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Sample records for gene-environment interaction based

  1. Gene-environment interaction.

    Science.gov (United States)

    Manuck, Stephen B; McCaffery, Jeanne M

    2014-01-01

    With the advent of increasingly accessible technologies for typing genetic variation, studies of gene-environment (G×E) interactions have proliferated in psychological research. Among the aims of such studies are testing developmental hypotheses and models of the etiology of behavioral disorders, defining boundaries of genetic and environmental influences, and identifying individuals most susceptible to risk exposures or most amenable to preventive and therapeutic interventions. This research also coincides with the emergence of unanticipated difficulties in detecting genetic variants of direct association with behavioral traits and disorders, which may be obscured if genetic effects are expressed only in predisposing environments. In this essay we consider these and other rationales for positing G×E interactions, review conceptual models meant to inform G×E interpretations from a psychological perspective, discuss points of common critique to which G×E research is vulnerable, and address the role of the environment in G×E interactions.

  2. Genotype-Based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors

    OpenAIRE

    Iryna Lobach; Ruzong Fan

    2012-01-01

    A key component to understanding etiology of complex diseases, such as cancer, diabetes, alcohol dependence, is to investigate gene-environment interactions. This work is motivated by the following two concerns in the analysis of gene-environment interactions. First, multiple genetic markers in moderate linkage disequilibrium may be involved in susceptibility to a complex disease. Second, environmental factors may be subject to misclassification. We develop a genotype based Bayesian pseudolik...

  3. Genotype-Based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors.

    Science.gov (United States)

    Lobach, Iryna; Fan, Ruzong

    A key component to understanding etiology of complex diseases, such as cancer, diabetes, alcohol dependence, is to investigate gene-environment interactions. This work is motivated by the following two concerns in the analysis of gene-environment interactions. First, multiple genetic markers in moderate linkage disequilibrium may be involved in susceptibility to a complex disease. Second, environmental factors may be subject to misclassification. We develop a genotype based Bayesian pseudolikelihood approach that accommodates linkage disequilibrium in genetic markers and misclassification in environmental factors. Since our approach is genotype based, it allows the observed genetic information to enter the model directly thus eliminating the need to infer haplotype phase and simplifying computations. Bayesian approach allows shrinking parameter estimates towards prior distribution to improve estimation and inference when environmental factors are subject to misclassification. Simulation experiments demonstrated that our method produced parameter estimates that are nearly unbiased even for small sample sizes. An application of our method is illustrated using a case-control study of interaction between early onset of drinking and genes involved in dopamine pathway.

  4. Genotype-Based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors

    Directory of Open Access Journals (Sweden)

    Iryna Lobach

    2012-01-01

    Full Text Available A key component to understanding etiology of complex diseases, such as cancer, diabetes, alcohol dependence, is to investigate gene-environment interactions. This work is motivated by the following two concerns in the analysis of gene-environment interactions. First, multiple genetic markers in moderate linkage disequilibrium may be involved in susceptibility to a complex disease. Second, environmental factors may be subject to misclassification. We develop a genotype based Bayesian pseudolikelihood approach that accommodates linkage disequilibrium in genetic markers and misclassification in environmental factors. Since our approach is genotype based, it allows the observed genetic information to enter the model directly thus eliminating the need to infer haplotype phase and simplifying computations. Bayesian approach allows shrinking parameter estimates towards prior distribution to improve estimation and inference when environmental factors are subject to misclassification. Simulation experiments demonstrated that our method produced parameter estimates that are nearly unbiased even for small sample sizes. An application of our method is illustrated using a case-control study of interaction between early onset of drinking and genes involved in dopamine pathway.

  5. Biological Implications of Gene-Environment Interaction

    Science.gov (United States)

    Rutter, Michael

    2008-01-01

    Gene-environment interaction (G x E) has been treated as both a statistical phenomenon and a biological reality. It is argued that, although there are important statistical issues that need to be considered, the focus has to be on the biological implications of G x E. Four reports of G x E deriving from the Dunedin longitudinal study are used as…

  6. Finding gene-environment interactions for Phobias

    OpenAIRE

    Gregory, Alice M.; Lau, Jennifer Y. F.; Eley, Thalia C

    2008-01-01

    Phobias are common disorders causing a great deal of suffering. Studies of gene-environment interaction (G × E) have revealed much about the complex processes underlying the development of various psychiatric disorders but have told us little about phobias. This article describes what is already known about genetic and environmental influences upon phobias and suggests how this information can be used to optimise the chances of discovering G × Es for phobias. In addition to the careful concep...

