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Sample records for multidimensional gene set

  1. Multidimensional scaling for large genomic data sets

    Directory of Open Access Journals (Sweden)

    Lu Henry

    2008-04-01

    Full Text Available Abstract Background Multi-dimensional scaling (MDS is aimed to represent high dimensional data in a low dimensional space with preservation of the similarities between data points. This reduction in dimensionality is crucial for analyzing and revealing the genuine structure hidden in the data. For noisy data, dimension reduction can effectively reduce the effect of noise on the embedded structure. For large data set, dimension reduction can effectively reduce information retrieval complexity. Thus, MDS techniques are used in many applications of data mining and gene network research. However, although there have been a number of studies that applied MDS techniques to genomics research, the number of analyzed data points was restricted by the high computational complexity of MDS. In general, a non-metric MDS method is faster than a metric MDS, but it does not preserve the true relationships. The computational complexity of most metric MDS methods is over O(N2, so that it is difficult to process a data set of a large number of genes N, such as in the case of whole genome microarray data. Results We developed a new rapid metric MDS method with a low computational complexity, making metric MDS applicable for large data sets. Computer simulation showed that the new method of split-and-combine MDS (SC-MDS is fast, accurate and efficient. Our empirical studies using microarray data on the yeast cell cycle showed that the performance of K-means in the reduced dimensional space is similar to or slightly better than that of K-means in the original space, but about three times faster to obtain the clustering results. Our clustering results using SC-MDS are more stable than those in the original space. Hence, the proposed SC-MDS is useful for analyzing whole genome data. Conclusion Our new method reduces the computational complexity from O(N3 to O(N when the dimension of the feature space is far less than the number of genes N, and it successfully

  2. A complete set of multidimensional Bell inequalities

    International Nuclear Information System (INIS)

    Arnault, François

    2012-01-01

    We give a multidimensional generalization of the complete set of Bell-correlation inequalities given by Werner and Wolf (2001 Phys. Rev. A 64 032112) and by Zukowski and Brukner (2002 Phys. Rev. Lett. 88 210401), for the two-dimensional case. Our construction applies to the n-party, two-observable case, where each observable is d-valued. The d d n inequalities obtained involve homogeneous polynomials. They define the facets of a polytope in a complex vector space of dimension d n . We detail the inequalities obtained in the case d = 3 and, from them, we recover known inequalities. We finally explain how the violations of our inequalities by quantum mechanics can be computed and could be observed, when using unitary observables. (paper)

  3. Joint mapping of genes and conditions via multidimensional unfolding analysis

    Directory of Open Access Journals (Sweden)

    Engelen Kristof

    2007-06-01

    Full Text Available Abstract Background Microarray compendia profile the expression of genes in a number of experimental conditions. Such data compendia are useful not only to group genes and conditions based on their similarity in overall expression over profiles but also to gain information on more subtle relations between genes and conditions. Getting a clear visual overview of all these patterns in a single easy-to-grasp representation is a useful preliminary analysis step: We propose to use for this purpose an advanced exploratory method, called multidimensional unfolding. Results We present a novel algorithm for multidimensional unfolding that overcomes both general problems and problems that are specific for the analysis of gene expression data sets. Applying the algorithm to two publicly available microarray compendia illustrates its power as a tool for exploratory data analysis: The unfolding analysis of a first data set resulted in a two-dimensional representation which clearly reveals temporal regulation patterns for the genes and a meaningful structure for the time points, while the analysis of a second data set showed the algorithm's ability to go beyond a mere identification of those genes that discriminate between different patient or tissue types. Conclusion Multidimensional unfolding offers a useful tool for preliminary explorations of microarray data: By relying on an easy-to-grasp low-dimensional geometric framework, relations among genes, among conditions and between genes and conditions are simultaneously represented in an accessible way which may reveal interesting patterns in the data. An additional advantage of the method is that it can be applied to the raw data without necessitating the choice of suitable genewise transformations of the data.

  4. Rapid prediction of multi-dimensional NMR data sets

    International Nuclear Information System (INIS)

    Gradmann, Sabine; Ader, Christian; Heinrich, Ines; Nand, Deepak; Dittmann, Marc; Cukkemane, Abhishek; Dijk, Marc van; Bonvin, Alexandre M. J. J.; Engelhard, Martin; Baldus, Marc

    2012-01-01

    We present a computational environment for Fast Analysis of multidimensional NMR DAta Sets (FANDAS) that allows assembling multidimensional data sets from a variety of input parameters and facilitates comparing and modifying such “in silico” data sets during the various stages of the NMR data analysis. The input parameters can vary from (partial) NMR assignments directly obtained from experiments to values retrieved from in silico prediction programs. The resulting predicted data sets enable a rapid evaluation of sample labeling in light of spectral resolution and structural content, using standard NMR software such as Sparky. In addition, direct comparison to experimental data sets can be used to validate NMR assignments, distinguish different molecular components, refine structural models or other parameters derived from NMR data. The method is demonstrated in the context of solid-state NMR data obtained for the cyclic nucleotide binding domain of a bacterial cyclic nucleotide-gated channel and on membrane-embedded sensory rhodopsin II. FANDAS is freely available as web portal under WeNMR (http://www.wenmr.eu/services/FANDAShttp://www.wenmr.eu/services/FANDAS).

  5. Rapid prediction of multi-dimensional NMR data sets

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    Gradmann, Sabine; Ader, Christian [Utrecht University, Faculty of Science, Bijvoet Center for Biomolecular Research (Netherlands); Heinrich, Ines [Max Planck Institute for Molecular Physiology, Department of Physical Biochemistry (Germany); Nand, Deepak [Utrecht University, Faculty of Science, Bijvoet Center for Biomolecular Research (Netherlands); Dittmann, Marc [Max Planck Institute for Molecular Physiology, Department of Physical Biochemistry (Germany); Cukkemane, Abhishek; Dijk, Marc van; Bonvin, Alexandre M. J. J. [Utrecht University, Faculty of Science, Bijvoet Center for Biomolecular Research (Netherlands); Engelhard, Martin [Max Planck Institute for Molecular Physiology, Department of Physical Biochemistry (Germany); Baldus, Marc, E-mail: m.baldus@uu.nl [Utrecht University, Faculty of Science, Bijvoet Center for Biomolecular Research (Netherlands)

    2012-12-15

    We present a computational environment for Fast Analysis of multidimensional NMR DAta Sets (FANDAS) that allows assembling multidimensional data sets from a variety of input parameters and facilitates comparing and modifying such 'in silico' data sets during the various stages of the NMR data analysis. The input parameters can vary from (partial) NMR assignments directly obtained from experiments to values retrieved from in silico prediction programs. The resulting predicted data sets enable a rapid evaluation of sample labeling in light of spectral resolution and structural content, using standard NMR software such as Sparky. In addition, direct comparison to experimental data sets can be used to validate NMR assignments, distinguish different molecular components, refine structural models or other parameters derived from NMR data. The method is demonstrated in the context of solid-state NMR data obtained for the cyclic nucleotide binding domain of a bacterial cyclic nucleotide-gated channel and on membrane-embedded sensory rhodopsin II. FANDAS is freely available as web portal under WeNMR (http://www.wenmr.eu/services/FANDAShttp://www.wenmr.eu/services/FANDAS).

  6. Skip-webs: Efficient distributed data structures for multi-dimensional data sets

    DEFF Research Database (Denmark)

    Arge, Lars; Eppstein, David; Goodrich, Michael T.

    2005-01-01

    querying scenarios, which include linear (one-dimensional) data, such as sorted sets, as well as multi-dimensional data, such as d-dimensional octrees and digital tries of character strings defined over a fixed alphabet. We show how to perform a query over such a set of n items spread among n hosts using O...

  7. Gene set analysis for GWAS

    DEFF Research Database (Denmark)

    Debrabant, Birgit; Soerensen, Mette

    2014-01-01

    Abstract We discuss the use of modified Kolmogorov-Smirnov (KS) statistics in the context of gene set analysis and review corresponding null and alternative hypotheses. Especially, we show that, when enhancing the impact of highly significant genes in the calculation of the test statistic, the co...

  8. MXA: a customizable HDF5-based data format for multi-dimensional data sets

    International Nuclear Information System (INIS)

    Jackson, M; Simmons, J P; De Graef, M

    2010-01-01

    A new digital file format is proposed for the long-term archival storage of experimental data sets generated by serial sectioning instruments. The format is known as the multi-dimensional eXtensible Archive (MXA) format and is based on the public domain Hierarchical Data Format (HDF5). The MXA data model, its description by means of an eXtensible Markup Language (XML) file with associated Document Type Definition (DTD) are described in detail. The public domain MXA package is available through a dedicated web site (mxa.web.cmu.edu), along with implementation details and example data files

  9. Gene set analysis using variance component tests.

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    Huang, Yen-Tsung; Lin, Xihong

    2013-06-28

    Gene set analyses have become increasingly important in genomic research, as many complex diseases are contributed jointly by alterations of numerous genes. Genes often coordinate together as a functional repertoire, e.g., a biological pathway/network and are highly correlated. However, most of the existing gene set analysis methods do not fully account for the correlation among the genes. Here we propose to tackle this important feature of a gene set to improve statistical power in gene set analyses. We propose to model the effects of an independent variable, e.g., exposure/biological status (yes/no), on multiple gene expression values in a gene set using a multivariate linear regression model, where the correlation among the genes is explicitly modeled using a working covariance matrix. We develop TEGS (Test for the Effect of a Gene Set), a variance component test for the gene set effects by assuming a common distribution for regression coefficients in multivariate linear regression models, and calculate the p-values using permutation and a scaled chi-square approximation. We show using simulations that type I error is protected under different choices of working covariance matrices and power is improved as the working covariance approaches the true covariance. The global test is a special case of TEGS when correlation among genes in a gene set is ignored. Using both simulation data and a published diabetes dataset, we show that our test outperforms the commonly used approaches, the global test and gene set enrichment analysis (GSEA). We develop a gene set analyses method (TEGS) under the multivariate regression framework, which directly models the interdependence of the expression values in a gene set using a working covariance. TEGS outperforms two widely used methods, GSEA and global test in both simulation and a diabetes microarray data.

  10. Gene set analysis of the EADGENE chicken data-set

    DEFF Research Database (Denmark)

    Skarman, Axel; Jiang, Li; Hornshøj, Henrik

    2009-01-01

     Abstract Background: Gene set analysis is considered to be a way of improving our biological interpretation of the observed expression patterns. This paper describes different methods applied to analyse expression data from a chicken DNA microarray dataset. Results: Applying different gene set...... analyses to the chicken expression data led to different ranking of the Gene Ontology terms tested. A method for prediction of possible annotations was applied. Conclusion: Biological interpretation based on gene set analyses dependent on the statistical method used. Methods for predicting the possible...

  11. Novel gene sets improve set-level classification of prokaryotic gene expression data.

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    Holec, Matěj; Kuželka, Ondřej; Železný, Filip

    2015-10-28

    Set-level classification of gene expression data has received significant attention recently. In this setting, high-dimensional vectors of features corresponding to genes are converted into lower-dimensional vectors of features corresponding to biologically interpretable gene sets. The dimensionality reduction brings the promise of a decreased risk of overfitting, potentially resulting in improved accuracy of the learned classifiers. However, recent empirical research has not confirmed this expectation. Here we hypothesize that the reported unfavorable classification results in the set-level framework were due to the adoption of unsuitable gene sets defined typically on the basis of the Gene ontology and the KEGG database of metabolic networks. We explore an alternative approach to defining gene sets, based on regulatory interactions, which we expect to collect genes with more correlated expression. We hypothesize that such more correlated gene sets will enable to learn more accurate classifiers. We define two families of gene sets using information on regulatory interactions, and evaluate them on phenotype-classification tasks using public prokaryotic gene expression data sets. From each of the two gene-set families, we first select the best-performing subtype. The two selected subtypes are then evaluated on independent (testing) data sets against state-of-the-art gene sets and against the conventional gene-level approach. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. Novel gene sets defined on the basis of regulatory interactions improve set-level classification of gene expression data. The experimental scripts and other material needed to reproduce the experiments are available at http://ida.felk.cvut.cz/novelgenesets.tar.gz.

  12. Gene set analysis for interpreting genetic studies

    DEFF Research Database (Denmark)

    Pers, Tune H

    2016-01-01

    Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways...

  13. Motivation and engagement in music and sport: testing a multidimensional framework in diverse performance settings.

    Science.gov (United States)

    Martin, Andrew J

    2008-02-01

    The present study assessed the application of a multidimensional model of motivation and engagement (the Motivation and Engagement Wheel) and its accompanying instrumentation (the Motivation and Engagement Scale) to the music and sport domains. Participants were 463 young classical musicians (N=224) and sportspeople (N=239). In both music and sport samples, the data confirmed the good fit of the four hypothesized higher-order dimensions and their 11 first-order dimensions: adaptive cognitions (self-efficacy, valuing, mastery orientation), adaptive behaviors (planning, task management, persistence), impeding/maladaptive cognitions (uncertain control, anxiety, failure avoidance), and maladaptive behaviors (self-handicapping, disengagement). Multigroup tests of factor invariance showed that in terms of underlying motivational constructs and the composition of and relationships among these constructs, key subsamples are not substantially different. Moreover-and of particular relevance to issues around the generalizability of the framework-the factor structure for music and sport samples was predominantly invariant.

  14. Inferring dynamic gene regulatory networks in cardiac differentiation through the integration of multi-dimensional data.

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    Gong, Wuming; Koyano-Nakagawa, Naoko; Li, Tongbin; Garry, Daniel J

    2015-03-07

    -CM transitions. We report a novel method to systematically integrate multi-dimensional -omics data and reconstruct the gene regulatory networks. This method will allow one to rapidly determine the cis-modules that regulate key genes during cardiac differentiation.

  15. Delimiting Coalescence Genes (C-Genes) in Phylogenomic Data Sets.

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    Springer, Mark S; Gatesy, John

    2018-02-26

    coalescence methods have emerged as a popular alternative for inferring species trees with large genomic datasets, because these methods explicitly account for incomplete lineage sorting. However, statistical consistency of summary coalescence methods is not guaranteed unless several model assumptions are true, including the critical assumption that recombination occurs freely among but not within coalescence genes (c-genes), which are the fundamental units of analysis for these methods. Each c-gene has a single branching history, and large sets of these independent gene histories should be the input for genome-scale coalescence estimates of phylogeny. By contrast, numerous studies have reported the results of coalescence analyses in which complete protein-coding sequences are treated as c-genes even though exons for these loci can span more than a megabase of DNA. Empirical estimates of recombination breakpoints suggest that c-genes may be much shorter, especially when large clades with many species are the focus of analysis. Although this idea has been challenged recently in the literature, the inverse relationship between c-gene size and increased taxon sampling in a dataset-the 'recombination ratchet'-is a fundamental property of c-genes. For taxonomic groups characterized by genes with long intron sequences, complete protein-coding sequences are likely not valid c-genes and are inappropriate units of analysis for summary coalescence methods unless they occur in recombination deserts that are devoid of incomplete lineage sorting (ILS). Finally, it has been argued that coalescence methods are robust when the no-recombination within loci assumption is violated, but recombination must matter at some scale because ILS, a by-product of recombination, is the raison d'etre for coalescence methods. That is, extensive recombination is required to yield the large number of independently segregating c-genes used to infer a species tree. If coalescent methods are powerful

  16. Frail Elders in an Urban District Setting in Malaysia: Multidimensional Frailty and Its Correlates.

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    Sathasivam, Jeyanthini; Kamaruzzaman, Shahrul Bahyah; Hairi, Farizah; Ng, Chiu Wan; Chinna, Karuthan

    2015-11-01

    In the past decade, the population in Malaysia has been rapidly ageing. This poses new challenges and issues that threaten the ability of the elderly to independently age in place. A multistage cross-sectional study on 789 community-dwelling elderly individuals aged 60 years and above was conducted in an urban district in Malaysia to assess the geriatric syndrome of frailty. Using a multidimensional frailty index, we detected 67.7% prefrail and 5.7% frail elders. Cognitive status was a significant correlate for frailty status among the respondents as well as those who perceived their health status as very poor or quite poor; but self-rated health was no longer significant when controlled for sociodemographic variables. Lower-body weakness and history of falls were associated with increasing frailty levels, and this association persisted in the multivariate model. This study offers support that physical disability, falls, and cognition are important determinants for frailty. This initial work on frailty among urban elders in Malaysia provides important correlations and identifies potential risk factors that can form the basis of information for targeted preventive measures for this vulnerable group in their prefrail state. © 2015 APJPH.

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

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    Lockwood William W

    2010-05-01

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

  18. Gene set analysis of purine and pyrimidine antimetabolites cancer therapies.

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    Fridley, Brooke L; Batzler, Anthony; Li, Liang; Li, Fang; Matimba, Alice; Jenkins, Gregory D; Ji, Yuan; Wang, Liewei; Weinshilboum, Richard M

    2011-11-01

    Responses to therapies, either with regard to toxicities or efficacy, are expected to involve complex relationships of gene products within the same molecular pathway or functional gene set. Therefore, pathways or gene sets, as opposed to single genes, may better reflect the true underlying biology and may be more appropriate units for analysis of pharmacogenomic studies. Application of such methods to pharmacogenomic studies may enable the detection of more subtle effects of multiple genes in the same pathway that may be missed by assessing each gene individually. A gene set analysis of 3821 gene sets is presented assessing the association between basal messenger RNA expression and drug cytotoxicity using ethnically defined human lymphoblastoid cell lines for two classes of drugs: pyrimidines [gemcitabine (dFdC) and arabinoside] and purines [6-thioguanine and 6-mercaptopurine]. The gene set nucleoside-diphosphatase activity was found to be significantly associated with both dFdC and arabinoside, whereas gene set γ-aminobutyric acid catabolic process was associated with dFdC and 6-thioguanine. These gene sets were significantly associated with the phenotype even after adjusting for multiple testing. In addition, five associated gene sets were found in common between the pyrimidines and two gene sets for the purines (3',5'-cyclic-AMP phosphodiesterase activity and γ-aminobutyric acid catabolic process) with a P value of less than 0.0001. Functional validation was attempted with four genes each in gene sets for thiopurine and pyrimidine antimetabolites. All four genes selected from the pyrimidine gene sets (PSME3, CANT1, ENTPD6, ADRM1) were validated, but only one (PDE4D) was validated for the thiopurine gene sets. In summary, results from the gene set analysis of pyrimidine and purine therapies, used often in the treatment of various cancers, provide novel insight into the relationship between genomic variation and drug response.

  19. MAGMA: generalized gene-set analysis of GWAS data.

    NARCIS (Netherlands)

    de Leeuw, C.A.; Mooij, J.M.; Heskes, T.; Posthuma, D.

    2015-01-01

    By aggregating data for complex traits in a biologically meaningful way, gene and gene-set analysis constitute a valuable addition to single-marker analysis. However, although various methods for gene and gene-set analysis currently exist, they generally suffer from a number of issues. Statistical

  20. MAGMA: Generalized Gene-Set Analysis of GWAS Data

    NARCIS (Netherlands)

    de Leeuw, C.A.; Mooij, J.M.; Heskes, T.; Posthuma, D.

    2015-01-01

    By aggregating data for complex traits in a biologically meaningful way, gene and gene-set analysis constitute a valuable addition to single-marker analysis. However, although various methods for gene and gene-set analysis currently exist, they generally suffer from a number of issues. Statistical

  1. Studying the Complex Expression Dependences between Sets of Coexpressed Genes

    Directory of Open Access Journals (Sweden)

    Mario Huerta

    2014-01-01

    Full Text Available Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments.

  2. MAGMA: generalized gene-set analysis of GWAS data.

    Science.gov (United States)

    de Leeuw, Christiaan A; Mooij, Joris M; Heskes, Tom; Posthuma, Danielle

    2015-04-01

    By aggregating data for complex traits in a biologically meaningful way, gene and gene-set analysis constitute a valuable addition to single-marker analysis. However, although various methods for gene and gene-set analysis currently exist, they generally suffer from a number of issues. Statistical power for most methods is strongly affected by linkage disequilibrium between markers, multi-marker associations are often hard to detect, and the reliance on permutation to compute p-values tends to make the analysis computationally very expensive. To address these issues we have developed MAGMA, a novel tool for gene and gene-set analysis. The gene analysis is based on a multiple regression model, to provide better statistical performance. The gene-set analysis is built as a separate layer around the gene analysis for additional flexibility. This gene-set analysis also uses a regression structure to allow generalization to analysis of continuous properties of genes and simultaneous analysis of multiple gene sets and other gene properties. Simulations and an analysis of Crohn's Disease data are used to evaluate the performance of MAGMA and to compare it to a number of other gene and gene-set analysis tools. The results show that MAGMA has significantly more power than other tools for both the gene and the gene-set analysis, identifying more genes and gene sets associated with Crohn's Disease while maintaining a correct type 1 error rate. Moreover, the MAGMA analysis of the Crohn's Disease data was found to be considerably faster as well.

  3. Vision from next generation sequencing: multi-dimensional genome-wide analysis for producing gene regulatory networks underlying retinal development, aging and disease.

    Science.gov (United States)

    Yang, Hyun-Jin; Ratnapriya, Rinki; Cogliati, Tiziana; Kim, Jung-Woong; Swaroop, Anand

    2015-05-01

    Genomics and genetics have invaded all aspects of biology and medicine, opening uncharted territory for scientific exploration. The definition of "gene" itself has become ambiguous, and the central dogma is continuously being revised and expanded. Computational biology and computational medicine are no longer intellectual domains of the chosen few. Next generation sequencing (NGS) technology, together with novel methods of pattern recognition and network analyses, has revolutionized the way we think about fundamental biological mechanisms and cellular pathways. In this review, we discuss NGS-based genome-wide approaches that can provide deeper insights into retinal development, aging and disease pathogenesis. We first focus on gene regulatory networks (GRNs) that govern the differentiation of retinal photoreceptors and modulate adaptive response during aging. Then, we discuss NGS technology in the context of retinal disease and develop a vision for therapies based on network biology. We should emphasize that basic strategies for network construction and analyses can be transported to any tissue or cell type. We believe that specific and uniform guidelines are required for generation of genome, transcriptome and epigenome data to facilitate comparative analysis and integration of multi-dimensional data sets, and for constructing networks underlying complex biological processes. As cellular homeostasis and organismal survival are dependent on gene-gene and gene-environment interactions, we believe that network-based biology will provide the foundation for deciphering disease mechanisms and discovering novel drug targets for retinal neurodegenerative diseases. Published by Elsevier Ltd.

  4. Using the gene ontology to scan multilevel gene sets for associations in genome wide association studies.

    Science.gov (United States)

    Schaid, Daniel J; Sinnwell, Jason P; Jenkins, Gregory D; McDonnell, Shannon K; Ingle, James N; Kubo, Michiaki; Goss, Paul E; Costantino, Joseph P; Wickerham, D Lawrence; Weinshilboum, Richard M

    2012-01-01

    Gene-set analyses have been widely used in gene expression studies, and some of the developed methods have been extended to genome wide association studies (GWAS). Yet, complications due to linkage disequilibrium (LD) among single nucleotide polymorphisms (SNPs), and variable numbers of SNPs per gene and genes per gene-set, have plagued current approaches, often leading to ad hoc "fixes." To overcome some of the current limitations, we developed a general approach to scan GWAS SNP data for both gene-level and gene-set analyses, building on score statistics for generalized linear models, and taking advantage of the directed acyclic graph structure of the gene ontology when creating gene-sets. However, other types of gene-set structures can be used, such as the popular Kyoto Encyclopedia of Genes and Genomes (KEGG). Our approach combines SNPs into genes, and genes into gene-sets, but assures that positive and negative effects of genes on a trait do not cancel. To control for multiple testing of many gene-sets, we use an efficient computational strategy that accounts for LD and provides accurate step-down adjusted P-values for each gene-set. Application of our methods to two different GWAS provide guidance on the potential strengths and weaknesses of our proposed gene-set analyses. © 2011 Wiley Periodicals, Inc.

  5. Principles for the organization of gene-sets.

    Science.gov (United States)

    Li, Wentian; Freudenberg, Jan; Oswald, Michaela

    2015-12-01

    A gene-set, an important concept in microarray expression analysis and systems biology, is a collection of genes and/or their products (i.e. proteins) that have some features in common. There are many different ways to construct gene-sets, but a systematic organization of these ways is lacking. Gene-sets are mainly organized ad hoc in current public-domain databases, with group header names often determined by practical reasons (such as the types of technology in obtaining the gene-sets or a balanced number of gene-sets under a header). Here we aim at providing a gene-set organization principle according to the level at which genes are connected: homology, physical map proximity, chemical interaction, biological, and phenotypic-medical levels. We also distinguish two types of connections between genes: actual connection versus sharing of a label. Actual connections denote direct biological interactions, whereas shared label connection denotes shared membership in a group. Some extensions of the framework are also addressed such as overlapping of gene-sets, modules, and the incorporation of other non-protein-coding entities such as microRNAs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. A Bayesian variable selection procedure for ranking overlapping gene sets

    DEFF Research Database (Denmark)

    Skarman, Axel; Mahdi Shariati, Mohammad; Janss, Luc

    2012-01-01

    Background Genome-wide expression profiling using microarrays or sequence-based technologies allows us to identify genes and genetic pathways whose expression patterns influence complex traits. Different methods to prioritize gene sets, such as the genes in a given molecular pathway, have been de...

  7. IGSA: Individual Gene Sets Analysis, including Enrichment and Clustering.

    Science.gov (United States)

    Wu, Lingxiang; Chen, Xiujie; Zhang, Denan; Zhang, Wubing; Liu, Lei; Ma, Hongzhe; Yang, Jingbo; Xie, Hongbo; Liu, Bo; Jin, Qing

    2016-01-01

    Analysis of gene sets has been widely applied in various high-throughput biological studies. One weakness in the traditional methods is that they neglect the heterogeneity of genes expressions in samples which may lead to the omission of some specific and important gene sets. It is also difficult for them to reflect the severities of disease and provide expression profiles of gene sets for individuals. We developed an application software called IGSA that leverages a powerful analytical capacity in gene sets enrichment and samples clustering. IGSA calculates gene sets expression scores for each sample and takes an accumulating clustering strategy to let the samples gather into the set according to the progress of disease from mild to severe. We focus on gastric, pancreatic and ovarian cancer data sets for the performance of IGSA. We also compared the results of IGSA in KEGG pathways enrichment with David, GSEA, SPIA, ssGSEA and analyzed the results of IGSA clustering and different similarity measurement methods. Notably, IGSA is proved to be more sensitive and specific in finding significant pathways, and can indicate related changes in pathways with the severity of disease. In addition, IGSA provides with significant gene sets profile for each sample.

  8. Multidimensional family therapy lowers the rate of cannabis dependence in adolescents: A randomised controlled trial in Western European outpatient settings

    NARCIS (Netherlands)

    H. Rigter (Henk); C.E. Henderson (Craig); I. Pelc (Isidore); P. Tossmann (Peter); O. Phan (Olivier); V. Hendriks (Vincent); M. Schaub (Michael); C. Rowe (Cindy)

    2013-01-01

    textabstractBackground: Noticing a lack of evidence-based programmes for treating adolescents heavily using cannabis in Europe, government representatives from Belgium, France, Germany, The Netherlands, and Switzerland decided to have U.S.-developed multidimensional family therapy (MDFT) tested in

  9. Evaluating the consistency of gene sets used in the analysis of bacterial gene expression data

    Directory of Open Access Journals (Sweden)

    Tintle Nathan L

    2012-08-01

    Full Text Available Abstract Background Statistical analyses of whole genome expression data require functional information about genes in order to yield meaningful biological conclusions. The Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG are common sources of functionally grouped gene sets. For bacteria, the SEED and MicrobesOnline provide alternative, complementary sources of gene sets. To date, no comprehensive evaluation of the data obtained from these resources has been performed. Results We define a series of gene set consistency metrics directly related to the most common classes of statistical analyses for gene expression data, and then perform a comprehensive analysis of 3581 Affymetrix® gene expression arrays across 17 diverse bacteria. We find that gene sets obtained from GO and KEGG demonstrate lower consistency than those obtained from the SEED and MicrobesOnline, regardless of gene set size. Conclusions Despite the widespread use of GO and KEGG gene sets in bacterial gene expression data analysis, the SEED and MicrobesOnline provide more consistent sets for a wide variety of statistical analyses. Increased use of the SEED and MicrobesOnline gene sets in the analysis of bacterial gene expression data may improve statistical power and utility of expression data.

  10. Multidimensional spectrometer

    Science.gov (United States)

    Zanni, Martin Thomas; Damrauer, Niels H.

    2010-07-20

    A multidimensional spectrometer for the infrared, visible, and ultraviolet regions of the electromagnetic spectrum, and a method for making multidimensional spectroscopic measurements in the infrared, visible, and ultraviolet regions of the electromagnetic spectrum. The multidimensional spectrometer facilitates measurements of inter- and intra-molecular interactions.

  11. A hybrid approach of gene sets and single genes for the prediction of survival risks with gene expression data.

    Science.gov (United States)

    Seok, Junhee; Davis, Ronald W; Xiao, Wenzhong

    2015-01-01

    Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn't been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge.

  12. Zebrafish Expression Ontology of Gene Sets (ZEOGS): a tool to analyze enrichment of zebrafish anatomical terms in large gene sets.

    Science.gov (United States)

    Prykhozhij, Sergey V; Marsico, Annalisa; Meijsing, Sebastiaan H

    2013-09-01

    The zebrafish (Danio rerio) is an established model organism for developmental and biomedical research. It is frequently used for high-throughput functional genomics experiments, such as genome-wide gene expression measurements, to systematically analyze molecular mechanisms. However, the use of whole embryos or larvae in such experiments leads to a loss of the spatial information. To address this problem, we have developed a tool called Zebrafish Expression Ontology of Gene Sets (ZEOGS) to assess the enrichment of anatomical terms in large gene sets. ZEOGS uses gene expression pattern data from several sources: first, in situ hybridization experiments from the Zebrafish Model Organism Database (ZFIN); second, it uses the Zebrafish Anatomical Ontology, a controlled vocabulary that describes connected anatomical structures; and third, the available connections between expression patterns and anatomical terms contained in ZFIN. Upon input of a gene set, ZEOGS determines which anatomical structures are overrepresented in the input gene set. ZEOGS allows one for the first time to look at groups of genes and to describe them in terms of shared anatomical structures. To establish ZEOGS, we first tested it on random gene selections and on two public microarray datasets with known tissue-specific gene expression changes. These tests showed that ZEOGS could reliably identify the tissues affected, whereas only very few enriched terms to none were found in the random gene sets. Next we applied ZEOGS to microarray datasets of 24 and 72 h postfertilization zebrafish embryos treated with beclomethasone, a potent glucocorticoid. This analysis resulted in the identification of several anatomical terms related to glucocorticoid-responsive tissues, some of which were stage-specific. Our studies highlight the ability of ZEOGS to extract spatial information from datasets derived from whole embryos, indicating that ZEOGS could be a useful tool to automatically analyze gene expression

  13. Zebrafish Expression Ontology of Gene Sets (ZEOGS): A Tool to Analyze Enrichment of Zebrafish Anatomical Terms in Large Gene Sets

    Science.gov (United States)

    Marsico, Annalisa

    2013-01-01

    Abstract The zebrafish (Danio rerio) is an established model organism for developmental and biomedical research. It is frequently used for high-throughput functional genomics experiments, such as genome-wide gene expression measurements, to systematically analyze molecular mechanisms. However, the use of whole embryos or larvae in such experiments leads to a loss of the spatial information. To address this problem, we have developed a tool called Zebrafish Expression Ontology of Gene Sets (ZEOGS) to assess the enrichment of anatomical terms in large gene sets. ZEOGS uses gene expression pattern data from several sources: first, in situ hybridization experiments from the Zebrafish Model Organism Database (ZFIN); second, it uses the Zebrafish Anatomical Ontology, a controlled vocabulary that describes connected anatomical structures; and third, the available connections between expression patterns and anatomical terms contained in ZFIN. Upon input of a gene set, ZEOGS determines which anatomical structures are overrepresented in the input gene set. ZEOGS allows one for the first time to look at groups of genes and to describe them in terms of shared anatomical structures. To establish ZEOGS, we first tested it on random gene selections and on two public microarray datasets with known tissue-specific gene expression changes. These tests showed that ZEOGS could reliably identify the tissues affected, whereas only very few enriched terms to none were found in the random gene sets. Next we applied ZEOGS to microarray datasets of 24 and 72 h postfertilization zebrafish embryos treated with beclomethasone, a potent glucocorticoid. This analysis resulted in the identification of several anatomical terms related to glucocorticoid-responsive tissues, some of which were stage-specific. Our studies highlight the ability of ZEOGS to extract spatial information from datasets derived from whole embryos, indicating that ZEOGS could be a useful tool to automatically analyze gene

  14. GO(vis), a gene ontology visualization tool based on multi-dimensional values.

    Science.gov (United States)

    Ning, Zi; Jiang, Zhenran

    2010-05-01

    Most of gene product similarity measurements concentrate on the information content of Gene Ontology (GO) terms or use a path-based similarity between GO terms, which may ignore other important information contained in the structure of the ontology. In our study, we integrate different GO similarity measure approaches to analyze the functional relationship of genes and gene products with a new triangle-based visualization tool called GO(Vis). The purpose of this tool is to demonstrate the effect of three important information factors when measuring the similarity between gene products. One advantage of this tool is that its important ratio can be adjusted to meet different measuring requirements according to the biological knowledge of each factor. The experimental results demonstrate that GO(Vis) can display diagrams of the functional relationship for gene products effectively.

  15. Discovery of cancer common and specific driver gene sets

    Science.gov (United States)

    2017-01-01

    Abstract Cancer is known as a disease mainly caused by gene alterations. Discovery of mutated driver pathways or gene sets is becoming an important step to understand molecular mechanisms of carcinogenesis. However, systematically investigating commonalities and specificities of driver gene sets among multiple cancer types is still a great challenge, but this investigation will undoubtedly benefit deciphering cancers and will be helpful for personalized therapy and precision medicine in cancer treatment. In this study, we propose two optimization models to de novo discover common driver gene sets among multiple cancer types (ComMDP) and specific driver gene sets of one certain or multiple cancer types to other cancers (SpeMDP), respectively. We first apply ComMDP and SpeMDP to simulated data to validate their efficiency. Then, we further apply these methods to 12 cancer types from The Cancer Genome Atlas (TCGA) and obtain several biologically meaningful driver pathways. As examples, we construct a common cancer pathway model for BRCA and OV, infer a complex driver pathway model for BRCA carcinogenesis based on common driver gene sets of BRCA with eight cancer types, and investigate specific driver pathways of the liquid cancer lymphoblastic acute myeloid leukemia (LAML) versus other solid cancer types. In these processes more candidate cancer genes are also found. PMID:28168295

  16. Time-Course Gene Set Analysis for Longitudinal Gene Expression Data.

    Directory of Open Access Journals (Sweden)

    Boris P Hejblum

    2015-06-01

    Full Text Available Gene set analysis methods, which consider predefined groups of genes in the analysis of genomic data, have been successfully applied for analyzing gene expression data in cross-sectional studies. The time-course gene set analysis (TcGSA introduced here is an extension of gene set analysis to longitudinal data. The proposed method relies on random effects modeling with maximum likelihood estimates. It allows to use all available repeated measurements while dealing with unbalanced data due to missing at random (MAR measurements. TcGSA is a hypothesis driven method that identifies a priori defined gene sets with significant expression variations over time, taking into account the potential heterogeneity of expression within gene sets. When biological conditions are compared, the method indicates if the time patterns of gene sets significantly differ according to these conditions. The interest of the method is illustrated by its application to two real life datasets: an HIV therapeutic vaccine trial (DALIA-1 trial, and data from a recent study on influenza and pneumococcal vaccines. In the DALIA-1 trial TcGSA revealed a significant change in gene expression over time within 69 gene sets during vaccination, while a standard univariate individual gene analysis corrected for multiple testing as well as a standard a Gene Set Enrichment Analysis (GSEA for time series both failed to detect any significant pattern change over time. When applied to the second illustrative data set, TcGSA allowed the identification of 4 gene sets finally found to be linked with the influenza vaccine too although they were found to be associated to the pneumococcal vaccine only in previous analyses. In our simulation study TcGSA exhibits good statistical properties, and an increased power compared to other approaches for analyzing time-course expression patterns of gene sets. The method is made available for the community through an R package.

  17. Effect of the absolute statistic on gene-sampling gene-set analysis methods.

    Science.gov (United States)

    Nam, Dougu

    2017-06-01

    Gene-set enrichment analysis and its modified versions have commonly been used for identifying altered functions or pathways in disease from microarray data. In particular, the simple gene-sampling gene-set analysis methods have been heavily used for datasets with only a few sample replicates. The biggest problem with this approach is the highly inflated false-positive rate. In this paper, the effect of absolute gene statistic on gene-sampling gene-set analysis methods is systematically investigated. Thus far, the absolute gene statistic has merely been regarded as a supplementary method for capturing the bidirectional changes in each gene set. Here, it is shown that incorporating the absolute gene statistic in gene-sampling gene-set analysis substantially reduces the false-positive rate and improves the overall discriminatory ability. Its effect was investigated by power, false-positive rate, and receiver operating curve for a number of simulated and real datasets. The performances of gene-set analysis methods in one-tailed (genome-wide association study) and two-tailed (gene expression data) tests were also compared and discussed.

  18. APPRIS 2017: principal isoforms for multiple gene sets

    Science.gov (United States)

    Rodriguez-Rivas, Juan; Di Domenico, Tomás; Vázquez, Jesús; Valencia, Alfonso

    2018-01-01

    Abstract The APPRIS database (http://appris-tools.org) uses protein structural and functional features and information from cross-species conservation to annotate splice isoforms in protein-coding genes. APPRIS selects a single protein isoform, the ‘principal’ isoform, as the reference for each gene based on these annotations. A single main splice isoform reflects the biological reality for most protein coding genes and APPRIS principal isoforms are the best predictors of these main proteins isoforms. Here, we present the updates to the database, new developments that include the addition of three new species (chimpanzee, Drosophila melangaster and Caenorhabditis elegans), the expansion of APPRIS to cover the RefSeq gene set and the UniProtKB proteome for six species and refinements in the core methods that make up the annotation pipeline. In addition APPRIS now provides a measure of reliability for individual principal isoforms and updates with each release of the GENCODE/Ensembl and RefSeq reference sets. The individual GENCODE/Ensembl, RefSeq and UniProtKB reference gene sets for six organisms have been merged to produce common sets of splice variants. PMID:29069475

  19. Ranking metrics in gene set enrichment analysis: do they matter?

    Science.gov (United States)

    Zyla, Joanna; Marczyk, Michal; Weiner, January; Polanska, Joanna

    2017-05-12

    There exist many methods for describing the complex relation between changes of gene expression in molecular pathways or gene ontologies under different experimental conditions. Among them, Gene Set Enrichment Analysis seems to be one of the most commonly used (over 10,000 citations). An important parameter, which could affect the final result, is the choice of a metric for the ranking of genes. Applying a default ranking metric may lead to poor results. In this work 28 benchmark data sets were used to evaluate the sensitivity and false positive rate of gene set analysis for 16 different ranking metrics including new proposals. Furthermore, the robustness of the chosen methods to sample size was tested. Using k-means clustering algorithm a group of four metrics with the highest performance in terms of overall sensitivity, overall false positive rate and computational load was established i.e. absolute value of Moderated Welch Test statistic, Minimum Significant Difference, absolute value of Signal-To-Noise ratio and Baumgartner-Weiss-Schindler test statistic. In case of false positive rate estimation, all selected ranking metrics were robust with respect to sample size. In case of sensitivity, the absolute value of Moderated Welch Test statistic and absolute value of Signal-To-Noise ratio gave stable results, while Baumgartner-Weiss-Schindler and Minimum Significant Difference showed better results for larger sample size. Finally, the Gene Set Enrichment Analysis method with all tested ranking metrics was parallelised and implemented in MATLAB, and is available at https://github.com/ZAEDPolSl/MrGSEA . Choosing a ranking metric in Gene Set Enrichment Analysis has critical impact on results of pathway enrichment analysis. The absolute value of Moderated Welch Test has the best overall sensitivity and Minimum Significant Difference has the best overall specificity of gene set analysis. When the number of non-normally distributed genes is high, using Baumgartner

  20. Model-based gene set analysis for Bioconductor.

    Science.gov (United States)

    Bauer, Sebastian; Robinson, Peter N; Gagneur, Julien

    2011-07-01

    Gene Ontology and other forms of gene-category analysis play a major role in the evaluation of high-throughput experiments in molecular biology. Single-category enrichment analysis procedures such as Fisher's exact test tend to flag large numbers of redundant categories as significant, which can complicate interpretation. We have recently developed an approach called model-based gene set analysis (MGSA), that substantially reduces the number of redundant categories returned by the gene-category analysis. In this work, we present the Bioconductor package mgsa, which makes the MGSA algorithm available to users of the R language. Our package provides a simple and flexible application programming interface for applying the approach. The mgsa package has been made available as part of Bioconductor 2.8. It is released under the conditions of the Artistic license 2.0. peter.robinson@charite.de; julien.gagneur@embl.de.

  1. GeneTopics - interpretation of gene sets via literature-driven topic models

    Science.gov (United States)

    2013-01-01

    Background Annotation of a set of genes is often accomplished through comparison to a library of labelled gene sets such as biological processes or canonical pathways. However, this approach might fail if the employed libraries are not up to date with the latest research, don't capture relevant biological themes or are curated at a different level of granularity than is required to appropriately analyze the input gene set. At the same time, the vast biomedical literature offers an unstructured repository of the latest research findings that can be tapped to provide thematic sub-groupings for any input gene set. Methods Our proposed method relies on a gene-specific text corpus and extracts commonalities between documents in an unsupervised manner using a topic model approach. We automatically determine the number of topics summarizing the corpus and calculate a gene relevancy score for each topic allowing us to eliminate non-specific topics. As a result we obtain a set of literature topics in which each topic is associated with a subset of the input genes providing directly interpretable keywords and corresponding documents for literature research. Results We validate our method based on labelled gene sets from the KEGG metabolic pathway collection and the genetic association database (GAD) and show that the approach is able to detect topics consistent with the labelled annotation. Furthermore, we discuss the results on three different types of experimentally derived gene sets, (1) differentially expressed genes from a cardiac hypertrophy experiment in mice, (2) altered transcript abundance in human pancreatic beta cells, and (3) genes implicated by GWA studies to be associated with metabolite levels in a healthy population. In all three cases, we are able to replicate findings from the original papers in a quick and semi-automated manner. Conclusions Our approach provides a novel way of automatically generating meaningful annotations for gene sets that are directly

  2. GSMA: Gene Set Matrix Analysis, An Automated Method for Rapid Hypothesis Testing of Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Chris Cheadle

    2007-01-01

    Full Text Available Background: Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. The assignment of functional information to these complex patterns remains a challenging task in effectively interpreting data and correlating results from across experiments, projects and laboratories. Methods which allow the rapid and robust evaluation of multiple functional hypotheses increase the power of individual researchers to data mine gene expression data more efficiently.Results: We have developed (gene set matrix analysis GSMA as a useful method for the rapid testing of group-wise up- or downregulation of gene expression simultaneously for multiple lists of genes (gene sets against entire distributions of gene expression changes (datasets for single or multiple experiments. The utility of GSMA lies in its flexibility to rapidly poll gene sets related by known biological function or as designated solely by the end-user against large numbers of datasets simultaneously.Conclusions: GSMA provides a simple and straightforward method for hypothesis testing in which genes are tested by groups across multiple datasets for patterns of expression enrichment.

  3. Multidimensional evaluation of a radio frequency identification wi-fi location tracking system in an acute-care hospital setting.

    Science.gov (United States)

    Okoniewska, Barbara; Graham, Alecia; Gavrilova, Marina; Wah, Dannel; Gilgen, Jonathan; Coke, Jason; Burden, Jack; Nayyar, Shikha; Kaunda, Joseph; Yergens, Dean; Baylis, Barry; Ghali, William A

    2012-01-01

    Real-time locating systems (RTLS) have the potential to enhance healthcare systems through the live tracking of assets, patients and staff. This study evaluated a commercially available RTLS system deployed in a clinical setting, with three objectives: (1) assessment of the location accuracy of the technology in a clinical setting; (2) assessment of the value of asset tracking to staff; and (3) assessment of threshold monitoring applications developed for patient tracking and inventory control. Simulated daily activities were monitored by RTLS and compared with direct research team observations. Staff surveys and interviews concerning the system's effectiveness and accuracy were also conducted and analyzed. The study showed only modest location accuracy, and mixed reactions in staff interviews. These findings reveal that the technology needs to be refined further for better specific location accuracy before full-scale implementation can be recommended.

  4. Integrative analysis of survival-associated gene sets in breast cancer.

    Science.gov (United States)

    Varn, Frederick S; Ung, Matthew H; Lou, Shao Ke; Cheng, Chao

    2015-03-12

    Patient gene expression information has recently become a clinical feature used to evaluate breast cancer prognosis. The emergence of prognostic gene sets that take advantage of these data has led to a rich library of information that can be used to characterize the molecular nature of a patient's cancer. Identifying robust gene sets that are consistently predictive of a patient's clinical outcome has become one of the main challenges in the field. We inputted our previously established BASE algorithm with patient gene expression data and gene sets from MSigDB to develop the gene set activity score (GSAS), a metric that quantitatively assesses a gene set's activity level in a given patient. We utilized this metric, along with patient time-to-event data, to perform survival analyses to identify the gene sets that were significantly correlated with patient survival. We then performed cross-dataset analyses to identify robust prognostic gene sets and to classify patients by metastasis status. Additionally, we created a gene set network based on component gene overlap to explore the relationship between gene sets derived from MSigDB. We developed a novel gene set based on this network's topology and applied the GSAS metric to characterize its role in patient survival. Using the GSAS metric, we identified 120 gene sets that were significantly associated with patient survival in all datasets tested. The gene overlap network analysis yielded a novel gene set enriched in genes shared by the robustly predictive gene sets. This gene set was highly correlated to patient survival when used alone. Most interestingly, removal of the genes in this gene set from the gene pool on MSigDB resulted in a large reduction in the number of predictive gene sets, suggesting a prominent role for these genes in breast cancer progression. The GSAS metric provided a useful medium by which we systematically investigated how gene sets from MSigDB relate to breast cancer patient survival. We used

  5. Multidimensional Databases and Data Warehousing

    CERN Document Server

    Jensen, Christian

    2010-01-01

    The present book's subject is multidimensional data models and data modeling concepts as they are applied in real data warehouses. The book aims to present the most important concepts within this subject in a precise and understandable manner. The book's coverage of fundamental concepts includes data cubes and their elements, such as dimensions, facts, and measures and their representation in a relational setting; it includes architecture-related concepts; and it includes the querying of multidimensional databases.The book also covers advanced multidimensional concepts that are considered to b

  6. Identification of a robust gene signature that predicts breast cancer outcome in independent data sets

    International Nuclear Information System (INIS)

    Korkola, James E; Waldman, Frederic M; Blaveri, Ekaterina; DeVries, Sandy; Moore, Dan H II; Hwang, E Shelley; Chen, Yunn-Yi; Estep, Anne LH; Chew, Karen L; Jensen, Ronald H

    2007-01-01

    Breast cancer is a heterogeneous disease, presenting with a wide range of histologic, clinical, and genetic features. Microarray technology has shown promise in predicting outcome in these patients. We profiled 162 breast tumors using expression microarrays to stratify tumors based on gene expression. A subset of 55 tumors with extensive follow-up was used to identify gene sets that predicted outcome. The predictive gene set was further tested in previously published data sets. We used different statistical methods to identify three gene sets associated with disease free survival. A fourth gene set, consisting of 21 genes in common to all three sets, also had the ability to predict patient outcome. To validate the predictive utility of this derived gene set, it was tested in two published data sets from other groups. This gene set resulted in significant separation of patients on the basis of survival in these data sets, correctly predicting outcome in 62–65% of patients. By comparing outcome prediction within subgroups based on ER status, grade, and nodal status, we found that our gene set was most effective in predicting outcome in ER positive and node negative tumors. This robust gene selection with extensive validation has identified a predictive gene set that may have clinical utility for outcome prediction in breast cancer patients

  7. Three gene expression vector sets for concurrently expressing multiple genes in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ishii, Jun; Kondo, Takashi; Makino, Harumi; Ogura, Akira; Matsuda, Fumio; Kondo, Akihiko

    2014-05-01

    Yeast has the potential to be used in bulk-scale fermentative production of fuels and chemicals due to its tolerance for low pH and robustness for autolysis. However, expression of multiple external genes in one host yeast strain is considerably labor-intensive due to the lack of polycistronic transcription. To promote the metabolic engineering of yeast, we generated systematic and convenient genetic engineering tools to express multiple genes in Saccharomyces cerevisiae. We constructed a series of multi-copy and integration vector sets for concurrently expressing two or three genes in S. cerevisiae by embedding three classical promoters. The comparative expression capabilities of the constructed vectors were monitored with green fluorescent protein, and the concurrent expression of genes was monitored with three different fluorescent proteins. Our multiple gene expression tool will be helpful to the advanced construction of genetically engineered yeast strains in a variety of research fields other than metabolic engineering. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  8. Tracking difference in gene expression in a time-course experiment using gene set enrichment analysis.

    Directory of Open Access Journals (Sweden)

    Pui Shan Wong

    Full Text Available Fistulifera sp. strain JPCC DA0580 is a newly sequenced pennate diatom that is capable of simultaneously growing and accumulating lipids. This is a unique trait, not found in other related microalgae so far. It is able to accumulate between 40 to 60% of its cell weight in lipids, making it a strong candidate for the production of biofuel. To investigate this characteristic, we used RNA-Seq data gathered at four different times while Fistulifera sp. strain JPCC DA0580 was grown in oil accumulating and non-oil accumulating conditions. We then adapted gene set enrichment analysis (GSEA to investigate the relationship between the difference in gene expression of 7,822 genes and metabolic functions in our data. We utilized information in the KEGG pathway database to create the gene sets and changed GSEA to use re-sampling so that data from the different time points could be included in the analysis. Our GSEA method identified photosynthesis, lipid synthesis and amino acid synthesis related pathways as processes that play a significant role in oil production and growth in Fistulifera sp. strain JPCC DA0580. In addition to GSEA, we visualized the results by creating a network of compounds and reactions, and plotted the expression data on top of the network. This made existing graph algorithms available to us which we then used to calculate a path that metabolizes glucose into triacylglycerol (TAG in the smallest number of steps. By visualizing the data this way, we observed a separate up-regulation of genes at different times instead of a concerted response. We also identified two metabolic paths that used less reactions than the one shown in KEGG and showed that the reactions were up-regulated during the experiment. The combination of analysis and visualization methods successfully analyzed time-course data, identified important metabolic pathways and provided new hypotheses for further research.

  9. MODELO MULTIDIMENSIONAL

    Directory of Open Access Journals (Sweden)

    Alexis Cedeño Trujillo

    2006-04-01

    Full Text Available

    Data Warehousing, es una tecnología para el almacenamiento de grandes volúmenes de datos en una amplia perspectiva de tiempo para el soporte a la toma de decisiones. Debido a su orientación analítica, impone un procesamiento distinto al de los sistemas operacionales y requiere de un diseño de base de datos más cercano a la visión de los usuarios finales, permitiendo que sea más fácil la recuperación de información y la navegación. Este diseño de base de datos se conoce como modelo multidimensional, este artículo, abordará sus características principales.

  10. Multi-Dimensional Path Queries

    DEFF Research Database (Denmark)

    Bækgaard, Lars

    1998-01-01

    to create nested path structures. We present an SQL-like query language that is based on path expressions and we show how to use it to express multi-dimensional path queries that are suited for advanced data analysis in decision support environments like data warehousing environments......We present the path-relationship model that supports multi-dimensional data modeling and querying. A path-relationship database is composed of sets of paths and sets of relationships. A path is a sequence of related elements (atoms, paths, and sets of paths). A relationship is a binary path...

  11. LEGO: a novel method for gene set over-representation analysis by incorporating network-based gene weights.

    Science.gov (United States)

    Dong, Xinran; Hao, Yun; Wang, Xiao; Tian, Weidong

    2016-01-11

    Pathway or gene set over-representation analysis (ORA) has become a routine task in functional genomics studies. However, currently widely used ORA tools employ statistical methods such as Fisher's exact test that reduce a pathway into a list of genes, ignoring the constitutive functional non-equivalent roles of genes and the complex gene-gene interactions. Here, we develop a novel method named LEGO (functional Link Enrichment of Gene Ontology or gene sets) that takes into consideration these two types of information by incorporating network-based gene weights in ORA analysis. In three benchmarks, LEGO achieves better performance than Fisher and three other network-based methods. To further evaluate LEGO's usefulness, we compare LEGO with five gene expression-based and three pathway topology-based methods using a benchmark of 34 disease gene expression datasets compiled by a recent publication, and show that LEGO is among the top-ranked methods in terms of both sensitivity and prioritization for detecting target KEGG pathways. In addition, we develop a cluster-and-filter approach to reduce the redundancy among the enriched gene sets, making the results more interpretable to biologists. Finally, we apply LEGO to two lists of autism genes, and identify relevant gene sets to autism that could not be found by Fisher.

  12. Beyond main effects of gene-sets: harsh parenting moderates the association between a dopamine gene-set and child externalizing behavior.

    Science.gov (United States)

    Windhorst, Dafna A; Mileva-Seitz, Viara R; Rippe, Ralph C A; Tiemeier, Henning; Jaddoe, Vincent W V; Verhulst, Frank C; van IJzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

    2016-08-01

    In a longitudinal cohort study, we investigated the interplay of harsh parenting and genetic variation across a set of functionally related dopamine genes, in association with children's externalizing behavior. This is one of the first studies to employ gene-based and gene-set approaches in tests of Gene by Environment (G × E) effects on complex behavior. This approach can offer an important alternative or complement to candidate gene and genome-wide environmental interaction (GWEI) studies in the search for genetic variation underlying individual differences in behavior. Genetic variants in 12 autosomal dopaminergic genes were available in an ethnically homogenous part of a population-based cohort. Harsh parenting was assessed with maternal (n = 1881) and paternal (n = 1710) reports at age 3. Externalizing behavior was assessed with the Child Behavior Checklist (CBCL) at age 5 (71 ± 3.7 months). We conducted gene-set analyses of the association between variation in dopaminergic genes and externalizing behavior, stratified for harsh parenting. The association was statistically significant or approached significance for children without harsh parenting experiences, but was absent in the group with harsh parenting. Similarly, significant associations between single genes and externalizing behavior were only found in the group without harsh parenting. Effect sizes in the groups with and without harsh parenting did not differ significantly. Gene-environment interaction tests were conducted for individual genetic variants, resulting in two significant interaction effects (rs1497023 and rs4922132) after correction for multiple testing. Our findings are suggestive of G × E interplay, with associations between dopamine genes and externalizing behavior present in children without harsh parenting, but not in children with harsh parenting experiences. Harsh parenting may overrule the role of genetic factors in externalizing behavior. Gene-based and gene-set

  13. Uniform approximation is more appropriate for Wilcoxon Rank-Sum Test in gene set analysis.

    Directory of Open Access Journals (Sweden)

    Zhide Fang

    Full Text Available Gene set analysis is widely used to facilitate biological interpretations in the analyses of differential expression from high throughput profiling data. Wilcoxon Rank-Sum (WRS test is one of the commonly used methods in gene set enrichment analysis. It compares the ranks of genes in a gene set against those of genes outside the gene set. This method is easy to implement and it eliminates the dichotomization of genes into significant and non-significant in a competitive hypothesis testing. Due to the large number of genes being examined, it is impractical to calculate the exact null distribution for the WRS test. Therefore, the normal distribution is commonly used as an approximation. However, as we demonstrate in this paper, the normal approximation is problematic when a gene set with relative small number of genes is tested against the large number of genes in the complementary set. In this situation, a uniform approximation is substantially more powerful, more accurate, and less intensive in computation. We demonstrate the advantage of the uniform approximations in Gene Ontology (GO term analysis using simulations and real data sets.

  14. Beyond main effects of gene-sets: harsh parenting moderates the association between a dopamine gene-set and child externalizing behavior

    NARCIS (Netherlands)

    J. Windhorst (Judith); V. Mileva-Seitz (Viara); R.C.A. Rippe (Ralph C.A.); H.W. Tiemeier (Henning); V.W.V. Jaddoe (Vincent); F.C. Verhulst (Frank); M.H. van IJzendoorn (Rien); M.J. Bakermans-Kranenburg (Marian)

    2016-01-01

    textabstractBackground: In a longitudinal cohort study, we investigated the interplay of harsh parenting and genetic variation across a set of functionally related dopamine genes, in association with children's externalizing behavior. This is one of the first studies to employ gene-based and

  15. Constellation Map: Downstream visualization and interpretation of gene set enrichment results [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Yan Tan

    2015-06-01

    Full Text Available Summary: Gene set enrichment analysis (GSEA approaches are widely used to identify coordinately regulated genes associated with phenotypes of interest. Here, we present Constellation Map, a tool to visualize and interpret the results when enrichment analyses yield a long list of significantly enriched gene sets. Constellation Map identifies commonalities that explain the enrichment of multiple top-scoring gene sets and maps the relationships between them. Constellation Map can help investigators take full advantage of GSEA and facilitates the biological interpretation of enrichment results. Availability: Constellation Map is freely available as a GenePattern module at http://www.genepattern.org.

  16. Gene set of nuclear-encoded mitochondrial regulators is enriched for common inherited variation in obesity.

    Directory of Open Access Journals (Sweden)

    Nadja Knoll

    Full Text Available There are hints of an altered mitochondrial function in obesity. Nuclear-encoded genes are relevant for mitochondrial function (3 gene sets of known relevant pathways: (1 16 nuclear regulators of mitochondrial genes, (2 91 genes for oxidative phosphorylation and (3 966 nuclear-encoded mitochondrial genes. Gene set enrichment analysis (GSEA showed no association with type 2 diabetes mellitus in these gene sets. Here we performed a GSEA for the same gene sets for obesity. Genome wide association study (GWAS data from a case-control approach on 453 extremely obese children and adolescents and 435 lean adult controls were used for GSEA. For independent confirmation, we analyzed 705 obesity GWAS trios (extremely obese child and both biological parents and a population-based GWAS sample (KORA F4, n = 1,743. A meta-analysis was performed on all three samples. In each sample, the distribution of significance levels between the respective gene set and those of all genes was compared using the leading-edge-fraction-comparison test (cut-offs between the 50(th and 95(th percentile of the set of all gene-wise corrected p-values as implemented in the MAGENTA software. In the case-control sample, significant enrichment of associations with obesity was observed above the 50(th percentile for the set of the 16 nuclear regulators of mitochondrial genes (p(GSEA,50 = 0.0103. This finding was not confirmed in the trios (p(GSEA,50 = 0.5991, but in KORA (p(GSEA,50 = 0.0398. The meta-analysis again indicated a trend for enrichment (p(MAGENTA,50 = 0.1052, p(MAGENTA,75 = 0.0251. The GSEA revealed that weak association signals for obesity might be enriched in the gene set of 16 nuclear regulators of mitochondrial genes.

  17. Candidate genes for COPD in two large data sets.

    Science.gov (United States)

    Bakke, P S; Zhu, G; Gulsvik, A; Kong, X; Agusti, A G N; Calverley, P M A; Donner, C F; Levy, R D; Make, B J; Paré, P D; Rennard, S I; Vestbo, J; Wouters, E F M; Anderson, W; Lomas, D A; Silverman, E K; Pillai, S G

    2011-02-01

    Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV₁) % predicted and FEV₁/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV₁ % predicted and FEV₁/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.

  18. Comparative study on gene set and pathway topology-based enrichment methods.

    Science.gov (United States)

    Bayerlová, Michaela; Jung, Klaus; Kramer, Frank; Klemm, Florian; Bleckmann, Annalen; Beißbarth, Tim

    2015-10-22

    Enrichment analysis is a popular approach to identify pathways or sets of genes which are significantly enriched in the context of differentially expressed genes. The traditional gene set enrichment approach considers a pathway as a simple gene list disregarding any knowledge of gene or protein interactions. In contrast, the new group of so called pathway topology-based methods integrates the topological structure of a pathway into the analysis. We comparatively investigated gene set and pathway topology-based enrichment approaches, considering three gene set and four topological methods. These methods were compared in two extensive simulation studies and on a benchmark of 36 real datasets, providing the same pathway input data for all methods. In the benchmark data analysis both types of methods showed a comparable ability to detect enriched pathways. The first simulation study was conducted with KEGG pathways, which showed considerable gene overlaps between each other. In this study with original KEGG pathways, none of the topology-based methods outperformed the gene set approach. Therefore, a second simulation study was performed on non-overlapping pathways created by unique gene IDs. Here, methods accounting for pathway topology reached higher accuracy than the gene set methods, however their sensitivity was lower. We conducted one of the first comprehensive comparative works on evaluating gene set against pathway topology-based enrichment methods. The topological methods showed better performance in the simulation scenarios with non-overlapping pathways, however, they were not conclusively better in the other scenarios. This suggests that simple gene set approach might be sufficient to detect an enriched pathway under realistic circumstances. Nevertheless, more extensive studies and further benchmark data are needed to systematically evaluate these methods and to assess what gain and cost pathway topology information introduces into enrichment analysis. Both

  19. Phylogenetics and evolution of Trx SET genes in fully sequenced land plants.

    Science.gov (United States)

    Zhu, Xinyu; Chen, Caoyi; Wang, Baohua

    2012-04-01

    Plant Trx SET proteins are involved in H3K4 methylation and play a key role in plant floral development. Genes encoding Trx SET proteins constitute a multigene family in which the copy number varies among plant species and functional divergence appears to have occurred repeatedly. To investigate the evolutionary history of the Trx SET gene family, we made a comprehensive evolutionary analysis on this gene family from 13 major representatives of green plants. A novel clustering (here named as cpTrx clade), which included the III-1, III-2, and III-4 orthologous groups, previously resolved was identified. Our analysis showed that plant Trx proteins possessed a variety of domain organizations and gene structures among paralogs. Additional domains such as PHD, PWWP, and FYR were early integrated into primordial SET-PostSET domain organization of cpTrx clade. We suggested that the PostSET domain was lost in some members of III-4 orthologous group during the evolution of land plants. At least four classes of gene structures had been formed at the early evolutionary stage of land plants. Three intronless orphan Trx SET genes from the Physcomitrella patens (moss) were identified, and supposedly, their parental genes have been eliminated from the genome. The structural differences among evolutionary groups of plant Trx SET genes with different functions were described, contributing to the design of further experimental studies.

  20. An Independent Filter for Gene Set Testing Based on Spectral Enrichment

    NARCIS (Netherlands)

    Frost, H Robert; Li, Zhigang; Asselbergs, Folkert W; Moore, Jason H

    2015-01-01

    Gene set testing has become an indispensable tool for the analysis of high-dimensional genomic data. An important motivation for testing gene sets, rather than individual genomic variables, is to improve statistical power by reducing the number of tested hypotheses. Given the dramatic growth in

  1. Principal Angle Enrichment Analysis (PAEA): Dimensionally Reduced Multivariate Gene Set Enrichment Analysis Tool.

    Science.gov (United States)

    Clark, Neil R; Szymkiewicz, Maciej; Wang, Zichen; Monteiro, Caroline D; Jones, Matthew R; Ma'ayan, Avi

    2015-11-01

    Gene set analysis of differential expression, which identifies collectively differentially expressed gene sets, has become an important tool for biology. The power of this approach lies in its reduction of the dimensionality of the statistical problem and its incorporation of biological interpretation by construction. Many approaches to gene set analysis have been proposed, but benchmarking their performance in the setting of real biological data is difficult due to the lack of a gold standard. In a previously published work we proposed a geometrical approach to differential expression which performed highly in benchmarking tests and compared well to the most popular methods of differential gene expression. As reported, this approach has a natural extension to gene set analysis which we call Principal Angle Enrichment Analysis (PAEA). PAEA employs dimensionality reduction and a multivariate approach for gene set enrichment analysis. However, the performance of this method has not been assessed nor its implementation as a web-based tool. Here we describe new benchmarking protocols for gene set analysis methods and find that PAEA performs highly. The PAEA method is implemented as a user-friendly web-based tool, which contains 70 gene set libraries and is freely available to the community.

  2. Annotating gene sets by mining large literature collections with protein networks.

    Science.gov (United States)

    Wang, Sheng; Ma, Jianzhu; Yu, Michael Ku; Zheng, Fan; Huang, Edward W; Han, Jiawei; Peng, Jian; Ideker, Trey

    2018-01-01

    Analysis of patient genomes and transcriptomes routinely recognizes new gene sets associated with human disease. Here we present an integrative natural language processing system which infers common functions for a gene set through automatic mining of the scientific literature with biological networks. This system links genes with associated literature phrases and combines these links with protein interactions in a single heterogeneous network. Multiscale functional annotations are inferred based on network distances between phrases and genes and then visualized as an ontology of biological concepts. To evaluate this system, we predict functions for gene sets representing known pathways and find that our approach achieves substantial improvement over the conventional text-mining baseline method. Moreover, our system discovers novel annotations for gene sets or pathways without previously known functions. Two case studies demonstrate how the system is used in discovery of new cancer-related pathways with ontological annotations.

