, Mattias; Gertow, Karl; Hamsten, Anders; Lagergren, Jens; Sennblad, Bengt

    2015-09-01

    Despite the success of genome-wide association studies in medical genetics, the underlying genetics of many complex diseases remains enigmatic. One plausible reason for this could be the failure to account for the presence of genetic interactions in current analyses. Exhaustive investigations of interactions are typically infeasible because the vast number of possible interactions impose hard statistical and computational challenges. There is, therefore, a need for computationally efficient methods that build on models appropriately capturing interaction. We introduce a new methodology where we augment the interaction hypothesis with a set of simpler hypotheses that are tested, in order of their complexity, against a saturated alternative hypothesis representing interaction. This sequential testing provides an efficient way to reduce the number of non-interacting variant pairs before the final interaction test. We devise two different methods, one that relies on a priori estimated numbers of marginally associated variants to correct for multiple tests, and a second that does this adaptively. We show that our methodology in general has an improved statistical power in comparison to seven other methods, and, using the idea of closed testing, that it controls the family-wise error rate. We apply our methodology to genetic data from the PROCARDIS coronary artery disease case/control cohort and discover three distinct interactions. While analyses on simulated data suggest that the statistical power may suffice for an exhaustive search of all variant pairs in ideal cases, we explore strategies for a priori selecting subsets of variant pairs to test. Our new methodology facilitates identification of new disease-relevant interactions from existing and future genome-wide association data, which may involve genes with previously unknown association to the disease. Moreover, it enables construction of interaction networks that provide a systems biology view of complex

  4. Discovering Genetic Interactions in Large-Scale Association Studies by Stage-wise Likelihood Ratio Tests

    PubMed Central

    Frånberg, Mattias; Gertow, Karl; Hamsten, Anders; Lagergren, Jens; Sennblad, Bengt

    2015-01-01

    Despite the success of genome-wide association studies in medical genetics, the underlying genetics of many complex diseases remains enigmatic. One plausible reason for this could be the failure to account for the presence of genetic interactions in current analyses. Exhaustive investigations of interactions are typically infeasible because the vast number of possible interactions impose hard statistical and computational challenges. There is, therefore, a need for computationally efficient methods that build on models appropriately capturing interaction. We introduce a new methodology where we augment the interaction hypothesis with a set of simpler hypotheses that are tested, in order of their complexity, against a saturated alternative hypothesis representing interaction. This sequential testing provides an efficient way to reduce the number of non-interacting variant pairs before the final interaction test. We devise two different methods, one that relies on a priori estimated numbers of marginally associated variants to correct for multiple tests, and a second that does this adaptively. We show that our methodology in general has an improved statistical power in comparison to seven other methods, and, using the idea of closed testing, that it controls the family-wise error rate. We apply our methodology to genetic data from the PROCARDIS coronary artery disease case/control cohort and discover three distinct interactions. While analyses on simulated data suggest that the statistical power may suffice for an exhaustive search of all variant pairs in ideal cases, we explore strategies for a priori selecting subsets of variant pairs to test. Our new methodology facilitates identification of new disease-relevant interactions from existing and future genome-wide association data, which may involve genes with previously unknown association to the disease. Moreover, it enables construction of interaction networks that provide a systems biology view of complex

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

    PubMed Central

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

    2015-01-01

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

  6. Discovering epistasis in large scale genetic association studies by exploiting graphics cards

    PubMed Central

    Chen, Gary K.; Guo, Yunfei

    2013-01-01

    Despite the enormous investments made in collecting DNA samples and generating germline variation data across thousands of individuals in modern genome-wide association studies (GWAS), progress has been frustratingly slow in explaining much of the heritability in common disease. Today's paradigm of testing independent hypotheses on each single nucleotide polymorphism (SNP) marker is unlikely to adequately reflect the complex biological processes in disease risk. Alternatively, modeling risk as an ensemble of SNPs that act in concert in a pathway, and/or interact non-additively on log risk for example, may be a more sensible way to approach gene mapping in modern studies. Implementing such analyzes genome-wide can quickly become intractable due to the fact that even modest size SNP panels on modern genotype arrays (500k markers) pose a combinatorial nightmare, require tens of billions of models to be tested for evidence of interaction. In this article, we provide an in-depth analysis of programs that have been developed to explicitly overcome these enormous computational barriers through the use of processors on graphics cards known as Graphics Processing Units (GPU). We include tutorials on GPU technology, which will convey why they are growing in appeal with today's numerical scientists. One obvious advantage is the impressive density of microprocessor cores that are available on only a single GPU. Whereas high end servers feature up to 24 Intel or AMD CPU cores, the latest GPU offerings from nVidia feature over 2600 cores. Each compute node may be outfitted with up to 4 GPU devices. Success on GPUs varies across problems. However, epistasis screens fare well due to the high degree of parallelism exposed in these problems. Papers that we review routinely report GPU speedups of over two orders of magnitude (>100x) over standard CPU implementations. PMID:24348518

  7. Discovering epistasis in large scale genetic association studies by exploiting graphics cards.

    PubMed

    Chen, Gary K; Guo, Yunfei

    2013-01-01

    Despite the enormous investments made in collecting DNA samples and generating germline variation data across thousands of individuals in modern genome-wide association studies (GWAS), progress has been frustratingly slow in explaining much of the heritability in common disease. Today's paradigm of testing independent hypotheses on each single nucleotide polymorphism (SNP) marker is unlikely to adequately reflect the complex biological processes in disease risk. Alternatively, modeling risk as an ensemble of SNPs that act in concert in a pathway, and/or interact non-additively on log risk for example, may be a more sensible way to approach gene mapping in modern studies. Implementing such analyzes genome-wide can quickly become intractable due to the fact that even modest size SNP panels on modern genotype arrays (500k markers) pose a combinatorial nightmare, require tens of billions of models to be tested for evidence of interaction. In this article, we provide an in-depth analysis of programs that have been developed to explicitly overcome these enormous computational barriers through the use of processors on graphics cards known as Graphics Processing Units (GPU). We include tutorials on GPU technology, which will convey why they are growing in appeal with today's numerical scientists. One obvious advantage is the impressive density of microprocessor cores that are available on only a single GPU. Whereas high end servers feature up to 24 Intel or AMD CPU cores, the latest GPU offerings from nVidia feature over 2600 cores. Each compute node may be outfitted with up to 4 GPU devices. Success on GPUs varies across problems. However, epistasis screens fare well due to the high degree of parallelism exposed in these problems. Papers that we review routinely report GPU speedups of over two orders of magnitude (>100x) over standard CPU implementations. PMID:24348518

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

    PubMed Central

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

    2016-01-01

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

  9. A Large-Scale Rheumatoid Arthritis Genetic Study Identifies Association at Chromosome 9q33.2

    PubMed Central

    Chang, Monica; Rowland, Charles M.; Garcia, Veronica E.; Schrodi, Steven J.; Catanese, Joseph J.; van der Helm-van Mil, Annette H. M.; Ardlie, Kristin G.; Amos, Christopher I.; Criswell, Lindsey A.; Kastner, Daniel L.; Gregersen, Peter K.; Kurreeman, Fina A. S.; Toes, Rene E. M.; Huizinga, Tom W. J.; Seldin, Michael F.; Begovich, Ann B.

    2008-01-01

    Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease affecting both joints and extra-articular tissues. Although some genetic risk factors for RA are well-established, most notably HLA-DRB1 and PTPN22, these markers do not fully account for the observed heritability. To identify additional susceptibility loci, we carried out a multi-tiered, case-control association study, genotyping 25,966 putative functional SNPs in 475 white North American RA patients and 475 matched controls. Significant markers were genotyped in two additional, independent, white case-control sample sets (661 cases/1322 controls from North America and 596 cases/705 controls from The Netherlands) identifying a SNP, rs1953126, on chromosome 9q33.2 that was significantly associated with RA (ORcommon = 1.28, trend Pcomb = 1.45E-06). Through a comprehensive fine-scale-mapping SNP-selection procedure, 137 additional SNPs in a 668 kb region from MEGF9 to STOM on 9q33.2 were chosen for follow-up genotyping in a staged-approach. Significant single marker results (Pcomb<0.01) spanned a large 525 kb region from FBXW2 to GSN. However, a variety of analyses identified SNPs in a 70 kb region extending from the third intron of PHF19 across TRAF1 into the TRAF1-C5 intergenic region, but excluding the C5 coding region, as the most interesting (trend Pcomb: 1.45E-06 → 5.41E-09). The observed association patterns for these SNPs had heightened statistical significance and a higher degree of consistency across sample sets. In addition, the allele frequencies for these SNPs displayed reduced variability between control groups when compared to other SNPs. Lastly, in combination with the other two known genetic risk factors, HLA-DRB1 and PTPN22, the variants reported here generate more than a 45-fold RA-risk differential. PMID:18648537

  10. Genetic Association of CD247 (CD3ζ) with SLE in a Large-Scale Multiethnic Study

    PubMed Central

    Martins, Madalena; Williams, Adrienne H.; Comeau, Mary; Marion, Miranda; Ziegler, Julie T.; Freedman, Barry I.; Merrill, Joan T.; Glenn, Stuart B.; Kelly, Jennifer A.; Sivils, Kathy M.; James, Judith A.; Guthridge, Joel M.; Alarcón-Riquelme, Marta E.; Bae, Sang-Cheol; Kim, Jae-Hoon; Kim, Dam; Anaya, Juan-Manuel; Boackle, Susan A.; Criswell, Lindsey A.; Kimberly, Robert P.; Alarcón, Graciela S.; Brown, Elizabeth E.; Vilá, Luis M.; Petri, Michelle A.; Ramsey-Goldman, Rosalind; Niewold, Timothy B.; Tsao, Betty P.; Gilkeson, Gary S.; Kamen, Diane L.; Jacob, Chaim O.; Stevens, Anne M.; Gaffney, Patrick M.; Harley, John B.; Langefeld, Carl D.; Fesel, Constantin

    2015-01-01

    A classic T-cell phenotype in Systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters TCR signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multi-ethnic population. We typed 44 contiguous CD247 SNPs in 8 922 SLE patients and 8 077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99×10−4genetic model adjusted for population proportions, showed 5 SNPs with significant P-values (1.40×10−3study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T cell-mediated mechanism. PMID:25569266

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

    PubMed Central

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

    2016-01-01

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

  12. Large-Scale PV Integration Study

    SciTech Connect

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

    2011-07-29

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

  13. Robust regression for large-scale neuroimaging studies.

    PubMed

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

    2015-05-01

    Multi-subject datasets used in neuroimaging group studies have a complex structure, as they exhibit non-stationary statistical properties across regions and display various artifacts. While studies with small sample sizes can rarely be shown to deviate from standard hypotheses (such as the normality of the residuals) due to the poor sensitivity of normality tests with low degrees of freedom, large-scale studies (e.g. >100 subjects) exhibit more obvious deviations from these hypotheses and call for more refined models for statistical inference. Here, we demonstrate the benefits of robust regression as a tool for analyzing large neuroimaging cohorts. First, we use an analytic test based on robust parameter estimates; based on simulations, this procedure is shown to provide an accurate statistical control without resorting to permutations. Second, we show that robust regression yields more detections than standard algorithms using as an example an imaging genetics study with 392 subjects. Third, we show that robust regression can avoid false positives in a large-scale analysis of brain-behavior relationships with over 1500 subjects. Finally we embed robust regression in the Randomized Parcellation Based Inference (RPBI) method and demonstrate that this combination further improves the sensitivity of tests carried out across the whole brain. Altogether, our results show that robust procedures provide important advantages in large-scale neuroimaging group studies. PMID:25731989

  14. Software for large scale tracking studies

    SciTech Connect

    Niederer, J.

    1984-05-01

    Over the past few years, Brookhaven accelerator physicists have been adapting particle tracking programs in planning local storage rings, and lately for SSC reference designs. In addition, the Laboratory is actively considering upgrades to its AGS capabilities aimed at higher proton intensity, polarized proton beams, and heavy ion acceleration. Further activity concerns heavy ion transfer, a proposed booster, and most recently design studies for a heavy ion collider to join to this complex. Circumstances have thus encouraged a search for common features among design and modeling programs and their data, and the corresponding controls efforts among present and tentative machines. Using a version of PATRICIA with nonlinear forces as a vehicle, we have experimented with formal ways to describe accelerator lattice problems to computers as well as to speed up the calculations for large storage ring models. Code treated by straightforward reorganization has served for SSC explorations. The representation work has led to a relational data base centered program, LILA, which has desirable properties for dealing with the many thousands of rapidly changing variables in tracking and other model programs. 13 references.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Winkler, Thomas W; Justice, Anne E; Graff, Mariaelisa; Barata, Llilda; Feitosa, Mary F; Chu, Su; Czajkowski, Jacek; Esko, Tõnu; Fall, Tove; Kilpeläinen, Tuomas O; Lu, Yingchang; Mägi, Reedik; Mihailov, Evelin; Pers, Tune H; Rüeger, Sina; Teumer, Alexander; Ehret, Georg B; Ferreira, Teresa; Heard-Costa, Nancy L; Karjalainen, Juha; Lagou, Vasiliki; Mahajan, Anubha; Neinast, Michael D; Prokopenko, Inga; Simino, Jeannette; Teslovich, Tanya M; Jansen, Rick; Westra, Harm-Jan; White, Charles C; Absher, Devin; Ahluwalia, Tarunveer S; Ahmad, Shafqat; Albrecht, Eva; Alves, Alexessander Couto; Bragg-Gresham, Jennifer L; de Craen, Anton J M; Bis, Joshua C; Bonnefond, Amélie; Boucher, Gabrielle; Cadby, Gemma; Cheng, Yu-Ching; Chiang, Charleston W K; Delgado, Graciela; Demirkan, Ayse; Dueker, Nicole; Eklund, Niina; Eiriksdottir, Gudny; Eriksson, Joel; Feenstra, Bjarke; Fischer, Krista; Frau, Francesca; Galesloot, Tessel E; Geller, Frank; Goel, Anuj; Gorski, Mathias; Grammer, Tanja B; Gustafsson, Stefan; Haitjema, Saskia; Hottenga, Jouke-Jan; Huffman, Jennifer E; Jackson, Anne U; Jacobs, Kevin B; Johansson, Åsa; Kaakinen, Marika; Kleber, Marcus E; Lahti, Jari; Mateo Leach, Irene; Lehne, Benjamin; Liu, Youfang; Lo, Ken Sin; Lorentzon, Mattias; Luan, Jian'an; Madden, Pamela A F; Mangino, Massimo; McKnight, Barbara; Medina-Gomez, Carolina; Monda, Keri L; Montasser, May E; Müller, Gabriele; Müller-Nurasyid, Martina; Nolte, Ilja M; Panoutsopoulou, Kalliope; Pascoe, Laura; Paternoster, Lavinia; Rayner, Nigel W; Renström, Frida; Rizzi, Federica; Rose, Lynda M; Ryan, Kathy A; Salo, Perttu; Sanna, Serena; Scharnagl, Hubert; Shi, Jianxin; Smith, Albert Vernon; Southam, Lorraine; Stančáková, Alena; Steinthorsdottir, Valgerdur; Strawbridge, Rona J; Sung, Yun Ju; Tachmazidou, Ioanna; Tanaka, Toshiko; Thorleifsson, Gudmar; Trompet, Stella; Pervjakova, Natalia; Tyrer, Jonathan P; Vandenput, Liesbeth; van der Laan, Sander W; van der Velde, Nathalie; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V; Verweij, Niek; Vlachopoulou, Efthymia; Waite, Lindsay L; Wang, Sophie R; Wang, Zhaoming; Wild, Sarah H; Willenborg, Christina; Wilson, James F; Wong, Andrew; Yang, Jian; Yengo, Loïc; Yerges-Armstrong, Laura M; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Andersson, Ehm A; Bakker, Stephan J L; Baldassarre, Damiano; Banasik, Karina; Barcella, Matteo; Barlassina, Cristina; Bellis, Claire; Benaglio, Paola; Blangero, John; Blüher, Matthias; Bonnet, Fabrice; Bonnycastle, Lori L; Boyd, Heather A; Bruinenberg, Marcel; Buchman, Aron S; Campbell, Harry; Chen, Yii-Der Ida; Chines, Peter S; Claudi-Boehm, Simone; Cole, John; Collins, Francis S; de Geus, Eco J C; de Groot, Lisette C P G M; Dimitriou, Maria; Duan, Jubao; Enroth, Stefan; Eury, Elodie; Farmaki, Aliki-Eleni; Forouhi, Nita G; Friedrich, Nele; Gejman, Pablo V; Gigante, Bruna; Glorioso, Nicola; Go, Alan S; Gottesman, Omri; Gräßler, Jürgen; Grallert, Harald; Grarup, Niels; Gu, Yu-Mei; Broer, Linda; Ham, Annelies C; Hansen, Torben; Harris, Tamara B; Hartman, Catharina A; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew T; Heath, Andrew C; Henders, Anjali K; Hernandez, Dena; Hillege, Hans; Holmen, Oddgeir; Hovingh, Kees G; Hui, Jennie; Husemoen, Lise L; Hutri-Kähönen, Nina; Hysi, Pirro G; Illig, Thomas; De Jager, Philip L; Jalilzadeh, Shapour; Jørgensen, Torben; Jukema, J Wouter; Juonala, Markus; Kanoni, Stavroula; Karaleftheri, Maria; Khaw, Kay Tee; Kinnunen, Leena; Kittner, Steven J; Koenig, Wolfgang; Kolcic, Ivana; Kovacs, Peter; Krarup, Nikolaj T; Kratzer, Wolfgang; Krüger, Janine; Kuh, Diana; Kumari, Meena; Kyriakou, Theodosios; Langenberg, Claudia; Lannfelt, Lars; Lanzani, Chiara; Lotay, Vaneet; Launer, Lenore J; Leander, Karin; Lindström, Jaana; Linneberg, Allan; Liu, Yan-Ping; Lobbens, Stéphane; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Magnusson, Patrik K; McArdle, Wendy L; Menni, Cristina; Merger, Sigrun; Milani, Lili; Montgomery, Grant W; Morris, Andrew P; Narisu, Narisu; Nelis, Mari; Ong, Ken K; Palotie, Aarno; Pérusse, Louis; Pichler, Irene; Pilia, Maria G; Pouta, Anneli; Rheinberger, Myriam; Ribel-Madsen, Rasmus; Richards, Marcus; Rice, Kenneth M; Rice, Treva K; Rivolta, Carlo; Salomaa, Veikko; Sanders, Alan R; Sarzynski, Mark A; Scholtens, Salome; Scott, Robert A; Scott, William R; Sebert, Sylvain; Sengupta, Sebanti; Sennblad, Bengt; Seufferlein, Thomas; Silveira, Angela; Slagboom, P Eline; Smit, Jan H; Sparsø, Thomas H; Stirrups, Kathleen; Stolk, Ronald P; Stringham, Heather M; Swertz, Morris A; Swift, Amy J; Syvänen, Ann-Christine; Tan, Sian-Tsung

    2015-10-01

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

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

    PubMed Central

    Feitosa, Mary F.; Chu, Su; Czajkowski, Jacek; Esko, Tõnu; Fall, Tove; Kilpeläinen, Tuomas O.; Lu, Yingchang; Mägi, Reedik; Mihailov, Evelin; Pers, Tune H.; Rüeger, Sina; Teumer, Alexander; Ehret, Georg B.; Ferreira, Teresa; Heard-Costa, Nancy L.; Karjalainen, Juha; Lagou, Vasiliki; Mahajan, Anubha; Neinast, Michael D.; Prokopenko, Inga; Simino, Jeannette; Teslovich, Tanya M.; Jansen, Rick; Westra, Harm-Jan; White, Charles C.; Absher, Devin; Ahluwalia, Tarunveer S.; Ahmad, Shafqat; Albrecht, Eva; Alves, Alexessander Couto; Bragg-Gresham, Jennifer L.; de Craen, Anton J. M.; Bis, Joshua C.; Bonnefond, Amélie; Boucher, Gabrielle; Cadby, Gemma; Cheng, Yu-Ching; Chiang, Charleston W. K.; Delgado, Graciela; Demirkan, Ayse; Dueker, Nicole; Eklund, Niina; Eiriksdottir, Gudny; Eriksson, Joel; Feenstra, Bjarke; Fischer, Krista; Frau, Francesca; Galesloot, Tessel E.; Geller, Frank; Goel, Anuj; Gorski, Mathias; Grammer, Tanja B.; Gustafsson, Stefan; Haitjema, Saskia; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Jackson, Anne U.; Jacobs, Kevin B.; Johansson, Åsa; Kaakinen, Marika; Kleber, Marcus E.; Lahti, Jari; Leach, Irene Mateo; Lehne, Benjamin; Liu, Youfang; Lo, Ken Sin; Lorentzon, Mattias; Luan, Jian'an; Madden, Pamela A. F.; Mangino, Massimo; McKnight, Barbara; Medina-Gomez, Carolina; Monda, Keri L.; Montasser, May E.; Müller, Gabriele; Müller-Nurasyid, Martina; Nolte, Ilja M.; Panoutsopoulou, Kalliope; Pascoe, Laura; Paternoster, Lavinia; Rayner, Nigel W.; Renström, Frida; Rizzi, Federica; Rose, Lynda M.; Ryan, Kathy A.; Salo, Perttu; Sanna, Serena; Scharnagl, Hubert; Shi, Jianxin; Smith, Albert Vernon; Southam, Lorraine; Stančáková, Alena; Steinthorsdottir, Valgerdur; Strawbridge, Rona J.; Sung, Yun Ju; Tachmazidou, Ioanna; Tanaka, Toshiko; Thorleifsson, Gudmar; Trompet, Stella; Pervjakova, Natalia; Tyrer, Jonathan P.; Vandenput, Liesbeth; van der Laan, Sander W; van der Velde, Nathalie; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Vlachopoulou, Efthymia; Waite, Lindsay L.; Wang, Sophie R.; Wang, Zhaoming; Wild, Sarah H.; Willenborg, Christina; Wilson, James F.; Wong, Andrew; Yang, Jian; Yengo, Loïc; Yerges-Armstrong, Laura M.; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Andersson, Ehm A.; Bakker, Stephan J. L.; Baldassarre, Damiano; Banasik, Karina; Barcella, Matteo; Barlassina, Cristina; Bellis, Claire; Benaglio, Paola; Blangero, John; Blüher, Matthias; Bonnet, Fabrice; Bonnycastle, Lori L.; Boyd, Heather A.; Bruinenberg, Marcel; Buchman, Aron S; Campbell, Harry; Chen, Yii-Der Ida; Chines, Peter S.; Claudi-Boehm, Simone; Cole, John; Collins, Francis S.; de Geus, Eco J. C.; de Groot, Lisette C. P. G. M.; Dimitriou, Maria; Duan, Jubao; Enroth, Stefan; Eury, Elodie; Farmaki, Aliki-Eleni; Forouhi, Nita G.; Friedrich, Nele; Gejman, Pablo V.; Gigante, Bruna; Glorioso, Nicola; Go, Alan S.; Gottesman, Omri; Gräßler, Jürgen; Grallert, Harald; Grarup, Niels; Gu, Yu-Mei; Broer, Linda; Ham, Annelies C.; Hansen, Torben; Harris, Tamara B.; Hartman, Catharina A.; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew T.; Heath, Andrew C.; Henders, Anjali K.; Hernandez, Dena; Hillege, Hans; Holmen, Oddgeir; Hovingh, Kees G; Hui, Jennie; Husemoen, Lise L.; Hutri-Kähönen, Nina; Hysi, Pirro G.; Illig, Thomas; De Jager, Philip L.; Jalilzadeh, Shapour; Jørgensen, Torben; Jukema, J. Wouter; Juonala, Markus; Kanoni, Stavroula; Karaleftheri, Maria; Khaw, Kay Tee; Kinnunen, Leena; Kittner, Steven J.; Koenig, Wolfgang; Kolcic, Ivana; Kovacs, Peter; Krarup, Nikolaj T.; Kratzer, Wolfgang; Krüger, Janine; Kuh, Diana; Kumari, Meena; Kyriakou, Theodosios; Langenberg, Claudia; Lannfelt, Lars; Lanzani, Chiara; Lotay, Vaneet; Launer, Lenore J.; Leander, Karin; Lindström, Jaana; Linneberg, Allan; Liu, Yan-Ping; Lobbens, Stéphane; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Magnusson, Patrik K.; McArdle, Wendy L.; Menni, Cristina; Merger, Sigrun; Milani, Lili; Montgomery, Grant W.; Morris, Andrew P.; Narisu, Narisu; Nelis, Mari; Ong, Ken K.; Palotie, Aarno; Pérusse, Louis; Pichler, Irene; Pilia, Maria G.; Pouta, Anneli; Rheinberger, Myriam; Ribel-Madsen, Rasmus; Richards, Marcus; Rice, Kenneth M.; Rice, Treva K.; Rivolta, Carlo; Salomaa, Veikko; Sanders, Alan R.; Sarzynski, Mark A.; Scholtens, Salome; Scott, Robert A.; Scott, William R.; Sebert, Sylvain; Sengupta, Sebanti; Sennblad, Bengt; Seufferlein, Thomas; Silveira, Angela; Slagboom, P. Eline; Smit, Jan H.; Sparsø, Thomas H.