  7. A new clinical evidence-based gene-environment interaction model of depression.

    Science.gov (United States)

    Bagdy, Gyorgy; Juhasz, Gabriella; Gonda, Xenia

    2012-12-01

    In our current understanding of mood disorders, the role of genes is diverse including the mediation of the effects of provoking and protective factors. Different or partially overlapping gene sets play a major role in the development of personality traits including also affective temperaments, in the mediation of the effects of environmental factors, and in the interaction of these elements in the development of depression. Certain genes are associated with personality traits and temperaments including e.g., neuroticism, impulsivity, openness, rumination and extroversion. Environmental factors consist of external (early and provoking life events, seasonal changes, social support etc.) and internal factors (hormones, biological rhythm generators, comorbid disorders etc). Some of these environmental factors, such as early life events and some prenatal events directly influence the development of personality traits and temperaments. In the NEWMOOD cohort polymorphisms of the genes of the serotonin transporter, 5-HT1A, 5-HT1B and 5-HT2A and endocannabinoid CB1 receptors, tryptophan hydroxylase, CREB1, BDNF and GIRK provide evidence for the involvement of these genes in the development of depression. Based on their role in this process they could be assigned to different gene sets. The role of certain genes, such as promoter polymorphisms of the serotonin transporter (5-HTTLPR) and CB1 receptor has been shown in more than one of the above factors. Furthermore, gene-gene interactions of these promoters associated with anxiety suggest the application of these polymorphisms in personalized medicine. In this review we introduce a new model including environmental factors, genes, trait and temperament markers based on human genetic studies.

  8. Genotype-based association models of complex diseases to detect gene-gene and gene-environment interactions.

    Science.gov (United States)

    Lobach, Iryna; Fan, Ruzong; Manga, Prashiela

    A central problem in genetic epidemiology is to identify and rank genetic markers involved in a disease. Complex diseases, such as cancer, hypertension, diabetes, are thought to be caused by an interaction of a panel of genetic factors, that can be identified by markers, which modulate environmental factors. Moreover, the effect of each genetic marker may be small. Hence, the association signal may be missed unless a large sample is considered, or a priori biomedical data are used. Recent advances generated a vast variety of a priori information, including linkage maps and information about gene regulatory dependence assembled into curated pathway databases. We propose a genotype-based approach that takes into account linkage disequilibrium (LD) information between genetic markers that are in moderate LD while modeling gene-gene and gene-environment interactions. A major advantage of our method is that the observed genetic information enters a model directly thus eliminating the need to estimate haplotype-phase. Our approach results in an algorithm that is inexpensive computationally and does not suffer from bias induced by haplotype-phase ambiguity. We investigated our model in a series of simulation experiments and demonstrated that the proposed approach results in estimates that are nearly unbiased and have small variability. We applied our method to the analysis of data from a melanoma case-control study and investigated interaction between a set of pigmentation genes and environmental factors defined by age and gender. Furthermore, an application of our method is demonstrated using a study of Alcohol Dependence.

  9. Artificial neural networks modeling gene-environment interaction

    Directory of Open Access Journals (Sweden)

    Günther Frauke

    2012-05-01

    Full Text Available Abstract Background Gene-environment interactions play an important role in the etiological pathway of complex diseases. An appropriate statistical method for handling a wide variety of complex situations involving interactions between variables is still lacking, especially when continuous variables are involved. The aim of this paper is to explore the ability of neural networks to model different structures of gene-environment interactions. A simulation study is set up to compare neural networks with standard logistic regression models. Eight different structures of gene-environment interactions are investigated. These structures are characterized by penetrance functions that are based on sigmoid functions or on combinations of linear and non-linear effects of a continuous environmental factor and a genetic factor with main effect or with a masking effect only. Results In our simulation study, neural networks are more successful in modeling gene-environment interactions than logistic regression models. This outperfomance is especially pronounced when modeling sigmoid penetrance functions, when distinguishing between linear and nonlinear components, and when modeling masking effects of the genetic factor. Conclusion Our study shows that neural networks are a promising approach for analyzing gene-environment interactions. Especially, if no prior knowledge of the correct nature of the relationship between co-variables and response variable is present, neural networks provide a valuable alternative to regression methods that are limited to the analysis of linearly separable data.