  3. The Molecular Signatures Database (MSigDB) hallmark gene set collection.

    Science.gov (United States)

    Liberzon, Arthur; Birger, Chet; Thorvaldsdóttir, Helga; Ghandi, Mahmoud; Mesirov, Jill P; Tamayo, Pablo

    2015-12-23

    The Molecular Signatures Database (MSigDB) is one of the most widely used and comprehensive databases of gene sets for performing gene set enrichment analysis. Since its creation, MSigDB has grown beyond its roots in metabolic disease and cancer to include >10,000 gene sets. These better represent a wider range of biological processes and diseases, but the utility of the database is reduced by increased redundancy across, and heterogeneity within, gene sets. To address this challenge, here we use a combination of automated approaches and expert curation to develop a collection of "hallmark" gene sets as part of MSigDB. Each hallmark in this collection consists of a "refined" gene set, derived from multiple "founder" sets, that conveys a specific biological state or process and displays coherent expression. The hallmarks effectively summarize most of the relevant information of the original founder sets and, by reducing both variation and redundancy, provide more refined and concise inputs for gene set enrichment analysis.

  4. Exploring and linking biomedical resources through multidimensional semantic spaces.

    Science.gov (United States)

    Berlanga, Rafael; Jiménez-Ruiz, Ernesto; Nebot, Victoria

    2012-01-25

    The semantic integration of biomedical resources is still a challenging issue which is required for effective information processing and data analysis. The availability of comprehensive knowledge resources such as biomedical ontologies and integrated thesauri greatly facilitates this integration effort by means of semantic annotation, which allows disparate data formats and contents to be expressed under a common semantic space. In this paper, we propose a multidimensional representation for such a semantic space, where dimensions regard the different perspectives in biomedical research (e.g., population, disease, anatomy and protein/genes). This paper presents a novel method for building multidimensional semantic spaces from semantically annotated biomedical data collections. This method consists of two main processes: knowledge and data normalization. The former one arranges the concepts provided by a reference knowledge resource (e.g., biomedical ontologies and thesauri) into a set of hierarchical dimensions for analysis purposes. The latter one reduces the annotation set associated to each collection item into a set of points of the multidimensional space. Additionally, we have developed a visual tool, called 3D-Browser, which implements OLAP-like operators over the generated multidimensional space. The method and the tool have been tested and evaluated in the context of the Health-e-Child (HeC) project. Automatic semantic annotation was applied to tag three collections of abstracts taken from PubMed, one for each target disease of the project, the Uniprot database, and the HeC patient record database. We adopted the UMLS Meta-thesaurus 2010AA as the reference knowledge resource. Current knowledge resources and semantic-aware technology make possible the integration of biomedical resources. Such an integration is performed through semantic annotation of the intended biomedical data resources. This paper shows how these annotations can be exploited for

  5. Multidimensional Heat Conduction

    DEFF Research Database (Denmark)

    Rode, Carsten

    1998-01-01

    Analytical theory of multidimensional heat conduction. General heat conduction equation in three dimensions. Steay state, analytical solutions. The Laplace equation. Method of separation of variables. Principle of superposition. Shape factors. Transient, multidimensional heat conduction....

  6. GeneAnalytics: An Integrative Gene Set Analysis Tool for Next Generation Sequencing, RNAseq and Microarray Data.

    Science.gov (United States)

    Ben-Ari Fuchs, Shani; Lieder, Iris; Stelzer, Gil; Mazor, Yaron; Buzhor, Ella; Kaplan, Sergey; Bogoch, Yoel; Plaschkes, Inbar; Shitrit, Alina; Rappaport, Noa; Kohn, Asher; Edgar, Ron; Shenhav, Liraz; Safran, Marilyn; Lancet, Doron; Guan-Golan, Yaron; Warshawsky, David; Shtrichman, Ronit

    2016-03-01

    Postgenomics data are produced in large volumes by life sciences and clinical applications of novel omics diagnostics and therapeutics for precision medicine. To move from "data-to-knowledge-to-innovation," a crucial missing step in the current era is, however, our limited understanding of biological and clinical contexts associated with data. Prominent among the emerging remedies to this challenge are the gene set enrichment tools. This study reports on GeneAnalytics™ ( geneanalytics.genecards.org ), a comprehensive and easy-to-apply gene set analysis tool for rapid contextualization of expression patterns and functional signatures embedded in the postgenomics Big Data domains, such as Next Generation Sequencing (NGS), RNAseq, and microarray experiments. GeneAnalytics' differentiating features include in-depth evidence-based scoring algorithms, an intuitive user interface and proprietary unified data. GeneAnalytics employs the LifeMap Science's GeneCards suite, including the GeneCards®--the human gene database; the MalaCards-the human diseases database; and the PathCards--the biological pathways database. Expression-based analysis in GeneAnalytics relies on the LifeMap Discovery®--the embryonic development and stem cells database, which includes manually curated expression data for normal and diseased tissues, enabling advanced matching algorithm for gene-tissue association. This assists in evaluating differentiation protocols and discovering biomarkers for tissues and cells. Results are directly linked to gene, disease, or cell "cards" in the GeneCards suite. Future developments aim to enhance the GeneAnalytics algorithm as well as visualizations, employing varied graphical display items. Such attributes make GeneAnalytics a broadly applicable postgenomics data analyses and interpretation tool for translation of data to knowledge-based innovation in various Big Data fields such as precision medicine, ecogenomics, nutrigenomics, pharmacogenomics, vaccinomics

  7. Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data

    NARCIS (Netherlands)

    Hettne, K.M.; Boorsma, A.; Dartel, D.A. van; Goeman, J.J.; Jong, E. de; Piersma, A.H.; Stierum, R.H.; Kleinjans, J.C.; Kors, J.A.

    2013-01-01

    BACKGROUND: Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with gene set

  8. Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data

    NARCIS (Netherlands)

    Hettne, K.M.; Boorsma, A.; Dartel, van D.A.M.; Goeman, J.J.; Jong, de E.; Piersma, A.H.; Stierum, R.H.; Kleinjans, J.C.; Kors, J.A.

    2013-01-01

    Background: Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with gene set

  9. The null hypothesis of GSEA, and a novel statistical model for competitive gene set analysis

    DEFF Research Database (Denmark)

    Debrabant, Birgit

    2017-01-01

    MOTIVATION: Competitive gene set analysis intends to assess whether a specific set of genes is more associated with a trait than the remaining genes. However, the statistical models assumed to date to underly these methods do not enable a clear cut formulation of the competitive null hypothesis....... This is a major handicap to the interpretation of results obtained from a gene set analysis. RESULTS: This work presents a hierarchical statistical model based on the notion of dependence measures, which overcomes this problem. The two levels of the model naturally reflect the modular structure of many gene set...... analysis methods. We apply the model to show that the popular GSEA method, which recently has been claimed to test the self-contained null hypothesis, actually tests the competitive null if the weight parameter is zero. However, for this result to hold strictly, the choice of the dependence measures...

  10. FunGeneNet: a web tool to estimate enrichment of functional interactions in experimental gene sets.

    Science.gov (United States)

    Tiys, Evgeny S; Ivanisenko, Timofey V; Demenkov, Pavel S; Ivanisenko, Vladimir A

    2018-02-09

    Estimation of functional connectivity in gene sets derived from genome-wide or other biological experiments is one of the essential tasks of bioinformatics. A promising approach for solving this problem is to compare gene networks built using experimental gene sets with random networks. One of the resources that make such an analysis possible is CrossTalkZ, which uses the FunCoup database. However, existing methods, including CrossTalkZ, do not take into account individual types of interactions, such as protein/protein interactions, expression regulation, transport regulation, catalytic reactions, etc., but rather work with generalized types characterizing the existence of any connection between network members. We developed the online tool FunGeneNet, which utilizes the ANDSystem and STRING to reconstruct gene networks using experimental gene sets and to estimate their difference from random networks. To compare the reconstructed networks with random ones, the node permutation algorithm implemented in CrossTalkZ was taken as a basis. To study the FunGeneNet applicability, the functional connectivity analysis of networks constructed for gene sets involved in the Gene Ontology biological processes was conducted. We showed that the method sensitivity exceeds 0.8 at a specificity of 0.95. We found that the significance level of the difference between gene networks of biological processes and random networks is determined by the type of connections considered between objects. At the same time, the highest reliability is achieved for the generalized form of connections that takes into account all the individual types of connections. By taking examples of the thyroid cancer networks and the apoptosis network, it is demonstrated that key participants in these processes are involved in the interactions of those types by which these networks differ from random ones. FunGeneNet is a web tool aimed at proving the functionality of networks in a wide range of sizes of

  11. Application of biclustering of gene expression data and gene set enrichment analysis methods to identify potentially disease causing nanomaterials

    Directory of Open Access Journals (Sweden)

    Andrew Williams

    2015-12-01

    Full Text Available Background: The presence of diverse types of nanomaterials (NMs in commerce is growing at an exponential pace. As a result, human exposure to these materials in the environment is inevitable, necessitating the need for rapid and reliable toxicity testing methods to accurately assess the potential hazards associated with NMs. In this study, we applied biclustering and gene set enrichment analysis methods to derive essential features of altered lung transcriptome following exposure to NMs that are associated with lung-specific diseases. Several datasets from public microarray repositories describing pulmonary diseases in mouse models following exposure to a variety of substances were examined and functionally related biclusters of genes showing similar expression profiles were identified. The identified biclusters were then used to conduct a gene set enrichment analysis on pulmonary gene expression profiles derived from mice exposed to nano-titanium dioxide (nano-TiO2, carbon black (CB or carbon nanotubes (CNTs to determine the disease significance of these data-driven gene sets.Results: Biclusters representing inflammation (chemokine activity, DNA binding, cell cycle, apoptosis, reactive oxygen species (ROS and fibrosis processes were identified. All of the NM studies were significant with respect to the bicluster related to chemokine activity (DAVID; FDR p-value = 0.032. The bicluster related to pulmonary fibrosis was enriched in studies where toxicity induced by CNT and CB studies was investigated, suggesting the potential for these materials to induce lung fibrosis. The pro-fibrogenic potential of CNTs is well established. Although CB has not been shown to induce fibrosis, it induces stronger inflammatory, oxidative stress and DNA damage responses than nano-TiO2 particles.Conclusion: The results of the analysis correctly identified all NMs to be inflammogenic and only CB and CNTs as potentially fibrogenic. In addition to identifying several

  12. Genome-wide survey and developmental expression mapping of zebrafish SET domain-containing genes.

    Directory of Open Access Journals (Sweden)

    Xiao-Jian Sun

    Full Text Available SET domain-containing proteins represent an evolutionarily conserved family of epigenetic regulators, which are responsible for most histone lysine methylation. Since some of these genes have been revealed to be essential for embryonic development, we propose that the zebrafish, a vertebrate model organism possessing many advantages for developmental studies, can be utilized to study the biological functions of these genes and the related epigenetic mechanisms during early development. To this end, we have performed a genome-wide survey of zebrafish SET domain genes. 58 genes total have been identified. Although gene duplication events give rise to several lineage-specific paralogs, clear reciprocal orthologous relationship reveals high conservation between zebrafish and human SET domain genes. These data were further subject to an evolutionary analysis ranging from yeast to human, leading to the identification of putative clusters of orthologous groups (COGs of this gene family. By means of whole-mount mRNA in situ hybridization strategy, we have also carried out a developmental expression mapping of these genes. A group of maternal SET domain genes, which are implicated in the programming of histone modification states in early development, have been identified and predicted to be responsible for all known sites of SET domain-mediated histone methylation. Furthermore, some genes show specific expression patterns in certain tissues at certain stages, suggesting the involvement of epigenetic mechanisms in the development of these systems. These results provide a global view of zebrafish SET domain histone methyltransferases in evolutionary and developmental dimensions and pave the way for using zebrafish to systematically study the roles of these genes during development.

  13. Gene set analysis: limitations in popular existing methods and proposed improvements.

    Science.gov (United States)

    Mishra, Pashupati; Törönen, Petri; Leino, Yrjö; Holm, Liisa

    2014-10-01

    Gene set analysis is the analysis of a set of genes that collectively contribute to a biological process. Most popular gene set analysis methods are based on empirical P-value that requires large number of permutations. Despite numerous gene set analysis methods developed in the past decade, the most popular methods still suffer from serious limitations. We present a gene set analysis method (mGSZ) based on Gene Set Z-scoring function (GSZ) and asymptotic P-values. Asymptotic P-value calculation requires fewer permutations, and thus speeds up the gene set analysis process. We compare the GSZ-scoring function with seven popular gene set scoring functions and show that GSZ stands out as the best scoring function. In addition, we show improved performance of the GSA method when the max-mean statistics is replaced by the GSZ scoring function. We demonstrate the importance of both gene and sample permutations by showing the consequences in the absence of one or the other. A comparison of asymptotic and empirical methods of P-value estimation demonstrates a clear advantage of asymptotic P-value over empirical P-value. We show that mGSZ outperforms the state-of-the-art methods based on two different evaluations. We compared mGSZ results with permutation and rotation tests and show that rotation does not improve our asymptotic P-values. We also propose well-known asymptotic distribution models for three of the compared methods. mGSZ is available as R package from cran.r-project.org. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. CAsubtype: An R Package to Identify Gene Sets Predictive of Cancer Subtypes and Clinical Outcomes.

    Science.gov (United States)

    Kong, Hualei; Tong, Pan; Zhao, Xiaodong; Sun, Jielin; Li, Hua

    2018-03-01

    In the past decade, molecular classification of cancer has gained high popularity owing to its high predictive power on clinical outcomes as compared with traditional methods commonly used in clinical practice. In particular, using gene expression profiles, recent studies have successfully identified a number of gene sets for the delineation of cancer subtypes that are associated with distinct prognosis. However, identification of such gene sets remains a laborious task due to the lack of tools with flexibility, integration and ease of use. To reduce the burden, we have developed an R package, CAsubtype, to efficiently identify gene sets predictive of cancer subtypes and clinical outcomes. By integrating more than 13,000 annotated gene sets, CAsubtype provides a comprehensive repertoire of candidates for new cancer subtype identification. For easy data access, CAsubtype further includes the gene expression and clinical data of more than 2000 cancer patients from TCGA. CAsubtype first employs principal component analysis to identify gene sets (from user-provided or package-integrated ones) with robust principal components representing significantly large variation between cancer samples. Based on these principal components, CAsubtype visualizes the sample distribution in low-dimensional space for better understanding of the distinction between samples and classifies samples into subgroups with prevalent clustering algorithms. Finally, CAsubtype performs survival analysis to compare the clinical outcomes between the identified subgroups, assessing their clinical value as potentially novel cancer subtypes. In conclusion, CAsubtype is a flexible and well-integrated tool in the R environment to identify gene sets for cancer subtype identification and clinical outcome prediction. Its simple R commands and comprehensive data sets enable efficient examination of the clinical value of any given gene set, thus facilitating hypothesis generating and testing in biological and

  15. Identification of a conserved set of upregulated genes in mouse skeletal muscle hypertrophy and regrowth.

    Science.gov (United States)

    Chaillou, Thomas; Jackson, Janna R; England, Jonathan H; Kirby, Tyler J; Richards-White, Jena; Esser, Karyn A; Dupont-Versteegden, Esther E; McCarthy, John J

    2015-01-01

    The purpose of this study was to compare the gene expression profile of mouse skeletal muscle undergoing two forms of growth (hypertrophy and regrowth) with the goal of identifying a conserved set of differentially expressed genes. Expression profiling by microarray was performed on the plantaris muscle subjected to 1, 3, 5, 7, 10, and 14 days of hypertrophy or regrowth following 2 wk of hind-limb suspension. We identified 97 differentially expressed genes (≥2-fold increase or ≥50% decrease compared with control muscle) that were conserved during the two forms of muscle growth. The vast majority (∼90%) of the differentially expressed genes was upregulated and occurred at a single time point (64 out of 86 genes), which most often was on the first day of the time course. Microarray analysis from the conserved upregulated genes showed a set of genes related to contractile apparatus and stress response at day 1, including three genes involved in mechanotransduction and four genes encoding heat shock proteins. Our analysis further identified three cell cycle-related genes at day and several genes associated with extracellular matrix (ECM) at both days 3 and 10. In conclusion, we have identified a core set of genes commonly upregulated in two forms of muscle growth that could play a role in the maintenance of sarcomere stability, ECM remodeling, cell proliferation, fast-to-slow fiber type transition, and the regulation of skeletal muscle growth. These findings suggest conserved regulatory mechanisms involved in the adaptation of skeletal muscle to increased mechanical loading. Copyright © 2015 the American Physiological Society.

  16. Mechanism-based biomarker gene sets for glutathione depletion-related hepatotoxicity in rats

    International Nuclear Information System (INIS)

    Gao Weihua; Mizukawa, Yumiko; Nakatsu, Noriyuki; Minowa, Yosuke; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

    2010-01-01

    Chemical-induced glutathione depletion is thought to be caused by two types of toxicological mechanisms: PHO-type glutathione depletion [glutathione conjugated with chemicals such as phorone (PHO) or diethyl maleate (DEM)], and BSO-type glutathione depletion [i.e., glutathione synthesis inhibited by chemicals such as L-buthionine-sulfoximine (BSO)]. In order to identify mechanism-based biomarker gene sets for glutathione depletion in rat liver, male SD rats were treated with various chemicals including PHO (40, 120 and 400 mg/kg), DEM (80, 240 and 800 mg/kg), BSO (150, 450 and 1500 mg/kg), and bromobenzene (BBZ, 10, 100 and 300 mg/kg). Liver samples were taken 3, 6, 9 and 24 h after administration and examined for hepatic glutathione content, physiological and pathological changes, and gene expression changes using Affymetrix GeneChip Arrays. To identify differentially expressed probe sets in response to glutathione depletion, we focused on the following two courses of events for the two types of mechanisms of glutathione depletion: a) gene expression changes occurring simultaneously in response to glutathione depletion, and b) gene expression changes after glutathione was depleted. The gene expression profiles of the identified probe sets for the two types of glutathione depletion differed markedly at times during and after glutathione depletion, whereas Srxn1 was markedly increased for both types as glutathione was depleted, suggesting that Srxn1 is a key molecule in oxidative stress related to glutathione. The extracted probe sets were refined and verified using various compounds including 13 additional positive or negative compounds, and they established two useful marker sets. One contained three probe sets (Akr7a3, Trib3 and Gstp1) that could detect conjugation-type glutathione depletors any time within 24 h after dosing, and the other contained 14 probe sets that could detect glutathione depletors by any mechanism. These two sets, with appropriate scoring

  17. Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data

    Science.gov (United States)

    2013-01-01

    Background Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with gene set analysis (GSA) methods for chemical treatment identification, for pharmacological mechanism elucidation, and for comparing compound toxicity profiles. Methods We created 30,211 chemical response-specific gene sets for human and mouse by next-gen TM, and derived 1,189 (human) and 588 (mouse) gene sets from the Comparative Toxicogenomics Database (CTD). We tested for significant differential expression (SDE) (false discovery rate -corrected p-values sets and the CTD-derived gene sets in gene expression (GE) data sets of five chemicals (from experimental models). We tested for SDE of gene sets for six fibrates in a peroxisome proliferator-activated receptor alpha (PPARA) knock-out GE dataset and compared to results from the Connectivity Map. We tested for SDE of 319 next-gen TM-derived gene sets for environmental toxicants in three GE data sets of triazoles, and tested for SDE of 442 gene sets associated with embryonic structures. We compared the gene sets to triazole effects seen in the Whole Embryo Culture (WEC), and used principal component analysis (PCA) to discriminate triazoles from other chemicals. Results Next-gen TM-derived gene sets matching the chemical treatment were significantly altered in three GE data sets, and the corresponding CTD-derived gene sets were significantly altered in five GE data sets. Six next-gen TM-derived and four CTD-derived fibrate gene sets were significantly altered in the PPARA knock-out GE dataset. None of the fibrate signatures in cMap scored significant against the PPARA GE signature. 33 environmental toxicant gene sets were significantly altered in the triazole GE data sets. 21 of these toxicants had a similar toxicity pattern as the

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  19. Accurate Gene Expression-Based Biodosimetry Using a Minimal Set of Human Gene Transcripts

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, James D., E-mail: jtucker@biology.biosci.wayne.edu [Department of Biological Sciences, Wayne State University, Detroit, Michigan (United States); Joiner, Michael C. [Department of Radiation Oncology, Wayne State University, Detroit, Michigan (United States); Thomas, Robert A.; Grever, William E.; Bakhmutsky, Marina V. [Department of Biological Sciences, Wayne State University, Detroit, Michigan (United States); Chinkhota, Chantelle N.; Smolinski, Joseph M. [Department of Electrical and Computer Engineering, Wayne State University, Detroit, Michigan (United States); Divine, George W. [Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan (United States); Auner, Gregory W. [Department of Electrical and Computer Engineering, Wayne State University, Detroit, Michigan (United States)

    2014-03-15

    Purpose: Rapid and reliable methods for conducting biological dosimetry are a necessity in the event of a large-scale nuclear event. Conventional biodosimetry methods lack the speed, portability, ease of use, and low cost required for triaging numerous victims. Here we address this need by showing that polymerase chain reaction (PCR) on a small number of gene transcripts can provide accurate and rapid dosimetry. The low cost and relative ease of PCR compared with existing dosimetry methods suggest that this approach may be useful in mass-casualty triage situations. Methods and Materials: Human peripheral blood from 60 adult donors was acutely exposed to cobalt-60 gamma rays at doses of 0 (control) to 10 Gy. mRNA expression levels of 121 selected genes were obtained 0.5, 1, and 2 days after exposure by reverse-transcriptase real-time PCR. Optimal dosimetry at each time point was obtained by stepwise regression of dose received against individual gene transcript expression levels. Results: Only 3 to 4 different gene transcripts, ASTN2, CDKN1A, GDF15, and ATM, are needed to explain ≥0.87 of the variance (R{sup 2}). Receiver-operator characteristics, a measure of sensitivity and specificity, of 0.98 for these statistical models were achieved at each time point. Conclusions: The actual and predicted radiation doses agree very closely up to 6 Gy. Dosimetry at 8 and 10 Gy shows some effect of saturation, thereby slightly diminishing the ability to quantify higher exposures. Analyses of these gene transcripts may be advantageous for use in a field-portable device designed to assess exposures in mass casualty situations or in clinical radiation emergencies.

  20. Investigating the effect of paralogs on microarray gene-set analysis

    LENUS (Irish Health Repository)

    Faure, Andre J

    2011-01-24

    Abstract Background In order to interpret the results obtained from a microarray experiment, researchers often shift focus from analysis of individual differentially expressed genes to analyses of sets of genes. These gene-set analysis (GSA) methods use previously accumulated biological knowledge to group genes into sets and then aim to rank these gene sets in a way that reflects their relative importance in the experimental situation in question. We suspect that the presence of paralogs affects the ability of GSA methods to accurately identify the most important sets of genes for subsequent research. Results We show that paralogs, which typically have high sequence identity and similar molecular functions, also exhibit high correlation in their expression patterns. We investigate this correlation as a potential confounding factor common to current GSA methods using Indygene http:\\/\\/www.cbio.uct.ac.za\\/indygene, a web tool that reduces a supplied list of genes so that it includes no pairwise paralogy relationships above a specified sequence similarity threshold. We use the tool to reanalyse previously published microarray datasets and determine the potential utility of accounting for the presence of paralogs. Conclusions The Indygene tool efficiently removes paralogy relationships from a given dataset and we found that such a reduction, performed prior to GSA, has the ability to generate significantly different results that often represent novel and plausible biological hypotheses. This was demonstrated for three different GSA approaches when applied to the reanalysis of previously published microarray datasets and suggests that the redundancy and non-independence of paralogs is an important consideration when dealing with GSA methodologies.

  1. SQL and Multidimensional Data

    Directory of Open Access Journals (Sweden)

    Mihaela MUNTEAN

    2006-01-01

    Full Text Available Using SQL you can manipulate multidimensional data and extract that data into a relational table. There are many PL/SQL packages that you can use directly in SQL*Plus or indirectly in Analytic Workspace Manager and OLAP Worksheet. In this article I discussed about some methods that you can use for manipulating and extracting multidimensional data.

  2. Multidimensional high harmonic spectroscopy

    International Nuclear Information System (INIS)

    Bruner, Barry D; Soifer, Hadas; Shafir, Dror; Dudovich, Nirit; Serbinenko, Valeria; Smirnova, Olga

    2015-01-01

    High harmonic generation (HHG) has opened up a new frontier in ultrafast science where attosecond time resolution and Angstrom spatial resolution are accessible in a single measurement. However, reconstructing the dynamics under study is limited by the multiple degrees of freedom involved in strong field interactions. In this paper we describe a new class of measurement schemes for resolving attosecond dynamics, integrating perturbative nonlinear optics with strong-field physics. These approaches serve as a basis for multidimensional high harmonic spectroscopy. Specifically, we show that multidimensional high harmonic spectroscopy can measure tunnel ionization dynamics with high precision, and resolves the interference between multiple ionization channels. In addition, we show how multidimensional HHG can function as a type of lock-in amplifier measurement. Similar to multi-dimensional approaches in nonlinear optical spectroscopy that have resolved correlated femtosecond dynamics, multi-dimensional high harmonic spectroscopy reveals the underlying complex dynamics behind attosecond scale phenomena. (paper)

  3. Structure of multidimensional patterns

    International Nuclear Information System (INIS)

    Smith, S.P.

    1982-01-01

    The problem of describing the structure of multidimensional data is important in exploratory data analysis, statistical pattern recognition, and image processing. A data set is viewed as a collection of points embedded in a high dimensional space. The primary goal of this research is to determine if the data have any clustering structure; such a structure implies the presence of class information (categories) in the data. A statistical hypothesis is used in the decision making. To this end, data with no structure are defined as data following the uniform distribution over some compact convex set in K-dimensional space, called the sampling window. This thesis defines two new tests for uniformity along with various sampling window estimators. The first test is a volume-based test which captures density changes in the data. The second test compares a uniformly distributed sample to the data by using the minimal spanning tree (MST) of the polled samples. Sampling window estimators are provided for simple sampling windows and use the convex hull of the data as a general sampling window estimator. For both of the tests for uniformity, theoretical results are provided on their size, and study their size and power against clustered alternatives is studied. Simulation is also used to study the efficacy of the sampling window estimators

  4. Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data

    Directory of Open Access Journals (Sweden)

    Hettne Kristina M

    2013-01-01

    Full Text Available Abstract Background Availability of chemical response-specific lists of genes (gene sets for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM, and that these can be used with gene set analysis (GSA methods for chemical treatment identification, for pharmacological mechanism elucidation, and for comparing compound toxicity profiles. Methods We created 30,211 chemical response-specific gene sets for human and mouse by next-gen TM, and derived 1,189 (human and 588 (mouse gene sets from the Comparative Toxicogenomics Database (CTD. We tested for significant differential expression (SDE (false discovery rate -corrected p-values Results Next-gen TM-derived gene sets matching the chemical treatment were significantly altered in three GE data sets, and the corresponding CTD-derived gene sets were significantly altered in five GE data sets. Six next-gen TM-derived and four CTD-derived fibrate gene sets were significantly altered in the PPARA knock-out GE dataset. None of the fibrate signatures in cMap scored significant against the PPARA GE signature. 33 environmental toxicant gene sets were significantly altered in the triazole GE data sets. 21 of these toxicants had a similar toxicity pattern as the triazoles. We confirmed embryotoxic effects, and discriminated triazoles from other chemicals. Conclusions Gene set analysis with next-gen TM-derived chemical response-specific gene sets is a scalable method for identifying similarities in gene responses to other chemicals, from which one may infer potential mode of action and/or toxic effect.

  5. Intervene: a tool for intersection and visualization of multiple gene or genomic region sets.

    Science.gov (United States)

    Khan, Aziz; Mathelier, Anthony

    2017-05-31

    A common task for scientists relies on comparing lists of genes or genomic regions derived from high-throughput sequencing experiments. While several tools exist to intersect and visualize sets of genes, similar tools dedicated to the visualization of genomic region sets are currently limited. To address this gap, we have developed the Intervene tool, which provides an easy and automated interface for the effective intersection and visualization of genomic region or list sets, thus facilitating their analysis and interpretation. Intervene contains three modules: venn to generate Venn diagrams of up to six sets, upset to generate UpSet plots of multiple sets, and pairwise to compute and visualize intersections of multiple sets as clustered heat maps. Intervene, and its interactive web ShinyApp companion, generate publication-quality figures for the interpretation of genomic region and list sets. Intervene and its web application companion provide an easy command line and an interactive web interface to compute intersections of multiple genomic and list sets. They have the capacity to plot intersections using easy-to-interpret visual approaches. Intervene is developed and designed to meet the needs of both computer scientists and biologists. The source code is freely available at https://bitbucket.org/CBGR/intervene , with the web application available at https://asntech.shinyapps.io/intervene .

  6. Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data

    NARCIS (Netherlands)

    K.M. Hettne (Kristina); J. Boorsma (Jeffrey); D.A.M. van Dartel (Dorien A M); J.J. Goeman (Jelle); E.C. de Jong (Esther); A.H. Piersma (Aldert); R.H. Stierum (Rob); J. Kleinjans (Jos); J.A. Kors (Jan)

    2013-01-01

    textabstractBackground: Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with

  7. Optimal structural inference of signaling pathways from unordered and overlapping gene sets.

    Science.gov (United States)

    Acharya, Lipi R; Judeh, Thair; Wang, Guangdi; Zhu, Dongxiao

    2012-02-15

    A plethora of bioinformatics analysis has led to the discovery of numerous gene sets, which can be interpreted as discrete measurements emitted from latent signaling pathways. Their potential to infer signaling pathway structures, however, has not been sufficiently exploited. Existing methods accommodating discrete data do not explicitly consider signal cascading mechanisms that characterize a signaling pathway. Novel computational methods are thus needed to fully utilize gene sets and broaden the scope from focusing only on pairwise interactions to the more general cascading events in the inference of signaling pathway structures. We propose a gene set based simulated annealing (SA) algorithm for the reconstruction of signaling pathway structures. A signaling pathway structure is a directed graph containing up to a few hundred nodes and many overlapping signal cascades, where each cascade represents a chain of molecular interactions from the cell surface to the nucleus. Gene sets in our context refer to discrete sets of genes participating in signal cascades, the basic building blocks of a signaling pathway, with no prior information about gene orderings in the cascades. From a compendium of gene sets related to a pathway, SA aims to search for signal cascades that characterize the optimal signaling pathway structure. In the search process, the extent of overlap among signal cascades is used to measure the optimality of a structure. Throughout, we treat gene sets as random samples from a first-order Markov chain model. We evaluated the performance of SA in three case studies. In the first study conducted on 83 KEGG pathways, SA demonstrated a significantly better performance than Bayesian network methods. Since both SA and Bayesian network methods accommodate discrete data, use a 'search and score' network learning strategy and output a directed network, they can be compared in terms of performance and computational time. In the second study, we compared SA and

  8. Meta-analysis of differentiating mouse embryonic stem cell gene expression kinetics reveals early change of a small gene set.

    Directory of Open Access Journals (Sweden)

    Clive H Glover

    2006-11-01

    Full Text Available Stem cell differentiation involves critical changes in gene expression. Identification of these should provide endpoints useful for optimizing stem cell propagation as well as potential clues about mechanisms governing stem cell maintenance. Here we describe the results of a new meta-analysis methodology applied to multiple gene expression datasets from three mouse embryonic stem cell (ESC lines obtained at specific time points during the course of their differentiation into various lineages. We developed methods to identify genes with expression changes that correlated with the altered frequency of functionally defined, undifferentiated ESC in culture. In each dataset, we computed a novel statistical confidence measure for every gene which captured the certainty that a particular gene exhibited an expression pattern of interest within that dataset. This permitted a joint analysis of the datasets, despite the different experimental designs. Using a ranking scheme that favored genes exhibiting patterns of interest, we focused on the top 88 genes whose expression was consistently changed when ESC were induced to differentiate. Seven of these (103728_at, 8430410A17Rik, Klf2, Nr0b1, Sox2, Tcl1, and Zfp42 showed a rapid decrease in expression concurrent with a decrease in frequency of undifferentiated cells and remained predictive when evaluated in additional maintenance and differentiating protocols. Through a novel meta-analysis, this study identifies a small set of genes whose expression is useful for identifying changes in stem cell frequencies in cultures of mouse ESC. The methods and findings have broader applicability to understanding the regulation of self-renewal of other stem cell types.

  9. Discovering Multidimensional Structure in Relational Data

    DEFF Research Database (Denmark)

    Jensen, Mikael Rune; Holmgren, Thomas; Pedersen, Torben Bach

    2004-01-01

    On-Line Analytical Processing (OLAP) systems based on multidimensional databases are essential elements of decision support. However, most existing data is stored in “ordinary” relational OLTP databases, i.e., data has to be (re-) modeled as multidimensional cubes before the advantages of OLAP to...... algorithms for discovering multidimensional schemas from relational databases. The algorithms take a wide range of available metadata into account in the discovery process, including functional and inclusion dependencies, and key and cardinality information....... tools are available. In this paper we present an approach for the automatic construction of multidimensional OLAP database schemas from existing relational OLTP databases, enabling easy OLAP design and analysis for most existing data sources. This is achieved through a set of practical and effective...

  10. CAMS: OLAPing Multidimensional Data Streams Efficiently

    Science.gov (United States)

    Cuzzocrea, Alfredo

    In the context of data stream research, taming the multidimensionality of real-life data streams in order to efficiently support OLAP analysis/mining tasks is a critical challenge. Inspired by this fundamental motivation, in this paper we introduce CAMS (C ube-based A cquisition model for M ultidimensional S treams), a model for efficiently OLAPing multidimensional data streams. CAMS combines a set of data stream processing methodologies, namely (i) the OLAP dimension flattening process, which allows us to obtain dimensionality reduction of multidimensional data streams, and (ii) the OLAP stream aggregation scheme, which aggregates data stream readings according to an OLAP-hierarchy-based membership approach. We complete our analytical contribution by means of experimental assessment and analysis of both the efficiency and the scalability of OLAPing capabilities of CAMS on synthetic multidimensional data streams. Both analytical and experimental results clearly connote CAMS as an enabling component for next-generation Data Stream Management Systems.

  11. Identification of a set of genes showing regionally enriched expression in the mouse brain

    Directory of Open Access Journals (Sweden)

    Marra Marco A

    2008-07-01

    Full Text Available Abstract Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters ( Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

  12. Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder

    DEFF Research Database (Denmark)

    Naaijen, Jill; Bralten, Janita; Poelmans, Geert

    2017-01-01

    Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance...... within glutamatergic and GABAergic genes were investigated using the MAGMA software in an ADHD case-only sample (n=931), in which we assessed ASD symptoms and response inhibition on a Stop task. Gene set analysis for ADHD symptom severity, divided into inattention and hyperactivity/impulsivity symptoms...... is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on gene set analysis, an approach to investigate multiple genetic variants simultaneously. Common variants...

  13. Selection and validation of a set of reliable reference genes for quantitative sod gene expression analysis in C. elegans

    Directory of Open Access Journals (Sweden)

    Vandesompele Jo

    2008-01-01

    Full Text Available Abstract Background In the nematode Caenorhabditis elegans the conserved Ins/IGF-1 signaling pathway regulates many biological processes including life span, stress response, dauer diapause and metabolism. Detection of differentially expressed genes may contribute to a better understanding of the mechanism by which the Ins/IGF-1 signaling pathway regulates these processes. Appropriate normalization is an essential prerequisite for obtaining accurate and reproducible quantification of gene expression levels. The aim of this study was to establish a reliable set of reference genes for gene expression analysis in C. elegans. Results Real-time quantitative PCR was used to evaluate the expression stability of 12 candidate reference genes (act-1, ama-1, cdc-42, csq-1, eif-3.C, mdh-1, gpd-2, pmp-3, tba-1, Y45F10D.4, rgs-6 and unc-16 in wild-type, three Ins/IGF-1 pathway mutants, dauers and L3 stage larvae. After geNorm analysis, cdc-42, pmp-3 and Y45F10D.4 showed the most stable expression pattern and were used to normalize 5 sod expression levels. Significant differences in mRNA levels were observed for sod-1 and sod-3 in daf-2 relative to wild-type animals, whereas in dauers sod-1, sod-3, sod-4 and sod-5 are differentially expressed relative to third stage larvae. Conclusion Our findings emphasize the importance of accurate normalization using stably expressed reference genes. The methodology used in this study is generally applicable to reliably quantify gene expression levels in the nematode C. elegans using quantitative PCR.

  14. Evidence for intron length conservation in a set of mammalian genes associated with embryonic development

    LENUS (Irish Health Repository)

    2011-10-05

    Abstract Background We carried out an analysis of intron length conservation across a diverse group of nineteen mammalian species. Motivated by recent research suggesting a role for time delays associated with intron transcription in gene expression oscillations required for early embryonic patterning, we searched for examples of genes that showed the most extreme conservation of total intron content in mammals. Results Gene sets annotated as being involved in pattern specification in the early embryo or containing the homeobox DNA-binding domain, were significantly enriched among genes with highly conserved intron content. We used ancestral sequences reconstructed with probabilistic models that account for insertion and deletion mutations to distinguish insertion and deletion events on lineages leading to human and mouse from their last common ancestor. Using a randomization procedure, we show that genes containing the homeobox domain show less change in intron content than expected, given the number of insertion and deletion events within their introns. Conclusions Our results suggest selection for gene expression precision or the existence of additional development-associated genes for which transcriptional delay is functionally significant.

  15. Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

    Directory of Open Access Journals (Sweden)

    Reverter Antonio

    2008-09-01

    Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing

  16. An investigation into multi-dimensional prediction models to estimate the pose error of a quadcopter in a CSP plant setting

    Science.gov (United States)

    Lock, Jacobus C.; Smit, Willie J.; Treurnicht, Johann

    2016-05-01

    The Solar Thermal Energy Research Group (STERG) is investigating ways to make heliostats cheaper to reduce the total cost of a concentrating solar power (CSP) plant. One avenue of research is to use unmanned aerial vehicles (UAVs) to automate and assist with the heliostat calibration process. To do this, the pose estimation error of each UAV must be determined and integrated into a calibration procedure. A computer vision (CV) system is used to measure the pose of a quadcopter UAV. However, this CV system contains considerable measurement errors. Since this is a high-dimensional problem, a sophisticated prediction model must be used to estimate the measurement error of the CV system for any given pose measurement vector. This paper attempts to train and validate such a model with the aim of using it to determine the pose error of a quadcopter in a CSP plant setting.

  17. Can survival prediction be improved by merging gene expression data sets?

    Directory of Open Access Journals (Sweden)

    Haleh Yasrebi

    Full Text Available BACKGROUND: High-throughput gene expression profiling technologies generating a wealth of data, are increasingly used for characterization of tumor biopsies for clinical trials. By applying machine learning algorithms to such clinically documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limited number of patients enrolled in a single trial study limits the power of machine learning approaches due to over-fitting. One could partially overcome this limitation by merging data from different studies. Nevertheless, such data sets differ from each other with regard to technical biases, patient selection criteria and follow-up treatment. It is therefore not clear at all whether the advantage of increased sample size outweighs the disadvantage of higher heterogeneity of merged data sets. Here, we present a systematic study to answer this question specifically for breast cancer data sets. We use survival prediction based on Cox regression as an assay to measure the added value of merged data sets. RESULTS: Using time-dependent Receiver Operating Characteristic-Area Under the Curve (ROC-AUC and hazard ratio as performance measures, we see in overall no significant improvement or deterioration of survival prediction with merged data sets as compared to individual data sets. This apparently was due to the fact that a few genes with strong prognostic power were not available on all microarray platforms and thus were not retained in the merged data sets. Surprisingly, we found that the overall best performance was achieved with a single-gene predictor consisting of CYB5D1. CONCLUSIONS: Merging did not deteriorate performance on average despite (a The diversity of microarray platforms used. (b The heterogeneity of patients cohorts. (c The heterogeneity of breast cancer disease. (d Substantial variation of time to death or relapse. (e The reduced number of genes in the merged data

  18. Identification of self-consistent modulons from bacterial microarray expression data with the help of structured regulon gene sets

    KAUST Repository

    Permina, Elizaveta A.; Medvedeva, Yulia; Baeck, Pia M.; Hegde, Shubhada R.; Mande, Shekhar C.; Makeev, Vsevolod J.

    2013-01-01

    interactions helps to evaluate parameters for regulatory subnetwork inference. We suggest a procedure for modulon construction where a seed regulon is iteratively updated with genes having expression patterns similar to those for regulon member genes. A set

  19. Using OWL reasoning to support the generation of novel gene sets for enrichment analysis.

    Science.gov (United States)

    Osumi-Sutherland, David J; Ponta, Enrico; Courtot, Melanie; Parkinson, Helen; Badi, Laura

    2018-02-14

    The Gene Ontology (GO) consists of over 40,000 terms for biological processes, cell components and gene product activities linked into a graph structure by over 90,000 relationships. It has been used to annotate the functions and cellular locations of several million gene products. The graph structure is used by a variety of tools to group annotated genes into sets whose products share function or location. These gene sets are widely used to interpret the results of genomics experiments by assessing which sets are significantly over- or under-represented in results lists. F Hoffmann-La Roche Ltd. has developed a bespoke, manually maintained controlled vocabulary (RCV) for use in over-representation analysis. Many terms in this vocabulary group GO terms in novel ways that cannot easily be derived using the graph structure of the GO. For example, some RCV terms group GO terms by the cell, chemical or tissue type they refer to. Recent improvements in the content and formal structure of the GO make it possible to use logical queries in Web Ontology Language (OWL) to automatically map these cross-cutting classifications to sets of GO terms. We used this approach to automate mapping between RCV and GO, largely replacing the increasingly unsustainable manual mapping process. We then tested the utility of the resulting groupings for over-representation analysis. We successfully mapped 85% of RCV terms to logical OWL definitions and showed that these could be used to recapitulate and extend manual mappings between RCV terms and the sets of GO terms subsumed by them. We also show that gene sets derived from the resulting GO terms sets can be used to detect the signatures of cell and tissue types in whole genome expression data. The rich formal structure of the GO makes it possible to use reasoning to dynamically generate novel, biologically relevant groupings of GO terms. GO term groupings generated with this approach can be used in. over-representation analysis to detect

  20. Shrinkage covariance matrix approach based on robust trimmed mean in gene sets detection

    Science.gov (United States)

    Karjanto, Suryaefiza; Ramli, Norazan Mohamed; Ghani, Nor Azura Md; Aripin, Rasimah; Yusop, Noorezatty Mohd

    2015-02-01

    Microarray involves of placing an orderly arrangement of thousands of gene sequences in a grid on a suitable surface. The technology has made a novelty discovery since its development and obtained an increasing attention among researchers. The widespread of microarray technology is largely due to its ability to perform simultaneous analysis of thousands of genes in a massively parallel manner in one experiment. Hence, it provides valuable knowledge on gene interaction and function. The microarray data set typically consists of tens of thousands of genes (variables) from just dozens of samples due to various constraints. Therefore, the sample covariance matrix in Hotelling's T2 statistic is not positive definite and become singular, thus it cannot be inverted. In this research, the Hotelling's T2 statistic is combined with a shrinkage approach as an alternative estimation to estimate the covariance matrix to detect significant gene sets. The use of shrinkage covariance matrix overcomes the singularity problem by converting an unbiased to an improved biased estimator of covariance matrix. Robust trimmed mean is integrated into the shrinkage matrix to reduce the influence of outliers and consequently increases its efficiency. The performance of the proposed method is measured using several simulation designs. The results are expected to outperform existing techniques in many tested conditions.

  1. A reference gene set for sex pheromone biosynthesis and degradation genes from the diamondback moth, Plutella xylostella, based on genome and transcriptome digital gene expression analyses.

    Science.gov (United States)

    He, Peng; Zhang, Yun-Fei; Hong, Duan-Yang; Wang, Jun; Wang, Xing-Liang; Zuo, Ling-Hua; Tang, Xian-Fu; Xu, Wei-Ming; He, Ming

    2017-03-01

    comprehensive gene data set of sex pheromone biosynthesis and degradation enzyme related genes in DBM created by genome- and transcriptome-wide identification, characterization and expression profiling. Our findings provide a basis to better understand the function of genes with tissue enriched expression. The results also provide information on the genes involved in sex pheromone biosynthesis and degradation, and may be useful to identify potential gene targets for pest control strategies by disrupting the insect-insect communication using pheromone-based behavioral antagonists.

  2. Coverage and characteristics of the Affymetrix GeneChip Human Mapping 100K SNP set.

    Directory of Open Access Journals (Sweden)

    2006-05-01

    Full Text Available Improvements in technology have made it possible to conduct genome-wide association mapping at costs within reach of academic investigators, and experiments are currently being conducted with a variety of high-throughput platforms. To provide an appropriate context for interpreting results of such studies, we summarize here results of an investigation of one of the first of these technologies to be publicly available, the Affymetrix GeneChip Human Mapping 100K set of single nucleotide polymorphisms (SNPs. In a systematic analysis of the pattern and distribution of SNPs in the Mapping 100K set, we find that SNPs in this set are undersampled from coding regions (both nonsynonymous and synonymous and oversampled from regions outside genes, relative to SNPs in the overall HapMap database. In addition, we utilize a novel multilocus linkage disequilibrium (LD coefficient based on information content (analogous to the information content scores commonly used for linkage mapping that is equivalent to the familiar measure r2 in the special case of two loci. Using this approach, we are able to summarize for any subset of markers, such as the Affymetrix Mapping 100K set, the information available for association mapping in that subset, relative to the information available in the full set of markers included in the HapMap, and highlight circumstances in which this multilocus measure of LD provides substantial additional insight about the haplotype structure in a region over pairwise measures of LD.

  3. ADAGE signature analysis: differential expression analysis with data-defined gene sets.

    Science.gov (United States)

    Tan, Jie; Huyck, Matthew; Hu, Dongbo; Zelaya, René A; Hogan, Deborah A; Greene, Casey S

    2017-11-22

    Gene set enrichment analysis and overrepresentation analyses are commonly used methods to determine the biological processes affected by a differential expression experiment. This approach requires biologically relevant gene sets, which are currently curated manually, limiting their availability and accuracy in many organisms without extensively curated resources. New feature learning approaches can now be paired with existing data collections to directly extract functional gene sets from big data. Here we introduce a method to identify perturbed processes. In contrast with methods that use curated gene sets, this approach uses signatures extracted from public expression data. We first extract expression signatures from public data using ADAGE, a neural network-based feature extraction approach. We next identify signatures that are differentially active under a given treatment. Our results demonstrate that these signatures represent biological processes that are perturbed by the experiment. Because these signatures are directly learned from data without supervision, they can identify uncurated or novel biological processes. We implemented ADAGE signature analysis for the bacterial pathogen Pseudomonas aeruginosa. For the convenience of different user groups, we implemented both an R package (ADAGEpath) and a web server ( http://adage.greenelab.com ) to run these analyses. Both are open-source to allow easy expansion to other organisms or signature generation methods. We applied ADAGE signature analysis to an example dataset in which wild-type and ∆anr mutant cells were grown as biofilms on the Cystic Fibrosis genotype bronchial epithelial cells. We mapped active signatures in the dataset to KEGG pathways and compared with pathways identified using GSEA. The two approaches generally return consistent results; however, ADAGE signature analysis also identified a signature that revealed the molecularly supported link between the MexT regulon and Anr. We designed

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

    Directory of Open Access Journals (Sweden)

    Bai Chunyan

    2009-09-01

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

  5. Gene set-based module discovery in the breast cancer transcriptome

    Directory of Open Access Journals (Sweden)

    Zhang Michael Q

    2009-02-01

    Full Text Available Abstract Background Although microarray-based studies have revealed global view of gene expression in cancer cells, we still have little knowledge about regulatory mechanisms underlying the transcriptome. Several computational methods applied to yeast data have recently succeeded in identifying expression modules, which is defined as co-expressed gene sets under common regulatory mechanisms. However, such module discovery methods are not applied cancer transcriptome data. Results In order to decode oncogenic regulatory programs in cancer cells, we developed a novel module discovery method termed EEM by extending a previously reported module discovery method, and applied it to breast cancer expression data. Starting from seed gene sets prepared based on cis-regulatory elements, ChIP-chip data, and gene locus information, EEM identified 10 principal expression modules in breast cancer based on their expression coherence. Moreover, EEM depicted their activity profiles, which predict regulatory programs in each subtypes of breast tumors. For example, our analysis revealed that the expression module regulated by the Polycomb repressive complex 2 (PRC2 is downregulated in triple negative breast cancers, suggesting similarity of transcriptional programs between stem cells and aggressive breast cancer cells. We also found that the activity of the PRC2 expression module is negatively correlated to the expression of EZH2, a component of PRC2 which belongs to the E2F expression module. E2F-driven EZH2 overexpression may be responsible for the repression of the PRC2 expression modules in triple negative tumors. Furthermore, our network analysis predicts regulatory circuits in breast cancer cells. Conclusion These results demonstrate that the gene set-based module discovery approach is a powerful tool to decode regulatory programs in cancer cells.

  6. Reduced Set of Virulence Genes Allows High Accuracy Prediction of Bacterial Pathogenicity in Humans

    Science.gov (United States)

    Iraola, Gregorio; Vazquez, Gustavo; Spangenberg, Lucía; Naya, Hugo

    2012-01-01

    Although there have been great advances in understanding bacterial pathogenesis, there is still a lack of integrative information about what makes a bacterium a human pathogen. The advent of high-throughput sequencing technologies has dramatically increased the amount of completed bacterial genomes, for both known human pathogenic and non-pathogenic strains; this information is now available to investigate genetic features that determine pathogenic phenotypes in bacteria. In this work we determined presence/absence patterns of different virulence-related genes among more than finished bacterial genomes from both human pathogenic and non-pathogenic strains, belonging to different taxonomic groups (i.e: Actinobacteria, Gammaproteobacteria, Firmicutes, etc.). An accuracy of 95% using a cross-fold validation scheme with in-fold feature selection is obtained when classifying human pathogens and non-pathogens. A reduced subset of highly informative genes () is presented and applied to an external validation set. The statistical model was implemented in the BacFier v1.0 software (freely available at ), that displays not only the prediction (pathogen/non-pathogen) and an associated probability for pathogenicity, but also the presence/absence vector for the analyzed genes, so it is possible to decipher the subset of virulence genes responsible for the classification on the analyzed genome. Furthermore, we discuss the biological relevance for bacterial pathogenesis of the core set of genes, corresponding to eight functional categories, all with evident and documented association with the phenotypes of interest. Also, we analyze which functional categories of virulence genes were more distinctive for pathogenicity in each taxonomic group, which seems to be a completely new kind of information and could lead to important evolutionary conclusions. PMID:22916122

  7. Identification of a core set of rhizobial infection genes using data from single cell-types

    Directory of Open Access Journals (Sweden)

    Da-Song eChen

    2015-07-01

    Full Text Available Genome-wide expression studies on nodulation have varied in their scale from entire root systems to dissected nodules or root sections containing nodule primordia. More recently efforts have focused on developing methods for isolation of root hairs from infected plants and the application of laser-capture microdissection technology to nodules. Here we analyze two published data sets to identify a core set of infection genes that are expressed in the nodule and in root hairs during infection. Among the genes identified were those encoding phenylpropanoid biosynthesis enzymes including Chalcone-O-Methyltransferase which is required for the production of the potent Nod gene inducer 4’,4-dihydroxy-2-methoxychalcone. A promoter-GUS analysis in transgenic hairy roots for two genes encoding Chalcone-O-Methyltransferase isoforms revealed their expression in rhizobially infected root hairs and the nodule infection zone but not in the nitrogen fixation zone. We also describe a group of Rhizobially Induced Peroxidases whose expression overlaps with the production of superoxide in rhizobially infected root hairs and in nodules and roots. Finally, we identify a cohort of co-regulated transcription factors as candidate regulators of these processes.

  8. Expression map of a complete set of gustatory receptor genes in chemosensory organs of Bombyx mori.

    Science.gov (United States)

    Guo, Huizhen; Cheng, Tingcai; Chen, Zhiwei; Jiang, Liang; Guo, Youbing; Liu, Jianqiu; Li, Shenglong; Taniai, Kiyoko; Asaoka, Kiyoshi; Kadono-Okuda, Keiko; Arunkumar, Kallare P; Wu, Jiaqi; Kishino, Hirohisa; Zhang, Huijie; Seth, Rakesh K; Gopinathan, Karumathil P; Montagné, Nicolas; Jacquin-Joly, Emmanuelle; Goldsmith, Marian R; Xia, Qingyou; Mita, Kazuei

    2017-03-01

    Most lepidopteran species are herbivores, and interaction with host plants affects their gene expression and behavior as well as their genome evolution. Gustatory receptors (Grs) are expected to mediate host plant selection, feeding, oviposition and courtship behavior. However, due to their high diversity, sequence divergence and extremely low level of expression it has been difficult to identify precisely a complete set of Grs in Lepidoptera. By manual annotation and BAC sequencing, we improved annotation of 43 gene sequences compared with previously reported Grs in the most studied lepidopteran model, the silkworm, Bombyx mori, and identified 7 new tandem copies of BmGr30 on chromosome 7, bringing the total number of BmGrs to 76. Among these, we mapped 68 genes to chromosomes in a newly constructed chromosome distribution map and 8 genes to scaffolds; we also found new evidence for large clusters of BmGrs, especially from the bitter receptor family. RNA-seq analysis of diverse BmGr expression patterns in chemosensory organs of larvae and adults enabled us to draw a precise organ specific map of BmGr expression. Interestingly, most of the clustered genes were expressed in the same tissues and more than half of the genes were expressed in larval maxillae, larval thoracic legs and adult legs. For example, BmGr63 showed high expression levels in all organs in both larval and adult stages. By contrast, some genes showed expression limited to specific developmental stages or organs and tissues. BmGr19 was highly expressed in larval chemosensory organs (especially antennae and thoracic legs), the single exon genes BmGr53 and BmGr67 were expressed exclusively in larval tissues, the BmGr27-BmGr31 gene cluster on chr7 displayed a high expression level limited to adult legs and the candidate CO 2 receptor BmGr2 was highly expressed in adult antennae, where few other Grs were expressed. Transcriptional analysis of the Grs in B. mori provides a valuable new reference for

  9. Multidimensional First-Order Dominance Comparisons of Population Wellbeing

    DEFF Research Database (Denmark)

    Siersbæk, Nikolaj; Østerdal, Lars Peter Raahave; Arndt, Thomas Channing

    2017-01-01

    This chapter conveys the concept of first-order dominance (FOD) with particular focus on applications to multidimensional population welfare comparisons. It gives an account of the fundamental equivalent definitions of FOD both in the one-dimensional and multidimensional setting, illustrated...

  10. Identification of the Core Set of Carbon-Associated Genes in a Bioenergy Grassland Soil.

    Directory of Open Access Journals (Sweden)

    Adina Howe

    Full Text Available Despite the central role of soil microbial communities in global carbon (C cycling, little is known about soil microbial community structure and even less about their metabolic pathways. Efforts to characterize soil communities often focus on identifying differences in gene content across environmental gradients, but an alternative question is what genes are similar in soils. These genes may indicate critical species or potential functions that are required in all soils. Here we identified the "core" set of C cycling sequences widely present in multiple soil metagenomes from a fertilized prairie (FP. Of 226,887 sequences associated with known enzymes involved in the synthesis, metabolism, and transport of carbohydrates, 843 were identified to be consistently prevalent across four replicate soil metagenomes. This core metagenome was functionally and taxonomically diverse, representing five enzyme classes and 99 enzyme families within the CAZy database. Though it only comprised 0.4% of all CAZy-associated genes identified in FP metagenomes, the core was found to be comprised of functions similar to those within cumulative soils. The FP CAZy-associated core sequences were present in multiple publicly available soil metagenomes and most similar to soils sharing geographic proximity. In soil ecosystems, where high diversity remains a key challenge for metagenomic investigations, these core genes represent a subset of critical functions necessary for carbohydrate metabolism, which can be targeted to evaluate important C fluxes in these and other similar soils.

  11. Genome-Wide Temporal Expression Profiling in Caenorhabditis elegans Identifies a Core Gene Set Related to Long-Term Memory.

    Science.gov (United States)

    Freytag, Virginie; Probst, Sabine; Hadziselimovic, Nils; Boglari, Csaba; Hauser, Yannick; Peter, Fabian; Gabor Fenyves, Bank; Milnik, Annette; Demougin, Philippe; Vukojevic, Vanja; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila

    2017-07-12

    The identification of genes related to encoding, storage, and retrieval of memories is a major interest in neuroscience. In the current study, we analyzed the temporal gene expression changes in a neuronal mRNA pool during an olfactory long-term associative memory (LTAM) in Caenorhabditis elegans hermaphrodites. Here, we identified a core set of 712 (538 upregulated and 174 downregulated) genes that follows three distinct temporal peaks demonstrating multiple gene regulation waves in LTAM. Compared with the previously published positive LTAM gene set (Lakhina et al., 2015), 50% of the identified upregulated genes here overlap with the previous dataset, possibly representing stimulus-independent memory-related genes. On the other hand, the remaining genes were not previously identified in positive associative memory and may specifically regulate aversive LTAM. Our results suggest a multistep gene activation process during the formation and retrieval of long-term memory and define general memory-implicated genes as well as conditioning-type-dependent gene sets. SIGNIFICANCE STATEMENT The identification of genes regulating different steps of memory is of major interest in neuroscience. Identification of common memory genes across different learning paradigms and the temporal activation of the genes are poorly studied. Here, we investigated the temporal aspects of Caenorhabditis elegans gene expression changes using aversive olfactory associative long-term memory (LTAM) and identified three major gene activation waves. Like in previous studies, aversive LTAM is also CREB dependent, and CREB activity is necessary immediately after training. Finally, we define a list of memory paradigm-independent core gene sets as well as conditioning-dependent genes. Copyright © 2017 the authors 0270-6474/17/376661-12$15.00/0.

  12. Applied multidimensional scaling and unfolding

    CERN Document Server

    Borg, Ingwer; Mair, Patrick

    2018-01-01

    This book introduces multidimensional scaling (MDS) and unfolding as data analysis techniques for applied researchers. MDS is used for the analysis of proximity data on a set of objects, representing the data as distances between points in a geometric space (usually of two dimensions). Unfolding is a related method that maps preference data (typically evaluative ratings of different persons on a set of objects) as distances between two sets of points (representing the persons and the objects, resp.). This second edition has been completely revised to reflect new developments and the coverage of unfolding has also been substantially expanded. Intended for applied researchers whose main interests are in using these methods as tools for building substantive theories, it discusses numerous applications (classical and recent), highlights practical issues (such as evaluating model fit), presents ways to enforce theoretical expectations for the scaling solutions, and addresses the typical mistakes that MDS/unfoldin...

  13. Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones

    Directory of Open Access Journals (Sweden)

    Gerosolimo Germano

    2008-06-01

    Full Text Available Abstract Background Hepatitis C virus (HCV RNA synthesis and protein expression affect cell homeostasis by modulation of gene expression. The impact of HCV replication on global cell transcription has not been fully evaluated. Thus, we analysed the expression profiles of different clones of human hepatoma-derived Huh-7 cells carrying a self-replicating HCV RNA which express all viral proteins (HCV replicon system. Results First, we compared the expression profile of HCV replicon clone 21-5 with both the Huh-7 parental cells and the 21-5 cured (21-5c cells. In these latter, the HCV RNA has been eliminated by IFN-α treatment. To confirm data, we also analyzed microarray results from both the 21-5 and two other HCV replicon clones, 22-6 and 21-7, compared to the Huh-7 cells. The study was carried out by using the Applied Biosystems (AB Human Genome Survey Microarray v1.0 which provides 31,700 probes that correspond to 27,868 human genes. Microarray analysis revealed a specific transcriptional program induced by HCV in replicon cells respect to both IFN-α-cured and Huh-7 cells. From the original datasets of differentially expressed genes, we selected by Venn diagrams a final list of 38 genes modulated by HCV in all clones. Most of the 38 genes have never been described before and showed high fold-change associated with significant p-value, strongly supporting data reliability. Classification of the 38 genes by Panther System identified functional categories that were significantly enriched in this gene set, such as histones and ribosomal proteins as well as extracellular matrix and intracellular protein traffic. The dataset also included new genes involved in lipid metabolism, extracellular matrix and cytoskeletal network, which may be critical for HCV replication and pathogenesis. Conclusion Our data provide a comprehensive analysis of alterations in gene expression induced by HCV replication and reveal modulation of new genes potentially useful

  14. Systems-based biological concordance and predictive reproducibility of gene set discovery methods in cardiovascular disease.

    Science.gov (United States)

    Azuaje, Francisco; Zheng, Huiru; Camargo, Anyela; Wang, Haiying

    2011-08-01

    The discovery of novel disease biomarkers is a crucial challenge for translational bioinformatics. Demonstration of both their classification power and reproducibility across independent datasets are essential requirements to assess their potential clinical relevance. Small datasets and multiplicity of putative biomarker sets may explain lack of predictive reproducibility. Studies based on pathway-driven discovery approaches have suggested that, despite such discrepancies, the resulting putative biomarkers tend to be implicated in common biological processes. Investigations of this problem have been mainly focused on datasets derived from cancer research. We investigated the predictive and functional concordance of five methods for discovering putative biomarkers in four independently-generated datasets from the cardiovascular disease domain. A diversity of biosignatures was identified by the different methods. However, we found strong biological process concordance between them, especially in the case of methods based on gene set analysis. With a few exceptions, we observed lack of classification reproducibility using independent datasets. Partial overlaps between our putative sets of biomarkers and the primary studies exist. Despite the observed limitations, pathway-driven or gene set analysis can predict potentially novel biomarkers and can jointly point to biomedically-relevant underlying molecular mechanisms. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-08-01

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

  16. Applied multidimensional systems theory

    CERN Document Server

    Bose, Nirmal K

    2017-01-01

    Revised and updated, this concise new edition of the pioneering book on multidimensional signal processing is ideal for a new generation of students. Multidimensional systems or m-D systems are the necessary mathematical background for modern digital image processing with applications in biomedicine, X-ray technology and satellite communications. Serving as a firm basis for graduate engineering students and researchers seeking applications in mathematical theories, this edition eschews detailed mathematical theory not useful to students. Presentation of the theory has been revised to make it more readable for students, and introduce some new topics that are emerging as multidimensional DSP topics in the interdisciplinary fields of image processing. New topics include Groebner bases, wavelets, and filter banks.

  17. Genome-Wide Gene Set Analysis for Identification of Pathways Associated with Alcohol Dependence

    Science.gov (United States)

    Biernacka, Joanna M.; Geske, Jennifer; Jenkins, Gregory D.; Colby, Colin; Rider, David N.; Karpyak, Victor M.; Choi, Doo-Sup; Fridley, Brooke L.

    2013-01-01

    It is believed that multiple genetic variants with small individual effects contribute to the risk of alcohol dependence. Such polygenic effects are difficult to detect in genome-wide association studies that test for association of the phenotype with each single nucleotide polymorphism (SNP) individually. To overcome this challenge, gene set analysis (GSA) methods that jointly test for the effects of pre-defined groups of genes have been proposed. Rather than testing for association between the phenotype and individual SNPs, these analyses evaluate the global evidence of association with a set of related genes enabling the identification of cellular or molecular pathways or biological processes that play a role in development of the disease. It is hoped that by aggregating the evidence of association for all available SNPs in a group of related genes, these approaches will have enhanced power to detect genetic associations with complex traits. We performed GSA using data from a genome-wide study of 1165 alcohol dependent cases and 1379 controls from the Study of Addiction: Genetics and Environment (SAGE), for all 200 pathways listed in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results demonstrated a potential role of the “Synthesis and Degradation of Ketone Bodies” pathway. Our results also support the potential involvement of the “Neuroactive Ligand Receptor Interaction” pathway, which has previously been implicated in addictive disorders. These findings demonstrate the utility of GSA in the study of complex disease, and suggest specific directions for further research into the genetic architecture of alcohol dependence. PMID:22717047

  18. Multi-dimensional imaging

    CERN Document Server

    Javidi, Bahram; Andres, Pedro

    2014-01-01

    Provides a broad overview of advanced multidimensional imaging systems with contributions from leading researchers in the field Multi-dimensional Imaging takes the reader from the introductory concepts through to the latest applications of these techniques. Split into 3 parts covering 3D image capture, processing, visualization and display, using 1) a Multi-View Approach and 2.) a Holographic Approach, followed by a 3rd part addressing other 3D systems approaches, applications and signal processing for advanced 3D imaging. This book describes recent developments, as well as the prospects and

  19. Simulation of a Multidimensional Input Quantum Perceptron

    Science.gov (United States)

    Yamamoto, Alexandre Y.; Sundqvist, Kyle M.; Li, Peng; Harris, H. Rusty

    2018-06-01

    In this work, we demonstrate the improved data separation capabilities of the Multidimensional Input Quantum Perceptron (MDIQP), a fundamental cell for the construction of more complex Quantum Artificial Neural Networks (QANNs). This is done by using input controlled alterations of ancillary qubits in combination with phase estimation and learning algorithms. The MDIQP is capable of processing quantum information and classifying multidimensional data that may not be linearly separable, extending the capabilities of the classical perceptron. With this powerful component, we get much closer to the achievement of a feedforward multilayer QANN, which would be able to represent and classify arbitrary sets of data (both quantum and classical).