    2015-01-01

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

  19. Acoustic Studies of the Large Scale Ocean Circulation

    NASA Technical Reports Server (NTRS)

    Menemenlis, Dimitris

    1999-01-01

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

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

    PubMed

    Ley, A C; Hardy, O J

    2013-04-01

    AFLP markers are often used to study patterns of population genetic variation and gene flow because they offer a good coverage of the nuclear genome, but the reliability of AFLP scoring is critical. To assess interspecific gene flow in two African rainforest liana species (Haumania danckelmaniana, H. liebrechtsiana) where previous evidence of chloroplast captures questioned the importance of hybridization and species boundaries, we developed new AFLP markers and a novel approach to select reliable bands from their degree of reproducibility. The latter is based on the estimation of the broad-sense heritability of AFLP phenotypes, an improvement over classical scoring error rates, which showed that the polymorphism of most AFLP bands was affected by a substantial nongenetic component. Therefore, using a quantitative genetics framework, we also modified an existing estimator of pairwise kinship coefficient between individuals correcting for the limited heritability of markers. Bayesian clustering confirms the recognition of the two Haumania species. Nevertheless, the decay of the relatedness between individuals of distinct species with geographic distance demonstrates that hybridization affects the nuclear genome. In conclusion, although we showed that AFLP markers might be substantially affected by nongenetic factors, their analysis using the new methods developed considerably advanced our understanding of the pattern of gene flow in our model species. PMID:23398575

  1. Exploring the Performance of Multifactor Dimensionality Reduction in Large Scale SNP Studies and in the Presence of Genetic Heterogeneity among Epistatic Disease Models

    PubMed Central

    Edwards, Todd L.; Lewis, Kenneth; Velez, Digna R.; Dudek, Scott; Ritchie, Marylyn D.

    2009-01-01

    Background/Aims In genetic studies of complex disease a consideration for the investigator is detection of joint effects. The Multifactor Dimensionality Reduction (MDR) algorithm searches for these effects with an exhaustive approach. Previously unknown aspects of MDR performance were the power to detect interactive effects given large numbers of non-model loci or varying degrees of heterogeneity among multiple epistatic disease models. Methods To address the performance with many non-model loci, datasets of 500 cases and 500 controls with 100 to 10,000 SNPs were simulated for two-locus models, and one hundred 500-case/500-control datasets with 100 and 500 SNPs were simulated for three-locus models. Multiple levels of locus heterogeneity were simulated in several sample sizes. Results These results show MDR is robust to locus heterogeneity when the definition of power is not as conservative as in previous simulation studies where all model loci were required to be found by the method. The results also indicate that MDR performance is related more strongly to broad-sense heritability than sample size and is not greatly affected by non-model loci. Conclusions A study in which a population with high heritability estimates is sampled predisposes the MDR study to success more than a larger ascertainment in a population with smaller estimates. PMID:19077437

  2. FVGWAS: Fast voxelwise genome wide association analysis of large-scale imaging genetic data.

    PubMed

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

    2015-09-01

    More and more large-scale imaging genetic studies are being widely conducted to collect a rich set of imaging, genetic, and clinical data to detect putative genes for complexly inherited neuropsychiatric and neurodegenerative disorders. Several major big-data challenges arise from testing genome-wide (NC>12 million known variants) associations with signals at millions of locations (NV~10(6)) in the brain from thousands of subjects (n~10(3)). The aim of this paper is to develop a Fast Voxelwise Genome Wide Association analysiS (FVGWAS) framework to efficiently carry out whole-genome analyses of whole-brain data. FVGWAS consists of three components including a heteroscedastic linear model, a global sure independence screening (GSIS) procedure, and a detection procedure based on wild bootstrap methods. Specifically, for standard linear association, the computational complexity is O (nNVNC) for voxelwise genome wide association analysis (VGWAS) method compared with O ((NC+NV)n(2)) for FVGWAS. Simulation studies show that FVGWAS is an efficient method of searching sparse signals in an extremely large search space, while controlling for the family-wise error rate. Finally, we have successfully applied FVGWAS to a large-scale imaging genetic data analysis of ADNI data with 708 subjects, 193,275voxels in RAVENS maps, and 501,584 SNPs, and the total processing time was 203,645s for a single CPU. Our FVGWAS may be a valuable statistical toolbox for large-scale imaging genetic analysis as the field is rapidly advancing with ultra-high-resolution imaging and whole-genome sequencing. PMID:26025292

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

    SciTech Connect

    Bird, L.; Milligan, M.

    2012-06-01

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

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

    PubMed

    Thompson, Paul M; Stein, Jason L; Medland, Sarah E; Hibar, Derrek P; Vasquez, Alejandro Arias; Renteria, Miguel E; Toro, Roberto; Jahanshad, Neda; Schumann, Gunter; Franke, Barbara; Wright, Margaret J; Martin, Nicholas G; Agartz, Ingrid; Alda, Martin; Alhusaini, Saud; Almasy, Laura; Almeida, Jorge; Alpert, Kathryn; Andreasen, Nancy C; Andreassen, Ole A; Apostolova, Liana G; Appel, Katja; Armstrong, Nicola J; Aribisala, Benjamin; Bastin, Mark E; Bauer, Michael; Bearden, Carrie E; Bergmann, Orjan; Binder, Elisabeth B; Blangero, John; Bockholt, Henry J; Bøen, Erlend; Bois, Catherine; Boomsma, Dorret I; Booth, Tom; Bowman, Ian J; Bralten, Janita; Brouwer, Rachel M; Brunner, Han G; Brohawn, David G; Buckner, Randy L; Buitelaar, Jan; Bulayeva, Kazima; Bustillo, Juan R; Calhoun, Vince D; Cannon, Dara M; Cantor, Rita M; Carless, Melanie A; Caseras, Xavier; Cavalleri, Gianpiero L; Chakravarty, M Mallar; Chang, Kiki D; Ching, Christopher R K; Christoforou, Andrea; Cichon, Sven; Clark, Vincent P; Conrod, Patricia; Coppola, Giovanni; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Deary, Ian J; de Geus, Eco J C; den Braber, Anouk; Delvecchio, Giuseppe; Depondt, Chantal; de Haan, Lieuwe; de Zubicaray, Greig I; Dima, Danai; Dimitrova, Rali; Djurovic, Srdjan; Dong, Hongwei; Donohoe, Gary; Duggirala, Ravindranath; Dyer, Thomas D; Ehrlich, Stefan; Ekman, Carl Johan; Elvsåshagen, Torbjørn; Emsell, Louise; Erk, Susanne; Espeseth, Thomas; Fagerness, Jesen; Fears, Scott; Fedko, Iryna; Fernández, Guillén; Fisher, Simon E; Foroud, Tatiana; Fox, Peter T; Francks, Clyde; Frangou, Sophia; Frey, Eva Maria; Frodl, Thomas; Frouin, Vincent; Garavan, Hugh; Giddaluru, Sudheer; Glahn, David C; Godlewska, Beata; Goldstein, Rita Z; Gollub, Randy L; Grabe, Hans J; Grimm, Oliver; Gruber, Oliver; Guadalupe, Tulio; Gur, Raquel E; Gur, Ruben C; Göring, Harald H H; Hagenaars, Saskia; Hajek, Tomas; Hall, Geoffrey B; Hall, Jeremy; Hardy, John; Hartman, Catharina A; Hass, Johanna; Hatton, Sean N; Haukvik, Unn K; Hegenscheid, Katrin; Heinz, Andreas; Hickie, Ian B; Ho, Beng-Choon; Hoehn, David; Hoekstra, Pieter J; Hollinshead, Marisa; Holmes, Avram J; Homuth, Georg; Hoogman, Martine; Hong, L Elliot; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Hwang, Kristy S; Jack, Clifford R; Jenkinson, Mark; Johnston, Caroline; Jönsson, Erik G; Kahn, René S; Kasperaviciute, Dalia; Kelly, Sinead; Kim, Sungeun; Kochunov, Peter; Koenders, Laura; Krämer, Bernd; Kwok, John B J; Lagopoulos, Jim; Laje, Gonzalo; Landen, Mikael; Landman, Bennett A; Lauriello, John; Lawrie, Stephen M; Lee, Phil H; Le Hellard, Stephanie; Lemaître, Herve; Leonardo, Cassandra D; Li, Chiang-Shan; Liberg, Benny; Liewald, David C; Liu, Xinmin; Lopez, Lorna M; Loth, Eva; Lourdusamy, Anbarasu; Luciano, Michelle; Macciardi, Fabio; Machielsen, Marise W J; Macqueen, Glenda M; Malt, Ulrik F; Mandl, René; Manoach, Dara S; Martinot, Jean-Luc; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mattingsdal, Morten; Meyer-Lindenberg, Andreas; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Milaneschi, Yuri; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Moses, Eric K; Mueller, Bryon A; Muñoz Maniega, Susana; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Mwangi, Benson; Nauck, Matthias; Nho, Kwangsik; Nichols, Thomas E; Nilsson, Lars-Göran; Nugent, Allison C; Nyberg, Lars; Olvera, Rene L; Oosterlaan, Jaap; Ophoff, Roel A; Pandolfo, Massimo; Papalampropoulou-Tsiridou, Melina; Papmeyer, Martina; Paus, Tomas; Pausova, Zdenka; Pearlson, Godfrey D; Penninx, Brenda W; Peterson, Charles P; Pfennig, Andrea; Phillips, Mary; Pike, G Bruce; Poline, Jean-Baptiste; Potkin, Steven G; Pütz, Benno; Ramasamy, Adaikalavan; Rasmussen, Jerod; Rietschel, Marcella; Rijpkema, Mark; Risacher, Shannon L; Roffman, Joshua L; Roiz-Santiañez, Roberto; Romanczuk-Seiferth, Nina; Rose, Emma J; Royle, Natalie A; Rujescu, Dan; Ryten, Mina; Sachdev, Perminder S; Salami, Alireza; Satterthwaite, Theodore D; Savitz, Jonathan; Saykin, Andrew J; Scanlon, Cathy; Schmaal, Lianne; Schnack, Hugo G; Schork, Andrew J; Schulz, S Charles; Schür, Remmelt; Seidman, Larry; Shen, Li; Shoemaker, Jody M; Simmons, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soares, Jair C; Sponheim, Scott R; Sprooten, Emma; Starr, John M; Steen, Vidar M; Strakowski, Stephen; Strike, Lachlan; Sussmann, Jessika; Sämann, Philipp G; Teumer, Alexander; Toga, Arthur W; Tordesillas-Gutierrez, Diana; Trabzuni, Daniah; Trost, Sarah; Turner, Jessica; Van den Heuvel, Martijn

    2014-06-01

    The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. PMID:24399358

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

    PubMed Central

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

    2014-01-01

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

  6. Large-scale replication and heterogeneity in Parkinson disease genetic loci

    PubMed Central

    Ioannidis, John P.A.; Aasly, Jan O.; Annesi, Grazia; Brice, Alexis; Van Broeckhoven, Christine; Bertram, Lars; Bozi, Maria; Crosiers, David; Clarke, Carl; Facheris, Maurizio; Farrer, Matthew; Garraux, Gaetan; Gispert, Suzana; Auburger, Georg; Vilariño-Güell, Carles; Hadjigeorgiou, Georgios M.; Hicks, Andrew A.; Hattori, Nobutaka; Jeon, Beom; Lesage, Suzanne; Lill, Christina M.; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E.; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D.; Morrison, Karen E.; Opala, Grzegorz; Pramstaller, Peter P.; Pichler, Irene; Park, Sung Sup; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A.; Stefanis, Leonidas; Stockton, Joanne D.; Satake, Wataru; Silburn, Peter A.; Theuns, Jessie; Tan, Eng-King; Toda, Tatsushi; Tomiyama, Hiroyuki; Uitti, Ryan J.; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius; Krüger, Rejko

    2012-01-01

    Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Methods: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. Results: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14–1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Conclusion: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology® 2012;79:659–667 PMID:22786590

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

    PubMed

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

    2010-09-01

    Large-scale exploitation of wild animals and plants through fishing, hunting and logging often depends on augmentation through releases of translocated or captively raised individuals. Such releases are performed worldwide in vast numbers. Augmentation can be demographically and economically beneficial but can also cause four types of adverse genetic change to wild populations: (1) loss of genetic variation, (2) loss of adaptations, (3) change of population composition, and (4) change of population structure. While adverse genetic impacts are recognized and documented in fisheries, little effort is devoted to actually monitoring them. In forestry and wildlife management, genetic risks associated with releases are largely neglected. We outline key features of programs to effectively monitor consequences of such releases on natural populations. PMID:20688414

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

    NASA Astrophysics Data System (ADS)

    Kashid, Satishkumar S.; Maity, Rajib

    2012-08-01

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

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

    NASA Technical Reports Server (NTRS)

    Dittmer, P. H.

    1977-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  11. Evaluation of Penalized and Nonpenalized Methods for Disease Prediction with Large-Scale Genetic Data

    PubMed Central

    Won, Sungho; Choi, Hosik; Park, Suyeon; Lee, Juyoung; Park, Changyi; Kwon, Sunghoon

    2015-01-01

    Owing to recent improvement of genotyping technology, large-scale genetic data can be utilized to identify disease susceptibility loci and this successful finding has substantially improved our understanding of complex diseases. However, in spite of these successes, most of the genetic effects for many complex diseases were found to be very small, which have been a big hurdle to build disease prediction model. Recently, many statistical methods based on penalized regressions have been proposed to tackle the so-called “large P and small N” problem. Penalized regressions including least absolute selection and shrinkage operator (LASSO) and ridge regression limit the space of parameters, and this constraint enables the estimation of effects for very large number of SNPs. Various extensions have been suggested, and, in this report, we compare their accuracy by applying them to several complex diseases. Our results show that penalized regressions are usually robust and provide better accuracy than the existing methods for at least diseases under consideration. PMID:26346893

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

    PubMed Central

    2010-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    ERIC Educational Resources Information Center

    Ernest, James M.

    2012-01-01

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

  15. Studies relating to temperature control of a large scale telescope

    NASA Technical Reports Server (NTRS)

    Katzoff, S.

    1973-01-01

    Analytical methods are developed for estimating the circumferential and longitudinal temperature distributions in a large space telescope, idealized as a simple insulated tube with a flat mirror across one end. The effects of wall conduction, multilayer insulation, thermal coatings, heat pipes, and heated collars are analyzed, with numerical examples. For most of the study, the only thermal input to the tube was assumed to be from steady solar irradiation from one side, as in a geosynchronous orbit. Unsteady heat flow through the insulation, as in alternating sunlight and shadow of a low orbit, is briefly discussed.

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

    NASA Technical Reports Server (NTRS)

    1998-01-01

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

  17. A large scale flume for hydro-environmental studies

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

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

    NASA Technical Reports Server (NTRS)

    1998-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  20. Ethnography and Case Study Methodology: An Approach to Large-Scale Policy Studies of Federal Programs.

    ERIC Educational Resources Information Center

    Deslonde, James L.

    Studies of the use of ethnography as an evaluation tool in large-scale contract research studies were reviewed before data collection and design decisions were finalized in response to a Request for Proposal (RFP). Five tasks had to be accomplished before data collection could begin: study sites were selected, a system for data collection was…

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

    PubMed Central

    Ding, Yezhang; Shaholli, Danjela; Mou, Zhonglin

    2014-01-01

    Salicylic acid (SA) is a key defense signal molecule against biotrophic and hemibiotrophic pathogens in plants, but how SA is synthesized in plant cells still remains elusive. Identification of new components involved in pathogen-induced SA accumulation would help address this question. To this end, we performed a large-scale genetic screen for mutants with altered SA accumulation during pathogen infection in Arabidopsis using a bacterial biosensor Acinetobacter sp. ADPWH_lux-based SA quantification method. A total of 35,000 M2 plants in the npr1-3 mutant background have been individually analyzed for the bacterial pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326-induced SA accumulation. Among the mutants isolated, 19 had SA levels lower than npr1 (sln) and two exhibited increased SA accumulation in npr1 (isn). Complementation tests revealed that seven of the sln mutants are new alleles of eds5/sid1, two are sid2/eds16 alleles, one is allelic to pad4, and the remaining seven sln and two isn mutants are new non-allelic SA accumulation mutants. Interestingly, a large group of mutants (in the npr1-3 background), in which Psm ES4326-induced SA levels were similar to those in the wild-type Columbia plants, were identified, suggesting that the signaling network fine-tuning pathogen-induced SA accumulation is complex. We further characterized the sln1 single mutant and found that Psm ES4326-induced defense responses were compromised in this mutant. These defense response defects could be rescued by exogenous SA, suggesting that SLN1 functions upstream of SA. The sln1 mutation was mapped to a region on the north arm of chromosome I, which contains no known genes regulating pathogen-induced SA accumulation, indicating that SLN1 likely encodes a new regulator of SA biosynthesis. Thus, the new sln and isn mutants identified in this genetic screen are valuable for dissecting the molecular mechanisms underlying pathogen-induced SA accumulation in plants. PMID:25610446

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-02-01

    Many inferences about contemporary rates of gene flow are based on the assumption that the observed genetic structure among populations is stable. Recent studies have uncovered several cases in which this assumption is tenuous. Most of those studies have focused on the effects that regular environmental fluctuations can have on genetic structure and gene flow patterns. Occasional catastrophic disturbances could also alter either the distribution of habitat or the spatial distribution of organisms in a way that affects population structure. However, evidence of such effects is sparse in the literature because it is difficult to obtain. Hurricanes, in particular, have the potential to exert dramatic effects on population structure of organisms found on islands or coral reefs or in near shore and coastal habitats. Here we draw on a historic genetic data set and new data to suggest that the genetic structure of sailfin molly (Poecilia latipinna) populations in north Florida was altered dramatically by an unusually large and uncommon type of storm surge associated with Hurricane Dennis in 2005. We compare the spatial pattern of genetic variation in these populations after Hurricane Dennis to the patterns described in an earlier study in this same area. We use comparable genetic data from another region of Florida, collected in the same two periods, to estimate the amount of change expected from typical temporal variation in population structure. The comparative natural history of sailfin mollies in these two regions indicates that the change in population structure produced by the storm surge is not the result of many local extinctions with recolonization from a few refugia but emerged from a pattern of mixing and redistribution. PMID:23348779

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

    PubMed

    2015-03-12

    Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders, up to half of children with severe developmental disorders of probable genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders. PMID:25533962

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

    USGS Publications Warehouse

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

    2005-01-01

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

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

    PubMed Central

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

    2014-01-01

    One important piece of information about the human Mendelian disorders is the mode of inheritance. Recent studies of human genetic diseases on a large scale have provided many novel insights into the underlying molecular mechanisms. However, most successful analyses ignored the mode of inheritance of diseases, which severely limits our understanding of human disease mechanisms relating to the mode of inheritance at the large scale. Therefore, we here conducted a systematic large-scale study of the inheritance mode of Mendelian disorders, to bring new insight into human diseases. Our analyses include the comparison between dominant and recessive disease genes on both genomic and proteomic characteristics, Mendelian mutations, protein network properties and disease connections on both the genetic and the population levels. We found that dominant disease genes are more functionally central, topological central and more sensitive to disease outcome. On the basis of these findings, we suggested that dominant diseases should have higher genetic heterogeneity and should have more comprehensive connections with each other compared with recessive diseases, a prediction we confirm by disease network and disease comorbidity. PMID:24448549

  7. Genetic diversity and molecular phylogeography of Chinese domestic goats by large-scale mitochondrial DNA analysis.

    PubMed

    Zhao, Yongju; Zhao, Runze; Zhao, Zhongquan; Xu, Huizhong; Zhao, Erhu; Zhang, Jiahua

    2014-06-01

    Mitochondrial DNA (mtDNA) D-loop sequences of 666 individuals (including 109 new individuals, 557 individuals retrieved from GenBank) from 33 Chinese domestic goat breeds throughout China were used to investigate their mtDNA variability and molecular phylogeography. The results showed that all goat breeds in this study proved to be extremely diverse, and the average haplotype diversity and nucleotide diversity were 0.990 ± 0.001 and 0.032 ± 0.001, respectively. The 666 sequences gave 326 different haplotypes. Phylogenetic analyses revealed that there were 4 mtDNA haplogroups identified in Chinese domestic goats, in which haplogroup A was predominant and widely distributed. Our finding was consistent with archaeological data and other genetic diversity studies. Amova analysis showed there was significant geographical structuring. Almost 84.31% of genetic variation was included in the within-breed variance component and only 4.69% was observed among the geographic distributions. This genetic diversity results further supported the previous view of multiple maternal origins of Chinese domestic goats, and the results on the phylogenetic relationship contributed to a better understanding of the history of goat domestication and modern production of domestic goats. PMID:24532161

  8. CYP1A1, GSTM1 and GSTT1 genetic polymorphisms and gastric cancer risk among Japanese: A nested case-control study within a large-scale population-based prospective study.

    PubMed

    Hidaka, Akihisa; Sasazuki, Shizuka; Matsuo, Keitaro; Ito, Hidemi; Charvat, Hadrien; Sawada, Norie; Shimazu, Taichi; Yamaji, Taiki; Iwasaki, Motoki; Inoue, Manami; Tsugane, Shoichiro

    2016-08-15

    Cytochrome P450 (CYP) 1A1 and glutathione S-transferases (GST) M1 and T1 are major enzymes in the carcinogen metabolizing pathway. We examined the association between single nucleotide polymorphisms (SNPs) of CYP1A1 (rs4646421, rs4646422 and rs1048943), GSTM1 and GSTT1 and gastric cancer risk in Japan. This is a nested case-control study (457 cases and 457 matched controls) of our population-based cohort involving 36,745 subjects who answered a baseline questionnaire and supplied blood samples. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using conditional logistic regression models. We found that CYP1A1 (rs4646422) variant allele was associated with a statistically significant increased risk of gastric cancer compared with the homozygous wild-type genotype (OR = 1.65; 95% CI = 1.17-2.32). GSTM1 null, GSTT1 null and GSTM1/T1 both or either null genotypes were associated with increased risk, but not statistically significantly. Combination of the CYP1A1 (rs4646422) variant allele and GSTM1/T1 both or either null genotypes was associated with a statistically significant increased risk compared with the combination of the CYP1A1 homozygous wild-type genotype and the GSTM1/T1 both active genotypes. In addition, compared with CYP1A1 (rs4646422) homozygous wild-type genotypes in those who were never-smokers, CYP1A1 variant alleles in those who smoked ≥30 pack-years were associated with an increased risk; neither gene-gene nor gene-environment interactions were significant. The CYP1A1 (rs4646422) polymorphism might be involved in gastric carcinogenesis among the Japanese population. PMID:27062139

  9. Large Scale Interventions: An Historical Case Study of Florida Schoolyear, 2000.

    ERIC Educational Resources Information Center

    Russo-Converso, Judith A.