  10. Plasma selenium levels and oxidative stress biomarkers: a gene-environment interaction population-based study.

    Science.gov (United States)

    Galan-Chilet, Inmaculada; Tellez-Plaza, Maria; Guallar, Eliseo; De Marco, Griselda; Lopez-Izquierdo, Raul; Gonzalez-Manzano, Isabel; Carmen Tormos, M; Martin-Nuñez, Gracia M; Rojo-Martinez, Gemma; Saez, Guillermo T; Martín-Escudero, Juan C; Redon, Josep; Javier Chaves, F

    2014-09-01

    The role of selenium exposure in preventing chronic disease is controversial, especially in selenium-repleted populations. At high concentrations, selenium exposure may increase oxidative stress. Studies evaluating the interaction of genetic variation in genes involved in oxidative stress pathways and selenium are scarce. We evaluated the cross-sectional association of plasma selenium concentrations with oxidative stress levels, measured as oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8-oxo-7,8-dihydroguanine (8-oxo-dG) in urine, and the interacting role of genetic variation in oxidative stress candidate genes, in a representative sample of 1445 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.76 µg/L. In fully adjusted models the geometric mean ratios for oxidative stress biomarker levels comparing the highest to the lowest quintiles of plasma selenium levels were 0.61 (0.50-0.76) for GSSG/GSH, 0.89 (0.79-1.00) for MDA, and 1.06 (0.96-1.18) for 8-oxo-dG. We observed nonlinear dose-responses of selenium exposure and oxidative stress biomarkers, with plasma selenium concentrations above ~110 μg/L being positively associated with 8-oxo-dG, but inversely associated with GSSG/GSH and MDA. In addition, we identified potential risk genotypes associated with increased levels of oxidative stress markers with high selenium levels. Our findings support that high selenium levels increase oxidative stress in some biological processes. More studies are needed to disentangle the complexity of selenium biology and the relevance of potential gene-selenium interactions in relation to health outcomes in human populations. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Finding gene-environment interactions for phobias.

    Science.gov (United States)

    Gregory, Alice M; Lau, Jennifer Y F; Eley, Thalia C

    2008-03-01

    Phobias are common disorders causing a great deal of suffering. Studies of gene-environment interaction (G x E) have revealed much about the complex processes underlying the development of various psychiatric disorders but have told us little about phobias. This article describes what is already known about genetic and environmental influences upon phobias and suggests how this information can be used to optimise the chances of discovering G x Es for phobias. In addition to the careful conceptualisation of new studies, it is suggested that data already collected should be re-analysed in light of increased understanding of processes influencing phobias.

  12. Comparison of 2 models for gene-environment interactions: an example of simulated gene-medication interactions on systolic blood pressure in family-based data.

    Science.gov (United States)

    Fernández-Rhodes, Lindsay; Hodonsky, Chani J; Graff, Mariaelisa; Love, Shelly-Ann M; Howard, Annie Green; Seyerle, Amanda A; Avery, Christy L; Chittoor, Geetha; Franceschini, Nora; Voruganti, V Saroja; Young, Kristin; O'Connell, Jeffrey R; North, Kari E; Justice, Anne E

    2016-01-01

    Nearly half of adults in the United States who are diagnosed with hypertension use blood-pressure-lowering medications. Yet there is a large interindividual variability in the response to these medications. Two complementary gene-environment interaction methods have been published and incorporated into publicly available software packages to examine interaction effects, including whether genetic variants modify the association between medication use and blood pressure. The first approach uses a gene-environment interaction term to measure the change in outcome when both the genetic marker and medication are present (the "interaction model"). The second approach tests for effect-size differences between strata of an environmental exposure (the "med-diff" approach). However, no studies have quantitatively compared how these methods perform with respect to 1 or 2 degree of freedom (DF) tests or in family-based data sets. We evaluated these 2 approaches using simulated genotype-medication response interactions at 3 single nucleotide polymorphisms (SNPs) across a range of minor allele frequencies (MAFs 0.1-5.4 %) using the Genetic Analysis Workshop 19 family sample. The estimated interaction effect sizes were on average larger in the interaction model approach compared to the med-diff approach. The true positive proportion was higher for the med-diff approach for SNPs less than 1 % MAF, but higher for the interaction model when common variants were evaluated (MAF >5 %). The interaction model produced lower false-positive proportions than expected (5 %) across a range of MAFs for both the 1DF and 2DF tests. In contrast, the med-diff approach produced higher but stable false-positive proportions around 5 % across MAFs for both tests. Although the 1DF tests both performed similarly for common variants, the interaction model estimated true interaction effects with less bias and higher true positive proportions than the med-diff approach. However, if rare variation (MAF

  13. Environmental confounding in gene-environment interaction studies.

    Science.gov (United States)

    Vanderweele, Tyler J; Ko, Yi-An; Mukherjee, Bhramar

    2013-07-01

    We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies.