  20. In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer

    International Nuclear Information System (INIS)

    Pandi, Narayanan Sathiya; Suganya, Sivagurunathan; Rajendran, Suriliyandi

    2013-01-01

    Highlights: •Identified stomach lineage specific gene set (SLSGS) was found to be under expressed in gastric tumors. •Elevated expression of SLSGS in gastric tumor is a molecular predictor of metabolic type gastric cancer. •In silico pathway scanning identified estrogen-α signaling is a putative regulator of SLSGS in gastric cancer. •Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. -- Abstract: Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However, the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC

  1. In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pandi, Narayanan Sathiya, E-mail: sathiyapandi@gmail.com; Suganya, Sivagurunathan; Rajendran, Suriliyandi

    2013-10-04

    Highlights: •Identified stomach lineage specific gene set (SLSGS) was found to be under expressed in gastric tumors. •Elevated expression of SLSGS in gastric tumor is a molecular predictor of metabolic type gastric cancer. •In silico pathway scanning identified estrogen-α signaling is a putative regulator of SLSGS in gastric cancer. •Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. -- Abstract: Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However, the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC.

  2. Symbolic Multidimensional Scaling

    NARCIS (Netherlands)

    P.J.F. Groenen (Patrick); Y. Terada

    2015-01-01

    markdownabstract__Abstract__ Multidimensional scaling (MDS) is a technique that visualizes dissimilarities between pairs of objects as distances between points in a low dimensional space. In symbolic MDS, a dissimilarity is not just a value but can represent an interval or even a histogram. Here,

  3. Prediction potential of candidate biomarker sets identified and validated on gene expression data from multiple datasets

    Directory of Open Access Journals (Sweden)

    Karacali Bilge

    2007-10-01

    Full Text Available Abstract Background Independently derived expression profiles of the same biological condition often have few genes in common. In this study, we created populations of expression profiles from publicly available microarray datasets of cancer (breast, lymphoma and renal samples linked to clinical information with an iterative machine learning algorithm. ROC curves were used to assess the prediction error of each profile for classification. We compared the prediction error of profiles correlated with molecular phenotype against profiles correlated with relapse-free status. Prediction error of profiles identified with supervised univariate feature selection algorithms were compared to profiles selected randomly from a all genes on the microarray platform and b a list of known disease-related genes (a priori selection. We also determined the relevance of expression profiles on test arrays from independent datasets, measured on either the same or different microarray platforms. Results Highly discriminative expression profiles were produced on both simulated gene expression data and expression data from breast cancer and lymphoma datasets on the basis of ER and BCL-6 expression, respectively. Use of relapse-free status to identify profiles for prognosis prediction resulted in poorly discriminative decision rules. Supervised feature selection resulted in more accurate classifications than random or a priori selection, however, the difference in prediction error decreased as the number of features increased. These results held when decision rules were applied across-datasets to samples profiled on the same microarray platform. Conclusion Our results show that many gene sets predict molecular phenotypes accurately. Given this, expression profiles identified using different training datasets should be expected to show little agreement. In addition, we demonstrate the difficulty in predicting relapse directly from microarray data using supervised machine

  4. MADS goes genomic in conifers: towards determining the ancestral set of MADS-box genes in seed plants.

    Science.gov (United States)

    Gramzow, Lydia; Weilandt, Lisa; Theißen, Günter

    2014-11-01

    MADS-box genes comprise a gene family coding for transcription factors. This gene family expanded greatly during land plant evolution such that the number of MADS-box genes ranges from one or two in green algae to around 100 in angiosperms. Given the crucial functions of MADS-box genes for nearly all aspects of plant development, the expansion of this gene family probably contributed to the increasing complexity of plants. However, the expansion of MADS-box genes during one important step of land plant evolution, namely the origin of seed plants, remains poorly understood due to the previous lack of whole-genome data for gymnosperms. The newly available genome sequences of Picea abies, Picea glauca and Pinus taeda were used to identify the complete set of MADS-box genes in these conifers. In addition, MADS-box genes were identified in the growing number of transcriptomes available for gymnosperms. With these datasets, phylogenies were constructed to determine the ancestral set of MADS-box genes of seed plants and to infer the ancestral functions of these genes. Type I MADS-box genes are under-represented in gymnosperms and only a minimum of two Type I MADS-box genes have been present in the most recent common ancestor (MRCA) of seed plants. In contrast, a large number of Type II MADS-box genes were found in gymnosperms. The MRCA of extant seed plants probably possessed at least 11-14 Type II MADS-box genes. In gymnosperms two duplications of Type II MADS-box genes were found, such that the MRCA of extant gymnosperms had at least 14-16 Type II MADS-box genes. The implied ancestral set of MADS-box genes for seed plants shows simplicity for Type I MADS-box genes and remarkable complexity for Type II MADS-box genes in terms of phylogeny and putative functions. The analysis of transcriptome data reveals that gymnosperm MADS-box genes are expressed in a great variety of tissues, indicating diverse roles of MADS-box genes for the development of gymnosperms. This study is

  5. Evaluation of endogenous control genes for gene expression studies across multiple tissues and in the specific sets of fat- and muscle-type samples of the pig.

    Science.gov (United States)

    Gu, Y R; Li, M Z; Zhang, K; Chen, L; Jiang, A A; Wang, J Y; Li, X W

    2011-08-01

    To normalize a set of quantitative real-time PCR (q-PCR) data, it is essential to determine an optimal number/set of housekeeping genes, as the abundance of housekeeping genes can vary across tissues or cells during different developmental stages, or even under certain environmental conditions. In this study, of the 20 commonly used endogenous control genes, 13, 18 and 17 genes exhibited credible stability in 56 different tissues, 10 types of adipose tissue and five types of muscle tissue, respectively. Our analysis clearly showed that three optimal housekeeping genes are adequate for an accurate normalization, which correlated well with the theoretical optimal number (r ≥ 0.94). In terms of economical and experimental feasibility, we recommend the use of the three most stable housekeeping genes for calculating the normalization factor. Based on our results, the three most stable housekeeping genes in all analysed samples (TOP2B, HSPCB and YWHAZ) are recommended for accurate normalization of q-PCR data. We also suggest that two different sets of housekeeping genes are appropriate for 10 types of adipose tissue (the HSPCB, ALDOA and GAPDH genes) and five types of muscle tissue (the TOP2B, HSPCB and YWHAZ genes), respectively. Our report will serve as a valuable reference for other studies aimed at measuring tissue-specific mRNA abundance in porcine samples. © 2011 Blackwell Verlag GmbH.

  6. In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer.

    Science.gov (United States)

    Pandi, Narayanan Sathiya; Suganya, Sivagurunathan; Rajendran, Suriliyandi

    2013-10-04

    Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However, the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder: association to overlapping traits in ADHD and autism.

    Science.gov (United States)

    Naaijen, J; Bralten, J; Poelmans, G; Glennon, J C; Franke, B; Buitelaar, J K

    2017-01-10

    Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on gene set analysis, an approach to investigate multiple genetic variants simultaneously. Common variants within glutamatergic and GABAergic genes were investigated using the MAGMA software in an ADHD case-only sample (n=931), in which we assessed ASD symptoms and response inhibition on a Stop task. Gene set analysis for ADHD symptom severity, divided into inattention and hyperactivity/impulsivity symptoms, autism symptom severity and inhibition were performed using principal component regression analyses. Subsequently, gene-wide association analyses were performed. The glutamate gene set showed an association with severity of hyperactivity/impulsivity (P=0.009), which was robust to correcting for genome-wide association levels. The GABA gene set showed nominally significant association with inhibition (P=0.04), but this did not survive correction for multiple comparisons. None of single gene or single variant associations was significant on their own. By analyzing multiple genetic variants within candidate gene sets together, we were able to find genetic associations supporting the involvement of excitatory and inhibitory neurotransmitter systems in ADHD and ASD symptom severity in ADHD.

  8. Numeric invariants from multidimensional persistence

    Energy Technology Data Exchange (ETDEWEB)

    Skryzalin, Jacek [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Carlsson, Gunnar [Stanford Univ., Stanford, CA (United States)

    2017-05-19

    In this paper, we analyze the space of multidimensional persistence modules from the perspectives of algebraic geometry. We first build a moduli space of a certain subclass of easily analyzed multidimensional persistence modules, which we construct specifically to capture much of the information which can be gained by using multidimensional persistence over one-dimensional persistence. We argue that the global sections of this space provide interesting numeric invariants when evaluated against our subclass of multidimensional persistence modules. Lastly, we extend these global sections to the space of all multidimensional persistence modules and discuss how the resulting numeric invariants might be used to study data.

  9. Meta-analysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes.

    Directory of Open Access Journals (Sweden)

    Kevin P Keegan

    2007-11-01

    Full Text Available Five independent groups have reported microarray studies that identify dozens of rhythmically expressed genes in the fruit fly Drosophila melanogaster. Limited overlap among the lists of discovered genes makes it difficult to determine which, if any, exhibit truly rhythmic patterns of expression. We reanalyzed data from all five reports and found two sources for the observed discrepancies, the use of different expression pattern detection algorithms and underlying variation among the datasets. To improve upon the methods originally employed, we developed a new analysis that involves compilation of all existing data, application of identical transformation and standardization procedures followed by ANOVA-based statistical prescreening, and three separate classes of post hoc analysis: cross-correlation to various cycling waveforms, autocorrelation, and a previously described fast Fourier transform-based technique. Permutation-based statistical tests were used to derive significance measures for all post hoc tests. We find application of our method, most significantly the ANOVA prescreening procedure, significantly reduces the false discovery rate relative to that observed among the results of the original five reports while maintaining desirable statistical power. We identify a set of 81 cycling transcripts previously found in one or more of the original reports as well as a novel set of 133 transcripts not found in any of the original studies. We introduce a novel analysis method that compensates for variability observed among the original five Drosophila circadian array reports. Based on the statistical fidelity of our meta-analysis results, and the results of our initial validation experiments (quantitative RT-PCR, we predict many of our newly found genes to be bona fide cyclers, and suggest that they may lead to new insights into the pathways through which clock mechanisms regulate behavioral rhythms.

  10. Metabolic Genetic Screens Reveal Multidimensional Regulation of Virulence Gene Expression in Listeria monocytogenes and an Aminopeptidase That Is Critical for PrfA Protein Activation.

    Science.gov (United States)

    Friedman, Sivan; Linsky, Marika; Lobel, Lior; Rabinovich, Lev; Sigal, Nadejda; Herskovits, Anat A

    2017-06-01

    Listeria monocytogenes is an environmental saprophyte and intracellular bacterial pathogen. Upon invading mammalian cells, the bacterium senses abrupt changes in its metabolic environment, which are rapidly transduced to regulation of virulence gene expression. To explore the relationship between L. monocytogenes metabolism and virulence, we monitored virulence gene expression dynamics across a library of genetic mutants grown under two metabolic conditions known to activate the virulent state: charcoal-treated rich medium containing glucose-1-phosphate and minimal defined medium containing limiting concentrations of branched-chain amino acids (BCAAs). We identified over 100 distinct mutants that exhibit aberrant virulence gene expression profiles, the majority of which mapped to nonessential metabolic genes. Mutants displayed enhanced, decreased, and early and late virulence gene expression profiles, as well as persistent levels, demonstrating a high plasticity in virulence gene regulation. Among the mutants, one was noteworthy for its particularly low virulence gene expression level and mapped to an X-prolyl aminopeptidase (PepP). We show that this peptidase plays a role in posttranslational activation of the major virulence regulator, PrfA. Specifically, PepP mediates recruitment of PrfA to the cytoplasmic membrane, a step identified as critical for PrfA protein activation. This study establishes a novel step in the complex mechanism of PrfA activation and further highlights the cross regulation of metabolism and virulence. Copyright © 2017 American Society for Microbiology.

  11. An ancient dental gene set governs development and continuous regeneration of teeth in sharks.

    Science.gov (United States)

    Rasch, Liam J; Martin, Kyle J; Cooper, Rory L; Metscher, Brian D; Underwood, Charlie J; Fraser, Gareth J

    2016-07-15

    The evolution of oral teeth is considered a major contributor to the overall success of jawed vertebrates. This is especially apparent in cartilaginous fishes including sharks and rays, which develop elaborate arrays of highly specialized teeth, organized in rows and retain the capacity for life-long regeneration. Perpetual regeneration of oral teeth has been either lost or highly reduced in many other lineages including important developmental model species, so cartilaginous fishes are uniquely suited for deep comparative analyses of tooth development and regeneration. Additionally, sharks and rays can offer crucial insights into the characters of the dentition in the ancestor of all jawed vertebrates. Despite this, tooth development and regeneration in chondrichthyans is poorly understood and remains virtually uncharacterized from a developmental genetic standpoint. Using the emerging chondrichthyan model, the catshark (Scyliorhinus spp.), we characterized the expression of genes homologous to those known to be expressed during stages of early dental competence, tooth initiation, morphogenesis, and regeneration in bony vertebrates. We have found that expression patterns of several genes from Hh, Wnt/β-catenin, Bmp and Fgf signalling pathways indicate deep conservation over ~450 million years of tooth development and regeneration. We describe how these genes participate in the initial emergence of the shark dentition and how they are redeployed during regeneration of successive tooth generations. We suggest that at the dawn of the vertebrate lineage, teeth (i) were most likely continuously regenerative structures, and (ii) utilised a core set of genes from members of key developmental signalling pathways that were instrumental in creating a dental legacy redeployed throughout vertebrate evolution. These data lay the foundation for further experimental investigations utilizing the unique regenerative capacity of chondrichthyan models to answer evolutionary

  12. Development of a set of SNP markers present in expressed genes of the apple.

    Science.gov (United States)

    Chagné, David; Gasic, Ksenija; Crowhurst, Ross N; Han, Yuepeng; Bassett, Heather C; Bowatte, Deepa R; Lawrence, Timothy J; Rikkerink, Erik H A; Gardiner, Susan E; Korban, Schuyler S

    2008-11-01

    Molecular markers associated with gene coding regions are useful tools for bridging functional and structural genomics. Due to their high abundance in plant genomes, single nucleotide polymorphisms (SNPs) are present within virtually all genomic regions, including most coding sequences. The objective of this study was to develop a set of SNPs for the apple by taking advantage of the wealth of genomics resources available for the apple, including a large collection of expressed sequenced tags (ESTs). Using bioinformatics tools, a search for SNPs within an EST database of approximately 350,000 sequences developed from a variety of apple accessions was conducted. This resulted in the identification of a total of 71,482 putative SNPs. As the apple genome is reported to be an ancient polyploid, attempts were made to verify whether those SNPs detected in silico were attributable either to allelic polymorphisms or to gene duplication or paralogous or homeologous sequence variations. To this end, a set of 464 PCR primer pairs was designed, PCR was amplified using two subsets of plants, and the PCR products were sequenced. The SNPs retrieved from these sequences were then mapped onto apple genetic maps, including a newly constructed map of a Royal Gala x A689-24 cross and a Malling 9 x Robusta 5, map using a bin mapping strategy. The SNP genotyping was performed using the high-resolution melting (HRM) technique. A total of 93 new markers containing 210 coding SNPs were successfully mapped. This new set of SNP markers for the apple offers new opportunities for understanding the genetic control of important horticultural traits using quantitative trait loci (QTL) or linkage disequilibrium analysis. These also serve as useful markers for aligning physical and genetic maps, and as potential transferable markers across the Rosaceae family.

  13. Multidimensional nonlinear descriptive analysis

    CERN Document Server

    Nishisato, Shizuhiko

    2006-01-01

    Quantification of categorical, or non-numerical, data is a problem that scientists face across a wide range of disciplines. Exploring data analysis in various areas of research, such as the social sciences and biology, Multidimensional Nonlinear Descriptive Analysis presents methods for analyzing categorical data that are not necessarily sampled randomly from a normal population and often involve nonlinear relations. This reference not only provides an overview of multidimensional nonlinear descriptive analysis (MUNDA) of discrete data, it also offers new results in a variety of fields. The first part of the book covers conceptual and technical preliminaries needed to understand the data analysis in subsequent chapters. The next two parts contain applications of MUNDA to diverse data types, with each chapter devoted to one type of categorical data, a brief historical comment, and basic skills peculiar to the data types. The final part examines several problems and then concludes with suggestions for futu...

  14. Intuitionistic fuzzy (IF) evaluations of multidimensional model

    International Nuclear Information System (INIS)

    Valova, I.

    2012-01-01

    There are different logical methods for data structuring, but no one is perfect enough. Multidimensional model-MD of data is presentation of data in a form of cube (referred also as info-cube or hypercube) with data or in form of 'star' type scheme (referred as multidimensional scheme), by use of F-structures (Facts) and set of D-structures (Dimensions), based on the notion of hierarchy of D-structures. The data, being subject of analysis in a specific multidimensional model is located in a Cartesian space, being restricted by D-structures. In fact, the data is either dispersed or 'concentrated', therefore the data cells are not distributed evenly within the respective space. The moment of occurrence of any event is difficult to be predicted and the data is concentrated as per time periods, location of performed business event, etc. To process such dispersed or concentrated data, various technical strategies are needed. The basic methods for presentation of such data should be selected. The approaches of data processing and respective calculations are connected with different options for data representation. The use of intuitionistic fuzzy evaluations (IFE) provide us new possibilities for alternative presentation and processing of data, subject of analysis in any OLAP application. The use of IFE at the evaluation of multidimensional models will result in the following advantages: analysts will dispose with more complete information for processing and analysis of respective data; benefit for the managers is that the final decisions will be more effective ones; enabling design of more functional multidimensional schemes. The purpose of this work is to apply intuitionistic fuzzy evaluations of multidimensional model of data. (authors)

  15. The multidimensional nucleon structure

    Directory of Open Access Journals (Sweden)

    Pasquini Barbara

    2016-01-01

    Full Text Available We discuss different kinds of parton distributions, which allow one to obtain a multidimensional picture of the internal structure of the nucleon. We use the concept of generalized transverse momentum dependent parton distributions and Wigner distributions, which combine the features of transverse-momentum dependent parton distributions and generalized parton distributions. We show examples of these functions within a phenomenological quark model, with focus on the role of the spin-spin and spin-orbit correlations of quarks.

  16. DNMT1 is associated with cell cycle and DNA replication gene sets in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Loo, Suet Kee; Ab Hamid, Suzina Sheikh; Musa, Mustaffa; Wong, Kah Keng

    2018-01-01

    Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR) 0.8) with DNMT1 expression and significantly downregulated (log fold-change <-1.35; p<0.05) following DNMT1 silencing in HT cells. These results suggest the involvement of DNMT1 in the activation of cell cycle and DNA replication in DLBCL cells. Copyright © 2017 Elsevier GmbH. All rights reserved.

  17. Identification of sparsely distributed clusters of cis-regulatory elements in sets of co-expressed genes

    OpenAIRE

    Kreiman, Gabriel

    2004-01-01

    Sequence information and high‐throughput methods to measure gene expression levels open the door to explore transcriptional regulation using computational tools. Combinatorial regulation and sparseness of regulatory elements throughout the genome allow organisms to control the spatial and temporal patterns of gene expression. Here we study the organization of cis‐regulatory elements in sets of co‐regulated genes. We build an algorithm to search for combinations of transcription factor binding...

  18. A novel CpG island set identifies tissue-specific methylation at developmental gene loci.

    Directory of Open Access Journals (Sweden)

    Robert Illingworth

    2008-01-01

    Full Text Available CpG islands (CGIs are dense clusters of CpG sequences that punctuate the CpG-deficient human genome and associate with many gene promoters. As CGIs also differ from bulk chromosomal DNA by their frequent lack of cytosine methylation, we devised a CGI enrichment method based on nonmethylated CpG affinity chromatography. The resulting library was sequenced to define a novel human blood CGI set that includes many that are not detected by current algorithms. Approximately half of CGIs were associated with annotated gene transcription start sites, the remainder being intra- or intergenic. Using an array representing over 17,000 CGIs, we established that 6%-8% of CGIs are methylated in genomic DNA of human blood, brain, muscle, and spleen. Inter- and intragenic CGIs are preferentially susceptible to methylation. CGIs showing tissue-specific methylation were overrepresented at numerous genetic loci that are essential for development, including HOX and PAX family members. The findings enable a comprehensive analysis of the roles played by CGI methylation in normal and diseased human tissues.

  19. Transcriptome-wide selection of a reliable set of reference genes for gene expression studies in potato cyst nematodes (Globodera spp.).

    Science.gov (United States)

    Sabeh, Michael; Duceppe, Marc-Olivier; St-Arnaud, Marc; Mimee, Benjamin

    2018-01-01

    Relative gene expression analyses by qRT-PCR (quantitative reverse transcription PCR) require an internal control to normalize the expression data of genes of interest and eliminate the unwanted variation introduced by sample preparation. A perfect reference gene should have a constant expression level under all the experimental conditions. However, the same few housekeeping genes selected from the literature or successfully used in previous unrelated experiments are often routinely used in new conditions without proper validation of their stability across treatments. The advent of RNA-Seq and the availability of public datasets for numerous organisms are opening the way to finding better reference genes for expression studies. Globodera rostochiensis is a plant-parasitic nematode that is particularly yield-limiting for potato. The aim of our study was to identify a reliable set of reference genes to study G. rostochiensis gene expression. Gene expression levels from an RNA-Seq database were used to identify putative reference genes and were validated with qRT-PCR analysis. Three genes, GR, PMP-3, and aaRS, were found to be very stable within the experimental conditions of this study and are proposed as reference genes for future work.

  20. A Meta-Analysis of Multiple Matched Copy Number and Transcriptomics Data Sets for Inferring Gene Regulatory Relationships

    Science.gov (United States)

    Newton, Richard; Wernisch, Lorenz

    2014-01-01

    Inferring gene regulatory relationships from observational data is challenging. Manipulation and intervention is often required to unravel causal relationships unambiguously. However, gene copy number changes, as they frequently occur in cancer cells, might be considered natural manipulation experiments on gene expression. An increasing number of data sets on matched array comparative genomic hybridisation and transcriptomics experiments from a variety of cancer pathologies are becoming publicly available. Here we explore the potential of a meta-analysis of thirty such data sets. The aim of our analysis was to assess the potential of in silico inference of trans-acting gene regulatory relationships from this type of data. We found sufficient correlation signal in the data to infer gene regulatory relationships, with interesting similarities between data sets. A number of genes had highly correlated copy number and expression changes in many of the data sets and we present predicted potential trans-acted regulatory relationships for each of these genes. The study also investigates to what extent heterogeneity between cell types and between pathologies determines the number of statistically significant predictions available from a meta-analysis of experiments. PMID:25148247

  1. Classification of Non-Small Cell Lung Cancer Using Significance Analysis of Microarray-Gene Set Reduction Algorithm

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2016-01-01

    Full Text Available Among non-small cell lung cancer (NSCLC, adenocarcinoma (AC, and squamous cell carcinoma (SCC are two major histology subtypes, accounting for roughly 40% and 30% of all lung cancer cases, respectively. Since AC and SCC differ in their cell of origin, location within the lung, and growth pattern, they are considered as distinct diseases. Gene expression signatures have been demonstrated to be an effective tool for distinguishing AC and SCC. Gene set analysis is regarded as irrelevant to the identification of gene expression signatures. Nevertheless, we found that one specific gene set analysis method, significance analysis of microarray-gene set reduction (SAMGSR, can be adopted directly to select relevant features and to construct gene expression signatures. In this study, we applied SAMGSR to a NSCLC gene expression dataset. When compared with several novel feature selection algorithms, for example, LASSO, SAMGSR has equivalent or better performance in terms of predictive ability and model parsimony. Therefore, SAMGSR is a feature selection algorithm, indeed. Additionally, we applied SAMGSR to AC and SCC subtypes separately to discriminate their respective stages, that is, stage II versus stage I. Few overlaps between these two resulting gene signatures illustrate that AC and SCC are technically distinct diseases. Therefore, stratified analyses on subtypes are recommended when diagnostic or prognostic signatures of these two NSCLC subtypes are constructed.

  2. Gene Set Analyses of Genome-Wide Association Studies on 49 Quantitative Traits Measured in a Single Genetic Epidemiology Dataset

    Directory of Open Access Journals (Sweden)

    Jihye Kim

    2013-09-01

    Full Text Available Gene set analysis is a powerful tool for interpreting a genome-wide association study result and is gaining popularity these days. Comparison of the gene sets obtained for a variety of traits measured from a single genetic epidemiology dataset may give insights into the biological mechanisms underlying these traits. Based on the previously published single nucleotide polymorphism (SNP genotype data on 8,842 individuals enrolled in the Korea Association Resource project, we performed a series of systematic genome-wide association analyses for 49 quantitative traits of basic epidemiological, anthropometric, or blood chemistry parameters. Each analysis result was subjected to subsequent gene set analyses based on Gene Ontology (GO terms using gene set analysis software, GSA-SNP, identifying a set of GO terms significantly associated to each trait (pcorr < 0.05. Pairwise comparison of the traits in terms of the semantic similarity in their GO sets revealed surprising cases where phenotypically uncorrelated traits showed high similarity in terms of biological pathways. For example, the pH level was related to 7 other traits that showed low phenotypic correlations with it. A literature survey implies that these traits may be regulated partly by common pathways that involve neuronal or nerve systems.

  3. Multidimensional Models of Information Need

    OpenAIRE

    Yun-jie (Calvin) Xu; Kai Huang (Joseph) Tan

    2009-01-01

    User studies in information science have recognised relevance as a multidimensional construct. An implication of multidimensional relevance is that a user's information need should be modeled by multiple data structures to represent different relevance dimensions. While the extant literature has attempted to model multiple dimensions of a user's information need, the fundamental assumption that a multidimensional model is better than a uni-dimensional model has not been addressed. This study ...

  4. A Conceptual Model for Multidimensional Analysis of Documents

    Science.gov (United States)

    Ravat, Franck; Teste, Olivier; Tournier, Ronan; Zurlfluh, Gilles

    Data warehousing and OLAP are mainly used for the analysis of transactional data. Nowadays, with the evolution of Internet, and the development of semi-structured data exchange format (such as XML), it is possible to consider entire fragments of data such as documents as analysis sources. As a consequence, an adapted multidimensional analysis framework needs to be provided. In this paper, we introduce an OLAP multidimensional conceptual model without facts. This model is based on the unique concept of dimensions and is adapted for multidimensional document analysis. We also provide a set of manipulation operations.

  5. SUSTAINABLE DEVELOPMENT, A MULTIDIMENSIONAL CONCEPT

    Directory of Open Access Journals (Sweden)

    TEODORESCU ANA MARIA

    2015-06-01

    Full Text Available Sustainable development imposed itself as a corollary of economic term "development". Sustainable development is meant to be the summation of economic, environmental and social considerations for the present and especially for the future. The concept of sustainable development plays an important role in european and global meetings since 1972, the year it has been set for the first time. Strategies necessary to achieve the objectives of sustainable development have been developed, indicators meant to indicate the result of the implementation of policies have been created, national plans were oriented towards achieving the proposed targets. I wanted to highlight the multidimensional character of the concept of sustainable development. Thus, using specialized national and international literature, I have revealed different approaches of one pillar to the detriment of another pillar depending on the specific field. In the different concepts of sustainable development, the consensus is undoubtedly agreed on its components: economic, social, environmental. Based on this fact, the concept of sustainability has different connotations depending on the specific content of each discipline: biology, economics, sociology, environmental ethics. The multidimensional valence of sustainable development consists of three pillars ability to act together for the benefit of present and future generations. Being a multidimensional concept, importance attached to a pillar over another is directed according to the particularities of each field: in economy profit prevails, in ecology care of natural resources is the most important, the social aims improving human living conditions. The challenge of sustainable development is to combine all the economic, environmental and social benefits and the present generation to come. Ecological approach is reflected in acceptance of limited natural resources by preserving natural capital. In terms of the importance of

  6. A dual origin of the Xist gene from a protein-coding gene and a set of transposable elements.

    Directory of Open Access Journals (Sweden)

    Eugeny A Elisaphenko

    2008-06-01

    Full Text Available X-chromosome inactivation, which occurs in female eutherian mammals is controlled by a complex X-linked locus termed the X-inactivation center (XIC. Previously it was proposed that genes of the XIC evolved, at least in part, as a result of pseudogenization of protein-coding genes. In this study we show that the key XIC gene Xist, which displays fragmentary homology to a protein-coding gene Lnx3, emerged de novo in early eutherians by integration of mobile elements which gave rise to simple tandem repeats. The Xist gene promoter region and four out of ten exons found in eutherians retain homology to exons of the Lnx3 gene. The remaining six Xist exons including those with simple tandem repeats detectable in their structure have similarity to different transposable elements. Integration of mobile elements into Xist accompanies the overall evolution of the gene and presumably continues in contemporary eutherian species. Additionally we showed that the combination of remnants of protein-coding sequences and mobile elements is not unique to the Xist gene and is found in other XIC genes producing non-coding nuclear RNA.

  7. Minimal models of multidimensional computations.

    Directory of Open Access Journals (Sweden)

    Jeffrey D Fitzgerald

    2011-03-01

    Full Text Available The multidimensional computations performed by many biological systems are often characterized with limited information about the correlations between inputs and outputs. Given this limitation, our approach is to construct the maximum noise entropy response function of the system, leading to a closed-form and minimally biased model consistent with a given set of constraints on the input/output moments; the result is equivalent to conditional random field models from machine learning. For systems with binary outputs, such as neurons encoding sensory stimuli, the maximum noise entropy models are logistic functions whose arguments depend on the constraints. A constraint on the average output turns the binary maximum noise entropy models into minimum mutual information models, allowing for the calculation of the information content of the constraints and an information theoretic characterization of the system's computations. We use this approach to analyze the nonlinear input/output functions in macaque retina and thalamus; although these systems have been previously shown to be responsive to two input dimensions, the functional form of the response function in this reduced space had not been unambiguously identified. A second order model based on the logistic function is found to be both necessary and sufficient to accurately describe the neural responses to naturalistic stimuli, accounting for an average of 93% of the mutual information with a small number of parameters. Thus, despite the fact that the stimulus is highly non-Gaussian, the vast majority of the information in the neural responses is related to first and second order correlations. Our results suggest a principled and unbiased way to model multidimensional computations and determine the statistics of the inputs that are being encoded in the outputs.

  8. GSHR, a Web-Based Platform Provides Gene Set-Level Analyses of Hormone Responses in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Xiaojuan Ran

    2018-01-01

    Full Text Available Phytohormones regulate diverse aspects of plant growth and environmental responses. Recent high-throughput technologies have promoted a more comprehensive profiling of genes regulated by different hormones. However, these omics data generally result in large gene lists that make it challenging to interpret the data and extract insights into biological significance. With the rapid accumulation of theses large-scale experiments, especially the transcriptomic data available in public databases, a means of using this information to explore the transcriptional networks is needed. Different platforms have different architectures and designs, and even similar studies using the same platform may obtain data with large variances because of the highly dynamic and flexible effects of plant hormones; this makes it difficult to make comparisons across different studies and platforms. Here, we present a web server providing gene set-level analyses of Arabidopsis thaliana hormone responses. GSHR collected 333 RNA-seq and 1,205 microarray datasets from the Gene Expression Omnibus, characterizing transcriptomic changes in Arabidopsis in response to phytohormones including abscisic acid, auxin, brassinosteroids, cytokinins, ethylene, gibberellins, jasmonic acid, salicylic acid, and strigolactones. These data were further processed and organized into 1,368 gene sets regulated by different hormones or hormone-related factors. By comparing input gene lists to these gene sets, GSHR helped to identify gene sets from the input gene list regulated by different phytohormones or related factors. Together, GSHR links prior information regarding transcriptomic changes induced by hormones and related factors to newly generated data and facilities cross-study and cross-platform comparisons; this helps facilitate the mining of biologically significant information from large-scale datasets. The GSHR is freely available at http://bioinfo.sibs.ac.cn/GSHR/.

  9. A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records.

    Science.gov (United States)

    Jiang, Li; Edwards, Stefan M; Thomsen, Bo; Workman, Christopher T; Guldbrandtsen, Bernt; Sørensen, Peter

    2014-09-24

    Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic profile of genes with respect to their connection to disease phenotypes. The importance of protein-protein interaction networks in the genetic heterogeneity of common diseases or complex traits is becoming increasingly recognized. Thus, the development of a network-based approach combined with phenotypic profiling would be useful for disease gene prioritization. We developed a random-set scoring model and implemented it to quantify phenotype relevance in a network-based disease gene-prioritization approach. We validated our approach based on different gene phenotypic profiles, which were generated from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining of the phenotype data. Our method demonstrated good precision and sensitivity compared with those of two alternative complex-based prioritization approaches. We then conducted a global ranking of all human genes according to their relevance to a range of human diseases. The resulting accurate ranking of known causal genes supported the reliability of our approach. Moreover, these data suggest many promising novel candidate genes for human disorders that have a complex mode of inheritance. We have implemented and validated a network-based approach to prioritize genes for human diseases based on their phenotypic profile. We have devised a powerful and transparent tool to identify and rank candidate genes. Our global gene prioritization provides a unique resource for the biological interpretation of data

  10. Performance of single and concatenated sets of mitochondrial genes at inferring metazoan relationships relative to full mitogenome data.

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    Justin C Havird

    Full Text Available Mitochondrial (mt genes are some of the most popular and widely-utilized genetic loci in phylogenetic studies of metazoan taxa. However, their linked nature has raised questions on whether using the entire mitogenome for phylogenetics is overkill (at best or pseudoreplication (at worst. Moreover, no studies have addressed the comparative phylogenetic utility of mitochondrial genes across individual lineages within the entire Metazoa. To comment on the phylogenetic utility of individual mt genes as well as concatenated subsets of genes, we analyzed mitogenomic data from 1865 metazoan taxa in 372 separate lineages spanning genera to subphyla. Specifically, phylogenies inferred from these datasets were statistically compared to ones generated from all 13 mt protein-coding (PC genes (i.e., the "supergene" set to determine which single genes performed "best" at, and the minimum number of genes required to, recover the "supergene" topology. Surprisingly, the popular marker COX1 performed poorest, while ND5, ND4, and ND2 were most likely to reproduce the "supergene" topology. Averaged across all lineages, the longest ∼2 mt PC genes were sufficient to recreate the "supergene" topology, although this average increased to ∼5 genes for datasets with 40 or more taxa. Furthermore, concatenation of the three "best" performing mt PC genes outperformed that of the three longest mt PC genes (i.e, ND5, COX1, and ND4. Taken together, while not all mt PC genes are equally interchangeable in phylogenetic studies of the metazoans, some subset can serve as a proxy for the 13 mt PC genes. However, the exact number and identity of these genes is specific to the lineage in question and cannot be applied indiscriminately across the Metazoa.

  11. Multidimensional sexual perfectionism.

    Science.gov (United States)

    Stoeber, Joachim; Harvey, Laura N; Almeida, Isabel; Lyons, Emma

    2013-11-01

    Perfectionism is a multidimensional personality characteristic that can affect all areas of life. This article presents the first systematic investigation of multidimensional perfectionism in the domain of sexuality exploring the unique relationships that different forms of sexual perfectionism show with positive and negative aspects of sexuality. A sample of 272 university students (52 male, 220 female) completed measures of four forms of sexual perfectionism: self-oriented, partner-oriented, partner-prescribed, and socially prescribed. In addition, they completed measures of sexual esteem, sexual self-efficacy, sexual optimism, sex life satisfaction (capturing positive aspects of sexuality) and sexual problem self-blame, sexual anxiety, sexual depression, and negative sexual perfectionism cognitions during sex (capturing negative aspects). Results showed unique patterns of relationships for the four forms of sexual perfectionism, suggesting that partner-prescribed and socially prescribed sexual perfectionism are maladaptive forms of sexual perfectionism associated with negative aspects of sexuality whereas self-oriented and partner-oriented sexual perfectionism emerged as ambivalent forms associated with positive and negative aspects.

  12. Expanding the net: The re-evaluation of the multidimensional nomogram calculating the upper limit of normal PTH (maxPTH) in the setting of secondary hyperparathyroidism and the development of the MultIdimensional Predictive hyperparaTHyroid model (Mi-PTH).

    Science.gov (United States)

    Rajhbeharrysingh, Uma; El Youssef, Joseph; Leon, Enrique; Lasarev, Michael R; Klein, Robert; Vanek, Chaim; Mattar, Samer; Berber, Eren; Siperstein, Allan; Shindo, Maisie; Milas, Mira

    2016-01-01

    The multidimensional nomogram calculating the upper limit of normal PTH (maxPTH) model identifies a personalized upper limit of normal parathyroid hormone (PTH) and successfully predicts classical primary hyperparathyroidism (PHP). We aimed to assess whether maxPTH can distinguish normocalcemic PHP (NCPHP) from secondary hyperparathyroidism (SHP), including subjects who underwent bariatric surgery (BrS). A total of 172 subjects with 359 complete datasets of serum calcium (Ca), 25-OH vitamin D, and intact PTH from Oregon were analyzed: 123 subjects (212 datasets) with PHP and 47 (143) with SHP, including 28 (100) with previous BrS. An improved prediction model, MultIdimensional evaluation for Primary hyperparaTHyroidism (Mi-PTH), was created with the same variables as maxPTH by the use of a combined cohort (995 subjects) including participants from previous studies. In the Oregon cohort, maxPTH's sensitivity was 100% for classical PHP and 89% for NCPHP, but only 50% for normohormonal PHP (NHPHP) and 40% specific for SHP. In comparison, although sensitivity for NCPHP was similar (89%), Mi-PTH vastly improved SHP specificity (85%). In the combined cohort, Mi-PTH had better sensitivity of 98.5% (vs 95%) and specificity 97% (vs 85%). MaxPTH was sensitive in detecting PHP; however, there was low specificity for SHP, especially in patients who underwent BrS. The creation of Mi-PTH provided improved performance measures but requires further prospective evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Comprehensive Analysis of MILE Gene Expression Data Set Advances Discovery of Leukaemia Type and Subtype Biomarkers.

    Science.gov (United States)

    Labaj, Wojciech; Papiez, Anna; Polanski, Andrzej; Polanska, Joanna

    2017-03-01

    Large collections of data in studies on cancer such as leukaemia provoke the necessity of applying tailored analysis algorithms to ensure supreme information extraction. In this work, a custom-fit pipeline is demonstrated for thorough investigation of the voluminous MILE gene expression data set. Three analyses are accomplished, each for gaining a deeper understanding of the processes underlying leukaemia types and subtypes. First, the main disease groups are tested for differential expression against the healthy control as in a standard case-control study. Here, the basic knowledge on molecular mechanisms is confirmed quantitatively and by literature references. Second, pairwise comparison testing is performed for juxtaposing the main leukaemia types among each other. In this case by means of the Dice coefficient similarity measure the general relations are pointed out. Moreover, lists of candidate main leukaemia group biomarkers are proposed. Finally, with this approach being successful, the third analysis provides insight into all of the studied subtypes, followed by the emergence of four leukaemia subtype biomarkers. In addition, the class enhanced DEG signature obtained on the basis of novel pipeline processing leads to significantly better classification power of multi-class data classifiers. The developed methodology consisting of batch effect adjustment, adaptive noise and feature filtration coupled with adequate statistical testing and biomarker definition proves to be an effective approach towards knowledge discovery in high-throughput molecular biology experiments.

  14. Quantitative modeling of gene networks of biological systems using fuzzy Petri nets and fuzzy sets

    Directory of Open Access Journals (Sweden)

    Raed I. Hamed

    2018-01-01

    Full Text Available Quantitative demonstrating of organic frameworks has turned into an essential computational methodology in the configuration of novel and investigation of existing natural frameworks. Be that as it may, active information that portrays the framework's elements should be known keeping in mind the end goal to get pertinent results with the routine displaying strategies. This information is frequently robust or even difficult to get. Here, we exhibit a model of quantitative fuzzy rational demonstrating approach that can adapt to obscure motor information and hence deliver applicable results despite the fact that dynamic information is fragmented or just dubiously characterized. Besides, the methodology can be utilized as a part of the blend with the current cutting edge quantitative demonstrating strategies just in specific parts of the framework, i.e., where the data are absent. The contextual analysis of the methodology suggested in this paper is performed on the model of nine-quality genes. We propose a kind of FPN model in light of fuzzy sets to manage the quantitative modeling of biological systems. The tests of our model appear that the model is practical and entirely powerful for information impersonation and thinking of fuzzy expert frameworks.

  15. The SET1 Complex Selects Actively Transcribed Target Genes via Multivalent Interaction with CpG Island Chromatin.

    Science.gov (United States)

    Brown, David A; Di Cerbo, Vincenzo; Feldmann, Angelika; Ahn, Jaewoo; Ito, Shinsuke; Blackledge, Neil P; Nakayama, Manabu; McClellan, Michael; Dimitrova, Emilia; Turberfield, Anne H; Long, Hannah K; King, Hamish W; Kriaucionis, Skirmantas; Schermelleh, Lothar; Kutateladze, Tatiana G; Koseki, Haruhiko; Klose, Robert J

    2017-09-05

    Chromatin modifications and the promoter-associated epigenome are important for the regulation of gene expression. However, the mechanisms by which chromatin-modifying complexes are targeted to the appropriate gene promoters in vertebrates and how they influence gene expression have remained poorly defined. Here, using a combination of live-cell imaging and functional genomics, we discover that the vertebrate SET1 complex is targeted to actively transcribed gene promoters through CFP1, which engages in a form of multivalent chromatin reading that involves recognition of non-methylated DNA and histone H3 lysine 4 trimethylation (H3K4me3). CFP1 defines SET1 complex occupancy on chromatin, and its multivalent interactions are required for the SET1 complex to place H3K4me3. In the absence of CFP1, gene expression is perturbed, suggesting that normal targeting and function of the SET1 complex are central to creating an appropriately functioning vertebrate promoter-associated epigenome. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. The SET1 Complex Selects Actively Transcribed Target Genes via Multivalent Interaction with CpG Island Chromatin

    Directory of Open Access Journals (Sweden)

    David A. Brown

    2017-09-01

    Full Text Available Chromatin modifications and the promoter-associated epigenome are important for the regulation of gene expression. However, the mechanisms by which chromatin-modifying complexes are targeted to the appropriate gene promoters in vertebrates and how they influence gene expression have remained poorly defined. Here, using a combination of live-cell imaging and functional genomics, we discover that the vertebrate SET1 complex is targeted to actively transcribed gene promoters through CFP1, which engages in a form of multivalent chromatin reading that involves recognition of non-methylated DNA and histone H3 lysine 4 trimethylation (H3K4me3. CFP1 defines SET1 complex occupancy on chromatin, and its multivalent interactions are required for the SET1 complex to place H3K4me3. In the absence of CFP1, gene expression is perturbed, suggesting that normal targeting and function of the SET1 complex are central to creating an appropriately functioning vertebrate promoter-associated epigenome.

  17. [Intraoperative multidimensional visualization].

    Science.gov (United States)

    Sperling, J; Kauffels, A; Grade, M; Alves, F; Kühn, P; Ghadimi, B M

    2016-12-01

    Modern intraoperative techniques of visualization are increasingly being applied in general and visceral surgery. The combination of diverse techniques provides the possibility of multidimensional intraoperative visualization of specific anatomical structures. Thus, it is possible to differentiate between normal tissue and tumor tissue and therefore exactly define tumor margins. The aim of intraoperative visualization of tissue that is to be resected and tissue that should be spared is to lead to a rational balance between oncological and functional results. Moreover, these techniques help to analyze the physiology and integrity of tissues. Using these methods surgeons are able to analyze tissue perfusion and oxygenation. However, to date it is not clear to what extent these imaging techniques are relevant in the clinical routine. The present manuscript reviews the relevant modern visualization techniques focusing on intraoperative computed tomography and magnetic resonance imaging as well as augmented reality, fluorescence imaging and optoacoustic imaging.

  18. Multidimensional HAM-conditions

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan de Place

    Heat, Air and Moisture (HAM) conditions, experimental data are needed. Tests were performed in the large climate simulator at SBi involving full-scale wall elements. The elements were exposed for steady-state conditions, and temperature cycles simulating April and September climate in Denmark....... The effect on the moisture and temperature conditions of the addition of a vapour barrier and an outer cladding on timber frame walls was studied. The report contains comprehensive appendices documenting the full-scale tests. The tests were performed as a part of the project 'Model for Multidimensional Heat......, Air and Moisture Conditions in Building Envelope Components' carried out as a co-project between DTU Byg and SBi....

  19. Genomic determinants of sporulation in Bacilli and Clostridia: towards the minimal set of sporulation-specific genes.

    Science.gov (United States)

    Galperin, Michael Y; Mekhedov, Sergei L; Puigbo, Pere; Smirnov, Sergey; Wolf, Yuri I; Rigden, Daniel J

    2012-11-01

    Three classes of low-G+C Gram-positive bacteria (Firmicutes), Bacilli, Clostridia and Negativicutes, include numerous members that are capable of producing heat-resistant endospores. Spore-forming firmicutes include many environmentally important organisms, such as insect pathogens and cellulose-degrading industrial strains, as well as human pathogens responsible for such diseases as anthrax, botulism, gas gangrene and tetanus. In the best-studied model organism Bacillus subtilis, sporulation involves over 500 genes, many of which are conserved among other bacilli and clostridia. This work aimed to define the genomic requirements for sporulation through an analysis of the presence of sporulation genes in various firmicutes, including those with smaller genomes than B. subtilis. Cultivable spore-formers were found to have genomes larger than 2300 kb and encompass over 2150 protein-coding genes of which 60 are orthologues of genes that are apparently essential for sporulation in B. subtilis. Clostridial spore-formers lack, among others, spoIIB, sda, spoVID and safA genes and have non-orthologous displacements of spoIIQ and spoIVFA, suggesting substantial differences between bacilli and clostridia in the engulfment and spore coat formation steps. Many B. subtilis sporulation genes, particularly those encoding small acid-soluble spore proteins and spore coat proteins, were found only in the family Bacillaceae, or even in a subset of Bacillus spp. Phylogenetic profiles of sporulation genes, compiled in this work, confirm the presence of a common sporulation gene core, but also illuminate the diversity of the sporulation processes within various lineages. These profiles should help further experimental studies of uncharacterized widespread sporulation genes, which would ultimately allow delineation of the minimal set(s) of sporulation-specific genes in Bacilli and Clostridia. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

  20. Using Variable Precision Rough Set for Selection and Classification of Biological Knowledge Integrated in DNA Gene Expression

    Directory of Open Access Journals (Sweden)

    Calvo-Dmgz D.

    2012-12-01

    Full Text Available DNA microarrays have contributed to the exponential growth of genomic and experimental data in the last decade. This large amount of gene expression data has been used by researchers seeking diagnosis of diseases like cancer using machine learning methods. In turn, explicit biological knowledge about gene functions has also grown tremendously over the last decade. This work integrates explicit biological knowledge, provided as gene sets, into the classication process by means of Variable Precision Rough Set Theory (VPRS. The proposed model is able to highlight which part of the provided biological knowledge has been important for classification. This paper presents a novel model for microarray data classification which is able to incorporate prior biological knowledge in the form of gene sets. Based on this knowledge, we transform the input microarray data into supergenes, and then we apply rough set theory to select the most promising supergenes and to derive a set of easy interpretable classification rules. The proposed model is evaluated over three breast cancer microarrays datasets obtaining successful results compared to classical classification techniques. The experimental results shows that there are not significat differences between our model and classical techniques but it is able to provide a biological-interpretable explanation of how it classifies new samples.

  1. Enriching the gene set analysis of genome-wide data by incorporating directionality of gene expression and combining statistical hypotheses and methods

    Science.gov (United States)

    Väremo, Leif; Nielsen, Jens; Nookaew, Intawat

    2013-01-01

    Gene set analysis (GSA) is used to elucidate genome-wide data, in particular transcriptome data. A multitude of methods have been proposed for this step of the analysis, and many of them have been compared and evaluated. Unfortunately, there is no consolidated opinion regarding what methods should be preferred, and the variety of available GSA software and implementations pose a difficulty for the end-user who wants to try out different methods. To address this, we have developed the R package Piano that collects a range of GSA methods into the same system, for the benefit of the end-user. Further on we refine the GSA workflow by using modifications of the gene-level statistics. This enables us to divide the resulting gene set P-values into three classes, describing different aspects of gene expression directionality at gene set level. We use our fully implemented workflow to investigate the impact of the individual components of GSA by using microarray and RNA-seq data. The results show that the evaluated methods are globally similar and the major separation correlates well with our defined directionality classes. As a consequence of this, we suggest to use a consensus scoring approach, based on multiple GSA runs. In combination with the directionality classes, this constitutes a more thorough basis for an enriched biological interpretation. PMID:23444143

  2. Platform dependence of inference on gene-wise and gene-set involvement in human lung development

    Directory of Open Access Journals (Sweden)

    Kho Alvin T

    2009-06-01

    Full Text Available Abstract Background With the recent development of microarray technologies, the comparability of gene expression data obtained from different platforms poses an important problem. We evaluated two widely used platforms, Affymetrix U133 Plus 2.0 and the Illumina HumanRef-8 v2 Expression Bead Chips, for comparability in a biological system in which changes may be subtle, namely fetal lung tissue as a function of gestational age. Results We performed the comparison via sequence-based probe matching between the two platforms. "Significance grouping" was defined as a measure of comparability. Using both expression correlation and significance grouping as measures of comparability, we demonstrated that despite overall cross-platform differences at the single gene level, increased correlation between the two platforms was found in genes with higher expression level, higher probe overlap, and lower p-value. We also demonstrated that biological function as determined via KEGG pathways or GO categories is more consistent across platforms than single gene analysis. Conclusion We conclude that while the comparability of the platforms at the single gene level may be increased by increasing sample size, they are highly comparable ontologically even for subtle differences in a relatively small sample size. Biologically relevant inference should therefore be reproducible across laboratories using different platforms.

  3. Automated Detection of Cancer Associated Genes Using a Combined Fuzzy-Rough-Set-Based F-Information and Water Swirl Algorithm of Human Gene Expression Data.

    Directory of Open Access Journals (Sweden)

    Pugalendhi Ganesh Kumar

    Full Text Available This study describes a novel approach to reducing the challenges of highly nonlinear multiclass gene expression values for cancer diagnosis. To build a fruitful system for cancer diagnosis, in this study, we introduced two levels of gene selection such as filtering and embedding for selection of potential genes and the most relevant genes associated with cancer, respectively. The filter procedure was implemented by developing a fuzzy rough set (FR-based method for redefining the criterion function of f-information (FI to identify the potential genes without discretizing the continuous gene expression values. The embedded procedure is implemented by means of a water swirl algorithm (WSA, which attempts to optimize the rule set and membership function required to classify samples using a fuzzy-rule-based multiclassification system (FRBMS. Two novel update equations are proposed in WSA, which have better exploration and exploitation abilities while designing a self-learning FRBMS. The efficiency of our new approach was evaluated on 13 multicategory and 9 binary datasets of cancer gene expression. Additionally, the performance of the proposed FRFI-WSA method in designing an FRBMS was compared with existing methods for gene selection and optimization such as genetic algorithm (GA, particle swarm optimization (PSO, and artificial bee colony algorithm (ABC on all the datasets. In the global cancer map with repeated measurements (GCM_RM dataset, the FRFI-WSA showed the smallest number of 16 most relevant genes associated with cancer using a minimal number of 26 compact rules with the highest classification accuracy (96.45%. In addition, the statistical validation used in this study revealed that the biological relevance of the most relevant genes associated with cancer and their linguistics detected by the proposed FRFI-WSA approach are better than those in the other methods. The simple interpretable rules with most relevant genes and effectively

  4. Identification of self-consistent modulons from bacterial microarray expression data with the help of structured regulon gene sets

    KAUST Repository

    Permina, Elizaveta A.

    2013-01-01

    Identification of bacterial modulons from series of gene expression measurements on microarrays is a principal problem, especially relevant for inadequately studied but practically important species. Usage of a priori information on regulatory interactions helps to evaluate parameters for regulatory subnetwork inference. We suggest a procedure for modulon construction where a seed regulon is iteratively updated with genes having expression patterns similar to those for regulon member genes. A set of genes essential for a regulon is used to control modulon updating. Essential genes for a regulon were selected as a subset of regulon genes highly related by different measures to each other. Using Escherichia coli as a model, we studied how modulon identification depends on the data, including the microarray experiments set, the adopted relevance measure and the regulon itself. We have found that results of modulon identification are highly dependent on all parameters studied and thus the resulting modulon varies substantially depending on the identification procedure. Yet, modulons that were identified correctly displayed higher stability during iterations, which allows developing a procedure for reliable modulon identification in the case of less studied species where the known regulatory interactions are sparse. Copyright © 2013 Taylor & Francis.

  5. The Schizophrenia-Associated BRD1 Gene Regulates Behavior, Neurotransmission, and Expression of Schizophrenia Risk Enriched Gene Sets in Mice.

    Science.gov (United States)

    Qvist, Per; Christensen, Jane Hvarregaard; Vardya, Irina; Rajkumar, Anto Praveen; Mørk, Arne; Paternoster, Veerle; Füchtbauer, Ernst-Martin; Pallesen, Jonatan; Fryland, Tue; Dyrvig, Mads; Hauberg, Mads Engel; Lundsberg, Birgitte; Fejgin, Kim; Nyegaard, Mette; Jensen, Kimmo; Nyengaard, Jens Randel; Mors, Ole; Didriksen, Michael; Børglum, Anders Dupont

    2017-07-01

    The schizophrenia-associated BRD1 gene encodes a transcriptional regulator whose comprehensive chromatin interactome is enriched with schizophrenia risk genes. However, the biology underlying the disease association of BRD1 remains speculative. This study assessed the transcriptional drive of a schizophrenia-associated BRD1 risk variant in vitro. Accordingly, to examine the effects of reduced Brd1 expression, we generated a genetically modified Brd1 +/- mouse and subjected it to behavioral, electrophysiological, molecular, and integrative genomic analyses with focus on schizophrenia-relevant parameters. Brd1 +/- mice displayed cerebral histone H3K14 hypoacetylation and a broad range of behavioral changes with translational relevance to schizophrenia. These behaviors were accompanied by striatal dopamine/serotonin abnormalities and cortical excitation-inhibition imbalances involving loss of parvalbumin immunoreactive interneurons. RNA-sequencing analyses of cortical and striatal micropunches from Brd1 +/- and wild-type mice revealed differential expression of genes enriched for schizophrenia risk, including several schizophrenia genome-wide association study risk genes (e.g., calcium channel subunits [Cacna1c and Cacnb2], cholinergic muscarinic receptor 4 [Chrm4)], dopamine receptor D 2 [Drd2], and transcription factor 4 [Tcf4]). Integrative analyses further found differentially expressed genes to cluster in functional networks and canonical pathways associated with mental illness and molecular signaling processes (e.g., glutamatergic, monoaminergic, calcium, cyclic adenosine monophosphate [cAMP], dopamine- and cAMP-regulated neuronal phosphoprotein 32 kDa [DARPP-32], and cAMP responsive element binding protein signaling [CREB]). Our study bridges the gap between genetic association and pathogenic effects and yields novel insights into the unfolding molecular changes in the brain of a new schizophrenia model that incorporates genetic risk at three levels: allelic

  6. Multidimensional scaling technique for analysis of magnetic storms ...

    Indian Academy of Sciences (India)

    R.Narasimhan(krishtel emaging) 1461 1996 Oct 15 13:05:22

    Multidimensional Scaling (MDS) comprises a set of models and associated methods for construct- ing a geometrical representation of proximity and dominance relationship between elements in one or more sets of entities. MDS can be applied to data that express two types of relationships: proxim- ity relations and ...

  7. A human rights-consistent approach to multidimensional welfare measurement applied to sub-Saharan Africa

    DEFF Research Database (Denmark)

    Arndt, Channing; Mahrt, Kristi; Hussain, Azhar

    2017-01-01

    is in reality inconsistent with the Universal Declaration of Human Rights principles of indivisibility, inalienability, and equality. We show that a first-order dominance methodology maintains consistency with basic principles, discuss the properties of the multidimensional poverty index and first......The rights-based approach to development targets progress towards the realization of 30 articles set forth in the Universal Declaration of Human Rights. Progress is frequently measured using the multidimensional poverty index. While elegant and useful, the multidimensional poverty index...

  8. Frost Multidimensional Perfectionism Scale: the portuguese version

    Directory of Open Access Journals (Sweden)

    Ana Paula Monteiro Amaral

    2013-01-01

    Full Text Available BACKGROUND: The Frost Multidimensional Perfectionism Scale is one of the most world widely used measures of perfectionism. OBJECTIVE: To analyze the psychometric properties of the Portuguese version of the Frost Multidimensional Perfectionism Scale. METHODS: Two hundred and seventeen (178 females students from two Portuguese Universities filled in the scale, and a subgroup (n = 166 completed a retest with a four weeks interval. RESULTS: The scale reliability was good (Cronbach alpha = .857. Corrected item-total correlations ranged from .019 to .548. The scale test-retest reliability suggested a good temporal stability with a test-retest correlation of .765. A principal component analysis with Varimax rotation was performed and based on the Scree plot, two robust factorial structures were found (four and six factors. The principal component analyses, using Monte Carlo PCA for parallel analyses confirmed the six factor solution. The concurrent validity with Hewitt and Flett MPS was high, as well as the discriminant validity of positive and negative affect (Profile of Mood Stats-POMS. DISCUSSION: The two factorial structures (of four and six dimensions of the Portuguese version of Frost Multidimensional Perfectionism Scale replicate the results from different authors, with different samples and cultures. This suggests this scale is a robust instrument to assess perfectionism, in several clinical and research settings as well as in transcultural studies.

  9. A reference gene set for sex pheromone biosynthesis and degradation genes from the diamondback moth, Plutella xylostella, based on genome and transcriptome digital gene expression analyses

    OpenAIRE

    He, Peng; Zhang, Yun-Fei; Hong, Duan-Yang; Wang, Jun; Wang, Xing-Liang; Zuo, Ling-Hua; Tang, Xian-Fu; Xu, Wei-Ming; He, Ming

    2017-01-01

    Background Female moths synthesize species-specific sex pheromone components and release them to attract male moths, which depend on precise sex pheromone chemosensory system to locate females. Two types of genes involved in the sex pheromone biosynthesis and degradation pathways play essential roles in this important moth behavior. To understand the function of genes in the sex pheromone pathway, this study investigated the genome-wide and digital gene expression of sex pheromone biosynthesi...

  10. Gene-set analysis based on the pharmacological profiles of drugs to identify repurposing opportunities in schizophrenia.

    Science.gov (United States)

    de Jong, Simone; Vidler, Lewis R; Mokrab, Younes; Collier, David A; Breen, Gerome

    2016-08-01

    Genome-wide association studies (GWAS) have identified thousands of novel genetic associations for complex genetic disorders, leading to the identification of potential pharmacological targets for novel drug development. In schizophrenia, 108 conservatively defined loci that meet genome-wide significance have been identified and hundreds of additional sub-threshold associations harbour information on the genetic aetiology of the disorder. In the present study, we used gene-set analysis based on the known binding targets of chemical compounds to identify the 'drug pathways' most strongly associated with schizophrenia-associated genes, with the aim of identifying potential drug repositioning opportunities and clues for novel treatment paradigms, especially in multi-target drug development. We compiled 9389 gene sets (2496 with unique gene content) and interrogated gene-based p-values from the PGC2-SCZ analysis. Although no single drug exceeded experiment wide significance (corrected pneratinib. This is a proof of principle analysis showing the potential utility of GWAS data of schizophrenia for the direct identification of candidate drugs and molecules that show polypharmacy. © The Author(s) 2016.

  11. Identification and Validation of a New Set of Five Genes for Prediction of Risk in Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Giorgio Mustacchi

    2013-05-01

    Full Text Available Molecular tests predicting the outcome of breast cancer patients based on gene expression levels can be used to assist in making treatment decisions after consideration of conventional markers. In this study we identified a subset of 20 mRNA differentially regulated in breast cancer analyzing several publicly available array gene expression data using R/Bioconductor package. Using RTqPCR we evaluate 261 consecutive invasive breast cancer cases not selected for age, adjuvant treatment, nodal and estrogen receptor status from paraffin embedded sections. The biological samples dataset was split into a training (137 cases and a validation set (124 cases. The gene signature was developed on the training set and a multivariate stepwise Cox analysis selected five genes independently associated with DFS: FGF18 (HR = 1.13, p = 0.05, BCL2 (HR = 0.57, p = 0.001, PRC1 (HR = 1.51, p = 0.001, MMP9 (HR = 1.11, p = 0.08, SERF1a (HR = 0.83, p = 0.007. These five genes were combined into a linear score (signature weighted according to the coefficients of the Cox model, as: 0.125FGF18 − 0.560BCL2 + 0.409PRC1 + 0.104MMP9 − 0.188SERF1A (HR = 2.7, 95% CI = 1.9–4.0, p < 0.001. The signature was then evaluated on the validation set assessing the discrimination ability by a Kaplan Meier analysis, using the same cut offs classifying patients at low, intermediate or high risk of disease relapse as defined on the training set (p < 0.001. Our signature, after a further clinical validation, could be proposed as prognostic signature for disease free survival in breast cancer patients where the indication for adjuvant chemotherapy added to endocrine treatment is uncertain.

  12. Identification of a set of endogenous reference genes for miRNA expression studies in Parkinson's disease blood samples.

    Science.gov (United States)

    Serafin, Alice; Foco, Luisa; Blankenburg, Hagen; Picard, Anne; Zanigni, Stefano; Zanon, Alessandra; Pramstaller, Peter P; Hicks, Andrew A; Schwienbacher, Christine

    2014-10-10

    Research on microRNAs (miRNAs) is becoming an increasingly attractive field, as these small RNA molecules are involved in several physiological functions and diseases. To date, only few studies have assessed the expression of blood miRNAs related to Parkinson's disease (PD) using microarray and quantitative real-time PCR (qRT-PCR). Measuring miRNA expression involves normalization of qRT-PCR data using endogenous reference genes for calibration, but their choice remains a delicate problem with serious impact on the resulting expression levels. The aim of the present study was to evaluate the suitability of a set of commonly used small RNAs as normalizers and to identify which of these miRNAs might be considered reliable reference genes in qRT-PCR expression analyses on PD blood samples. Commonly used reference genes snoRNA RNU24, snRNA RNU6B, snoRNA Z30 and miR-103a-3p were selected from the literature. We then analyzed the effect of using these genes as reference, alone or in any possible combination, on the measured expression levels of the target genes miR-30b-5p and miR-29a-3p, which have been previously reported to be deregulated in PD blood samples. We identified RNU24 and Z30 as a reliable and stable pair of reference genes in PD blood samples.

  13. A set of vectors for introduction of antibiotic resistance genes by in vitro Cre-mediated recombination

    Directory of Open Access Journals (Sweden)

    Vassetzky Yegor S

    2008-12-01

    Full Text Available Abstract Background Introduction of new antibiotic resistance genes in the plasmids of interest is a frequent task in molecular cloning practice. Classical approaches involving digestion with restriction endonucleases and ligation are time-consuming. Findings We have created a set of insertion vectors (pINS carrying genes that provide resistance to various antibiotics (puromycin, blasticidin and G418 and containing a loxP site. Each vector (pINS-Puro, pINS-Blast or pINS-Neo contains either a chloramphenicol or a kanamycin resistance gene and is unable to replicate in most E. coli strains as it contains a conditional R6Kγ replication origin. Introduction of the antibiotic resistance genes into the vector of interest is achieved by Cre-mediated recombination between the replication-incompetent pINS and a replication-competent target vector. The recombination mix is then transformed into E. coli and selected by the resistance marker (kanamycin or chloramphenicol present in pINS, which allows to recover the recombinant plasmids with 100% efficiency. Conclusion Here we propose a simple strategy that allows to introduce various antibiotic-resistance genes into any plasmid containing a replication origin, an ampicillin resistance gene and a loxP site.

  14. Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells

    Directory of Open Access Journals (Sweden)

    Monticone Massimiliano

    2012-08-01

    Full Text Available Abstract Background Most patients affected by Glioblastoma multiforme (GBM, grade IV glioma experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting. We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type or highly diffuse single tumor cell infiltration (HD-type. Methods We determined by DNA microarrays the gene expression profiles of three NL-type and three HD-type long-term GBM cultures. Subsequently, individual genes with different expression levels between the two groups were identified using Significance Analysis of Microarrays (SAM. Real time RT-PCR, immunofluorescence and immunoblot analyses, were performed for a selected subgroup of regulated gene products to confirm the results obtained by the expression analysis. Results Here, we report the identification of a set of 34 differentially expressed genes in the two types of GBM cultures. Twenty-three of these genes encode for proteins localized to the plasma membrane and 9 of these for proteins are involved in the process of cell adhesion. Conclusions This study suggests the participation in the diffuse infiltrative/invasive process of GBM cells within the CNS of a novel set of genes coding for membrane-associated proteins, which should be thus susceptible to an inhibition strategy by specific targeting. Massimiliano Monticone and Antonio Daga contributed equally to this work

  15. Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells.

    Science.gov (United States)

    Monticone, Massimiliano; Daga, Antonio; Candiani, Simona; Romeo, Francesco; Mirisola, Valentina; Viaggi, Silvia; Melloni, Ilaria; Pedemonte, Simona; Zona, Gianluigi; Giaretti, Walter; Pfeffer, Ulrich; Castagnola, Patrizio

    2012-08-17

    Most patients affected by Glioblastoma multiforme (GBM, grade IV glioma) experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting.We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type) or highly diffuse single tumor cell infiltration (HD-type). We determined by DNA microarrays the gene expression profiles of three NL-type and three HD-type long-term GBM cultures. Subsequently, individual genes with different expression levels between the two groups were identified using Significance Analysis of Microarrays (SAM). Real time RT-PCR, immunofluorescence and immunoblot analyses, were performed for a selected subgroup of regulated gene products to confirm the results obtained by the expression analysis. Here, we report the identification of a set of 34 differentially expressed genes in the two types of GBM cultures. Twenty-three of these genes encode for proteins localized to the plasma membrane and 9 of these for proteins are involved in the process of cell adhesion. This study suggests the participation in the diffuse infiltrative/invasive process of GBM cells within the CNS of a novel set of genes coding for membrane-associated proteins, which should be thus susceptible to an inhibition strategy by specific targeting.Massimiliano Monticone and Antonio Daga contributed equally to this work.