    This research study focuses an historical case study on a large-scale intervention called Florida SchoolYear (SY2000), which was a visionary example of how the state of Florida tried to design and develop a means for delivering quality education. By studying the Florida SY2000 Initiative, this research study examined issue-oriented questions…

  10. Genetically encoded voltage indicators for large scale cortical imaging come of age.

    PubMed

    Knöpfel, Thomas; Gallero-Salas, Yasir; Song, Chenchen

    2015-08-01

    Electrical signals are fundamental to cellular sensing, communication and motility. In the nervous system, information is represented as receptor, synaptic and action potentials. Understanding how brain functions emerge from these electrical signals is one of the ultimate challenges in neuroscience and requires a methodology to monitor membrane voltage transients from large numbers of cells at high spatio-temporal resolution. Optical voltage imaging holds longstanding promises to achieve this, and has gained a fresh powerful momentum with the development of genetically encoded voltage indicators (GEVIs). With a focus on neuroimaging studies on intact mouse brains, we highlight recent advances in this field. PMID:26115448

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

    PubMed Central

    Lu, Wenbin; Tzeng, Jung-Ying

    2016-01-01

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

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

    PubMed

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

    2014-10-01

    The captive genetic management of threatened species strives to preserve genetic diversity and avoid inbreeding to ensure populations remain available, healthy, and viable for future reintroduction. Determining and responding to the genetic status of captive populations is therefore paramount to these programs. Here, we genotyped 19 microsatellite loci for 240 captive giant pandas (Ailuropoda melanoleuca) (∼64% of the captive population) from four breeding centers, Wolong (WL), Chengdu (CD), Louguantai (LGT), and Beijing (BJ), and analyzed 655 bp of mitochondrial DNA control region sequence for 220 of these animals. High levels of genetic diversity and low levels of inbreeding were estimated in the breeding centers, indicating that the captive population is genetically healthy and deliberate further genetic input from wild animals is unnecessary. However, the LGT population faces a higher risk of inbreeding, and significant genetic structure was detected among breeding centers, with LGT-CD and WL-BJ clustering separately. Based on these findings, we highlight that: 1) the LGT population should be managed as an independent captive population to resemble the genetic distinctness of their Qinling Mountain origins; 2) exchange between CD and WL should be encouraged because of similar wild founder sources; 3) the selection of captive individuals for reintroduction should consider their geographic origin, genetic background, and genetic contribution to wild populations; and 4) combining our molecular genetic data with existing pedigree data will better guide giant panda breeding and further reduce inbreeding into the future. PMID:25015646

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    ERIC Educational Resources Information Center

    Reynolds, Sue; MacKay, Tommy; Kearney, Maura

    2009-01-01

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

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

    EPA Science Inventory

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

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

    PubMed

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

    2010-01-01

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

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

    PubMed

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

    2012-10-01

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

  20. Large-scale risk prediction applied to Genetic Analysis Workshop 17 mini-exome sequence data

    PubMed Central

    2011-01-01

    We consider the application of Efron’s empirical Bayes classification method to risk prediction in a genome-wide association study using the Genetic Analysis Workshop 17 (GAW17) data. A major advantage of using this method is that the effect size distribution for the set of possible features is empirically estimated and that all subsequent parameter estimation and risk prediction is guided by this distribution. Here, we generalize Efron’s method to allow for some of the peculiarities of the GAW17 data. In particular, we introduce two ways to extend Efron’s model: a weighted empirical Bayes model and a joint covariance model that allows the model to properly incorporate the annotation information of single-nucleotide polymorphisms (SNPs). In the course of our analysis, we examine several aspects of the possible simulation model, including the identity of the most important genes, the differing effects of synonymous and nonsynonymous SNPs, and the relative roles of covariates and genes in conferring disease risk. Finally, we compare the three methods to each other and to other classifiers (random forest and neural network). PMID:22373389

  1. A large-scale genetic screen in Arabidopsis to identify genes involved in pollen exine production.

    PubMed

    Dobritsa, Anna A; Geanconteri, Aliza; Shrestha, Jay; Carlson, Ann; Kooyers, Nicholas; Coerper, Daniel; Urbanczyk-Wochniak, Ewa; Bench, Bennie J; Sumner, Lloyd W; Swanson, Robert; Preuss, Daphne

    2011-10-01

    Exine, the outer plant pollen wall, has elaborate species-specific patterns, provides a protective barrier for male gametophytes, and serves as a mediator of strong and species-specific pollen-stigma adhesion. Exine is made of sporopollenin, a material remarkable for its strength, elasticity, and chemical durability. The chemical nature of sporopollenin, as well as the developmental mechanisms that govern its assembly into diverse patterns in different species, are poorly understood. Here, we describe a simple yet effective genetic screen in Arabidopsis (Arabidopsis thaliana) that was undertaken to advance our understanding of sporopollenin synthesis and exine assembly. This screen led to the recovery of mutants with a variety of defects in exine structure, including multiple mutants with novel phenotypes. Fifty-six mutants were selected for further characterization and are reported here. In 14 cases, we have mapped defects to specific genes, including four with previously demonstrated or suggested roles in exine development (MALE STERILITY2, CYP703A2, ANTHER-SPECIFIC PROTEIN6, TETRAKETIDE α-PYRONE REDUCTASE/DIHYDROFLAVONOL-4-REDUCTASE-LIKE1), and a number of genes that have not been implicated in exine production prior to this screen (among them, fatty acid ω-hydroxylase CYP704B1, putative glycosyl transferases At1g27600 and At1g33430, 4-coumarate-coenzyme A ligase 4CL3, polygalacturonase QUARTET3, novel gene At5g58100, and nucleotide-sugar transporter At5g65000). Our study illustrates that morphological screens of pollen can be extremely fruitful in identifying previously unknown exine genes and lays the foundation for biochemical, developmental, and evolutionary studies of exine production. PMID:21849515

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

    PubMed Central

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

    2015-01-01

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

  3. Impacts of Large-Scale Circulation on Convection: A 2-D Cloud Resolving Model Study

    NASA Technical Reports Server (NTRS)

    Li, X; Sui, C.-H.; Lau, K.-M.

    1999-01-01

    Studies of impacts of large-scale circulation on convection, and the roles of convection in heat and water balances over tropical region are fundamentally important for understanding global climate changes. Heat and water budgets over warm pool (SST=29.5 C) and cold pool (SST=26 C) were analyzed based on simulations of the two-dimensional cloud resolving model. Here the sensitivity of heat and water budgets to different sizes of warm and cold pools is examined.

  4. Ethical and practical challenges to studying patients who opt out of large-scale biorepository research

    PubMed Central

    Rosenbloom, S Trent; Madison, Jennifer L; Brothers, Kyle B; Bowton, Erica A; Clayton, Ellen Wright; Malin, Bradley A; Roden, Dan M; Pulley, Jill

    2013-01-01

    Large-scale biorepositories that couple biologic specimens with electronic health records containing documentation of phenotypic expression can accelerate scientific research and discovery. However, differences between those subjects who participate in biorepository-based research and the population from which they are drawn may influence research validity. While an opt-out approach to biorepository-based research enhances inclusiveness, empirical research evaluating voluntariness, risk, and the feasibility of an opt-out approach is sparse, and factors influencing patients’ decisions to opt out are understudied. Determining why patients choose to opt out may help to improve voluntariness, however there may be ethical and logistical challenges to studying those who opt out. In this perspective paper, the authors explore what is known about research based on the opt-out model, describe a large-scale biorepository that leverages the opt-out model, and review specific ethical and logistical challenges to bridging the research gaps that remain. PMID:23886923

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

    PubMed Central

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

    2016-01-01

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

  6. Large-Scale Single-Guide RNA Library Construction and Use for Genetic Screens

    PubMed Central

    Wang, Tim; Lander, Eric S.; Sabatini, David M.

    2016-01-01

    The ability to systematically disrupt genes serves as a powerful tool for understanding their function. The programmable Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system enables efficient targeting of large numbers of genes through the use of single-guide RNA (sgRNA) libraries. In cultured mammalian cells, collections of knockout mutants can be readily generated via transduction of Cas9/sgRNA lentiviral pools, screened for a phenotype of interest, and tracked using high-throughput DNA sequencing. This technique represents the first general method for undertaking systematic loss-of-function genetic screens in mammalian cells. In this chapter, we outline the steps for conducting CRISPR-based screens from the initial library design to final data analysis and provide guidelines for developing an appropriate screening strategy. PMID:26933254

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

    PubMed

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

    2016-01-01

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

  8. Solving large-scale real-world telecommunication problems using a grid-based genetic algorithm

    NASA Astrophysics Data System (ADS)

    Luna, Francisco; Nebro, Antonio; Alba, Enrique; Durillo, Juan

    2008-11-01

    This article analyses the use of a grid-based genetic algorithm (GrEA) to solve a real-world instance of a problem from the telecommunication domain. The problem, known as automatic frequency planning (AFP), is used in a global system for mobile communications (GSM) networks to assign a number of fixed frequencies to a set of GSM transceivers located in the antennae of a cellular phone network. Real data instances of the AFP are very difficult to solve owing to the NP-hard nature of the problem, so combining grid computing and metaheuristics turns out to be a way to provide satisfactory solutions in a reasonable amount of time. GrEA has been deployed on a grid with up to 300 processors to solve an AFP instance of 2612 transceivers. The results not only show that significant running time reductions are achieved, but that the search capability of GrEA clearly outperforms that of the equivalent non-grid algorithm.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-01-01

    Detecting and quantifying the timing and the genetic contributions of parental populations to a hybrid population is an important but challenging problem in reconstructing evolutionary histories from genetic variation data. With the advent of high throughput genotyping technologies, new methods suitable for large-scale data are especially needed. Furthermore, existing methods typically assume the assignment of individuals into subpopulations is known, when that itself is a difficult problem often unresolved for real data. Here, we propose a novel method that combines prior work for inferring non reticulate population structures with an MCMC scheme for sampling over admixture scenarios to both identify population assignments and learn divergence times and admixture proportions for those populations using genome-scale admixed genetic variation data. We validated our method using coalescent simulations and a collection of real bovine and human variation data. On simulated sequences, our methods show better accuracy and faster run time than leading competitive methods in estimating admixture fractions and divergence times. Analysis on the real data further shows our methods to be effective at matching our best current knowledge about the relevant populations. PMID:23959633

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

    PubMed Central

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

    2003-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  14. Study on tsunami generation and propagation in a large scale wave flume

    NASA Astrophysics Data System (ADS)

    Schimmels, Stefan; Venkatachalam, Sriram; Didenkulova, Ira

    2015-04-01

    In this paper we study very long, i.e. real tsunami-like wave generation in a large scale wave flume using a piston type wave maker. Waves of periods between 30 s and more than 100 s were generated at 1 m water depth using two different approaches: (i) deriving the wave board motion directly by integration of the water surface elevation, composed of a different number of solitons (sech2 waves) and (ii) using an iterative self correcting method (SCM). The importance of very long wave generation instead of solitary waves and the necessity for long testing facilities is discussed and results from GWK experiments are presented for single pulses (elongated solitons), N-waves and real tsunami records, either approximated as a combination of solitons or applying the SCM to the time series directly. The possibility to study propagation, shoaling and run-up of these waves over a slope in a 300-meter long large wave flume (GWK), Hannover is dicsussed. Experimental data of long wave propagation in the flume are compared with numerical simulations performed within the fully nonlinear potential flow theory and KdV equations. Shoaling and run-up of waves on different mild slopes is studied hypothetically using nonlinear shallow water theory. The paper ends with the conclusions about the feasibility of using large scale experimental facility (GWK) to study tsunami wave propagation and run-up.

  15. Studying populations of eclipsing binaries using large scale multi-epoch photometric surveys

    NASA Astrophysics Data System (ADS)

    Mowlavi, Nami; Barblan, Fabio; Holl, Berry; Rimoldini, Lorenzo; Lecoeur-Taïbi, Isabelle; Süveges, Maria; Eyer, Laurent; Guy, Leanne; Nienartowicz, Krzysztof; Ordonez, Diego; Charnas, Jonathan; Jévardat de Fombelle, Grégory

    2015-08-01

    Large scale multi-epoch photometric surveys provide unique opportunities to study populations of binary stars through the study of eclipsing binaries, provided the basic properties of binary systems can be derived from their light curves without the need to fully model the binary system. Those systems can then be classified into various types from, for example, close to wide systems, from circular to highly elliptical systems, or from systems with similar components to highly asymmetric systems. The challenge is to extract physically relevant information from the light curve geometry.In this contribution, we present the study of eclipsing binaries in the Large Magellanic Clouds (LMC) from the OGLE-III survey. The study is based on the analysis of the geometry of their light curves parameterized using a two-Gaussian model. We show what physical parameters could be extracted from such an analysis, and the results for the LMC eclipsing binaries. The method is very well adapted to process large-scale surveys containing millions of eclipsing binaries, such as is expected from the current Gaia mission or the future LSST survey.

  16. Flaglets for studying the large-scale structure of the Universe

    NASA Astrophysics Data System (ADS)

    Leistedt, Boris; Peiris, Hiranya V.; McEwen, Jason D.

    2013-09-01

    Pressing questions in cosmology such as the nature of dark matter and dark energy can be addressed using large galaxy surveys, which measure the positions, properties and redshifts of galaxies in order to map the large-scale structure of the Universe. We review the Fourier-Laguerre transform, a novel transform in 3D spherical coordinates which is based on spherical harmonics combined with damped Laguerre polynomials and appropriate for analysing galaxy surveys. We also recall the construction of aglets, 3D wavelets obtained through a tiling of the Fourier-Laguerre space, which can be used to extract scale-dependent, spatially localised features on the ball. We exploit a sampling theorem to obtain exact Fourier-Laguerre and aglet transforms, such that band-limited signals can analysed and reconstructed at oating point accuracy on a nite number of voxels on the ball. We present a potential application of the aglet transform for nding voids in galaxy surveys and studying the large-scale structure of the Universe.

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

    SciTech Connect

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

    1996-12-31

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  19. Transport of iron oxide nanoparticles in saturated porous media: a large-scale 3D study

    NASA Astrophysics Data System (ADS)

    Velimirovic, Milica; Schmid, Doris; Micić, Vesna; Miyajima, Kumiko; Klaas, Norbert; Braun, Jürgen; Bosch, Julian; Meckenstock, Rainer; von der Kammer, Frank; Hofmann, Thilo

    2016-04-01

    Iron oxide nanoparticles (FeOxNp) have a high potential as electron acceptor for in situ microbial oxidation of a wide range of recalcitrant groundwater contaminants (Bosch et al., 2010). Tosco et al. (2012) reported on high colloidal stability of FeOxNp dispersed in water, their low deposition behavior, and consequently improved transport in column experiments compared to extensively studied zerovalent iron nanoparticles. However, determination of FeOxNp transport behavior at the field-relevant conditions has not been done before. The present work is aimed to evaluate different complementary methods for detection, quantification and transport characterization of FeOxNp in a large-scale three-dimensional (3D) model aquifer. Prior to that, batch-scale experiments were performed in order to elucidate the potential of the selected methods for direct and indirect characterization and detection of FeOxNp. Direct methods included measurements of particle size distribution, particle concentration, Fetot content and turbidity of the FeOxNp suspension. Indirect methods included measurements of particle zeta potential, as well as TOC content and pH of the FeOxNp suspension. The results of the batch experiments indicated that the most suitable approach for detecting and quantifying FeOxNp was measuring Fetot content and suspension turbidity, as well as particle size determined using dynamic light scattering principle. These complementary methods were further applied in a large-scale 3D study containing medium and coarse sand in order to 1) assess the transport of FeOxNp in saturated porous medium during injection (VFeOx = 6 m3, cparticle = 20 g/L, Qinj = 0.7 m3/h), and 2) illustrate their spatial distribution after injection. The outcomes of the large-scale 3D study confirmed that FeOxNp transport can be successfully investigated applying complementary methods. Monitoring data including Fetot content, turbidity and particle size showed the transport of particles towards the

  20. A large-scale study of epilepsy in Ecuador: methodological aspects.

    PubMed

    Placencia, M; Suarez, J; Crespo, F; Sander, J W; Shorvon, S D; Ellison, R H; Cascante, S M

    1992-01-01

    The methodology is presented of a large-scale study of epilepsy carried out in a highland area in northern Ecuador, South America, covering a population of 72,121 people; The study was carried out in two phases, the first, a cross-sectional phase, consisted of a house-to-house survey of all persons in this population, screening for epileptic seizures using a specially designed questionnaire. Possible cases identified in screening were assessed in a cascade diagnostic procedure applied by general doctors and neurologists. Its objectives were: to establish a comprehensive epidemiological profile of epileptic seizures; to describe the clinical phenomenology of this condition in the community; to validate methods for diagnosis and classification of epileptic seizures by a non-specialised team; and to ascertain the community's knowledge, attitudes and practices regarding epilepsy. A sample was selected in this phase in order to study the social aspects of epilepsy in this community. The second phase, which was longitudinal, assessed the ability of non-specialist care in the treatment of epilepsy. It consisted of a prospective clinical trial of antiepileptic therapy in untreated patients using two standard anti-epileptic drugs. Patients were followed for 12 months by a multidisciplinary team consisting of a primary health worker, rural doctor, neurologist, anthropologist, and psychologist. Standardised, reproducible instruments and methods were used. This study was carried out through co-operation between the medical profession, political agencies and the pharmaceutical industry, at an international level. We consider this a model for further large-scale studies of this type. PMID:1495577

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

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

    PubMed

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

    2015-05-01

    The objective of this study was to assess the costs, energy consumption and greenhouse gas (GHG) emissions throughout the biomass supply chain for large scale biofuel production. Two types of energy crop were considered, switchgrass and loblolly pine, as representative of herbaceous and woody biomass. A biomass logistics model has been developed to estimate the feedstock supply system from biomass production through transportation. Biomass in the form of woodchip, bale and pellet was investigated with road, railway and waterway transportation options. Our analysis indicated that the farm or forest gate cost is lowest for loblolly pine whole tree woodchip at $39.7/dry tonne and highest for switchgrass round bale at $72.3/dry tonne. Switchgrass farm gate GHG emissions is approximately 146kgCO2e/dry tonne, about 4 times higher than loblolly pine. The optimum biomass transportation mode and delivered form are determined by the tradeoff between fixed and variable costs for feedstock shipment. PMID:25710677

  3. Parallel computing study for the large-scale generalized eigenvalue problems in modal analysis

    NASA Astrophysics Data System (ADS)

    Fan, XuanHua; Chen, Pu; Wu, RuiAn; Xiao, ShiFu

    2014-03-01

    In this paper we study the algorithms and their parallel implementation for solving large-scale generalized eigenvalue problems in modal analysis. Three predominant subspace algorithms, i.e., Krylov-Schur method, implicitly restarted Arnoldi method and Jacobi-Davidson method, are modified with some complementary techniques to make them suitable for modal analysis. Detailed descriptions of the three algorithms are given. Based on these algorithms, a parallel solution procedure is established via the PANDA framework and its associated eigensolvers. Using the solution procedure on a machine equipped with up to 4800 processors, the parallel performance of the three predominant methods is evaluated via numerical experiments with typical engineering structures, where the maximum testing scale attains twenty million degrees of freedom. The speedup curves for different cases are obtained and compared. The results show that the three methods are good for modal analysis in the scale of ten million degrees of freedom with a favorable parallel scalability.

  4. Large-scale mutagenesis of the mouse to understand the genetic bases of nervous system structure and function

    PubMed Central

    Goldowitz, Dan; Frankel, Wayne N.; Takahashi, Joseph S.; Holtz-Vitaterna, Martha; Bult, Carol; Kibbe, Warren A.; Snoddy, Jay; Li, Yanxia; Pretel, Stephanie; Yates, Jeana; Swanson, Douglas J.

    2013-01-01

    N-ethyl-N-nitrosourea (ENU) mutagenesis is presented as a powerful approach to developing models for human disease. The efforts of three NIH Mutagenesis Centers established for the detection of neuroscience-related phenotypes are described. Each center has developed an extensive panel of phenotype screens that assess nervous system structure and function. In particular, these screens focus on complex behavioral traits from drug and alcohol responses to circadian rhythms to epilepsy. Each of these centers has developed a bioinformatics infrastructure to track the extensive number of transactions that are inherent in these large-scale projects. Over 100 new mouse mutant lines have been defined through the efforts of these three mutagenesis centers and are presented to the research community via the centralized Web presence of the Neuromice.org consortium (http://www.neuromice.org). This community resource provides visitors with the ability to search for specific mutant phenotypes, to view the genetic and phenotypic details of mutant mouse lines, and to order these mice for use in their own research program. PMID:15582151

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. Large-Scale SNP Discovery and Genotyping for Constructing a High-Density Genetic Map of Tea Plant Using Specific-Locus Amplified Fragment Sequencing (SLAF-seq).

    PubMed

    Ma, Jian-Qiang; Huang, Long; Ma, Chun-Lei; Jin, Ji-Qiang; Li, Chun-Fang; Wang, Rong-Kai; Zheng, Hong-Kun; Yao, Ming-Zhe; Chen, Liang

    2015-01-01

    Genetic maps are important tools in plant genomics and breeding. The present study reports the large-scale discovery of single nucleotide polymorphisms (SNPs) for genetic map construction in tea plant. We developed a total of 6,042 valid SNP markers using specific-locus amplified fragment sequencing (SLAF-seq), and subsequently mapped them into the previous framework map. The final map contained 6,448 molecular markers, distributing on fifteen linkage groups corresponding to the number of tea plant chromosomes. The total map length was 3,965 cM, with an average inter-locus distance of 1.0 cM. This map is the first SNP-based reference map of tea plant, as well as the most saturated one developed to date. The SNP markers and map resources generated in this study provide a wealth of genetic information that can serve as a foundation for downstream genetic analyses, such as the fine mapping of quantitative trait loci (QTL), map-based cloning, marker-assisted selection, and anchoring of scaffolds to facilitate the process of whole genome sequencing projects for tea plant. PMID:26035838

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

    USGS Publications Warehouse

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

    2002-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-08-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Young, Erick T.

    1990-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Young, Erick T.

    1993-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

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

    SciTech Connect

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

    2013-01-02

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

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

    PubMed

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

    2012-03-01

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

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

    PubMed

    Lai, Xuelei; Soler-Lopez, Montserrat; Wichers, Harry J; Dijkstra, Bauke W

    2016-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Blair, M.F. )

    1994-01-01

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

  2. Analytical Study on the Cosmological Large-scale Structure in an Accelerating Universe

    NASA Astrophysics Data System (ADS)

    Wang, Xin

    2012-01-01

    Motivated by the roughly log-normal probability density distribution function (PDF) of the small scale density field, we develop cosmological perturbation theory for the power spectrum of a logarithmically transformed density field with the formalism which is developed in the context of the cosmological renormalized perturbation theory. Compared with the standard perturbation theory, our approach help to regulate the convergence behavior of the perturbation series, and of the Taylor series expansion we use for the logarithmic mapping. The perturbation calculation achieved good agreement with simulation results. Then we consider the topology of the iso-density contour of the density field, especially the genus. The genus is relatively insensitive to nonlinear gravitational evolution, clustering bias and redshift distortion, and is approximately conserved over time as structures grow in Einstein's general relativity, hence it can be used as a robust standard ruler for cosmological measurements. However, in modified gravity models where structures grow with different rates on different scales, the genus should change over time, and therefore it can be used to test the gravity models on large scales. We studied the case of the f(R) theory, DGP brane-world theory as well as phenomenological models. We also forecast how the modified gravity models can be constrained with optical/IR or 21cm surveys in the near future.

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

    NASA Technical Reports Server (NTRS)

    Blair, Michael F.

    1992-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. Large-scale studies of spontaneous combustion of coal. Rept. of investigations/1991

    SciTech Connect

    Smith, A.C.; Miron, Y.; Lazzara, C.P.

    1991-01-01

    The U.S. Bureau of Mines constructed a large-scale facility to study the self-heating of a large coal mass under conditions that simulate a gob area of a mine. The insulated coal chamber can hold up to 13 short tons (st) of coal and is provided with a forced ventilation system and computer-controlled temperature and gas measurement systems to monitor the heat and mass transfer phenomena that occur in the coalbed. Three experiments were completed with high-volatile C bituminous coals that exhibited high spontaneous combustion potentials in laboratory-scale tests. In the first two tests, a sustained heating was not achieved. In the third test, temperatures throughout the coalbed increased steadily from the start, with thermal runaway occurring near the center of the coalbed after 23 days. The thermal reaction zone then moved toward the front of the coalbed. The results of these tests showed that the self-heating of a large coal mass depends not just on the reactivity of the coal, but also on the particle size of the coal, the freshness of the coal surfaces, the heat-of-wetting effect, and the availability of O2 at optimum ventilation rates.

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

    SciTech Connect

    Jiang, Huijun; Hou, Zhonghuai

    2015-08-28

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

  7. Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

    PubMed Central

    Tang, Wenbo; Kowgier, Matthew; Loth, Daan W.; Soler Artigas, María; Joubert, Bonnie R.; Hodge, Emily; Gharib, Sina A.; Smith, Albert V.; Ruczinski, Ingo; Gudnason, Vilmundur; Mathias, Rasika A.; Harris, Tamara B.; Hansel, Nadia N.; Launer, Lenore J.; Barnes, Kathleen C.; Hansen, Joyanna G.; Albrecht, Eva; Aldrich, Melinda C.; Allerhand, Michael; Barr, R. Graham; Brusselle, Guy G.; Couper, David J.; Curjuric, Ivan; Davies, Gail; Deary, Ian J.; Dupuis, Josée; Fall, Tove; Foy, Millennia; Franceschini, Nora; Gao, Wei; Gläser, Sven; Gu, Xiangjun; Hancock, Dana B.; Heinrich, Joachim; Hofman, Albert; Imboden, Medea; Ingelsson, Erik; James, Alan; Karrasch, Stefan; Koch, Beate; Kritchevsky, Stephen B.; Kumar, Ashish; Lahousse, Lies; Li, Guo; Lind, Lars; Lindgren, Cecilia; Liu, Yongmei; Lohman, Kurt; Lumley, Thomas; McArdle, Wendy L.; Meibohm, Bernd; Morris, Andrew P.; Morrison, Alanna C.; Musk, Bill; North, Kari E.; Palmer, Lyle J.; Probst-Hensch, Nicole M.; Psaty, Bruce M.; Rivadeneira, Fernando; Rotter, Jerome I.; Schulz, Holger; Smith, Lewis J.; Sood, Akshay; Starr, John M.; Strachan, David P.; Teumer, Alexander; Uitterlinden, André G.; Völzke, Henry; Voorman, Arend; Wain, Louise V.; Wells, Martin T.; Wilk, Jemma B.; Williams, O. Dale; Heckbert, Susan R.; Stricker, Bruno H.; London, Stephanie J.; Fornage, Myriam; Tobin, Martin D.; O′Connor, George T.; Hall, Ian P.; Cassano, Patricia A.