  14. Gene-Environment Interaction in Parkinson's Disease

    DEFF Research Database (Denmark)

    Chuang, Yu-Hsuan; Lill, Christina M; Lee, Pei-Chen

    2016-01-01

    ) metabolizes caffeine; thus, gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk. METHODS: In a population-based case-control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and gender-matched controls), we assessed interactions between...... interactions for ADORA2A rs5760423 and heavy vs. light coffee consumption in incident (OR interaction = 0.66 [95% CI 0.46-0.94], p = 0.02) but not prevalent PD. We did not observe interactions for CYP1A2 rs762551 and rs2472304 in incident or prevalent PD. In meta-analyses, PD associations with daily coffee...... consumption were strongest among carriers of variant alleles in both ADORA2A and CYP1A2. CONCLUSION: We corroborated results from a previous report that described interactions between ADORA2A and CYP1A2 polymorphisms and coffee consumption. Our results also suggest that survivor bias may affect results...

  15. The importance of gene-environment interactions in human obesity.

    Science.gov (United States)

    Reddon, Hudson; Guéant, Jean-Louis; Meyre, David

    2016-09-01

    The worldwide obesity epidemic has been mainly attributed to lifestyle changes. However, who becomes obese in an obesity-prone environment is largely determined by genetic factors. In the last 20 years, important progress has been made in the elucidation of the genetic architecture of obesity. In parallel with successful gene identifications, the number of gene-environment interaction (GEI) studies has grown rapidly. This paper reviews the growing body of evidence supporting gene-environment interactions in the field of obesity. Heritability, monogenic and polygenic obesity studies provide converging evidence that obesity-predisposing genes interact with a variety of environmental, lifestyle and treatment exposures. However, some skepticism remains regarding the validity of these studies based on several issues, which include statistical modelling, confounding, low replication rate, underpowered analyses, biological assumptions and measurement precision. What follows in this review includes (1) an introduction to the study of GEI, (2) the evidence of GEI in the field of obesity, (3) an outline of the biological mechanisms that may explain these interaction effects, (4) methodological challenges associated with GEI studies and potential solutions, and (5) future directions of GEI research. Thus far, this growing body of evidence has provided a deeper understanding of GEI influencing obesity and may have tremendous applications in the emerging field of personalized medicine and individualized lifestyle recommendations. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  16. Gene-environment interaction in atopic diseases

    DEFF Research Database (Denmark)

    Kahr, Niklas; Naeser, Vibeke; Stensballe, Lone Graff

    2015-01-01

    INTRODUCTION: The development of atopic diseases early in life suggests an important role of perinatal risk factors. OBJECTIVES: To study whether early-life exposures modify the genetic influence on atopic diseases in a twin population. METHODS: Questionnaire data on atopic diseases from 850....... Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis. RESULTS: After multivariable adjustment, prematurity (gestational age below 32 weeks) [odds ratio (OR) = 1.93, confidence interval (CI...... stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors. CONCLUSION: In this population-based study of children, there was no evidence of genetic effect modification of atopic diseases by several identified early-life risk factors...

  17. Semiparametric bayesian analysis of gene-environment interactions

    OpenAIRE

    Lobach, I.

    2010-01-01

    A key component to prevention and control of complex diseases, such as cancer, diabetes, hypertension, is to analyze the genetic and environmental factors that lead to the development of these complex diseases. We propose a Bayesian approach for analysis of gene-environment interactions that efficiently models information available in the observed data and a priori biomedical knowledge.

  18. Neural correlates of gene-environment interactions in ADHD

    NARCIS (Netherlands)

    van der Meer, Dennis

    2016-01-01

    The way we respond to our environment partly depends on our genes. So-called gene-environment interactions (GxE) may explain why some children develop attention-deficit/hyperactivity disorder (ADHD) when exposed to a stressful environment, whereas others do not. Knowledge of GxE may therefore not on

  19. Genotype-based association mapping of complex diseases: gene-environment interactions with multiple genetic markers and measurement error in environmental exposures.