  16. Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells

    International Nuclear Information System (INIS)

    Monticone, Massimiliano; Giaretti, Walter; Pfeffer, Ulrich; Daga, Antonio; Candiani, Simona; Romeo, Francesco; Mirisola, Valentina; Viaggi, Silvia; Melloni, Ilaria; Pedemonte, Simona; Zona, Gianluigi

    2012-01-01

    Most patients affected by Glioblastoma multiforme (GBM, grade IV glioma) experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting. We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type) or highly diffuse single tumor cell infiltration (HD-type). We determined by DNA microarrays the gene expression profiles of three NL-type and three HD-type long-term GBM cultures. Subsequently, individual genes with different expression levels between the two groups were identified using Significance Analysis of Microarrays (SAM). Real time RT-PCR, immunofluorescence and immunoblot analyses, were performed for a selected subgroup of regulated gene products to confirm the results obtained by the expression analysis. Here, we report the identification of a set of 34 differentially expressed genes in the two types of GBM cultures. Twenty-three of these genes encode for proteins localized to the plasma membrane and 9 of these for proteins are involved in the process of cell adhesion. This study suggests the participation in the diffuse infiltrative/invasive process of GBM cells within the CNS of a novel set of genes coding for membrane-associated proteins, which should be thus susceptible to an inhibition strategy by specific targeting. Massimiliano Monticone and Antonio Daga contributed equally to this work

  17. Genetic investigation of 100 heart genes in sudden unexplained death victims in a forensic setting

    DEFF Research Database (Denmark)

    Christiansen, Sofie Lindgren; Hertz, Christin Løth; Ferrero, Laura

    2016-01-01

    indicate that broad genetic investigation of SUD victims increases the diagnostic outcome, and the investigation should comprise genes involved in both cardiomyopathies and cardiac channelopathies.European Journal of Human Genetics advance online publication, 21 September 2016; doi:10.1038/ejhg.2016.118....

  18. Comparative genomics identification of a novel set of temporally regulated hedgehog target genes in the retina.

    Science.gov (United States)

    McNeill, Brian; Perez-Iratxeta, Carol; Mazerolle, Chantal; Furimsky, Marosh; Mishina, Yuji; Andrade-Navarro, Miguel A; Wallace, Valerie A

    2012-03-01

    The hedgehog (Hh) signaling pathway is involved in numerous developmental and adult processes with many links to cancer. In vertebrates, the activity of the Hh pathway is mediated primarily through three Gli transcription factors (Gli1, 2 and 3) that can serve as transcriptional activators or repressors. The identification of Gli target genes is essential for the understanding of the Hh-mediated processes. We used a comparative genomics approach using the mouse and human genomes to identify 390 genes that contained conserved Gli binding sites. RT-qPCR validation of 46 target genes in E14.5 and P0.5 retinal explants revealed that Hh pathway activation resulted in the modulation of 30 of these targets, 25 of which demonstrated a temporal regulation. Further validation revealed that the expression of Bok, FoxA1, Sox8 and Wnt7a was dependent upon Sonic Hh (Shh) signaling in the retina and their regulation is under positive and negative controls by Gli2 and Gli3, respectively. We also show using chromatin immunoprecipitation that Gli2 binds to the Sox8 promoter, suggesting that Sox8 is an Hh-dependent direct target of Gli2. Finally, we demonstrate that the Hh pathway also modulates the expression of Sox9 and Sox10, which together with Sox8 make up the SoxE group. Previously, it has been shown that Hh and SoxE group genes promote Müller glial cell development in the retina. Our data are consistent with the possibility for a role of SoxE group genes downstream of Hh signaling on Müller cell development. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  19. The imprinted brain: how genes set the balance between autism and psychosis.

    Science.gov (United States)

    Badcock, Christopher

    2011-06-01

    The imprinted brain theory proposes that autism spectrum disorder (ASD) represents a paternal bias in the expression of imprinted genes. This is reflected in a preference for mechanistic cognition and in the corresponding mentalistic deficits symptomatic of ASD. Psychotic spectrum disorder (PSD) would correspondingly result from an imbalance in favor of maternal and/or X-chromosome gene expression. If differences in gene expression were reflected locally in the human brain as mouse models and other evidence suggests they are, ASD would represent not so much an 'extreme male brain' as an extreme paternal one, with PSD correspondingly representing an extreme maternal brain. To the extent that copy number variation resembles imprinting and aneuploidy in nullifying or multiplying the expression of particular genes, it has been found to conform to the diametric model of mental illness peculiar to the imprinted brain theory. The fact that nongenetic factors such as nutrition in pregnancy can mimic and/or interact with imprinted gene expression suggests that the theory might even be able to explain the notable effect of maternal starvation on the risk of PSD - not to mention the 'autism epidemic' of modern affluent societies. Finally, the theory suggests that normality represents balanced cognition, and that genius is an extraordinary extension of cognitive configuration in both mentalistic and mechanistic directions. Were it to be proven correct, the imprinted brain theory would represent one of the biggest single advances in our understanding of the mind and of mental illness that has ever taken place, and would revolutionize psychiatric diagnosis, prevention and treatment - not to mention our understanding of epigenomics.

  20. Equating Multidimensional Tests under a Random Groups Design: A Comparison of Various Equating Procedures

    Science.gov (United States)

    Lee, Eunjung

    2013-01-01

    The purpose of this research was to compare the equating performance of various equating procedures for the multidimensional tests. To examine the various equating procedures, simulated data sets were used that were generated based on a multidimensional item response theory (MIRT) framework. Various equating procedures were examined, including…

  1. An 80-gene set to predict response to preoperative chemoradiotherapy for rectal cancer by principle component analysis.

    Science.gov (United States)

    Empuku, Shinichiro; Nakajima, Kentaro; Akagi, Tomonori; Kaneko, Kunihiko; Hijiya, Naoki; Etoh, Tsuyoshi; Shiraishi, Norio; Moriyama, Masatsugu; Inomata, Masafumi

    2016-05-01

    Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer not only improves the postoperative local control rate, but also induces downstaging. However, it has not been established how to individually select patients who receive effective preoperative CRT. The aim of this study was to identify a predictor of response to preoperative CRT for locally advanced rectal cancer. This study is additional to our multicenter phase II study evaluating the safety and efficacy of preoperative CRT using oral fluorouracil (UMIN ID: 03396). From April, 2009 to August, 2011, 26 biopsy specimens obtained prior to CRT were analyzed by cyclopedic microarray analysis. Response to CRT was evaluated according to a histological grading system using surgically resected specimens. To decide on the number of genes for dividing into responder and non-responder groups, we statistically analyzed the data using a dimension reduction method, a principle component analysis. Of the 26 cases, 11 were responders and 15 non-responders. No significant difference was found in clinical background data between the two groups. We determined that the optimal number of genes for the prediction of response was 80 of 40,000 and the functions of these genes were analyzed. When comparing non-responders with responders, genes expressed at a high level functioned in alternative splicing, whereas those expressed at a low level functioned in the septin complex. Thus, an 80-gene expression set that predicts response to preoperative CRT for locally advanced rectal cancer was identified using a novel statistical method.

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

    Science.gov (United States)

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

    2016-09-09

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

  3. Contributions to multidimensional quadrature formulas

    International Nuclear Information System (INIS)

    Guenther, C.

    1976-11-01

    The general objective of this paper is to construct multidimensional quadrature formulas similar to the Gaussian Quadrature Formulas in one dimension. The correspondence between these formulas and orthogonal and nonnegative polynomials is established. One part of the paper considers the construction of multidimensional quadrature formulas using only methods of algebraic geometry, on the other part it is tried to obtain results on quadrature formulas with real nodes and, if possible, with positive weights. The results include the existence of quadrature formulas, information on the number resp. on the maximum possible number of points in the formulas for given polynomial degree N and the construction of formulas. (orig.) [de

  4. Multidimensional real analysis I differentiation

    CERN Document Server

    Duistermaat, J J; van Braam Houckgeest, J P

    2004-01-01

    Part one of the authors' comprehensive and innovative work on multidimensional real analysis. This book is based on extensive teaching experience at Utrecht University and gives a thorough account of differential analysis in multidimensional Euclidean space. It is an ideal preparation for students who wish to go on to more advanced study. The notation is carefully organized and all proofs are clean, complete and rigorous. The authors have taken care to pay proper attention to all aspects of the theory. In many respects this book presents an original treatment of the subject and it contains man

  5. Image matrix processor for fast multi-dimensional computations

    Science.gov (United States)

    Roberson, George P.; Skeate, Michael F.

    1996-01-01

    An apparatus for multi-dimensional computation which comprises a computation engine, including a plurality of processing modules. The processing modules are configured in parallel and compute respective contributions to a computed multi-dimensional image of respective two dimensional data sets. A high-speed, parallel access storage system is provided which stores the multi-dimensional data sets, and a switching circuit routes the data among the processing modules in the computation engine and the storage system. A data acquisition port receives the two dimensional data sets representing projections through an image, for reconstruction algorithms such as encountered in computerized tomography. The processing modules include a programmable local host, by which they may be configured to execute a plurality of different types of multi-dimensional algorithms. The processing modules thus include an image manipulation processor, which includes a source cache, a target cache, a coefficient table, and control software for executing image transformation routines using data in the source cache and the coefficient table and loading resulting data in the target cache. The local host processor operates to load the source cache with a two dimensional data set, loads the coefficient table, and transfers resulting data out of the target cache to the storage system, or to another destination.

  6. Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects.

    Science.gov (United States)

    Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling; Wang, Xianhui; Kang, Le

    2017-06-01

    The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain-containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. © The Authors 2017. Published by Oxford University Press.

  7. The impact of ACE gene polymorphism on the incidence and phenotype of sarcoidosis in rural and urban settings.

    Science.gov (United States)

    Kieszko, Robert; Krawczyk, Paweł; Powrózek, Tomasz; Szudy-Szczyrek, Aneta; Szczyrek, Michał; Homa, Iwona; Daniluk, Jadwiga; Milanowski, Janusz

    2016-12-01

    Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Current theory on the etiology of this disease involves participation of genetic factors and unknown antigens present in the patients' environment. The aim of the study was to evaluate the prevalence of different polymorphic forms of the ACE gene in healthy individuals and sarcoidosis patients, and to estimate the risk of sarcoidosis in carriers of different ACE genotypes living in rural and urban settings. The study group included 180 patients with pulmonary sarcoidosis. Assessment of the disease was based on clinical features, laboratory and imaging examinations, as well as bronchoscopy with bronchoalveolar lavage (BAL). ACE gene polymorphism was examined in DNA isolated from peripheral blood or BAL fluid (BALF) leukocytes. Incidence of sarcoidosis was not influenced by gender, age or place of residence of the patients. There were no differences in the frequency of particular genotypes in patients with sarcoidosis and in healthy individuals. The risk of disease did not depend on the ACE gene polymorphism. There were no differences in the frequencies of the different genotypes and alleles of the ACE gene in patients with sarcoidosis divided by gender, age and place of residence or by clinical manifestation of sarcoidosis. Our results do not support the previous concept which suggested a higher incidence of sarcoidosis in individuals living in rural areas and in carriers of selected ACE genotypes. It is possible that this is related to the changing environment of rural areas, increasing urbanization and pollution.

  8. The first set of EST resource for gene discovery and marker development in pigeonpea (Cajanus cajan L.

    Directory of Open Access Journals (Sweden)

    Byregowda Munishamappa

    2010-03-01

    .8% in molecular function. Further, 19 genes were identified differentially expressed between FW- responsive genotypes and 20 between SMD- responsive genotypes. Generated ESTs were compiled together with 908 ESTs available in public domain, at the time of analysis, and a set of 5,085 unigenes were defined that were used for identification of molecular markers in pigeonpea. For instance, 3,583 simple sequence repeat (SSR motifs were identified in 1,365 unigenes and 383 primer pairs were designed. Assessment of a set of 84 primer pairs on 40 elite pigeonpea lines showed polymorphism with 15 (28.8% markers with an average of four alleles per marker and an average polymorphic information content (PIC value of 0.40. Similarly, in silico mining of 133 contigs with ≥ 5 sequences detected 102 single nucleotide polymorphisms (SNPs in 37 contigs. As an example, a set of 10 contigs were used for confirming in silico predicted SNPs in a set of four genotypes using wet lab experiments. Occurrence of SNPs were confirmed for all the 6 contigs for which scorable and sequenceable amplicons were generated. PCR amplicons were not obtained in case of 4 contigs. Recognition sites for restriction enzymes were identified for 102 SNPs in 37 contigs that indicates possibility of assaying SNPs in 37 genes using cleaved amplified polymorphic sequences (CAPS assay. Conclusion The pigeonpea EST dataset generated here provides a transcriptomic resource for gene discovery and development of functional markers associated with biotic stress resistance. Sequence analyses of this dataset have showed conservation of a considerable number of pigeonpea transcripts across legume and model plant species analysed as well as some putative pigeonpea specific genes. Validation of identified biotic stress responsive genes should provide candidate genes for allele mining as well as candidate markers for molecular breeding.

  9. Multidimensional poverty: an alternative measurement approach for the United States?

    Science.gov (United States)

    Waglé, Udaya R

    2008-06-01

    International poverty research has increasingly underscored the need to use multidimensional approaches to measure poverty. Largely embraced in Europe and elsewhere, this has not had much impact on the way poverty is measured in the United States. In this paper, I use a comprehensive multidimensional framework including economic well-being, capability, and social inclusion to examine poverty in the US. Data from the 2004 General Social Survey support the interconnectedness among these poverty dimensions, indicating that the multidimensional framework utilizing a comprehensive set of information provides a compelling value added to poverty measurement. The suggested demographic characteristics of the various categories of the poor are somewhat similar between this approach and other traditional approaches. But the more comprehensive and accurate measurement outcomes from this approach help policymakers target resources at the specific groups.

  10. Candidate genes for chronic obstructive pulmonary disease in two large data sets

    DEFF Research Database (Denmark)

    Bakke, P S; Zhu, G; Gulsvik, A

    2011-01-01

    Lack of reproducibility of findings has been a criticism of genetic association studies in complex diseases like chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationshipsto COPD and genotyped these variants in a case......-control study which included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post bronchodilator FEV1 in percent predicted and FEV1/FVC). The polymorphisms significantly associated...... to these phenotypes in this first study were tested in a second, family based, study that included 635 pedigrees with 1910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p

  11. A Multidimensional Software Engineering Course

    Science.gov (United States)

    Barzilay, O.; Hazzan, O.; Yehudai, A.

    2009-01-01

    Software engineering (SE) is a multidimensional field that involves activities in various areas and disciplines, such as computer science, project management, and system engineering. Though modern SE curricula include designated courses that address these various subjects, an advanced summary course that synthesizes them is still missing. Such a…

  12. Multidimensional Databases and Data Warehousing

    DEFF Research Database (Denmark)

    Jensen, Christian S.; Pedersen, Torben Bach; Thomsen, Christian

    The present book's subject is multidimensional data models and data modeling concepts as they are applied in real data warehouses. The book aims to present the most important concepts within this subject in a precise and understandable manner. The book's coverage of fundamental concepts includes...

  13. Recycling Behavior: A Multidimensional Approach

    Science.gov (United States)

    Meneses, Gonzalo Diaz; Palacio, Asuncion Beerli

    2005-01-01

    This work centers on the study of consumer recycling roles to examine the sociodemographic and psychographic profile of the distribution of recycling tasks and roles within the household. With this aim in mind, an empirical work was carried out, the results of which suggest that recycling behavior is multidimensional and comprises the undertaking…

  14. Repression of Middle Sporulation Genes in Saccharomyces cerevisiae by the Sum1-Rfm1-Hst1 Complex Is Maintained by Set1 and H3K4 Methylation

    Science.gov (United States)

    Jaiswal, Deepika; Jezek, Meagan; Quijote, Jeremiah; Lum, Joanna; Choi, Grace; Kulkarni, Rushmie; Park, DoHwan; Green, Erin M.

    2017-01-01

    The conserved yeast histone methyltransferase Set1 targets H3 lysine 4 (H3K4) for mono, di, and trimethylation and is linked to active transcription due to the euchromatic distribution of these methyl marks and the recruitment of Set1 during transcription. However, loss of Set1 results in increased expression of multiple classes of genes, including genes adjacent to telomeres and middle sporulation genes, which are repressed under normal growth conditions because they function in meiotic progression and spore formation. The mechanisms underlying Set1-mediated gene repression are varied, and still unclear in some cases, although repression has been linked to both direct and indirect action of Set1, associated with noncoding transcription, and is often dependent on the H3K4me2 mark. We show that Set1, and particularly the H3K4me2 mark, are implicated in repression of a subset of middle sporulation genes during vegetative growth. In the absence of Set1, there is loss of the DNA-binding transcriptional regulator Sum1 and the associated histone deacetylase Hst1 from chromatin in a locus-specific manner. This is linked to increased H4K5ac at these loci and aberrant middle gene expression. These data indicate that, in addition to DNA sequence, histone modification status also contributes to proper localization of Sum1. Our results also show that the role for Set1 in middle gene expression control diverges as cells receive signals to undergo meiosis. Overall, this work dissects an unexplored role for Set1 in gene-specific repression, and provides important insights into a new mechanism associated with the control of gene expression linked to meiotic differentiation. PMID:29066473

  15. A summarization approach for Affymetrix GeneChip data using a reference training set from a large, biologically diverse database

    Directory of Open Access Journals (Sweden)

    Tripputi Mark

    2006-10-01

    Full Text Available Abstract Background Many of the most popular pre-processing methods for Affymetrix expression arrays, such as RMA, gcRMA, and PLIER, simultaneously analyze data across a set of predetermined arrays to improve precision of the final measures of expression. One problem associated with these algorithms is that expression measurements for a particular sample are highly dependent on the set of samples used for normalization and results obtained by normalization with a different set may not be comparable. A related problem is that an organization producing and/or storing large amounts of data in a sequential fashion will need to either re-run the pre-processing algorithm every time an array is added or store them in batches that are pre-processed together. Furthermore, pre-processing of large numbers of arrays requires loading all the feature-level data into memory which is a difficult task even with modern computers. We utilize a scheme that produces all the information necessary for pre-processing using a very large training set that can be used for summarization of samples outside of the training set. All subsequent pre-processing tasks can be done on an individual array basis. We demonstrate the utility of this approach by defining a new version of the Robust Multi-chip Averaging (RMA algorithm which we refer to as refRMA. Results We assess performance based on multiple sets of samples processed over HG U133A Affymetrix GeneChip® arrays. We show that the refRMA workflow, when used in conjunction with a large, biologically diverse training set, results in the same general characteristics as that of RMA in its classic form when comparing overall data structure, sample-to-sample correlation, and variation. Further, we demonstrate that the refRMA workflow and reference set can be robustly applied to naïve organ types and to benchmark data where its performance indicates respectable results. Conclusion Our results indicate that a biologically diverse

  16. Benchmarking the Multidimensional Stellar Implicit Code MUSIC

    Science.gov (United States)

    Goffrey, T.; Pratt, J.; Viallet, M.; Baraffe, I.; Popov, M. V.; Walder, R.; Folini, D.; Geroux, C.; Constantino, T.

    2017-04-01

    We present the results of a numerical benchmark study for the MUltidimensional Stellar Implicit Code (MUSIC) based on widely applicable two- and three-dimensional compressible hydrodynamics problems relevant to stellar interiors. MUSIC is an implicit large eddy simulation code that uses implicit time integration, implemented as a Jacobian-free Newton Krylov method. A physics based preconditioning technique which can be adjusted to target varying physics is used to improve the performance of the solver. The problems used for this benchmark study include the Rayleigh-Taylor and Kelvin-Helmholtz instabilities, and the decay of the Taylor-Green vortex. Additionally we show a test of hydrostatic equilibrium, in a stellar environment which is dominated by radiative effects. In this setting the flexibility of the preconditioning technique is demonstrated. This work aims to bridge the gap between the hydrodynamic test problems typically used during development of numerical methods and the complex flows of stellar interiors. A series of multidimensional tests were performed and analysed. Each of these test cases was analysed with a simple, scalar diagnostic, with the aim of enabling direct code comparisons. As the tests performed do not have analytic solutions, we verify MUSIC by comparing it to established codes including ATHENA and the PENCIL code. MUSIC is able to both reproduce behaviour from established and widely-used codes as well as results expected from theoretical predictions. This benchmarking study concludes a series of papers describing the development of the MUSIC code and provides confidence in future applications.

  17. MULTIDIMENSIONAL MODELING OF CORONAL RAIN DYNAMICS

    Energy Technology Data Exchange (ETDEWEB)

    Fang, X.; Xia, C.; Keppens, R. [Centre for mathematical Plasma Astrophysics, Department of Mathematics, KU Leuven, B-3001 Leuven (Belgium)

    2013-07-10

    We present the first multidimensional, magnetohydrodynamic simulations that capture the initial formation and long-term sustainment of the enigmatic coronal rain phenomenon. We demonstrate how thermal instability can induce a spectacular display of in situ forming blob-like condensations which then start their intimate ballet on top of initially linear force-free arcades. Our magnetic arcades host a chromospheric, transition region, and coronal plasma. Following coronal rain dynamics for over 80 minutes of physical time, we collect enough statistics to quantify blob widths, lengths, velocity distributions, and other characteristics which directly match modern observational knowledge. Our virtual coronal rain displays the deformation of blobs into V-shaped features, interactions of blobs due to mostly pressure-mediated levitations, and gives the first views of blobs that evaporate in situ or are siphoned over the apex of the background arcade. Our simulations pave the way for systematic surveys of coronal rain showers in true multidimensional settings to connect parameterized heating prescriptions with rain statistics, ultimately allowing us to quantify the coronal heating input.

  18. MULTIDIMENSIONAL MODELING OF CORONAL RAIN DYNAMICS

    International Nuclear Information System (INIS)

    Fang, X.; Xia, C.; Keppens, R.

    2013-01-01

    We present the first multidimensional, magnetohydrodynamic simulations that capture the initial formation and long-term sustainment of the enigmatic coronal rain phenomenon. We demonstrate how thermal instability can induce a spectacular display of in situ forming blob-like condensations which then start their intimate ballet on top of initially linear force-free arcades. Our magnetic arcades host a chromospheric, transition region, and coronal plasma. Following coronal rain dynamics for over 80 minutes of physical time, we collect enough statistics to quantify blob widths, lengths, velocity distributions, and other characteristics which directly match modern observational knowledge. Our virtual coronal rain displays the deformation of blobs into V-shaped features, interactions of blobs due to mostly pressure-mediated levitations, and gives the first views of blobs that evaporate in situ or are siphoned over the apex of the background arcade. Our simulations pave the way for systematic surveys of coronal rain showers in true multidimensional settings to connect parameterized heating prescriptions with rain statistics, ultimately allowing us to quantify the coronal heating input.

  19. Testlet-Based Multidimensional Adaptive Testing.

    Science.gov (United States)

    Frey, Andreas; Seitz, Nicki-Nils; Brandt, Steffen

    2016-01-01

    Multidimensional adaptive testing (MAT) is a highly efficient method for the simultaneous measurement of several latent traits. Currently, no psychometrically sound approach is available for the use of MAT in testlet-based tests. Testlets are sets of items sharing a common stimulus such as a graph or a text. They are frequently used in large operational testing programs like TOEFL, PISA, PIRLS, or NAEP. To make MAT accessible for such testing programs, we present a novel combination of MAT with a multidimensional generalization of the random effects testlet model (MAT-MTIRT). MAT-MTIRT compared to non-adaptive testing is examined for several combinations of testlet effect variances (0.0, 0.5, 1.0, and 1.5) and testlet sizes (3, 6, and 9 items) with a simulation study considering three ability dimensions with simple loading structure. MAT-MTIRT outperformed non-adaptive testing regarding the measurement precision of the ability estimates. Further, the measurement precision decreased when testlet effect variances and testlet sizes increased. The suggested combination of the MTIRT model therefore provides a solution to the substantial problems of testlet-based tests while keeping the length of the test within an acceptable range.

  20. Testlet-based Multidimensional Adaptive Testing

    Directory of Open Access Journals (Sweden)

    Andreas Frey

    2016-11-01

    Full Text Available Multidimensional adaptive testing (MAT is a highly efficient method for the simultaneous measurement of several latent traits. Currently, no psychometrically sound approach is available for the use of MAT in testlet-based tests. Testlets are sets of items sharing a common stimulus such as a graph or a text. They are frequently used in large operational testing programs like TOEFL, PISA, PIRLS, or NAEP. To make MAT accessible for such testing programs, we present a novel combination of MAT with a multidimensional generalization of the random effects testlet model (MAT-MTIRT. MAT-MTIRT compared to non-adaptive testing is examined for several combinations of testlet effect variances (0.0, 0.5, 1.0, 1.5 and testlet sizes (3 items, 6 items, 9 items with a simulation study considering three ability dimensions with simple loading structure. MAT-MTIRT outperformed non-adaptive testing regarding the measurement precision of the ability estimates. Further, the measurement precision decreased when testlet effect variances and testlet sizes increased. The suggested combination of the MTIRT model therefore provides a solution to the substantial problems of testlet-based tests while keeping the length of the test within an acceptable range.

  1. A new sequence data set of SSU rRNA gene for Scleractinia and its phylogenetic and ecological applications

    KAUST Repository

    Arrigoni, Roberto; Vacherie, Benoî t; Benzoni, Francesca; Stefani, Fabrizio; Karsenti, Eric; Jaillon, Olivier; Not, Fabrice; Nunes, Flavia; Payri, Claude; Wincker, Patrick; Barbe, Valé rie

    2016-01-01

    Scleractinian corals (i.e. hard corals) play a fundamental role in building and maintaining coral reefs, one of the most diverse ecosystems on Earth. Nevertheless, their phylogenies remain largely unresolved and little is known about dispersal and survival of their planktonic larval phase. The small subunit ribosomal RNA (SSU rRNA) is a commonly used gene for DNA barcoding in several metazoans, and small variable regions of SSU rRNA are widely adopted as barcode marker to investigate marine plankton community structure worldwide. Here, we provide a large sequence data set of the complete SSU rRNA gene from 298 specimens, representing all known extant reef coral families and a total of 106 genera. The secondary structure was extremely conserved within the order with few exceptions due to insertions or deletions occurring in the variable regions. Remarkable differences in SSU rRNA length and base composition were detected between and within acroporids (Acropora, Montipora, Isopora and Alveopora) compared to other corals. The V4 and V9 regions seem to be promising barcode loci because variation at commonly used barcode primer binding sites was extremely low, while their levels of divergence allowed families and genera to be distinguished. A time-calibrated phylogeny of Scleractinia is provided, and mutation rate heterogeneity is demonstrated across main lineages. The use of this data set as a valuable reference for investigating aspects of ecology, biology, molecular taxonomy and evolution of scleractinian corals is discussed.

  2. Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes.

    Science.gov (United States)

    Auvergne, Romane M; Sim, Fraser J; Wang, Su; Chandler-Militello, Devin; Burch, Jaclyn; Al Fanek, Yazan; Davis, Danielle; Benraiss, Abdellatif; Walter, Kevin; Achanta, Pragathi; Johnson, Mahlon; Quinones-Hinojosa, Alfredo; Natesan, Sridaran; Ford, Heide L; Goldman, Steven A

    2013-06-27

    Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning World Health Organization grades II-IV. Messenger RNA profiling identified a cohort of genes that distinguished A2B5+ glioma tumor progenitor cells (TPCs) from A2B5+ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5+ TPCs, which included the transcription factor SIX1 and its principal cofactors, EYA1 and DACH2. Small hairpin RNAi silencing of SIX1 inhibited the expansion of glioma TPCs in vitro and in vivo, suggesting a critical and unrecognized role of the SIX1-EYA1-DACH2 system in glioma genesis or progression. By comparing the expression patterns of glioma TPCs with those of normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood and more specifically targeted. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  3. A new sequence data set of SSU rRNA gene for Scleractinia and its phylogenetic and ecological applications

    KAUST Repository

    Arrigoni, Roberto

    2016-11-27

    Scleractinian corals (i.e. hard corals) play a fundamental role in building and maintaining coral reefs, one of the most diverse ecosystems on Earth. Nevertheless, their phylogenies remain largely unresolved and little is known about dispersal and survival of their planktonic larval phase. The small subunit ribosomal RNA (SSU rRNA) is a commonly used gene for DNA barcoding in several metazoans, and small variable regions of SSU rRNA are widely adopted as barcode marker to investigate marine plankton community structure worldwide. Here, we provide a large sequence data set of the complete SSU rRNA gene from 298 specimens, representing all known extant reef coral families and a total of 106 genera. The secondary structure was extremely conserved within the order with few exceptions due to insertions or deletions occurring in the variable regions. Remarkable differences in SSU rRNA length and base composition were detected between and within acroporids (Acropora, Montipora, Isopora and Alveopora) compared to other corals. The V4 and V9 regions seem to be promising barcode loci because variation at commonly used barcode primer binding sites was extremely low, while their levels of divergence allowed families and genera to be distinguished. A time-calibrated phylogeny of Scleractinia is provided, and mutation rate heterogeneity is demonstrated across main lineages. The use of this data set as a valuable reference for investigating aspects of ecology, biology, molecular taxonomy and evolution of scleractinian corals is discussed.

  4. Reconstruction of gene regulatory modules from RNA silencing of IFN-α modulators: experimental set-up and inference method.

    Science.gov (United States)

    Grassi, Angela; Di Camillo, Barbara; Ciccarese, Francesco; Agnusdei, Valentina; Zanovello, Paola; Amadori, Alberto; Finesso, Lorenzo; Indraccolo, Stefano; Toffolo, Gianna Maria

    2016-03-12

    Inference of gene regulation from expression data may help to unravel regulatory mechanisms involved in complex diseases or in the action of specific drugs. A challenging task for many researchers working in the field of systems biology is to build up an experiment with a limited budget and produce a dataset suitable to reconstruct putative regulatory modules worth of biological validation. Here, we focus on small-scale gene expression screens and we introduce a novel experimental set-up and a customized method of analysis to make inference on regulatory modules starting from genetic perturbation data, e.g. knockdown and overexpression data. To illustrate the utility of our strategy, it was applied to produce and analyze a dataset of quantitative real-time RT-PCR data, in which interferon-α (IFN-α) transcriptional response in endothelial cells is investigated by RNA silencing of two candidate IFN-α modulators, STAT1 and IFIH1. A putative regulatory module was reconstructed by our method, revealing an intriguing feed-forward loop, in which STAT1 regulates IFIH1 and they both negatively regulate IFNAR1. STAT1 regulation on IFNAR1 was object of experimental validation at the protein level. Detailed description of the experimental set-up and of the analysis procedure is reported, with the intent to be of inspiration for other scientists who want to realize similar experiments to reconstruct gene regulatory modules starting from perturbations of possible regulators. Application of our approach to the study of IFN-α transcriptional response modulators in endothelial cells has led to many interesting novel findings and new biological hypotheses worth of validation.

  5. Multi-dimensional Fuzzy Euler Approximation

    Directory of Open Access Journals (Sweden)

    Yangyang Hao

    2017-05-01

    Full Text Available Multi-dimensional Fuzzy differential equations driven by multi-dimen-sional Liu process, have been intensively applied in many fields. However, we can not obtain the analytic solution of every multi-dimensional fuzzy differential equation. Then, it is necessary for us to discuss the numerical results in most situations. This paper focuses on the numerical method of multi-dimensional fuzzy differential equations. The multi-dimensional fuzzy Taylor expansion is given, based on this expansion, a numerical method which is designed for giving the solution of multi-dimensional fuzzy differential equation via multi-dimensional Euler method will be presented, and its local convergence also will be discussed.

  6. Executive Information Systems' Multidimensional Models

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available Executive Information Systems are design to improve the quality of strategic level of management in organization through a new type of technology and several techniques for extracting, transforming, processing, integrating and presenting data in such a way that the organizational knowledge filters can easily associate with this data and turn it into information for the organization. These technologies are known as Business Intelligence Tools. But in order to build analytic reports for Executive Information Systems (EIS in an organization we need to design a multidimensional model based on the business model from the organization. This paper presents some multidimensional models that can be used in EIS development and propose a new model that is suitable for strategic business requests.

  7. Lagrangian multiforms and multidimensional consistency

    Energy Technology Data Exchange (ETDEWEB)

    Lobb, Sarah; Nijhoff, Frank [Department of Applied Mathematics, University of Leeds, Leeds LS2 9JT (United Kingdom)

    2009-10-30

    We show that well-chosen Lagrangians for a class of two-dimensional integrable lattice equations obey a closure relation when embedded in a higher dimensional lattice. On the basis of this property we formulate a Lagrangian description for such systems in terms of Lagrangian multiforms. We discuss the connection of this formalism with the notion of multidimensional consistency, and the role of the lattice from the point of view of the relevant variational principle.

  8. Cuba: Multidimensional numerical integration library

    Science.gov (United States)

    Hahn, Thomas

    2016-08-01

    The Cuba library offers four independent routines for multidimensional numerical integration: Vegas, Suave, Divonne, and Cuhre. The four algorithms work by very different methods, and can integrate vector integrands and have very similar Fortran, C/C++, and Mathematica interfaces. Their invocation is very similar, making it easy to cross-check by substituting one method by another. For further safeguarding, the output is supplemented by a chi-square probability which quantifies the reliability of the error estimate.

  9. Association between expression of random gene sets and survival is evident in multiple cancer types and may be explained by sub-classification

    Science.gov (United States)

    2018-01-01

    One of the goals of cancer research is to identify a set of genes that cause or control disease progression. However, although multiple such gene sets were published, these are usually in very poor agreement with each other, and very few of the genes proved to be functional therapeutic targets. Furthermore, recent findings from a breast cancer gene-expression cohort showed that sets of genes selected randomly can be used to predict survival with a much higher probability than expected. These results imply that many of the genes identified in breast cancer gene expression analysis may not be causal of cancer progression, even though they can still be highly predictive of prognosis. We performed a similar analysis on all the cancer types available in the cancer genome atlas (TCGA), namely, estimating the predictive power of random gene sets for survival. Our work shows that most cancer types exhibit the property that random selections of genes are more predictive of survival than expected. In contrast to previous work, this property is not removed by using a proliferation signature, which implies that proliferation may not always be the confounder that drives this property. We suggest one possible solution in the form of data-driven sub-classification to reduce this property significantly. Our results suggest that the predictive power of random gene sets may be used to identify the existence of sub-classes in the data, and thus may allow better understanding of patient stratification. Furthermore, by reducing the observed bias this may allow more direct identification of biologically relevant, and potentially causal, genes. PMID:29470520

  10. Multidimensional splines for modeling FET nonlinearities

    Energy Technology Data Exchange (ETDEWEB)

    Barby, J A

    1986-01-01

    Circuit simulators like SPICE and timing simulators like MOTIS are used extensively for critical path verification of integrated circuits. MOSFET model evaluation dominates the run time of these simulators. Changes in technology results in costly updates, since modifications require reprogramming of the functions and their derivatives. The computational cost of MOSFET models can be reduced by using multidimensional polynomial splines. Since simulators based on the Newton Raphson algorithm require the function and first derivative, quadratic splines are sufficient for this purpose. The cost of updating the MOSFET model due to technology changes is greatly reduced since splines are derived from a set of points. Crucial for convergence speed of simulators is the fact that MOSFET characteristic equations are monotonic. This must be maintained by any simulation model. The splines the author designed do maintain monotonicity.

  11. Multidimensional scaling of musical time estimations.

    Science.gov (United States)

    Cocenas-Silva, Raquel; Bueno, José Lino Oliveira; Molin, Paul; Bigand, Emmanuel

    2011-06-01

    The aim of this study was to identify the psycho-musical factors that govern time evaluation in Western music from baroque, classic, romantic, and modern repertoires. The excerpts were previously found to represent variability in musical properties and to induce four main categories of emotions. 48 participants (musicians and nonmusicians) freely listened to 16 musical excerpts (lasting 20 sec. each) and grouped those that seemed to have the same duration. Then, participants associated each group of excerpts to one of a set of sine wave tones varying in duration from 16 to 24 sec. Multidimensional scaling analysis generated a two-dimensional solution for these time judgments. Musical excerpts with high arousal produced an overestimation of time, and affective valence had little influence on time perception. The duration was also overestimated when tempo and loudness were higher, and to a lesser extent, timbre density. In contrast, musical tension had little influence.

  12. Gene Sets for Utilization of Primary and Secondary Nutrition Supplies in the Distal Gut of Endangered Iberian Lynx

    Science.gov (United States)

    Alcaide, María; Messina, Enzo; Richter, Michael; Bargiela, Rafael; Peplies, Jörg; Huws, Sharon A.; Newbold, Charles J.; Golyshin, Peter N.; Simón, Miguel A.; López, Guillermo; Yakimov, Michail M.; Ferrer, Manuel

    2012-01-01

    Recent studies have indicated the existence of an extensive trans-genomic trans-mural co-metabolism between gut microbes and animal hosts that is diet-, host phylogeny- and provenance-influenced. Here, we analyzed the biodiversity at the level of small subunit rRNA gene sequence and the metabolic composition of 18 Mbp of consensus metagenome sequences and activity characteristics of bacterial intra-cellular extracts, in wild Iberian lynx (Lynx pardinus) fecal samples. Bacterial signatures (14.43% of all of the Firmicutes reads and 6.36% of total reads) related to the uncultured anaerobic commensals Anaeroplasma spp., which are typically found in ovine and bovine rumen, were first identified. The lynx gut was further characterized by an over-representation of ‘presumptive’ aquaporin aqpZ genes and genes encoding ‘active’ lysosomal-like digestive enzymes that are possibly needed to acquire glycerol, sugars and amino acids from glycoproteins, glyco(amino)lipids, glyco(amino)glycans and nucleoside diphosphate sugars. Lynx gut was highly enriched (28% of the total glycosidases) in genes encoding α-amylase and related enzymes, although it exhibited low rate of enzymatic activity indicative of starch degradation. The preponderance of β-xylosidase activity in protein extracts further suggests lynx gut microbes being most active for the metabolism of β-xylose containing plant N-glycans, although β-xylosidases sequences constituted only 1.5% of total glycosidases. These collective and unique bacterial, genetic and enzymatic activity signatures suggest that the wild lynx gut microbiota not only harbors gene sets underpinning sugar uptake from primary animal tissues (with the monotypic dietary profile of the wild lynx consisting of 80–100% wild rabbits) but also for the hydrolysis of prey-derived plant biomass. Although, the present investigation corresponds to a single sample and some of the statements should be considered qualitative, the data most likely

  13. Gene sets for utilization of primary and secondary nutrition supplies in the distal gut of endangered Iberian lynx.

    Directory of Open Access Journals (Sweden)

    María Alcaide

    Full Text Available Recent studies have indicated the existence of an extensive trans-genomic trans-mural co-metabolism between gut microbes and animal hosts that is diet-, host phylogeny- and provenance-influenced. Here, we analyzed the biodiversity at the level of small subunit rRNA gene sequence and the metabolic composition of 18 Mbp of consensus metagenome sequences and activity characteristics of bacterial intra-cellular extracts, in wild Iberian lynx (Lynx pardinus fecal samples. Bacterial signatures (14.43% of all of the Firmicutes reads and 6.36% of total reads related to the uncultured anaerobic commensals Anaeroplasma spp., which are typically found in ovine and bovine rumen, were first identified. The lynx gut was further characterized by an over-representation of 'presumptive' aquaporin aqpZ genes and genes encoding 'active' lysosomal-like digestive enzymes that are possibly needed to acquire glycerol, sugars and amino acids from glycoproteins, glyco(aminolipids, glyco(aminoglycans and nucleoside diphosphate sugars. Lynx gut was highly enriched (28% of the total glycosidases in genes encoding α-amylase and related enzymes, although it exhibited low rate of enzymatic activity indicative of starch degradation. The preponderance of β-xylosidase activity in protein extracts further suggests lynx gut microbes being most active for the metabolism of β-xylose containing plant N-glycans, although β-xylosidases sequences constituted only 1.5% of total glycosidases. These collective and unique bacterial, genetic and enzymatic activity signatures suggest that the wild lynx gut microbiota not only harbors gene sets underpinning sugar uptake from primary animal tissues (with the monotypic dietary profile of the wild lynx consisting of 80-100% wild rabbits but also for the hydrolysis of prey-derived plant biomass. Although, the present investigation corresponds to a single sample and some of the statements should be considered qualitative, the data most likely

  14. A support vector machine based test for incongruence between sets of trees in tree space

    Science.gov (United States)

    2012-01-01

    Background The increased use of multi-locus data sets for phylogenetic reconstruction has increased the need to determine whether a set of gene trees significantly deviate from the phylogenetic patterns of other genes. Such unusual gene trees may have been influenced by other evolutionary processes such as selection, gene duplication, or horizontal gene transfer. Results Motivated by this problem we propose a nonparametric goodness-of-fit test for two empirical distributions of gene trees, and we developed the software GeneOut to estimate a p-value for the test. Our approach maps trees into a multi-dimensional vector space and then applies support vector machines (SVMs) to measure the separation between two sets of pre-defined trees. We use a permutation test to assess the significance of the SVM separation. To demonstrate the performance of GeneOut, we applied it to the comparison of gene trees simulated within different species trees across a range of species tree depths. Applied directly to sets of simulated gene trees with large sample sizes, GeneOut was able to detect very small differences between two set of gene trees generated under different species trees. Our statistical test can also include tree reconstruction into its test framework through a variety of phylogenetic optimality criteria. When applied to DNA sequence data simulated from different sets of gene trees, results in the form of receiver operating characteristic (ROC) curves indicated that GeneOut performed well in the detection of differences between sets of trees with different distributions in a multi-dimensional space. Furthermore, it controlled false positive and false negative rates very well, indicating a high degree of accuracy. Conclusions The non-parametric nature of our statistical test provides fast and efficient analyses, and makes it an applicable test for any scenario where evolutionary or other factors can lead to trees with different multi-dimensional distributions. The

  15. Optimization to the Culture Conditions for Phellinus Production with Regression Analysis and Gene-Set Based Genetic Algorithm

    Science.gov (United States)

    Li, Zhongwei; Xin, Yuezhen; Wang, Xun; Sun, Beibei; Xia, Shengyu; Li, Hui

    2016-01-01

    Phellinus is a kind of fungus and is known as one of the elemental components in drugs to avoid cancers. With the purpose of finding optimized culture conditions for Phellinus production in the laboratory, plenty of experiments focusing on single factor were operated and large scale of experimental data were generated. In this work, we use the data collected from experiments for regression analysis, and then a mathematical model of predicting Phellinus production is achieved. Subsequently, a gene-set based genetic algorithm is developed to optimize the values of parameters involved in culture conditions, including inoculum size, PH value, initial liquid volume, temperature, seed age, fermentation time, and rotation speed. These optimized values of the parameters have accordance with biological experimental results, which indicate that our method has a good predictability for culture conditions optimization. PMID:27610365

  16. NetGen: a novel network-based probabilistic generative model for gene set functional enrichment analysis.

    Science.gov (United States)

    Sun, Duanchen; Liu, Yinliang; Zhang, Xiang-Sun; Wu, Ling-Yun

    2017-09-21

    High-throughput experimental techniques have been dramatically improved and widely applied in the past decades. However, biological interpretation of the high-throughput experimental results, such as differential expression gene sets derived from microarray or RNA-seq experiments, is still a challenging task. Gene Ontology (GO) is commonly used in the functional enrichment studies. The GO terms identified via current functional enrichment analysis tools often contain direct parent or descendant terms in the GO hierarchical structure. Highly redundant terms make users difficult to analyze the underlying biological processes. In this paper, a novel network-based probabilistic generative model, NetGen, was proposed to perform the functional enrichment analysis. An additional protein-protein interaction (PPI) network was explicitly used to assist the identification of significantly enriched GO terms. NetGen achieved a superior performance than the existing methods in the simulation studies. The effectiveness of NetGen was explored further on four real datasets. Notably, several GO terms which were not directly linked with the active gene list for each disease were identified. These terms were closely related to the corresponding diseases when accessed to the curated literatures. NetGen has been implemented in the R package CopTea publicly available at GitHub ( http://github.com/wulingyun/CopTea/ ). Our procedure leads to a more reasonable and interpretable result of the functional enrichment analysis. As a novel term combination-based functional enrichment analysis method, NetGen is complementary to current individual term-based methods, and can help to explore the underlying pathogenesis of complex diseases.

  17. Comparative genomic analysis of Brucella abortus vaccine strain 104M reveals a set of candidate genes associated with its virulence attenuation.

    Science.gov (United States)

    Yu, Dong; Hui, Yiming; Zai, Xiaodong; Xu, Junjie; Liang, Long; Wang, Bingxiang; Yue, Junjie; Li, Shanhu

    2015-01-01

    The Brucella abortus strain 104M, a spontaneously attenuated strain, has been used as a vaccine strain in humans against brucellosis for 6 decades in China. Despite many studies, the molecular mechanisms that cause the attenuation are still unclear. Here, we determined the whole-genome sequence of 104M and conducted a comprehensive comparative analysis against the whole genome sequences of the virulent strain, A13334, and other reference strains. This analysis revealed a highly similar genome structure between 104M and A13334. The further comparative genomic analysis between 104M and A13334 revealed a set of genes missing in 104M. Some of these genes were identified to be directly or indirectly associated with virulence. Similarly, a set of mutations in the virulence-related genes was also identified, which may be related to virulence alteration. This study provides a set of candidate genes associated with virulence attenuation in B.abortus vaccine strain 104M.

  18. A MULTIDIMENSIONAL AND MULTIPHYSICS APPROACH TO NUCLEAR FUEL BEHAVIOR SIMULATION

    Energy Technology Data Exchange (ETDEWEB)

    R. L. Williamson; J. D. Hales; S. R. Novascone; M. R. Tonks; D. R. Gaston; C. J. Permann; D. Andrs; R. C. Martineau

    2012-04-01

    Important aspects of fuel rod behavior, for example pellet-clad mechanical interaction (PCMI), fuel fracture, oxide formation, non-axisymmetric cooling, and response to fuel manufacturing defects, are inherently multidimensional in addition to being complicated multiphysics problems. Many current modeling tools are strictly 2D axisymmetric or even 1.5D. This paper outlines the capabilities of a new fuel modeling tool able to analyze either 2D axisymmetric or fully 3D models. These capabilities include temperature-dependent thermal conductivity of fuel; swelling and densification; fuel creep; pellet fracture; fission gas release; cladding creep; irradiation growth; and gap mechanics (contact and gap heat transfer). The need for multiphysics, multidimensional modeling is then demonstrated through a discussion of results for a set of example problems. The first, a 10-pellet rodlet, demonstrates the viability of the solution method employed. This example highlights the effect of our smeared cracking model and also shows the multidimensional nature of discrete fuel pellet modeling. The second example relies on our the multidimensional, multiphysics approach to analyze a missing pellet surface problem. As a final example, we show a lower-length-scale simulation coupled to a continuum-scale simulation.

  19. Measures for a multidimensional multiverse

    Science.gov (United States)

    Chung, Hyeyoun

    2015-04-01

    We explore the phenomenological implications of generalizing the causal patch and fat geodesic measures to a multidimensional multiverse, where the vacua can have differing numbers of large dimensions. We consider a simple model in which the vacua are nucleated from a D -dimensional parent spacetime through dynamical compactification of the extra dimensions, and compute the geometric contribution to the probability distribution of observations within the multiverse for each measure. We then study how the shape of this probability distribution depends on the time scales for the existence of observers, for vacuum domination, and for curvature domination (tobs,tΛ , and tc, respectively.) In this work we restrict ourselves to bubbles with positive cosmological constant, Λ . We find that in the case of the causal patch cutoff, when the bubble universes have p +1 large spatial dimensions with p ≥2 , the shape of the probability distribution is such that we obtain the coincidence of time scales tobs˜tΛ˜tc . Moreover, the size of the cosmological constant is related to the size of the landscape. However, the exact shape of the probability distribution is different in the case p =2 , compared to p ≥3 . In the case of the fat geodesic measure, the result is even more robust: the shape of the probability distribution is the same for all p ≥2 , and we once again obtain the coincidence tobs˜tΛ˜tc . These results require only very mild conditions on the prior probability of the distribution of vacua in the landscape. Our work shows that the observed double coincidence of time scales is a robust prediction even when the multiverse is generalized to be multidimensional; that this coincidence is not a consequence of our particular Universe being (3 +1 )-dimensional; and that this observable cannot be used to preferentially select one measure over another in a multidimensional multiverse.

  20. Ordinal Comparison of Multidimensional Deprivation

    DEFF Research Database (Denmark)

    Sonne-Schmidt, Christoffer Scavenius; Tarp, Finn; Østerdal, Lars Peter

    This paper develops an ordinal method of comparison of multidimensional inequality. In our model, population distribution g is more unequal than f when the distributions have common median and can be obtained from f  by one or more shifts in population density that increase inequality. For our be...... benchmark 2x2 case (i.e. the case of two binary outcome variables), we derive an empirical method for making inequality comparisons. As an illustration, we apply the model to childhood poverty in Mozambique....

  1. Structural modeling of the production quality as a multidimensional object of measurement and control

    OpenAIRE

    Зубрецкая, Наталья Анатольевна

    2015-01-01

    The structural-analytical models of product quality as a multidimensional process of evaluation, measurement and control are developed. The product quality is represented as a multi-factor, multi-criteria and multi-parameter estimation object. This structural formalization of quality demonstrates the multidimensional qualities: comprehensiveness due to a set of environmental factors; multicriteriality due collectively evaluated quality criteria; multiparameter information models that describe...

  2. Gene set-based analysis of polymorphisms: finding pathways or biological processes associated to traits in genome-wide association studies

    Science.gov (United States)

    Medina, Ignacio; Montaner, David; Bonifaci, Nuria; Pujana, Miguel Angel; Carbonell, José; Tarraga, Joaquin; Al-Shahrour, Fatima; Dopazo, Joaquin

    2009-01-01

    Genome-wide association studies have become a popular strategy to find associations of genes to traits of interest. Despite the high-resolution available today to carry out genotyping studies, the success of its application in real studies has been limited by the testing strategy used. As an alternative to brute force solutions involving the use of very large cohorts, we propose the use of the Gene Set Analysis (GSA), a different analysis strategy based on testing the association of modules of functionally related genes. We show here how the Gene Set-based Analysis of Polymorphisms (GeSBAP), which is a simple implementation of the GSA strategy for the analysis of genome-wide association studies, provides a significant increase in the power testing for this type of studies. GeSBAP is freely available at http://bioinfo.cipf.es/gesbap/ PMID:19502494

  3. A MultiSite GatewayTM vector set for the functional analysis of genes in the model Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Nagels Durand Astrid

    2012-09-01

    Full Text Available Abstract Background Recombinatorial cloning using the GatewayTM technology has been the method of choice for high-throughput omics projects, resulting in the availability of entire ORFeomes in GatewayTM compatible vectors. The MultiSite GatewayTM system allows combining multiple genetic fragments such as promoter, ORF and epitope tag in one single reaction. To date, this technology has not been accessible in the yeast Saccharomyces cerevisiae, one of the most widely used experimental systems in molecular biology, due to the lack of appropriate destination vectors. Results Here, we present a set of three-fragment MultiSite GatewayTM destination vectors that have been developed for gene expression in S. cerevisiae and that allow the assembly of any promoter, open reading frame, epitope tag arrangement in combination with any of four auxotrophic markers and three distinct replication mechanisms. As an example of its applicability, we used yeast three-hybrid to provide evidence for the assembly of a ternary complex of plant proteins involved in jasmonate signalling and consisting of the JAZ, NINJA and TOPLESS proteins. Conclusion Our vectors make MultiSite GatewayTM cloning accessible in S. cerevisiae and implement a fast and versatile cloning method for the high-throughput functional analysis of (heterologous proteins in one of the most widely used model organisms for molecular biology research.

  4. Perceptual Salience and Children's Multidimensional Problem Solving

    Science.gov (United States)

    Odom, Richard D.; Corbin, David W.

    1973-01-01

    Uni- and multidimensional processing of 6- to 9-year olds was studied using recall tasks in which an array of stimuli was reconstructed to match a model array. Results indicated that both age groups were able to solve multidimensional problems, but that solution rate was retarded by the unidimensional processing of highly salient dimensions.…

  5. Association of Protein Translation and Extracellular Matrix Gene Sets with Breast Cancer Metastasis: Findings Uncovered on Analysis of Multiple Publicly Available Datasets Using Individual Patient Data Approach.

    Directory of Open Access Journals (Sweden)

    Nilotpal Chowdhury

    Full Text Available Microarray analysis has revolutionized the role of genomic prognostication in breast cancer. However, most studies are single series studies, and suffer from methodological problems. We sought to use a meta-analytic approach in combining multiple publicly available datasets, while correcting for batch effects, to reach a more robust oncogenomic analysis.The aim of the present study was to find gene sets associated with distant metastasis free survival (DMFS in systemically untreated, node-negative breast cancer patients, from publicly available genomic microarray datasets.Four microarray series (having 742 patients were selected after a systematic search and combined. Cox regression for each gene was done for the combined dataset (univariate, as well as multivariate - adjusted for expression of Cell cycle related genes and for the 4 major molecular subtypes. The centre and microarray batch effects were adjusted by including them as random effects variables. The Cox regression coefficients for each analysis were then ranked and subjected to a Gene Set Enrichment Analysis (GSEA.Gene sets representing protein translation were independently negatively associated with metastasis in the Luminal A and Luminal B subtypes, but positively associated with metastasis in Basal tumors. Proteinaceous extracellular matrix (ECM gene set expression was positively associated with metastasis, after adjustment for expression of cell cycle related genes on the combined dataset. Finally, the positive association of the proliferation-related genes with metastases was confirmed.To the best of our knowledge, the results depicting mixed prognostic significance of protein translation in breast cancer subtypes are being reported for the first time. We attribute this to our study combining multiple series and performing a more robust meta-analytic Cox regression modeling on the combined dataset, thus discovering 'hidden' associations. This methodology seems to yield new and

  6. Association of Protein Translation and Extracellular Matrix Gene Sets with Breast Cancer Metastasis: Findings Uncovered on Analysis of Multiple Publicly Available Datasets Using Individual Patient Data Approach.

    Science.gov (United States)

    Chowdhury, Nilotpal; Sapru, Shantanu

    2015-01-01

    Microarray analysis has revolutionized the role of genomic prognostication in breast cancer. However, most studies are single series studies, and suffer from methodological problems. We sought to use a meta-analytic approach in combining multiple publicly available datasets, while correcting for batch effects, to reach a more robust oncogenomic analysis. The aim of the present study was to find gene sets associated with distant metastasis free survival (DMFS) in systemically untreated, node-negative breast cancer patients, from publicly available genomic microarray datasets. Four microarray series (having 742 patients) were selected after a systematic search and combined. Cox regression for each gene was done for the combined dataset (univariate, as well as multivariate - adjusted for expression of Cell cycle related genes) and for the 4 major molecular subtypes. The centre and microarray batch effects were adjusted by including them as random effects variables. The Cox regression coefficients for each analysis were then ranked and subjected to a Gene Set Enrichment Analysis (GSEA). Gene sets representing protein translation were independently negatively associated with metastasis in the Luminal A and Luminal B subtypes, but positively associated with metastasis in Basal tumors. Proteinaceous extracellular matrix (ECM) gene set expression was positively associated with metastasis, after adjustment for expression of cell cycle related genes on the combined dataset. Finally, the positive association of the proliferation-related genes with metastases was confirmed. To the best of our knowledge, the results depicting mixed prognostic significance of protein translation in breast cancer subtypes are being reported for the first time. We attribute this to our study combining multiple series and performing a more robust meta-analytic Cox regression modeling on the combined dataset, thus discovering 'hidden' associations. This methodology seems to yield new and interesting

  7. Multidimensional fatigue and its correlates in hospitalised advanced cancer patients.

    NARCIS (Netherlands)

    Echteld, M.A.; Passchier, J.; Teunissen, S.; Claessen, S.; Wit, R. de; Rijt, C.C.D. van der

    2007-01-01

    Although fatigue is a multidimensional concept, multidimensional fatigue is rarely investigated in hospitalised cancer patients. We determined the levels and correlates of multidimensional fatigue in 100 advanced cancer patients admitted for symptom control. Fatigue dimensions were general fatigue

  8. Heuristics for Multidimensional Packing Problems

    DEFF Research Database (Denmark)

    Egeblad, Jens

    for a minimum height container required for the items. The main contributions of the thesis are three new heuristics for strip-packing and knapsack packing problems where items are both rectangular and irregular. In the two first papers we describe a heuristic for the multidimensional strip-packing problem...... that is based on a relaxed placement principle. The heuristic starts with a random overlapping placement of items and large container dimensions. From the overlapping placement overlap is reduced iteratively until a non-overlapping placement is found and a new problem is solved with a smaller container size...... of this heuristic are among the best published in the literature both for two- and three-dimensional strip-packing problems for irregular shapes. In the third paper, we introduce a heuristic for two- and three-dimensional rectangular knapsack packing problems. The two-dimensional heuristic uses the sequence pair...

  9. The 'thousand words' problem: Summarizing multi-dimensional data

    International Nuclear Information System (INIS)

    Scott, David M.

    2011-01-01

    Research highlights: → Sophisticated process sensors produce large multi-dimensional data sets. → Plant control systems cannot handle images or large amounts of data. → Various techniques reduce the dimensionality, extracting information from raw data. → Simple 1D and 2D methods can often be extended to 3D and 4D applications. - Abstract: An inherent difficulty in the application of multi-dimensional sensing to process monitoring and control is the extraction and interpretation of useful information. Ultimately the measured data must be collapsed into a relatively small number of values that capture the salient characteristics of the process. Although multiple dimensions are frequently necessary to isolate a particular physical attribute (such as the distribution of a particular chemical species in a reactor), plant control systems are not equipped to use such data directly. The production of a multi-dimensional data set (often displayed as an image) is not the final step of the measurement process, because information must still be extracted from the raw data. In the metaphor of one picture being equal to a thousand words, the problem becomes one of paraphrasing a lengthy description of the image with one or two well-chosen words. Various approaches to solving this problem are discussed using examples from the fields of particle characterization, image processing, and process tomography.

  10. Multi-dimensional Bin Packing Problems with Guillotine Constraints

    DEFF Research Database (Denmark)

    Amossen, Rasmus Resen; Pisinger, David

    2010-01-01

    The problem addressed in this paper is the decision problem of determining if a set of multi-dimensional rectangular boxes can be orthogonally packed into a rectangular bin while satisfying the requirement that the packing should be guillotine cuttable. That is, there should exist a series of face...... parallel straight cuts that can recursively cut the bin into pieces so that each piece contains a box and no box has been intersected by a cut. The unrestricted problem is known to be NP-hard. In this paper we present a generalization of a constructive algorithm for the multi-dimensional bin packing...... problem, with and without the guillotine constraint, based on constraint programming....

  11. The West Haven-Yale Multidimensional Pain Inventory (WHYMPI).

    Science.gov (United States)

    Kerns, R D; Turk, D C; Rudy, T E

    1985-12-01

    The complexity of chronic pain has represented a major dilemma for clinical researchers interested in the reliable and valid assessment of the problem and the evaluation of treatment approaches. The West Haven-Yale Multidimensional Pain Inventory (WHYMPI) was developed in order to fill a widely recognized void in the assessment of clinical pain. Assets of the inventory are its brevity and clarity, its foundation in contemporary psychological theory, its multidimensional focus, and its strong psychometric properties. Three parts of the inventory, comprised of 12 scales, examine the impact of pain on the patients' lives, the responses of others to the patients' communications of pain, and the extent to which patients participate in common daily activities. The instrument is recommended for use in conjunction with behavioral and psychophysiological assessment strategies in the evaluation of chronic pain patients in clinical settings. The utility of the WHYMPI in empirical investigations of chronic pain is also discussed.

  12. Fundamentals of applied multidimensional scaling for educational and psychological research

    CERN Document Server

    Ding, Cody S

    2018-01-01

    This book explores the fundamentals of multidimensional scaling (MDS) and how this analytic method can be used in applied setting for educational and psychological research. The book tries to make MDS more accessible to a wider audience in terms of the language and examples that are more relevant to educational and psychological research and less technical so that the readers are not overwhelmed by equations. The goal is for readers to learn the methods described in this book and immediately start using MDS via available software programs. The book also examines new applications that have previously not been discussed in MDS literature. It should be an ideal book for graduate students and researchers to better understand MDS. Fundamentals of Applied Multidimensional Scaling for Educational and Psychological Research is divided into three parts. Part I covers the basic and fundamental features of MDS models pertaining to applied research applications. Chapters in this section cover the essential features of da...

  13. Multidimensional epidemic thresholds in diffusion processes over interdependent networks

    International Nuclear Information System (INIS)

    Salehi, Mostafa; Siyari, Payam; Magnani, Matteo; Montesi, Danilo

    2015-01-01

    Highlights: •We propose a new concept of multidimensional epidemic threshold for interdependent networks. •We analytically derive and numerically illustrate the conditions for multilayer epidemics. •We study the evolution of infection density and diffusion dynamics. -- Abstract: Several systems can be modeled as sets of interdependent networks where each network contains distinct nodes. Diffusion processes like the spreading of a disease or the propagation of information constitute fundamental phenomena occurring over such coupled networks. In this paper we propose a new concept of multidimensional epidemic threshold characterizing diffusion processes over interdependent networks, allowing different diffusion rates on the different networks and arbitrary degree distributions. We analytically derive and numerically illustrate the conditions for multilayer epidemics, i.e., the appearance of a giant connected component spanning all the networks. Furthermore, we study the evolution of infection density and diffusion dynamics with extensive simulation experiments on synthetic and real networks

  14. The map-1 gene family in root-knot nematodes, Meloidogyne spp.: a set of taxonomically restricted genes specific to clonal species.

    Directory of Open Access Journals (Sweden)

    Iva Tomalova

    Full Text Available Taxonomically restricted genes (TRGs, i.e., genes that are restricted to a limited subset of phylogenetically related organisms, may be important in adaptation. In parasitic organisms, TRG-encoded proteins are possible determinants of the specificity of host-parasite interactions. In the root-knot nematode (RKN Meloidogyne incognita, the map-1 gene family encodes expansin-like proteins that are secreted into plant tissues during parasitism, thought to act as effectors to promote successful root infection. MAP-1 proteins exhibit a modular architecture, with variable number and arrangement of 58 and 13-aa domains in their central part. Here, we address the evolutionary origins of this gene family using a combination of bioinformatics and molecular biology approaches. Map-1 genes were solely identified in one single member of the phylum Nematoda, i.e., the genus Meloidogyne, and not detected in any other nematode, thus indicating that the map-1 gene family is indeed a TRG family. A phylogenetic analysis of the distribution of map-1 genes in RKNs further showed that these genes are specifically present in species that reproduce by mitotic parthenogenesis, with the exception of M. floridensis, and could not be detected in RKNs reproducing by either meiotic parthenogenesis or amphimixis. These results highlight the divergence between mitotic and meiotic RKN species as a critical transition in the evolutionary history of these parasites. Analysis of the sequence conservation and organization of repeated domains in map-1 genes suggests that gene duplication(s together with domain loss/duplication have contributed to the evolution of the map-1 family, and that some strong selection mechanism may be acting upon these genes to maintain their functional role(s in the specificity of the plant-RKN interactions.

  15. Successful Ageing and Multidimensional Poverty: The case of Peru

    OpenAIRE

    Olivera Angulo, Javier; Tournier, Isabelle

    2016-01-01

    This study investigated the determinants of Successful Ageing (SA) in a sample of 4,151 Peruvians aged between 65 and 80 years and living in poverty. A key contribution of this study is to combine the conceptual appeal of SA to measure well-being in old age with the multi-dimensional poverty counting approach developed in the economic literature. This setting allows for moving beyond the dichotomy of successful and usual ageing to take advantage of the full distribution of success along a set...

  16. A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records

    DEFF Research Database (Denmark)

    Jiang, Li; Edwards, Stefan M.; Thomsen, Bo

    2014-01-01

    from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text...

  17. Interaction between Social/Psychosocial Factors and Genetic Variants on Body Mass Index: A Gene-Environment Interaction Analysis in a Longitudinal Setting.

    Science.gov (United States)

    Zhao, Wei; Ware, Erin B; He, Zihuai; Kardia, Sharon L R; Faul, Jessica D; Smith, Jennifer A

    2017-09-29

    Obesity, which develops over time, is one of the leading causes of chronic diseases such as cardiovascular disease. However, hundreds of BMI (body mass index)-associated genetic loci identified through large-scale genome-wide association studies (GWAS) only explain about 2.7% of BMI variation. Most common human traits are believed to be influenced by both genetic and environmental factors. Past studies suggest a variety of environmental features that are associated with obesity, including socioeconomic status and psychosocial factors. This study combines both gene/regions and environmental factors to explore whether social/psychosocial factors (childhood and adult socioeconomic status, social support, anger, chronic burden, stressful life events, and depressive symptoms) modify the effect of sets of genetic variants on BMI in European American and African American participants in the Health and Retirement Study (HRS). In order to incorporate longitudinal phenotype data collected in the HRS and investigate entire sets of single nucleotide polymorphisms (SNPs) within gene/region simultaneously, we applied a novel set-based test for gene-environment interaction in longitudinal studies (LGEWIS). Childhood socioeconomic status (parental education) was found to modify the genetic effect in the gene/region around SNP rs9540493 on BMI in European Americans in the HRS. The most significant SNP (rs9540488) by childhood socioeconomic status interaction within the rs9540493 gene/region was suggestively replicated in the Multi-Ethnic Study of Atherosclerosis (MESA) ( p = 0.07).