    2014-01-01

    Background Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. Methods We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. Results The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10-7). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10-8) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. Conclusions In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function. PMID:24983941

  8. A general framework for association tests with multivariate traits in large-scale genomics studies.

    PubMed

    He, Qianchuan; Avery, Christy L; Lin, Dan-Yu

    2013-12-01

    Genetic association studies often collect data on multiple traits that are correlated. Discovery of genetic variants influencing multiple traits can lead to better understanding of the etiology of complex human diseases. Conventional univariate association tests may miss variants that have weak or moderate effects on individual traits. We propose several multivariate test statistics to complement univariate tests. Our framework covers both studies of unrelated individuals and family studies and allows any type/mixture of traits. We relate the marginal distributions of multivariate traits to genetic variants and covariates through generalized linear models without modeling the dependence among the traits or family members. We construct score-type statistics, which are computationally fast and numerically stable even in the presence of covariates and which can be combined efficiently across studies with different designs and arbitrary patterns of missing data. We compare the power of the test statistics both theoretically and empirically. We provide a strategy to determine genome-wide significance that properly accounts for the linkage disequilibrium (LD) of genetic variants. The application of the new methods to the meta-analysis of five major cardiovascular cohort studies identifies a new locus (HSCB) that is pleiotropic for the four traits analyzed. PMID:24227293

  9. RACORO continental boundary layer cloud investigations: 1. Case study development and ensemble large-scale forcings

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  10. Large-scale structure studies with the unresolved CXB - Challenges from XBOOTES

    NASA Astrophysics Data System (ADS)

    Kolodzig, Alexander; Gilfanov, Marat; Hütsi, Gert; Sunyaev, Rashid

    2015-08-01

    The scientific significance of large-scale structure (LSS) studies with X-ray surveys can be greatly enhanced by analysis of the surface brightness fluctuations of the unresolved cosmic X-ray background (CXB). It enables us to study the clustering properties of source populations, which are otherwise inaccessible with clustering studies of resolved sources of current X-ray surveys due to the lack of deep-wide surveys and selection effects.We have conducted the most accurate measurement to date of the brightness fluctuations of the unresolved CXB in the 0.5-2.0keV band for angular scales of <~17', using XBOOTES, the currently largest continuous Chandra survey (~9 deg2).We find that on small angular scales (<~2') the observed power spectrum of the brightness fluctuations is broadly consistent with the conventional AGN clustering model, although with a ~30% deviation. This deviation demonstrates the current poor knowledge of the clustering properties of AGN within their dark matter halo (DMH). We provide possible explanations for this deviation.For angular scales of >~2' we measure a significant excess with up to an order of magnitude difference in comparison to the standard AGN clustering model. We demonstrate that an instrumental origin can be excluded but also that it can neither be explained with any known X-ray source population based on its clustering strength and the shape of its energy spectrum. We speculate that the excess is caused by more than one type of source and that its dominant source appears to have extragalactic origin.Finally, we make predictions on how the eROSITA all-sky survey (eRASS) will be able to advance the studies of the unresolved CXB.

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

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Bowman, Kenneth P.

    1997-01-01

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

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

    PubMed

    Ahrens, Wolfgang; Jöckel, K-H

    2015-08-01

    The prospective nature of large-scale epidemiological multi-purpose cohort studies with long observation periods facilitates the search for complex causes of diseases, the analysis of the natural history of diseases and the identification of novel pre-clinical markers of disease. The German National Cohort (GNC) is a population-based, highly standardised and in-depth phenotyped cohort. It shall create the basis for new strategies for risk assessment and identification, early diagnosis and prevention of multifactorial diseases. The GNC is the largest population-based cohort study in Germany to date. In the year 2014 the examination of 200,000 women and men aged 20-69 years started in 18 study centers. The study facilitates the investigation of the etiology of chronic diseases in relation to lifestyle, genetic, socioeconomic, psychosocial and environmental factors. By this the GNC creates the basis for the development of methods for early diagnosis and prevention of these diseases. Cardiovascular and respiratory diseases, cancer, diabetes, neurodegenerative/-psychiatric diseases, musculoskeletal and infectious diseases are in focus of this study. Due to its mere size, the study could be characterized as a Big Data project. We deduce that this is not the case. PMID:26077870

  14. Study of the structure and physical properties of quasicrystals using large scale facilities

    NASA Astrophysics Data System (ADS)

    de Boissieu, Marc

    2012-04-01

    Quasicrystals have been puzzling scientists since their discovery. In this article we review some of the recent advances in this field and show how the use of large scale facilities has brought in decisive information for the understanding of their structure and physical properties.

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

    ERIC Educational Resources Information Center

    Hodnett, P. F.; Courtney, C.

    2007-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  17. Image-guided Coring for Large-scale Studies in Molecular Pathology.

    PubMed

    Montaser-Kouhsari, Laleh; Knoblauch, Nicholas W; Oh, Eun-Yeong; Baker, Gabrielle; Christensen, Stephen; Hazra, Aditi; Tamimi, Rulla M; Beck, Andrew H

    2016-07-01

    Sampling of formalin-fixed paraffin-embedded (FFPE) tissue blocks is a critical initial step in molecular pathology. Image-guided coring (IGC) is a new method for using digital pathology images to guide tissue block coring for molecular analyses. The goal of our study is to evaluate the use of IGC for both tissue-based and nucleic acid-based projects in molecular pathology. First, we used IGC to construct a tissue microarray (TMA); second, we used IGC for FFPE block sampling followed by RNA extraction; and third, we assessed the correlation between nuclear counts quantitated from the IGC images and RNA yields. We used IGC to construct a TMA containing 198 normal and breast cancer cores. Histopathologic analysis showed high accuracy for obtaining tumor and normal breast tissue. Next, we used IGC to obtain normal and tumor breast samples before RNA extraction. We selected a random subset of tumor and normal samples to perform computational image analysis to quantify nuclear density, and we built regression models to estimate RNA yields from nuclear count, age of the block, and core diameter. Number of nuclei and core diameter were the strongest predictors of RNA yields in both normal and tumor tissue. IGC is an effective method for sampling FFPE tissue blocks for TMA construction and nucleic acid extraction. We identify significant associations between quantitative nuclear counts obtained from IGC images and RNA yields, suggesting that the integration of computational image analysis with IGC may be an effective approach for tumor sampling in large-scale molecular studies. PMID:26186251

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

    USGS Publications Warehouse

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

    2005-01-01

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

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

    SciTech Connect

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

    2010-10-01

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

  20. Image-guided Coring for Large-scale Studies in Molecular Pathology

    PubMed Central

    Montaser-Kouhsari, Laleh; Knoblauch, Nicholas W.; Oh, Eun-Yeong; Baker, Gabrielle; Christensen, Stephen; Hazra, Aditi; Tamimi, Rulla M.

    2016-01-01

    Sampling of formalin-fixed paraffin-embedded (FFPE) tissue blocks is a critical initial step in molecular pathology. Image-guided coring (IGC) is a new method for using digital pathology images to guide tissue block coring for molecular analyses. The goal of our study is to evaluate the use of IGC for both tissue-based and nucleic acid–based projects in molecular pathology. First, we used IGC to construct a tissue microarray (TMA); second, we used IGC for FFPE block sampling followed by RNA extraction; and third, we assessed the correlation between nuclear counts quantitated from the IGC images and RNA yields. We used IGC to construct a TMA containing 198 normal and breast cancer cores. Histopathologic analysis showed high accuracy for obtaining tumor and normal breast tissue. Next, we used IGC to obtain normal and tumor breast samples before RNA extraction. We selected a random subset of tumor and normal samples to perform computational image analysis to quantify nuclear density, and we built regression models to estimate RNA yields from nuclear count, age of the block, and core diameter. Number of nuclei and core diameter were the strongest predictors of RNA yields in both normal and tumor tissue. IGC is an effective method for sampling FFPE tissue blocks for TMA construction and nucleic acid extraction. We identify significant associations between quantitative nuclear counts obtained from IGC images and RNA yields, suggesting that the integration of computational image analysis with IGC may be an effective approach for tumor sampling in large-scale molecular studies. PMID:26186251

  1. Research guidelines in the era of large-scale collaborations: an analysis of Genome-wide Association Study Consortia.

    PubMed

    Austin, Melissa A; Hair, Marilyn S; Fullerton, Stephanie M

    2012-05-01

    Scientific research has shifted from studies conducted by single investigators to the creation of large consortia. Genetic epidemiologists, for example, now collaborate extensively for genome-wide association studies (GWAS). The effect has been a stream of confirmed disease-gene associations. However, effects on human subjects oversight, data-sharing, publication and authorship practices, research organization and productivity, and intellectual property remain to be examined. The aim of this analysis was to identify all research consortia that had published the results of a GWAS analysis since 2005, characterize them, determine which have publicly accessible guidelines for research practices, and summarize the policies in these guidelines. A review of the National Human Genome Research Institute's Catalog of Published Genome-Wide Association Studies identified 55 GWAS consortia as of April 1, 2011. These consortia were comprised of individual investigators, research centers, studies, or other consortia and studied 48 different diseases or traits. Only 14 (25%) were found to have publicly accessible research guidelines on consortia websites. The available guidelines provide information on organization, governance, and research protocols; half address institutional review board approval. Details of publication, authorship, data-sharing, and intellectual property vary considerably. Wider access to consortia guidelines is needed to establish appropriate research standards with broad applicability to emerging forms of large-scale collaboration. PMID:22491085

  2. Research Guidelines in the Era of Large-scale Collaborations: An Analysis of Genome-wide Association Study Consortia

    PubMed Central

    Austin, Melissa A.; Hair, Marilyn S.; Fullerton, Stephanie M.

    2012-01-01

    Scientific research has shifted from studies conducted by single investigators to the creation of large consortia. Genetic epidemiologists, for example, now collaborate extensively for genome-wide association studies (GWAS). The effect has been a stream of confirmed disease-gene associations. However, effects on human subjects oversight, data-sharing, publication and authorship practices, research organization and productivity, and intellectual property remain to be examined. The aim of this analysis was to identify all research consortia that had published the results of a GWAS analysis since 2005, characterize them, determine which have publicly accessible guidelines for research practices, and summarize the policies in these guidelines. A review of the National Human Genome Research Institute’s Catalog of Published Genome-Wide Association Studies identified 55 GWAS consortia as of April 1, 2011. These consortia were comprised of individual investigators, research centers, studies, or other consortia and studied 48 different diseases or traits. Only 14 (25%) were found to have publicly accessible research guidelines on consortia websites. The available guidelines provide information on organization, governance, and research protocols; half address institutional review board approval. Details of publication, authorship, data-sharing, and intellectual property vary considerably. Wider access to consortia guidelines is needed to establish appropriate research standards with broad applicability to emerging forms of large-scale collaboration. PMID:22491085

  3. Evaluation of Kirkwood-Buff integrals via finite size scaling: a large scale molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Dednam, W.; Botha, A. E.

    2015-01-01

    Solvation of bio-molecules in water is severely affected by the presence of co-solvent within the hydration shell of the solute structure. Furthermore, since solute molecules can range from small molecules, such as methane, to very large protein structures, it is imperative to understand the detailed structure-function relationship on the microscopic level. For example, it is useful know the conformational transitions that occur in protein structures. Although such an understanding can be obtained through large-scale molecular dynamic simulations, it is often the case that such simulations would require excessively large simulation times. In this context, Kirkwood-Buff theory, which connects the microscopic pair-wise molecular distributions to global thermodynamic properties, together with the recently developed technique, called finite size scaling, may provide a better method to reduce system sizes, and hence also the computational times. In this paper, we present molecular dynamics trial simulations of biologically relevant low-concentration solvents, solvated by aqueous co-solvent solutions. In particular we compare two different methods of calculating the relevant Kirkwood-Buff integrals. The first (traditional) method computes running integrals over the radial distribution functions, which must be obtained from large system-size NVT or NpT simulations. The second, newer method, employs finite size scaling to obtain the Kirkwood-Buff integrals directly by counting the particle number fluctuations in small, open sub-volumes embedded within a larger reservoir that can be well approximated by a much smaller simulation cell. In agreement with previous studies, which made a similar comparison for aqueous co-solvent solutions, without the additional solvent, we conclude that the finite size scaling method is also applicable to the present case, since it can produce computationally more efficient results which are equivalent to the more costly radial distribution

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

    PubMed

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

    2009-12-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  6. Study of Aerodynamic Design Procedure of a Large-Scale Aircraft Noise Suppression Facility

    NASA Astrophysics Data System (ADS)

    Kawai, Masafumi; Nagai, Kiyoyuki; Aso, Shigeru

    The aerodynamic design procedure of a large-scale aircraft noise suppression facility has been developed. Flow quality required for the engine inlet flow has been determined through basic experiment. Aerodynamic design of the facility has been performed by using wind tunnel experiment and CFD. Important relationship between the length of the facility and the inlet flow quality has been found. The operational envelope of the designed facility has been estimated. Then, the aerodynamic characteristics of an actual large-scale aircraft noise suppression facility, constructed based on the new design procedure, have been measured. Obtained flow field showed good agreement with CFD results, and the effectiveness of the design procedure based on CFD and wind tunnel experiment has been confirmed. The engine operations were satisfactory under various wind conditions. Furthermore, the data under commercial operations thereafter have been collected and analyzed. As the result, the aerodynamic design procedure has been validated.

  7. Study of very-large-scale motions in turbulent pipe flow

    NASA Astrophysics Data System (ADS)

    Lee, Jae Hwa; Sung, Hyung Jin

    2012-11-01

    Direct numerical simulation (DNS) of turbulent pipe flow was performed at Reτ=544 to investigate the spatial organization of the very large-scale motions (VLSMs). The streamwise domain length employed here was 30 R, where R is the pipe radius. Inspection of the three-dimensional instantaneous fields showed that adjacent large-scale packet-like structures combine to form the VLSMs, and this formation process was attributed to continuous stretching of the hairpins coupled with lifting-up and backward curling of the vortices. To support our results found in the analysis of the instantaneous flow fields, we applied the spatial filter to decompose the signal into two length scales related to the VLSMs and smaller structures. The resulting streamwise length scale from the streamwise two-point correlations showed that the magnitude of the correlations for the VLSMs is larger than that from the large-scale motions (LSMs) through all directions. In addition, the mean inclination angle to the wall for the smaller scale structures was found to be larger than that of the VLSMs. These findings support the previous conjecture of Kim & Adrian (1999) that the coherent alignment of LSMs creates the VLSMs. This work was supported by KISTI under the Strategic Supercomputing.

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

    NASA Astrophysics Data System (ADS)

    Aulinger, A.; Petersen, G.

    2003-12-01

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

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

    PubMed

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

    2016-03-01

    Sporadic amyotrophic lateral sclerosis (ALS) is considered to be a complex disease with multiple genetic risk factors contributing to the pathogenesis. Identification of genetic risk factors that co-occur frequently could provide relevant insight into underlying mechanisms of motor neuron degeneration. To dissect the genetic architecture of sporadic ALS, we undertook a large sequencing study in 755 apparently sporadic ALS cases and 959 controls, analyzing 10 ALS genes: SOD1, C9orf72, TARDBP, FUS, ANG, CHMP2B, ATXN2, NIPA1, SMN1, and UNC13A. We observed sporadic cases with multiple genetic risk variants in 4.1% compared with 1.3% in controls. The overall difference was not in excess of what is to be expected by chance (binomial test, p = 0.59). We did, however, observe a higher frequency than expected of C9orf72 repeat carriers with co-occurring susceptibility variants (ATXN2, NIPA1, and SMN1; p = 0.001), which is mainly because of the co-occurrence of NIPA1 repeats in 15% of C9orf72 repeat carriers (p = 0.006). PMID:26777436

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  11. Unraveling Kinase Activation Dynamics Using Kinase-Substrate Relationships from Temporal Large-Scale Phosphoproteomics Studies.

    PubMed

    Domanova, Westa; Krycer, James; Chaudhuri, Rima; Yang, Pengyi; Vafaee, Fatemeh; Fazakerley, Daniel; Humphrey, Sean; James, David; Kuncic, Zdenka

    2016-01-01

    In response to stimuli, biological processes are tightly controlled by dynamic cellular signaling mechanisms. Reversible protein phosphorylation occurs on rapid time-scales (milliseconds to seconds), making it an ideal carrier of these signals. Advances in mass spectrometry-based proteomics have led to the identification of many tens of thousands of phosphorylation sites, yet for the majority of these the kinase is unknown and the underlying network topology of signaling networks therefore remains obscured. Identifying kinase substrate relationships (KSRs) is therefore an important goal in cell signaling research. Existing consensus sequence motif based prediction algorithms do not consider the biological context of KSRs, and are therefore insensitive to many other mechanisms guiding kinase-substrate recognition in cellular contexts. Here, we use temporal information to identify biologically relevant KSRs from Large-scale In Vivo Experiments (KSR-LIVE) in a data-dependent and automated fashion. First, we used available phosphorylation databases to construct a repository of existing experimentally-predicted KSRs. For each kinase in this database, we used time-resolved phosphoproteomics data to examine how its substrates changed in phosphorylation over time. Although substrates for a particular kinase clustered together, they often exhibited a different temporal pattern to the phosphorylation of the kinase. Therefore, although phosphorylation regulates kinase activity, our findings imply that substrate phosphorylation likely serve as a better proxy for kinase activity than kinase phosphorylation. KSR-LIVE can thereby infer which kinases are regulated within a biological context. Moreover, KSR-LIVE can also be used to automatically generate positive training sets for the subsequent prediction of novel KSRs using machine learning approaches. We demonstrate that this approach can distinguish between Akt and Rps6kb1, two kinases that share the same linear consensus motif

  12. Unraveling Kinase Activation Dynamics Using Kinase-Substrate Relationships from Temporal Large-Scale Phosphoproteomics Studies

    PubMed Central

    Chaudhuri, Rima; Yang, Pengyi; Vafaee, Fatemeh; Fazakerley, Daniel; Humphrey, Sean; James, David; Kuncic, Zdenka

    2016-01-01

    In response to stimuli, biological processes are tightly controlled by dynamic cellular signaling mechanisms. Reversible protein phosphorylation occurs on rapid time-scales (milliseconds to seconds), making it an ideal carrier of these signals. Advances in mass spectrometry-based proteomics have led to the identification of many tens of thousands of phosphorylation sites, yet for the majority of these the kinase is unknown and the underlying network topology of signaling networks therefore remains obscured. Identifying kinase substrate relationships (KSRs) is therefore an important goal in cell signaling research. Existing consensus sequence motif based prediction algorithms do not consider the biological context of KSRs, and are therefore insensitive to many other mechanisms guiding kinase-substrate recognition in cellular contexts. Here, we use temporal information to identify biologically relevant KSRs from Large-scale In Vivo Experiments (KSR-LIVE) in a data-dependent and automated fashion. First, we used available phosphorylation databases to construct a repository of existing experimentally-predicted KSRs. For each kinase in this database, we used time-resolved phosphoproteomics data to examine how its substrates changed in phosphorylation over time. Although substrates for a particular kinase clustered together, they often exhibited a different temporal pattern to the phosphorylation of the kinase. Therefore, although phosphorylation regulates kinase activity, our findings imply that substrate phosphorylation likely serve as a better proxy for kinase activity than kinase phosphorylation. KSR-LIVE can thereby infer which kinases are regulated within a biological context. Moreover, KSR-LIVE can also be used to automatically generate positive training sets for the subsequent prediction of novel KSRs using machine learning approaches. We demonstrate that this approach can distinguish between Akt and Rps6kb1, two kinases that share the same linear consensus motif

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

    PubMed

    Sirdah, Mahmoud M

    2014-02-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    SciTech Connect

    Dwyer, S.F.

    1998-09-01

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

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

    Abramovich, Samuel; Schunn, Christian

    2012-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

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

    2000-01-01

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

  1. Feasibility study of a large-scale tuned mass damper with eddy current damping mechanism

    NASA Astrophysics Data System (ADS)

    Wang, Zhihao; Chen, Zhengqing; Wang, Jianhui

    2012-09-01

    Tuned mass dampers (TMDs) have been widely used in recent years to mitigate structural vibration. However, the damping mechanisms employed in the TMDs are mostly based on viscous dampers, which have several well-known disadvantages, such as oil leakage and difficult adjustment of damping ratio for an operating TMD. Alternatively, eddy current damping (ECD) that does not require any contact with the main structure is a potential solution. This paper discusses the design, analysis, manufacture and testing of a large-scale horizontal TMD based on ECD. First, the theoretical model of ECD is formulated, then one large-scale horizontal TMD using ECD is constructed, and finally performance tests of the TMD are conducted. The test results show that the proposed TMD has a very low intrinsic damping ratio, while the damping ratio due to ECD is the dominant damping source, which can be as large as 15% in a proper configuration. In addition, the damping ratios estimated with the theoretical model are roughly consistent with those identified from the test results, and the source of this error is investigated. Moreover, it is demonstrated that the damping ratio in the proposed TMD can be easily adjusted by varying the air gap between permanent magnets and conductive plates. In view of practical applications, possible improvements and feasibility considerations for the proposed TMD are then discussed. It is confirmed that the proposed TMD with ECD is reliable and feasible for use in structural vibration control.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    ERIC Educational Resources Information Center

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

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  7. A Chandra Study of the Large-Scale Shock Front in Abell 2219

    NASA Astrophysics Data System (ADS)

    Allen, Steven

    2011-09-01

    Abell 2219 (z=0.225) is the third galaxy cluster in which a clear, large-scale shock front, viewed approximately edge-on and generated by ongoing merging activity, has been discovered. It is highly X-ray luminous and 2.5 times brighter in X-rays than either 1E0657-56 or A520. We propose a 150ks ACIS-I observation to obtain the first precise measurements of the pre- and post-shock gas temperature, enabling improved estimates of the Mach number and shock velocity. The observed gradient of the temperature jump across the shock will constrain the process of post-shock electron-ion equilibration. We will probe the origin of very hot (kT>20 keV) gas observed in the cluster center. High quality radio, optical-dynamical, and ground- and space-based gravitational lensing data are in hand.

  8. A modelling case study of a large-scale cirrus in the tropical tropopause layer

    NASA Astrophysics Data System (ADS)

    Podglajen, Aurélien; Plougonven, Riwal; Hertzog, Albert; Legras, Bernard

    2016-03-01

    We use the Weather Research and Forecast (WRF) model to simulate a large-scale tropical tropopause layer (TTL) cirrus in order to understand the formation and life cycle of the cloud. This cirrus event has been previously described through satellite observations by Taylor et al. (2011). Comparisons of the simulated and observed cirrus show a fair agreement and validate the reference simulation regarding cloud extension, location and life time. The validated simulation is used to understand the causes of cloud formation. It is shown that several cirrus clouds successively form in the region due to adiabatic cooling and large-scale uplift rather than from convective anvils. The structure of the uplift is tied to the equatorial response (equatorial wave excitation) to a potential vorticity intrusion from the midlatitudes. Sensitivity tests are then performed to assess the relative importance of the choice of the microphysics parameterization and of the initial and boundary conditions. The initial dynamical conditions (wind and temperature) essentially control the horizontal location and area of the cloud. However, the choice of the microphysics scheme influences the ice water content and the cloud vertical position. Last, the fair agreement with the observations allows to estimate the cloud impact in the TTL in the simulations. The cirrus clouds have a small but not negligible impact on the radiative budget of the local TTL. However, for this particular case, the cloud radiative heating does not significantly influence the simulated dynamics. This result is due to (1) the lifetime of air parcels in the cloud system, which is too short to significantly influence the dynamics, and (2) the fact that induced vertical motions would be comparable to or smaller than the typical mesoscale motions present. Finally, the simulation also provides an estimate of the vertical redistribution of water by the cloud and the results emphasize the importance in our case of both

  9. A modelling case study of a large-scale cirrus in the tropical tropopause layer

    NASA Astrophysics Data System (ADS)

    Podglajen, A.; Plougonven, R.; Hertzog, A.; Legras, B.

    2015-11-01

    We use the Weather Research and Forecast (WRF) model to simulate a large-scale tropical tropopause layer (TTL) cirrus, in order to understand the formation and life cycle of the cloud. This cirrus event has been previously described through satellite observations by Taylor et al. (2011). Comparisons of the simulated and observed cirrus show a fair agreement, and validate the reference simulation regarding cloud extension, location and life time. The validated simulation is used to understand the causes of cloud formation. It is shown that several cirrus clouds successively form in the region due to adiabatic cooling and large-scale uplift rather than from ice lofting from convective anvils. The equatorial response (equatorial wave excitation) to a midlatitude potential vorticity (PV) intrusion structures the uplift. Sensitivity tests are then performed to assess the relative importance of the choice of the microphysics parametrisation and of the initial and boundary conditions. The initial dynamical conditions (wind and temperature) essentially control the horizontal location and area of the cloud. On the other hand, the choice of the microphysics scheme influences the ice water content and the cloud vertical position. Last, the fair agreement with the observations allows to estimate the cloud impact in the TTL in the simulations. The cirrus clouds have a small but not negligible impact on the radiative budget of the local TTL. However, the cloud radiative heating does not significantly influence the simulated dynamics. The simulation also provides an estimate of the vertical redistribution of water by the cloud and the results emphasize the importance in our case of both re and dehydration in the vicinity of the cirrus.