    Science.gov (United States)

    Lobach, Iryna; Fan, Ruzong; Carroll, Raymond J

    2010-12-01

    With the advent of dense single nucleotide polymorphism genotyping, population-based association studies have become the major tools for identifying human disease genes and for fine gene mapping of complex traits. We develop a genotype-based approach for association analysis of case-control studies of gene-environment interactions in the case when environmental factors are measured with error and genotype data are available on multiple genetic markers. To directly use the observed genotype data, we propose two genotype-based models: genotype effect and additive effect models. Our approach offers several advantages. First, the proposed risk functions can directly incorporate the observed genotype data while modeling the linkage disequilibrium information in the regression coefficients, thus eliminating the need to infer haplotype phase. Compared with the haplotype-based approach, an estimating procedure based on the proposed methods can be much simpler and significantly faster. In addition, there is no potential risk due to haplotype phase estimation. Further, by fitting the proposed models, it is possible to analyze the risk alleles/variants of complex diseases, including their dominant or additive effects. To model measurement error, we adopt the pseudo-likelihood method by Lobach et al. [2008]. Performance of the proposed method is examined using simulation experiments. An application of our method is illustrated using a population-based case-control study of association between calcium intake with the risk of colorectal adenoma development.

  20. Gene-Environment Interactions in Severe Mental Illness

    Directory of Open Access Journals (Sweden)

    Rudolf eUher

    2014-05-01

    Full Text Available Severe mental illness is a broad category that includes schizophrenia, bipolar disorder and severe depression. Both genetic disposition and environmental exposures play important roles in the development of severe mental illness. Multiple lines of evidence suggest that the roles of genetic and environmental depend on each other. Gene-environment interactions may underlie the paradox of strong environmental factors for highly heritable disorders, the low estimates of shared environmental influences in twin studies of severe mental illness and the heritability gap between twin and molecular heritability estimates. Sons and daughters of parents with severe mental illness are more vulnerable to the effects of prenatal and postnatal environmental exposures, suggesting that the expression of genetic liability depends on environment. In the last decade, gene-environment interactions involving specific molecular variants in candidate genes have been identified. Replicated findings include an interaction between a polymorphism in the AKT1 gene and cannabis use in the development of psychosis and an interaction between the length polymorphism of the serotonin transporter gene and childhood maltreatment in the development of persistent depressive disorder. Bipolar disorder has been underinvestigated, with only a single study showing an interaction between a functional polymorphism in BDNF and stressful life events triggering bipolar depressive episodes. The first systematic search for gene-environment interactions has found that a polymorphism in CTNNA3 may sensitise the developing brain to the pathogenic effect of cytomegalovirus in utero, leading to schizophrenia in adulthood. Strategies for genome-wide investigations will likely include coordination between epidemiological and genetic research efforts, systematic assessment of multiple environmental factors in large samples, and prioritization of genetic variants.

  1. Gene-Environment Interactions in Asthma: Genetic and Epigenetic Effects.

    Science.gov (United States)

    Lee, Jong-Uk; Kim, Jeong Dong; Park, Choon-Sik

    2015-07-01

    Over the past three decades, a large number of genetic studies have been aimed at finding genetic variants associated with the risk of asthma, applying various genetic and genomic approaches including linkage analysis, candidate gene polymorphism studies, and genome-wide association studies (GWAS). However, contrary to general expectation, even single nucleotide polymorphisms (SNPs) discovered by GWAS failed to fully explain the heritability of asthma. Thus, application of rare allele polymorphisms in well defined phenotypes and clarification of environmental factors have been suggested to overcome the problem of 'missing' heritability. Such factors include allergens, cigarette smoke, air pollutants, and infectious agents during pre- and post-natal periods. The first and simplest interaction between a gene and the environment is a candidate interaction of both a well known gene and environmental factor in a direct physical or chemical interaction such as between CD14 and endotoxin or between HLA and allergens. Several GWAS have found environmental interactions with occupational asthma, aspirin exacerbated respiratory disease, tobacco smoke-related airway dysfunction, and farm-related atopic diseases. As one of the mechanisms behind gene-environment interaction is epigenetics, a few studies on DNA CpG methylation have been reported on subphenotypes of asthma, pitching the exciting idea that it may be possible to intervene at the junction between the genome and the environment. Epigenetic studies are starting to include data from clinical samples, which will make them another powerful tool for re-search on gene-environment interactions in asthma.