  18. Interaction between Social/Psychosocial Factors and Genetic Variants on Body Mass Index: A Gene-Environment Interaction Analysis in a Longitudinal Setting

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    2017-09-01

    Full Text Available Obesity, which develops over time, is one of the leading causes of chronic diseases such as cardiovascular disease. However, hundreds of BMI (body mass index-associated genetic loci identified through large-scale genome-wide association studies (GWAS only explain about 2.7% of BMI variation. Most common human traits are believed to be influenced by both genetic and environmental factors. Past studies suggest a variety of environmental features that are associated with obesity, including socioeconomic status and psychosocial factors. This study combines both gene/regions and environmental factors to explore whether social/psychosocial factors (childhood and adult socioeconomic status, social support, anger, chronic burden, stressful life events, and depressive symptoms modify the effect of sets of genetic variants on BMI in European American and African American participants in the Health and Retirement Study (HRS. In order to incorporate longitudinal phenotype data collected in the HRS and investigate entire sets of single nucleotide polymorphisms (SNPs within gene/region simultaneously, we applied a novel set-based test for gene-environment interaction in longitudinal studies (LGEWIS. Childhood socioeconomic status (parental education was found to modify the genetic effect in the gene/region around SNP rs9540493 on BMI in European Americans in the HRS. The most significant SNP (rs9540488 by childhood socioeconomic status interaction within the rs9540493 gene/region was suggestively replicated in the Multi-Ethnic Study of Atherosclerosis (MESA (p = 0.07.

  19. Differential gene expression in granulosa cells from polycystic ovary syndrome patients with and without insulin resistance: identification of susceptibility gene sets through network analysis.

    Science.gov (United States)

    Kaur, Surleen; Archer, Kellie J; Devi, M Gouri; Kriplani, Alka; Strauss, Jerome F; Singh, Rita

    2012-10-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous, genetically complex, endocrine disorder of uncertain etiology in women. Our aim was to compare the gene expression profiles in stimulated granulosa cells of PCOS women with and without insulin resistance vs. matched controls. This study included 12 normal ovulatory women (controls), 12 women with PCOS without evidence for insulin resistance (PCOS non-IR), and 16 women with insulin resistance (PCOS-IR) undergoing in vitro fertilization. Granulosa cell gene expression profiling was accomplished using Affymetrix Human Genome-U133 arrays. Differentially expressed genes were classified according to gene ontology using ingenuity pathway analysis tools. Microarray results for selected genes were confirmed by real-time quantitative PCR. A total of 211 genes were differentially expressed in PCOS non-IR and PCOS-IR granulosa cells (fold change≥1.5; P≤0.001) vs. matched controls. Diabetes mellitus and inflammation genes were significantly increased in PCOS-IR patients. Real-time quantitative PCR confirmed higher expression of NCF2 (2.13-fold), TCF7L2 (1.92-fold), and SERPINA1 (5.35-fold). Increased expression of inflammation genes ITGAX (3.68-fold) and TAB2 (1.86-fold) was confirmed in PCOS non-IR. Different cardiometabolic disease genes were differentially expressed in the two groups. Decreased expression of CAV1 (-3.58-fold) in PCOS non-IR and SPARC (-1.88-fold) in PCOS-IR was confirmed. Differential expression of genes involved in TGF-β signaling (IGF2R, increased; and HAS2, decreased), and oxidative stress (TXNIP, increased) was confirmed in both groups. Microarray analysis demonstrated differential expression of genes linked to diabetes mellitus, inflammation, cardiovascular diseases, and infertility in the granulosa cells of PCOS women with and without insulin resistance. Because these dysregulated genes are also involved in oxidative stress, lipid metabolism, and insulin signaling, we hypothesize that these

  20. Interaction between dopamine D2 receptor genotype and parental rule-setting in adolescent alcohol use: evidence for a gene-parenting interaction.

    NARCIS (Netherlands)

    Zwaluw, C.S. van der; Engels, R.C.E.M.; Vermulst, A.A.; Franke, B.; Buitelaar, J.K.; Verkes, R.J.; Scholte, R.H.

    2010-01-01

    Association studies investigating the link between the dopamine D2 receptor gene (DRD2) and alcohol (mis)use have shown inconsistent results. This may be due to lack of attention for environmental factors. High levels of parental rule-setting are associated with lower levels of adolescent alcohol

  1. Bridging cancer biology with the clinic: relative expression of a GRHL2-mediated gene-set pair predicts breast cancer metastasis.

    Directory of Open Access Journals (Sweden)

    Xinan Yang

    Full Text Available Identification and characterization of crucial gene target(s that will allow focused therapeutics development remains a challenge. We have interrogated the putative therapeutic targets associated with the transcription factor Grainy head-like 2 (GRHL2, a critical epithelial regulatory factor. We demonstrate the possibility to define the molecular functions of critical genes in terms of their personalized expression profiles, allowing appropriate functional conclusions to be derived. A novel methodology, relative expression analysis with gene-set pairs (RXA-GSP, is designed to explore the potential clinical utility of cancer-biology discovery. Observing that Grhl2-overexpression leads to increased metastatic potential in vitro, we established a model assuming Grhl2-induced or -inhibited genes confer poor or favorable prognosis respectively for cancer metastasis. Training on public gene expression profiles of 995 breast cancer patients, this method prioritized one gene-set pair (GRHL2, CDH2, FN1, CITED2, MKI67 versus CTNNB1 and CTNNA3 from all 2717 possible gene-set pairs (GSPs. The identified GSP significantly dichotomized 295 independent patients for metastasis-free survival (log-rank tested p = 0.002; severe empirical p = 0.035. It also showed evidence of clinical prognostication in another independent 388 patients collected from three studies (log-rank tested p = 3.3e-6. This GSP is independent of most traditional prognostic indicators, and is only significantly associated with the histological grade of breast cancer (p = 0.0017, a GRHL2-associated clinical character (p = 6.8e-6, Spearman correlation, suggesting that this GSP is reflective of GRHL2-mediated events. Furthermore, a literature review indicates the therapeutic potential of the identified genes. This research demonstrates a novel strategy to integrate both biological experiments and clinical gene expression profiles for extracting and elucidating the genomic

  2. Multidimensional singular integrals and integral equations

    CERN Document Server

    Mikhlin, Solomon Grigorievich; Stark, M; Ulam, S

    1965-01-01

    Multidimensional Singular Integrals and Integral Equations presents the results of the theory of multidimensional singular integrals and of equations containing such integrals. Emphasis is on singular integrals taken over Euclidean space or in the closed manifold of Liapounov and equations containing such integrals. This volume is comprised of eight chapters and begins with an overview of some theorems on linear equations in Banach spaces, followed by a discussion on the simplest properties of multidimensional singular integrals. Subsequent chapters deal with compounding of singular integrals

  3. Wild immunology assessed by multidimensional mass cytometry.

    Science.gov (United States)

    Japp, Alberto Sada; Hoffmann, Kerstin; Schlickeiser, Stephan; Glauben, Rainer; Nikolaou, Christos; Maecker, Holden T; Braun, Julian; Matzmohr, Nadine; Sawitzki, Birgit; Siegmund, Britta; Radbruch, Andreas; Volk, Hans-Dieter; Frentsch, Marco; Kunkel, Desiree; Thiel, Andreas

    2017-01-01

    A great part of our knowledge on mammalian immunology has been established in laboratory settings. The use of inbred mouse strains enabled controlled studies of immune cell and molecule functions in defined settings. These studies were usually performed in specific-pathogen free (SPF) environments providing standardized conditions. In contrast, mammalians including humans living in their natural habitat are continuously facing pathogen encounters throughout their life. The influences of environmental conditions on the signatures of the immune system and on experimental outcomes are yet not well defined. Thus, the transferability of results obtained in current experimental systems to the physiological human situation has always been a matter of debate. Studies elucidating the diversity of "wild immunology" imprintings in detail and comparing it with those of "clean" lab mice are sparse. Here, we applied multidimensional mass cytometry to dissect phenotypic and functional differences between distinct groups of laboratory and pet shop mice as a source for "wild mice". For this purpose, we developed a 31-antibody panel for murine leukocyte subsets identification and a 35-antibody panel assessing various cytokines. Established murine leukocyte populations were easily identified and diverse immune signatures indicative of numerous pathogen encounters were classified particularly in pet shop mice and to a lesser extent in quarantine and non-SPF mice as compared to SPF mice. In addition, unsupervised analysis identified distinct clusters that associated strongly with the degree of pathogenic priming, including increased frequencies of activated NK cells and antigen-experienced B- and T-cell subsets. Our study unravels the complexity of immune signatures altered under physiological pathogen challenges and highlights the importance of carefully adapting laboratory settings for immunological studies in mice, including drug and therapy testing. © 2016 International Society

  4. A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records

    DEFF Research Database (Denmark)

    Jiang, Li; Edwards, Stefan M.; Thomsen, Bo

    2014-01-01

    from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining......Background: Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic...

  5. Selection and validation of a set of reliable reference genes for quantitative RT-PCR studies in the brain of the Cephalopod Mollusc Octopus vulgaris

    Directory of Open Access Journals (Sweden)

    Biffali Elio

    2009-07-01

    Full Text Available Abstract Background Quantitative real-time polymerase chain reaction (RT-qPCR is valuable for studying the molecular events underlying physiological and behavioral phenomena. Normalization of real-time PCR data is critical for a reliable mRNA quantification. Here we identify reference genes to be utilized in RT-qPCR experiments to normalize and monitor the expression of target genes in the brain of the cephalopod mollusc Octopus vulgaris, an invertebrate. Such an approach is novel for this taxon and of advantage in future experiments given the complexity of the behavioral repertoire of this species when compared with its relatively simple neural organization. Results We chose 16S, and 18S rRNA, actB, EEF1A, tubA and ubi as candidate reference genes (housekeeping genes, HKG. The expression of 16S and 18S was highly variable and did not meet the requirements of candidate HKG. The expression of the other genes was almost stable and uniform among samples. We analyzed the expression of HKG into two different set of animals using tissues taken from the central nervous system (brain parts and mantle (here considered as control tissue by BestKeeper, geNorm and NormFinder. We found that HKG expressions differed considerably with respect to brain area and octopus samples in an HKG-specific manner. However, when the mantle is treated as control tissue and the entire central nervous system is considered, NormFinder revealed tubA and ubi as the most suitable HKG pair. These two genes were utilized to evaluate the relative expression of the genes FoxP, creb, dat and TH in O. vulgaris. Conclusion We analyzed the expression profiles of some genes here identified for O. vulgaris by applying RT-qPCR analysis for the first time in cephalopods. We validated candidate reference genes and found the expression of ubi and tubA to be the most appropriate to evaluate the expression of target genes in the brain of different octopuses. Our results also underline the

  6. Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Gaora Peadar Ó

    2010-10-01

    Full Text Available Abstract Background Currently, a number of bioinformatics methods are available to generate appropriate lists of genes from a microarray experiment. While these lists represent an accurate primary analysis of the data, fewer options exist to contextualise those lists. The development and validation of such methods is crucial to the wider application of microarray technology in the clinical setting. Two key challenges in clinical bioinformatics involve appropriate statistical modelling of dynamic transcriptomic changes, and extraction of clinically relevant meaning from very large datasets. Results Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p Conclusion Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest correlation with the clinical markers of interest. In this case, we have identified selenoamino acid metabolism and steroid biosynthesis as key pathways mediating the observed relationship between metabolic health and high-CLA beef. These results indicate that this type of

  7. Phase space eigenfunctions of multidimensional quadratic Hamiltonians

    International Nuclear Information System (INIS)

    Dodonov, V.V.; Man'ko, V.I.

    1986-01-01

    We obtain the explicit expressions for phace space eigenfunctions (PSE),i.e. Weyl's symbols of dyadic operators like vertical stroken> ,vertical strokem>, being the solution of the Schroedinger equation with the Hamiltonian which is a quite arbitrary multidimensional quadratic form of the operators of Cartesian coordinates and conjugated to them momenta with time-dependent coefficients. It is shown that for an arbitrary quadratic Hamiltonian one can always construct the set of completely factorized PSE which are products of N factors, each factor being dependent only on two arguments for nnot=m and on a single argument for n=m. These arguments are nothing but constants of motion of the correspondent classical system. PSE are expressed in terms of the associated Laguerre polynomials in the case of a discrete spectrum and in terms of the Airy functions in the continuous spectrum case. Three examples are considered: a harmonic oscillator with a time-dependent frequency, a charged particle in a nonstationary uniform magnetic field, and a particle in a time-dependent uniform potential field. (orig.)

  8. A tandem sequence motif acts as a distance-dependent enhancer in a set of genes involved in translation by binding the proteins NonO and SFPQ

    Directory of Open Access Journals (Sweden)

    Roepcke Stefan

    2011-12-01

    Full Text Available Abstract Background Bioinformatic analyses of expression control sequences in promoters of co-expressed or functionally related genes enable the discovery of common regulatory sequence motifs that might be involved in co-ordinated gene expression. By studying promoter sequences of the human ribosomal protein genes we recently identified a novel highly specific Localized Tandem Sequence Motif (LTSM. In this work we sought to identify additional genes and LTSM-binding proteins to elucidate potential regulatory mechanisms. Results Genome-wide analyses allowed finding a considerable number of additional LTSM-positive genes, the products of which are involved in translation, among them, translation initiation and elongation factors, and 5S rRNA. Electromobility shift assays then showed specific signals demonstrating the binding of protein complexes to LTSM in ribosomal protein gene promoters. Pull-down assays with LTSM-containing oligonucleotides and subsequent mass spectrometric analysis identified the related multifunctional nucleotide binding proteins NonO and SFPQ in the binding complex. Functional characterization then revealed that LTSM enhances the transcriptional activity of the promoters in dependency of the distance from the transcription start site. Conclusions Our data demonstrate the power of bioinformatic analyses for the identification of biologically relevant sequence motifs. LTSM and the here found LTSM-binding proteins NonO and SFPQ were discovered through a synergistic combination of bioinformatic and biochemical methods and are regulators of the expression of a set of genes of the translational apparatus in a distance-dependent manner.

  9. Taxonomically Different Co-Microsymbionts of a Relict Legume, Oxytropis popoviana, Have Complementary Sets of Symbiotic Genes and Together Increase the Efficiency of Plant Nodulation.

    Science.gov (United States)

    Safronova, Vera I; Belimov, Andrey A; Sazanova, Anna L; Chirak, Elizaveta R; Verkhozina, Alla V; Kuznetsova, Irina G; Andronov, Evgeny E; Puhalsky, Jan V; Tikhonovich, Igor A

    2018-06-20

    Ten rhizobial strains were isolated from root nodules of a relict legume Oxytropis popoviana Peschkova. For identification of the isolates, sequencing of rrs, the internal transcribed spacer region, and housekeeping genes recA, glnII, and rpoB was used. Nine fast-growing isolates were Mesorhizobium-related; eight strains were identified as M. japonicum and one isolate belonged to M. kowhaii. The only slow-growing isolate was identified as a Bradyrhizobium sp. Two strains, M. japonicum Opo-242 and Bradyrhizobium sp. strain Opo-243, were isolated from the same nodule. Symbiotic genes of these isolates were searched throughout the whole-genome sequences. The common nodABC genes and other symbiotic genes required for plant nodulation and nitrogen fixation were present in the isolate Opo-242. Strain Opo-243 did not contain the principal nod, nif, and fix genes; however, five genes (nodP, nodQ, nifL, nolK, and noeL) affecting the specificity of plant-rhizobia interactions but absent in isolate Opo-242 were detected. Strain Opo-243 could not induce nodules but significantly accelerated the root nodule formation after coinoculation with isolate Opo-242. Thus, we demonstrated that taxonomically different strains of the archaic symbiotic system can be co-microsymbionts infecting the same nodule and promoting the nodulation process due to complementary sets of symbiotic genes.

  10. Identification and Construction of Combinatory Cancer Hallmark-Based Gene Signature Sets to Predict Recurrence and Chemotherapy Benefit in Stage II Colorectal Cancer.

    Science.gov (United States)

    Gao, Shanwu; Tibiche, Chabane; Zou, Jinfeng; Zaman, Naif; Trifiro, Mark; O'Connor-McCourt, Maureen; Wang, Edwin

    2016-01-01

    Decisions regarding adjuvant therapy in patients with stage II colorectal cancer (CRC) have been among the most challenging and controversial in oncology over the past 20 years. To develop robust combinatory cancer hallmark-based gene signature sets (CSS sets) that more accurately predict prognosis and identify a subset of patients with stage II CRC who could gain survival benefits from adjuvant chemotherapy. Thirteen retrospective studies of patients with stage II CRC who had clinical follow-up and adjuvant chemotherapy were analyzed. Respective totals of 162 and 843 patients from 2 and 11 independent cohorts were used as the discovery and validation cohorts, respectively. A total of 1005 patients with stage II CRC were included in the 13 cohorts. Among them, 84 of 416 patients in 3 independent cohorts received fluorouracil-based adjuvant chemotherapy. Identification of CSS sets to predict relapse-free survival and identify a subset of patients with stage II CRC who could gain substantial survival benefits from fluorouracil-based adjuvant chemotherapy. Eight cancer hallmark-based gene signatures (30 genes each) were identified and used to construct CSS sets for determining prognosis. The CSS sets were validated in 11 independent cohorts of 767 patients with stage II CRC who did not receive adjuvant chemotherapy. The CSS sets accurately stratified patients into low-, intermediate-, and high-risk groups. Five-year relapse-free survival rates were 94%, 78%, and 45%, respectively, representing 60%, 28%, and 12% of patients with stage II disease. The 416 patients with CSS set-defined high-risk stage II CRC who received fluorouracil-based adjuvant chemotherapy showed a substantial gain in survival benefits from the treatment (ie, recurrence reduced by 30%-40% in 5 years). The CSS sets substantially outperformed other prognostic predictors of stage 2 CRC. They are more accurate and robust for prognostic predictions and facilitate the identification of patients with stage

  11. Multidimensionally encoded magnetic resonance imaging.

    Science.gov (United States)

    Lin, Fa-Hsuan

    2013-07-01

    Magnetic resonance imaging (MRI) typically achieves spatial encoding by measuring the projection of a q-dimensional object over q-dimensional spatial bases created by linear spatial encoding magnetic fields (SEMs). Recently, imaging strategies using nonlinear SEMs have demonstrated potential advantages for reconstructing images with higher spatiotemporal resolution and reducing peripheral nerve stimulation. In practice, nonlinear SEMs and linear SEMs can be used jointly to further improve the image reconstruction performance. Here, we propose the multidimensionally encoded (MDE) MRI to map a q-dimensional object onto a p-dimensional encoding space where p > q. MDE MRI is a theoretical framework linking imaging strategies using linear and nonlinear SEMs. Using a system of eight surface SEM coils with an eight-channel radiofrequency coil array, we demonstrate the five-dimensional MDE MRI for a two-dimensional object as a further generalization of PatLoc imaging and O-space imaging. We also present a method of optimizing spatial bases in MDE MRI. Results show that MDE MRI with a higher dimensional encoding space can reconstruct images more efficiently and with a smaller reconstruction error when the k-space sampling distribution and the number of samples are controlled. Copyright © 2012 Wiley Periodicals, Inc.

  12. Two multi-dimensional uncertainty relations

    International Nuclear Information System (INIS)

    Skala, L; Kapsa, V

    2008-01-01

    Two multi-dimensional uncertainty relations, one related to the probability density and the other one related to the probability density current, are derived and discussed. Both relations are stronger than the usual uncertainty relations for the coordinates and momentum

  13. Multidimensional artificial field embedding with spatial sensitivity

    CSIR Research Space (South Africa)

    Lunga, D

    2013-06-01

    Full Text Available Multidimensional embedding is a technique useful for characterizing spectral signature relations in hyperspectral images. However, such images consist of disjoint similar spectral classes that are spatially sensitive, thus presenting challenges...

  14. AnovArray: a set of SAS macros for the analysis of variance of gene expression data

    Directory of Open Access Journals (Sweden)

    Renard Jean-Paul

    2005-06-01

    Full Text Available Abstract Background Analysis of variance is a powerful approach to identify differentially expressed genes in a complex experimental design for microarray and macroarray data. The advantage of the anova model is the possibility to evaluate multiple sources of variation in an experiment. Results AnovArray is a package implementing ANOVA for gene expression data using SAS® statistical software. The originality of the package is 1 to quantify the different sources of variation on all genes together, 2 to provide a quality control of the model, 3 to propose two models for a gene's variance estimation and to perform a correction for multiple comparisons. Conclusion AnovArray is freely available at http://www-mig.jouy.inra.fr/stat/AnovArray and requires only SAS® statistical software.

  15. Multidimensional Poverty and Child Survival in India

    Science.gov (United States)

    Mohanty, Sanjay K.

    2011-01-01

    Background Though the concept of multidimensional poverty has been acknowledged cutting across the disciplines (among economists, public health professionals, development thinkers, social scientists, policy makers and international organizations) and included in the development agenda, its measurement and application are still limited. Objectives and Methodology Using unit data from the National Family and Health Survey 3, India, this paper measures poverty in multidimensional space and examine the linkages of multidimensional poverty with child survival. The multidimensional poverty is measured in the dimension of knowledge, health and wealth and the child survival is measured with respect to infant mortality and under-five mortality. Descriptive statistics, principal component analyses and the life table methods are used in the analyses. Results The estimates of multidimensional poverty are robust and the inter-state differentials are large. While infant mortality rate and under-five mortality rate are disproportionately higher among the abject poor compared to the non-poor, there are no significant differences in child survival among educationally, economically and health poor at the national level. State pattern in child survival among the education, economical and health poor are mixed. Conclusion Use of multidimensional poverty measures help to identify abject poor who are unlikely to come out of poverty trap. The child survival is significantly lower among abject poor compared to moderate poor and non-poor. We urge to popularize the concept of multiple deprivations in research and program so as to reduce poverty and inequality in the population. PMID:22046384

  16. Multidimensional poverty and child survival in India.

    Science.gov (United States)

    Mohanty, Sanjay K

    2011-01-01

    Though the concept of multidimensional poverty has been acknowledged cutting across the disciplines (among economists, public health professionals, development thinkers, social scientists, policy makers and international organizations) and included in the development agenda, its measurement and application are still limited. OBJECTIVES AND METHODOLOGY: Using unit data from the National Family and Health Survey 3, India, this paper measures poverty in multidimensional space and examine the linkages of multidimensional poverty with child survival. The multidimensional poverty is measured in the dimension of knowledge, health and wealth and the child survival is measured with respect to infant mortality and under-five mortality. Descriptive statistics, principal component analyses and the life table methods are used in the analyses. The estimates of multidimensional poverty are robust and the inter-state differentials are large. While infant mortality rate and under-five mortality rate are disproportionately higher among the abject poor compared to the non-poor, there are no significant differences in child survival among educationally, economically and health poor at the national level. State pattern in child survival among the education, economical and health poor are mixed. Use of multidimensional poverty measures help to identify abject poor who are unlikely to come out of poverty trap. The child survival is significantly lower among abject poor compared to moderate poor and non-poor. We urge to popularize the concept of multiple deprivations in research and program so as to reduce poverty and inequality in the population.

  17. Multidimensional poverty and child survival in India.

    Directory of Open Access Journals (Sweden)

    Sanjay K Mohanty

    Full Text Available Though the concept of multidimensional poverty has been acknowledged cutting across the disciplines (among economists, public health professionals, development thinkers, social scientists, policy makers and international organizations and included in the development agenda, its measurement and application are still limited. OBJECTIVES AND METHODOLOGY: Using unit data from the National Family and Health Survey 3, India, this paper measures poverty in multidimensional space and examine the linkages of multidimensional poverty with child survival. The multidimensional poverty is measured in the dimension of knowledge, health and wealth and the child survival is measured with respect to infant mortality and under-five mortality. Descriptive statistics, principal component analyses and the life table methods are used in the analyses.The estimates of multidimensional poverty are robust and the inter-state differentials are large. While infant mortality rate and under-five mortality rate are disproportionately higher among the abject poor compared to the non-poor, there are no significant differences in child survival among educationally, economically and health poor at the national level. State pattern in child survival among the education, economical and health poor are mixed.Use of multidimensional poverty measures help to identify abject poor who are unlikely to come out of poverty trap. The child survival is significantly lower among abject poor compared to moderate poor and non-poor. We urge to popularize the concept of multiple deprivations in research and program so as to reduce poverty and inequality in the population.

  18. Two new loci and gene sets related to sex determination and cancer progression are associated with susceptibility to testicular germ cell tumor.

    Science.gov (United States)

    Kristiansen, Wenche; Karlsson, Robert; Rounge, Trine B; Whitington, Thomas; Andreassen, Bettina K; Magnusson, Patrik K; Fosså, Sophie D; Adami, Hans-Olov; Turnbull, Clare; Haugen, Trine B; Grotmol, Tom; Wiklund, Fredrik

    2015-07-15

    Genome-wide association (GWA) studies have reported 19 distinct susceptibility loci for testicular germ cell tumor (TGCT). A GWA study for TGCT was performed by genotyping 610 240 single-nucleotide polymorphisms (SNPs) in 1326 cases and 6687 controls from Sweden and Norway. No novel genome-wide significant associations were observed in this discovery stage. We put forward 27 SNPs from 15 novel regions and 12 SNPs previously reported, for replication in 710 case-parent triads and 289 cases and 290 controls. Predefined biological pathways and processes, in addition to a custom-built sex-determination gene set, were subject to enrichment analyses using Meta-Analysis Gene Set Enrichment of Variant Associations (M) and Improved Gene Set Enrichment Analysis for Genome-wide Association Study (I). In the combined meta-analysis, we observed genome-wide significant association for rs7501939 on chromosome 17q12 (OR = 0.78, 95% CI = 0.72-0.84, P = 1.1 × 10(-9)) and rs2195987 on chromosome 19p12 (OR = 0.76, 95% CI: 0.69-0.84, P = 3.2 × 10(-8)). The marker rs7501939 on chromosome 17q12 is located in an intron of the HNF1B gene, encoding a member of the homeodomain-containing superfamily of transcription factors. The sex-determination gene set (false discovery rate, FDRM cancer and apoptosis, was associated with TGCT (FDR utero are implicated in the development of TGCT. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. SNP-SNP interactions of three new pri-miRNAs with the target gene PGC and multidimensional analysis of H. pylori in the gastric cancer/atrophic gastritis risk in a Chinese population.

    Science.gov (United States)

    Xu, Qian; Wu, Ye-Feng; Li, Ying; He, Cai-Yun; Sun, Li-Ping; Liu, Jing-Wei; Yuan, Yuan

    2016-04-26

    Gastric cancer (GC) is a multistep complex disease involving multiple genes, and gene-gene interactions have a greater effect than a single gene in determining cancer susceptibility. This study aimed to explore the interaction of the let-7e rs8111742, miR-365b rs121224, and miR-4795 rs1002765 single nucleotide polymorphisms (SNPs) with SNPs of the predicted target gene PGC and Helicobacter pylori status in GC and atrophic gastritis (AG) risk. Three miRNA SNPs and seven PGC SNPs were detected in 2448 cases using the Sequenom MassArray platform. Two pairwise combinations of miRNA and PGC SNPs were associated with increased AG risk (let-7e rs8111742 - PGC rs6458238 and miR-4795 rs1002765 - PGC rs9471643). Singly, miR-365b rs121224 and PGC rs6912200 had no effect individually but in combination they demonstrated an epistatic interaction associated with AG risk. Similarly, let-7e rs8111742 and miR-4795 rs1002765 SNPs interacted with H. pylori infection to increase GC risk (rs8111742: Pinteraction = 0.024; rs1002765: Pinteraction = 0.031, respectively). A three-dimensional interaction analysis found miR-4795 rs1002765, PGC rs9471643, and H. pylori infection positively interacted to increase AG risk (Pinteraction = 0.027). Also, let-7e rs8111742, PGC rs6458238, and H. pylori infection positively interacted to increase GC risk (Pinteraction = 0.036). Furthermore, both of these three-dimensional interactions had a dosage-effect correspondence (Ptrend < 0.001) and were verified by MDR. In conclusion, the miRNAs SNPs (let-7e rs8111742 and miR-4795 rs1002765) might have more superior efficiency when combined with PGC SNPs and/or H. pylori for GC or AG risk than a single SNP on its own.

  20. Multidimensional building objects in a Danish geo-information infrastructure perspective

    DEFF Research Database (Denmark)

    Schrøder, Lise

    2002-01-01

    The emerging multidimensional GI- and VR-technologies within the professional disciplines dealing with design, planning and management processes is leading to a demand for four-dimensional building objects as part of the public geo-information infrastructure. The other way around the recognition...... of the building as a four-dimensional geo-phenomenon will provide a reference between different data sets whether representing buildings in two, three or four dimensions. Finally a central issue is the potential in using frameworks of multidimensional representations as interfaces to the available data sets...

  1. Improved multidimensional semiclassical tunneling theory.

    Science.gov (United States)

    Wagner, Albert F

    2013-12-12

    We show that the analytic multidimensional semiclassical tunneling formula of Miller et al. [Miller, W. H.; Hernandez, R.; Handy, N. C.; Jayatilaka, D.; Willets, A. Chem. Phys. Lett. 1990, 172, 62] is qualitatively incorrect for deep tunneling at energies well below the top of the barrier. The origin of this deficiency is that the formula uses an effective barrier weakly related to the true energetics but correctly adjusted to reproduce the harmonic description and anharmonic corrections of the reaction path at the saddle point as determined by second order vibrational perturbation theory. We present an analytic improved semiclassical formula that correctly includes energetic information and allows a qualitatively correct representation of deep tunneling. This is done by constructing a three segment composite Eckart potential that is continuous everywhere in both value and derivative. This composite potential has an analytic barrier penetration integral from which the semiclassical action can be derived and then used to define the semiclassical tunneling probability. The middle segment of the composite potential by itself is superior to the original formula of Miller et al. because it incorporates the asymmetry of the reaction barrier produced by the known reaction exoergicity. Comparison of the semiclassical and exact quantum tunneling probability for the pure Eckart potential suggests a simple threshold multiplicative factor to the improved formula to account for quantum effects very near threshold not represented by semiclassical theory. The deep tunneling limitations of the original formula are echoed in semiclassical high-energy descriptions of bound vibrational states perpendicular to the reaction path at the saddle point. However, typically ab initio energetic information is not available to correct it. The Supporting Information contains a Fortran code, test input, and test output that implements the improved semiclassical tunneling formula.

  2. Heat Stress and Lipopolysaccharide Stimulation of Chicken Macrophage-Like Cell Line Activates Expression of Distinct Sets of Genes.

    Directory of Open Access Journals (Sweden)

    Anna Slawinska

    Full Text Available Acute heat stress requires immediate adjustment of the stressed individual to sudden changes of ambient temperatures. Chickens are particularly sensitive to heat stress due to development of insufficient physiological mechanisms to mitigate its effects. One of the symptoms of heat stress is endotoxemia that results from release of the lipopolysaccharide (LPS from the guts. Heat-related cytotoxicity is mitigated by the innate immune system, which is comprised mostly of phagocytic cells such as monocytes and macrophages. The objective of this study was to analyze the molecular responses of the chicken macrophage-like HD11 cell line to combined heat stress and lipopolysaccharide treatment in vitro. The cells were heat-stressed and then allowed a temperature-recovery period, during which the gene expression was investigated. LPS was added to the cells to mimic the heat-stress-related endotoxemia. Semi high-throughput gene expression analysis was used to study a gene panel comprised of heat shock proteins, stress-related genes, signaling molecules and immune response genes. HD11 cell line responded to heat stress with increased mRNA abundance of the HSP25, HSPA2 and HSPH1 chaperones as well as DNAJA4 and DNAJB6 co-chaperones. The anti-apoptotic gene BAG3 was also highly up-regulated, providing evidence that the cells expressed pro-survival processes. The immune response of the HD11 cell line to LPS in the heat stress environment (up-regulation of CCL4, CCL5, IL1B, IL8 and iNOS was higher than in thermoneutral conditions. However, the peak in the transcriptional regulation of the immune genes was after two hours of temperature-recovery. Therefore, we propose the potential influence of the extracellular heat shock proteins not only in mitigating effects of abiotic stress but also in triggering the higher level of the immune responses. Finally, use of correlation networks for the data analysis aided in discovering subtle differences in the gene

  3. Literature mining, gene-set enrichment and pathway analysis for target identification in Behçet's disease.

    Science.gov (United States)

    Wilson, Paul; Larminie, Christopher; Smith, Rona

    2016-01-01

    To use literature mining to catalogue Behçet's associated genes, and advanced computational methods to improve the understanding of the pathways and signalling mechanisms that lead to the typical clinical characteristics of Behçet's patients. To extend this technique to identify potential treatment targets for further experimental validation. Text mining methods combined with gene enrichment tools, pathway analysis and causal analysis algorithms. This approach identified 247 human genes associated with Behçet's disease and the resulting disease map, comprising 644 nodes and 19220 edges, captured important details of the relationships between these genes and their associated pathways, as described in diverse data repositories. Pathway analysis has identified how Behçet's associated genes are likely to participate in innate and adaptive immune responses. Causal analysis algorithms have identified a number of potential therapeutic strategies for further investigation. Computational methods have captured pertinent features of the prominent disease characteristics presented in Behçet's disease and have highlighted NOD2, ICOS and IL18 signalling as potential therapeutic strategies.

  4. A multi-dimensional sampling method for locating small scatterers

    International Nuclear Information System (INIS)

    Song, Rencheng; Zhong, Yu; Chen, Xudong

    2012-01-01

    A multiple signal classification (MUSIC)-like multi-dimensional sampling method (MDSM) is introduced to locate small three-dimensional scatterers using electromagnetic waves. The indicator is built with the most stable part of signal subspace of the multi-static response matrix on a set of combinatorial sampling nodes inside the domain of interest. It has two main advantages compared to the conventional MUSIC methods. First, the MDSM is more robust against noise. Second, it can work with a single incidence even for multi-scatterers. Numerical simulations are presented to show the good performance of the proposed method. (paper)

  5. A multidimensional continued fraction and some of its statistical properties

    International Nuclear Information System (INIS)

    Baldwin, P.R.

    1992-01-01

    The problem of simultaneously approximating a vector of irrational numbers with rationals is analyzed in a geometrical setting using notions of dynamical systems theory. The author discusses here a (vectorial) multidimensional continued-fraction algorithm (MCFA) of additive type, the generalized mediant algorithm (GMA), and gives a geometrical interpretation to it. He calculates the invariant measure of the GMA shift as well as its Kolmogorov-Sinai (KS) entropy for arbitrary number of irrationals. The KS entropy is related to the growth rate of denominators of the Euclidean algorithm. This is the first analytical calculation of the growth rate of denominators for any MCFA

  6. Sexual and asexual oogenesis require the expression of unique and shared sets of genes in the insect Acyrthosiphon pisum

    Directory of Open Access Journals (Sweden)

    Gallot Aurore

    2012-02-01

    Full Text Available Abstract Background Although sexual reproduction is dominant within eukaryotes, asexual reproduction is widespread and has evolved independently as a derived trait in almost all major taxa. How asexuality evolved in sexual organisms is unclear. Aphids, such as Acyrthosiphon pisum, alternate between asexual and sexual reproductive means, as the production of parthenogenetic viviparous females or sexual oviparous females and males varies in response to seasonal photoperiodism. Consequently, sexual and asexual development in aphids can be analyzed simultaneously in genetically identical individuals. Results We compared the transcriptomes of aphid embryos in the stages of development during which the trajectory of oogenesis is determined for producing sexual or asexual gametes. This study design aimed at identifying genes involved in the onset of the divergent mechanisms that result in the sexual or asexual phenotype. We detected 33 genes that were differentially transcribed in sexual and asexual embryos. Functional annotation by gene ontology (GO showed a biological signature of oogenesis, cell cycle regulation, epigenetic regulation and RNA maturation. In situ hybridizations demonstrated that 16 of the differentially-transcribed genes were specifically expressed in germ cells and/or oocytes of asexual and/or sexual ovaries, and therefore may contribute to aphid oogenesis. We categorized these 16 genes by their transcription patterns in the two types of ovaries; they were: i expressed during sexual and asexual oogenesis; ii expressed during sexual and asexual oogenesis but with different localizations; or iii expressed only during sexual or asexual oogenesis. Conclusions Our results show that asexual and sexual oogenesis in aphids share common genetic programs but diverge by adapting specificities in their respective gene expression profiles in germ cells and oocytes.

  7. gsSKAT: Rapid gene set analysis and multiple testing correction for rare-variant association studies using weighted linear kernels.

    Science.gov (United States)

    Larson, Nicholas B; McDonnell, Shannon; Cannon Albright, Lisa; Teerlink, Craig; Stanford, Janet; Ostrander, Elaine A; Isaacs, William B; Xu, Jianfeng; Cooney, Kathleen A; Lange, Ethan; Schleutker, Johanna; Carpten, John D; Powell, Isaac; Bailey-Wilson, Joan E; Cussenot, Olivier; Cancel-Tassin, Geraldine; Giles, Graham G; MacInnis, Robert J; Maier, Christiane; Whittemore, Alice S; Hsieh, Chih-Lin; Wiklund, Fredrik; Catalona, William J; Foulkes, William; Mandal, Diptasri; Eeles, Rosalind; Kote-Jarai, Zsofia; Ackerman, Michael J; Olson, Timothy M; Klein, Christopher J; Thibodeau, Stephen N; Schaid, Daniel J

    2017-05-01

    Next-generation sequencing technologies have afforded unprecedented characterization of low-frequency and rare genetic variation. Due to low power for single-variant testing, aggregative methods are commonly used to combine observed rare variation within a single gene. Causal variation may also aggregate across multiple genes within relevant biomolecular pathways. Kernel-machine regression and adaptive testing methods for aggregative rare-variant association testing have been demonstrated to be powerful approaches for pathway-level analysis, although these methods tend to be computationally intensive at high-variant dimensionality and require access to complete data. An additional analytical issue in scans of large pathway definition sets is multiple testing correction. Gene set definitions may exhibit substantial genic overlap, and the impact of the resultant correlation in test statistics on Type I error rate control for large agnostic gene set scans has not been fully explored. Herein, we first outline a statistical strategy for aggregative rare-variant analysis using component gene-level linear kernel score test summary statistics as well as derive simple estimators of the effective number of tests for family-wise error rate control. We then conduct extensive simulation studies to characterize the behavior of our approach relative to direct application of kernel and adaptive methods under a variety of conditions. We also apply our method to two case-control studies, respectively, evaluating rare variation in hereditary prostate cancer and schizophrenia. Finally, we provide open-source R code for public use to facilitate easy application of our methods to existing rare-variant analysis results. © 2017 WILEY PERIODICALS, INC.

  8. Cogena, a novel tool for co-expressed gene-set enrichment analysis, applied to drug repositioning and drug mode of action discovery.

    Science.gov (United States)

    Jia, Zhilong; Liu, Ying; Guan, Naiyang; Bo, Xiaochen; Luo, Zhigang; Barnes, Michael R

    2016-05-27

    Drug repositioning, finding new indications for existing drugs, has gained much recent attention as a potentially efficient and economical strategy for accelerating new therapies into the clinic. Although improvement in the sensitivity of computational drug repositioning methods has identified numerous credible repositioning opportunities, few have been progressed. Arguably the "black box" nature of drug action in a new indication is one of the main blocks to progression, highlighting the need for methods that inform on the broader target mechanism in the disease context. We demonstrate that the analysis of co-expressed genes may be a critical first step towards illumination of both disease pathology and mode of drug action. We achieve this using a novel framework, co-expressed gene-set enrichment analysis (cogena) for co-expression analysis of gene expression signatures and gene set enrichment analysis of co-expressed genes. The cogena framework enables simultaneous, pathway driven, disease and drug repositioning analysis. Cogena can be used to illuminate coordinated changes within disease transcriptomes and identify drugs acting mechanistically within this framework. We illustrate this using a psoriatic skin transcriptome, as an exemplar, and recover two widely used Psoriasis drugs (Methotrexate and Ciclosporin) with distinct modes of action. Cogena out-performs the results of Connectivity Map and NFFinder webservers in similar disease transcriptome analyses. Furthermore, we investigated the literature support for the other top-ranked compounds to treat psoriasis and showed how the outputs of cogena analysis can contribute new insight to support the progression of drugs into the clinic. We have made cogena freely available within Bioconductor or https://github.com/zhilongjia/cogena . In conclusion, by targeting co-expressed genes within disease transcriptomes, cogena offers novel biological insight, which can be effectively harnessed for drug discovery and

  9. Redundancy control in pathway databases (ReCiPa): an application for improving gene-set enrichment analysis in Omics studies and "Big data" biology.

    Science.gov (United States)

    Vivar, Juan C; Pemu, Priscilla; McPherson, Ruth; Ghosh, Sujoy

    2013-08-01

    Abstract Unparalleled technological advances have fueled an explosive growth in the scope and scale of biological data and have propelled life sciences into the realm of "Big Data" that cannot be managed or analyzed by conventional approaches. Big Data in the life sciences are driven primarily via a diverse collection of 'omics'-based technologies, including genomics, proteomics, metabolomics, transcriptomics, metagenomics, and lipidomics. Gene-set enrichment analysis is a powerful approach for interrogating large 'omics' datasets, leading to the identification of biological mechanisms associated with observed outcomes. While several factors influence the results from such analysis, the impact from the contents of pathway databases is often under-appreciated. Pathway databases often contain variously named pathways that overlap with one another to varying degrees. Ignoring such redundancies during pathway analysis can lead to the designation of several pathways as being significant due to high content-similarity, rather than truly independent biological mechanisms. Statistically, such dependencies also result in correlated p values and overdispersion, leading to biased results. We investigated the level of redundancies in multiple pathway databases and observed large discrepancies in the nature and extent of pathway overlap. This prompted us to develop the application, ReCiPa (Redundancy Control in Pathway Databases), to control redundancies in pathway databases based on user-defined thresholds. Analysis of genomic and genetic datasets, using ReCiPa-generated overlap-controlled versions of KEGG and Reactome pathways, led to a reduction in redundancy among the top-scoring gene-sets and allowed for the inclusion of additional gene-sets representing possibly novel biological mechanisms. Using obesity as an example, bioinformatic analysis further demonstrated that gene-sets identified from overlap-controlled pathway databases show stronger evidence of prior association

  10. Assessment of topoisomerase II-alpha gene status by dual color chromogenic in situ hybridization in a set of Iraqi patients with invasive breast carcinoma

    Directory of Open Access Journals (Sweden)

    Rasha Abd Alraouf Neama

    2017-01-01

    Full Text Available Background: The human epidermal growth factor receptor 2(HER2 proto-oncogene is overexpressed or amplified in approximately 15%–25% of invasive breast cancers. Approximately 35% of HER2-amplified breast cancers have coamplification of the topoisomerase II-alpha (TOP2A gene encoding an enzyme that is a major target of anthracyclines. Hence, the determination of genetic alteration (amplification or deletion of both genes is considered as an important predictive factor that determines the response of breast cancer patients to treatment. The aims of this study are to determinate TOP2A status gene amplification in a set of Iraqi patients with breast cancer that have had an equivocal (2+ and positive HER2/neu by immunohistochemistry (IHC and to compare the results with estrogen receptor (ER and progesterone receptor (PR and HER2/neu status. Patients and Methods: A cross-sectional prospective study done on 53 patients with invasive breast carcinoma. Twenty-six out of total 53 cases were positive HER2/neu (3+, the remaining 27 equivocal HER2-IHC (2+ cases reanalyzed using dual-color chromogenic in situ hybridization (ZytoVision probe kit for further identification of HER2/neu gene amplification. Using chromogenic in situ hybridization (CISH, TOP2A gene status determination was done for all cases. Results: There is a direct significant correlation between TOP2A gene amplification and HER2/neu positivity, P < 0.05 in that 15 (39.4% out of 38 positive HER2/neu cases were associated with topoisomerase gene amplification. Regarding relation of topoisomerase gene to hormone receptor status (ER and PR, there was a significant negative relationship between the gene and ER receptor status. The higher level of gene amplification was noticed in ER and PR negative cases in about 13 (43.3% and 14 (48.2% for ER and PR, respectively. Conclusion: TOP2A gene status has a significantly positive correlation with HER2/neu status while it has a significantly negative

  11. Genetic variations in the CLNK gene and ZNF518B gene are associated with gout in case-control sample sets.

    Science.gov (United States)

    Jin, Tian-Bo; Ren, Yongchao; Shi, Xugang; Jiri, Mutu; He, Na; Feng, Tian; Yuan, Dongya; Kang, Longli

    2015-07-01

    A genome-wide association study of gout in European populations identified 12 genetic variants strongly associated with risk of gout, but it is unknown whether these variants are also associated with gout risk in Chinese populations. A total of 145 patients with gout and 310 healthy control patients were recruited for a case-control association study. Twelve SNPs of CLNK and ZNF518B gene were genotyped, and association analysis was performed. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the association. Overall, we found four risk alleles for gout in patients: the allele "G" of rs2041215 and rs1686947 in the CLNK gene by dominant model (OR 1.66; 95 % CI 1.04-2.63; p = 0.031) (OR 2.19; 95 % CI 1.38-3.46; p = 0.001) and additive model (OR 1.39; 95 % CI 1.00-1.93; p = 0.049) (OR 1.67; 95 % CI 1.19-2.32; p = 0.003), respectively, and the allele "A" of rs10938799 and rs10016022 in ZNF518B gene by recessive model (OR 4.66; 95 % CI 1.44-15.09; p = 0.008) (OR 4.54; 95 % CI 1.23-16.76; p = 0.020). Further haplotype analysis showed that the TCATTCTGA haplotype of CLNK was more frequent among patients with gout (adjusted OR 0.48; 95 % CI 0.24-0.95; p = 0.036). Additionally, polymorphisms of rs2041215, rs10938799, and rs17467273 were also correlated with clinical pathological parameters. This study provides evidence for gout susceptibility genes, CLNK and ZNF518B, in a Chinese population, which may have potential as diagnostic and prognostic marker for gout patients.

  12. Timing and related artifacts in multidimensional NMR

    International Nuclear Information System (INIS)

    Marion, Dominique

    2012-01-01

    The information content of multidimensional NMR spectra is limited by the presence of several kinds of artifacts that originate from incorrect timing of evolution periods. The objective of this review is to provide tools for successful implementation of published pulse sequences, in which timing and pulse compensations are often implicit. We will analyze the constraints set by the use of Fourier transformation, the spin precession during rectangular or shaped pulses, the Bloch-Siegert effects due to pulse on other spins and the delay introduced by the filters for the acquisition dimension. A frequency dependent phase correction or an incorrect scaling of the first data point leads to baseline offsets or curvature due to the properties of the Fourier transform. Because any r.f. pulse has a finite length, chemical shift is always active during excitation, flip-back, inversion, and refocusing pulses. Rectangular or selective shaped pulses can be split into three periods: an ideal rotation surrounded by two chemical shift evolution periods, which should be subtracted from the adjacent delays to avoid linear phase correction. Bloch-Siegert effects originate from irradiation at frequencies near those observed in the spectrum and can lead to phase or frequency shifts. They can be minimized by simultaneous irradiation on both sides of the observed spins. In terms of timing, the very end of the pulse sequence the acquisition behaves differently since the data are filtered by either analog or digital means. This additional delay is filter and spectrometer specific and should be tuned to minimize the required phase correction. Combined together, all these adjustments lead to perfectly phased spectra with flat baseline and no peak shifts or distortion. (author)

  13. Genetic analysis and fine mapping of LH1 and LH2, a set of complementary genes controlling late heading in rice (Oryza sativa L.).

    Science.gov (United States)

    Liu, Shuang; Wang, Feng; Gao, Li Jun; Li, Jin Hua; Li, Rong Bai; Gao, Han Liang; Deng, Guo Fu; Yang, Jin Shui; Luo, Xiao Jin

    2012-12-01

    Heading date in rice (Oryza sativa L.) is a critical agronomic trait with a complex inheritance. To investigate the genetic basis and mechanism of gene interaction in heading date, we conducted genetic analysis on segregation populations derived from crosses among the indica cultivars Bo B, Yuefeng B and Baoxuan 2. A set of dominant complementary genes controlling late heading, designated LH1 and LH2, were detected by molecular marker mapping. Genetic analysis revealed that Baoxuan 2 contains both dominant genes, while Bo B and Yuefeng B each possess either LH1 or LH2. Using larger populations with segregant ratios of 3 : 1, we fine-mapped LH1 to a 63-kb region near the centromere of chromosome 7 flanked by markers RM5436 and RM8034, and LH2 to a 177-kb region on the short arm of chromosome 8 between flanking markers Indel22468-3 and RM25. Some candidate genes were identified through sequencing of Bo B and Yuefeng B in these target regions. Our work provides a solid foundation for further study on gene interaction in heading date and has application in marker-assisted breeding of photosensitive hybrid rice in China.

  14. Genome-wide methylation analysis identifies a core set of hypermethylated genes in CIMP-H colorectal cancer.

    Science.gov (United States)

    McInnes, Tyler; Zou, Donghui; Rao, Dasari S; Munro, Francesca M; Phillips, Vicky L; McCall, John L; Black, Michael A; Reeve, Anthony E; Guilford, Parry J

    2017-03-28

    Aberrant DNA methylation profiles are a characteristic of all known cancer types, epitomized by the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). Hypermethylation has been observed at CpG islands throughout the genome, but it is unclear which factors determine whether an individual island becomes methylated in cancer. DNA methylation in CRC was analysed using the Illumina HumanMethylation450K array. Differentially methylated loci were identified using Significance Analysis of Microarrays (SAM) and the Wilcoxon Signed Rank (WSR) test. Unsupervised hierarchical clustering was used to identify methylation subtypes in CRC. In this study we characterized the DNA methylation profiles of 94 CRC tissues and their matched normal counterparts. Consistent with previous studies, unsupervized hierarchical clustering of genome-wide methylation data identified three subtypes within the tumour samples, designated CIMP-H, CIMP-L and CIMP-N, that showed high, low and very low methylation levels, respectively. Differential methylation between normal and tumour samples was analysed at the individual CpG level, and at the gene level. The distribution of hypermethylation in CIMP-N tumours showed high inter-tumour variability and appeared to be highly stochastic in nature, whereas CIMP-H tumours exhibited consistent hypermethylation at a subset of genes, in addition to a highly variable background of hypermethylated genes. EYA4, TFPI2 and TLX1 were hypermethylated in more than 90% of all tumours examined. One-hundred thirty-two genes were hypermethylated in 100% of CIMP-H tumours studied and these were highly enriched for functions relating to skeletal system development (Bonferroni adjusted p value =2.88E-15), segment specification (adjusted p value =9.62E-11), embryonic development (adjusted p value =1.52E-04), mesoderm development (adjusted p value =1.14E-20), and ectoderm development (adjusted p value =7.94E-16). Our genome-wide characterization of DNA

  15. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  16. Processing multidimensional nuclear physics data

    Energy Technology Data Exchange (ETDEWEB)

    Becker, J. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    Modern Ge detector arrays for gamma-ray spectroscopy are producing data sets unprecedented in size and event multiplicity. Gammasphere, the DOE sponsored array, has the following characteristics: (1) High granularity (110 detectors); (2) High efficiency (10%); and (3) Precision energy measurements (Delta EE = 0.2%). Characteristics of detector line shape, the data set, and the standard practice in the nuclear physics community to the nuclear gamma-ray cascades from the 4096 times 4096 times 4096 data cube will be discussed.

  17. Poster: Observing change in crowded data sets in 3D space - Visualizing gene expression in human tissues

    KAUST Repository

    Rogowski, Marcin

    2013-03-01

    We have been confronted with a real-world problem of visualizing and observing change of gene expression between different human tissues. In this paper, we are presenting a universal representation space based on two-dimensional gel electrophoresis as opposed to force-directed layouts encountered most often in similar problems. We are discussing the methods we devised to make observing change more convenient in a 3D virtual reality environment. © 2013 IEEE.

  18. Independent evolution of the core and accessory gene sets in the genus Neisseria: insights gained from the genome of Neisseria lactamica isolate 020-06

    Directory of Open Access Journals (Sweden)

    White Brian

    2010-11-01

    Full Text Available Abstract Background The genus Neisseria contains two important yet very different pathogens, N. meningitidis and N. gonorrhoeae, in addition to non-pathogenic species, of which N. lactamica is the best characterized. Genomic comparisons of these three bacteria will provide insights into the mechanisms and evolution of pathogenesis in this group of organisms, which are applicable to understanding these processes more generally. Results Non-pathogenic N. lactamica exhibits very similar population structure and levels of diversity to the meningococcus, whilst gonococci are essentially recent descendents of a single clone. All three species share a common core gene set estimated to comprise around 1190 CDSs, corresponding to about 60% of the genome. However, some of the nucleotide sequence diversity within this core genome is particular to each group, indicating that cross-species recombination is rare in this shared core gene set. Other than the meningococcal cps region, which encodes the polysaccharide capsule, relatively few members of the large accessory gene pool are exclusive to one species group, and cross-species recombination within this accessory genome is frequent. Conclusion The three Neisseria species groups represent coherent biological and genetic groupings which appear to be maintained by low rates of inter-species horizontal genetic exchange within the core genome. There is extensive evidence for exchange among positively selected genes and the accessory genome and some evidence of hitch-hiking of housekeeping genes with other loci. It is not possible to define a 'pathogenome' for this group of organisms and the disease causing phenotypes are therefore likely to be complex, polygenic, and different among the various disease-associated phenotypes observed.

  19. Multi-Dimensional Aggregation for Temporal Data

    DEFF Research Database (Denmark)

    Böhlen, M. H.; Gamper, J.; Jensen, Christian Søndergaard

    2006-01-01

    Business Intelligence solutions, encompassing technologies such as multi-dimensional data modeling and aggregate query processing, are being applied increasingly to non-traditional data. This paper extends multi-dimensional aggregation to apply to data with associated interval values that capture...... that the data holds for each point in the interval, as well as the case where the data holds only for the entire interval, but must be adjusted to apply to sub-intervals. The paper reports on an implementation of the new operator and on an empirical study that indicates that the operator scales to large data...

  20. Multi-dimensional Laplace transforms and applications

    International Nuclear Information System (INIS)

    Mughrabi, T.A.

    1988-01-01

    In this dissertation we establish new theorems for computing certain types of multidimensional Laplace transform pairs from known one-dimensional Laplace transforms. The theorems are applied to the most commonly used special functions and so we obtain many two and three dimensional Laplace transform pairs. As applications, some boundary value problems involving linear partial differential equations are solved by the use of multi-dimensional Laplace transformation. Also we establish some relations between the Laplace transformation and other integral transformation in two variables

  1. Finite Mixture Multilevel Multidimensional Ordinal IRT Models for Large Scale Cross-Cultural Research

    Science.gov (United States)

    de Jong, Martijn G.; Steenkamp, Jan-Benedict E. M.

    2010-01-01

    We present a class of finite mixture multilevel multidimensional ordinal IRT models for large scale cross-cultural research. Our model is proposed for confirmatory research settings. Our prior for item parameters is a mixture distribution to accommodate situations where different groups of countries have different measurement operations, while…

  2. Developing a Multi-Dimensional Evaluation Framework for Faculty Teaching and Service Performance

    Science.gov (United States)

    Baker, Diane F.; Neely, Walter P.; Prenshaw, Penelope J.; Taylor, Patrick A.

    2015-01-01

    A task force was created in a small, AACSB-accredited business school to develop a more comprehensive set of standards for faculty performance. The task force relied heavily on faculty input to identify and describe key dimensions that capture effective teaching and service performance. The result is a multi-dimensional framework that will be used…

  3. Developing Multi-Dimensional Evaluation Criteria for English Learning Websites with University Students and Professors

    Science.gov (United States)

    Liu, Gi-Zen; Liu, Zih-Hui; Hwang, Gwo-Jen

    2011-01-01

    Many English learning websites have been developed worldwide, but little research has been conducted concerning the development of comprehensive evaluation criteria. The main purpose of this study is thus to construct a multi-dimensional set of criteria to help learners and teachers evaluate the quality of English learning websites. These…

  4. Adaptive Multidimensional Scaling : The Spatial Representation of Brand Consideration and Dissimilarity Judgments

    NARCIS (Netherlands)

    Bijmolt, T.H.A.; Wedel, M.; DeSarbo, W.S.

    2002-01-01

    We propose Adaptive Multidimensional Scaling (AMDS) for simultaneously deriving a brand map and market segments using consumer data on cognitive decision sets and brand dissimilarities.In AMDS, the judgment task is adapted to the individual respondent: dissimilarity judgments are collected only for

  5. Exploring Children's Face-Space: A Multidimensional Scaling Analysis of the Mental Representation of Facial Identity

    Science.gov (United States)

    Nishimura, Mayu; Maurer, Daphne; Gao, Xiaoqing

    2009-01-01

    We explored differences in the mental representation of facial identity between 8-year-olds and adults. The 8-year-olds and adults made similarity judgments of a homogeneous set of faces (individual hair cues removed) using an "odd-man-out" paradigm. Multidimensional scaling (MDS) analyses were performed to represent perceived similarity of faces…

  6. UMD-USHbases: a comprehensive set of databases to record and analyse pathogenic mutations and unclassified variants in seven Usher syndrome causing genes.

    Science.gov (United States)

    Baux, David; Faugère, Valérie; Larrieu, Lise; Le Guédard-Méreuze, Sandie; Hamroun, Dalil; Béroud, Christophe; Malcolm, Sue; Claustres, Mireille; Roux, Anne-Françoise

    2008-08-01

    Using the Universal Mutation Database (UMD) software, we have constructed "UMD-USHbases", a set of relational databases of nucleotide variations for seven genes involved in Usher syndrome (MYO7A, CDH23, PCDH15, USH1C, USH1G, USH3A and USH2A). Mutations in the Usher syndrome type I causing genes are also recorded in non-syndromic hearing loss cases and mutations in USH2A in non-syndromic retinitis pigmentosa. Usher syndrome provides a particular challenge for molecular diagnostics because of the clinical and molecular heterogeneity. As many mutations are missense changes, and all the genes also contain apparently non-pathogenic polymorphisms, well-curated databases are crucial for accurate interpretation of pathogenicity. Tools are provided to assess the pathogenicity of mutations, including conservation of amino acids and analysis of splice-sites. Reference amino acid alignments are provided. Apparently non-pathogenic variants in patients with Usher syndrome, at both the nucleotide and amino acid level, are included. The UMD-USHbases currently contain more than 2,830 entries including disease causing mutations, unclassified variants or non-pathogenic polymorphisms identified in over 938 patients. In addition to data collected from 89 publications, 15 novel mutations identified in our laboratory are recorded in MYO7A (6), CDH23 (8), or PCDH15 (1) genes. Information is given on the relative involvement of the seven genes, the number and distribution of variants in each gene. UMD-USHbases give access to a software package that provides specific routines and optimized multicriteria research and sorting tools. These databases should assist clinicians and geneticists seeking information about mutations responsible for Usher syndrome.

  7. Application of multidimensional IRT models to longitudinal data

    NARCIS (Netherlands)

    te Marvelde, J.M.; Glas, Cornelis A.W.; Van Landeghem, Georges; Van Damme, Jan

    2006-01-01

    The application of multidimensional item response theory (IRT) models to longitudinal educational surveys where students are repeatedly measured is discussed and exemplified. A marginal maximum likelihood (MML) method to estimate the parameters of a multidimensional generalized partial credit model

  8. The emergence and evolution of the multidimensional organization

    NARCIS (Netherlands)

    Strikwerda, J.; Stoelhorst, J.W.

    2009-01-01

    The article discusses multidimensional organizations and the evolution of complex organizations. The six characteristics of multidimensional organizations, disadvantages of the successful organizational structure that is categorized as a multidivisional, multi-unit or M-form, research by the

  9. Improving Multidimensional Wireless Sensor Network Lifetime Using Pearson Correlation and Fractal Clustering.

    Science.gov (United States)

    Almeida, Fernando R; Brayner, Angelo; Rodrigues, Joel J P C; Maia, Jose E Bessa

    2017-06-07

    An efficient strategy for reducing message transmission in a wireless sensor network (WSN) is to group sensors by means of an abstraction denoted cluster. The key idea behind the cluster formation process is to identify a set of sensors whose sensed values present some data correlation. Nowadays, sensors are able to simultaneously sense multiple different physical phenomena, yielding in this way multidimensional data. This paper presents three methods for clustering sensors in WSNs whose sensors collect multidimensional data. The proposed approaches implement the concept of multidimensional behavioral clustering . To show the benefits introduced by the proposed methods, a prototype has been implemented and experiments have been carried out on real data. The results prove that the proposed methods decrease the amount of data flowing in the network and present low root-mean-square error (RMSE).

  10. The Role of a Multidimensional Concept of Trust in the Performance of Global Virtual Teams

    Science.gov (United States)

    Bodensteiner, Nan Muir; Stecklein, Jonette M.

    2002-01-01

    This paper focuses on the concept of trust as an important ingredient of effective global virtual team performance. Definitions of trust and virtual teams are presented. The concept of trust is developed from its unilateral application (trust, absence of trust) to a multidimensional concept including cognitive and affective components. The special challenges of a virtual team are then discussed with particular emphasis on how a multidimensional concept of trust impacts these challenges. Propositions suggesting the multidimensional concept of trust moderates the negative impacts of distance, cross cultural and organizational differences, the effects of electronically mediated communication, reluctance to share information and a lack of hi story/future on the performance of virtual teams are stated. The paper concludes with recommendations and a set of techniques to build both cognitive and affective trust in virtual teams.

  11. SAGE - MULTIDIMENSIONAL SELF-ADAPTIVE GRID CODE

    Science.gov (United States)

    Davies, C. B.

    1994-01-01

    acceptable since it makes possible an overall and local error reduction through grid redistribution. SAGE includes the ability to modify the adaption techniques in boundary regions, which substantially improves the flexibility of the adaptive scheme. The vectorial approach used in the analysis also provides flexibility. The user has complete choice of adaption direction and order of sequential adaptions without concern for the computational data structure. Multiple passes are available with no restraint on stepping directions; for each adaptive pass the user can choose a completely new set of adaptive parameters. This facility, combined with the capability of edge boundary control, enables the code to individually adapt multi-dimensional multiple grids. Zonal grids can be adapted while maintaining continuity along the common boundaries. For patched grids, the multiple-pass capability enables complete adaption. SAGE is written in FORTRAN 77 and is intended to be machine independent; however, it requires a FORTRAN compiler which supports NAMELIST input. It has been successfully implemented on Sun series computers, SGI IRIS's, DEC MicroVAX computers, HP series computers, the Cray YMP, and IBM PC compatibles. Source code is provided, but no sample input and output files are provided. The code reads three datafiles: one that contains the initial grid coordinates (x,y,z), one that contains corresponding flow-field variables, and one that contains the user control parameters. It is assumed that the first two datasets are formatted as defined in the plotting software package PLOT3D. Several machine versions of PLOT3D are available from COSMIC. The amount of main memory is dependent on the size of the matrix. The standard distribution medium for SAGE is a 5.25 inch 360K MS-DOS format diskette. It is also available on a .25 inch streaming magnetic tape cartridge in UNIX tar format or on a 9-track 1600 BPI ASCII CARD IMAGE format magnetic tape. SAGE was developed in 1989, first

  12. Multidimensional signaling via wavelet packets

    Science.gov (United States)

    Lindsey, Alan R.

    1995-04-01

    This work presents a generalized signaling strategy for orthogonally multiplexed communication. Wavelet packet modulation (WPM) employs the basis functions from an arbitrary pruning of a full dyadic tree structured filter bank as orthogonal pulse shapes for conventional QAM symbols. The multi-scale modulation (MSM) and M-band wavelet modulation (MWM) schemes which have been recently introduced are handled as special cases, with the added benefit of an entire library of potentially superior sets of basis functions. The figures of merit are derived and it is shown that the power spectral density is equivalent to that for QAM (in fact, QAM is another special case) and hence directly applicable in existing systems employing this standard modulation. Two key advantages of this method are increased flexibility in time-frequency partitioning and an efficient all-digital filter bank implementation, making the WPM scheme more robust to a larger set of interferences (both temporal and sinusoidal) and computationally attractive as well.

  13. Multidimensional Screening as a Pharmacology Laboratory Experience.

    Science.gov (United States)

    Malone, Marvin H.; And Others

    1979-01-01

    A multidimensional pharmacodynamic screening experiment that addresses drug interaction is included in the pharmacology-toxicology laboratory experience of pharmacy students at the University of the Pacific. The student handout with directions for the procedure is reproduced, drug compounds tested are listed, and laboratory evaluation results are…

  14. Continued validation of the Multidimensional Perfectionism Scale.

    Science.gov (United States)

    Clavin, S L; Clavin, R H; Gayton, W F; Broida, J

    1996-06-01

    Scores on the Multidimensional Perfectionism Scale have been correlated with measures of obsessive-compulsive tendencies for women, so the validity of scores on this scale for 41 men was examined. Scores on the Perfectionism Scale were significantly correlated (.47-.03) with scores on the Maudsley Obsessive-Compulsive Inventory.