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

    PubMed

    Aittokallio, Tero

    2010-03-01

    High-throughput biotechnologies, such as gene expression microarrays or mass-spectrometry-based proteomic assays, suffer from frequent missing values due to various experimental reasons. Since the missing data points can hinder downstream analyses, there exists a wide variety of ways in which to deal with missing values in large-scale data sets. Nowadays, it has become routine to estimate (or impute) the missing values prior to the actual data analysis. After nearly a decade since the publication of the first missing value imputation methods for gene expression microarray data, new imputation approaches are still being developed at an increasing rate. However, what is lagging behind is a systematic and objective evaluation of the strengths and weaknesses of the different approaches when faced with different types of data sets and experimental questions. In this review, the present strategies for missing value imputation and the measures for evaluating their performance are described. The imputation methods are first reviewed in the context of gene expression microarray data, since most of the methods have been developed for estimating gene expression levels; then, we turn to other large-scale data sets that also suffer from the problems posed by missing values, together with pointers to possible imputation approaches in these settings. Along with a description of the basic principles behind the different imputation approaches, the review tries to provide practical guidance for the users of high-throughput technologies on how to choose the imputation tool for their data and questions, and some additional research directions for the developers of imputation methodologies. PMID:19965979

  11. PlasmoGEM, a database supporting a community resource for large-scale experimental genetics in malaria parasites.

    PubMed

    Schwach, Frank; Bushell, Ellen; Gomes, Ana Rita; Anar, Burcu; Girling, Gareth; Herd, Colin; Rayner, Julian C; Billker, Oliver

    2015-01-01

    The Plasmodium Genetic Modification (PlasmoGEM) database (http://plasmogem.sanger.ac.uk) provides access to a resource of modular, versatile and adaptable vectors for genome modification of Plasmodium spp. parasites. PlasmoGEM currently consists of >2000 plasmids designed to modify the genome of Plasmodium berghei, a malaria parasite of rodents, which can be requested by non-profit research organisations free of charge. PlasmoGEM vectors are designed with long homology arms for efficient genome integration and carry gene specific barcodes to identify individual mutants. They can be used for a wide array of applications, including protein localisation, gene interaction studies and high-throughput genetic screens. The vector production pipeline is supported by a custom software suite that automates both the vector design process and quality control by full-length sequencing of the finished vectors. The PlasmoGEM web interface allows users to search a database of finished knock-out and gene tagging vectors, view details of their designs, download vector sequence in different formats and view available quality control data as well as suggested genotyping strategies. We also make gDNA library clones and intermediate vectors available for researchers to produce vectors for themselves. PMID:25593348

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

    Li, Sen; Schlebusch, Carina; Jakobsson, Mattias

    2014-01-01

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

  14. Large-scale gene expression profiling of discrete brain regions: potential, limitations, and application in genetics of aggressive behavior.

    PubMed

    Feldker, Dorine E M; de Kloet, E Ronald; Kruk, Menno R; Datson, Nicole A

    2003-09-01

    Many behavioral geneticists are interested in unraveling the molecular mechanisms underlying aggressive behavior. So far, most scientists have based their search for aggression-related genes on a preliminary functional hypothesis. Large-scale gene expression profiling techniques, such as serial analysis of gene expression (SAGE) and DNA microarrays, now enable the screening of expression levels of thousands of genes simultaneously, allowing the identification of new candidate aggression-related genes expressed in brain and thus the generation of new hypotheses. However, expression profiling in the brain is challenging, as brain is a complex heterogeneous tissue where large numbers of genes are expressed and relatively small changes in gene expression occur. In this special issue, we focus on the principles of SAGE and DNA microarrays, as well as their advantages and disadvantages and application to analysis in brain tissue in order to identify aggression-related genes. PMID:14574131

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

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

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

  16. Small-Scale Screening to Large-Scale Over-Expression of Human Membrane Proteins for Structural Studies.

    PubMed

    Chaudhary, Sarika; Saha, Sukanya; Thamminana, Sobrahani; Stroud, Robert M

    2016-01-01

    Membrane protein structural studies are frequently hampered by poor expression. The low natural abundance of these proteins implies a need for utilizing different heterologous expression systems. E. coli and yeast are commonly used expression systems due to rapid cell growth at high cell density, economical production, and ease of manipulation. Here we report a simplified, systematically developed robust strategy from small-scale screening to large-scale over-expression of human integral membrane proteins in the mammalian expression system for structural studies. This methodology streamlines small-scale screening of several different constructs utilizing fluorescence size-exclusion chromatography (FSEC) towards optimization of buffer, additives, and detergents for achieving stability and homogeneity. This is followed by the generation of stable clonal cell lines expressing desired constructs, and lastly large-scale expression for crystallization. These techniques are designed to rapidly advance the structural studies of eukaryotic integral membrane proteins including that of human membrane proteins. PMID:27485338

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

    PubMed Central

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

    2016-01-01

    Massively parallel sequencing is rapidly emerging as an efficient way to quantify biodiversity at all levels, from genetic variation and expression to ecological community assemblage. However, the number of reads produced per sequencing run far exceeds the number required per sample for many applications, compelling researchers to sequence multiple samples per run in order to maximize efficiency. For studies that include a PCR step, this can be accomplished using primers that include an index sequence allowing sample origin to be determined after sequencing. The use of indexed primers assumes they behave no differently than standard primers; however, we found that indexed primers cause substantial template sequence-specific bias, resulting in radically different profiles of the same environmental sample. Likely the outcome of differential amplification efficiency due to primer-template mismatch, two indexed primer sets spuriously change the inferred sequence abundance from the same DNA extraction by up to 77.1%. We demonstrate that a double PCR approach alleviates these effects in applications where indexed primers are necessary. PMID:26950069

  18. An Infrared Study of the Large-Scale Jet in Quasar PKS 1136-135

    SciTech Connect

    Uchiyama, Yasunobu; Urry, C.Megan; Coppi, Paolo; Van Duyne, Jeffrey; Cheung, C.C.; Sambruna, Rita M.; Takahashi, Tadayuki; Tavecchio, Fabrizio; Maraschi, Laura; /Brera Observ.

    2007-03-16

    We present Spitzer IRAC imaging of the large-scale jet in the quasar PKS 1136-135 at wavelengths of 3.6 and 5.8 {micro}m, combined with previous VLA, HST, and Chandra observations. We clearly detect infrared emission from the jet, resulting in the most detailed multifrequency data among the jets in lobe-dominated quasars. The spectral energy distributions of the jet knots have significant variations along the jet, like the archetypal jet in 3C 273. The infrared measurements with IRAC are consistent with the previous idea that the jet has two spectral components, namely (1) the low-energy synchrotron spectrum extending from radio to infrared, and (2) the high-energy component responsible for the X-ray flux. The optical fluxes may be a mixture of the two components. We consider three radiation models for the high-energy component: inverse Compton scattering of cosmic microwave background (CMB) photons by radio-emitting electrons in a highly relativistic jet, synchrotron radiation by a second distinct electron population, and synchrotron radiation by ultra high energy protons. Each hypothesis leads to important insights into and constraints on particle acceleration in the jet, as well as the basic physical properties of the jet such as bulk velocity, transporting power, and particle contents.

  19. Infrared study of large scale h-BN film and graphene/h-BN heterostructure

    NASA Astrophysics Data System (ADS)

    Yu, Kwangnam; Kim, Jiho; Lee, Chul; Jang, A.-Rang; Shin, Hyeon Suk; Kim, Keun Soo; Yu, Young-Jun; Choi, E. J.

    2016-06-01

    We synthesize a series of CVD h-BN films and perform critical infrared spectroscopic characterization. For high-temperature (HT, Temp = 1400 °C) grown h-BN thin film, only E1 u -mode infrared phonon is activated demonstrating highly aligned 2D h-BN planes over large area, whereas low-temperature (LT, Temp = 1000 °C) grown film shows two phonon peaks, E1 u and A2 u , due to stacking of h-BN plane at tilted angle. For CVD graphene transferred on HT h-BN/SiO2/Si substrate, interband transition spectrum σ1 shifts strongly to lower energy compared with that on LT h-BN/SiO2/Si and on bare SiO2/Si substrates, revealing that the residual carrier density n in graphene is suppressed by the use of HT h-BN layer. Also, the interband transition width of σ1 defined by effective temperature is reduced from 400 K for G/SiO2/Si to 300 K for HT h-BN/SiO2/Si. The behaviors of n and effective temperature show that the HT h-BN film can decouple CVD graphene from the impurity and defect of SiO2 leading to a large scale free-standing like graphene.

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

    SciTech Connect

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

    2011-09-21

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

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

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

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

    PubMed

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

    2015-07-27

    Large-scale databases are important sources of training sets for various QSAR modeling approaches. Generally, these databases contain information extracted from different sources. This variety of sources can produce inconsistency in the data, defined as sometimes widely diverging activity results for the same compound against the same target. Because such inconsistency can reduce the accuracy of predictive models built from these data, we are addressing the question of how best to use data from publicly and commercially accessible databases to create accurate and predictive QSAR models. We investigate the suitability of commercially and publicly available databases to QSAR modeling of antiviral activity (HIV-1 reverse transcriptase (RT) inhibition). We present several methods for the creation of modeling (i.e., training and test) sets from two, either commercially or freely available, databases: Thomson Reuters Integrity and ChEMBL. We found that the typical predictivities of QSAR models obtained using these different modeling set compilation methods differ significantly from each other. The best results were obtained using training sets compiled for compounds tested using only one method and material (i.e., a specific type of biological assay). Compound sets aggregated by target only typically yielded poorly predictive models. We discuss the possibility of "mix-and-matching" assay data across aggregating databases such as ChEMBL and Integrity and their current severe limitations for this purpose. One of them is the general lack of complete and semantic/computer-parsable descriptions of assay methodology carried by these databases that would allow one to determine mix-and-matchability of result sets at the assay level. PMID:26046311

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

    NASA Astrophysics Data System (ADS)

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

    1996-09-01

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

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

    PubMed

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

    2012-11-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

    Brese, Falk; Mirazchiyski, Plamen

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2012-09-01

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

  9. Large-Scale Development of Gene-Associated Single-Nucleotide Polymorphism Markers for Molluscan Population Genomic, Comparative Genomic, and Genome-Wide Association Studies

    PubMed Central

    Jiao, Wenqian; Fu, Xiaoteng; Li, Jinqin; Li, Ling; Feng, Liying; Lv, Jia; Zhang, Lu; Wang, Xiaojian; Li, Yangping; Hou, Rui; Zhang, Lingling; Hu, Xiaoli; Wang, Shi; Bao, Zhenmin

    2014-01-01

    Mollusca is the second most diverse group of animals in the world. Despite their perceived importance, omics-level studies have seldom been applied to this group of animals largely due to a paucity of genomic resources. Here, we report the first large-scale gene-associated marker development and evaluation for a bivalve mollusc, Chlamys farreri. More than 21,000 putative single-nucleotide polymorphisms (SNPs) were identified from the C. farreri transcriptome. Primers and probes were designed and synthesized for 4500 SNPs, and 1492 polymorphic markers were successfully developed using a high-resolution melting genotyping platform. These markers are particularly suitable for population genomic analysis due to high polymorphism within and across populations, a low frequency of null alleles, and conformation to neutral expectations. Unexpectedly, high cross-species transferability was observed, suggesting that the transferable SNPs may largely represent ancestral genetic variations that have been preserved differentially among subfamilies of Pectinidae. Gene annotations were available for 73% of the markers, and 65% could be anchored to the recently released Pacific oyster genome. Large-scale association analysis revealed key candidate genes responsible for scallop growth regulation, and provided markers for further genetic improvement of C. farreri in breeding programmes. PMID:24277739

  10. A rat genetic map constructed by representational difference analysis markers with suitability for large-scale typing.

    PubMed Central

    Toyota, M; Canzian, F; Ushijima, T; Hosoya, Y; Kuramoto, T; Serikawa, T; Imai, K; Sugimura, T; Nagao, M

    1996-01-01

    Representational difference analysis (RDA) was applied to isolate chromosomal markers in the rat. Four series of RDA [restriction enzymes, BamHI and HindIII; subtraction of ACI/N (ACI) amplicon from BUF/Nac (BUF) amplicon and vice versa] yielded 131 polymorphic markers; 125 of these markers were mapped to all chromosomes except for chromosome X. This was done by using a mapping panel of 105 ACI x BUF F2 rats. To complement the relative paucity of chromosomal markers in the rat, genetically directed RDA, which allows isolation of polymorphic markers in the specific chromosomal region, was performed. By changing the F2 driver-DNA allele frequency around the region, four markers were isolated from the D1Ncc1 locus. Twenty-five of 27 RDA markers were informative regarding the dot blot analysis of amplicons, hybridizing only with tester amplicons. Dot blot analysis at a high density per unit of area made it possible to process a large number of samples. Quantitative trait loci can now be mapped in the rat genome by processing a large number of samples with RDA markers and then by isolating markers close to the loci of interest by genetically directed RDA. Images Fig. 1 Fig. 3 Fig. 4 PMID:8632989

  11. Identification of Genes Important for Cutaneous Function Revealed by a Large Scale Reverse Genetic Screen in the Mouse

    PubMed Central

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

    2014-01-01

    The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP). A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1), while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1). The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation. PMID:25340873

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

    NASA Astrophysics Data System (ADS)

    Böhringer, Hans; Chon, Gayoung

    2016-07-01

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

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

    USGS Publications Warehouse

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

    2005-01-01

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

  14. Genetic Diversity and Ecological Niche Modelling of Wild Barley: Refugia, Large-Scale Post-LGM Range Expansion and Limited Mid-Future Climate Threats?

    PubMed Central

    Russell, Joanne; van Zonneveld, Maarten; Dawson, Ian K.; Booth, Allan; Waugh, Robbie; Steffenson, Brian

    2014-01-01

    Describing genetic diversity in wild barley (Hordeum vulgare ssp. spontaneum) in geographic and environmental space in the context of current, past and potential future climates is important for conservation and for breeding the domesticated crop (Hordeum vulgare ssp. vulgare). Spatial genetic diversity in wild barley was revealed by both nuclear- (2,505 SNP, 24 nSSR) and chloroplast-derived (5 cpSSR) markers in 256 widely-sampled geo-referenced accessions. Results were compared with MaxEnt-modelled geographic distributions under current, past (Last Glacial Maximum, LGM) and mid-term future (anthropogenic scenario A2, the 2080s) climates. Comparisons suggest large-scale post-LGM range expansion in Central Asia and relatively small, but statistically significant, reductions in range-wide genetic diversity under future climate. Our analyses support the utility of ecological niche modelling for locating genetic diversity hotspots and determine priority geographic areas for wild barley conservation under anthropogenic climate change. Similar research on other cereal crop progenitors could play an important role in tailoring conservation and crop improvement strategies to support future human food security. PMID:24505252

  15. Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days

    PubMed Central

    Aubry, Fabien; Gould, Ernest A.; de Lamballerie, Xavier

    2016-01-01

    Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re-encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re-encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines. PMID:27548676

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    DOE PAGESBeta

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

    2016-07-26

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

  18. Submarine ridges do not prevent large-scale dispersal of abyssal fauna: A case study of Mesocletodes (Crustacea, Copepoda, Harpacticoida)

    NASA Astrophysics Data System (ADS)

    Menzel, Lena; George, Kai Horst; Arbizu, Pedro Martínez

    2011-08-01

    We examined the large-scale distribution of deep-sea harpacticoid copepods at the species level, in order to clarify the underlying processes of copepod dispersal. The study was based on samples collected from 12 regions and a total of 113 stations: 57 stations at depths between 1107 and 5655 m on abyssal plains in the South and North Atlantic, Southern Ocean, southern Indian Ocean, and the Pacific Ocean, and 56 stations above 900 m in the North Atlantic and eastern Mediterranean Sea. We chose the genus Mesocletodes Sars, 1909 as an ideal group to study the large-scale distribution of harpacticoid copepods in the deep oceans. Clear apomorphies and a comparatively large body size of about 1 mm allow rapid recognition of allied species in meiofauna samples. In addition, Mesocletodes represents more than 50% of the family Argestidae Por, 1986, one of the most abundant harpacticoid families in the deep sea. The geographical distributions of 793 adult females of Mesocletodes belonging to 61 species throughout the South and North Atlantic, Southern Ocean, southern Indian Ocean, Pacific Ocean, and eastern Mediterranean Sea indicated that most species are cosmopolitan. Neither the topography of the sea bottom nor long distances seem to prevent species from dispersing. Passive transport by bottom currents after resuspension is likely the propulsive factor for the dispersal of Harpacticoida, while plate tectonics and movement of individuals in the sediment may play relatively minor roles.

  19. Development of Residential Prototype Building Models and Analysis System for Large-Scale Energy Efficiency Studies Using EnergyPlus

    SciTech Connect

    Mendon, Vrushali V.; Taylor, Zachary T.

    2014-09-10

    ABSTRACT: Recent advances in residential building energy efficiency and codes have resulted in increased interest in detailed residential building energy models using the latest energy simulation software. One of the challenges of developing residential building models to characterize new residential building stock is to allow for flexibility to address variability in house features like geometry, configuration, HVAC systems etc. Researchers solved this problem in a novel way by creating a simulation structure capable of creating fully-functional EnergyPlus batch runs using a completely scalable residential EnergyPlus template system. This system was used to create a set of thirty-two residential prototype building models covering single- and multifamily buildings, four common foundation types and four common heating system types found in the United States (US). A weighting scheme with detailed state-wise and national weighting factors was designed to supplement the residential prototype models. The complete set is designed to represent a majority of new residential construction stock. The entire structure consists of a system of utility programs developed around the core EnergyPlus simulation engine to automate the creation and management of large-scale simulation studies with minimal human effort. The simulation structure and the residential prototype building models have been used for numerous large-scale studies, one of which is briefly discussed in this paper.

  20. Stormbow: A Cloud-Based Tool for Reads Mapping and Expression Quantification in Large-Scale RNA-Seq Studies

    PubMed Central

    Zhao, Shanrong; Prenger, Kurt; Smith, Lance

    2013-01-01

    RNA-Seq is becoming a promising replacement to microarrays in transcriptome profiling and differential gene expression study. Technical improvements have decreased sequencing costs and, as a result, the size and number of RNA-Seq datasets have increased rapidly. However, the increasing volume of data from large-scale RNA-Seq studies poses a practical challenge for data analysis in a local environment. To meet this challenge, we developed Stormbow, a cloud-based software package, to process large volumes of RNA-Seq data in parallel. The performance of Stormbow has been tested by practically applying it to analyse 178 RNA-Seq samples in the cloud. In our test, it took 6 to 8 hours to process an RNA-Seq sample with 100 million reads, and the average cost was $3.50 per sample. Utilizing Amazon Web Services as the infrastructure for Stormbow allows us to easily scale up to handle large datasets with on-demand computational resources. Stormbow is a scalable, cost effective, and open-source based tool for large-scale RNA-Seq data analysis. Stormbow can be freely downloaded and can be used out of box to process Illumina RNA-Seq datasets. PMID:25937948

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

    ERIC Educational Resources Information Center

    Byrnes, Vaughan; Ruby, Allen

    2007-01-01

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

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

    ERIC Educational Resources Information Center

    Kaspar, Roman; Hartig, Johannes

    2016-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    ERIC Educational Resources Information Center

    De Winter, Joeri; Wagemans, Johan

    2006-01-01

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

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

    ERIC Educational Resources Information Center

    Stains, Marilyne; Sevian, Hannah

    2015-01-01

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

  8. Study of the high energy Cosmic Rays large scale anisotropies with the ANTARES neutrino telescope

    NASA Astrophysics Data System (ADS)

    Illuminati, Giulia

    2016-02-01

    We present the analysis method used to search for an anisotropy in the high energy Cosmic Rays arrival distribution using data collected by the ANTARES telescope. ANTARES is a neutrino detector, where the collected data are dominated by a large background of cosmic ray muons. Therefore, the background data are suitable for high-statistics studies of cosmic rays in the Northern sky. The main challenge for this analysis is accounting for those effects which can mimic an apparent anisotropy in the muon arrival direction: the detector exposure asymmetries, non-uniform time coverage, diurnal and seasonal variation of the atmospheric temperature. Once all these effects have been corrected, a study of the anisotropy profiles along the right ascension can be performed.

  9. Large scale dynamic systems

    NASA Technical Reports Server (NTRS)

    Doolin, B. F.

    1975-01-01

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

  10. Study of an engine flow diverter system for a large scale ejector powered aircraft model

    NASA Technical Reports Server (NTRS)

    Springer, R. J.; Langley, B.; Plant, T.; Hunter, L.; Brock, O.

    1981-01-01

    Requirements were established for a conceptual design study to analyze and design an engine flow diverter system and to include accommodations for an ejector system in an existing 3/4 scale fighter model equipped with YJ-79 engines. Model constraints were identified and cost-effective limited modification was proposed to accept the ejectors, ducting and flow diverter valves. Complete system performance was calculated and a versatile computer program capable of analyzing any ejector system was developed.

  11. Weather and headache onset: a large-scale study of headache medicine purchases

    NASA Astrophysics Data System (ADS)

    Ozeki, Kayoko; Noda, Tatsuya; Nakamura, Mieko; Ojima, Toshiyuki

    2015-04-01

    It is widely recognized that weather changes can trigger headache onset. Most people who develop headaches choose to self-medicate rather than visit a hospital or clinic. We investigated the association between weather and headache onset using large-sample sales of the headache medicine, loxoprofen. We collected daily sales figures of loxoprofen and over-the-counter drugs over a 1-year period from a drugstore chain in western Shizuoka prefecture, Japan. To adjust for changes in daily sales of loxoprofen due to social environmental factors, we calculated a proportion of loxoprofen daily sales to over-the-counter drug daily sales. At the same time, we obtained weather data for the study region from the website of the Japan Meteorological Agency. We performed linear regression analysis to ascertain the association between weather conditions and the loxoprofen daily sales proportion. We also conducted a separate questionnaire survey at the same drugstores to determine the reason why people purchased loxoprofen. Over the study period, we surveyed the sale of hundreds of thousands of loxoprofen tablets. Most people purchased loxoprofen because they had a headache. We found that the sales proportion of loxoprofen increased when average barometric pressure decreased, and that precipitation, average humidity, and minimum humidity increased on loxoprofen purchase days compared to the previous day of purchases. This study, performed using a large dataset that was easy-to-collect and representative of the general population, revealed that sales of loxoprofen, which can represent the onset and aggravation of headache, significantly increased with worsening weather conditions.

  12. User Friendly Open GIS Tool for Large Scale Data Assimilation - a Case Study of Hydrological Modelling

    NASA Astrophysics Data System (ADS)

    Gupta, P. K.

    2012-08-01

    Open source software (OSS) coding has tremendous advantages over proprietary software. These are primarily fuelled by high level programming languages (JAVA, C++, Python etc...) and open source geospatial libraries (GDAL/OGR, GEOS, GeoTools etc.). Quantum GIS (QGIS) is a popular open source GIS package, which is licensed under GNU GPL and is written in C++. It allows users to perform specialised tasks by creating plugins in C++ and Python. This research article emphasises on exploiting this capability of QGIS to build and implement plugins across multiple platforms using the easy to learn - Python programming language. In the present study, a tool has been developed to assimilate large spatio-temporal datasets such as national level gridded rainfall, temperature, topographic (digital elevation model, slope, aspect), landuse/landcover and multi-layer soil data for input into hydrological models. At present this tool has been developed for Indian sub-continent. An attempt is also made to use popular scientific and numerical libraries to create custom applications for digital inclusion. In the hydrological modelling calibration and validation are important steps which are repetitively carried out for the same study region. As such the developed tool will be user friendly and used efficiently for these repetitive processes by reducing the time required for data management and handling. Moreover, it was found that the developed tool can easily assimilate large dataset in an organised manner.

  13. Infrared and Raman screening of seized novel psychoactive substances: a large scale study of >200 samples.

    PubMed

    Jones, L E; Stewart, A; Peters, K L; McNaul, M; Speers, S J; Fletcher, N C; Bell, S E J

    2016-02-01

    The potential of IR absorption and Raman spectroscopy for rapid identification of novel psychoactive substances (NPS) has been tested using a set of 221 unsorted seized samples suspected of containing NPS. Both IR and Raman spectra showed large variation between the different sub-classifications of NPS and smaller, but still distinguishable, differences between closely related compounds within the same class. In initial tests, screening the samples using spectral searching against a limited reference library allowed only 41% of the samples to be fully identified. The limiting factor in the identification was the large number of active compounds in the seized samples for which no reference vibrational data were available in the libraries rather than poor spectral quality. Therefore, when 33 of these compounds were independently identified by NMR and mass spectrometry and their spectra used to extend the libraries, the percentage of samples identified by IR and Raman screening alone increased to 76%, with only 7% of samples having no identifiable constituents. This study, which is the largest of its type ever carried out, therefore demonstrates that this approach of detecting non-matching samples and then identifying them using standard analytical methods has considerable potential in NPS screening since it allows rapid identification of the constituents of the majority of street quality samples. Only one complete feedback cycle was carried out in this study but there is clearly the potential to carry out continuous identification/updating when this system is used in operational settings. PMID:26779571

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

    NASA Astrophysics Data System (ADS)

    Stains, Marilyne; Sevian, Hannah

    2015-12-01

    Students' mental models of diffusion in a gas phase solution were studied through the use of the Structure and Motion of Matter (SAMM) survey. This survey permits identification of categories of ways students think about the structure of the gaseous solute and solvent, the origin of motion of gas particles, and trajectories of solute particles in the gaseous medium. A large sample of data ( N = 423) from students across grade 8 (age 13) through upper-level undergraduate was subjected to a cluster analysis to determine the main mental models present. The cluster analysis resulted in a reduced data set ( N = 308), and then, mental models were ascertained from robust clusters. The mental models that emerged from analysis were triangulated through interview data and characterised according to underlying implicit assumptions that guide and constrain thinking about diffusion of a solute in a gaseous medium. Impacts of students' level of preparation in science and relationships of mental models to science disciplines studied by students were examined. Implications are discussed for the value of this approach to identify typical mental models and the sets of implicit assumptions that constrain them.