  2. Gene-environment interactions in sporadic Parkinson's disease.

    Science.gov (United States)

    Benmoyal-Segal, Liat; Soreq, Hermona

    2006-06-01

    Much has been learned in recent years about the genetics of familial Parkinson's disease. However, far less is known about those malfunctioning genes which contribute to the emergence and/or progression of the vast majority of cases, the 'sporadic Parkinson's disease', which is the focus of our current review. Drastic differences in the reported prevalence of Parkinson's disease in different continents and countries suggest ethnic and/or environmental-associated multigenic contributions to this disease. Numerous association studies showing variable involvement of multiple tested genes in these distinct locations support this notion. Also, variable increases in the risk of Parkinson's disease due to exposure to agricultural insecticides indicate complex gene-environment interactions, especially when genes involved in protection from oxidative stress are explored. Further consideration of the brain regions damaged in Parkinson's disease points at the age-vulnerable cholinergic-dopaminergic balance as being involved in the emergence of sporadic Parkinson's disease in general and in the exposure-induced risks in particular. More specifically, the chromosome 7 ACHE/PON1 locus emerges as a key region controlling this sensitive balance, and animal model experiments are compatible with this concept. Future progress in the understanding of the genetics of sporadic Parkinson's disease depends on globally coordinated, multileveled studies of gene-environment interactions.

  3. Gene-environment interactions and alcohol use and dependence: current status and future challenges

    NARCIS (Netherlands)

    Zwaluw, C.S. van der; Engels, R.C.M.E.

    2009-01-01

    To discuss the current status of gene-environment interaction research with regard to alcohol use and dependence. Further, we highlight the difficulties concerning gene-environment studies. Overview of the current evidence for gene-environment interactions in alcohol outcomes, and of the associated

  4. Gene-environment Interactions in the Etiology of Dental Caries.

    Science.gov (United States)

    Yildiz, G; Ermis, R B; Calapoglu, N S; Celik, E U; Türel, G Y

    2016-01-01

    Dental caries is a multifactorial disease that can be conceptualized as an interaction between genetic and environmental risk factors. The aim of this study is to examine the effects of AMELX, CA6, DEFB1, and TAS2R38 gene polymorphism and gene-environment interactions on caries etiology and susceptibility in adults. Genomic DNA was extracted from the buccal mucosa, and adults aged 20 to 60 y were placed into 1 of 2 groups: low caries risk (DMFT ≤ 5; n = 77) and high caries risk (DMFT ≥ 14; n = 77). The frequency of AMELX (+522), CA6 (T55M), DEFB1 (G-20A), and TAS2R38 (A49P) single-nucleotide polymorphisms was genotyped with the polymerase chain reaction-restriction fragment length polymorphism method. Environmental risk factors examined in the study included plaque amount, toothbrushing frequency, dietary intake between meals, saliva secretion rate, saliva buffer capacity, mutans streptococci counts, and lactobacilli counts. There was no difference between the caries risk groups in relation to AMELX (+522) polymorphism (χ(2) test, P > 0.05). The distribution of CA6 genotype and allele frequencies in the low caries risk group did not differ from the high caries risk group (χ(2) test, P > 0.05). Polymorphism of DEFB1 (G-20A) was positively associated, and TAS2R38 (A49P) negatively associated, with caries risk (χ(2) test, P = 0.000). There were significant differences between caries susceptibility and each environmental risk factor, except for the saliva secretion rate (Mann-Whitney U test, P = 0.000). Based on stepwise multiple linear regression analyses, dental plaque amount, lactobacilli count, age, and saliva buffer capacity, as well as DEFB1 (G-20A), TAS2R38 (A49P), and CA6 (T55M) gene polymorphism, explained a total of 87.8% of the variations in DMFT scores. It can be concluded that variation in CA6 (T55M), DEFB1 (G-20A), and TAS2R38 (A49P) may be associated with caries experience in Turkish adults with a high level of dental plaque, lactobacilli count

  5. Sleep Duration and Depressive Symptoms: A Gene-Environment Interaction

    Science.gov (United States)

    Watson, Nathaniel F.; Harden, Kathryn Paige; Buchwald, Dedra; Vitiello, Michael V.; Pack, Allan I.; Strachan, Eric; Goldberg, Jack