  15. Multi-dimensional indoor location information model

    NARCIS (Netherlands)

    Xiong, Q.; Zhu, Q.; Zlatanova, S.; Huang, L.; Zhou, Y.; Du, Z.

    2013-01-01

    Aiming at the increasing requirements of seamless indoor and outdoor navigation and location service, a Chinese standard of Multidimensional Indoor Location Information Model is being developed, which defines ontology of indoor location. The model is complementary to 3D concepts like CityGML and

  16. Multi-dimensional quasitoeplitz Markov chains

    Directory of Open Access Journals (Sweden)

    Alexander N. Dudin

    1999-01-01

    Full Text Available This paper deals with multi-dimensional quasitoeplitz Markov chains. We establish a sufficient equilibrium condition and derive a functional matrix equation for the corresponding vector-generating function, whose solution is given algorithmically. The results are demonstrated in the form of examples and applications in queues with BMAP-input, which operate in synchronous random environment.

  17. Multidimensional human dynamics in mobile phone communications.

    Science.gov (United States)

    Quadri, Christian; Zignani, Matteo; Capra, Lorenzo; Gaito, Sabrina; Rossi, Gian Paolo

    2014-01-01

    In today's technology-assisted society, social interactions may be expressed through a variety of techno-communication channels, including online social networks, email and mobile phones (calls, text messages). Consequently, a clear grasp of human behavior through the diverse communication media is considered a key factor in understanding the formation of the today's information society. So far, all previous research on user communication behavior has focused on a sole communication activity. In this paper we move forward another step on this research path by performing a multidimensional study of human sociality as an expression of the use of mobile phones. The paper focuses on user temporal communication behavior in the interplay between the two complementary communication media, text messages and phone calls, that represent the bi-dimensional scenario of analysis. Our study provides a theoretical framework for analyzing multidimensional bursts as the most general burst category, that includes one-dimensional bursts as the simplest case, and offers empirical evidence of their nature by following the combined phone call/text message communication patterns of approximately one million people over three-month period. This quantitative approach enables the design of a generative model rooted in the three most significant features of the multidimensional burst - the number of dimensions, prevalence and interleaving degree - able to reproduce the main media usage attitude. The other findings of the paper include a novel multidimensional burst detection algorithm and an insight analysis of the human media selection process.

  18. Multidimensional stochastic approximation using locally contractive functions

    Science.gov (United States)

    Lawton, W. M.

    1975-01-01

    A Robbins-Monro type multidimensional stochastic approximation algorithm which converges in mean square and with probability one to the fixed point of a locally contractive regression function is developed. The algorithm is applied to obtain maximum likelihood estimates of the parameters for a mixture of multivariate normal distributions.

  19. Multidimensional human dynamics in mobile phone communications.

    Directory of Open Access Journals (Sweden)

    Christian Quadri

    Full Text Available In today's technology-assisted society, social interactions may be expressed through a variety of techno-communication channels, including online social networks, email and mobile phones (calls, text messages. Consequently, a clear grasp of human behavior through the diverse communication media is considered a key factor in understanding the formation of the today's information society. So far, all previous research on user communication behavior has focused on a sole communication activity. In this paper we move forward another step on this research path by performing a multidimensional study of human sociality as an expression of the use of mobile phones. The paper focuses on user temporal communication behavior in the interplay between the two complementary communication media, text messages and phone calls, that represent the bi-dimensional scenario of analysis. Our study provides a theoretical framework for analyzing multidimensional bursts as the most general burst category, that includes one-dimensional bursts as the simplest case, and offers empirical evidence of their nature by following the combined phone call/text message communication patterns of approximately one million people over three-month period. This quantitative approach enables the design of a generative model rooted in the three most significant features of the multidimensional burst - the number of dimensions, prevalence and interleaving degree - able to reproduce the main media usage attitude. The other findings of the paper include a novel multidimensional burst detection algorithm and an insight analysis of the human media selection process.

  20. MCMC estimation of multidimensional IRT models

    NARCIS (Netherlands)

    Beguin, Anton; Glas, Cornelis A.W.

    1998-01-01

    A Bayesian procedure to estimate the three-parameter normal ogive model and a generalization to a model with multidimensional ability parameters are discussed. The procedure is a generalization of a procedure by J. Albert (1992) for estimating the two-parameter normal ogive model. The procedure will

  1. Multidimensional Analysis of Nuclear Detonations

    Science.gov (United States)

    2015-09-17

    Training Command in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Robert C. Slaughter, B.S., M.S. Captain, USAF 16...15-S-029 Abstract Digitized versions of atmospheric nuclear testing films represent a unique data set that enables the scientific community to create...temperature distribution of a nuclear fireball using digitized film . This temperature analysis underwent verification using the Digital Imaging and Remote

  2. Multidimensional Data Model and Query Language for Informetrics.

    Science.gov (United States)

    Niemi, Timo; Hirvonen, Lasse; Jarvelin, Kalervo

    2003-01-01

    Discusses multidimensional data analysis, or online analytical processing (OLAP), which offer a single subject-oriented source for analyzing summary data based on various dimensions. Develops a conceptual/logical multidimensional model for supporting the needs of informetrics, including a multidimensional query language whose basic idea is to…

  3. Alpha-gliadin genes from the A, B, and D genomes of wheat contain different sets of celiac disease epitopes

    Directory of Open Access Journals (Sweden)

    van Veelen Peter A

    2006-01-01

    Full Text Available Abstract Background Bread wheat (Triticum aestivum is an important staple food. However, wheat gluten proteins cause celiac disease (CD in 0.5 to 1% of the general population. Among these proteins, the α-gliadins contain several peptides that are associated to the disease. Results We obtained 230 distinct α-gliadin gene sequences from severaldiploid wheat species representing the ancestral A, B, and D genomes of the hexaploid bread wheat. The large majority of these sequences (87% contained an internal stop codon. All α-gliadin sequences could be distinguished according to the genome of origin on the basis of sequence similarity, of the average length of the polyglutamine repeats, and of the differences in the presence of four peptides that have been identified as T cell stimulatory epitopes in CD patients through binding to HLA-DQ2/8. By sequence similarity, α-gliadins from the public database of hexaploid T. aestivum could be assigned directly to chromosome 6A, 6B, or 6D. T. monococcum (A genome sequences, as well as those from chromosome 6A of bread wheat, almost invariably contained epitope glia-α9 and glia-α20, but never the intact epitopes glia-α and glia-α2. A number of sequences from T. speltoides, as well as a number of sequences fromchromosome 6B of bread wheat, did not contain any of the four T cell epitopes screened for. The sequences from T. tauschii (D genome, as well as those from chromosome 6D of bread wheat, were found to contain all of these T cell epitopes in variable combinations per gene. The differences in epitope composition resulted mainly from point mutations. These substitutions appeared to be genome specific. Conclusion Our analysis shows that α-gliadin sequences from the three genomes of bread wheat form distinct groups. The four known T cell stimulatory epitopes are distributed non-randomly across the sequences, indicating that the three genomes contribute differently to epitope content. A systematic

  4. Multidimensional flamelet-generated manifolds for partially premixed combustion

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Phuc-Danh; Vervisch, Luc; Subramanian, Vallinayagam; Domingo, Pascale [CORIA - CNRS and INSA de Rouen, Technopole du Madrillet, BP 8, 76801 Saint-Etienne-du-Rouvray (France)

    2010-01-15

    Flamelet-generated manifolds have been restricted so far to premixed or diffusion flame archetypes, even though the resulting tables have been applied to nonpremixed and partially premixed flame simulations. By using a projection of the full set of mass conservation species balance equations into a restricted subset of the composition space, unsteady multidimensional flamelet governing equations are derived from first principles, under given hypotheses. During the projection, as in usual one-dimensional flamelets, the tangential strain rate of scalar isosurfaces is expressed in the form of the scalar dissipation rates of the control parameters of the multidimensional flamelet-generated manifold (MFM), which is tested in its five-dimensional form for partially premixed combustion, with two composition space directions and three scalar dissipation rates. It is shown that strain-rate-induced effects can hardly be fully neglected in chemistry tabulation of partially premixed combustion, because of fluxes across iso-equivalence-ratio and iso-progress-of-reaction surfaces. This is illustrated by comparing the 5D flamelet-generated manifold with one-dimensional premixed flame and unsteady strained diffusion flame composition space trajectories. The formal links between the asymptotic behavior of MFM and stratified flame, weakly varying partially premixed front, triple-flame, premixed and nonpremixed edge flames are also evidenced. (author)

  5. Influence of fusion dynamics on fission observables: A multidimensional analysis

    Science.gov (United States)

    Schmitt, C.; Mazurek, K.; Nadtochy, P. N.

    2018-01-01

    An attempt to unfold the respective influence of the fusion and fission stages on typical fission observables, and namely the neutron prescission multiplicity, is proposed. A four-dimensional dynamical stochastic Langevin model is used to calculate the decay by fission of excited compound nuclei produced in a wide set of heavy-ion collisions. The comparison of the results from such a calculation and experimental data is discussed, guided by predictions of the dynamical deterministic HICOL code for the compound-nucleus formation time. While the dependence of the latter on the entrance-channel properties can straigthforwardly explain some observations, a complex interplay between the various parameters of the reaction is found to occur in other cases. A multidimensional analysis of the respective role of these parameters, including entrance-channel asymmetry, bombarding energy, compound-nucleus fissility, angular momentum, and excitation energy, is proposed. It is shown that, depending on the size of the system, apparent inconsistencies may be deduced when projecting onto specific ordering parameters. The work suggests the possibility of delicate compensation effects in governing the measured fission observables, thereby highlighting the necessity of a multidimensional discussion.

  6. Genetic variation in a microRNA-502 minding site in SET8 gene confers clinical outcome of non-small cell lung cancer in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Jiali Xu

    Full Text Available BACKGROUND: Genetic variants may influence microRNA-target interaction through modulate their binding affinity, creating or destroying miRNA-binding sites. SET8, a member of the SET domain-containing methyltransferase, has been implicated in a variety array of biological processes. METHODS: Using Taqman assay, we genotyped a polymorphism rs16917496 T>C within the miR-502 binding site in the 3'-untranslated region of the SET8 gene in 576 non-small cell lung cancer (NSCLC patients. Functions of rs16917496 were investigated using luciferase activity assay and validated by immunostaining. RESULTS: Log-rank test and cox regression indicated that the CC genotype was associated with a longer survival and a reduced risk of death for NSCLC [58.0 vs. 41.0 months, P = 0.031; hazard ratio = 0.44, 95% confidential interval: 0.26-0.74]. Further stepwise regression analysis suggested rs16917496 was an independently favorable factor for prognosis and the protective effect more prominent in never smokers, patients without diabetes and patients who received chemotherapy. A significant interaction was observed between rs16917496 and smoking status in relation to NSCLC survival (PC located at miR-502 binding site contributes to NSCLC survival by altering SET8 expression through modulating miRNA-target interaction.

  7. HU participates in expression of a specific set of genes required for growth and survival at acidic pH in Escherichia coli.

    Science.gov (United States)

    Bi, Hongkai; Sun, Lianle; Fukamachi, Toshihiko; Saito, Hiromi; Kobayashi, Hiroshi

    2009-05-01

    The major histone-like Escherichia coli protein, HU, is composed of alpha and beta subunits respectively encoded by hupA and hupB in Escherichia coli. A mutant deficient in both hupA and hupB grew at a slightly slower rate than the wild type at pH 7.5. Growth of the mutant diminished with a decrease in pH, and no growth was observed at pH 4.6. Mutants of either hupA or hupB grew at all pH levels tested. The arginine-dependent survival at pH 2.5 was diminished approximately 60-fold by the deletion of both hupA and hupB, whereas the survival was slightly affected by the deletion of either hupA or hupB. The mRNA levels of adiA and adiC, which respectively encode arginine decarboxylase and arginine/agmatine antiporter, were low in the mutant deficient in both hupA and hupB. The deletion of both hupA and hupB had little effect on survival at pH 2.5 in the presence of glutamate or lysine, and expression of the genes for glutamate and lysine decarboxylases was not impaired by the deletion of the HU genes. These results suggest that HU regulates expression of the specific set of genes required for growth and survival in acidic environments.

  8. Multidimensional Balanced Efficiency Decision Model

    Directory of Open Access Journals (Sweden)

    Antonella Petrillo

    2015-10-01

    Full Text Available In this paper a multicriteria methodological approach, based on Balanced Scorecard (BSC and Analytic Network Process (ANP, is proposed to evaluate competitiveness performance in luxury sector. A set of specific key performance indicators (KPIs have been proposed. The contribution of our paper is to present the integration of two methodologies, BSC – a multiple perspective framework for performance assessment – and ANP – a decision-making tool to prioritize multiple performance perspectives and indicators and to generate a unified metric that incorporates diversified issues for conducting supply chain improvements. The BSC/ANP model is used to prioritize all performances within a luxury industry. A real case study is presented.

  9. Chunking of Large Multidimensional Arrays

    Energy Technology Data Exchange (ETDEWEB)

    Rotem, Doron; Otoo, Ekow J.; Seshadri, Sridhar

    2007-02-28

    Data intensive scientific computations as well on-lineanalytical processing applications as are done on very large datasetsthat are modeled as k-dimensional arrays. The storage organization ofsuch arrays on disks is done by partitioning the large global array intofixed size hyper-rectangular sub-arrays called chunks or tiles that formthe units of data transfer between disk and memory. Typical queriesinvolve the retrieval of sub-arrays in a manner that accesses all chunksthat overlap the query results. An important metric of the storageefficiency is the expected number of chunks retrieved over all suchqueries. The question that immediately arises is "what shapes of arraychunks give the minimum expected number of chunks over a query workload?"In this paper we develop two probabilistic mathematical models of theproblem and provide exact solutions using steepest descent and geometricprogramming methods. Experimental results, using synthetic workloads onreal life data sets, show that our chunking is much more efficient thanthe existing approximate solutions.

  10. Multidimensional integral representations problems of analytic continuation

    CERN Document Server

    Kytmanov, Alexander M

    2015-01-01

    The monograph is devoted to integral representations for holomorphic functions in several complex variables, such as Bochner-Martinelli, Cauchy-Fantappiè, Koppelman, multidimensional logarithmic residue etc., and their boundary properties. The applications considered are problems of analytic continuation of functions from the boundary of a bounded domain in C^n. In contrast to the well-known Hartogs-Bochner theorem, this book investigates functions with the one-dimensional property of holomorphic extension along complex lines, and includes the problems of receiving multidimensional boundary analogs of the Morera theorem.   This book is a valuable resource for specialists in complex analysis, theoretical physics, as well as graduate and postgraduate students with an understanding of standard university courses in complex, real and functional analysis, as well as algebra and geometry.

  11. Applications of Convex Analysis to Multidimensional Scaling

    OpenAIRE

    Jan de Leeuw

    2011-01-01

    In this paper we discuss the convergence of an algorithm for metric and nonmetric multidimensional scaling that is very similar to the C-matrix algorithm of Guttman. The paper improves some earlier results in two respects. In the first place the analysis is extended to cover general Minkovski metrics, in the second place a more elementary proof of convergence based on results of Robert is presented.

  12. Multidimensional Scaling Visualization using Parametric Similarity Indices

    OpenAIRE

    Machado, J. A. Tenreiro; Lopes, António M.; Galhano, A.M.

    2015-01-01

    In this paper, we apply multidimensional scaling (MDS) and parametric similarity indices (PSI) in the analysis of complex systems (CS). Each CS is viewed as a dynamical system, exhibiting an output time-series to be interpreted as a manifestation of its behavior. We start by adopting a sliding window to sample the original data into several consecutive time periods. Second, we define a given PSI for tracking pieces of data. We then compare the windows for different values of the parameter, an...

  13. Fast multi-dimensional NMR by minimal sampling

    Science.gov (United States)

    Kupče, Ēriks; Freeman, Ray

    2008-03-01

    A new scheme is proposed for very fast acquisition of three-dimensional NMR spectra based on minimal sampling, instead of the customary step-wise exploration of all of evolution space. The method relies on prior experiments to determine accurate values for the evolving frequencies and intensities from the two-dimensional 'first planes' recorded by setting t1 = 0 or t2 = 0. With this prior knowledge, the entire three-dimensional spectrum can be reconstructed by an additional measurement of the response at a single location (t1∗,t2∗) where t1∗ and t2∗ are fixed values of the evolution times. A key feature is the ability to resolve problems of overlap in the acquisition dimension. Applied to a small protein, agitoxin, the three-dimensional HNCO spectrum is obtained 35 times faster than systematic Cartesian sampling of the evolution domain. The extension to multi-dimensional spectroscopy is outlined.

  14. Multi-dimensional virtual system introduced to enhance canonical sampling

    Science.gov (United States)

    Higo, Junichi; Kasahara, Kota; Nakamura, Haruki

    2017-10-01

    When an important process of a molecular system occurs via a combination of two or more rare events, which occur almost independently to one another, computational sampling for the important process is difficult. Here, to sample such a process effectively, we developed a new method, named the "multi-dimensional Virtual-system coupled Monte Carlo (multi-dimensional-VcMC)" method, where the system interacts with a virtual system expressed by two or more virtual coordinates. Each virtual coordinate controls sampling along a reaction coordinate. By setting multiple reaction coordinates to be related to the corresponding rare events, sampling of the important process can be enhanced. An advantage of multi-dimensional-VcMC is its simplicity: Namely, the conformation moves widely in the multi-dimensional reaction coordinate space without knowledge of canonical distribution functions of the system. To examine the effectiveness of the algorithm, we introduced a toy model where two molecules (receptor and its ligand) bind and unbind to each other. The receptor has a deep binding pocket, to which the ligand enters for binding. Furthermore, a gate is set at the entrance of the pocket, and the gate is usually closed. Thus, the molecular binding takes place via the two events: ligand approach to the pocket and gate opening. In two-dimensional (2D)-VcMC, the two molecules exhibited repeated binding and unbinding, and an equilibrated distribution was obtained as expected. A conventional canonical simulation, which was 200 times longer than 2D-VcMC, failed in sampling the binding/unbinding effectively. The current method is applicable to various biological systems.

  15. Fine-scale linkage mapping reveals a small set of candidate genes influencing honey bee grooming behavior in response to Varroa mites.

    Directory of Open Access Journals (Sweden)

    Miguel E Arechavaleta-Velasco

    Full Text Available Populations of honey bees in North America have been experiencing high annual colony mortality for 15-20 years. Many apicultural researchers believe that introduced parasites called Varroa mites (V. destructor are the most important factor in colony deaths. One important resistance mechanism that limits mite population growth in colonies is the ability of some lines of honey bees to groom mites from their bodies. To search for genes influencing this trait, we used an Illumina Bead Station genotyping array to determine the genotypes of several hundred worker bees at over a thousand single-nucleotide polymorphisms in a family that was apparently segregating for alleles influencing this behavior. Linkage analyses provided a genetic map with 1,313 markers anchored to genome sequence. Genotypes were analyzed for association with grooming behavior, measured as the time that individual bees took to initiate grooming after mites were placed on their thoraces. Quantitative-trait-locus interval mapping identified a single chromosomal region that was significant at the chromosome-wide level (p<0.05 on chromosome 5 with a LOD score of 2.72. The 95% confidence interval for quantitative trait locus location contained only 27 genes (honey bee official gene annotation set 2 including Atlastin, Ataxin and Neurexin-1 (AmNrx1, which have potential neurodevelopmental and behavioral effects. Atlastin and Ataxin homologs are associated with neurological diseases in humans. AmNrx1 codes for a presynaptic protein with many alternatively spliced isoforms. Neurexin-1 influences the growth, maintenance and maturation of synapses in the brain, as well as the type of receptors most prominent within synapses. Neurexin-1 has also been associated with autism spectrum disorder and schizophrenia in humans, and self-grooming behavior in mice.

  16. Pathway profiles based on gene-set enrichment analysis in the honey bee Apis mellifera under brood rearing-suppressed conditions.

    Science.gov (United States)

    Kim, Kyungmun; Kim, Ju Hyeon; Kim, Young Ho; Hong, Seong-Eui; Lee, Si Hyeock

    2018-01-01

    Perturbation of normal behaviors in honey bee colonies by any external factor can immediately reduce the colony's capacity for brood rearing, which can eventually lead to colony collapse. To investigate the effects of brood-rearing suppression on the biology of honey bee workers, gene-set enrichment analysis of the transcriptomes of worker bees with or without suppressed brood rearing was performed. When brood rearing was suppressed, pathways associated with both protein degradation and synthesis were simultaneously over-represented in both nurses and foragers, and their overall pathway representation profiles resembled those of normal foragers and nurses, respectively. Thus, obstruction of normal labor induced over-representation in pathways related with reshaping of worker bee physiology, suggesting that transition of labor is physiologically reversible. In addition, some genes associated with the regulation of neuronal excitability, cellular and nutritional stress and aggressiveness were over-expressed under brood rearing suppression perhaps to manage in-hive stress under unfavorable conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Thy1.2 driven expression of transgenic His₆-SUMO2 in the brain of mice alters a restricted set of genes.

    Science.gov (United States)

    Rossner, Moritz J; Tirard, Marilyn

    2014-08-05

    Protein SUMOylation is a post-translational protein modification with a key regulatory role in nerve cell development and function, but its function in mammals in vivo has only been studied cursorily. We generated two new transgenic mouse lines that express His6-tagged SUMO1 and SUMO2 driven by the Thy1.2 promoter. The brains of mice of the two lines express transgenic His6-SUMO peptides and conjugate them to substrates in vivo but cytoarchitecture and synaptic organization of adult transgenic mouse brains are indistinguishable from the wild-type situation. We investigated the impact of transgenic SUMO expression on gene transcription in the hippocampus by performing genome wide analyses using microarrays. Surprisingly, no changes were observed in Thy1.2::His6-SUMO1 transgenic mice and only a restricted set of genes were upregulated in Thy1.2::His6-SUMO2 mice. Among these, Penk1 (Preproenkephalin 1), which encodes Met-enkephalin neuropeptides, showed the highest degree of alteration. Accordingly, a significant increase in Met-enkephalin peptide levels in the hippocampus of Thy1.2::His6-SUMO2 was detected, but the expression levels and cellular localization of Met-enkephalin receptors were not changed. Thus, transgenic neuronal expression of His6-SUMO1 or His6-SUMO2 only induces very minor phenotypical changes in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. A set of genes previously implicated in the hypoxia response might be an important modulator in the rat ear tissue response to mechanical stretch

    Directory of Open Access Journals (Sweden)

    Orgill Dennis

    2007-11-01

    Full Text Available Abstract Background Wounds are increasingly important in our aging societies. Pathologies such as diabetes predispose patients to chronic wounds that can cause pain, infection, and amputation. The vacuum assisted closure device shows remarkable outcomes in wound healing. Its mechanism of action is unclear despite several hypotheses advanced. We previously hypothesized that micromechanical forces can heal wounds. To understand better the biological response of soft tissue to forces, rat ears in vivo were stretched and their gene expression patterns over time obtained. The absolute enrichment (AE algorithm that obtains a combined up and down regulated picture of the expression analysis was implemented. Results With the use of AE, the hypoxia gene set was the most important at a highly significant level. A co-expression network analysis showed that important co-regulated members of the hypoxia pathway include a glucose transporter (slc2a8, heme oxygenase, and nitric oxide synthase2 among others. Conclusion It appears that the hypoxia pathway may be an important modulator of response of soft tissue to forces. This finding gives us insights not only into the underlying biology, but also into clinical interventions that could be designed to mimic within wounded tissue the effects of forces without all the negative effects that forces themselves create.

  19. On fully multidimensional and high order non oscillatory finite volume methods, I

    International Nuclear Information System (INIS)

    Lafon, F.

    1992-11-01

    A fully multidimensional flux formulation for solving nonlinear conservation laws of hyperbolic type is introduced to perform calculations on unstructured grids made of triangular or quadrangular cells. Fluxes are computed across dual median cells with a multidimensional 2D Riemann Solver (R2D Solver) whose intermediate states depend on either a three (on triangle R2DT solver) of four (on quadrangle, R2DQ solver) state solutions prescribed on the three or four sides of a gravity cell. Approximate Riemann solutions are computed via a linearization process of Roe's type involving multidimensional effects. Moreover, a monotonous scheme using stencil and central Lax-Friedrichs corrections on sonic curves are built in. Finally, high order accurate ENO-like (Essentially Non Oscillatory) reconstructions using plane and higher degree polynomial limitations are defined in the set up of finite element Lagrange spaces P k and Q k for k≥0, on triangles and quadrangles, respectively. Numerical experiments involving both linear and nonlinear conservation laws to be solved on unstructured grids indicate the ability of our techniques when dealing with strong multidimensional effects. An application to Euler's equations for the Mach three step problem illustrates the robustness and usefulness of our techniques using triangular and quadrangular grids. (Author). 33 refs., 13 figs

  20. On simplified application of multidimensional Savitzky-Golay filters and differentiators

    Science.gov (United States)

    Shekhar, Chandra

    2016-02-01

    I propose a simplified approach for multidimensional Savitzky-Golay filtering, to enable its fast and easy implementation in scientific and engineering applications. The proposed method, which is derived from a generalized framework laid out by Thornley (D. J. Thornley, "Novel anisotropic multidimensional convolution filters for derivative estimation and reconstruction" in Proceedings of International Conference on Signal Processing and Communications, November 2007), first transforms any given multidimensional problem into a unique one, by transforming coordinates of the sampled data nodes to unity-spaced, uniform data nodes, and then performs filtering and calculates partial derivatives on the unity-spaced nodes. It is followed by transporting the calculated derivatives back onto the original data nodes by using the chain rule of differentiation. The burden to performing the most cumbersome task, which is to carry out the filtering and to obtain derivatives on the unity-spaced nodes, is almost eliminated by providing convolution coefficients for a number of convolution kernel sizes and polynomial orders, up to four spatial dimensions. With the availability of the convolution coefficients, the task of filtering at a data node reduces merely to multiplication of two known matrices. Simplified strategies to adequately address near-boundary data nodes and to calculate partial derivatives there are also proposed. Finally, the proposed methodologies are applied to a three-dimensional experimentally obtained data set, which shows that multidimensional Savitzky-Golay filters and differentiators perform well in both the internal and the near-boundary regions of the domain.

  1. Using the Andrews Plotss to Visualize Multidimensional Data in Multi-criteria Optimization

    Directory of Open Access Journals (Sweden)

    S. V. Groshev

    2015-01-01

    Full Text Available Currently, issues on processing of large data volumes are of great importance. Initially, the Andrews plots have been proposed to show multidimensional statistics on the plane. But as the Andrews plots retain information on the average values of the represented values, distances, and dispersion, the distances between the plots linearly indicate distances between the data points, and it becomes possible to use the plots under consideration for the graphical representation of multi-dimensional data of various kinds. The paper analyses a diversity of various mathematical apparatus for Andrews plotting to visualize multi-dimensional data.The first section provides basic information about the Andrews plots, as well as about a test set of multidimensional data in Iris Fischer’s literature. Analysis of the Andrews plot properties shows that they provide a limitlessly many one-dimensional projections on the vectors and, furthermore, the plots, which are nearer to each other, correspond to nearly points. All this makes it possible to use the plots under consideration for multi-dimensional data representation. The paper considers the Andrews plot formation based on Fourier transform functions, and from the analysis results of plotting based on a set of the test, it draws a conclusion that in this way it is possible to provide clustering of multidimensional data.The second section of the work deals with research of different ways to modify the Andrews plots in order to improve the perception of the graphical representation of multidimensional data. Different variants of the Andrews plot projections on the coordinate planes and arbitrary subspaces are considered. In addition, the paper studies an effect of the Andrews plot scaling on the visual perception of multidimensional data.The paper’s third section describes Andrews plotting based on different polynomials, in particular, Chebyshev and Legendre polynomials. It is shown that the resulting image is

  2. The emergence and evolution of the multidimensional organization

    OpenAIRE

    Strikwerda, J.; Stoelhorst, J.W.

    2009-01-01

    The article discusses multidimensional organizations and the evolution of complex organizations. The six characteristics of multidimensional organizations, disadvantages of the successful organizational structure that is categorized as a multidivisional, multi-unit or M-form, research by the Foundation for Management Studies which suggests that synergies across business divisions can be exploited by the M-form, a team approach to creating economic value, examples of multidimensional firms suc...

  3. An Improved Multidimensional MPA Procedure for Bidirectional Earthquake Excitations

    OpenAIRE

    Wang, Feng; Sun, Jian-Gang; Zhang, Ning

    2014-01-01

    Presently, the modal pushover analysis procedure is extended to multidimensional analysis of structures subjected to multidimensional earthquake excitations. an improved multidimensional modal pushover analysis (IMMPA) method is presented in the paper in order to estimate the response demands of structures subjected to bidirectional earthquake excitations, in which the unidirectional earthquake excitation applied on equivalent SDOF system is replaced by the direct superposition of two compone...

  4. Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity

    Directory of Open Access Journals (Sweden)

    John R. Speakman

    2011-11-01

    Full Text Available The close correspondence between energy intake and expenditure over prolonged time periods, coupled with an apparent protection of the level of body adiposity in the face of perturbations of energy balance, has led to the idea that body fatness is regulated via mechanisms that control intake and energy expenditure. Two models have dominated the discussion of how this regulation might take place. The set point model is rooted in physiology, genetics and molecular biology, and suggests that there is an active feedback mechanism linking adipose tissue (stored energy to intake and expenditure via a set point, presumably encoded in the brain. This model is consistent with many of the biological aspects of energy balance, but struggles to explain the many significant environmental and social influences on obesity, food intake and physical activity. More importantly, the set point model does not effectively explain the ‘obesity epidemic’ – the large increase in body weight and adiposity of a large proportion of individuals in many countries since the 1980s. An alternative model, called the settling point model, is based on the idea that there is passive feedback between the size of the body stores and aspects of expenditure. This model accommodates many of the social and environmental characteristics of energy balance, but struggles to explain some of the biological and genetic aspects. The shortcomings of these two models reflect their failure to address the gene-by-environment interactions that dominate the regulation of body weight. We discuss two additional models – the general intake model and the dual intervention point model – that address this issue and might offer better ways to understand how body fatness is controlled.

  5. Multidimensional Risk Management for Underground Electricity Networks

    Directory of Open Access Journals (Sweden)

    Garcez Thalles V.

    2014-08-01

    Full Text Available In the paper we consider an electricity provider company that makes decision on allocating resources on electric network maintenance. The investments decrease malfunction rate of network nodes. An accidental event (explosion, fire, etc. or a malfunctioning on underground system can have various consequences and in different perspectives, such as deaths and injuries of pedestrians, fires in nearby locations, disturbances in the flow of vehicular traffic, loss to the company image, operating and financial losses, etc. For this reason it is necessary to apply an approach of the risk management that considers the multidimensional view of the consequences. Furthermore an analysis of decision making should consider network dependencies between the nodes of the electricity distribution system. In the paper we propose the use of the simulation to assess the network effects (such as the increase of the probability of other accidental event and the occurrence of blackouts of the dependent nodes in the multidimensional risk assessment in electricity grid. The analyzed effects include node overloading due to malfunction of adjacent nodes and blackouts that take place where there is temporarily no path in the grid between the power plant and a node. The simulation results show that network effects have crucial role for decisions in the network maintenance – outcomes of decisions to repair a particular node in the network can have significant influence on performance of other nodes. However, those dependencies are non-linear. The effects of network connectivity (number of connections between nodes on its multidimensional performance assessment depend heavily on the overloading effect level. The simulation results do not depend on network type structure (random or small world – however simulation outcomes for random networks have shown higher variance compared to small-world networks.

  6. Trust and credibility: measured by multidimensional scaling

    International Nuclear Information System (INIS)

    Warg, L.E.; Bodin, L.

    1998-01-01

    Full text of publication follows: in focus of much of today's research interest in risk communication, is the fact that the communities do not trust policy and decision makers such as politicians, government or industry people. This is especially serious in the years to come when we are expecting risk issues concerning for example the nuclear industry, global warming and hazardous waste, to be even higher on the political and social agenda all over the world. Despite the research efforts devoted to trust, society needs an in depth understanding of trust for conducting successful communication regarding environmental hazards. The present abstract is about an experimental study in psychology where focus has been on the possibility to use the multidimensional scaling technique to explore the characteristics people consider to be of importance when they say that certain persons are credible. In the study, a total of 61 students of the University of Oerebro, Sweden, were required to make comparisons of the similarity between 12 well-known swedish persons from politics science, media, industry, 'TV-world' and literature (two persons at a time), regarding their credibility when making statements about risks in society. In addition, the subjects were rating the importance of 19 factors for the credibility of a source. These 61 persons comprised three groups of students: pedagogists, business economists, and chemists. There were 61 % women and 39% men and the mean age was 23 years. The results will be analyzed using multidimensional scaling technique. Differences between the three groups will be analyzed and presented as well as those between men and women. In addition, the 19 factors will be discussed and considered when trying to label the dimensions accounted for by the multidimensional scaling technique. The result from this study will contribute to our understanding of important factors behind human judgments concerning trust and credibility. It will also point to a

  7. Multidimensional flux-limited advection schemes

    International Nuclear Information System (INIS)

    Thuburn, J.

    1996-01-01

    A general method for building multidimensional shape preserving advection schemes using flux limiters is presented. The method works for advected passive scalars in either compressible or incompressible flow and on arbitrary grids. With a minor modification it can be applied to the equation for fluid density. Schemes using the simplest form of the flux limiter can cause distortion of the advected profile, particularly sideways spreading, depending on the orientation of the flow relative to the grid. This is partly because the simple limiter is too restrictive. However, some straightforward refinements lead to a shape-preserving scheme that gives satisfactory results, with negligible grid-flow angle-dependent distortion

  8. Point Information Gain and Multidimensional Data Analysis

    Directory of Open Access Journals (Sweden)

    Renata Rychtáriková

    2016-10-01

    Full Text Available We generalize the point information gain (PIG and derived quantities, i.e., point information gain entropy (PIE and point information gain entropy density (PIED, for the case of the Rényi entropy and simulate the behavior of PIG for typical distributions. We also use these methods for the analysis of multidimensional datasets. We demonstrate the main properties of PIE/PIED spectra for the real data with the examples of several images and discuss further possible utilizations in other fields of data processing.

  9. New method for solving multidimensional scattering problem

    International Nuclear Information System (INIS)

    Melezhik, V.S.

    1991-01-01

    A new method is developed for solving the quantum mechanical problem of scattering of a particle with internal structure. The multichannel scattering problem is formulated as a system of nonlinear functional equations for the wave function and reaction matrix. The method is successfully tested for the scattering from a nonspherical potential well and a long-range nonspherical scatterer. The method is also applicable to solving the multidimensional Schroedinger equation with a discrete spectrum. As an example the known problem of a hydrogen atom in a homogeneous magnetic field is analyzed

  10. An example of multidimensional analysis: Discriminant analysis

    International Nuclear Information System (INIS)

    Lutz, P.

    1990-01-01

    Among the approaches on the data multi-dimensional analysis, lectures on the discriminant analysis including theoretical and practical aspects are presented. The discrimination problem, the analysis steps and the discrimination categories are stressed. Examples on the descriptive historical analysis, the discrimination for decision making, the demonstration and separation of the top quark are given. In the linear discriminant analysis the following subjects are discussed: Huyghens theorem, projection, discriminant variable, geometrical interpretation, case for g=2, classification method, separation of the top events. Criteria allowing the obtention of relevant results are included [fr

  11. Compositional models for credal sets

    Czech Academy of Sciences Publication Activity Database

    Vejnarová, Jiřina

    2017-01-01

    Roč. 90, č. 1 (2017), s. 359-373 ISSN 0888-613X R&D Projects: GA ČR(CZ) GA16-12010S Institutional support: RVO:67985556 Keywords : Imprecise probabilities * Credal sets * Multidimensional models * Conditional independence Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 2.845, year: 2016 http://library.utia.cas.cz/separaty/2017/MTR/vejnarova-0483288.pdf

  12. Fuzzy Clustering based Methodology for Multidimensional Data Analysis in Computational Forensic Domain

    OpenAIRE

    Kilian Stoffel; Paul Cotofrei; Dong Han

    2012-01-01

    As interdisciplinary domain requiring advanced and innovative methodologies the computational forensics domain is characterized by data being simultaneously large scaled and uncertain multidimensional and approximate. Forensic domain experts trained to discover hidden pattern from crime data are limited in their analysis without the assistance of a computational intelligence approach. In this paper a methodology and an automatic procedure based on fuzzy set theory and designed to infer precis...

  13. Multidimensional improvements induced by an intensive obesity inpatients rehabilitation programme.

    Science.gov (United States)

    Giordano, Francesca; Berteotti, Michela; Budui, Simona; Calgaro, Nicole; Franceschini, Laura; Gilli, Federica; Masiero, Marina; Raschellà, Guido; Salvetti, Sabrina; Taddei, Micol; Schena, Federico; Busetto, Luca

    2017-06-01

    To analyse the short-term effectiveness of an intensive multidimensional inpatient programme specifically developed for patients with severe obesity. A multidisciplinary team managed a 3-week residential programme characterised by the integration of nutritional and physical rehabilitation with psychological and educational intervention. All patients consecutively admitted in 10 months were analysed at admission and discharge for changes in the following domains: anthropometry (weight, body mass index (BMI), waist and neck circumferences), cardiovascular risk factors (glycaemia, HbA1c, lipid profile, blood pressure), quality of life, eating behaviour, and physical performance (VO 2peak by incremental cycle ergometer test, 6-min walking test (6MWT), chair stands test). 136 subjects (61% females, median age 52.7 years) with obesity (mean BMI 43.2 kg/m 2 ) and multiple comorbidities were analysed. A 3.9% BMI reduction and a reduction in waist (-3.8%) and neck (-3.3%) circumferences were observed. Glycaemic control was achieved in 68% of patients with uncontrolled diabetes at admission. Blood pressure control was achieved in all patients with uncontrolled hypertension at admission. Total cholesterol (-16%), LDL-cholesterol (-19%) and triglycerides (-9%) were significantly reduced. Psychometric assessment showed improvements in quality of life perception and binge eating disorder. Finally, a significant improvement in physical performance (+4.7% improvement in VO 2peak , with longer distances in 6MWT and a higher number of standings) was observed. Our preliminary data prove that a 3-week programme determined a clinically significant multi-dimensional improvement in patients with severe obesity. Long-term follow-up data are needed to confirm the efficacy of our rehabilitation setting.

  14. Resolution Improvement in Multidimensional Nuclear Magnetic Resonance Spectroscopy of Proteins

    International Nuclear Information System (INIS)

    Duma, L.

    2004-01-01

    The work presented in this thesis is concerned with both liquid-state and solid-state nuclear magnetic resonance (NMR) spectroscopy. Most of this work is devoted to the investigation by solid-state NMR of C 13 -enriched compounds with the principal aim of presenting techniques devised for further improving the spectral resolution in multidimensional NMR of microcrystalline proteins. In fully C 13 -labelled compounds, the J-coupling induces a broadening of the carbon lineshapes. We show that spin-state-selective technique called IPAP can be successfully combined with standard polarisation transfer schemes in order to remove the J-broadening in multidimensional solid-state NMR correlation experiments of fully C 13 -enriched proteins. We present subsequently two techniques tailored for liquid-state NMR spectroscopy. The carbon directly detected techniques provide chemical shift information for all backbone hetero-nuclei. They are very attracting for the study of large bio-molecular systems or for the investigation of paramagnetic proteins. In the last part of this thesis, we study the spin-echo J-modulation for homonuclear two-spin 1/2 systems. Under magic-angle spinning, the theory of J-induced spin-echo modulation allows to derive a set of modulation regimes which give a spin-echo modulation exactly equal to the J-coupling. We show that the chemical-shift anisotropy and the dipolar interaction tend to stabilize the spin-echo J-modulation. The theoretical conclusions are supported by numerical simulations and experimental results obtained for three representative samples containing C 13 spin pairs. (author)

  15. Multidimensional Learner Model In Intelligent Learning System

    Science.gov (United States)

    Deliyska, B.; Rozeva, A.

    2009-11-01

    The learner model in an intelligent learning system (ILS) has to ensure the personalization (individualization) and the adaptability of e-learning in an online learner-centered environment. ILS is a distributed e-learning system whose modules can be independent and located in different nodes (servers) on the Web. This kind of e-learning is achieved through the resources of the Semantic Web and is designed and developed around a course, group of courses or specialty. An essential part of ILS is learner model database which contains structured data about learner profile and temporal status in the learning process of one or more courses. In the paper a learner model position in ILS is considered and a relational database is designed from learner's domain ontology. Multidimensional modeling agent for the source database is designed and resultant learner data cube is presented. Agent's modules are proposed with corresponding algorithms and procedures. Multidimensional (OLAP) analysis guidelines on the resultant learner module for designing dynamic learning strategy have been highlighted.

  16. Multidimensional biochemical information processing of dynamical patterns.

    Science.gov (United States)

    Hasegawa, Yoshihiko

    2018-02-01

    Cells receive signaling molecules by receptors and relay information via sensory networks so that they can respond properly depending on the type of signal. Recent studies have shown that cells can extract multidimensional information from dynamical concentration patterns of signaling molecules. We herein study how biochemical systems can process multidimensional information embedded in dynamical patterns. We model the decoding networks by linear response functions, and optimize the functions with the calculus of variations to maximize the mutual information between patterns and output. We find that, when the noise intensity is lower, decoders with different linear response functions, i.e., distinct decoders, can extract much information. However, when the noise intensity is higher, distinct decoders do not provide the maximum amount of information. This indicates that, when transmitting information by dynamical patterns, embedding information in multiple patterns is not optimal when the noise intensity is very large. Furthermore, we explore the biochemical implementations of these decoders using control theory and demonstrate that these decoders can be implemented biochemically through the modification of cascade-type networks, which are prevalent in actual signaling pathways.

  17. A Multidimensional Theory of Suicide.

    Science.gov (United States)

    Leenaars, Antoon A; Dieserud, Gudrun; Wenckstern, Susanne; Dyregrov, Kari; Lester, David; Lyke, Jennifer

    2018-04-05

    Theory is the foundation of science; this is true in suicidology. Over decades of studies of suicide notes, Leenaars developed a multidimensional model of suicide, with international (crosscultural) studies and independent verification. To corroborate Leenaars's theory with a psychological autopsy (PA) study, examining age and sex of the decedent, and survivor's relationship to deceased. A PA study in Norway, with 120 survivors/informants was undertaken. Leenaars' theoretical-conceptual (protocol) analysis was undertaken of the survivors' narratives and in-depth interviews combined. Substantial interjudge reliability was noted (κ = .632). Overall, there was considerable confirmatory evidence of Leenaars's intrapsychic and interpersonal factors in suicide survivors' narratives. Differences were found in the age of the decedent, but not in sex, nor in the survivor's closeness of the relationship. Older deceased people were perceived to exhibit more heightened unbearable intrapsychic pain, associated with the suicide. Leenaars's theory has corroborative verification, through the decedents' suicide notes and the survivors' narratives. However, the multidimensional model needs further testing to develop a better evidence-based way of understanding suicide.

  18. CELF family RNA-binding protein UNC-75 regulates two sets of mutually exclusive exons of the unc-32 gene in neuron-specific manners in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Hidehito Kuroyanagi

    Full Text Available An enormous number of alternative pre-mRNA splicing patterns in multicellular organisms are coordinately defined by a limited number of regulatory proteins and cis elements. Mutually exclusive alternative splicing should be strictly regulated and is a challenging model for elucidating regulation mechanisms. Here we provide models of the regulation of two sets of mutually exclusive exons, 4a-4c and 7a-7b, of the Caenorhabditis elegans uncoordinated (unc-32 gene, encoding the a subunit of V0 complex of vacuolar-type H(+-ATPases. We visualize selection patterns of exon 4 and exon 7 in vivo by utilizing a trio and a pair of symmetric fluorescence splicing reporter minigenes, respectively, to demonstrate that they are regulated in tissue-specific manners. Genetic analyses reveal that RBFOX family RNA-binding proteins ASD-1 and FOX-1 and a UGCAUG stretch in intron 7b are involved in the neuron-specific selection of exon 7a. Through further forward genetic screening, we identify UNC-75, a neuron-specific CELF family RNA-binding protein of unknown function, as an essential regulator for the exon 7a selection. Electrophoretic mobility shift assays specify a short fragment in intron 7a as the recognition site for UNC-75 and demonstrate that UNC-75 specifically binds via its three RNA recognition motifs to the element including a UUGUUGUGUUGU stretch. The UUGUUGUGUUGU stretch in the reporter minigenes is actually required for the selection of exon 7a in the nervous system. We compare the amounts of partially spliced RNAs in the wild-type and unc-75 mutant backgrounds and raise a model for the mutually exclusive selection of unc-32 exon 7 by the RBFOX family and UNC-75. The neuron-specific selection of unc-32 exon 4b is also regulated by UNC-75 and the unc-75 mutation suppresses the Unc phenotype of the exon-4b-specific allele of unc-32 mutants. Taken together, UNC-75 is the neuron-specific splicing factor and regulates both sets of the mutually exclusive

  19. [Multidimensional family therapy: which influences, which specificities?].

    Science.gov (United States)

    Bonnaire, C; Bastard, N; Couteron, J-P; Har, A; Phan, O

    2014-10-01

    Among illegal psycho-active drugs, cannabis is the most consumed by French adolescents. Multidimensional family therapy (MDFT) is a family-based outpatient therapy which has been developed for adolescents with drug and behavioral problems. MDFT has shown its effectiveness in adolescents with substance abuse disorders (notably cannabis abuse) not only in the United States but also in Europe (International Cannabis Need of Treatment project). MDFT is a multidisciplinary approach and an evidence-based treatment, at the crossroads of developmental psychology, ecological theories and family therapy. Its psychotherapeutic techniques find its roots in a variety of approaches which include systemic family therapy and cognitive therapy. The aims of this paper are: to describe all the backgrounds of MDFT by highlighting its characteristics; to explain how structural and strategy therapies have influenced this approach; to explore the links between MDFT, brief strategic family therapy and multi systemic family therapy; and to underline the specificities of this family therapy method. The multidimensional family therapy was created on the bases of 1) the integration of multiple therapeutic techniques stemming from various family therapy theories; and 2) studies which have shown family therapy efficiency. Several trials have shown a better efficiency of MDFT compared to group treatment, cognitive-behavioral therapy and home-based treatment. Studies have also highlighted that MDFT led to superior treatment outcomes, especially among young people with severe drug use and psychiatric co-morbidities. In the field of systemic family therapies, MDFT was influenced by: 1) the structural family therapy (S. Minuchin), 2) the strategic family theory (J. Haley), and 3) the intergenerational family therapy (Bowen and Boszormenyi-Nagy). MDFT has specific aspects: MDFT therapists think in a multidimensional perspective (because an adolescent's drug abuse is a multidimensional disorder), they

  20. Multi-dimensional conversion to the ion-hybrid mode

    International Nuclear Information System (INIS)

    Tracy, E.R.; Kaufman, A.N.; Brizard, A.J.; Morehead, J.J.

    1996-01-01

    We first demonstrate that the dispersion matrix for linear conversion of a magnetosonic wave to an ion-hybrid wave (as in a D-T plasma) can be congruently transformed to Friedland's normal form. As a result, this conversion can be represented as a two-step process of successive linear conversions in phase space. We then proceed to study the multi-dimensional case of tokamak geometry. After fourier transforming the toroidal dependence, we deal with the two-dimensional poloidal xy-plane and the two-dimensional k x k y -plane, forming a four-dimensional phase space. The dispersion manifolds for the magnetosonic wave [D M (x, k) = 0] and the ion-hybrid wave [D H (x, k) = 0] are each three-dimensional. (Their intersection, on which mode conversion occurs, is two-dimensional.) The incident magnetosonic wave (radiated by an antenna) is a two-dimensional set of rays (a lagrangian manifold): k(x) = ∇θ(x), with θ(x) the phase of the magnetosonic wave. When these rays pierce the ion-hybrid dispersion manifold, they convert to a set of ion-hybrid rays. Then, when those rays intersect the magnetosonic dispersion manifold, they convert to a set of open-quotes reflectedclose quotes magnetosonic rays. This set of rays is distinct from the set of incident rays that have been reflected by the inner surface of the tokamak plasma. As a result, the total destructive interference that can occur in the one-dimensional case may become only partial. We explore the implications of this startling phenomenon both analytically and geometrically

  1. Improving personality facet scores with multidimensional computer adaptive testing

    DEFF Research Database (Denmark)

    Makransky, Guido; Mortensen, Erik Lykke; Glas, Cees A W

    2013-01-01

    personality tests contain many highly correlated facets. This article investigates the possibility of increasing the precision of the NEO PI-R facet scores by scoring items with multidimensional item response theory and by efficiently administering and scoring items with multidimensional computer adaptive...

  2. Multidimensional Computerized Adaptive Testing for Indonesia Junior High School Biology

    Science.gov (United States)

    Kuo, Bor-Chen; Daud, Muslem; Yang, Chih-Wei

    2015-01-01

    This paper describes a curriculum-based multidimensional computerized adaptive test that was developed for Indonesia junior high school Biology. In adherence to the Indonesian curriculum of different Biology dimensions, 300 items was constructed, and then tested to 2238 students. A multidimensional random coefficients multinomial logit model was…

  3. The Tunneling Method for Global Optimization in Multidimensional Scaling.

    Science.gov (United States)

    Groenen, Patrick J. F.; Heiser, Willem J.

    1996-01-01

    A tunneling method for global minimization in multidimensional scaling is introduced and adjusted for multidimensional scaling with general Minkowski distances. The method alternates a local search step with a tunneling step in which a different configuration is sought with the same STRESS implementation. (SLD)

  4. Multidimensional Physical Self-Concept of Athletes with Physical Disabilities

    Science.gov (United States)

    Shapiro, Deborah R.; Martin, Jeffrey J.

    2010-01-01

    The purposes of this investigation were first to predict reported PA (physical activity) behavior and self-esteem using a multidimensional physical self-concept model and second to describe perceptions of multidimensional physical self-concept (e.g., strength, endurance, sport competence) among athletes with physical disabilities. Athletes (N =…

  5. Multidimensional filter banks and wavelets research developments and applications

    CERN Document Server

    Levy, Bernard

    1997-01-01

    Multidimensional Filter Banks and Wavelets: Reserach Developments and Applications brings together in one place important contributions and up-to-date research results in this important area. Multidimensional Filter Banks and Wavelets: Research Developments and Applications serves as an excellent reference, providing insight into some of the most important research issues in the field.

  6. Supervised and Unsupervised Learning of Multidimensional Acoustic Categories

    Science.gov (United States)

    Goudbeek, Martijn; Swingley, Daniel; Smits, Roel

    2009-01-01

    Learning to recognize the contrasts of a language-specific phonemic repertoire can be viewed as forming categories in a multidimensional psychophysical space. Research on the learning of distributionally defined visual categories has shown that categories defined over 1 dimension are easy to learn and that learning multidimensional categories is…

  7. The PR/SET Domain Zinc Finger Protein Prdm4 Regulates Gene Expression in Embryonic Stem Cells but Plays a Nonessential Role in the Developing Mouse Embryo

    Science.gov (United States)

    Bogani, Debora; Morgan, Marc A. J.; Nelson, Andrew C.; Costello, Ita; McGouran, Joanna F.; Kessler, Benedikt M.

    2013-01-01

    Prdm4 is a highly conserved member of the Prdm family of PR/SET domain zinc finger proteins. Many well-studied Prdm family members play critical roles in development and display striking loss-of-function phenotypes. Prdm4 functional contributions have yet to be characterized. Here, we describe its widespread expression in the early embryo and adult tissues. We demonstrate that DNA binding is exclusively mediated by the Prdm4 zinc finger domain, and we characterize its tripartite consensus sequence via SELEX (systematic evolution of ligands by exponential enrichment) and ChIP-seq (chromatin immunoprecipitation-sequencing) experiments. In embryonic stem cells (ESCs), Prdm4 regulates key pluripotency and differentiation pathways. Two independent strategies, namely, targeted deletion of the zinc finger domain and generation of a EUCOMM LacZ reporter allele, resulted in functional null alleles. However, homozygous mutant embryos develop normally and adults are healthy and fertile. Collectively, these results strongly suggest that Prdm4 functions redundantly with other transcriptional partners to cooperatively regulate gene expression in the embryo and adult animal. PMID:23918801

  8. The AHL- and BDSF-dependent quorum sensing systems control specific and overlapping sets of genes in Burkholderia cenocepacia H111.

    Directory of Open Access Journals (Sweden)

    Nadine Schmid

    Full Text Available Quorum sensing in Burkholderia cenocepacia H111 involves two signalling systems that depend on different signal molecules, namely N-acyl homoserine lactones (AHLs and the diffusible signal factor cis-2-dodecenoic acid (BDSF. Previous studies have shown that AHLs and BDSF control similar phenotypic traits, including biofilm formation, proteolytic activity and pathogenicity. In this study we mapped the BDSF stimulon by RNA-Seq and shotgun proteomics analysis. We demonstrate that a set of the identified BDSF-regulated genes or proteins are also controlled by AHLs, suggesting that the two regulons partially overlap. The detailed analysis of two mutually regulated operons, one encoding three lectins and the other one encoding the large surface protein BapA and its type I secretion machinery, revealed that both AHLs and BDSF are required for full expression, suggesting that the two signalling systems operate in parallel. In accordance with this, we show that both AHLs and BDSF are required for biofilm formation and protease production.

  9. Multidimensional quantum entanglement with large-scale integrated optics.

    Science.gov (United States)

    Wang, Jianwei; Paesani, Stefano; Ding, Yunhong; Santagati, Raffaele; Skrzypczyk, Paul; Salavrakos, Alexia; Tura, Jordi; Augusiak, Remigiusz; Mančinska, Laura; Bacco, Davide; Bonneau, Damien; Silverstone, Joshua W; Gong, Qihuang; Acín, Antonio; Rottwitt, Karsten; Oxenløwe, Leif K; O'Brien, Jeremy L; Laing, Anthony; Thompson, Mark G

    2018-04-20

    The ability to control multidimensional quantum systems is central to the development of advanced quantum technologies. We demonstrate a multidimensional integrated quantum photonic platform able to generate, control, and analyze high-dimensional entanglement. A programmable bipartite entangled system is realized with dimensions up to 15 × 15 on a large-scale silicon photonics quantum circuit. The device integrates more than 550 photonic components on a single chip, including 16 identical photon-pair sources. We verify the high precision, generality, and controllability of our multidimensional technology, and further exploit these abilities to demonstrate previously unexplored quantum applications, such as quantum randomness expansion and self-testing on multidimensional states. Our work provides an experimental platform for the development of multidimensional quantum technologies. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  10. Advanced multi-dimensional imaging of gamma-ray radiation

    International Nuclear Information System (INIS)

    Woodring, Mitchell; Beddingfield, David; Souza, David; Entine, Gerald; Squillante, Michael; Christian, James; Kogan, Alex

    2003-01-01

    The tracking of radiation contamination and distribution has become a high-priority US DOE task. To support DOE needs, Radiation Monitoring Devices Inc. has been actively carrying out research and development on a gamma-radiation imager, RadCam 2000 TM . The imager is based upon a position-sensitive PMT coupled to a scintillator near a MURA coded aperture. The modulated gamma flux detected by the PSPMT is mathematically decoded to produce images that are computer displayed in near real time. Additionally, we have developed a data-manipulation scheme which allows a multi-dimensional data array, comprised of x position, y position, and energy, to be used in the imaging process. In the imager software a gate can be set on a specific isotope energy to reveal where in the field of view the gated data lies or, conversely, a gate can be set on an area in the field of view to examine what isotopes are present in that area. This process is complicated by the FFT decoding process used with the coded aperture; however, we have achieved excellent performance and results are presented here

  11. Development and assessment of Multi-dimensional flow models in the thermal-hydraulic system analysis code MARS

    Energy Technology Data Exchange (ETDEWEB)

    Chung, B. D.; Bae, S. W.; Jeong, J. J.; Lee, S. M

    2005-04-15

    A new multi-dimensional component has been developed to allow for more flexible 3D capabilities in the system code, MARS. This component can be applied in the Cartesian and cylindrical coordinates. For the development of this model, the 3D convection and diffusion terms are implemented in the momentum and energy equation. And a simple Prandtl's mixing length model is applied for the turbulent viscosity. The developed multi-dimensional component was assessed against five conceptual problems with analytic solution. And some SETs are calculated and compared with experimental data. With this newly developed multi-dimensional flow module, the MARS code can realistic calculate the flow fields in pools such as those occurring in the core, steam generators and IRWST.

  12. Development and assessment of Multi-dimensional flow models in the thermal-hydraulic system analysis code MARS

    International Nuclear Information System (INIS)

    Chung, B. D.; Bae, S. W.; Jeong, J. J.; Lee, S. M.

    2005-04-01

    A new multi-dimensional component has been developed to allow for more flexible 3D capabilities in the system code, MARS. This component can be applied in the Cartesian and cylindrical coordinates. For the development of this model, the 3D convection and diffusion terms are implemented in the momentum and energy equation. And a simple Prandtl's mixing length model is applied for the turbulent viscosity. The developed multi-dimensional component was assessed against five conceptual problems with analytic solution. And some SETs are calculated and compared with experimental data. With this newly developed multi-dimensional flow module, the MARS code can realistic calculate the flow fields in pools such as those occurring in the core, steam generators and IRWST

  13. Optical Multidimensional Switching for Data Center Networks

    DEFF Research Database (Denmark)

    Kamchevska, Valerija

    2017-01-01

    . Software controlled switching using an on-chip integrated fiber switch is demonstrated and enabling of additional network functionalities such as multicast and optical grooming is experimentally confirmed. Altogether this work demonstrates the potential of optical switching technologies...... for the purpose of deploying optical switching within the network. First, the Hi-Ring data center architecture is proposed. It is based on optical multidimensional switching nodes that provide switching in hierarchically layered space, wavelength and time domain. The performance of the Hi-Ring architecture...... is evaluated experimentally and successful switching of both high capacity wavelength connections and time-shared subwavelengthconnections is demonstrated. Error-free performance is also achieved when transmitting 7 Tbit/s using multicore fiber, confirming the ability to scale the network. Moreover...

  14. The simulation of multidimensional multiphase flows

    International Nuclear Information System (INIS)

    Lahey, Richard T.

    2005-01-01

    This paper presents an assessment of various models which can be used for the multidimensional simulation of multiphase flows, such as may occur in nuclear reactors. In particular, a model appropriate for the direct numerical simulation (DNS) of multiphase flows and a mechanistically based, three-dimensional, four-field, turbulent, two-fluid computational multiphase fluid dynamics (CMFD) model are discussed. A two-fluid bubbly flow model, which was derived using potential flow theory, can be extended to other flow regimes, but this will normally involve ensemble-averaging the results from direct numerical simulations (DNS) of various flow regimes to provide the detailed numerical data necessary for the development of flow-regime-specific interfacial and wall closure laws

  15. Constraint theory multidimensional mathematical model management

    CERN Document Server

    Friedman, George J

    2017-01-01

    Packed with new material and research, this second edition of George Friedman’s bestselling Constraint Theory remains an invaluable reference for all engineers, mathematicians, and managers concerned with modeling. As in the first edition, this text analyzes the way Constraint Theory employs bipartite graphs and presents the process of locating the “kernel of constraint” trillions of times faster than brute-force approaches, determining model consistency and computational allowability. Unique in its abundance of topological pictures of the material, this book balances left- and right-brain perceptions to provide a thorough explanation of multidimensional mathematical models. Much of the extended material in this new edition also comes from Phan Phan’s PhD dissertation in 2011, titled “Expanding Constraint Theory to Determine Well-Posedness of Large Mathematical Models.” Praise for the first edition: "Dr. George Friedman is indisputably the father of the very powerful methods of constraint theory...

  16. Path integral approach to multidimensional quantum tunnelling

    International Nuclear Information System (INIS)

    Balantekin, A.B.; Takigawa, N.

    1985-01-01

    Path integral formulation of the coupled channel problem in the case of multidimensional quantum tunneling is presented and two-time influence functionals are introduced. The two-time influence functionals are calculated explicitly for the three simplest cases: Harmonic oscillators linearly or quadratically coupled to the translational motion and a system with finite number of equidistant energy levels linearly coupled to the translational motion. The effects of these couplings on the transmission probability are studied for two limiting cases, adiabatic case and when the internal system has a degenerate energy spectrum. The condition for the transmission probability to show a resonant structure is discussed and exemplified. Finally, the properties of the dissipation factor in the adiabatic limit and its correlation with the friction coefficient in the classically accessible region are studied

  17. Security Contents: Politico-Military or Multidimensional?

    Directory of Open Access Journals (Sweden)

    Pere Vilanova

    1997-12-01

    Full Text Available The description of security problems has dramatically changed since the end of the bipolar system, and there are difficulties in building new concepts to comprehend a new and not yet defined international system. In the bipolar world, based on the North-South and East-West axes, security was described as systemic stability built upon deterrence and the defense of the statu quo. After the end of the Cold War, a new concept of multidimensional security was formulated. It lay emphasis on political, social (economic development andinternational (peaceful international relations democracy and the rule of law, putting aside too rapidly the military dimension. Vilanova argues that what have been identified as sources of new threats –narcotrafficking, ecology, migration, terrorism and fundamentalism– are not really new. There is a need to formulate political responses to these risks factors by means of public policies and intergovernmental and supranational action.

  18. Multidimensional Scaling for Orthodontic Root Resorption

    Directory of Open Access Journals (Sweden)

    Cristina Teodora Preoteasa

    2013-01-01

    Full Text Available The paper investigates the risk factors for the severity of orthodontic root resorption. The multidimensional scaling (MDS visualization method is used to investigate the experimental data from patients who received orthodontic treatment at the Department of Orthodontics and Dentofacial Orthopedics, Faculty of Dentistry, “Carol Davila” University of Medicine and Pharmacy, during a period of 4 years. The clusters emerging in the MDS plots reveal features and properties not easily captured by classical statistical tools. The results support the adoption of MDS for tackling the dentistry information and overcoming noise embedded into the data. The method introduced in this paper is rapid, efficient, and very useful for treating the risk factors for the severity of orthodontic root resorption.

  19. Multidimensional student skills with collaborative filtering

    Science.gov (United States)

    Bergner, Yoav; Rayyan, Saif; Seaton, Daniel; Pritchard, David E.

    2013-01-01

    Despite the fact that a physics course typically culminates in one final grade for the student, many instructors and researchers believe that there are multiple skills that students acquire to achieve mastery. Assessment validation and data analysis in general may thus benefit from extension to multidimensional ability. This paper introduces an approach for model determination and dimensionality analysis using collaborative filtering (CF), which is related to factor analysis and item response theory (IRT). Model selection is guided by machine learning perspectives, seeking to maximize the accuracy in predicting which students will answer which items correctly. We apply the CF to response data for the Mechanics Baseline Test and combine the results with prior analysis using unidimensional IRT.

  20. Gender Ideologies in Europe: A Multidimensional Framework.

    Science.gov (United States)

    Grunow, Daniela; Begall, Katia; Buchler, Sandra

    2018-02-01

    The authors argue, in line with recent research, that operationalizing gender ideology as a unidimensional construct ranging from traditional to egalitarian is problematic and propose an alternative framework that takes the multidimensionality of gender ideologies into account. Using latent class analysis, they operationalize their gender ideology framework based on data from the 2008 European Values Study, of which eight European countries reflecting the spectrum of current work-family policies were selected. The authors examine the form in which gender ideologies cluster in the various countries. Five ideology profiles were identified: egalitarian, egalitarian essentialism, intensive parenting, moderate traditional, and traditional. The five ideology profiles were found in all countries, but with pronounced variation in size. Ideologies mixing gender essentialist and egalitarian views appear to have replaced traditional ideologies, even in countries offering some institutional support for gendered separate spheres.

  1. Transport stochastic multi-dimensional media

    International Nuclear Information System (INIS)

    Haran, O.; Shvarts, D.

    1996-01-01

    Many physical phenomena evolve according to known deterministic rules, but in a stochastic media in which the composition changes in space and time. Examples to such phenomena are heat transfer in turbulent atmosphere with non uniform diffraction coefficients, neutron transfer in boiling coolant of a nuclear reactor and radiation transfer through concrete shields. The results of measurements conducted upon such a media are stochastic by nature, and depend on the specific realization of the media. In the last decade there has been a considerable efforts to describe linear particle transport in one dimensional stochastic media composed of several immiscible materials. However, transport in two or three dimensional stochastic media has been rarely addressed. The important effect in multi-dimensional transport that does not appear in one dimension is the ability to bypass obstacles. The current work is an attempt to quantify this effect. (authors)

  2. Transport stochastic multi-dimensional media

    Energy Technology Data Exchange (ETDEWEB)

    Haran, O; Shvarts, D [Israel Atomic Energy Commission, Beersheba (Israel). Nuclear Research Center-Negev; Thiberger, R [Ben-Gurion Univ. of the Negev, Beersheba (Israel)

    1996-12-01

    Many physical phenomena evolve according to known deterministic rules, but in a stochastic media in which the composition changes in space and time. Examples to such phenomena are heat transfer in turbulent atmosphere with non uniform diffraction coefficients, neutron transfer in boiling coolant of a nuclear reactor and radiation transfer through concrete shields. The results of measurements conducted upon such a media are stochastic by nature, and depend on the specific realization of the media. In the last decade there has been a considerable efforts to describe linear particle transport in one dimensional stochastic media composed of several immiscible materials. However, transport in two or three dimensional stochastic media has been rarely addressed. The important effect in multi-dimensional transport that does not appear in one dimension is the ability to bypass obstacles. The current work is an attempt to quantify this effect. (authors).