  15. Study on the sensing performance of OFBG under large-scale negative strain

    NASA Astrophysics Data System (ADS)

    Wang, Chuan; Hu, Qingli; Ou, Jinping

    2010-03-01

    As a new and sensitive sensing element, OFBG(Optical Fiber Bragg Grating) has been widely used in aerospace engineering and civil engineering. The sensing mechanism and properties have been widely studied by lots of researchers, but the sensing properties of OFBG under large negative strain are still destitute. In this paper, with the aids of large shrinkage performance of PP(polypropylene) during its curing, we gained about -13000 μɛ's strain changes by embeding bare OFBG inside the PP bar to study the sensing properties of OFBG in this strain level. The results show that OFBG can remain its sensing properties well---- linearity, repeatability and the shape of centre wavelength are both reasonably. And the strain sensitivity coefficient of PP-OFBG is about 0.85 pm/μɛ, this is very near with that of calculating results considering strain transmission between PP and OFBG. Which are all helpful and useful for further use of OFBG in other applications.

  16. Large scale prop-fan structural design study. Volume 1: Initial concepts

    NASA Technical Reports Server (NTRS)

    Billman, L. C.; Gruska, C. J.; Ladden, R. M.; Leishman, D. K.; Turnberg, J. E.

    1988-01-01

    In recent years, considerable attention has been directed toward improving aircraft fuel consumption. Studies have shown that the inherent efficiency advantage that turboprop propulsion systems have demonstrated at lower cruise speeds may now be extended to the higher speeds of today's turbofan and turbojet-powered aircraft. To achieve this goal, new propeller designs will require features such as thin, high speed airfoils and aerodynamic sweep, features currently found only in wing designs for high speed aircraft. This is Volume 1 of a 2 volume study to establish structural concepts for such advanced propeller blades, to define their structural properties, to identify any new design, analysis, or fabrication techniques which were required, and to determine the structural tradeoffs involved with several blade shapes selected primarily on the basis of aero/acoustic design considerations. The feasibility of fabricating and testing dynamically scaled models of these blades for aeroelastic testing was also established. The preliminary design of a blade suitable for flight use in a testbed advanced turboprop was conducted and is described in Volume 2.

  17. Large scale prop-fan structural design study. Volume 2: Preliminary design of SR-7

    NASA Technical Reports Server (NTRS)

    Billman, L. C.; Gruska, C. J.; Ladden, R. M.; Leishman, D. K.; Turnberg, J. E.

    1988-01-01

    In recent years, considerable attention has been directed toward improving aircraft fuel consumption. Studies have shown that the inherent efficiency advantage that turboprop propulsion systems have demonstrated at lower cruise speeds may now be extended to the higher speeds of today's turbofan and turbojet-powered aircraft. To achieve this goal, new propeller designs will require features such as thin, high speed airfoils and aerodynamic sweep, features currently found only in wing designs for high speed aircraft. This is Volume 2 of a 2 volume study to establish structural concepts for such advanced propeller blades, to define their structural properties, to identify any new design, analysis, or fabrication techniques which were required, and to determine the structural tradeoffs involved with several blade shapes selected primarily on the basis of aero/acoustic design considerations. The feasibility of fabricating and testing dynamically scaled models of these blades for aeroelastic testing was also established. The preliminary design of a blade suitable for flight use in a testbed advanced turboprop was conducted and is described.

  18. A comparative study of all-vanadium and iron-chromium redox flow batteries for large-scale energy storage

    NASA Astrophysics Data System (ADS)

    Zeng, Y. K.; Zhao, T. S.; An, L.; Zhou, X. L.; Wei, L.

    2015-12-01

    The promise of redox flow batteries (RFBs) utilizing soluble redox couples, such as all vanadium ions as well as iron and chromium ions, is becoming increasingly recognized for large-scale energy storage of renewables such as wind and solar, owing to their unique advantages including scalability, intrinsic safety, and long cycle life. An ongoing question associated with these two RFBs is determining whether the vanadium redox flow battery (VRFB) or iron-chromium redox flow battery (ICRFB) is more suitable and competitive for large-scale energy storage. To address this concern, a comparative study has been conducted for the two types of battery based on their charge-discharge performance, cycle performance, and capital cost. It is found that: i) the two batteries have similar energy efficiencies at high current densities; ii) the ICRFB exhibits a higher capacity decay rate than does the VRFB; and iii) the ICRFB is much less expensive in capital costs when operated at high power densities or at large capacities.

  19. Efficient and large scale synthesis of graphene from coal and its film electrical properties studies.

    PubMed

    Wu, Yingpeng; Ma, Yanfeng; Wang, Yan; Huang, Lu; Li, Na; Zhang, Tengfei; Zhang, Yi; Wan, Xiangjian; Huang, Yi; Chen, Yongsheng

    2013-02-01

    Coal, which is abundant and has an incompact structure, is a good candidate to replace graphite as the raw material for the production of graphene. Here, a new solution phase technique for the preparation of graphene from coal has been developed. The precursor: graphene oxide got from coal was examined by atomic force microscopy, dynamic light scattering and X-ray diffraction, the results showed the GO was a small and single layer sheet. The graphene was examined by X-ray photoelectron spectroscopy, and Raman spectroscopy. Furthermore, graphene films have been prepared using direct solution process and the electrical conductivity and Hall effect have been studied. The results showed the conductivity of the films could reach as high as 2.5 x 10(5) Sm(-1) and exhibited an n-type behavior. PMID:23646544

  20. Atmospheric pressure photoionization as a powerful tool for large-scale lipidomic studies.

    PubMed

    Gaudin, Mathieu; Imbert, Laurent; Libong, Danielle; Chaminade, Pierre; Brunelle, Alain; Touboul, David; Laprévote, Olivier

    2012-05-01

    Lipidomic studies often use liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) for separation, identification, and quantification. However, due to the wide structural diversity of lipids, the most apolar part of the lipidome is often detected with low sensitivity in ESI. Atmospheric pressure (APPI) can be an alternative ionization source since normal-phase solvents are known to enhance photoionization of these classes. In this paper, we intend to show the efficiency of APPI to identify different lipid classes, with a special interest on sphingolipids. In-source APPI fragmentation appears to be an added value for the structural analysis of lipids. It provides a detailed characterization of both the polar head and the non polar moiety of most lipid classes, and it makes possible the detection of all lipids in both polarities, which is not always possible with ESI. PMID:22359092

  1. The relationship between religiosity and cardiovascular risk factors in Japan: a large-scale cohort study.

    PubMed

    Kobayashi, Daiki; Shimbo, Takuro; Takahashi, Osamu; Davis, Roger B; Wee, Christina C

    2015-07-01

    The goal of this study was to examine the relationship between religiosity and cardiovascular risk factors in a Japanese population. A retrospective cohort study was conducted involving individuals who underwent annual health check-ups at St. Luke's International Hospital from 2005 to 2010. Data collected included self-reported demographics, clinical information, and health habits, as well as religiosity, baseline examination, and laboratory measures. We conducted multivariable regression analyses to examine the associations between religiosity and cardiovascular risk factors at baseline and longitudinally. The analyses were performed in 2012. A total of 36,965 participants were enrolled, and 13,846 (37.8%) reported being at least somewhat religious. Compared with those who were not religious at baseline, religious participants (n = 3685) were less likely to be current smokers (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.53-0.67) and to report excessive alcohol consumption (OR, 0.74; 95% CI, 0.67-0.82), and more likely to exercise at least three times a week (OR, 1.27; 95% CI,1.16-1.39) and to be obese (OR, 1.32; 95% CI, 1.19-1.47). There were no significant differences in the rate of hypertension, diabetes mellitus, or dyslipidemia prevalence. In longitudinal data analyses, religiosity was associated with a lower likelihood of smoking and excessive alcohol consumption, and a higher likelihood of regular exercise and a lower incidence of diabetes over time. Individuals who were more religious were significantly more likely to have favorable health habits and fewer cardiovascular risk factors, except for a higher prevalence of overweight/obesity at baseline. Religiosity was also associated with better health habits over time and less likely to be associated with future diabetes but not with blood pressure or lipid levels. PMID:26188400

  2. A large-scale study of CAPE-based mass-flux closures and precipitation

    NASA Astrophysics Data System (ADS)

    Jeevanjee, N.; Romps, D. M.; Sugioka, K.

    2013-12-01

    A popular way to close mass-flux-based deep-convective parameterizations is to assume that convective available potential energy (CAPE) is consumed by convection on some fixed time-scale. Such schemes predict that cloud-base mass fluxes, and hence precipitation rates, are tightly correlated with CAPE values. Previous studies, which have found this prediction unrealistic, have typically tested it by running global circulation models in single-column mode, forced by data from highly localized observational campaigns. Here, we extend these studies by using data from 50 radiosonde stations across the continental US, along with comprehensive radar/rain gauge US precipitation data. We compare correlations between CAPE and precipitation in these observations to that produced by the Community Atmosphere Model (CAM) 5.1, which uses a CAPE-based mass-flux closure. Our results strongly reinforce the finding that such closures predict unrealistically tight temporal correlations between CAPE and precipitation, at least on hourly time scales. If we perform a seasonal average, however, we find that the spatial correlation between seasonal-mean CAPE and precipitation predicted by CAM's convection scheme is reasonably well borne-out by observations. This may help account for the longevity of these otherwise problematic parameterizations. R-values between observed CAPE and precipitation time series for JJA 2011 for 48 radiosonde sites around CONUS. No discernible correlation is evident at any location R-values between model ouput CAPE and precipitation time series for JJA 2011 for 48 locations around CONUS. Note high correlation in most locations.

  3. Treatability studies and large-scale treatment of aqueous mixed waste containing heavy metals

    SciTech Connect

    Haefner, D.R.

    1995-12-01

    Wastes have accumulated at the Idaho National Engineering Laboratory through routine laboratory practices, experimental engineering operations, and decommissioning and decontamination of nuclear reactor facilities. A storage tank at the Test Area North held approximately 129,000 L of acidic wastewater and contained prohibited levels of lead and mercury. Radioactive constituents were also present; the most predominant being radiocesium Cs-137 and radiocobalt Co-60. Bench-scale studio were undertaken to evaluate ion exchange as a means of removing the contaminants. A set of breakthrough curves was obtained and identified capacity constraints, selectivities, and operating requirements of candidate resins. Treatment studies indicated that Purolite S-920 resin could effectively remove mercury, while Rohm and Haas` Amberlite 200-CH was used for lead and radionuclide removal. Based on these laboratory tests a full-scale facility, using multiple ion exchange columns, was designed and operated in the spring of 1994. The liquid effluents were discharged to an onsite evaporation pond and met RCRA disposal limits for hazardous metals and self-imposed radionuclide limits. All secondary wastes and residues were sampled and subjected to the to)dc characteristic leaching procedure. The resulting leachate concentrations were below RCRA discharge limits and, therefore, these will be disposed of at the onsite low-level disposal facility. After concluding the tank wastewater operations, enough reserve resin capacity was available to treat three additional mixed wastes residing onsite. These totaled about 1,900 L (500 gal) and contained prohibited levels of chromium, cadmium, and barium. Laboratory studies demonstrated that these heavy metals could also be removed by the existing resins. Treatment was performed at the full-scale facility with the effluents discharged to the evaporation pond.

  4. Study of fog in Bulgaria by using the GNSS tropospheric products and large scale dynamic analysis

    NASA Astrophysics Data System (ADS)

    Stoycheva, A.; Guerova, G.

    2015-10-01

    The fog formation, development, and dissipation are studied by employing the synergy between surface observations and vertically Integrated Water Vapor (IWV) from Global Navigation Satellite Systems (GNSS). Selected are three fog cases in February and November 2012 and the fog development in 4 locations in north Bulgaria is analysed. It is found that the IWV tends to decrease during fog formation, and densification. Increase of IWV leads to fog dispersion and can be a result of evaporation or advection of new humid air mass. The mixing ratio also decreases during the fog formation and increases during dissipation but has a distinct diurnal variability, which limits its short range forecasting potential. IWV is found to have a very high sensitivity to both air mass transformation and/or advection at altitude. In one case it is found that the arrival time of a new air mass at altitude is of key importance for further fog development or suppression. The change of the air mass leads to change of the diurnal cycle of surface parameters like temperature thus controlling the fog life cycle. Further complication of fog diagnosis is introduced by a dynamic component, reflecting the orography difference in west and east part of Bulgaria. The behaviour of the IWV and mixing ratio can be a valuable additional tool in decision making processes for very short range fog diagnosis and prognosis. For monitoring fog life cycle hourly or sub-hourly data-sets will be an advantage.

  5. Emotional competencies in geriatric nursing: empirical evidence from a computer based large scale assessment calibration study.

    PubMed

    Kaspar, Roman; Hartig, Johannes

    2016-03-01

    The care of older people was described as involving substantial emotion-related affordances. Scholars in vocational training and nursing disagree whether emotion-related skills could be conceptualized and assessed as a professional competence. Studies on emotion work and empathy regularly neglect the multidimensionality of these phenomena and their relation to the care process, and are rarely conclusive with respect to nursing behavior in practice. To test the status of emotion-related skills as a facet of client-directed geriatric nursing competence, 402 final-year nursing students from 24 German schools responded to a 62-item computer-based test. 14 items were developed to represent emotion-related affordances. Multi-dimensional IRT modeling was employed to assess a potential subdomain structure. Emotion-related test items did not form a separate subdomain, and were found to be discriminating across the whole competence continuum. Tasks concerning emotion work and empathy are reliable indicators for various levels of client-directed nursing competence. Claims for a distinct emotion-related competence in geriatric nursing, however, appear excessive with a process-oriented perspective. PMID:26108300

  6. Large-Scale Overexpression and Purification of ADARs from Saccharomyces cerevisiae for Biophysical and Biochemical Studies

    PubMed Central

    Macbeth, Mark R.; Bass, Brenda L.

    2008-01-01

    Many biochemical and biophysical analyses of enzymes require quantities of protein that are difficult to obtain from expression in an endogenous system. To further complicate matters, native adenosine deaminases that act on RNA (ADARs) are expressed at very low levels, and overexpression of active protein has been unsuccessful in common bacterial systems. Here we describe the plasmid construction, expression, and purification procedures for ADARs overexpressed in the yeast Saccharomyces cerevisiae. ADAR expression is controlled by the Gal promoter, which allows for rapid induction of transcription when the yeast are grown in media containing galactose. The ADAR is translated with an N-terminal histidine tag that is cleaved by the tobacco etch virus protease, generating one nonnative glycine residue at the N-terminus of the ADAR protein. ADARs expressed using this system can be purified to homogeneity, are highly active in deaminating RNA, and are produced in quantities (from 3 to 10 mg of pure protein per liter of yeast culture) that are sufficient for most biophysical studies. PMID:17662848

  7. An HST Proper-motion Study of the Large-scale Jet of 3C273

    NASA Astrophysics Data System (ADS)

    Meyer, Eileen T.; Sparks, William B.; Georganopoulos, Markos; Anderson, Jay; van der Marel, Roeland; Biretta, John; Sohn, Sangmo Tony; Chiaberge, Marco; Perlman, Eric; Norman, Colin

    2016-02-01

    The radio galaxy 3C 273 hosts one of the nearest and best-studied powerful quasar jets. Having been imaged repeatedly by the Hubble Space Telescope (HST) over the past twenty years, it was chosen for an HST program to measure proper motions in the kiloparsec-scale resolved jets of nearby radio-loud active galaxies. The jet in 3C 273 is highly relativistic on sub-parsec scales, with apparent proper motions up to 15c observed by very long baseline interferometry. In contrast, we find that the kiloparsec-scale knots are compatible with being stationary, with a mean speed of -0.2 ± 0.5c over the whole jet. Assuming the knots are packets of moving plasma, an upper limit of 1c implies a bulk Lorentz factor Γ < 2.9. This suggests that the jet has either decelerated significantly by the time it reaches the kiloparsec scale, or that the knots in the jet are standing shock features. The second scenario is incompatible with the inverse Compton off the Cosmic Microwave Background (IC/CMB) model for the X-ray emission of these knots, which requires the knots to be in motion, but IC/CMB is also disfavored in the first scenario due to energetic considerations, in agreement with the recent finding of Meyer & Georganopoulos which ruled out the IC/CMB model for the X-ray emission of 3C 273 via gamma-ray upper limits.

  8. Determinants of brominated flame retardants in breast milk from a large scale Norwegian study.

    PubMed

    Thomsen, Cathrine; Stigum, Hein; Frøshaug, May; Broadwell, Sharon L; Becher, Georg; Eggesbø, Merete

    2010-01-01

    Brominated flame retardants (BFRs), particularly polybrominated diphenyl ethers (PBDEs), are widely present in human populations. In order to investigate human exposure pathways and associations with socioeconomic and lifestyle factors, 393 breast milk samples from mothers living in various regions throughout Norway were analyzed. Up to ten PBDE congeners were measured in all the samples, hexabromocyclododecane (HBCD) and BDE-209 in subsets of 310 and 46, respectively. The median concentrations of the sum of the seven most prominent PBDEs (BDE-28, 47, 99, 100, 153, 154 and 183), BDE-209 and HBCD were 2.1, 0.32 and 0.86ng/g lipids, respectively. These concentrations are comparable to the levels generally observed in human populations in Europe. The frequency distributions were quite skewed with long tails towards higher concentrations. Maternal age, parity, education, having a cohabitant employed as electrician, and ventilation were factors significantly associated with some of the BFRs, although these factors only explained a small amount of the variability (R(2) 0.04-0.16). The mothers' diet was not found to influence the breast milk PBDE and HBCD levels. Our results show that sources other than the diet are important for the variability seen in breast milk BFR concentrations and that exposure from the indoor atmosphere should be emphasized in future studies. PMID:19889457

  9. A large-scale validation study of the Medication Adherence Rating Scale (MARS).

    PubMed

    Fialko, Laura; Garety, Philippa A; Kuipers, Elizabeth; Dunn, Graham; Bebbington, Paul E; Fowler, David; Freeman, Daniel

    2008-03-01

    Adherence to medication is an important predictor of illness course and outcome in psychosis. The Medication Adherence Rating Scale (MARS) is a ten-item self-report measure of medication adherence in psychosis [Thompson, K., Kulkarni, J., Sergejew, A.A., 2000. Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses. Schizophrenia Research. 42. 241-247]. Although initial results suggested that the scale has good reliability and validity, the development sample was small. The current study aimed to establish the psychometric properties of the MARS in a sample over four times larger. The scale was administered to 277 individuals with psychosis, along with measures of insight and psychopathology. Medication adherence was independently rated by each individual's keyworker. Results showed the internal consistency of the MARS to be lower than in the original sample, though adequate. MARS total score correlated weakly with keyworker-rated adherence, hence concurrent validity of the scale appeared only moderate to weak. The three factor structure of the MARS was replicated. Examination of the factor scores suggested that the factor 1 total score, which corresponds to the Medication Adherence Questionnaire [Morisky,D.E., Green,L.W. and Levine,D.M., 1986. Concurrent and predictive validity of a self-reported measure of medication adherence. Medical Care. 24, 67-74] may be a preferable measure of medication adherence behaviour to the total scale score. PMID:18083007

  10. Clinical prediction from structural brain MRI scans: a large-scale empirical study.

    PubMed

    Sabuncu, Mert R; Konukoglu, Ender

    2015-01-01

    Multivariate pattern analysis (MVPA) methods have become an important tool in neuroimaging, revealing complex associations and yielding powerful prediction models. Despite methodological developments and novel application domains, there has been little effort to compile benchmark results that researchers can reference and compare against. This study takes a significant step in this direction. We employed three classes of state-of-the-art MVPA algorithms and common types of structural measurements from brain Magnetic Resonance Imaging (MRI) scans to predict an array of clinically relevant variables (diagnosis of Alzheimer's, schizophrenia, autism, and attention deficit and hyperactivity disorder; age, cerebrospinal fluid derived amyloid-β levels and mini-mental state exam score). We analyzed data from over 2,800 subjects, compiled from six publicly available datasets. The employed data and computational tools are freely distributed ( https://www.nmr.mgh.harvard.edu/lab/mripredict), making this the largest, most comprehensive, reproducible benchmark image-based prediction experiment to date in structural neuroimaging. Finally, we make several observations regarding the factors that influence prediction performance and point to future research directions. Unsurprisingly, our results suggest that the biological footprint (effect size) has a dramatic influence on prediction performance. Though the choice of image measurement and MVPA algorithm can impact the result, there was no universally optimal selection. Intriguingly, the choice of algorithm seemed to be less critical than the choice of measurement type. Finally, our results showed that cross-validation estimates of performance, while generally optimistic, correlate well with generalization accuracy on a new dataset. PMID:25048627

  11. A New Model for Conducting Large-Scale Aerogeophysical Studies in Antarctica Through International Collaboration

    NASA Astrophysics Data System (ADS)

    Holt, J. W.; Blankenship, D. D.; Peters, M. E.; Vaughan, D. G.; Corr, H. F.

    2006-12-01

    The aerogeophysical surveys of the 1970's conducted by the Scott Polar Research Institute (SPRI), the National Science Foundation (NSF), and the Technical University of Denmark (TUD) were the successful result of an international collaboration to implement geophysical capabilities, primarily ice penetrating radar, onto a long-range aircraft and operate that system in Antarctica for multiple field seasons in a reconnaissance mode. This produced the first continental-scale insights into the Antarctic ice sheet and subglacial geomorphology, and this context made it possible to plan more detailed studies with new geophysical systems. The University of Texas Institute for Geophysics (UTIG) led such an effort through the successful implementation of a multi-instrumented Twin Otter aerogeophysical platform. UTIG, in collaboration with others, modified the 60 MHz TUD radar used in the SPRI/NSF/TUD survey and integrated it with a gravity meter, towed magnetometer, and laser altimeter. First used in 1991, this system later became the basis for the Support Office for Aerogeophysical Research (SOAR), an NSF facility operated by UTIG from 1994 2001. SOAR acquired over 200,000 line-km of data in both East and West Antarctica during seven field seasons. Subsequent to this, UTIG further modified the system, combining components of a coherent, chirped radar built by NASA's Jet Propulsion Laboratory with the TUD high power transmitter. Meanwhile, the British Antarctic Survey (BAS) designed and built a 150 MHz coherent radar system and integrated it into their Twin Otter aerogeophysical platform with gravity meter and wingtip magnetometers. In 2004-05, UTIG and BAS joined forces to conduct the largest single aerogeophysical survey undertaken in Antarctica to date. The target was the Amundsen Sea Embayment, a largely unexplored and scientifically critical area located far from the logistical centers of the US and UK. Both aerogeophysical systems were deployed using two temporary field

  12. Quantifying Uncertainties in Large Scale Water Budget: Case Study in Siberia

    NASA Astrophysics Data System (ADS)

    Joe, S.; Brubaker, K. L.