    2014-01-01

    Objective: We used quantitative genetic models to assess whether sleep duration modifies genetic and environmental influences on depressive symptoms. Method: Participants were 1,788 adult twins from 894 same-sex twin pairs (192 male and 412 female monozygotic [MZ] pairs, and 81 male and 209 female dizygotic [DZ] pairs] from the University of Washington Twin Registry. Participants self-reported habitual sleep duration and depressive symptoms. Data were analyzed using quantitative genetic interaction models, which allowed the magnitude of additive genetic, shared environmental, and non-shared environmental influences on depressive symptoms to vary with sleep duration. Results: Within MZ twin pairs, the twin who reported longer sleep duration reported fewer depressive symptoms (ec = -0.17, SE = 0.06, P sleep duration interaction effect on depressive symptoms (a'c = 0.23, SE = 0.08, P sleep duration and depressive symptoms. Among individuals with sleep duration within the normal range (7-8.9 h/night), the total heritability (h2) of depressive symptoms was approximately 27%. However, among individuals with sleep duration within the low (sleep duration extremes (5 h/night: h2 = 53%; 10 h/night: h2 = 49%). Conclusion: Genetic contributions to depressive symptoms increase at both short and long sleep durations. Citation: Watson NF; Harden KP; Buchwald D; Vitiello MV; Pack AI; Stachan E; Goldberg J. Sleep duration and depressive symptoms: a gene-environment interaction. SLEEP 2014;37(2):351-358. PMID:24497663

  6. Study of oral clefts: Indication of gene-environment interaction

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, S.J.; Beaty, T.H.; Panny, S. [Johns Hopkins Univ., Baltimore, MD (United States)] [and others

    1994-09-01

    In this study of infants with isolated birth defects, 69 cleft palate-only (CPO) cases, 114 cleft lip with or without palate (CL/P), and 284 controls with non-cleft birth defects (all born in Maryland during 1984-1992) were examined to test for associations among genetic markers and different oral clefts. Modest associations were found between transforming growth factor {alpha} (TGF{alpha}) marker and CPO, as well as that between D17S579 (Mfd188) and CL/P in this study. The association between TGF{alpha} marker and CPO reflects a statistical interaction between mother`s smoking and child`s TGF{alpha} genotype. A significantly higher risk of CPO was found among those reporting maternal smoking during pregnancy and carrying less common TGF{alpha} TaqI allele (odds ratio=7.02 with 95% confidence interval 1.8-27.6). This gene-environment interaction was also found among those who reported no family history of any type of birth defect (odds ratio=5.60 with 95% confidence interval 1.4-22.9). Similar associations were seen for CL/P, but these were not statistically significant.

  7. Music training and speech perception: a gene-environment interaction.

    Science.gov (United States)

    Schellenberg, E Glenn

    2015-03-01

    Claims of beneficial side effects of music training are made for many different abilities, including verbal and visuospatial abilities, executive functions, working memory, IQ, and speech perception in particular. Such claims assume that music training causes the associations even though children who take music lessons are likely to differ from other children in music aptitude, which is associated with many aspects of speech perception. Music training in childhood is also associated with cognitive, personality, and demographic variables, and it is well established that IQ and personality are determined largely by genetics. Recent evidence also indicates that the role of genetics in music aptitude and music achievement is much larger than previously thought. In short, music training is an ideal model for the study of gene-environment interactions but far less appropriate as a model for the study of plasticity. Children seek out environments, including those with music lessons, that are consistent with their predispositions; such environments exaggerate preexisting individual differences. © 2015 New York Academy of Sciences.

  8. Subtle gene-environment interactions driving paranoia in daily life.

    Science.gov (United States)

    Simons, C J P; Wichers, M; Derom, C; Thiery, E; Myin-Germeys, I; Krabbendam, L; van Os, J

    2009-02-01

    It has been suggested that genes impact on the degree to which minor daily stressors cause variation in the intensity of subtle paranoid experiences. The objective of the present study was to test the hypothesis that catechol-O-methyltransferase (COMT) Val(158)Met and brain-derived neurotrophic factor (BDNF) Val(66)Met in part mediate genetic effects on paranoid reactivity to minor stressors. In a general population sample of 579 young adult female twins, on the one hand, appraisals of (1) event-related stress and (2) social stress and, on the other hand, feelings of paranoia in the flow of daily life were assessed using momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of daily life stress-induced paranoia by COMT Val(158)Met and BDNF Val(66)Met genotypes. Catechol-O-methyltransferase Val carriers displayed more feelings of paranoia in response to event stress compared with Met carriers. Brain-derived neurotrophic factor Met carriers showed more social-stress-induced paranoia than individuals with the Val/Val genotype. Thus, paranoia in the flow of daily life may be the result of gene-environment interactions that can be traced to different types of stress being moderated by different types of genetic variation.