  3. Multidimensional fractional Schrödinger equation

    Science.gov (United States)

    Rodrigues, M. M.; Vieira, N.

    2012-11-01

    This work is intended to investigate the multi-dimensional space-time fractional Schrödinger equation of the form (CDt0+αu)(t,x) = iħ/2m(C∇βu)(t,x), with ħ the Planck's constant divided by 2π, m is the mass and u(t,x) is a wave function of the particle. Here (CDt0+α,C∇β are operators of the Caputo fractional derivatives, where α ∈]0,1] and β ∈]1,2]. The wave function is obtained using Laplace and Fourier transforms methods and a symbolic operational form of solutions in terms of the Mittag-Leffler functions is exhibited. It is presented an expression for the wave function and for the quantum mechanical probability density. Using Banach fixed point theorem, the existence and uniqueness of solutions is studied for this kind of fractional differential equations.

  4. Multidimensional evaluation on FR cycle systems

    International Nuclear Information System (INIS)

    Nakai, Ryodai; Fujii, Sumio; Takakuma, Katsuyuki; Katoh, Atsushi; Ono, Kiyoshi; Ohtaki, Akira; Shiotani, Hiroki

    2004-01-01

    This report explains some results of the multidimensional evaluation on various fast reactor cycle system concepts from an interim report of the 2nd phase of ''Feasibility Study on Commercialized FR Cycle System''. This method is designed to give more objective and more quantitative evaluations to clarify commercialized system candidate concepts. Here we brief current evaluation method from the five viewpoints of safety, economy, environment, resource and non-proliferation, with some trial evaluation results for some cycles consist of promising technologies in reactor, core and fuel, reprocessing and fuel manufacture. Moreover, we describe FR cycle deployment scenarios which describe advantages and disadvantages of the cycles from the viewpoints of uranium resource and radioactive waste based on long-term nuclear material mass flow analyses and advantages of the deployment of FR cycle itself from the viewpoints of the comparison with alternative power supplies as well as cost and benefit. (author)

  5. Gender Ideologies in Europe: A Multidimensional Framework

    Science.gov (United States)

    Begall, Katia; Buchler, Sandra

    2018-01-01

    The authors argue, in line with recent research, that operationalizing gender ideology as a unidimensional construct ranging from traditional to egalitarian is problematic and propose an alternative framework that takes the multidimensionality of gender ideologies into account. Using latent class analysis, they operationalize their gender ideology framework based on data from the 2008 European Values Study, of which eight European countries reflecting the spectrum of current work–family policies were selected. The authors examine the form in which gender ideologies cluster in the various countries. Five ideology profiles were identified: egalitarian, egalitarian essentialism, intensive parenting, moderate traditional, and traditional. The five ideology profiles were found in all countries, but with pronounced variation in size. Ideologies mixing gender essentialist and egalitarian views appear to have replaced traditional ideologies, even in countries offering some institutional support for gendered separate spheres. PMID:29491532

  6. Polymorphisms in sodium-dependent vitamin C transporter genes and plasma, aqueous humor and lens nucleus ascorbate concentrations in an ascorbate depleted setting.

    Science.gov (United States)

    Senthilkumari, Srinivasan; Talwar, Badri; Dharmalingam, Kuppamuthu; Ravindran, Ravilla D; Jayanthi, Ramamurthy; Sundaresan, Periasamy; Saravanan, Charu; Young, Ian S; Dangour, Alan D; Fletcher, Astrid E

    2014-07-01

    We have previously reported low concentrations of plasma ascorbate and low dietary vitamin C intake in the older Indian population and a strong inverse association of these with cataract. Little is known about ascorbate levels in aqueous humor and lens in populations habitually depleted of ascorbate and no studies in any setting have investigated whether genetic polymorphisms influence ascorbate levels in ocular tissues. Our objectives were to investigate relationships between ascorbate concentrations in plasma, aqueous humor and lens and whether these relationships are influenced by Single Nucleotide Polymorphisms (SNPs) in sodium-dependent vitamin C transporter genes (SLC23A1 and SLC23A2). We enrolled sixty patients (equal numbers of men and women, mean age 63 years) undergoing small incision cataract surgery in southern India. We measured ascorbate concentrations in plasma, aqueous humor and lens nucleus using high performance liquid chromatography. SLC23A1 SNPs (rs4257763, rs6596473) and SLC23A2 SNPs (rs1279683 and rs12479919) were genotyped using a TaqMan assay. Patients were interviewed for lifestyle factors which might influence ascorbate. Plasma vitamin C was normalized by a log10 transformation. Statistical analysis used linear regression with the slope of the within-subject associations estimated using beta (β) coefficients. The ascorbate concentrations (μmol/L) were: plasma ascorbate, median and inter-quartile range (IQR), 15.2 (7.8, 34.5), mean (SD) of aqueous humor ascorbate, 1074 (545) and lens nucleus ascorbate, 0.42 (0.16) (μmol/g lens nucleus wet weight). Minimum allele frequencies were: rs1279683 (0.28), rs12479919 (0.30), rs659647 (0.48). Decreasing concentrations of ocular ascorbate from the common to the rare genotype were observed for rs6596473 and rs12479919. The per allele difference in aqueous humor ascorbate for rs6596473 was -217 μmol/L, p humor ascorbate were higher for the GG genotype of rs6596473: GG, β = 1460 compared to

  7. The necessity-concerns framework: a multidimensional theory benefits from multidimensional analysis.

    Science.gov (United States)

    Phillips, L Alison; Diefenbach, Michael A; Kronish, Ian M; Negron, Rennie M; Horowitz, Carol R

    2014-08-01

    Patients' medication-related concerns and necessity-beliefs predict adherence. Evaluation of the potentially complex interplay of these two dimensions has been limited because of methods that reduce them to a single dimension (difference scores). We use polynomial regression to assess the multidimensional effect of stroke-event survivors' medication-related concerns and necessity beliefs on their adherence to stroke-prevention medication. Survivors (n = 600) rated their concerns, necessity beliefs, and adherence to medication. Confirmatory and exploratory polynomial regression determined the best-fitting multidimensional model. As posited by the necessity-concerns framework (NCF), the greatest and lowest adherence was reported by those necessity weak concerns and strong concerns/weak Necessity-Beliefs, respectively. However, as could not be assessed using a difference-score model, patients with ambivalent beliefs were less adherent than those exhibiting indifference. Polynomial regression allows for assessment of the multidimensional nature of the NCF. Clinicians/Researchers should be aware that concerns and necessity dimensions are not polar opposites.

  8. The Necessity-Concerns-Framework: A Multidimensional Theory Benefits from Multidimensional Analysis

    Science.gov (United States)

    Phillips, L. Alison; Diefenbach, Michael; Kronish, Ian M.; Negron, Rennie M.; Horowitz, Carol R.

    2014-01-01

    Background Patients’ medication-related concerns and necessity-beliefs predict adherence. Evaluation of the potentially complex interplay of these two dimensions has been limited because of methods that reduce them to a single dimension (difference scores). Purpose We use polynomial regression to assess the multidimensional effect of stroke-event survivors’ medication-related concerns and necessity-beliefs on their adherence to stroke-prevention medication. Methods Survivors (n=600) rated their concerns, necessity-beliefs, and adherence to medication. Confirmatory and exploratory polynomial regression determined the best-fitting multidimensional model. Results As posited by the Necessity-Concerns Framework (NCF), the greatest and lowest adherence was reported by those with strong necessity-beliefs/weak concerns and strong concerns/weak necessity-beliefs, respectively. However, as could not be assessed using a difference-score model, patients with ambivalent beliefs were less adherent than those exhibiting indifference. Conclusions Polynomial regression allows for assessment of the multidimensional nature of the NCF. Clinicians/Researchers should be aware that concerns and necessity dimensions are not polar opposites. PMID:24500078

  9. Selecting a set of housekeeping genes for quantitative real-time PCR in normal and tetraploid haemocytes of soft-shell clams, Mya arenaria.

    Science.gov (United States)

    Siah, A; Dohoo, C; McKenna, P; Delaporte, M; Berthe, F C J

    2008-09-01

    The transcripts involved in the molecular mechanisms of haemic neoplasia in relation to the haemocyte ploidy status of the soft-shell clam, Mya arenaria, have yet to be identified. For this purpose, real-time quantitative RT-PCR constitutes a sensitive and efficient technique, which can help determine the gene expression involved in haemocyte tetraploid status in clams affected by haemic neoplasia. One of the critical steps in comparing transcription profiles is the stability of selected housekeeping genes, as well as an accurate normalization. In this study, we selected five reference genes, S18, L37, EF1, EF2 and actin, generally used as single control genes. Their expression was analyzed by real-time quantitative RT-PCR at different levels of haemocyte ploidy status in order to select the most stable genes. Using the geNorm software, our results showed that L37, EF1 and S18 represent the most stable gene expressions related to various ploidy status ranging from 0 to 78% of tetraploid haemocytes in clams sampled in North River (Prince Edward Island, Canada). However, actin gene expression appeared to be highly regulated. Hence, using it as a housekeeping gene in tetraploid haemocytes can result in inaccurate data. To compare gene expression levels related to haemocyte ploidy status in Mya arenaria, using L37, EF1 and S18 as housekeeping genes for accurate normalization is therefore recommended.

  10. Using logistic regression to improve the prognostic value of microarray gene expression data sets: application to early-stage squamous cell carcinoma of the lung and triple negative breast carcinoma.

    Science.gov (United States)

    Mount, David W; Putnam, Charles W; Centouri, Sara M; Manziello, Ann M; Pandey, Ritu; Garland, Linda L; Martinez, Jesse D

    2014-06-10

    Numerous microarray-based prognostic gene expression signatures of primary neoplasms have been published but often with little concurrence between studies, thus limiting their clinical utility. We describe a methodology using logistic regression, which circumvents limitations of conventional Kaplan Meier analysis. We applied this approach to a thrice-analyzed and published squamous cell carcinoma (SQCC) of the lung data set, with the objective of identifying gene expressions predictive of early death versus long survival in early-stage disease. A similar analysis was applied to a data set of triple negative breast carcinoma cases, which present similar clinical challenges. Important to our approach is the selection of homogenous patient groups for comparison. In the lung study, we selected two groups (including only stages I and II), equal in size, of earliest deaths and longest survivors. Genes varying at least four-fold were tested by logistic regression for accuracy of prediction (area under a ROC plot). The gene list was refined by applying two sliding-window analyses and by validations using a leave-one-out approach and model building with validation subsets. In the breast study, a similar logistic regression analysis was used after selecting appropriate cases for comparison. A total of 8594 variable genes were tested for accuracy in predicting earliest deaths versus longest survivors in SQCC. After applying the two sliding window and the leave-one-out analyses, 24 prognostic genes were identified; most of them were B-cell related. When the same data set of stage I and II cases was analyzed using a conventional Kaplan Meier (KM) approach, we identified fewer immune-related genes among the most statistically significant hits; when stage III cases were included, most of the prognostic genes were missed. Interestingly, logistic regression analysis of the breast cancer data set identified many immune-related genes predictive of clinical outcome. Stratification of

  11. Median Modified Wiener Filter for nonlinear adaptive spatial denoising of protein NMR multidimensional spectra

    KAUST Repository

    Cannistraci, Carlo Vittorio

    2015-01-26

    Denoising multidimensional NMR-spectra is a fundamental step in NMR protein structure determination. The state-of-the-art method uses wavelet-denoising, which may suffer when applied to non-stationary signals affected by Gaussian-white-noise mixed with strong impulsive artifacts, like those in multi-dimensional NMR-spectra. Regrettably, Wavelet\\'s performance depends on a combinatorial search of wavelet shapes and parameters; and multi-dimensional extension of wavelet-denoising is highly non-trivial, which hampers its application to multidimensional NMR-spectra. Here, we endorse a diverse philosophy of denoising NMR-spectra: less is more! We consider spatial filters that have only one parameter to tune: the window-size. We propose, for the first time, the 3D extension of the median-modified-Wiener-filter (MMWF), an adaptive variant of the median-filter, and also its novel variation named MMWF*. We test the proposed filters and the Wiener-filter, an adaptive variant of the mean-filter, on a benchmark set that contains 16 two-dimensional and three-dimensional NMR-spectra extracted from eight proteins. Our results demonstrate that the adaptive spatial filters significantly outperform their non-adaptive versions. The performance of the new MMWF* on 2D/3D-spectra is even better than wavelet-denoising. Noticeably, MMWF* produces stable high performance almost invariant for diverse window-size settings: this signifies a consistent advantage in the implementation of automatic pipelines for protein NMR-spectra analysis.

  12. Median Modified Wiener Filter for nonlinear adaptive spatial denoising of protein NMR multidimensional spectra

    KAUST Repository

    Cannistraci, Carlo Vittorio; Abbas, Ahmed; Gao, Xin

    2015-01-01

    Denoising multidimensional NMR-spectra is a fundamental step in NMR protein structure determination. The state-of-the-art method uses wavelet-denoising, which may suffer when applied to non-stationary signals affected by Gaussian-white-noise mixed with strong impulsive artifacts, like those in multi-dimensional NMR-spectra. Regrettably, Wavelet's performance depends on a combinatorial search of wavelet shapes and parameters; and multi-dimensional extension of wavelet-denoising is highly non-trivial, which hampers its application to multidimensional NMR-spectra. Here, we endorse a diverse philosophy of denoising NMR-spectra: less is more! We consider spatial filters that have only one parameter to tune: the window-size. We propose, for the first time, the 3D extension of the median-modified-Wiener-filter (MMWF), an adaptive variant of the median-filter, and also its novel variation named MMWF*. We test the proposed filters and the Wiener-filter, an adaptive variant of the mean-filter, on a benchmark set that contains 16 two-dimensional and three-dimensional NMR-spectra extracted from eight proteins. Our results demonstrate that the adaptive spatial filters significantly outperform their non-adaptive versions. The performance of the new MMWF* on 2D/3D-spectra is even better than wavelet-denoising. Noticeably, MMWF* produces stable high performance almost invariant for diverse window-size settings: this signifies a consistent advantage in the implementation of automatic pipelines for protein NMR-spectra analysis.

  13. PCOTH, a novel gene overexpressed in prostate cancers, promotes prostate cancer cell growth through phosphorylation of oncoprotein TAF-Ibeta/SET.

    Science.gov (United States)

    Anazawa, Yoshio; Nakagawa, Hidewaki; Furihara, Mutsuo; Ashida, Shingo; Tamura, Kenji; Yoshioka, Hiroki; Shuin, Taro; Fujioka, Tomoaki; Katagiri, Toyomasa; Nakamura, Yusuke

    2005-06-01

    Through genome-wide cDNA microarray analysis coupled with microdissection of prostate cancer cells, we identified a novel gene, prostate collagen triple helix (PCOTH), showing overexpression in prostate cancer cells and its precursor cells, prostatic intraepithelial neoplasia (PIN). Immunohistochemical analysis using polyclonal anti-PCOTH antibody confirmed elevated expression of PCOTH, a 100-amino-acid protein containing collagen triple-helix repeats, in prostate cancer cells and PINs. Knocking down PCOTH expression by small interfering RNA (siRNA) resulted in drastic attenuation of prostate cancer cell growth, and concordantly, LNCaP derivative cells that were designed to constitutively express exogenous PCOTH showed higher growth rate than LNCaP cells transfected with mock vector, suggesting the growth-promoting effect of PCOTH on prostate cancer cell. To investigate the biological mechanisms of this growth-promoting effect, we applied two-dimensional differential gel electrophoresis (2D-DIGE) to analyze the phospho-protein fractions in LNCaP cells transfected with PCOTH. We found that the phosphorylation level of oncoprotein TAF-Ibeta/SET was significantly elevated in LNCaP cells transfected with PCOTH than control LNCaP cells, and these findings were confirmed by Western blotting and in-gel kinase assay. Furthermore, knockdown of endogenous TAF-Ibeta expression by siRNA also attenuated viability of prostate cancer cells as well. These findings suggest that PCOTH is involved in growth and survival of prostate cancer cells thorough, in parts, the TAF-Ibeta pathway, and that this molecule should be a promising target for development of new therapeutic strategies for prostate cancers.

  14. ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences

    Directory of Open Access Journals (Sweden)

    Pesole Graziano

    2005-10-01

    Full Text Available Abstract Background: Currently available methods to predict splice sites are mainly based on the independent and progressive alignment of transcript data (mostly ESTs to the genomic sequence. Apart from often being computationally expensive, this approach is vulnerable to several problems – hence the need to develop novel strategies. Results: We propose a method, based on a novel multiple genome-EST alignment algorithm, for the detection of splice sites. To avoid limitations of splice sites prediction (mainly, over-predictions due to independent single EST alignments to the genomic sequence our approach performs a multiple alignment of transcript data to the genomic sequence based on the combined analysis of all available data. We recast the problem of predicting constitutive and alternative splicing as an optimization problem, where the optimal multiple transcript alignment minimizes the number of exons and hence of splice site observations. We have implemented a splice site predictor based on this algorithm in the software tool ASPIC (Alternative Splicing PredICtion. It is distinguished from other methods based on BLAST-like tools by the incorporation of entirely new ad hoc procedures for accurate and computationally efficient transcript alignment and adopts dynamic programming for the refinement of intron boundaries. ASPIC also provides the minimal set of non-mergeable transcript isoforms compatible with the detected splicing events. The ASPIC web resource is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility. Conclusion: Extensive bench marking shows that ASPIC outperforms other existing methods in the detection of novel splicing isoforms and in the minimization of over-predictions. ASPIC also requires a lower computation time for processing a single gene and an EST cluster. The ASPIC web resource is available at http://aspic.algo.disco.unimib.it/aspic-devel/.

  15. RBiomirGS: an all-in-one miRNA gene set analysis solution featuring target mRNA mapping and expression profile integration

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    2018-01-01

    Full Text Available Background With the continuous discovery of microRNA’s (miRNA association with a wide range of biological and cellular processes, expression profile-based functional characterization of such post-transcriptional regulation is crucial for revealing its significance behind particular phenotypes. Profound advancement in bioinformatics has been made to enable in depth investigation of miRNA’s role in regulating cellular and molecular events, resulting in a huge quantity of software packages covering different aspects of miRNA functional analysis. Therefore, an all-in-one software solution is in demand for a comprehensive yet highly efficient workflow. Here we present RBiomirGS, an R package for a miRNA gene set (GS analysis. Methods The package utilizes multiple databases for target mRNA mapping, estimates miRNA effect on the target mRNAs through miRNA expression profile and conducts a logistic regression-based GS enrichment. Additionally, human ortholog Entrez ID conversion functionality is included for target mRNAs. Results By incorporating all the core steps into one package, RBiomirGS eliminates the need for switching between different software packages. The modular structure of RBiomirGS enables various access points to the analysis, with which users can choose the most relevant functionalities for their workflow. Conclusions With RBiomirGS, users are able to assess the functional significance of the miRNA expression profile under the corresponding experimental condition by minimal input and intervention. Accordingly, RBiomirGS encompasses an all-in-one solution for miRNA GS analysis. RBiomirGS is available on GitHub (http://github.com/jzhangc/RBiomirGS. More information including instruction and examples can be found on website (http://kenstoreylab.com/?page_id=2865.

  16. Multi-dimensional discovery of biomarker and phenotype complexes

    Directory of Open Access Journals (Sweden)

    Huang Kun

    2010-10-01

    Full Text Available Abstract Background Given the rapid growth of translational research and personalized healthcare paradigms, the ability to relate and reason upon networks of bio-molecular and phenotypic variables at various levels of granularity in order to diagnose, stage and plan treatments for disease states is highly desirable. Numerous techniques exist that can be used to develop networks of co-expressed or otherwise related genes and clinical features. Such techniques can also be used to create formalized knowledge collections based upon the information incumbent to ontologies and domain literature. However, reports of integrative approaches that bridge such networks to create systems-level models of disease or wellness are notably lacking in the contemporary literature. Results In response to the preceding gap in knowledge and practice, we report upon a prototypical series of experiments that utilize multi-modal approaches to network induction. These experiments are intended to elicit meaningful and significant biomarker-phenotype complexes spanning multiple levels of granularity. This work has been performed in the experimental context of a large-scale clinical and basic science data repository maintained by the National Cancer Institute (NCI funded Chronic Lymphocytic Leukemia Research Consortium. Conclusions Our results indicate that it is computationally tractable to link orthogonal networks of genes, clinical features, and conceptual knowledge to create multi-dimensional models of interrelated biomarkers and phenotypes. Further, our results indicate that such systems-level models contain interrelated bio-molecular and clinical markers capable of supporting hypothesis discovery and testing. Based on such findings, we propose a conceptual model intended to inform the cross-linkage of the results of such methods. This model has as its aim the identification of novel and knowledge-anchored biomarker-phenotype complexes.

  17. Activated Glucocorticoid Receptor Interacts with the INHAT Component Set/TAF-Iβ and Releases it from a Glucocorticoid-responsive Gene Promoter, Relieving Repression: Implications for the Pathogenesis of Glucocorticoid Resistance in Acute Undifferentiated Leukemia with Set-Can Translocation

    Science.gov (United States)

    Ichijo, Takamasa; Chrousos, George P.; Kino, Tomoshige

    2008-01-01

    SUMMARY Set/template-activating factor (TAF)-Iβ, part of the Set-Can oncogene product found in acute undifferentiated leukemia, is a component of the inhibitor of acetyltransferases (INHAT) complex. Set/TAF-Iβ interacted with the DNA-binding domain of the glucocorticoid receptor (GR) in yeast two-hybrid screening, and repressed GR-induced transcriptional activity of a chromatin-integrated glucocorticoid-responsive and a natural promoter. Set/TAF-Iβ was co-precipitated with glucocorticoid response elements (GREs) of these promoters in the absence of dexamethasone, while addition of the hormone caused dissociation of Set/TAF-Iβ from and attraction of the p160-type coactivator GRIP1 to the promoter GREs. Set-Can fusion protein, on the other hand, did not interact with GR, was constitutively co-precipitated with GREs and suppressed GRIP1-induced enhancement of GR transcriptional activity and histone acetylation. Thus, Set/TAF-Iβ acts as a ligand-activated GR-responsive transcriptional repressor, while Set-Can does not retain physiologic responsiveness to ligand-bound GR, possibly contributing to the poor responsiveness of Set-Can-harboring leukemic cells to glucocorticoids. PMID:18096310

  18. Activated glucocorticoid receptor interacts with the INHAT component Set/TAF-Ibeta and releases it from a glucocorticoid-responsive gene promoter, relieving repression: implications for the pathogenesis of glucocorticoid resistance in acute undifferentiated leukemia with Set-Can translocation.

    Science.gov (United States)

    Ichijo, Takamasa; Chrousos, George P; Kino, Tomoshige

    2008-02-13

    Set/template-activating factor (TAF)-Ibeta, part of the Set-Can oncogene product found in acute undifferentiated leukemia, is a component of the inhibitor of acetyltransferases (INHAT) complex. Set/TAF-Ibeta interacted with the DNA-binding domain of the glucocorticoid receptor (GR) in yeast two-hybrid screening, and repressed GR-induced transcriptional activity of a chromatin-integrated glucocorticoid-responsive and a natural promoter. Set/TAF-Ibeta was co-precipitated with glucocorticoid response elements (GREs) of these promoters in the absence of dexamethasone, while addition of the hormone caused dissociation of Set/TAF-Ibeta from and attraction of the p160-type coactivator GRIP1 to the promoter GREs. Set-Can fusion protein, on the other hand, did not interact with GR, was constitutively co-precipitated with GREs and suppressed GRIP1-induced enhancement of GR transcriptional activity and histone acetylation. Thus, Set/TAF-Ibeta acts as a ligand-activated GR-responsive transcriptional repressor, while Set-Can does not retain physiologic responsiveness to ligand-bound GR, possibly contributing to the poor responsiveness of Set-Can-harboring leukemic cells to glucocorticoids.

  19. Bateria Multidimensional de Inteligência Infantil: desenvolvimento de instrumento Multidimensional Battery for Children's Intelligence: development of an instrument

    Directory of Open Access Journals (Sweden)

    Patrícia Waltz Schelini

    2005-12-01

    Full Text Available O estudo objetivou elaborar um conjunto de testes, denominado "Bateria Multidimensional de Inteligência Infantil" ou BMI, para avaliar capacidades do Modelo Cattell-Horn-Carroll. Entre as capacidades avaliadas estão as de inteligência cristalizada, inteligência fluida, velocidade de processamento cognitivo, memória a curto prazo, armazenamento e recuperação associativa a longo prazo e conhecimento quantitativo. A BMI foi composta por nove testes, apresentados a duas amostras de participantes. A primeira foi formada por 240 crianças, com idade entre sete e 12 anos. Constituída para que novos itens fossem testados, a segunda amostra foi formada por outras 206 crianças. Os resultados demonstraram a influência altamente significativa da idade sobre o desempenho dos testes. Os testes Informação Geral, Indução, Desempenho em Matemática, Vocabulário Geral e Vocabulário Ilus-trado apresentaram elevados coeficientes de precisão. A análise dos índices de dificuldade e do poder discriminativo permitiu a seleção do conjunto mais adequado de questões para compor a configuração final da Bateria.The goal of this study was elaborate a set of tests, "Multidimensional Battery for Children's Intelligence" or "BMI", according to the abilities included in the Cattell-Horn-Carroll's Model. Among these abilities are the ability of crystallized intelligence, fluid intelligence, processing speed, short-term memory, long-term storage and retrieval and quantitative knowledge. The BMI was composed by nine tests, presented to two samples of participants. The first sample comprised 240 children whose age ranged from seven to 12 years old. Constituted for the testing of new items, the second sample comprised another 206 children. The results demonstrated that the age had a high influence on the tests performance. Were found high reliability coefficients for the tests General Information, Induction, Mathematics Achievment, General Vocabulary and

  20. A study of multidimensional modeling approaches for data warehouse

    Science.gov (United States)

    Yusof, Sharmila Mat; Sidi, Fatimah; Ibrahim, Hamidah; Affendey, Lilly Suriani

    2016-08-01

    Data warehouse system is used to support the process of organizational decision making. Hence, the system must extract and integrate information from heterogeneous data sources in order to uncover relevant knowledge suitable for decision making process. However, the development of data warehouse is a difficult and complex process especially in its conceptual design (multidimensional modeling). Thus, there have been various approaches proposed to overcome the difficulty. This study surveys and compares the approaches of multidimensional modeling and highlights the issues, trend and solution proposed to date. The contribution is on the state of the art of the multidimensional modeling design.

  1. Secondary Channel Bifurcation Geometry: A Multi-dimensional Problem

    Science.gov (United States)

    Gaeuman, D.; Stewart, R. L.

    2017-12-01

    The construction of secondary channels (or side channels) is a popular strategy for increasing aquatic habitat complexity in managed rivers. Such channels, however, frequently experience aggradation that prevents surface water from entering the side channels near their bifurcation points during periods of relatively low discharge. This failure to maintain an uninterrupted surface water connection with the main channel can reduce the habitat value of side channels for fish species that prefer lotic conditions. Various factors have been proposed as potential controls on the fate of side channels, including water surface slope differences between the main and secondary channels, the presence of main channel secondary circulation, transverse bed slopes, and bifurcation angle. A quantitative assessment of more than 50 natural and constructed secondary channels in the Trinity River of northern California indicates that bifurcations can assume a variety of configurations that are formed by different processes and whose longevity is governed by different sets of factors. Moreover, factors such as bifurcation angle and water surface slope vary with discharge level and are continuously distributed in space, such that they must be viewed as a multi-dimensional field rather than a single-valued attribute that can be assigned to a particular bifurcation.

  2. Multidimensional-DSP Beamformers Using the ROACH-2 FPGA Platform

    Directory of Open Access Journals (Sweden)

    Vishwa Seneviratne

    2017-07-01

    Full Text Available Antenna array-based multi-dimensional infinite-impulse response (IIR digital beamformers are employed in a multitude of radio frequency (RF applications ranging from electronically-scanned radar, radio telescopes, long-range detection and target tracking. A method to design 3D IIR beam filters using 2D IIR beam filters is described. A cascaded 2D IIR beam filter architecture is proposed based on systolic array architecture as an alternative for an existing radar application. Differential-form transfer function and polyphase structures are employed in the design to gain an increase in the speed of operation to gigahertz range. The feasibility of practical implementation of a 4-phase polyphase 2D IIR beam filter is explored. A digital hardware prototype is designed, implemented and tested using a ROACH-2 Field Programmable Gate Array (FPGA platform fitted with a Xilinx Virtex-6 SX475T FPGA chip and multi-input analog-to-digital converters (ADC boards set to a maximum sampling rate of 960 MHz. The article describes a method to build a 3D IIR beamformer using polyphase structures. A comparison of technical specifications of an existing radar application based on phased-array and the proposed 3D IIR beamformer is also explained to illustrate the proposed method to be a better alternative for such applications.

  3. Developing Affective Mental Imagery Stimuli with Multidimensional Scaling

    Directory of Open Access Journals (Sweden)

    Matthew J. Facciani

    2015-06-01

    Full Text Available The goal of this paper is to provide an example of how multidimensional scaling (MDS can be used for stimuli development. The study described in this paper illustrates this process by developing affective mental imagery stimuli using the circumplex model of affect as a guide. The circumplex model of affect argues that all emotions can be described in terms of two underlying primary dimensions: valence and arousal (Russel, 1980. We used MDS to determine if affective mental imagery stimuli obtained from verbal prompts could be separated by arousal and valence to create four distinct categories (high –positive, low-positive, high-negative, and low-negative as seen in other stimuli. 60 students from the University of South Carolina participated in the first experiment to evaluate three sets of stimuli. After being analyzed using MDS, selected stimuli were then assessed again in a second experiment to validate their robust valence and arousal distinctions. The second experiment was conducted with 34 subjects to validate 40 of the best stimuli from experiment 1. It was found that mental imagery stimuli can produce a reliable affective response for the dimensions of valence and arousal and that MDS can be an effective tool for stimuli development.

  4. SIDIS transverse spin azimuthal asymmetries at COMPASS: Multidimensional analysis

    CERN Document Server

    Parsamyan, Bakur

    2015-01-01

    Exploration of transverse spin structure of the nucleon via study of the spin (in)dependent azimuthal asymmetries in semi-inclusive deep inelastic scattering (SIDIS) and Drell-Yan (DY) reactions is one of the main aspects of the broad physics program of the COMPASS experiment (CERN, Switzerland). In past decade COMPASS has collected a considerable amount of polarized deuteron and proton SIDIS data while 2014 and 2015 runs were dedicated to the Drell-Yan measurements. Results on SIDIS azimuthal effects provided so far by COMPASS play an important role in general understanding of the three-dimensional nature of the nucleon. Giving access to the entire "twist-2" set of transverse momentum dependent (TMD) parton distribution functions (PDFs) and fragmentation functions (FFs) COMPASS data are being widely used in phenomenological analyses and experimental data fits. Recent unique and first ever x-$Q^{2}$-z-pT multidimensional results for transverse spin asymmetries obtained by COMPASS serve as a direct and unprece...

  5. [Measuring job satisfaction: development of a multidimensional scale].

    Science.gov (United States)

    Faraci, Palmira; Valenti, Giusy

    2016-01-01

    Although numerous studies have been done on the topic ofjob satisfaction, as regards the Italian research, the construction of specific psychometric instruments is lacking. The present paper is aimed to develop a scale to measure job satisfaction referring to our cultural context. Participants were 222 workers (36.5% males, 63.5% females) with an average age of 38.39 years (SD = 10.91). The formulated items were selected from a large item pool on the basis of the evaluation by a group of expert judges, and the item analysis procedure. In order to establish test validity, the following instruments were also administered: Occupational Stress Indicator, Satisfaction With Life Scale, Rosenberg Self-Esteem Scale, Multidimensional Scale of Perceived Social Support, and Beck Depression Inventory. Both exploratory and confirmatory factor analyses highlighted a 6-factor structure. Those factors were responsible for 51.30% of the total variance. Reliability analyses indicated satisfying internal consistency (ranging from alpha = .73 to alpha = .86). Construct validity was supported by results obtained calculating correlations with the theoretically associated variables. Our findings suggest promising psychometric properties for the presented measure. The instrument could be used in specific programs developed to promote well-being conditions in work settings.

  6. Spatial and multidimensional visualization of Indonesia's village health statistics.

    Science.gov (United States)

    Parmanto, Bambang; Paramita, Maria V; Sugiantara, Wayan; Pramana, Gede; Scotch, Matthew; Burke, Donald S

    2008-06-11

    A community health assessment (CHA) is used to identify and address health issues in a given population. Effective CHA requires timely and comprehensive information from a wide variety of sources, such as: socio-economic data, disease surveillance, healthcare utilization, environmental data, and health resource allocation. Indonesia is a developing country with 235 million inhabitants over 13,000 islands. There are significant barriers to conducting CHA in developing countries like Indonesia, such as the high cost of computing resources and the lack of computing skills necessary to support such an assessment. At the University of Pittsburgh, we have developed the Spatial OLAP (On-Line Analytical Processing) Visualization and Analysis Tool (SOVAT) for performing CHA. SOVAT combines Geographic Information System (GIS) technology along with an advanced multidimensional data warehouse structure to facilitate analysis of large, disparate health, environmental, population, and spatial data. The objective of this paper is to demonstrate the potential of SOVAT for facilitating CHA among developing countries by using health, population, healthcare resources, and spatial data from Indonesia for use in two CHA cases studies. Bureau of Statistics administered data sets from the Indonesian Census, and the Indonesian village statistics, were used in the case studies. The data consisted of: healthcare resources (number of healthcare professionals and facilities), population (census), morbidity and mortality, and spatial (GIS-formatted) information. The data was formatted, combined, and populated into SOVAT for CHA use. Case study 1 involves the distribution of healthcare professionals in Indonesia, while case study 2 involves malaria mortality. Screen shots are shown for both cases. The results for the CHA were retrieved in seconds and presented through the geospatial and numerical SOVAT interface. The case studies show the potential of spatial and multidimensional analysis using

  7. Utilization of the Discrete Differential Evolution for Optimization in Multidimensional Point Clouds.

    Science.gov (United States)

    Uher, Vojtěch; Gajdoš, Petr; Radecký, Michal; Snášel, Václav

    2016-01-01

    The Differential Evolution (DE) is a widely used bioinspired optimization algorithm developed by Storn and Price. It is popular for its simplicity and robustness. This algorithm was primarily designed for real-valued problems and continuous functions, but several modified versions optimizing both integer and discrete-valued problems have been developed. The discrete-coded DE has been mostly used for combinatorial problems in a set of enumerative variants. However, the DE has a great potential in the spatial data analysis and pattern recognition. This paper formulates the problem as a search of a combination of distinct vertices which meet the specified conditions. It proposes a novel approach called the Multidimensional Discrete Differential Evolution (MDDE) applying the principle of the discrete-coded DE in discrete point clouds (PCs). The paper examines the local searching abilities of the MDDE and its convergence to the global optimum in the PCs. The multidimensional discrete vertices cannot be simply ordered to get a convenient course of the discrete data, which is crucial for good convergence of a population. A novel mutation operator utilizing linear ordering of spatial data based on the space filling curves is introduced. The algorithm is tested on several spatial datasets and optimization problems. The experiments show that the MDDE is an efficient and fast method for discrete optimizations in the multidimensional point clouds.

  8. Multidimensional poverty measure and analysis: a case study from Hechi City, China.

    Science.gov (United States)

    Wang, Yanhui; Wang, Baixue

    2016-01-01

    Aiming at the anti-poverty outline of China and the human-environment sustainable development, we propose a multidimensional poverty measure and analysis methodology for measuring the poverty-stricken counties and their contributing factors. We build a set of multidimensional poverty indicators with Chinese characteristics, integrating A-F double cutoffs, dimensional aggregation and decomposition approach, and GIS spatial analysis to evaluate the poor's multidimensional poverty characteristics under different geographic and socioeconomic conditions. The case study from 11 counties of Hechi City shows that, firstly, each county existed at least four respects of poverty, and overall the poverty level showed the spatial pattern of surrounding higher versus middle lower. Secondly, three main poverty contributing factors were unsafe housing, family health and adults' illiteracy, while the secondary factors include fuel type and children enrollment rate, etc., generally demonstrating strong autocorrelation; in terms of poverty degree, the western of the research area shows a significant aggregation effect, whereas the central and the eastern represent significant spatial heterogeneous distribution. Thirdly, under three kinds of socioeconomic classifications, the intra-classification diversities of H, A, and MPI are greater than their inter-classification ones, while each of the three indexes has a positive correlation with both the rocky desertification degree and topographic fragmentation degree, respectively. This study could help policymakers better understand the local poverty by identifying the poor, locating them and describing their characteristics, so as to take differentiated poverty alleviation measures according to specific conditions of each county.

  9. A PCA-Based Change Detection Framework for Multidimensional Data Streams

    KAUST Repository

    Qahtan, Abdulhakim Ali Ali

    2015-08-10

    Detecting changes in multidimensional data streams is an important and challenging task. In unsupervised change detection, changes are usually detected by comparing the distribution in a current (test) window with a reference window. It is thus essential to design divergence metrics and density estimators for comparing the data distributions, which are mostly done for univariate data. Detecting changes in multidimensional data streams brings difficulties to the density estimation and comparisons. In this paper, we propose a framework for detecting changes in multidimensional data streams based on principal component analysis, which is used for projecting data into a lower dimensional space, thus facilitating density estimation and change-score calculations. The proposed framework also has advantages over existing approaches by reducing computational costs with an efficient density estimator, promoting the change-score calculation by introducing effective divergence metrics, and by minimizing the efforts required from users on the threshold parameter setting by using the Page-Hinkley test. The evaluation results on synthetic and real data show that our framework outperforms two baseline methods in terms of both detection accuracy and computational costs.

  10. A DYNAMIC INDEXING SCHEME FOR MULTIDIMENSIONAL DATA

    Directory of Open Access Journals (Sweden)

    Manuk G. Manukyan

    2018-03-01

    Full Text Available We present a new dynamic index structure for multidimensional data. The considered index structure is based on an extended grid file concept. Strengths and weaknesses of the grid files were analyzed. Based on that analysis we proposed to strengthen the concept of grid files by considering their stripes as linear hash tables, introducing the concept of chunk and representing the grid file structure as a graph. As a result we significantly reduced the amount of disk operations. Efficient algorithms for storage and access of index directory are proposed, in order to minimize memory usage and lookup operations complexities. Estimations of complexities for these algorithms are presented. A comparison of our approach to support effective grid file structure with other known approaches is presented. This comparison shows effectiveness of suggested metadata storage environment. An estimation of directory size is presented. A prototype to support of our grid file concept has been created and experimentally compared with MongoDB (a renowned NoSQL database. Comparison results show effectiveness of our approach in the cases of given point lookup, lookup by wide ranges and closest objects lookup when considering more than one dimension, and also better memory usage.

  11. Statistical segmentation of multidimensional brain datasets

    Science.gov (United States)

    Desco, Manuel; Gispert, Juan D.; Reig, Santiago; Santos, Andres; Pascau, Javier; Malpica, Norberto; Garcia-Barreno, Pedro

    2001-07-01

    This paper presents an automatic segmentation procedure for MRI neuroimages that overcomes part of the problems involved in multidimensional clustering techniques like partial volume effects (PVE), processing speed and difficulty of incorporating a priori knowledge. The method is a three-stage procedure: 1) Exclusion of background and skull voxels using threshold-based region growing techniques with fully automated seed selection. 2) Expectation Maximization algorithms are used to estimate the probability density function (PDF) of the remaining pixels, which are assumed to be mixtures of gaussians. These pixels can then be classified into cerebrospinal fluid (CSF), white matter and grey matter. Using this procedure, our method takes advantage of using the full covariance matrix (instead of the diagonal) for the joint PDF estimation. On the other hand, logistic discrimination techniques are more robust against violation of multi-gaussian assumptions. 3) A priori knowledge is added using Markov Random Field techniques. The algorithm has been tested with a dataset of 30 brain MRI studies (co-registered T1 and T2 MRI). Our method was compared with clustering techniques and with template-based statistical segmentation, using manual segmentation as a gold-standard. Our results were more robust and closer to the gold-standard.

  12. Proposed empirical gas geothermometer using multidimensional approach

    Energy Technology Data Exchange (ETDEWEB)

    Supranto; Sudjatmiko; Toha, Budianto; Wintolo, Djoko; Alhamid, Idrus

    1996-01-24

    Several formulas of surface gas geothermometer have been developed to utilize in geothermal exploration, i.e. by D'Amore and Panichi (1980) and by Darling and Talbot (1992). This paper presents an empirical gas geothermometer formula using multidimensional approach. The formula was derived from 37 selected chemical data of the 5 production wells from the Awibengkok Geothermal Volcanic Field in West Java. Seven components, i.e., gas volume percentage, CO2, H2S, CH4, H2, N2, and NH3, from these data are utilize to developed three model equations which represent relationship between temperature and gas compositions. These formulas are then tested by several fumarolic chemical data from Sibual-buali Area (North Sumatera) and from Ringgit Area (South Sumatera). Preliminary result indicated that gas volume percentage, H2S and CO2 concentrations have a significant role in term of gas geothermometer. Further verification is currently in progress.

  13. Multi-dimensional cosmology and GUP

    Energy Technology Data Exchange (ETDEWEB)

    Zeynali, K.; Motavalli, H. [Department of Theoretical Physics and Astrophysics, University of Tabriz, 51666-16471, Tabriz (Iran, Islamic Republic of); Darabi, F., E-mail: k.zeinali@arums.ac.ir, E-mail: f.darabi@azaruniv.edu, E-mail: motavalli@tabrizu.ac.ir [Department of Physics, Azarbaijan Shahid Madani University, 53714-161, Tabriz (Iran, Islamic Republic of)

    2012-12-01

    We consider a multidimensional cosmological model with FRW type metric having 4-dimensional space-time and d-dimensional Ricci-flat internal space sectors with a higher dimensional cosmological constant. We study the classical cosmology in commutative and GUP cases and obtain the corresponding exact solutions for negative and positive cosmological constants. It is shown that for negative cosmological constant, the commutative and GUP cases result in finite size universes with smaller size and longer ages, and larger size and shorter age, respectively. For positive cosmological constant, the commutative and GUP cases result in infinite size universes having late time accelerating behavior in good agreement with current observations. The accelerating phase starts in the GUP case sooner than the commutative case. In both commutative and GUP cases, and for both negative and positive cosmological constants, the internal space is stabilized to the sub-Planck size, at least within the present age of the universe. Then, we study the quantum cosmology by deriving the Wheeler-DeWitt equation, and obtain the exact solutions in the commutative case and the perturbative solutions in GUP case, to first order in the GUP small parameter, for both negative and positive cosmological constants. It is shown that good correspondence exists between the classical and quantum solutions.

  14. Multi-dimensional cosmology and GUP

    International Nuclear Information System (INIS)

    Zeynali, K.; Motavalli, H.; Darabi, F.

    2012-01-01

    We consider a multidimensional cosmological model with FRW type metric having 4-dimensional space-time and d-dimensional Ricci-flat internal space sectors with a higher dimensional cosmological constant. We study the classical cosmology in commutative and GUP cases and obtain the corresponding exact solutions for negative and positive cosmological constants. It is shown that for negative cosmological constant, the commutative and GUP cases result in finite size universes with smaller size and longer ages, and larger size and shorter age, respectively. For positive cosmological constant, the commutative and GUP cases result in infinite size universes having late time accelerating behavior in good agreement with current observations. The accelerating phase starts in the GUP case sooner than the commutative case. In both commutative and GUP cases, and for both negative and positive cosmological constants, the internal space is stabilized to the sub-Planck size, at least within the present age of the universe. Then, we study the quantum cosmology by deriving the Wheeler-DeWitt equation, and obtain the exact solutions in the commutative case and the perturbative solutions in GUP case, to first order in the GUP small parameter, for both negative and positive cosmological constants. It is shown that good correspondence exists between the classical and quantum solutions

  15. Convergence almost everywhere of multidimensional vectors

    International Nuclear Information System (INIS)

    El Berdan, Kassem; Zeineddine, Hassan

    2000-01-01

    Let X be a reflexive Banach space, Ω a measure space, T 1 ,...,T d be linear not commuting operators on L 1 (Ω,X)=L 1 (X) which are strictly contracting in L 1 (X) (i.e. there exist αjbelong to ]0,1[ such that ||T j f||≤αj||f|| for all j=1....,d and f belong to L 1 (X), and contracting in L ∞ (X). We prove a maximal equality for the averages: A n (T 1 ,...,T d )f= n d /1 i1=0 Σ n-1 ... id=0 Σ n-1 T 1 i1 ...T d id f and the convergence almost everywhere of it for all f in L 1 (X). This result generalizes Chacon's theorem (Chacon 19620 to the multidimensional case for this operators class. Finally, we give two operators which are strictly contracting in L 1 (X) and contracting in L ∞ (X) such that the convergence of the averages is not trivial. (author)

  16. Multidimensional Scaling Visualization Using Parametric Similarity Indices

    Directory of Open Access Journals (Sweden)

    J. A. Tenreiro Machado

    2015-03-01

    Full Text Available In this paper, we apply multidimensional scaling (MDS and parametric similarity indices (PSI in the analysis of complex systems (CS. Each CS is viewed as a dynamical system, exhibiting an output time-series to be interpreted as a manifestation of its behavior. We start by adopting a sliding window to sample the original data into several consecutive time periods. Second, we define a given PSI for tracking pieces of data. We then compare the windows for different values of the parameter, and we generate the corresponding MDS maps of ‘points’. Third, we use Procrustes analysis to linearly transform the MDS charts for maximum superposition and to build a globalMDS map of “shapes”. This final plot captures the time evolution of the phenomena and is sensitive to the PSI adopted. The generalized correlation, theMinkowski distance and four entropy-based indices are tested. The proposed approach is applied to the Dow Jones Industrial Average stock market index and the Europe Brent Spot Price FOB time-series.

  17. Energy Poverty in Europe: A Multidimensional Approach

    Directory of Open Access Journals (Sweden)

    Carlo Andrea Bollino

    2017-12-01

    Full Text Available With the European Commission’s “Third Energy Package”, the challenges posed by energy poverty have been recently acknowledged by European legislation. The paper develops a synthetic indicator of energy poverty for the purpose of assessing households’ well-being across different domains of inequality in access to energy services and to a healthy domestic environment. These dimensions are broadly defined in terms of energy affordability and thermal efficiency, two of the main manifestations of energy poverty. The analysis focuses on Europe and expands on existing economic literature by employing a fuzzy analysis for the definition of a multidimensional energy poverty index, which is then used to investigate the role of individual and household characteristics in shaping energy poverty. We find that during the European crisis energy poverty has been more stable than monetary poverty, and that thermal efficiency plays a crucial role in shaping individual and countries’ average degrees of energy poverty. JEL codes: I32; Q41; D10; D63

  18. Control of multidimensional systems on complex network

    Science.gov (United States)

    Bagnoli, Franco; Battistelli, Giorgio; Chisci, Luigi; Fanelli, Duccio

    2017-01-01

    Multidimensional systems coupled via complex networks are widespread in nature and thus frequently invoked for a large plethora of interesting applications. From ecology to physics, individual entities in mutual interactions are grouped in families, homogeneous in kind. These latter interact selectively, through a sequence of self-consistently regulated steps, whose deeply rooted architecture is stored in the assigned matrix of connections. The asymptotic equilibrium eventually attained by the system, and its associated stability, can be assessed by employing standard nonlinear dynamics tools. For many practical applications, it is however important to externally drive the system towards a desired equilibrium, which is resilient, hence stable, to external perturbations. To this end we here consider a system made up of N interacting populations which evolve according to general rate equations, bearing attributes of universality. One species is added to the pool of interacting families and used as a dynamical controller to induce novel stable equilibria. Use can be made of the root locus method to shape the needed control, in terms of intrinsic reactivity and adopted protocol of injection. The proposed method is tested on both synthetic and real data, thus enabling to demonstrate its robustness and versatility. PMID:28892493

  19. Indexación multidimensional configurable

    Directory of Open Access Journals (Sweden)

    José L. Zechinelli M.

    2004-01-01

    Full Text Available Existe una gran cantidad de métodos de indexado para datos multidimensionales. La idea fundamental de éstos es generar estructuras dinámicas para organizar objetos complejos, de tal manera que se puedan consultar de forma rápida y efectiva. Aunque existen taxonomías que definen las propiedades de cada método de indexado. A un usuario no experto le es difícil decidir cuál método podría ser apropiado para un conjunto particular de datos. En este artículo describimos la arquitectura de un framework el cual ofrece herramientas de análisis e implementación de diversos métodos de indexado multidimensional y que ayuda a un usuario a determinar el método más adecuado, para un conjunto de datos. Además se analizan ciertas propiedades de los mismos y el tipo de consultas que se llevarán a cabo en ellos.

  20. Experimental verification of multidimensional quantum steering

    Science.gov (United States)

    Li, Che-Ming; Lo, Hsin-Pin; Chen, Liang-Yu; Yabushita, Atsushi

    2018-03-01

    Quantum steering enables one party to communicate with another remote party even if the sender is untrusted. Such characteristics of quantum systems not only provide direct applications to quantum information science, but are also conceptually important for distinguishing between quantum and classical resources. While concrete illustrations of steering have been shown in several experiments, quantum steering has not been certified for higher dimensional systems. Here, we introduce a simple method to experimentally certify two different kinds of quantum steering: Einstein-Podolsky-Rosen (EPR) steering and single-system (SS) steering (i.e., temporal steering), for dimensionality (d) up to d = 16. The former reveals the steerability among bipartite systems, whereas the latter manifests itself in single quantum objects. We use multidimensional steering witnesses to verify EPR steering of polarization-entangled pairs and SS steering of single photons. The ratios between the measured witnesses and the maximum values achieved by classical mimicries are observed to increase with d for both EPR and SS steering. The designed scenario offers a new method to study further the genuine multipartite steering of large dimensionality and potential uses in quantum information processing.

  1. Analysis of Multidimensional Poverty: Theory and Case Studies ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2009-08-18

    Aug 18, 2009 ... ... of applying a factorial technique, Multiple Correspondence Analysis, to poverty analysis. ... Analysis of Multidimensional Poverty: Theory and Case Studies ... agreement to support joint research projects in December 2017.

  2. The Multicultural Personality Questionnaire : A multidimensional instrument of multicultural effectiveness

    NARCIS (Netherlands)

    Van der Zee, KI; Van Oudenhoven, JP

    2000-01-01

    In today's global business environment, executive work is becoming more international in orientation. Several skills and traits may underlie executive success in an inter national environment. The Multicultural Personality Questionnaire was developed as a multidimensional instrument aimed at

  3. Capturing Complex Multidimensional Data in Location-Based Data Warehouses

    DEFF Research Database (Denmark)

    Timko, Igor; Pedersen, Torben Bach

    2004-01-01

    Motivated by the increasing need to handle complex multidimensional data inlocation-based data warehouses, this paper proposes apowerful data model that is able to capture the complexities of such data. The model provides a foundation for handling complex transportationinfrastructures...

  4. Benefits of Multidimensional Measures of Child Well Being in China.

    Science.gov (United States)

    Gatenio Gabel, Shirley; Zhang, Yiwei

    2017-11-06

    In recent decades, measures of child well-being have evolved from single dimension to multidimensional measures. Multi-dimensional measures deepen and broaden our understanding of child well-being and inform us of areas of neglect. Child well-being in China today is measured through proxy measures of household need. This paper discusses the evolution of child well-being measures more generally, explores the benefits of positive indicators and multiple dimensions in formulating policy, and then reviews efforts to date by the Chinese government, researchers, and non-governmental and intergovernmental organizations to develop comprehensive multidimensional measures of child well-being in China. The domains and their potential interactions, as well as data sources and availability, are presented. The authors believe that child well-being in China would benefit from the development of a multidimensional index and that there is sufficient data to develop such an index.

  5. A multidimensional subdiffusion model: An arbitrage-free market

    International Nuclear Information System (INIS)

    Li Guo-Hua; Zhang Hong; Luo Mao-Kang

    2012-01-01

    To capture the subdiffusive characteristics of financial markets, the subordinated process, directed by the inverse α-stale subordinator S α (t) for 0 < α < 1, has been employed as the model of asset prices. In this article, we introduce a multidimensional subdiffusion model that has a bond and K correlated stocks. The stock price process is a multidimensional subdiffusion process directed by the inverse α-stable subordinator. This model describes the period of stagnation for each stock and the behavior of the dependency between multiple stocks. Moreover, we derive the multidimensional fractional backward Kolmogorov equation for the subordinated process using the Laplace transform technique. Finally, using a martingale approach, we prove that the multidimensional subdiffusion model is arbitrage-free, and also gives an arbitrage-free pricing rule for contingent claims associated with the martingale measure. (interdisciplinary physics and related areas of science and technology)

  6. A new set of ESTs and cDNA clones from full-length and normalized libraries for gene discovery and functional characterization in citrus

    Directory of Open Access Journals (Sweden)

    Alamar Santiago

    2009-09-01

    Full Text Available Abstract Background Interpretation of ever-increasing raw sequence information generated by modern genome sequencing technologies faces multiple challenges, such as gene function analysis and genome annotation. Indeed, nearly 40% of genes in plants encode proteins of unknown function. Functional characterization of these genes is one of the main challenges in modern biology. In this regard, the availability of full-length cDNA clones may fill in the gap created between sequence information and biological knowledge. Full-length cDNA clones facilitate functional analysis of the corresponding genes enabling manipulation of their expression in heterologous systems and the generation of a variety of tagged versions of the native protein. In addition, the development of full-length cDNA sequences has the power to improve the quality of genome annotation. Results We developed an integrated method to generate a new normalized EST collection enriched in full-length and rare transcripts of different citrus species from multiple tissues and developmental stages. We constructed a total of 15 cDNA libraries, from which we isolated 10,898 high-quality ESTs representing 6142 different genes. Percentages of redundancy and proportion of full-length clones range from 8 to 33, and 67 to 85, respectively, indicating good efficiency of the approach employed. The new EST collection adds 2113 new citrus ESTs, representing 1831 unigenes, to the collection of citrus genes available in the public databases. To facilitate functional analysis, cDNAs were introduced in a Gateway-based cloning vector for high-throughput functional analysis of genes in planta. Herein, we describe the technical methods used in the library construction, sequence analysis of clones and the overexpression of CitrSEP, a citrus homolog to the Arabidopsis SEP3 gene, in Arabidopsis as an example of a practical application of the engineered Gateway vector for functional analysis. Conclusion The new

  7. A new set of ESTs and cDNA clones from full-length and normalized libraries for gene discovery and functional characterization in citrus

    Science.gov (United States)

    Marques, M Carmen; Alonso-Cantabrana, Hugo; Forment, Javier; Arribas, Raquel; Alamar, Santiago; Conejero, Vicente; Perez-Amador, Miguel A

    2009-01-01

    Background Interpretation of ever-increasing raw sequence information generated by modern genome sequencing technologies faces multiple challenges, such as gene function analysis and genome annotation. Indeed, nearly 40% of genes in plants encode proteins of unknown function. Functional characterization of these genes is one of the main challenges in modern biology. In this regard, the availability of full-length cDNA clones may fill in the gap created between sequence information and biological knowledge. Full-length cDNA clones facilitate functional analysis of the corresponding genes enabling manipulation of their expression in heterologous systems and the generation of a variety of tagged versions of the native protein. In addition, the development of full-length cDNA sequences has the power to improve the quality of genome annotation. Results We developed an integrated method to generate a new normalized EST collection enriched in full-length and rare transcripts of different citrus species from multiple tissues and developmental stages. We constructed a total of 15 cDNA libraries, from which we isolated 10,898 high-quality ESTs representing 6142 different genes. Percentages of redundancy and proportion of full-length clones range from 8 to 33, and 67 to 85, respectively, indicating good efficiency of the approach employed. The new EST collection adds 2113 new citrus ESTs, representing 1831 unigenes, to the collection of citrus genes available in the public databases. To facilitate functional analysis, cDNAs were introduced in a Gateway-based cloning vector for high-throughput functional analysis of genes in planta. Herein, we describe the technical methods used in the library construction, sequence analysis of clones and the overexpression of CitrSEP, a citrus homolog to the Arabidopsis SEP3 gene, in Arabidopsis as an example of a practical application of the engineered Gateway vector for functional analysis. Conclusion The new EST collection denotes an

  8. On new physics searches with multidimensional differential shapes

    Science.gov (United States)

    Ferreira, Felipe; Fichet, Sylvain; Sanz, Veronica

    2018-03-01

    In the context of upcoming new physics searches at the LHC, we investigate the impact of multidimensional differential rates in typical LHC analyses. We discuss the properties of shape information, and argue that multidimensional rates bring limited information in the scope of a discovery, but can have a large impact on model discrimination. We also point out subtleties about systematic uncertainties cancellations and the Cauchy-Schwarz bound on interference terms.

  9. An Analysis of Multi-dimensional Gender Inequality in Pakistan

    OpenAIRE

    Abdul Hamid; Aisha M. Ahmed

    2011-01-01

    Women make almost half of the population of Pakistan. They also contribute significantly to economic and social growth. However, in developing countries like Pakistan, women usually suffer from multidimensional inequality of opportunities leading to multidimensional poverty. The dimensions of family, women identity, health, education and women access to economic resources and employment contribute significantly to the discrimination of women. The provision of more opportunities to women in th...

  10. On multidimensional item response theory -- a coordinate free approach

    OpenAIRE

    Antal, Tamás

    2007-01-01

    A coordinate system free definition of complex structure multidimensional item response theory (MIRT) for dichotomously scored items is presented. The point of view taken emphasizes the possibilities and subtleties of understanding MIRT as a multidimensional extension of the ``classical'' unidimensional item response theory models. The main theorem of the paper is that every monotonic MIRT model looks the same; they are all trivial extensions of univariate item response theory.

  11. Background elimination methods for multidimensional coincidence γ-ray spectra

    International Nuclear Information System (INIS)

    Morhac, M.

    1997-01-01

    In the paper new methods to separate useful information from background in one, two, three and multidimensional spectra (histograms) measured in large multidetector γ-ray arrays are derived. The sensitive nonlinear peak clipping algorithm is the basis of the methods for estimation of the background in multidimensional spectra. The derived procedures are simple and therefore have a very low cost in terms of computing time. (orig.)

  12. Modelling of multidimensional quantum systems by the numerical functional integration

    International Nuclear Information System (INIS)

    Lobanov, Yu.Yu.; Zhidkov, E.P.

    1990-01-01

    The employment of the numerical functional integration for the description of multidimensional systems in quantum and statistical physics is considered. For the multiple functional integrals with respect to Gaussian measures in the full separable metric spaces the new approximation formulas exact on a class of polynomial functionals of a given summary degree are constructed. The use of the formulas is demonstrated on example of computation of the Green function and the ground state energy in multidimensional Calogero model. 15 refs.; 2 tabs

  13. Fatigue and multidimensional disease severity in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Inal-Ince Deniz

    2010-06-01

    Full Text Available Abstract Background and aims Fatigue is associated with longitudinal ratings of health in patients with chronic obstructive pulmonary disease (COPD. Although the degree of airflow obstruction is often used to grade disease severity in patients with COPD, multidimensional grading systems have recently been developed. The aim of this study was to investigate the relationship between perceived and actual fatigue level and multidimensional disease severity in patients with COPD. Materials and methods Twenty-two patients with COPD (aged 52-74 years took part in the study. Multidimensional disease severity was measured using the SAFE and BODE indices. Perceived fatigue was assessed using the Fatigue Severity Scale (FSS and the Fatigue Impact Scale (FIS. Peripheral muscle endurance was evaluated using the number of sit-ups, squats, and modified push-ups that each patient could do. Results Thirteen patients (59% had severe fatigue, and their St George's Respiratory Questionnaire scores were significantly higher (p Conclusions Peripheral muscle endurance and fatigue perception in patients with COPD was related to multidimensional disease severity measured with both the SAFE and BODE indices. Improvements in perceived and actual fatigue levels may positively affect multidimensional disease severity and health status in COPD patients. Further research is needed to investigate the effects of fatigue perception and exercise training on patients with different stages of multidimensional COPD severity.

  14. Can the Frost Multidimensional Perfectionism Scale assess perfeccionismo?

    Science.gov (United States)

    Burgess, Alexandra M; DiBartolo, Patricia Marten; Rendón, María Jose

    2017-07-01

    Although culture-based measurement bias threatens the validity of intergroup comparison research, measurement invariance is often assumed rather than demonstrated by researchers who draw conclusions about cross-cultural similarities or differences. The current article investigates the cross-cultural invariance of a popular measure of perfectionism, the Frost Multidimensional Perfectionism Scale (F-MPS; Frost, Marten, Lahart, & Rosenblate, 1990) for a Hispanic/Latina sample. Perfectionism, which encompasses high goal setting and sensitivity to critical evaluation, is a transdiagnostic risk factor for internalizing psychopathology that especially warrants focus among groups burdened by mental health disparities. Multiple samples were used in a series of analyses to construct a baseline first-order measurement model and test for cross-group equivalence. For model development, confirmatory factor analyses (CFAs) were used with 320 female participants (M age = 19.61 years) who identified primarily (n = 301) as European/European American. Measurement invariance testing was conducted with multigroup CFAs using another sample of female adults (n = 574; Mage = 21.21 years), identifying either as European/European American (n = 217) or Hispanic/Latina/Latin American (n = 357). Evidence was found for invariance across the revised F-MPS factor structure, pattern of factor loadings, and factor variances/covariances. Results indicate that predictive relationships may be compared across these groups, but caution is suggested when interpreting raw mean score differences due to intercept nonequivalence. Further, second-order model testing demonstrated support for the bidimensional model of perfectionism cross-culturally. Future research on perfectionism within the Latino/a population is encouraged using this equivalent item set. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  15. Multidimensional clinical phenotyping of an adult cystic fibrosis patient population.

    Directory of Open Access Journals (Sweden)

    Douglas J Conrad

    Full Text Available Cystic Fibrosis (CF is a multi-systemic disease resulting from mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR gene and has major manifestations in the sino-pulmonary, and gastro-intestinal tracts. Clinical phenotypes were generated using 26 common clinical variables to generate classes that overlapped quantiles of lung function and were based on multiple aspects of CF systemic disease.The variables included age, gender, CFTR mutations, FEV1% predicted, FVC% predicted, height, weight, Brasfield chest xray score, pancreatic sufficiency status and clinical microbiology results. Complete datasets were compiled on 211 subjects. Phenotypes were identified using a proximity matrix generated by the unsupervised Random Forests algorithm and subsequent clustering by the Partitioning around Medoids (PAM algorithm. The final phenotypic classes were then characterized and compared to a similar dataset obtained three years earlier.Clinical phenotypes were identified using a clustering strategy that generated four and five phenotypes. Each strategy identified 1 a low lung health scores phenotype, 2 a younger, well-nourished, male-dominated class, 3 various high lung health score phenotypes that varied in terms of age, gender and nutritional status. This multidimensional clinical phenotyping strategy identified classes with expected microbiology results and low risk clinical phenotypes with pancreatic sufficiency.This study demonstrated regional adult CF clinical phenotypes using non-parametric, continuous, ordinal and categorical data with a minimal amount of subjective data to identify clinically relevant phenotypes. These studies identified the relative stability of the phenotypes, demonstrated specific phenotypes consistent with published findings and identified others needing further study.

  16. Multidimensional analysis: B-tagging at LEP

    International Nuclear Information System (INIS)

    de la Vaissiere, C.; Palma-Lopes, S.

    1989-01-01

    At the Z 0 , the cross-section for e + e - → b anti b is large (6.5 nb), as is the fraction of hadronic events leading to b anti b (22%). A jet topology allows to distinguish naturally the products of the b and anti b fragmentation and decays. The Z 0 looks therefore an attractive place to pursue B physics. Techniques previously used at PEP and PETRA to tag the b-flavor, have provided reasonable b-purities, at the cost of poor efficiencies. A first technique originally proposed to measure the b-lifetime was to use leptonic decays, but the corresponding branching ratios are at the 10% level. At Z 0 energies, P. Roudeau shows that a 91% purity and 6% efficiency can be obtained. The TASSO collaboration was the first to use a vertex detector for b-enrichment. They achieved a b-purity of about 68%, with a 16%-efficiency. The best way to increase these low yields is to improve the resolution of vertex detectors on impact parameters. DELPHI will be equipped with a silicon microstrip vertex detector which will provide an asymptotic accuracy of 20 μm on impact parameters in the plane transverse to the beam, to be compared with the 150 μm quoted by TASSO. However this 20 μm, combined with limited coverage, can not disentangle the multiple decays occurring in a b anti b event. In this intermediate situation multidimensional analysis may provide tagging of b anti b events with high purity and good efficiency. 11 refs., 2 figs., 2 tabs

  17. PERSPECTIVA MULTIDIMENSIONAL DO TRABALHO NA CONTEMPORANEIDADE

    Directory of Open Access Journals (Sweden)

    Lilian Carminatti

    2015-12-01

    Full Text Available O objetivo deste estudo é analisar a evolução do tema trabalho e novas formas de flexibilização das relações laborais que proporcionam identidade, significado e bem-estar. O trabalho, como uma atividade prazerosa, passa por uma mudança de postura das pessoas frente à atividade ocupacional, a partir do autoconhecimento, planejamento de carreira e de uma jornada de trabalho que vislumbre a melhora na qualidade de vida. A promoção do bem-estar presume a articulação entre as relações de trabalho atravessadas pelo sistema capitalista e a importância de equilibrar necessidades individuais e a competitividade organizacional. Como elementos balizadores surgem: a relação com os significados do trabalho, o planejamento de carreira e pós-carreira e a conexão entre valores pessoais e organizacionais. Adotou-se para a pesquisa uma estratégia metodológica qualitativa que se propõe a investigar a partir da exploração e descrição as dimensões do tema trabalho na sociedade contemporânea. Dessa forma, a promoção do bem-estar e o planejamento de carreira devem ser tratados como planejamento de vida durante todo o período funcional, a partir de uma visão multidimensional do colaborador inserida em um amplo contexto cultural e social que ultrapassa o ambiente organizacional.