    2004-12-01

    Assessment and prediction of Arctic River flows' effects on ocean circulation and climate are hindered by lack of knowledge about the terrestial water balance in remote regions. In this study, we quantify the components of the annual water budget for a large Siberian river basin and -- most importantly -- the uncertainty in the components. The water budget for a watershed can be simplified to basic inputs and outputs: Precipitation (P), Streamflow (Q), and Evapotranspiration (E). Over the long term, assuming negligible change in storage, inputs and outputs should balance, P = Q + E. However, errors in measuring and estimating the components lead to a nonzero closure error, CE = P - Q - E. The uncertainty in the water balance can be quantified by the variance of CE, which is equal to the sum of the component variances (assumed independent). The closure error and its variance were estimated for the 57000 km2 Tom River basin (a subbasin of the Ob River) for five water years, 1981- 1985. We hypothesized that (a) the CE would be negative due to underestimation of P by the sparse, low-elevation precipitation network, and (b) statistical hypothesis testing would show that the CE is not significantly different from 0, due to uncertainty in the components. The basin mean and variance of P were estimated by kriging station observations. The annual mean Q was obtained from discharge measurements at Tomsk, Russia; the uncertainty in Q was based on published estimates of rating curve error bars. The basin mean and variance of E were computed from a derived distribution based on Monte Carlo simulation of the Penman Monteith model, driven by measured meteorological data at Tomsk, and accounting for variation in elevation and vegetation. Annual CEs were negative, ranging from -160 to -325 mm, and the standard deviations ranged from 50 to 60 mm. The CE was significantly different from 0 for all five water years, supporting the belief that annual P is underestimated by the gage

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

    PubMed

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

    2015-04-01

    We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10(-40), OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1(∗)04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10(-43)) and HLA-DQα1 47 (p = 4.02 × 10(-46)), 56, and 76 (both p = 1.84 × 10(-45)) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10(-6), OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10(-6), OR = 1.20), and REL (rs115674477, p = 1.10 × 10(-5), OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function. PMID:25817017

  14. A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility

    PubMed Central

    Carmona, F. David; Mackie, Sarah L.; Martín, Jose-Ezequiel; Taylor, John C.; Vaglio, Augusto; Eyre, Stephen; Bossini-Castillo, Lara; Castañeda, Santos; Cid, Maria C.; Hernández-Rodríguez, José; Prieto-González, Sergio; Solans, Roser; Ramentol-Sintas, Marc; González-Escribano, M. Francisca; Ortiz-Fernández, Lourdes; Morado, Inmaculada C.; Narváez, Javier; Miranda-Filloy, José A.; Martínez-Berriochoa, Agustín; Unzurrunzaga, Ainhoa; Hidalgo-Conde, Ana; Madroñero-Vuelta, Ana B.; Fernández-Nebro, Antonio; Ordóñez-Cañizares, M. Carmen; Escalante, Begoña; Marí-Alfonso, Begoña; Sopeña, Bernardo; Magro, César; Raya, Enrique; Grau, Elena; Román, José A.; de Miguel, Eugenio; López-Longo, F. Javier; Martínez, Lina; Gómez-Vaquero, Carmen; Fernández-Gutiérrez, Benjamín; Rodríguez-Rodríguez, Luis; Díaz-López, J. Bernardino; Caminal-Montero, Luis; Martínez-Zapico, Aleida; Monfort, Jordi; Tío, Laura; Sánchez-Martín, Julio; Alegre-Sancho, Juan J.; Sáez-Comet, Luis; Pérez-Conesa, Mercedes; Corbera-Bellalta, Marc; García-Villanueva, M. Jesús; Fernández-Contreras, M. Encarnación; Sanchez-Pernaute, Olga; Blanco, Ricardo; Ortego-Centeno, Norberto; Ríos-Fernández, Raquel; Callejas, José L.; Fanlo-Mateo, Patricia; Martínez-Taboada, Víctor M.; Beretta, Lorenzo; Lunardi, Claudio; Cimmino, Marco A.; Gianfreda, Davide; Santilli, Daniele; Ramirez, Giuseppe A.; Soriano, Alessandra; Muratore, Francesco; Pazzola, Giulia; Addimanda, Olga; Wijmenga, Cisca; Witte, Torsten; Schirmer, Jan H.; Moosig, Frank; Schönau, Verena; Franke, Andre; Palm, Øyvind; Molberg, Øyvind; Diamantopoulos, Andreas P.; Carette, Simon; Cuthbertson, David; Forbess, Lindsy J.; Hoffman, Gary S.; Khalidi, Nader A.; Koening, Curry L.; Langford, Carol A.; McAlear, Carol A.; Moreland, Larry; Monach, Paul A.; Pagnoux, Christian; Seo, Philip; Spiera, Robert; Sreih, Antoine G.; Warrington, Kenneth J.; Ytterberg, Steven R.; Gregersen, Peter K.; Pease, Colin T.; Gough, Andrew; Green, Michael; Hordon, Lesley; Jarrett, Stephen; Watts, Richard; Levy, Sarah; Patel, Yusuf; Kamath, Sanjeet; Dasgupta, Bhaskar; Worthington, Jane; Koeleman, Bobby P.C.; de Bakker, Paul I.W.; Barrett, Jennifer H.; Salvarani, Carlo; Merkel, Peter A.; González-Gay, Miguel A.; Morgan, Ann W.; Martín, Javier

    2015-01-01

    We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10−40, OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1∗04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10−43) and HLA-DQα1 47 (p = 4.02 × 10−46), 56, and 76 (both p = 1.84 × 10−45) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10−6, OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10−6, OR = 1.20), and REL (rs115674477, p = 1.10 × 10−5, OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function. PMID:25817017

  15. High-throughput genotyping assay for the large-scale genetic characterization of Cryptosporidium parasites from human and bovine samples.

    PubMed

    Abal-Fabeiro, J L; Maside, X; Llovo, J; Bello, X; Torres, M; Treviño, M; Moldes, L; Muñoz, A; Carracedo, A; Bartolomé, C

    2014-04-01

    The epidemiological study of human cryptosporidiosis requires the characterization of species and subtypes involved in human disease in large sample collections. Molecular genotyping is costly and time-consuming, making the implementation of low-cost, highly efficient technologies increasingly necessary. Here, we designed a protocol based on MALDI-TOF mass spectrometry for the high-throughput genotyping of a panel of 55 single nucleotide variants (SNVs) selected as markers for the identification of common gp60 subtypes of four Cryptosporidium species that infect humans. The method was applied to a panel of 608 human and 63 bovine isolates and the results were compared with control samples typed by Sanger sequencing. The method allowed the identification of species in 610 specimens (90·9%) and gp60 subtype in 605 (90·2%). It displayed excellent performance, with sensitivity and specificity values of 87·3 and 98·0%, respectively. Up to nine genotypes from four different Cryptosporidium species (C. hominis, C. parvum, C. meleagridis and C. felis) were detected in humans; the most common ones were C. hominis subtype Ib, and C. parvum IIa (61·3 and 28·3%, respectively). 96·5% of the bovine samples were typed as IIa. The method performs as well as the widely used Sanger sequencing and is more cost-effective and less time consuming. PMID:24238396

  16. Large-scale Clinical Endodontic Research in The National Dental Practice-Based Research Network: Study Overview and Methods

    PubMed Central

    Nixdorf, Donald R.; Law, Alan S.; Look, John O.; Rindal, D. Brad; Durand, Emily U.; Kang, Wenjun; Agee, Bonita S.; Fellows, Jeffrey L.; Gordan, Valeria V.; Gilbert, Gregg H.

    2013-01-01

    Introduction This paper reports on the feasibility of conducting a large-scale endodontic prospective cohort study in The National Dental Practice-Based Research Network. This study was designed to measure pain and burden associated with initial orthograde root canal therapy (RCT) and to explore potential prognostic factors for pain outcomes. The main objectives of this first report in a series are to describe the project’s feasibility and methods and the demographics of the sample obtained. Methods Sixty-two dentist practitioner-investigators (46 generalists, 16 endodontists) in five geographical areas were certified within the network and trained regarding the standardized study protocol. Enrollment and baseline data collection occurred over 6 months, with post-obturation follow-up for another 6 months. Patients and dentists completed questionnaires before and immediately after treatment visits. Patients also completed questionnaires at 1 week, 3 months, and 6 months after obturation. Results Enrollment exceeded target expectations, with 708 eligible patient-participants. Questionnaire return rates were good, ranging between 90% to 100%. Patient demographics were typical of persons who receive RCT in the United States: mean age 48 years (SD 13 years), with most being female (59%), college-educated (81%), white non-Hispanic (86%), and having dental insurance (81%). The tooth types being treated were also typical: 61% molars, 28% premolars, and 11% anteriors, with maxillary teeth being predominant (59%). Conclusions This study demonstrates the feasibility of conducting large-scale endodontic prospective cohort studies in the network. Patients were rapidly recruited, with high levels of compliance in data collection. PMID:23063220

  17. The tensorial nature of effective porosity and large-scale dispersion coefficients: Application to the Creston study area, Eastern Washington

    SciTech Connect

    McKee, C.R.; Way, S.C.

    1988-12-01

    To describe flow in a complex system of fractures requires an understanding of the effects of direction or orientation on several hydrologic characteristics, such as hydraulic conductivity, porosity, and dispersion coefficient. The theory for hydraulic conductivity is well understood; this report deals with the effects of fracture orientation on porosity and dispersion coefficient. The tensorial nature of effective porosity was examined and was found to be a second-rank tensor in fractured rock units. Porosity varies at a fixed point, depending on its orientation. A method to calculate a dispersion coefficient from field tracer tests is described. The components of the dispersion coefficient can be calculated from the concentration profiles observed in downgradient observation wells. The method provides a procedure for studying the dispersion effect in large-scale field testing. The application of this method was successfully demonstrated in a tracer test performed in the research wellfield at the Creston study area, Lincoln County, Washington.

  18. A topological analysis of large-scale structure, studied using the CMASS sample of SDSS-III

    SciTech Connect

    Parihar, Prachi; Gott, J. Richard III; Vogeley, Michael S.; Choi, Yun-Young; Kim, Juhan; Kim, Sungsoo S.; Speare, Robert; Brownstein, Joel R.; Brinkmann, J. E-mail: yy.choi@khu.ac.kr

    2014-12-01

    We study the three-dimensional genus topology of large-scale structure using the northern region of the CMASS Data Release 10 (DR10) sample of the SDSS-III Baryon Oscillation Spectroscopic Survey. We select galaxies with redshift 0.452 < z < 0.625 and with a stellar mass M {sub stellar} > 10{sup 11.56} M {sub ☉}. We study the topology at two smoothing lengths: R {sub G} = 21 h {sup –1} Mpc and R {sub G} = 34 h {sup –1} Mpc. The genus topology studied at the R {sub G} = 21 h {sup –1} Mpc scale results in the highest genus amplitude observed to date. The CMASS sample yields a genus curve that is characteristic of one produced by Gaussian random phase initial conditions. The data thus support the standard model of inflation where random quantum fluctuations in the early universe produced Gaussian random phase initial conditions. Modest deviations in the observed genus from random phase are as expected from shot noise effects and the nonlinear evolution of structure. We suggest the use of a fitting formula motivated by perturbation theory to characterize the shift and asymmetries in the observed genus curve with a single parameter. We construct 54 mock SDSS CMASS surveys along the past light cone from the Horizon Run 3 (HR3) N-body simulations, where gravitationally bound dark matter subhalos are identified as the sites of galaxy formation. We study the genus topology of the HR3 mock surveys with the same geometry and sampling density as the observational sample and find the observed genus topology to be consistent with ΛCDM as simulated by the HR3 mock samples. We conclude that the topology of the large-scale structure in the SDSS CMASS sample is consistent with cosmological models having primordial Gaussian density fluctuations growing in accordance with general relativity to form galaxies in massive dark matter halos.

  19. Self-sampling for analysis of respiratory viruses in a large-scale epidemiological study in Sweden.

    PubMed

    Plymoth, A; Rotzen-Ostlund, M; Zweygberg-Wirgart, B; Sundin, C G; Ploner, A; Nyren, O; Linde, A

    2015-01-01

    Viral diagnosis of respiratory tract infections has so far required sampling by health professionals,hampering large-scale epidemiological studies of virus-specific disease outcomes. As part of a population-based, prospective study of work-related risk factors for transmission of viral infections (SWEDE-I), we developed a scheme for self-sampling with nasal swabs. Random selection from the gainfully employed population of a medium-sized town in central Sweden resulted in a study cohort of 2,237 men and women aged 25 to 63 years. From September 2011 through May 2012, the cohort reported all instances of respiratory tract infection or gastroenteritis and participants concomitantly sent self-sampled nasal swabs for analysis using regular mail. Diagnosis of 14 viruses was performed. A total of 1,843 samples were received. The week-wise average delay between disease on set and arrival of the specimens at the laboratory varied between four and six days, and the corresponding median delay was between 3.5 and six days. In line with previous community-based studies, picorna- and coronaviruses dominated in specimens obtained from the self-sampling scheme. The results of self-sampling were contrasted to those from contemporaneous routine clinical sampling, on the same age group, in the adjacent Stockholm county. Although higher proportions of positive samples for respiratory syncytial virus and influenza were observed in the clinical sampling scheme, estimations of seasonality for influenza A and picornaviruses derived from both schemes were similar. Our findings show that nasal self-sampling is feasible in large-scale surveillance of respiratory infections and opens new prospects for population based,virologically verified research on virus spread,burden of disease, and effects of environmental factors or interventions. PMID:25811646

  20. Parents' perceived vulnerability and perceived control in preventing Meningococcal C infection: a large-scale interview study about vaccination

    PubMed Central

    Timmermans, Danielle RM; Henneman, Lidewij; Hirasing, Remy A; van der Wal, Gerrit

    2008-01-01

    Background Parents' reported ambivalence toward large-scale vaccination programs for childhood diseases may be related to their perception of the risks of side-effects or safety of vaccination and the risk of contracting the disease. The aim of this study is to evaluate parents' perceptions of their child's risk contracting a Meningococcal C infection and parents' perceived control in preventing infection in relation to their evaluation of the safety, effectiveness and usefulness of vaccination. Methods In a large-scale interview study, a random sample of parents was interviewed after their children had received vaccination against Meningococcal C in a catch-up campaign. Questions were asked about the perceived relative vulnerability of their child contracting an infection, perceived control in preventing an infection, and parents' evaluation of the safety, usefulness and effectiveness of vaccination. Results 61% of 2910 (N = 1763) parents who were approached participated. A higher perceived relative vulnerability of their own child contracting the disease was related to a more positive evaluation of the vaccination campaign, while a lower perceived vulnerability did not result in a more negative evaluation. A higher perceived control in being able to prevent an infection was, however, related to a more critical attitude toward the safety, usefulness and effectiveness of vaccination. Conclusion Perceived relative vulnerability contracting an infection and parents' perceived control in preventing an infection seem to influence parents' evaluation of the vaccination programme. Future studies should determine if, and under which circumstances, these perceptions also affect parents' vaccination behaviour and would be relevant to be taken into account when educating parents about vaccination. PMID:18241345

  1. Experimental study on seismic responses of piping systems with friction. Part 1: Large-scale shaking table vibration test

    SciTech Connect

    Suzuki, K.; Watanabe, T.; Mitsumori, T.; Shimizu, N.; Kobayashi, H.; Ogawa, N.

    1995-08-01

    This report deals with the experimental study of seismic response behavior of piping systems in industrial facilities such as petrochemical, oil refinery, and nuclear plants. Special attention is focused on the nonlinear dynamic response of piping systems due to frictional vibration appearing in piping and supporting devices. A three-dimensional mock-up piping and supporting structure model wherein piping is of 30-m length and 200-mm diameter is excited by a large-scale (15 m x 15 m) shaking table belong to the National Research Institute for Earth Science and Disaster Prevention in Tsukuba, Ibaraki. Power spectra of the response vibration and the loading-response relationship in the form of a hysteresis loop under several loading conditions are obtained. The response reduction effect caused by frictional vibration is evaluated and demonstrated in terms of response reduction factor.

  2. Large-Scale Urban Riots and Residential Segregation: A Case Study of the 1960s U.S. Riots.

    PubMed

    Brazil, Noli

    2016-04-01

    Despite a well-established literature investigating race-related predictors of riot incidence, the racial aftermath of riots remains unexamined. In this study, I use the 1960s U.S. race riots to investigate trends in black residential segregation levels following large-scale riot activity in seven major U.S. cities. I use a novel approach--namely, synthetic control matching--to select a group of cities against which segregation trends can be compared. I find that levels of black segregation rose in 1970 for four of the seven cities, but these increases disappeared in 1980 and 1990 except in Detroit. These results mask differential trends at lower geographic levels: suburban neighborhoods in affected areas experienced larger and longer-term increases in segregation, particularly in traditionally hypersegregated cities in the Midwest and Northeast. PMID:26940025

  3. Large Scale Computing

    NASA Astrophysics Data System (ADS)

    Capiluppi, Paolo

    2005-04-01

    Large Scale Computing is acquiring an important role in the field of data analysis and treatment for many Sciences and also for some Social activities. The present paper discusses the characteristics of Computing when it becomes "Large Scale" and the current state of the art for some particular application needing such a large distributed resources and organization. High Energy Particle Physics (HEP) Experiments are discussed in this respect; in particular the Large Hadron Collider (LHC) Experiments are analyzed. The Computing Models of LHC Experiments represent the current prototype implementation of Large Scale Computing and describe the level of maturity of the possible deployment solutions. Some of the most recent results on the measurements of the performances and functionalities of the LHC Experiments' testing are discussed.

  4. Multiresolution analysis of precipitation teleconnections with large-scale climate signals: A case study in South Australia

    NASA Astrophysics Data System (ADS)

    He, Xinguang; Guan, Huade

    2013-10-01

    Climatic teleconnections are often used to interpret and sometimes to predict precipitation temporal variability at various time scales. However, the teleconnections are intertwined between the effects of multiple large-scale climate signals which are often interdependent. Each climate signal is composed of multitemporal components, which may result in different teleconnection patterns. The time lags of precipitation response may vary with climate signals and their multitemporal components. In order to effectively address these problems, a multiresolution analysis (MRA) with a discrete wavelet transform is utilized, and a stepwise linear regression model based on MRA and cross correlation analysis is developed in this study. The method is applied to examine monthly precipitation teleconnections in South Australia (SA) with five large-scale climate signals. The MRA first decomposes each of original monthly precipitation anomaly and climate signals into several component series at different temporal scales. Then the hierarchical lag relationships between them are determined for regression modeling using cross-correlation analysis. The results indicate that the MRA-based method is able to reveal at which time scale(s) and with what time lag(s) the teleconnections occur, and their spatial patterns. The method is also useful to examine the time-scale patterns of the interdependence between climate signals. These altogether make the MRA-based method a promising tool to address the difficulties in the climate teleconnection studies. The multiple linear regression based on MRA-decomposed climate signals is expected to better interpret monthly precipitation temporal variability than that based on the original climate signals.

  5. Assessment of climate change impacts on rainfall using large scale climate variables and downscaling models - A case study

    NASA Astrophysics Data System (ADS)

    Ahmadi, Azadeh; Moridi, Ali; Lafdani, Elham Kakaei; Kianpisheh, Ghasem

    2014-10-01

    Many of the applied techniques in water resources management can be directly or indirectly influenced by hydro-climatology predictions. In recent decades, utilizing the large scale climate variables as predictors of hydrological phenomena and downscaling numerical weather ensemble forecasts has revolutionized the long-lead predictions. In this study, two types of rainfall prediction models are developed to predict the rainfall of the Zayandehrood dam basin located in the central part of Iran. The first seasonal model is based on large scale climate signals data around the world. In order to determine the inputs of the seasonal rainfall prediction model, the correlation coefficient analysis and the new Gamma Test (GT) method are utilized. Comparison of modelling results shows that the Gamma test method improves the Nash-Sutcliffe efficiency coefficient of modelling performance as 8% and 10% for dry and wet seasons, respectively. In this study, Support Vector Machine (SVM) model for predicting rainfall in the region has been used and its results are compared with the benchmark models such as K-nearest neighbours (KNN) and Artificial Neural Network (ANN). The results show better performance of the SVM model at testing stage. In the second model, statistical downscaling model (SDSM) as a popular downscaling tool has been used. In this model, using the outputs from GCM, the rainfall of Zayandehrood dam is projected under two climate change scenarios. Most effective variables have been identified among 26 predictor variables. Comparison of the results of the two models shows that the developed SVM model has lesser errors in monthly rainfall estimation. The results show that the rainfall in the future wet periods are more than historical values and it is lower than historical values in the dry periods. The highest monthly uncertainty of future rainfall occurs in March and the lowest in July.

  6. Assimilation of satellite data to optimize large-scale hydrological model parameters: a case study for the SWOT mission

    NASA Astrophysics Data System (ADS)

    Pedinotti, V.; Boone, A.; Ricci, S.; Biancamaria, S.; Mognard, N.

    2014-11-01

    During the last few decades, satellite measurements have been widely used to study the continental water cycle, especially in regions where in situ measurements are not readily available. The future Surface Water and Ocean Topography (SWOT) satellite mission will deliver maps of water surface elevation (WSE) with an unprecedented resolution and provide observation of rivers wider than 100 m and water surface areas greater than approximately 250 x 250 m over continental surfaces between 78° S and 78° N. This study aims to investigate the potential of SWOT data for parameter optimization for large-scale river routing models. The method consists in applying a data assimilation approach, the extended Kalman filter (EKF) algorithm, to correct the Manning roughness coefficients of the ISBA (Interactions between Soil, Biosphere, and Atmosphere)-TRIP (Total Runoff Integrating Pathways) continental hydrologic system. Parameters such as the Manning coefficient, used within such models to describe water basin characteristics, are generally derived from geomorphological relationships, which leads to significant errors at reach and large scales. The current study focuses on the Niger Basin, a transboundary river. Since the SWOT observations are not available yet and also to assess the proposed assimilation method, the study is carried out under the framework of an observing system simulation experiment (OSSE). It is assumed that modeling errors are only due to uncertainties in the Manning coefficient. The true Manning coefficients are then supposed to be known and are used to generate synthetic SWOT observations over the period 2002-2003. The impact of the assimilation system on the Niger Basin hydrological cycle is then quantified. The optimization of the Manning coefficient using the EKF (extended Kalman filter) algorithm over an 18-month period led to a significant improvement of the river water levels. The relative bias of the water level is globally improved (a 30

  7. An experimentally verified finite element study of the stress-strain response of crack geometries experiencing large-scale yielding

    SciTech Connect

    Panontin, T.L.; Sheppard, S.D.

    1997-12-01

    Large-strain, 3-D finite element analyses with incremental plasticity were performed for a variety of crack geometries to study local crack-tip stress-strain fields and associated global fracture parameters under conditions of large-scale yielding. The geometries analyzed include thin, single-edge crack tension, single-edge crack bending, and center-crack tension fracture specimens with varying crack depth (a/W) ratios. Two materials were investigated: a high-hardening, low-strength steel and a moderate-hardening, high-strength steel. Mesh refinement studies were performed to ensure convergence of the finite element predictions. The studies examine the effects of in-plane crack-tip element size, initial crack-tip radius size, and number of through-thickness layers on predicted distributions of crack-tip stress and plastic strain and predicted values of the J-integral and CTOD. In addition, the finite element predictions of specimen behavior were verified experimentally by direct measurements, namely load displacement, load longitudinal strain, and load CTOS, made during and following testing of the fracture specimens. Representative results of the finite element analyses are presented and compared to previously published data where pertinent. Results from the mesh refinement studies and the verification testing are shown. Predicted trends among the specimens and materials in local distributions of crack-tip plastic strain, triaxiality, and opening stress as well as in global parameters, J-integral and m-factor, are discussed.

  8. Organizational aspects and implementation of data systems in large-scale epidemiological studies in less developed countries

    PubMed Central

    Ali, Mohammad; Park, Jin-Kyung; von Seidlein, Lorenz; Acosta, Camilo J; Deen, Jacqueline L; Clemens, John D

    2006-01-01

    Background In the conduct of epidemiological studies in less developed countries, while great emphasis is placed on study design, data collection, and analysis, often little attention is paid to data management. As a consequence, investigators working in these countries frequently face challenges in cleaning, analyzing and interpreting data. In most research settings, the data management team is formed with temporary and unskilled persons. A proper working environment and training or guidance in constructing a reliable database is rarely available. There is little information available that describes data management problems and solutions to those problems. Usually a line or two can be obtained in the methods section of research papers stating that the data are doubly-entered and that outliers and inconsistencies were removed from the data. Such information provides little assurance that the data are reliable. There are several issues in data management that if not properly practiced may create an unreliable database, and outcomes of this database will be spurious. Results We have outlined the data management practices for epidemiological studies that we have modeled for our research sites in seven Asian countries and one African country. Conclusion Information from this model data management structure may help others construct reliable databases for large-scale epidemiological studies in less developed countries. PMID:16584571

  9. A large-scale study of the world wide web: network correlation functions with scale-invariant boundaries

    NASA Astrophysics Data System (ADS)

    Ludueña, Guillermo A.; Meixner, Harald; Kaczor, Gregor; Gros, Claudius

    2013-08-01

    We performed a large-scale crawl of the world wide web, covering 6.9 million domains and 57 million subdomains, including all high-traffic sites of the internet. We present a study of the correlations found between quantities measuring the structural relevance of each node in the network (the in- and out-degree, the local clustering coefficient, the first-neighbor in-degree and the Alexa rank). We find that some of these properties show strong correlation effects and that the dependencies occurring out of these correlations follow power laws not only for the averages, but also for the boundaries of the respective density distributions. In addition, these scale-free limits do not follow the same exponents as the corresponding averages. In our study we retain the directionality of the hyperlinks and develop a statistical estimate for the clustering coefficient of directed graphs. We include in our study the correlations between the in-degree and the Alexa traffic rank, a popular index for the traffic volume, finding non-trivial power-law correlations. We find that sites with more/less than about 103 links from different domains have remarkably different statistical properties, for all correlation functions studied, indicating towards an underlying hierarchical structure of the world wide web.

  10. Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review

    PubMed Central

    2011-01-01

    Background Observational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality. Methods We included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted. Results Thirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and

  11. Large-Scale Disasters

    NASA Astrophysics Data System (ADS)

    Gad-El-Hak, Mohamed

    "Extreme" events - including climatic events, such as hurricanes, tornadoes, and drought - can cause massive disruption to society, including large death tolls and property damage in the billions of dollars. Events in recent years have shown the importance of being prepared and that countries need to work together to help alleviate the resulting pain and suffering. This volume presents a review of the broad research field of large-scale disasters. It establishes a common framework for predicting, controlling and managing both manmade and natural disasters. There is a particular focus on events caused by weather and climate change. Other topics include air pollution, tsunamis, disaster modeling, the use of remote sensing and the logistics of disaster management. It will appeal to scientists, engineers, first responders and health-care professionals, in addition to graduate students and researchers who have an interest in the prediction, prevention or mitigation of large-scale disasters.