  18. Visualizing information across multidimensional post-genomic structured and textual databases.

    Science.gov (United States)

    Tao, Ying; Friedman, Carol; Lussier, Yves A

    2005-04-15

    Visualizing relationships among biological information to facilitate understanding is crucial to biological research during the post-genomic era. Although different systems have been developed to view gene-phenotype relationships for specific databases, very few have been designed specifically as a general flexible tool for visualizing multidimensional genotypic and phenotypic information together. Our goal is to develop a method for visualizing multidimensional genotypic and phenotypic information and a model that unifies different biological databases in order to present the integrated knowledge using a uniform interface. We developed a novel, flexible and generalizable visualization tool, called PhenoGenesviewer (PGviewer), which in this paper was used to display gene-phenotype relationships from a human-curated database (OMIM) and from an automatic method using a Natural Language Processing tool called BioMedLEE. Data obtained from multiple databases were first integrated into a uniform structure and then organized by PGviewer. PGviewer provides a flexible query interface that allows dynamic selection and ordering of any desired dimension in the databases. Based on users' queries, results can be visualized using hierarchical expandable trees that present views specified by users according to their research interests. We believe that this method, which allows users to dynamically organize and visualize multiple dimensions, is a potentially powerful and promising tool that should substantially facilitate biological research. PhenogenesViewer as well as its support and tutorial are available at http://www.dbmi.columbia.edu/pgviewer/ Lussier@dbmi.columbia.edu.

  19. GLO-Roots: an imaging platform enabling multidimensional characterization of soil-grown root systems

    Science.gov (United States)

    Rellán-Álvarez, Rubén; Lobet, Guillaume; Lindner, Heike; Pradier, Pierre-Luc; Sebastian, Jose; Yee, Muh-Ching; Geng, Yu; Trontin, Charlotte; LaRue, Therese; Schrager-Lavelle, Amanda; Haney, Cara H; Nieu, Rita; Maloof, Julin; Vogel, John P; Dinneny, José R

    2015-01-01

    Root systems develop different root types that individually sense cues from their local environment and integrate this information with systemic signals. This complex multi-dimensional amalgam of inputs enables continuous adjustment of root growth rates, direction, and metabolic activity that define a dynamic physical network. Current methods for analyzing root biology balance physiological relevance with imaging capability. To bridge this divide, we developed an integrated-imaging system called Growth and Luminescence Observatory for Roots (GLO-Roots) that uses luminescence-based reporters to enable studies of root architecture and gene expression patterns in soil-grown, light-shielded roots. We have developed image analysis algorithms that allow the spatial integration of soil properties, gene expression, and root system architecture traits. We propose GLO-Roots as a system that has great utility in presenting environmental stimuli to roots in ways that evoke natural adaptive responses and in providing tools for studying the multi-dimensional nature of such processes. DOI: http://dx.doi.org/10.7554/eLife.07597.001 PMID:26287479

  20. On the use of multi-dimensional scaling and electromagnetic tracking in high dose rate brachytherapy

    Science.gov (United States)

    Götz, Th I.; Ermer, M.; Salas-González, D.; Kellermeier, M.; Strnad, V.; Bert, Ch; Hensel, B.; Tomé, A. M.; Lang, E. W.

    2017-10-01

    High dose rate brachytherapy affords a frequent reassurance of the precise dwell positions of the radiation source. The current investigation proposes a multi-dimensional scaling transformation of both data sets to estimate dwell positions without any external reference. Furthermore, the related distributions of dwell positions are characterized by uni—or bi—modal heavy—tailed distributions. The latter are well represented by α—stable distributions. The newly proposed data analysis provides dwell position deviations with high accuracy, and, furthermore, offers a convenient visualization of the actual shapes of the catheters which guide the radiation source during the treatment.

  1. DNA methylation polymorphism in a set of elite rice cultivars and its possible contribution to inter-cultivar differential gene expression.

    Science.gov (United States)

    Wang, Yongming; Lin, Xiuyun; Dong, Bo; Wang, Yingdian; Liu, Bao

    2004-01-01

    RAPD (randomly amplified polymorphic DNA) and ISSR (inter-simple sequence repeat) fingerprinting on HpaII/MspI-digested genomic DNA of nine elite japonica rice cultivars implies inter-cultivar DNA methylation polymorphism. Using both DNA fragments isolated from RAPD or ISSR gels and selected low-copy sequences as probes, methylation-sensitive Southern blot analysis confirms the existence of extensive DNA methylation polymorphism in both genes and DNA repeats among the rice cultivars. The cultivar-specific methylation patterns are stably maintained, and can be used as reliable molecular markers. Transcriptional analysis of four selected sequences (RdRP, AC9, HSP90 and MMR) on leaves and roots from normal and 5-azacytidine-treated seedlings of three representative cultivars shows an association between the transcriptional activity of one of the genes, the mismatch repair (MMR) gene, and its CG methylation patterns.

  2. Identifying genetic marker sets associated with phenotypes via an efficient adaptive score test

    KAUST Repository

    Cai, T.; Lin, X.; Carroll, R. J.

    2012-01-01

    the overall effect of a marker-set have been actively studied in recent years. For example, score tests derived under an Empirical Bayes (EB) framework (Liu and others, 2007. Semiparametric regression of multidimensional genetic pathway data: least

  3. Chronic activation of the epithelial immune system of the fruit fly's salivary glands has a negative effect on organismal growth and induces a peculiar set of target genes

    Directory of Open Access Journals (Sweden)

    Abdelsadik Ahmed

    2010-04-01

    Full Text Available Abstract Background Epithelial and especially mucosal immunity represents the first line of defence against the plethora of potential pathogens trying to invade via the gastrointestinal tract. The salivary glands of the fruit fly are an indispensable part of the gastrointestinal tract, but their contribution to the mucosal immunity has almost completely been neglected. Our major goal was to elucidate if the fly's salivary glands are able to mount an immune response and what the major characteristics of this immune response are. Results Ectopic activation of the IMD-pathway within the salivary gland cells is able to induce an immune response, indicating that the salivary glands are indeed immune competent. This reaction is characterized by the concurrent expression of numerous antimicrobial peptide genes. In addition, ectopic activation of the salivary gland's immune response induces morphological changes such as dwarfism throughout all developmental stages and a significantly decreased length of the salivary glands themselves. DNA-microarray analyses of the reaction revealed a complex pattern of up- and downregulated genes. Gene ontology analyses of regulated genes revealed a significant increase in genes associated with ribosomal and proteasomal function. On the other hand, genes coding for peptide receptors and some potassium channels are downregulated. In addition, the comparison of the transcriptional events induced following IMD-activation in the trachea and the salivary glands shows also only a small overlap, indicating that the general IMD-activated core transcriptome is rather small and that the tissue specific component of this response is dominating. Among the regulated genes, those that code for signaling associated protease activity are significantly modulated. Conclusions The salivary glands are immune-competent and they contribute to the overall intestinal immune system. Although they produce antimicrobial peptides, their overall

  4. Definition of the low molecular weight glutenin subunit gene family members in a set of standard bread wheat (Triticum aestivum L.) varieties

    Science.gov (United States)

    Low-molecular-weight glutenin subunits (LMW-GS) are a class of seed storage proteins that play a major role in the determination of the viscoelastic properties of wheat dough. Most of the LMW-GSs are encoded by a multi-gene family located on the short arms of the homoeologous group 1 chromosomes, at...

  5. Multiplex reverse transcription-polymerase chain reaction combined with on-chip electrophoresis as a rapid screening tool for candidate gene sets

    DEFF Research Database (Denmark)

    Wittig, Rainer; Salowsky, Rüdiger; Blaich, Stephanie

    2005-01-01

    Combining multiplex reverse transcription-polymerase chain reaction (mRT-PCR) with microfluidic amplicon analysis, we developed an assay for the rapid and reliable semiquantitative expression screening of 11 candidate genes for drug resistance in human malignant melanoma. The functionality of thi...

  6. Characterization of the CrbS/R Two-Component System in Pseudomonas fluorescens Reveals a New Set of Genes under Its Control and a DNA Motif Required for CrbR-Mediated Transcriptional Activation

    Directory of Open Access Journals (Sweden)

    Edgardo Sepulveda

    2017-11-01

    Full Text Available The CrbS/R system is a two-component signal transduction system that regulates acetate utilization in Vibrio cholerae, P. aeruginosa, and P. entomophila. CrbS is a hybrid histidine kinase that belongs to a recently identified family, in which the signaling domain is fused to an SLC5 solute symporter domain through aSTAC domain. Upon activation by CrbS, CrbR activates transcription of the acs gene, which encodes an acetyl-CoA synthase (ACS, and the actP gene, which encodes an acetate/solute symporter. In this work, we characterized the CrbS/R system in Pseudomonas fluorescens SBW25. Through the quantitative proteome analysis of different mutants, we were able to identify a new set of genes under its control, which play an important role during growth on acetate. These results led us to the identification of a conserved DNA motif in the putative promoter region of acetate-utilization genes in the Gammaproteobacteria that is essential for the CrbR-mediated transcriptional activation of genes under acetate-utilizing conditions. Finally, we took advantage of the existence of a second SLC5-containing two-component signal transduction system in P. fluorescens, CbrA/B, to demonstrate that the activation of the response regulator by the histidine kinase is not dependent on substrate transport through the SLC5 domain.

  7. Dynamic MR mammography: multidimensional visualization of contrast enhancement in virtual reality

    International Nuclear Information System (INIS)

    Englmeier, K.-H.; Siebert, M.; Griebel, J.; Lucht, R.; Brix, G.; Knopp, M.

    2000-01-01

    Background: The purpose of this study was the development of a method for fast and efficient analysis of dynamic MR images of the female breast. The image data sets were acquired with a saturation-recovery turbo-FLASH sequence which enables the detection of the kinetics of the contrast agent concentration in the whole breast with a high temporal and spatial resolution. In addition, a morphologic 3D-FLASH data set was acquired. Methods: The dynamic image datasets were analyzed by a pharmacokinetic model which enables the representation of the relevant functional tissue information by two parameters. In order to display simultaneously morphologic and functional tissue information, we developed a multidimensional visualization system, which enables a practical and intuitive human-computer interface in virtual reality. Discussions: The developed system allows the fast and efficient analysis of dynamic MR data sets. An important clinical application is the localization and definition of multiple lesions of the female breast. (orig.) [de

  8. [Dynamic MR mammography. Multidimensional visualization of contrast medium enhancement in virtual reality].

    Science.gov (United States)

    Englmeier, K H; Griebel, J; Lucht, R; Knopp, M; Siebert, M; Brix, G

    2000-03-01

    The purpose of this study was the development of a method for fast and efficient analysis of dynamic MR images of the female breast. The image data sets were acquired with a saturation-recovery turbo-FLASH sequence which enables the detection of the kinetics of the contrast agent concentration in the whole breast with a high temporal and spatial resolution. In addition, a morphologic 3D-FLASH data set was acquired. The dynamic image datasets were analyzed by a pharmacokinetic model which enables the representation of the relevant functional tissue information by two parameters. In order to display simultaneously morphologic and functional tissue information, we developed a multidimensional visualization system, which enables a practical and intuitive human-computer interface in virtual reality. The developed system allows the fast and efficient analysis of dynamic MR data sets. An important clinical application is the localization and definition of multiple lesions of the female breast.

  9. Gene expression analysis by cDNA-AFLP highlights a set of new signaling networks and translational control during seed dormancy breaking in Nicotiana plumbaginifolia.

    Science.gov (United States)

    Bove, Jérôme; Lucas, Philippe; Godin, Béatrice; Ogé, Laurent; Jullien, Marc; Grappin, Philippe

    2005-03-01

    Seed dormancy in Nicotiana plumbaginifolia is characterized by an abscisic acid accumulation linked to a pronounced germination delay. Dormancy can be released by 1 year after-ripening treatment. Using a cDNA-amplified fragment length polymorphism (cDNA-AFLP) approach we compared the gene expression patterns of dormant and after-ripened seeds, air-dry or during one day imbibition and analyzed 15,000 cDNA fragments. Among them 1020 were found to be differentially regulated by dormancy. Of 412 sequenced cDNA fragments, 83 were assigned to a known function by search similarities to public databases. The functional categories of the identified dormancy maintenance and breaking responsive genes, give evidence that after-ripening turns in the air-dry seed to a new developmental program that modulates, at the RNA level, components of translational control, signaling networks, transcriptional control and regulated proteolysis.

  10. Setting the pace: host rhythmic behaviour and gene expression patterns in the facultatively symbiotic cnidarian Aiptasia are determined largely by Symbiodinium.

    Science.gov (United States)

    Sorek, Michal; Schnytzer, Yisrael; Ben-Asher, Hiba Waldman; Caspi, Vered Chalifa; Chen, Chii-Shiarng; Miller, David J; Levy, Oren

    2018-05-09

    All organisms employ biological clocks to anticipate physical changes in the environment; however, the integration of biological clocks in symbiotic systems has received limited attention. In corals, the interpretation of rhythmic behaviours is complicated by the daily oscillations in tissue oxygen tension resulting from the photosynthetic and respiratory activities of the associated algal endosymbiont Symbiodinium. In order to better understand the integration of biological clocks in cnidarian hosts of Symbiodinium, daily rhythms of behaviour and gene expression were studied in symbiotic and aposymbiotic morphs of the sea-anemone Aiptasia diaphana. The results showed that whereas circatidal (approx. 12-h) cycles of activity and gene expression predominated in aposymbiotic morphs, circadian (approx. 24-h) patterns were the more common in symbiotic morphs, where the expression of a significant number of genes shifted from a 12- to 24-h rhythm. The behavioural experiments on symbiotic A. diaphana displayed diel (24-h) rhythmicity in body and tentacle contraction under the light/dark cycles, whereas aposymbiotic morphs showed approximately 12-h (circatidal) rhythmicity. Reinfection experiments represent an important step in understanding the hierarchy of endogenous clocks in symbiotic associations, where the aposymbiotic Aiptasia morphs returned to a 24-h behavioural rhythm after repopulation with algae. Whilst some modification of host metabolism is to be expected, the extent to which the presence of the algae modified host endogenous behavioural and transcriptional rhythms implies that it is the symbionts that influence the pace. Our results clearly demonstrate the importance of the endosymbiotic algae in determining the timing and the duration of the extension and contraction of the body and tentacles and temporal gene expression.

  11. Sampling gene diversity across the supergroup Amoebozoa: large EST data sets from Acanthamoeba castellanii, Hartmannella vermiformis, Physarum polycephalum, Hyperamoeba dachnaya and Hyperamoeba sp.

    Science.gov (United States)

    Watkins, Russell F; Gray, Michael W

    2008-04-01

    From comparative analysis of EST data for five taxa within the eukaryotic supergroup Amoebozoa, including two free-living amoebae (Acanthamoeba castellanii, Hartmannella vermiformis) and three slime molds (Physarum polycephalum, Hyperamoeba dachnaya and Hyperamoeba sp.), we obtained new broad-range perspectives on the evolution and biosynthetic capacity of this assemblage. Together with genome sequences for the amoebozoans Dictyostelium discoideum and Entamoeba histolytica, and including partial genome sequence available for A. castellanii, we used the EST data to identify genes that appear to be exclusive to the supergroup, and to specific clades therein. Many of these genes are likely involved in cell-cell communication or differentiation. In examining on a broad scale a number of characters that previously have been considered in simpler cross-species comparisons, typically between Dictyostelium and Entamoeba, we find that Amoebozoa as a whole exhibits striking variation in the number and distribution of biosynthetic pathways, for example, ones for certain critical stress-response molecules, including trehalose and mannitol. Finally, we report additional compelling cases of lateral gene transfer within Amoebozoa, further emphasizing that although this process has influenced genome evolution in all examined amoebozoan taxa, it has done so to a variable extent.

  12. Witnessing stressful events induces glutamatergic synapse pathway alterations and gene set enrichment of positive EPSP regulation within the VTA of adult mice: An ontology based approach

    Science.gov (United States)

    Brewer, Jacob S.

    It is well known that exposure to severe stress increases the risk for developing mood disorders. Currently, the neurobiological and genetic mechanisms underlying the functional effects of psychological stress are poorly understood. Presenting a major obstacle to the study of psychological stress is the inability of current animal models of stress to distinguish between physical and psychological stressors. A novel paradigm recently developed by Warren et al., is able to tease apart the effects of physical and psychological stress in adult mice by allowing these mice to "witness," the social defeat of another mouse thus removing confounding variables associated with physical stressors. Using this 'witness' model of stress and RNA-Seq technology, the current study aims to study the genetic effects of psychological stress. After, witnessing the social defeat of another mouse, VTA tissue was extracted, sequenced, and analyzed for differential expression. Since genes often work together in complex networks, a pathway and gene ontology (GO) analysis was performed using data from the differential expression analysis. The pathway and GO analyzes revealed a perturbation of the glutamatergic synapse pathway and an enrichment of positive excitatory post-synaptic potential regulation. This is consistent with the excitatory synapse theory of depression. Together these findings demonstrate a dysregulation of the mesolimbic reward pathway at the gene level as a result of psychological stress potentially contributing to depressive like behaviors.

  13. Visual modeling in an analysis of multidimensional data

    Science.gov (United States)

    Zakharova, A. A.; Vekhter, E. V.; Shklyar, A. V.; Pak, A. J.

    2018-01-01

    The article proposes an approach to solve visualization problems and the subsequent analysis of multidimensional data. Requirements to the properties of visual models, which were created to solve analysis problems, are described. As a perspective direction for the development of visual analysis tools for multidimensional and voluminous data, there was suggested an active use of factors of subjective perception and dynamic visualization. Practical results of solving the problem of multidimensional data analysis are shown using the example of a visual model of empirical data on the current state of studying processes of obtaining silicon carbide by an electric arc method. There are several results of solving this problem. At first, an idea of possibilities of determining the strategy for the development of the domain, secondly, the reliability of the published data on this subject, and changes in the areas of attention of researchers over time.

  14. A new multidimensional model with text dimensions: definition and implementation

    Directory of Open Access Journals (Sweden)

    MariaJ. Martin-Bautista

    2013-02-01

    Full Text Available We present a new multidimensional model with textual dimensions based on a knowledge structure extracted from the texts, where any textual attribute in a database can be processed, and not only XML texts. This dimension allows to treat the textual data in the same way as the non-textual one in an automatic way, without user's intervention, so all the classical operations in the multidimensional model can been defined for this textual dimension. While most of the models dealing with texts that can be found in the literature are not implemented, in this proposal, the multidimensional model and the OLAP system have been implemented in a software tool, so it can be tested on real data. A case study with medical data is included in this work.

  15. Multidimensional Scaling Localization Algorithm in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Zhang Dongyang

    2014-02-01

    Full Text Available Due to the localization algorithm in large-scale wireless sensor network exists shortcomings both in positioning accuracy and time complexity compared to traditional localization algorithm, this paper presents a fast multidimensional scaling location algorithm. By positioning algorithm for fast multidimensional scaling, fast mapping initialization, fast mapping and coordinate transform can get schematic coordinates of node, coordinates Initialize of MDS algorithm, an accurate estimate of the node coordinates and using the PRORUSTES to analysis alignment of the coordinate and final position coordinates of nodes etc. There are four steps, and the thesis gives specific implementation steps of the algorithm. Finally, compared with stochastic algorithms and classical MDS algorithm experiment, the thesis takes application of specific examples. Experimental results show that: the proposed localization algorithm has fast multidimensional scaling positioning accuracy in ensuring certain circumstances, but also greatly improves the speed of operation.

  16. Quantum and Multidimensional Explanations in a Neurobiological Context of Mind.

    Science.gov (United States)

    Korf, Jakob

    2015-08-01

    This article examines the possible relevance of physical-mathematical multidimensional or quantum concepts aiming at understanding the (human) mind in a neurobiological context. Some typical features of the quantum and multidimensional concepts are briefly introduced, including entanglement, superposition, holonomic, and quantum field theories. Next, we consider neurobiological principles, such as the brain and its emerging (physical) mind, evolutionary and ontological origins, entropy, syntropy/neg-entropy, causation, and brain energy metabolism. In many biological processes, including biochemical conversions, protein folding, and sensory perception, the ubiquitous involvement of quantum mechanisms is well recognized. Quantum and multidimensional approaches might be expected to help describe and model both brain and mental processes, but an understanding of their direct involvement in mental activity, that is, without mediation by molecular processes, remains elusive. More work has to be done to bridge the gap between current neurobiological and physical-mathematical concepts with their associated quantum-mind theories. © The Author(s) 2014.

  17. Conservative Initial Mapping For Multidimensional Simulations of Stellar Explosions

    International Nuclear Information System (INIS)

    Chen, Ke-Jung; Heger, Alexander; Almgren, Ann

    2012-01-01

    Mapping one-dimensional stellar profiles onto multidimensional grids as initial conditions for hydrodynamics calculations can lead to numerical artifacts, one of the most severe of which is the violation of conservation laws for physical quantities such as energy and mass. Here we introduce a numerical scheme for mapping one-dimensional spherically-symmetric data onto multidimensional meshes so that these physical quantities are conserved. We validate our scheme by porting a realistic 1D Lagrangian stellar profile to the new multidimensional Eulerian hydro code CASTRO. Our results show that all important features in the profiles are reproduced on the new grid and that conservation laws are enforced at all resolutions after mapping.

  18. Counting SET-free sets

    OpenAIRE

    Harman, Nate

    2016-01-01

    We consider the following counting problem related to the card game SET: How many $k$-element SET-free sets are there in an $n$-dimensional SET deck? Through a series of algebraic reformulations and reinterpretations, we show the answer to this question satisfies two polynomiality conditions.

  19. Shroud leakage flow models and a multi-dimensional coupling CFD (computational fluid dynamics) method for shrouded turbines

    International Nuclear Information System (INIS)

    Zou, Zhengping; Liu, Jingyuan; Zhang, Weihao; Wang, Peng

    2016-01-01

    Multi-dimensional coupling simulation is an effective approach for evaluating the flow and aero-thermal performance of shrouded turbines, which can balance the simulation accuracy and computing cost effectively. In this paper, 1D leakage models are proposed based on classical jet theories and dynamics equations, which can be used to evaluate most of the main features of shroud leakage flow, including the mass flow rate, radial and circumferential momentum, temperature and the jet width. Then, the 1D models are expanded to 2D distributions on the interface by using a multi-dimensional scaling method. Based on the models and multi-dimensional scaling, a multi-dimensional coupling simulation method for shrouded turbines is developed, in which, some boundary source and sink are set on the interface between the shroud and the main flow passage. To verify the precision, some simulations on the design point and off design points of a 1.5 stage turbine are conducted. It is indicated that the models and methods can give predictions with sufficient accuracy for most of the flow field features and will contribute to pursue deeper understanding and better design methods of shrouded axial turbines, which are the important devices in energy engineering. - Highlights: • Free and wall attached jet theories are used to model the leakage flow in shrouds. • Leakage flow rate is modeled by virtual labyrinth number and residual-energy factor. • A scaling method is applied to 1D model to obtain 2D distributions on interfaces. • A multi-dimensional coupling CFD method for shrouded turbines is proposed. • The proposed coupling method can give accurate predictions with low computing cost.

  20. Visualization and Dissemination of Multidimensional Proteomics Data Comparing Protein Abundance During Caenorhabditis elegans Development

    Science.gov (United States)

    Riffle, Michael; Merrihew, Gennifer E.; Jaschob, Daniel; Sharma, Vagisha; Davis, Trisha N.; Noble, William S.; MacCoss, Michael J.

    2015-11-01

    Regulation of protein abundance is a critical aspect of cellular function, organism development, and aging. Alternative splicing may give rise to multiple possible proteoforms of gene products where the abundance of each proteoform is independently regulated. Understanding how the abundances of these distinct gene products change is essential to understanding the underlying mechanisms of many biological processes. Bottom-up proteomics mass spectrometry techniques may be used to estimate protein abundance indirectly by sequencing and quantifying peptides that are later mapped to proteins based on sequence. However, quantifying the abundance of distinct gene products is routinely confounded by peptides that map to multiple possible proteoforms. In this work, we describe a technique that may be used to help mitigate the effects of confounding ambiguous peptides and multiple proteoforms when quantifying proteins. We have applied this technique to visualize the distribution of distinct gene products for the whole proteome across 11 developmental stages of the model organism Caenorhabditis elegans. The result is a large multidimensional dataset for which web-based tools were developed for visualizing how translated gene products change during development and identifying possible proteoforms. The underlying instrument raw files and tandem mass spectra may also be downloaded. The data resource is freely available on the web at http://www.yeastrc.org/wormpes/.

  1. Reprogramming the body weight set point by a reciprocal interaction of hypothalamic leptin sensitivity and Pomc gene expression reverts extreme obesity

    Directory of Open Access Journals (Sweden)

    Kavaljit H. Chhabra

    2016-10-01

    Conclusions: Pomc reactivation in previously obese, calorie-restricted ArcPomc−/− mice normalized energy homeostasis, suggesting that their body weight set point was restored to control levels. In contrast, massively obese and hyperleptinemic ArcPomc−/− mice or those weight-matched and treated with PASylated leptin to maintain extreme hyperleptinemia prior to Pomc reactivation converged to an intermediate set point relative to lean control and obese ArcPomc−/− mice. We conclude that restoration of hypothalamic leptin sensitivity and Pomc expression is necessary for obese ArcPomc−/− mice to achieve and sustain normal metabolic homeostasis; whereas deficits in either parameter set a maladaptive allostatic balance that defends increased adiposity and body weight.

  2. SM4MQ: A Semantic Model for Multidimensional Queries

    DEFF Research Database (Denmark)

    Varga, Jovan; Dobrokhotova, Ekaterina; Romero, Oscar

    2017-01-01

    On-Line Analytical Processing (OLAP) is a data analysis approach to support decision-making. On top of that, Exploratory OLAP is a novel initiative for the convergence of OLAP and the Semantic Web (SW) that enables the use of OLAP techniques on SW data. Moreover, OLAP approaches exploit different......, sharing, and reuse on the SW. As OLAP is based on the underlying multidimensional (MD) data model we denote such queries as MD queries and define SM4MQ: A Semantic Model for Multidimensional Queries. Furthermore, we propose a method to automate the exploitation of queries by means of SPARQL. We apply...

  3. Multidimensional quantum entanglement with large-scale integrated optics

    DEFF Research Database (Denmark)

    Wang, Jianwei; Paesani, Stefano; Ding, Yunhong

    2018-01-01

    -dimensional entanglement. A programmable bipartite entangled system is realized with dimension up to 15 × 15 on a large-scale silicon-photonics quantum circuit. The device integrates more than 550 photonic components on a single chip, including 16 identical photon-pair sources. We verify the high precision, generality......The ability to control multidimensional quantum systems is key for the investigation of fundamental science and for the development of advanced quantum technologies. We demonstrate a multidimensional integrated quantum photonic platform able to generate, control and analyze high...

  4. Multi-Dimensional Customer Data Analysis in Online Auctions

    Institute of Scientific and Technical Information of China (English)

    LAO Guoling; XIONG Kuan; QIN Zheng

    2007-01-01

    In this paper, we designed a customer-centered data warehouse system with five subjects: listing, bidding, transaction,accounts, and customer contact based on the business process of online auction companies. For each subject, we analyzed its fact indexes and dimensions. Then take transaction subject as example,analyzed the data warehouse model in detail, and got the multi-dimensional analysis structure of transaction subject. At last, using data mining to do customer segmentation, we divided customers into four types: impulse customer, prudent customer, potential customer, and ordinary customer. By the result of multi-dimensional customer data analysis, online auction companies can do more target marketing and increase customer loyalty.

  5. Meta-modelling, visualization and emulation of multi-dimensional data for virtual production intelligence

    Science.gov (United States)

    Schulz, Wolfgang; Hermanns, Torsten; Al Khawli, Toufik

    2017-07-01

    Decision making for competitive production in high-wage countries is a daily challenge where rational and irrational methods are used. The design of decision making processes is an intriguing, discipline spanning science. However, there are gaps in understanding the impact of the known mathematical and procedural methods on the usage of rational choice theory. Following Benjamin Franklin's rule for decision making formulated in London 1772, he called "Prudential Algebra" with the meaning of prudential reasons, one of the major ingredients of Meta-Modelling can be identified finally leading to one algebraic value labelling the results (criteria settings) of alternative decisions (parameter settings). This work describes the advances in Meta-Modelling techniques applied to multi-dimensional and multi-criterial optimization by identifying the persistence level of the corresponding Morse-Smale Complex. Implementations for laser cutting and laser drilling are presented, including the generation of fast and frugal Meta-Models with controlled error based on mathematical model reduction Reduced Models are derived to avoid any unnecessary complexity. Both, model reduction and analysis of multi-dimensional parameter space are used to enable interactive communication between Discovery Finders and Invention Makers. Emulators and visualizations of a metamodel are introduced as components of Virtual Production Intelligence making applicable the methods of Scientific Design Thinking and getting the developer as well as the operator more skilled.

  6. A gene-environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactive disorder.

    Science.gov (United States)

    Jacob, Christian P; Nguyen, Thuy Trang; Dempfle, Astrid; Heine, Monika; Windemuth-Kieselbach, Christine; Baumann, Katarina; Jacob, Florian; Prechtl, Julian; Wittlich, Maike; Herrmann, Martin J; Gross-Lesch, Silke; Lesch, Klaus-Peter; Reif, Andreas

    2010-06-01

    While an interactive effect of genes with adverse life events is increasingly appreciated in current concepts of depression etiology, no data are presently available on interactions between genetic and environmental (G x E) factors with respect to personality and related disorders. The present study therefore aimed to detect main effects as well as interactions of serotonergic candidate genes (coding for the serotonin transporter, 5-HTT; the serotonin autoreceptor, HTR1A; and the enzyme which synthesizes serotonin in the brain, TPH2) with the burden of life events (#LE) in two independent samples consisting of 183 patients suffering from personality disorders and 123 patients suffering from adult attention deficit/hyperactivity disorder (aADHD). Simple analyses ignoring possible G x E interactions revealed no evidence for associations of either #LE or of the considered polymorphisms in 5-HTT and TPH2. Only the G allele of HTR1A rs6295 seemed to increase the risk of emotional-dramatic cluster B personality disorders (p = 0.019, in the personality disorder sample) and to decrease the risk of anxious-fearful cluster C personality disorders (p = 0.016, in the aADHD sample). We extended the initial simple model by taking a G x E interaction term into account, since this approach may better fit the data indicating that the effect of a gene is modified by stressful life events or, vice versa, that stressful life events only have an effect in the presence of a susceptibility genotype. By doing so, we observed nominal evidence for G x E effects as well as main effects of 5-HTT-LPR and the TPH2 SNP rs4570625 on the occurrence of personality disorders. Further replication studies, however, are necessary to validate the apparent complexity of G x E interactions in disorders of human personality.

  7. High Diversity of Myocyanophage in Various Aquatic Environments Revealed by High-Throughput Sequencing of Major Capsid Protein Gene With a New Set of Primers

    Directory of Open Access Journals (Sweden)

    Weiguo Hou

    2018-05-01

    Full Text Available Myocyanophages, a group of viruses infecting cyanobacteria, are abundant and play important roles in elemental cycling. Here we investigated the particle-associated viral communities retained on 0.2 μm filters and in sediment samples (representing ancient cyanophage communities from four ocean and three lake locations, using high-throughput sequencing and a newly designed primer pair targeting a gene fragment (∼145-bp in length encoding the cyanophage gp23 major capsid protein (MCP. Diverse viral communities were detected in all samples. The fragments of 142-, 145-, and 148-bp in length were most abundant in the amplicons, and most sequences (>92% belonged to cyanophages. Additionally, different sequencing depths resulted in different diversity estimates of the viral community. Operational taxonomic units obtained from deep sequencing of the MCP gene covered the majority of those obtained from shallow sequencing, suggesting that deep sequencing exhibited a more complete picture of cyanophage community than shallow sequencing. Our results also revealed a wide geographic distribution of marine myocyanophages, i.e., higher dissimilarities of the myocyanophage communities corresponded with the larger distances between the sampling sites. Collectively, this study suggests that the newly designed primer pair can be effectively used to study the community and diversity of myocyanophage from different environments, and the high-throughput sequencing represents a good method to understand viral diversity.

  8. Expression patterns of porcine Toll-like receptors family set of genes (TLR1-10) in gut-associated lymphoid tissues alter with age.

    Science.gov (United States)

    Uddin, Muhammad Jasim; Kaewmala, Kanokwan; Tesfaye, Dawit; Tholen, Ernst; Looft, Christian; Hoelker, Michael; Schellander, Karl; Cinar, Mehmet Ulas

    2013-08-01

    The aim was to study the expression pattern of the porcine TLR family (TLR1-10) genes in gut-associated lymphoid tissues (GALT) of varying ages. A total of nine clinically healthy pigs of three ages group (1 day, 2 months and 5 months old) were selected for this experiment (three pigs in each group). Tissues from intestinal mucosa in stomach, duodenum, jejunum and ileum and mesenteric lymph node (MLN) were used. mRNA expression of TLRs (1-10) was detectable in all tissues and TLR3 showed the highest mRNA abundance among TLRs. TLR3 expression in stomach, and TLR1 and TLR6 expression in MLN were higher in adult than newborn pigs. The western blot results of TLR2, 3 and 9 in some cases, did not coincide with the mRNA expression results. The protein localization of TLR2, 3 and 9 showed that TLR expressing cells were abundant in the lamina propria, Peyer's patches in intestine, and around and within the lymphoid follicles in the MLN. This expressions study sheds the first light on the expression patterns of all TLR genes in GALT at different ages of pigs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Genomic characteristics comparisons of 12 food-related filamentous fungi in tRNA gene set, codon usage and amino acid composition.

    Science.gov (United States)

    Chen, Wanping; Xie, Ting; Shao, Yanchun; Chen, Fusheng

    2012-04-10

    Filamentous fungi are widely exploited in food industry due to their abilities to secrete large amounts of enzymes and metabolites. The recent availability of fungal genome sequences has provided an opportunity to explore the genomic characteristics of these food-related filamentous fungi. In this paper, we selected 12 representative filamentous fungi in the areas of food processing and safety, which were Aspergillus clavatus, A. flavus, A. fumigatus, A. nidulans, A. niger, A. oryzae, A. terreus, Monascus ruber, Neurospora crassa, Penicillium chrysogenum, Rhizopus oryzae and Trichoderma reesei, and did the comparative studies of their genomic characteristics of tRNA gene distribution, codon usage pattern and amino acid composition. The results showed that the copy numbers greatly differed among isoaccepting tRNA genes and the distribution seemed to be related with translation process. The results also revealed that genome compositional variation probably constrained the base choice at the third codon, and affected the overall amino acid composition but seemed to have little effect on the integrated physicochemical characteristics of overall amino acids. The further analysis suggested that the wobble pairing and base modification were the important mechanisms in codon-anticodon interaction. In the scope of authors' knowledge, it is the first report about the genomic characteristics analysis of food-related filamentous fungi, which would be informative for the analysis of filamentous fungal genome evolution and their practical application in food industry. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Balanced sensitivity functions for tuning multi-dimensional Bayesian network classifiers

    NARCIS (Netherlands)

    Bolt, J.H.; van der Gaag, L.C.

    Multi-dimensional Bayesian network classifiers are Bayesian networks of restricted topological structure, which are tailored to classifying data instances into multiple dimensions. Like more traditional classifiers, multi-dimensional classifiers are typically learned from data and may include

  11. Analysis of Local Dependence and Multidimensionality in Graphical Loglinear Rasch Models

    DEFF Research Database (Denmark)

    Kreiner, Svend; Christensen, Karl Bang

    2004-01-01

    Local independence; Multidimensionality; Differential item functioning; Uniform local dependence and DIF; Graphical Rasch models; Loglinear Rasch model......Local independence; Multidimensionality; Differential item functioning; Uniform local dependence and DIF; Graphical Rasch models; Loglinear Rasch model...

  12. DaqProVis, a toolkit for acquisition, interactive analysis, processing and visualization of multidimensional data

    Energy Technology Data Exchange (ETDEWEB)

    Morhac, M. [Institute of Physics, Slovak Academy of Sciences, Dubravska cesta 9, 845 11 Bratislava (Slovakia)]. E-mail: fyzimiro@savba.sk; Matousek, V. [Institute of Physics, Slovak Academy of Sciences, Dubravska cesta 9, 845 11 Bratislava (Slovakia); Turzo, I. [Institute of Physics, Slovak Academy of Sciences, Dubravska cesta 9, 845 11 Bratislava (Slovakia); Kliman, J. [Institute of Physics, Slovak Academy of Sciences, Dubravska cesta 9, 845 11 Bratislava (Slovakia)

    2006-04-01

    Multidimensional data acquisition, processing and visualization system to analyze experimental data in nuclear physics is described. It includes a large number of sophisticated algorithms of the multidimensional spectra processing, including background elimination, deconvolution, peak searching and fitting.

  13. Confirmatory factor analysis of the Multi-dimensional Emotional Empathy Scale in the South African context

    Directory of Open Access Journals (Sweden)

    Chantal Olckers

    2010-11-01

    Full Text Available Orientation: Empathy is a core competency in aiding individuals to address the challenges of social living. An indicator of emotional intelligence, it is useful in a globalising and cosmopolitan world. Moreover, managing staff, stakeholders and conflict in many social settings relies on communicative skills, of which empathy forms a large part. Empathy plays a pivotal role in negotiating, persuading and influencing behaviour. The skill of being able to empathise thus enables the possessor to attune to the needs of clients and employees and provides opportunities to become responsive to these needs. Research purpose: This study attempted to determine the construct validity of the Multi-dimensional Emotional Empathy Scale within the South African context. Motivation for the study: In South Africa, a large number of psychometrical instruments have been adopted directly from abroad. Studies determining the construct validity of several of these imported instruments, however, have shown that these instruments are not suited for use in the South African context. Research design, approach and method: The study was based on a quantitative research method with a survey design. A convenience sample of 212 respondents completed the Multi-dimensional Emotional Empathy Scale. The constructs explored were Suffering, Positive Sharing, Responsive Crying, Emotional Attention, a Feel for Others and Emotional Contagion. The statistical procedure used was a confirmatory factor analysis. Main findings: The study showed that, from a South African perspective, the Multi-dimensional Emotional Empathy Scale lacks sufficient construct validity. Practical/managerial implications: Further refinement of the model would provide valuable information that would aid people to be more appreciative of individual contributions, to meet client needs and to understand the motivations of others. Contribution/value-add: From a South African perspective, the findings of this study are

  14. The role of multidimensional instabilities in direct initiation of gaseous detonations in free space

    KAUST Repository

    Shen, Hua

    2017-01-20

    We numerically investigate the direct initiation of detonations driven by the propagation of a blast wave into a unconfined gaseous combustible mixture to study the role played by multidimensional instabilities in direct initiation of stable and unstable detonations. To this end, we first model the dynamics of unsteady propagation of detonation using the one-dimensional compressible Euler equations with a one-step chemical reaction model and cylindrical geometrical source terms. Subsequently, we use two-dimensional compressible Euler equations with just the chemical reaction source term to directly model cylindrical detonations. The one-dimensional results suggest that there are three regimes in the direct initiation for stable detonations, that the critical energy for mildly unstable detonations is not unique, and that highly unstable detonations are not self-sustainable. These phenomena agree well with one-dimensional theories and computations available in the literature. However, our two-dimensional results indicate that one-dimensional approaches are valid only for stable detonations. In mildly and highly unstable detonations, one-dimensional approaches break down because they cannot take the effects and interactions of multidimensional instabilities into account. In fact, instabilities generated in multidimensional settings yield the formation of strong transverse waves that, on one hand, increase the risk of failure of the detonation and, on the other hand, lead to the initiation of local over-driven detonations that enhance the overall self-sustainability of the global process. The competition between these two possible outcomes plays an important role in the direct initiation of detonations.

  15. Multidimensional Analyses of Long-Term Clinical Courses of Asthma and Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Toru Oga

    Full Text Available ABSTRACT: Asthma and chronic obstructive pulmonary disease (COPD are chronic respiratory disorders involving obstructive airway defects. There have been many discussions on their similarities and differences. Although airflow limitation expressed as forced expiratory volume in one second (FEV1 has been considered to be the main diagnostic assessment in both diseases, it does not reflect the functional impairment imparted to the patients by these diseases. Therefore, multidimensional approaches using multiple measurements in assessing disease control or severity have been recommended, and multiple endpoints in addition to FEV1 have been set recently in clinical trials so as not to miss the overall effects. In particular, as improving symptoms and health status as well as pulmonary function are important goals in the management of asthma and COPD, some patient-reported measurements such as health-related quality of life or dyspnea should be included. Nonetheless, there have been few reviews on the long-term clinical course comparing asthma and COPD as predicted by measurements other than airflow limitation. Here, we therefore analyzed and compared longitudinal changes in both physiological measurements and patient-reported measurements in asthma and COPD. Although both diseases showed similar long-term progressive airflow limitation similarly despite guideline-based therapies, disease progression was different in asthma and COPD. In asthma, patient-reported assessments of health status, disability and psychological status remained clinically stable over time, in contrast to the significant deterioration of these parameters in COPD. Thus, because a single measurement of airflow limitation is insufficient to monitor these diseases, multidimensional analyses are important not only for disease control but also for understanding disease progression in asthma and COPD. KEY WORDS: asthma, COPD, longitudinal survey, multidimensional analysis, patient

  16. Conservation laws for multidimensional systems and related linear algebra problems

    NARCIS (Netherlands)

    Igonine, Sergei

    2002-01-01

    We consider multidimensional systems of PDEs of generalized evolution form with t-derivatives of arbitrary order on the left-hand side and with the right-hand side dependent on lower order t-derivatives and arbitrary space derivatives. For such systems we find an explicit necessary condition for the

  17. Conservation laws for multidimensional systems and related linear algebra problems

    NARCIS (Netherlands)

    Igonin, S.

    2002-01-01

    We consider multidimensional systems of PDEs of generalized evolution form with $t$-derivatives of arbitrary order on the left-hand side and with the right-hand side dependent on lower order $t$-derivatives and arbitrary space derivatives. For such systems we find an explicit necessary condition for

  18. The Measurement of Multidimensional Gender Inequality: Continuing the Debate

    Science.gov (United States)

    Permanyer, Inaki

    2010-01-01

    The measurement of multidimensional gender inequality is an increasingly important topic that has very relevant policy applications and implications but which has not received much attention from the academic literature. In this paper I make a comprehensive and critical review of the indices proposed in recent years in order to systematise the…

  19. The Structure and Validity of the Multidimensional Social Support Questionnaire

    Science.gov (United States)

    Hardesty, Patrick H.; Richardson, George B.

    2012-01-01

    The factor structure and concurrent validity of the Multidimensional Social Support Questionnaire, a brief measure of perceived social support for use with adolescents, was examined. Findings suggest that four dimensions of perceived social support may yield more information than assessments of the unitary construct of support. (Contains 8 tables…

  20. Multidimensional Poverty in China: Findings Based on the CHNS

    Science.gov (United States)

    Yu, Jiantuo

    2013-01-01

    This paper estimates multidimensional poverty in China by applying the Alkire-Foster methodology to the China Health and Nutrition Survey 2000-2009 data. Five dimensions are included: income, living standard, education, health and social security. Results suggest that rapid economic growth has resulted not only in a reduction in income poverty but…

  1. Integral and Multidimensional Linear Distinguishers with Correlation Zero

    DEFF Research Database (Denmark)

    Bogdanov, Andrey; Leander, Gregor; Nyberg, Kaisa

    2012-01-01

    Zero-correlation cryptanalysis uses linear approximations holding with probability exactly 1/2. In this paper, we reveal fundamental links of zero-correlation distinguishers to integral distinguishers and multidimensional linear distinguishers. We show that an integral implies zero-correlation li...... weak key assumptions. © International Association for Cryptologic Research 2012....

  2. Theme section: Multi-dimensional modelling, analysis and visualization

    DEFF Research Database (Denmark)

    Guilbert, Éric; Coltekin, Arzu; Antón Castro, Francesc/François

    2016-01-01

    (Biljecki et al., 2015) as well as the temporal, but also the scale dimension (Van Oosterom and Stoter, 2010) or, as mentioned by(Lu et al., 2016), multi-spectral and multi-sensor data. Such a view provides an organisation of multidimensional data around these different axes and it is time to explore each...

  3. Income and beyond: Multidimensional Poverty in Six Latin American Countries

    Science.gov (United States)

    Battiston, Diego; Cruces, Guillermo; Lopez-Calva, Luis Felipe; Lugo, Maria Ana; Santos, Maria Emma

    2013-01-01

    This paper studies multidimensional poverty for Argentina, Brazil, Chile, El Salvador, Mexico and Uruguay for the period 1992-2006. The approach overcomes the limitations of the two traditional methods of poverty analysis in Latin America (income-based and unmet basic needs) by combining income with five other dimensions: school attendance for…

  4. Nonparametric Bayesian inference for multidimensional compound Poisson processes

    NARCIS (Netherlands)

    Gugushvili, S.; van der Meulen, F.; Spreij, P.

    2015-01-01

    Given a sample from a discretely observed multidimensional compound Poisson process, we study the problem of nonparametric estimation of its jump size density r0 and intensity λ0. We take a nonparametric Bayesian approach to the problem and determine posterior contraction rates in this context,

  5. Evidence for a Multidimensional Self-Efficacy for Exercise Scale

    Science.gov (United States)

    Rodgers, W. M.; Wilson, P. M.; Hall, C. R.; Fraser, S. N.; Murray, T. C.

    2008-01-01

    This series of three studies considers the multidimensionality of exercise self-efficacy by examining the psychometric characteristics of an instrument designed to assess three behavioral subdomains: task, scheduling, and coping. In Study 1, exploratory factor analysis revealed the expected factor structure in a sample of 395 students.…

  6. Multidimensional adaptive testing with a minimum error-variance criterion

    NARCIS (Netherlands)

    van der Linden, Willem J.

    1997-01-01

    The case of adaptive testing under a multidimensional logistic response model is addressed. An adaptive algorithm is proposed that minimizes the (asymptotic) variance of the maximum-likelihood (ML) estimator of a linear combination of abilities of interest. The item selection criterion is a simple

  7. Psychometric properties of the Multidimensional Anxiety Scale for ...

    African Journals Online (AJOL)

    Aim: To determine the psychometric properties of the Multidimensional Anxiety Scale for Children (MASC) in Nairobi public secondary school children, Kenya. Method: Concurrent self-administration of the MASC and Children's Depression Inventory (CDI) to students in Nairobi public secondary schools. Results: The MASC ...

  8. Cognitive Age: A New Multidimensional Approach to Measuring Age Identity.

    Science.gov (United States)

    Barak, Benny

    1987-01-01

    Conducted exploratory field study to examine how age-concepts are experienced and to assess relationship of age identities to each other. Proposes Cognitive Age as a new multidimensional age scale that merges the standard scale, Identity Age, and Personal Age. Study results attest to Cognitive Age scale's reliability and validity. (Author/NB)

  9. Decay rate in a multi-dimensional fission problem

    Energy Technology Data Exchange (ETDEWEB)

    Brink, D M; Canto, L F

    1986-06-01

    The multi-dimensional diffusion approach of Zhang Jing Shang and Weidenmueller (1983 Phys. Rev. C28, 2190) is used to study a simplified model for induced fission. In this model it is shown that the coupling of the fission coordinate to the intrinsic degrees of freedom is equivalent to an extra friction and a mass correction in the corresponding one-dimensional problem.

  10. A comparison of multidimensional scaling methods for perceptual mapping

    NARCIS (Netherlands)

    Bijmolt, T.H.A.; Wedel, M.

    Multidimensional scaling has been applied to a wide range of marketing problems, in particular to perceptual mapping based on dissimilarity judgments. The introduction of methods based on the maximum likelihood principle is one of the most important developments. In this article, the authors compare

  11. The Multidimensionality of Child Poverty: Evidence from Afghanistan

    Science.gov (United States)

    Trani, Jean-Francois; Biggeri, Mario; Mauro, Vincenzo

    2013-01-01

    This paper examines multidimensional poverty among children in Afghanistan using the Alkire-Foster method. Several previous studies have underlined the need to separate children from their adult nexus when studying poverty and treat them according to their own specificities. From the capability approach, child poverty is understood to be the lack…

  12. Multidimensional Data Modeling For Location-Based Services

    DEFF Research Database (Denmark)

    Jensen, Christian Søndergaard; Kligys, Augustas; Pedersen, Torben Bach

    2004-01-01

    and requests of their users in multidimensional databases, i.e., data warehouses, and content delivery may be based on the results of complex queries on these data warehouses. Such queries aggregate detailed data in order to find useful patterns, e.g., in the interaction of a particular user with the services...

  13. Multidimensional Data Modeling For Location-Based Services

    DEFF Research Database (Denmark)

    Jensen, Christian Søndergaard; Kligys, A.; Pedersen, Torben Bach

    2003-01-01

    and requests of their users in multidimensional databases, i.e., data warehouses; and content delivery may be based on the results of complex queries on these data warehouses. Such queries aggregate detailed data in order to find useful patterns, e.g., in the interaction of a particular user with the services...

  14. Application of Andrew's Plots to Visualization of Multidimensional Data

    Science.gov (United States)

    Grinshpun, Vadim

    2016-01-01

    Importance: The article raises a point of visual representation of big data, recently considered to be demanded for many scientific and real-life applications, and analyzes particulars for visualization of multi-dimensional data, giving examples of the visual analytics-related problems. Objectives: The purpose of this paper is to study application…

  15. Turkish Validity Examination of the Multidimensional Students' Life Satisfaction Scale

    Science.gov (United States)

    Irmak, Sezgin; Kuruuzum, Ayse

    2009-01-01

    The validation studies of the Multidimensional Students' Life Satisfaction Scale (MSLSS) have been conducted with samples from different nations but mostly from western individualistic cultures. Life satisfaction and its constructs could differ depending on cultural characteristics and life satisfaction scales should be validated in different…

  16. Five Evils: Multidimensional Poverty and Race in America

    Science.gov (United States)

    Reeves, Richard; Rodrigue, Edward; Kneebone, Elizabeth

    2016-01-01

    Poverty is about a lack of money, but it's not only about that. As a lived experience, poverty is also characterized by ill health, insecurity, discomfort, isolation, and more. To put it another way: Poverty is multidimensional, and its dimensions often cluster together to intensify the negative effects of being poor. In this first of a two-part…

  17. A Review of the Brief Multidimensional Students' Life Satisfaction Scale

    Science.gov (United States)

    Huebner, E. Scott; Seligson, Julie L.; Valois, Robert F.; Suldo, Shannon M.

    2006-01-01

    There are few psychometrically sound measures of life satisfaction suitable for children and adolescents. The purpose of this paper is to describe the rationale, development, and psychometric properties of a brief multidimensional life satisfaction scale appropriate for use with children of ages 8-18. The paper summarizes extant studies of its…

  18. A scalable pairwise class interaction framework for multidimensional classification

    DEFF Research Database (Denmark)

    Arias, Jacinto; Gámez, Jose A.; Nielsen, Thomas Dyhre

    2016-01-01

    We present a general framework for multidimensional classification that cap- tures the pairwise interactions between class variables. The pairwise class inter- actions are encoded using a collection of base classifiers (Phase 1), for which the class predictions are combined in a Markov random fie...

  19. A Template Model for Multidimensional Inter-Transactional Association Rules

    NARCIS (Netherlands)

    Feng, L.; Yu, J.X.; Lu, H.J.; Han, J.W.

    2002-01-01

    Multidimensional inter-transactional association rules extend the traditional association rules to describe more general associations among items with multiple properties across transactions. “After McDonald and Burger King open branches, KFC will open a branch two months later and one mile away��?

  20. Efficient algorithms of multidimensional γ-ray spectra compression

    International Nuclear Information System (INIS)

    Morhac, M.; Matousek, V.

    2006-01-01

    The efficient algorithms to compress multidimensional γ-ray events are presented. Two alternative kinds of compression algorithms based on both the adaptive orthogonal and randomizing transforms are proposed. In both algorithms we employ the reduction of data volume due to the symmetry of the γ-ray spectra

  1. Adaptation of the multidimensional scale of perceived social support ...

    African Journals Online (AJOL)

    Background: The Multidimensional Scale of Perceived Social Support (MSPSS) was developed in the USA. The adequacy of its use in Uganda to guarantee its reliability and validity has not been ascertained. Aim: Thus the aim of the present study was to adapt the MSPSS scale by testing the validity and reliability of the ...

  2. Development and Validation of Multi-Dimensional Personality ...

    African Journals Online (AJOL)

    This study was carried out to establish the scientific processes for the development and validation of Multi-dimensional Personality Inventory (MPI). The process of development and validation occurred in three phases with five components of Agreeableness, Conscientiousness, Emotional stability, Extroversion, and ...

  3. Loglinear multidimensional IRT models for polytomously scired Items

    NARCIS (Netherlands)

    Kelderman, Henk

    1988-01-01

    A loglinear item response theory (IRT) model is proposed that relates polytomously scored item responses to a multidimensional latent space. Each item may have a different response function where each item response may be explained by one or more latent traits. Item response functions may follow a

  4. Loglinear multidimensional IRT models for polytomously scored items

    NARCIS (Netherlands)

    Kelderman, Henk; Rijkes, Carl P.M.; Rijkes, Carl

    1994-01-01

    A loglinear IRT model is proposed that relates polytomously scored item responses to a multidimensional latent space. The analyst may specify a response function for each response, indicating which latent abilities are necessary to arrive at that response. Each item may have a different number of

  5. Income Tax Preparation Assistance Service Learning Program: A Multidimensional Assessment

    Science.gov (United States)

    Aldridge, Richard; Callahan, Richard A.; Chen, Yining; Wade, Stacy R.

    2015-01-01

    The authors present a multidimensional assessment of the outcomes and benefits of an income tax preparation assistance (ITPA) service learning program. They measure the perceived proximate benefits at the delivery of the service program, the actual learning outcome benefits prior to graduation, and the perceived long-term benefits from a…

  6. Multidimensional Model of Trauma and Correlated Antisocial Personality Disorder

    Science.gov (United States)

    Martens, Willem H. J.

    2005-01-01

    Many studies have revealed an important relationship between psychosocial trauma and antisocial personality disorder. A multidimensional model is presented which describes the psychopathological route from trauma to antisocial development. A case report is also included that can illustrate the etiological process from trauma to severe antisocial…

  7. Multidimensional poverty dynamics in Ethiopia: how do they differ ...

    African Journals Online (AJOL)

    Poverty can take many different forms, ranging widely over dimensions both monetary, such as consumption or income, and nonmonetary, such as health and education. One large class of nonmonetary measures of poverty is the multidimensional poverty index (MPI); recent studies document that people identified as poor ...

  8. Identification of peaks in multidimensional coincidence {gamma}-ray spectra

    Energy Technology Data Exchange (ETDEWEB)

    Morhac, Miroslav E-mail: fyzimiro@savba.sk; Kliman, Jan; Matousek, Vladislav; Veselsky, Martin; Turzo, Ivan

    2000-03-21

    In the paper a new algorithm to find peaks in two, three and multidimensional spectra, measured in large multidetector {gamma}-ray arrays, is derived. Given the dimension m, the algorithm is selective to m-fold coincidence peaks. It is insensitive to intersections of lower-fold coincidences, hereinafter called ridges.

  9. Assessment of health surveys: fitting a multidimensional graded response model.

    Science.gov (United States)

    Depaoli, Sarah; Tiemensma, Jitske; Felt, John M

    The multidimensional graded response model, an item response theory (IRT) model, can be used to improve the assessment of surveys, even when sample sizes are restricted. Typically, health-based survey development utilizes classical statistical techniques (e.g. reliability and factor analysis). In a review of four prominent journals within the field of Health Psychology, we found that IRT-based models were used in less than 10% of the studies examining scale development or assessment. However, implementing IRT-based methods can provide more details about individual survey items, which is useful when determining the final item content of surveys. An example using a quality of life survey for Cushing's syndrome (CushingQoL) highlights the main components for implementing the multidimensional graded response model. Patients with Cushing's syndrome (n = 397) completed the CushingQoL. Results from the multidimensional graded response model supported a 2-subscale scoring process for the survey. All items were deemed as worthy contributors to the survey. The graded response model can accommodate unidimensional or multidimensional scales, be used with relatively lower sample sizes, and is implemented in free software (example code provided in online Appendix). Use of this model can help to improve the quality of health-based scales being developed within the Health Sciences.

  10. Asymptotic time dependent neutron transport in multidimensional systems

    International Nuclear Information System (INIS)

    Nagy, M.E.; Sawan, M.E.; Wassef, W.A.; El-Gueraly, L.A.

    1983-01-01

    A model which predicts the asymptotic time behavior of the neutron distribution in multi-dimensional systems is presented. The model is based on the kernel factorization method used for stationary neutron transport in a rectangular parallelepiped. The accuracy of diffusion theory in predicting the asymptotic time dependence is assessed. The use of neutron pulse experiments for predicting the diffusion parameters is also investigated

  11. Extending Validity Evidence for Multidimensional Measures of Coaching Competency

    Science.gov (United States)

    Myers, Nicholas D.; Wolfe, Edward W.; Maier, Kimberly S.; Feltz, Deborah L.; Reckase, Mark D.

    2006-01-01

    This study extended validity evidence for multidimensional measures of coaching competency derived from the Coaching Competency Scale (CCS; Myers, Feltz, Maier, Wolfe, & Reckase, 2006) by examining use of the original rating scale structure and testing how measures related to satisfaction with the head coach within teams and between teams.…

  12. Almost-sure identifiability of multidimensional harmonic retrieval

    NARCIS (Netherlands)

    Jiang, T; Sidiropoulos, ND; ten Berge, JMF

    Two-dimensional (2-D) and, more generally, multidimensional harmonic retrieval is of interest in a variety of applications, including transmitter localization and joint time and frequency offset estimation in wireless communications. The associated identifiability problem is key in understanding the

  13. Identification of peaks in multidimensional coincidence γ-ray spectra

    International Nuclear Information System (INIS)

    Morhac, Miroslav; Kliman, Jan; Matousek, Vladislav; Veselsky, Martin; Turzo, Ivan

    2000-01-01

    In the paper a new algorithm to find peaks in two, three and multidimensional spectra, measured in large multidetector γ-ray arrays, is derived. Given the dimension m, the algorithm is selective to m-fold coincidence peaks. It is insensitive to intersections of lower-fold coincidences, hereinafter called ridges

  14. Multidimensional first-order dominance comparisons of population wellbeing

    DEFF Research Database (Denmark)

    Arndt, Thomas Channing; Siersbæk, Nikolaj; Østerdal, Lars Peter Raahave

    In this paper, we convey the concept of first-order dominance (FOD) with particular focus on applications to multidimensional population welfare comparisons. We give an account of the fundamental equivalent definitions of FOD, illustrated with simple numerical examples. An implementable method...

  15. Toolbox Approaches Using Molecular Markers and 16S rRNA Gene Amplicon Data Sets for Identification of Fecal Pollution in Surface Water.

    Science.gov (United States)

    Ahmed, W; Staley, C; Sadowsky, M J; Gyawali, P; Sidhu, J P S; Palmer, A; Beale, D J; Toze, S

    2015-10-01

    In this study, host-associated molecular markers and bacterial 16S rRNA gene community analysis using high-throughput sequencing were used to identify the sources of fecal pollution in environmental waters in Brisbane, Australia. A total of 92 fecal and composite wastewater samples were collected from different host groups (cat, cattle, dog, horse, human, and kangaroo), and 18 water samples were collected from six sites (BR1 to BR6) along the Brisbane River in Queensland, Australia. Bacterial communities in the fecal, wastewater, and river water samples were sequenced. Water samples were also tested for the presence of bird-associated (GFD), cattle-associated (CowM3), horse-associated, and human-associated (HF183) molecular markers, to provide multiple lines of evidence regarding the possible presence of fecal pollution associated with specific hosts. Among the 18 water samples tested, 83%, 33%, 17%, and 17% were real-time PCR positive for the GFD, HF183, CowM3, and horse markers, respectively. Among the potential sources of fecal pollution in water samples from the river, DNA sequencing tended to show relatively small contributions from wastewater treatment plants (up to 13% of sequence reads). Contributions from other animal sources were rarely detected and were very small (molecular markers showed variable agreement. A lack of relationships among fecal indicator bacteria, host-associated molecular markers, and 16S rRNA gene community analysis data was also observed. Nonetheless, we show that bacterial community and host-associated molecular marker analyses can be combined to identify potential sources of fecal pollution in an urban river. This study is a proof of concept, and based on the results, we recommend using bacterial community analysis (where possible) along with PCR detection or quantification of host-associated molecular markers to provide information on the sources of fecal pollution in waterways. Copyright © 2015, American Society for Microbiology

  16. A Molecular Approach to Nested RT-PCR Using a New Set of Primers for the Detection of the Human Immunodeficiency Virus Protease Gene.

    Science.gov (United States)

    Zarei, Mohammad; Ravanshad, Mehrdad; Bagban, Ashraf; Fallahi, Shahab

    2016-07-01

    The human immunodeficiency virus (HIV-1) is the etiologic agent of AIDS. The disease can be transmitted via blood in the window period prior to the development of antibodies to the disease. Thus, an appropriate method for the detection of HIV-1 during this window period is very important. This descriptive study proposes a sensitive, efficient, inexpensive, and easy method to detect HIV-1. In this study 25 serum samples of patients under treatment and also 10 positive and 10 negative control samples were studied. Twenty-five blood samples were obtained from HIV-1-infected individuals who were receiving treatment at the acquired immune deficiency syndrome (AIDS) research center of Imam Khomeini hospital in Tehran. The identification of HIV-1-positive samples was done by using reverse transcription to produce copy deoxyribonucleic acid (cDNA) and then optimizing the nested polymerase chain reaction (PCR) method. Two pairs of primers were then designed specifically for the protease gene fragment of the nested real time-PCR (RT-PCR) samples. Electrophoresis was used to examine the PCR products. The results were analyzed using statistical tests, including Fisher's exact test, and SPSS17 software. The 325 bp band of the protease gene was observed in all the positive control samples and in none of the negative control samples. The proposed method correctly identified HIV-1 in 23 of the 25 samples. These results suggest that, in comparison with viral cultures, antibody detection by enzyme linked immunosorbent assay (ELISAs), and conventional PCR methods, the proposed method has high sensitivity and specificity for the detection of HIV-1.

  17. Automatic sets and Delone sets

    International Nuclear Information System (INIS)

    Barbe, A; Haeseler, F von

    2004-01-01

    Automatic sets D part of Z m are characterized by having a finite number of decimations. They are equivalently generated by fixed points of certain substitution systems, or by certain finite automata. As examples, two-dimensional versions of the Thue-Morse, Baum-Sweet, Rudin-Shapiro and paperfolding sequences are presented. We give a necessary and sufficient condition for an automatic set D part of Z m to be a Delone set in R m . The result is then extended to automatic sets that are defined as fixed points of certain substitutions. The morphology of automatic sets is discussed by means of examples

  18. A second-order cell-centered Lagrangian ADER-MOOD finite volume scheme on multidimensional unstructured meshes for hydrodynamics

    Science.gov (United States)

    Boscheri, Walter; Dumbser, Michael; Loubère, Raphaël; Maire, Pierre-Henri

    2018-04-01

    In this paper we develop a conservative cell-centered Lagrangian finite volume scheme for the solution of the hydrodynamics equations on unstructured multidimensional grids. The method is derived from the Eucclhyd scheme discussed in [47,43,45]. It is second-order accurate in space and is combined with the a posteriori Multidimensional Optimal Order Detection (MOOD) limiting strategy to ensure robustness and stability at shock waves. Second-order of accuracy in time is achieved via the ADER (Arbitrary high order schemes using DERivatives) approach. A large set of numerical test cases is proposed to assess the ability of the method to achieve effective second order of accuracy on smooth flows, maintaining an essentially non-oscillatory behavior on discontinuous profiles, general robustness ensuring physical admissibility of the numerical solution, and precision where appropriate.

  19. On the control of distributed parameter systems using a multidimensional systems setting

    Czech Academy of Sciences Publication Activity Database

    Cichy, B.; Augusta, Petr; Rogers, E.; Galkowski, K.; Hurák, Z.

    2008-01-01

    Roč. 22, č. 7 (2008), s. 1566-1581 ISSN 0888-3270 R&D Projects: GA MŠk(CZ) 1M0567 Institutional research plan: CEZ:AV0Z10750506 Keywords : Distributed parameter systems * Modelling * Control law design Subject RIV: BC - Control Systems Theory Impact factor: 1.984, year: 2008

  20. PrIMe Next Frontier: Large, Multi-Dimensional Data Sets

    Science.gov (United States)

    2015-07-21

    is provided below.  3.4.2 Entities  Figure  4  is  a  diagram  that  represents  the  datatypes   of  objects/instances  that  are  used  within  the...ajax({ type: ’GET’, url: 𔃻.html’, dataType : ’text’, success: function(res) { $(’body’).append(res... dataType : ’script’, success: function() { if (++counter == libraries.length) createSpecWindow(callback