  12. Study of materials and machines for 3D printed large-scale, flexible electronic structures using fused deposition modeling

    NASA Astrophysics Data System (ADS)

    Hwang, Seyeon

    The 3 dimensional printing (3DP), called to additive manufacturing (AM) or rapid prototyping (RP), is emerged to revolutionize manufacturing and completely transform how products are designed and fabricated. A great deal of research activities have been carried out to apply this new technology to a variety of fields. In spite of many endeavors, much more research is still required to perfect the processes of the 3D printing techniques especially in the area of the large-scale additive manufacturing and flexible printed electronics. The principles of various 3D printing processes are briefly outlined in the Introduction Section. New types of thermoplastic polymer composites aiming to specified functional applications are also introduced in this section. Chapter 2 shows studies about the metal/polymer composite filaments for fused deposition modeling (FDM) process. Various metal particles, copper and iron particles, are added into thermoplastics polymer matrices as the reinforcement filler. The thermo-mechanical properties, such as thermal conductivity, hardness, tensile strength, and fracture mechanism, of composites are tested to figure out the effects of metal fillers on 3D printed composite structures for the large-scale printing process. In Chapter 3, carbon/polymer composite filaments are developed by a simple mechanical blending process with an aim of fabricating the flexible 3D printed electronics as a single structure. Various types of carbon particles consisting of multi-wall carbon nanotube (MWCNT), conductive carbon black (CCB), and graphite are used as the conductive fillers to provide the thermoplastic polyurethane (TPU) with improved electrical conductivity. The mechanical behavior and conduction mechanisms of the developed composite materials are observed in terms of the loading amount of carbon fillers in this section. Finally, the prototype flexible electronics are modeled and manufactured by the FDM process using Carbon/TPU composite filaments and

  13. Characterizing Coherent Wind Structures using Large-Scale Particle Tracking Velocimetry: A Proof-of-Principle Study

    NASA Astrophysics Data System (ADS)

    Rosi, G. A.; la Bastide, B.; Gaebler, J.; Kinzel, M.; Rival, D. E.

    2014-12-01

    The following study proposes a two-dimensional large-scale particle tracking velocimetry (LS-PTV) system to characterize coherent wind structures. Seven minutes of LS-PTV data is collected via an apparatus that seeds fog-filled soap bubbles into the wind at a height of 6m from the ground. The LS-PTV data is compared to 20 minutes of data collected concurrently from a wind mast at the same site. The LS-PTV system recorded a mean streamwise velocity of 1.35m/s with a standard deviation of 0.23m/s at a mean height of 2.50m with a standard deviation of 0.7m, which agrees well with the velocity profile measured by the wind mast. Furthermore, the Reynolds stresses measured by the LS-PTV system are found to compare to those measured by the wind mast and by Klebanoff [1] for a canonical turbulent boundary layer. The current study assumes that the centre-of-curvature trajectories of the particle pathlines are representative of the trajectories followed by the spanwise vortices. As a proof-of-principle study, this work has been successful in accurately describing the vortex distribution very near to the ground. However, the trajectories followed by the centres-of- curvat.ure belonging to pathlines concurrently passing through the field-of-view were sporadic and uncorrelated.

  14. Sensitivity study of a large-scale air pollution model by using high-performance computations and Monte Carlo algorithms

    NASA Astrophysics Data System (ADS)

    Ostromsky, Tz.; Dimov, I.; Georgieva, R.; Marinov, P.; Zlatev, Z.

    2013-10-01

    In this paper we present some new results of our work on sensitivity analysis of a large-scale air pollution model, more specificly the Danish Eulerian Model (DEM). The main purpose of this study is to analyse the sensitivity of ozone concentrations with respect to the rates of some chemical reactions. The current sensitivity study considers the rates of six important chemical reactions and is done for the areas of several European cities with different geographical locations, climate, industrialization and population density. One of the most widely used variance-based techniques for sensitivity analysis, such as Sobol estimates and their modifications, have been used in this study. A vast number of numerical experiments with a specially adapted for the purpose version of the Danish Eulerian Model (SA-DEM) were carried out to compute global Sobol sensitivity measures. SA-DEM was implemented and run on two powerful cluster supercomputers: IBM Blue Gene/P, the most powerful parallel supercomputer in Bulgaria and IBM MareNostrum III, the most powerful parallel supercomputer in Spain. The refined (480 × 480) mesh version of the model was used in the experiments on MareNostrum III, which is a challenging computational problem even on such a powerful machine. Some optimizations of the code with respect to the parallel efficiency and the memory use were performed. Tables with performance results of a number of numerical experiments on IBM BlueGene/P and on IBM MareNostrum III are presented and analysed.

  15. Large-scale introduction of the Indo-Pacific damselfish Abudefduf vaigiensis into Hawai'i promotes genetic swamping of the endemic congener A. abdominalis.

    PubMed

    Coleman, Richard R; Gaither, Michelle R; Kimokeo, Bethany; Stanton, Frank G; Bowen, Brian W; Toonen, Robert J

    2014-11-01

    Hybridization in the ocean was once considered rare, a process prohibited by the rapid evolution of intrinsic reproductive barriers in a high-dispersal medium. However, recent genetic surveys have prompted a reappraisal of marine hybridization as an important demographic and evolutionary process. The Hawaiian Archipelago offers an unusual case history in this arena, due to the recent arrival of the widely distributed Indo-Pacific sergeant (Abudefduf vaigiensis), which is hybridizing with the endemic congener, A. abdominalis. Surveys of mtDNA and three nuclear loci across Hawai'i (N = 396, Abudefduf abdominalis and N = 314, A. vaigiensis) reveal that hybridization is significantly higher in the human-perturbed southeast archipelago (19.8%), tapering off to 5.9% in the pristine northwest archipelago. While densities of the two species varied throughout Hawai'i, hybridization was highest in regions with similar species densities, contradicting the generalization that the rarity of one species promotes interspecific mating. Our finding of later generation hybrids throughout the archipelago invokes the possibility of genetic swamping of the endemic species. Exaptation, an adaptation with unintended consequences, may explain these findings: the endemic species has transient yellow coloration during reproduction, whereas the introduced species has yellow coloration continuously as adults, in effect a permanent signal of reproductive receptivity. Haplotype diversity is higher in Hawaiian A. vaigiensis than in our samples from the native range, indicating large-scale colonization almost certainly facilitated by the historically recent surge of marine debris. In this chain of events, marine debris promotes colonization, exaptation promotes hybridization, and introgression invokes the possible collapse of an endemic species. PMID:25283736

  16. Programmed Nanomaterial Assemblies in Large Scales: Applications of Synthetic and Genetically- Engineered Peptides to Bridge Nano-Assemblies and Macro-Assemblies

    SciTech Connect

    Matsui, Hiroshi

    2014-09-09

    Work is reported in these areas: Large-scale & reconfigurable 3D structures of precise nanoparticle assemblies in self-assembled collagen peptide grids; Binary QD-Au NP 3D superlattices assembled with collagen-like peptides and energy transfer between QD and Au NP in 3D peptide frameworks; Catalytic peptides discovered by new hydrogel-based combinatorial phage display approach and their enzyme-mimicking 2D assembly; New autonomous motors of metal-organic frameworks (MOFs) powered by reorganization of self-assembled peptides at interfaces; Biomimetic assembly of proteins into microcapsules on oil-in-water droplets with structural reinforcement via biomolecular recognition-based cross-linking of surface peptides; and Biomimetic fabrication of strong freestanding genetically-engineered collagen peptide films reinforced by quantum dot joints. We gained the broad knowledge about biomimetic material assembly from nanoscale to microscale ranges by coassembling peptides and NPs via biomolecular recognition. We discovered: Genetically-engineered collagen-like peptides can be self-assembled with Au NPs to generate 3D superlattices in large volumes (> μm{sup 3}); The assembly of the 3D peptide-Au NP superstructures is dynamic and the interparticle distance changes with assembly time as the reconfiguration of structure is triggered by pH change; QDs/NPs can be assembled with the peptide frameworks to generate 3D superlattices and these QDs/NPs can be electronically coupled for the efficient energy transfer; The controlled assembly of catalytic peptides mimicking the catalytic pocket of enzymes can catalyze chemical reactions with high selectivity; and, For the bacteria-mimicking swimmer fabrication, peptide-MOF superlattices can power translational and propellant motions by the reconfiguration of peptide assembly at the MOF-liquid interface.

  17. Development of the first marmoset-specific DNA microarray (EUMAMA): a new genetic tool for large-scale expression profiling in a non-human primate

    PubMed Central

    Datson, Nicole A; Morsink, Maarten C; Atanasova, Srebrena; Armstrong, Victor W; Zischler, Hans; Schlumbohm, Christina; Dutilh, Bas E; Huynen, Martijn A; Waegele, Brigitte; Ruepp, Andreas; de Kloet, E Ronald; Fuchs, Eberhard

    2007-01-01

    Background The common marmoset monkey (Callithrix jacchus), a small non-endangered New World primate native to eastern Brazil, is becoming increasingly used as a non-human primate model in biomedical research, drug development and safety assessment. In contrast to the growing interest for the marmoset as an animal model, the molecular tools for genetic analysis are extremely limited. Results Here we report the development of the first marmoset-specific oligonucleotide microarray (EUMAMA) containing probe sets targeting 1541 different marmoset transcripts expressed in hippocampus. These 1541 transcripts represent a wide variety of different functional gene classes. Hybridisation of the marmoset microarray with labelled RNA from hippocampus, cortex and a panel of 7 different peripheral tissues resulted in high detection rates of 85% in the neuronal tissues and on average 70% in the non-neuronal tissues. The expression profiles of the 2 neuronal tissues, hippocampus and cortex, were highly similar, as indicated by a correlation coefficient of 0.96. Several transcripts with a tissue-specific pattern of expression were identified. Besides the marmoset microarray we have generated 3215 ESTs derived from marmoset hippocampus, which have been annotated and submitted to GenBank [GenBank: EF214838 – EF215447, EH380242 – EH382846]. Conclusion We have generated the first marmoset-specific DNA microarray and demonstrated its use to characterise large-scale gene expression profiles of hippocampus but also of other neuronal and non-neuronal tissues. In addition, we have generated a large collection of ESTs of marmoset origin, which are now available in the public domain. These new tools will facilitate molecular genetic research into this non-human primate animal model. PMID:17592630

  18. Stick-slip behavior of Indian gabbro as studied using a NIED large-scale biaxial friction apparatus

    NASA Astrophysics Data System (ADS)

    Togo, Tetsuhiro; Shimamoto, Toshihiko; Yamashita, Futoshi; Fukuyama, Eiichi; Mizoguchi, Kazuo; Urata, Yumi

    2015-04-01

    This paper reports stick-slip behaviors of Indian gabbro as studied using a new large-scale biaxial friction apparatus, built in the National Research Institute for Earth Science and Disaster Prevention (NIED), Tsukuba, Japan. The apparatus consists of the existing shaking table as the shear-loading device up to 3,600 kN, the main frame for holding two large rectangular prismatic specimens with a sliding area of 0.75 m2 and for applying normal stresses σ n up to 1.33 MPa, and a reaction force unit holding the stationary specimen to the ground. The shaking table can produce loading rates v up to 1.0 m/s, accelerations up to 9.4 m/s2, and displacements d up to 0.44 m, using four servocontrolled actuators. We report results from eight preliminary experiments conducted with room humidity on the same gabbro specimens at v = 0.1-100 mm/s and σ n = 0.66-1.33 MPa, and with d of about 0.39 m. The peak and steady-state friction coefficients were about 0.8 and 0.6, respectively, consistent with the Byerlee friction. The axial force drop or shear stress drop during an abrupt slip is linearly proportional to the amount of displacement, and the slope of this relationship determines the stiffness of the apparatus as 1.15 × 108 N/m or 153 MPa/m for the specimens we used. This low stiffness makes fault motion very unstable and the overshooting of shear stress to a negative value was recognized in some violent stick-slip events. An abrupt slip occurred in a constant rise time of 16-18 ms despite wide variation of the stress drop, and an average velocity during an abrupt slip is linearly proportional to the stress drop. The use of a large-scale shaking table has a great potential in increasing the slip rate and total displacement in biaxial friction experiments with large specimens.

  19. Concurrent Validity and Feasibility of Short Tests Currently Used to Measure Early Childhood Development in Large Scale Studies.

    PubMed

    Rubio-Codina, Marta; Araujo, M Caridad; Attanasio, Orazio; Muñoz, Pablo; Grantham-McGregor, Sally

    2016-01-01

    months, and language above. Predictive validity investigation is needed to further guide the choice of instruments for large scale studies. PMID:27548634

  20. Concurrent Validity and Feasibility of Short Tests Currently Used to Measure Early Childhood Development in Large Scale Studies

    PubMed Central

    Rubio-Codina, Marta; Araujo, M. Caridad; Attanasio, Orazio; Muñoz, Pablo; Grantham-McGregor, Sally

    2016-01-01

    below 19 months, and language above. Predictive validity investigation is needed to further guide the choice of instruments for large scale studies. PMID:27548634

  1. High Intake of Manganese During Second Trimester, Increases the Risk of Preterm Delivery: A Large Scale Cohort Study

    PubMed Central

    Bakouei, Sare; Reisian, Fatemeh; Lamyian, Minoor; Zadeh, Ebrahim Haji; Zamanian, Hadi; Kharameh, Zahra Taheri

    2015-01-01

    Evidence indicates that nutrients and minerals might play an important role in preterm delivery (PTD). The aim of this study was to determine maternal nutritional status during second trimester of pregnancy and its association with preterm delivery (< 34 weeks gestation) in Iranian women. In a large scale longitudinal study, 1033 pregnant women were recruited from prenatal clinics since December 2012 to June 2013. Dietary intake was assessed by Food Frequency Questionnaire (FFQ) in pregnant women of 14 to 20 weeks gestational age. The participants were followed up until delivery. Dietary intake of women with preterm delivery was compared with women who had term delivery. The results show that 61.2% of women were primiparous and that the incidence of preterm delivery was 7%. Manganese dietary intake was significantly higher in mothers with preterm delivery than those with term delivery (P = .03). Manganese was the only micronutrient correlated with preterm delivery after adjustment for maternal characteristics during second trimesters of pregnancy (OR = 1.12; P = .01). These results suggest that high maternal manganese dietary intake during the second trimester of pregnancy may be associated with the risk of preterm delivery in Iranian pregnant women. PMID:26156900

  2. Calibration of a large-scale groundwater flow model using GRACE data: a case study in the Qaidam Basin, China

    NASA Astrophysics Data System (ADS)

    Hu, Litang; Jiao, Jiu Jimmy

    2015-11-01

    Traditional numerical models usually use extensive observed hydraulic-head data as calibration targets. However, this calibration process is not applicable in remote areas with limited or no monitoring data. This study presents an approach to calibrate a large-scale groundwater flow model using the monthly Gravity Recovery and Climate Experiment (GRACE) satellite data, which have been available globally on a spatial grid of 1° in the geographic coordinate system since 2002. A groundwater storage anomaly isolated from the terrestrial water storage (TWS) anomaly is converted into hydraulic head at the center of the grid, which is then used as observed data to calibrate a numerical model to estimate aquifer hydraulic conductivity. The aquifer system in the remote and hyperarid Qaidam Basin, China, is used as a case study to demonstrate the applicability of this approach. A groundwater model using FEFLOW is constructed for the Qaidam Basin and the GRACE-derived groundwater storage anomaly over the period 2003-2012 is included to calibrate the model, which is done using an automatic estimation method (PEST). The calibrated model is then run to output hydraulic heads at three sites where long-term hydraulic head data are available. The reasonably good fit between the calculated and observed hydraulic heads, together with the very similar groundwater storage anomalies from the numerical model and GRACE data, demonstrate that this approach is generally applicable in regions of groundwater data scarcity.

  3. A large-scale study of the random variability of a coding sequence: a study on the CFTR gene.

    PubMed

    Modiano, Guido; Bombieri, Cristina; Ciminelli, Bianca Maria; Belpinati, Francesca; Giorgi, Silvia; Georges, Marie des; Scotet, Virginie; Pompei, Fiorenza; Ciccacci, Cinzia; Guittard, Caroline; Audrézet, Marie Pierre; Begnini, Angela; Toepfer, Michael; Macek, Milan; Ferec, Claude; Claustres, Mireille; Pignatti, Pier Franco

    2005-02-01

    Coding single nucleotide substitutions (cSNSs) have been studied on hundreds of genes using small samples (n(g) approximately 100-150 genes). In the present investigation, a large random European population sample (average n(g) approximately 1500) was studied for a single gene, the CFTR (Cystic Fibrosis Transmembrane conductance Regulator). The nonsynonymous (NS) substitutions exhibited, in accordance with previous reports, a mean probability of being polymorphic (q > 0.005), much lower than that of the synonymous (S) substitutions, but they showed a similar rate of subpolymorphic (q < 0.005) variability. This indicates that, in autosomal genes that may have harmful recessive alleles (nonduplicated genes with important functions), genetic drift overwhelms selection in the subpolymorphic range of variability, making disadvantageous alleles behave as neutral. These results imply that the majority of the subpolymorphic nonsynonymous alleles of these genes are selectively negative or even pathogenic. PMID:15536480

  4. Comparative climatological study of large-scale traveling ionospheric disturbances over North America and China in 2011-2012

    NASA Astrophysics Data System (ADS)

    Ding, Feng; Wan, Weixing; Li, Qiang; Zhang, Rui; Song, Qian; Ning, Baiqi; Liu, Libo; Zhao, Biqiang; Xiong, Bo

    2014-01-01

    This paper describes a comparative study of the climatology of large-scale traveling ionospheric disturbances (LSTIDs) over North America and China based on observations obtained in 2011-2012 using two GPS networks characterized by dense regional coverage. We identified a total of 390 LSTIDs in China and 363 events in North America. These can be categorized into three types, namely south, north, and westward propagating LSTIDs. The southward LSTIDs over North America show similar diurnal and seasonal variations to those of geomagnetic disturbances, but the southward LSTIDs over China do not show such variations. The occurrence of southward LSTIDs over China increases at ~1-2 h after the time of geomagnetic activity maximum; this increase lasts several hours until the geomagnetic minimum, which happens during the local evening. The southward LSTIDs over North America show a semiannual variation with two peaks in March and October, while the southward LSTIDs over China show a major peak in January. Northward LSTIDs occur much less frequently than their southward counterparts, and they are mainly observed in China. They mostly occur during geomagnetic activity maximum, indicating a possible relation with the degree of geomagnetic activity. Westward LSTIDs are seen in both regions during local sunrise and may be excited by the moving solar terminator. No relationship was found between these latter LSTIDs and the geomagnetic disturbances. The propagation direction of westward events changed from northwestward during winter solstice to southwestward at summer solstice. This is consistent with the seasonal orientation of the solar terminator.

  5. The importance of large scale flood over the regular sedimentation in delta development: A case study involving Wax lake delta

    NASA Astrophysics Data System (ADS)

    Ullah, M. S.; Kolker, A.; Li, C.

    2011-12-01

    It has been widely hypothesized that catastrophic floods can play an important role in the development of a young and growing delta. This study examines the nature and rate of sediment deposition in the Wax lake delta in the Atchafalaya Basin of Louisiana during the Mississippi River flood of from April, 2011 to June, 2011. We hypothesize that the deposition rate that results from large scales floods in the Mississippi/Atchafalaya river outlets have a greater impact in the Wax lake delta development than the deposition rates that result from typical yearly sedimentation. Preliminary results from the cosmogenic 7Be counts from sediment collected from the delta show distinct regional and local sediment deposition patterns during the flood, and rates that are significantly higher when compared to the sedimentation rate of the last few decades. This application of cosmogenic 7Be to distinguish the sediment deposition rate provides a first-order understanding of the deltaic evolution and stratigraphic sequence development in a high-discharge setting.

  6. Absolute pitch among students at the Shanghai Conservatory of Music: a large-scale direct-test study.

    PubMed

    Deutsch, Diana; Li, Xiaonuo; Shen, Jing

    2013-11-01

    This paper reports a large-scale direct-test study of absolute pitch (AP) in students at the Shanghai Conservatory of Music. Overall note-naming scores were very high, with high scores correlating positively with early onset of musical training. Students who had begun training at age ≤5 yr scored 83% correct not allowing for semitone errors and 90% correct allowing for semitone errors. Performance levels were higher for white key pitches than for black key pitches. This effect was greater for orchestral performers than for pianists, indicating that it cannot be attributed to early training on the piano. Rather, accuracy in identifying notes of different names (C, C#, D, etc.) correlated with their frequency of occurrence in a large sample of music taken from the Western tonal repertoire. There was also an effect of pitch range, so that performance on tones in the two-octave range beginning on Middle C was higher than on tones in the octave below Middle C. In addition, semitone errors tended to be on the sharp side. The evidence also ran counter to the hypothesis, previously advanced by others, that the note A plays a special role in pitch identification judgments. PMID:24180794

  7. Large-scale traveling ionospheric disturbances using ionospheric imaging at storm time: A case study on 17 march 2013

    NASA Astrophysics Data System (ADS)

    Tang, Jun; Yao, Yibin; Kong, Jian; Zhang, Liang

    2016-07-01

    A moderate geomagnetic storm occurred on March 17, 2013, during which large-scale traveling ionospheric disturbances (LSTIDs) are observed over China by ionosondes and GPS from Crustal Movement Observation Network of China (CMONOC) and the International GNSS Service (IGS). Ionosonde data and computerized ionospheric tomography (CIT) technique are employed to analyze the disturbances in our study. The maximum entropy cross spectral analysis (MECSA) method is used to obtain the propagation parameters of the LSTIDs. Spatio-temporal variations of ionospheric electron density (IED) and total electron content (TEC) during this geomagnetic storm over China are investigated. Disturbance images of IED and TEC are also presented in the paper. The results show two LSTID events at about 12:00 UT and 15:00 UT during the main phase of the storm. Besides, the LSTIDs with a duration of 40 min are detected over China. It is confirmed that the LSTIDs travel from north to south with a horizontal velocity of 400-500 m/s, and moved southwestwards with a horizontal velocity of 250-300 m/s, respectively.

  8. The importance of combining MRI and large-scale digital histology in neuroimaging studies of brain connectivity and disease

    PubMed Central

    Annese, Jacopo

    2012-01-01

    One of the major issues hindering a comprehensive connectivity model for the human brain is the difficulty in linking Magnetic Resonance Imaging (MRI) measurements to anatomical evidence produced by histological methods. In vivo and postmortem neuroimaging methodologies are still largely incompatible in terms of sample size, scale, and resolution. To help bridge the hiatus between different approaches we have established a program that characterizes the brain of individual subjects, combining MRI with postmortem neuroanatomy. The direct correlation of MRI and histological features is possible, because registered images from different modalities represent the same regions in the same brain. Comparisons are also facilitated by large-scale, digital microscopy techniques that afford images of the whole-brain sections at cellular resolution. The goal is to create a neuroimaging catalog representative of discrete age groups and specific neurological conditions. Individually, the datasets allow for investigating the relationship between different modalities; combined, they provide sufficient predictive power to inform analyses and interpretations made in the context of non-invasive studies of brain connectivity and disease. PMID:22536182

  9. Large scale dynamics of the Michaelis complex in Bacillus stearothermophilus lactate dehydrogenase revealed by a single-tryptophan mutant study.

    PubMed

    Nie, Beining; Deng, Hua; Desamero, Ruel; Callender, Robert

    2013-03-19

    Large scale dynamics within the Michaelis complex mimic of Bacillus stearothermophilus thermophilic lactate dehydrogenase, bsLDH·NADH·oxamate, were studied with site specific resolution by laser-induced temperature jump relaxation spectroscopy with a time resolution of 20 ns. NADH emission and Trp emission from the wild type and a series of single-tryptophan bsLDH mutants, with the tryptophan positions different distances from the active site, were used as reporters of evolving structure in response to the rapid change in temperature. Several distinct dynamical events were observed on the millisecond to microsecond time scale involving motion of atoms spread over the protein, some occurring concomitantly or nearly concomitantly with structural changes at the active site. This suggests that a large portion of the protein-substrate complex moves in a rather concerted fashion to bring about catalysis. The catalytically important surface loop undergoes two distinct movements, both needed for a competent enzyme. Our results also suggest that what is called "loop motion" is not just localized to the loop and active site residues. Rather, it involves the motion of atoms spread over the protein, even some quite distal from the active site. How these results bear on the catalytic mechanism of bsLDH is discussed. PMID:23428201

  10. A field study of large-scale oscillation ripples in a very coarse-grained, high-energy marine environment

    USGS Publications Warehouse

    Hirschaut, D.W.; Dingler, J.R.

    1982-01-01

    Monastery Beach, Carmel, California is a pocket beach that sits within 200 m of the head of Carmel Submarine Canyon. Coarse to very coarse sand covers both the beach and adjacent shelf; in the latter area incoming waves have shaped the sand into large oscillation ripples. The accessibility of this area and a variable wave climate produce a unique opportunity to study large-scale coarse-grained ripples in a high-energy environment. These ripples, which only occur in very coarse sand, form under the intense, wave-generated currents that exist during storm conditions. Once formed, these ripples do not significantly change under lower energy waves. On three separate occasions scuba divers measured ripples and collected sand samples from ripple crests near fixed reference stakes along three transects. Ripple wavelength and grain size decreased with an increase in water depth. Sediment sorting was best closest to the surf zone and poorest at the rim of Carmel Canyon. Cobbles and gravel observed in ripple troughs represent lag deposits. Carmel Canyon refracts waves approaching Monastery Beach such that wave energy is focused towards the northern and southern portions of the beach, leaving the central part of the beach lower in energy. This energy distribution causes spatial variations in the ripples and grain sizes with the shortest wavelengths and smallest grain sizes being in the central part of the shelf.