  9. A novel approach to simulate gene-environment interactions in complex diseases

    Directory of Open Access Journals (Sweden)

    Nicodemi Mario

    2010-01-01

    Full Text Available Abstract Background Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.. Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. Results We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS, a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. Conclusions By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte

  10. Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate

    DEFF Research Database (Denmark)

    Beaty, Terri H; Ruczinski, Ingo; Murray, Jeffrey C

    2011-01-01

    consortium. Family-based association tests of single nucleotide polymorphisms (SNP) and three common maternal exposures (maternal smoking, alcohol consumption, and multivitamin supplementation) were used in a combined 2 df test for gene (G) and gene-environment (G × E) interaction simultaneously, plus...... G × E interaction was included. Among these, MLLT3 and SMC2 on chromosome 9 showed multiple SNPs resulting in an increased risk if the mother consumed alcohol during the peri-conceptual period (3 months prior to conception through the first trimester). TBK1 on chr. 12 and ZNF236 on chr. 18 showed...

  11. Comparisons of power of statistical methods for gene-environment interaction analyses.

    Science.gov (United States)

    Ege, Markus J; Strachan, David P

    2013-10-01

    Any genome-wide analysis is hampered by reduced statistical power due to multiple comparisons. This is particularly true for interaction analyses, which have lower statistical power than analyses of associations. To assess gene-environment interactions in population settings we have recently proposed a statistical method based on a modified two-step approach, where first genetic loci are selected by their associations with disease and environment, respectively, and subsequently tested for interactions. We have simulated various data sets resembling real world scenarios and compared single-step and two-step approaches with respect to true positive rate (TPR) in 486 scenarios and (study-wide) false positive rate (FPR) in 252 scenarios. Our simulations confirmed that in all two-step methods the two steps are not correlated. In terms of TPR, two-step approaches combining information on gene-disease association and gene-environment association in the first step were superior to all other methods, while preserving a low FPR in over 250 million simulations under the null hypothesis. Our weighted modification yielded the highest power across various degrees of gene-environment association in the controls. An optimal threshold for step 1 depended on the interacting allele frequency and the disease prevalence. In all scenarios, the least powerful method was to proceed directly to an unbiased full interaction model, applying conventional genome-wide significance thresholds. This simulation study confirms the practical advantage of two-step approaches to interaction testing over more conventional one-step designs, at least in the context of dichotomous disease outcomes and other parameters that might apply in real-world settings.

  12. CYP1A1 genetic polymorphism and polycyclic aromatic hydrocarbons on pulmonary function in the elderly: haplotype-based approach for gene-environment interaction.

    Science.gov (United States)

    Choi, Yoon-Hyeong; Kim, Jin Hee; Hong, Yun-Chul

    2013-08-29

    Lung function may be impaired by environmental pollutants not only acting alone, but working with genetic factors as well. Few epidemiologic studies have been conducted to explore the interplay of polycyclic aromatic hydrocarbons (PAHs) exposure and genetic polymorphism on lung function in the elderly. For genetic polymorphism, haplotype is considered a more informative unit than single nucleotide polymorphism markers. Therefore, we examined the role of haplotype based-CYP1A1 polymorphism in the effect of PAHs exposure on lung function in 422 participants from a community-based panel of elderly adults in Seoul, Korea. Linear mixed effect models were fit to evaluate the association of PAH exposure markers (urinary 1-hydroxypyrene and 2-naphthol) with FVC, FEV₁, FEV₁/FVC, and FEF₂₅₋₇₅, and then the interaction with CYP1A1 haplotype constructed from three single nucleotide polymorphisms of the gene (rs4646421/rs4646422/rs1048943). Urinary 1-hydroxypyrene levels were inversely associated with FEV₁/FVC (ppolymorphisms on lung functions. Our findings suggest that PAH exposure producing 1-hydroxypyrene as a metabolite compromises lung function in the elderly, and that haplotype-based CYP1A1 polymorphism modifies the risk.

  13. Review of the Gene-Environment Interaction Literature in Cancer: What Do We Know?

    Science.gov (United States)

    Simonds, Naoko I; Ghazarian, Armen A; Pimentel, Camilla B; Schully, Sheri D; Ellison, Gary L; Gillanders, Elizabeth M; Mechanic, Leah E

    2016-07-01

    Risk of cancer is determined by a complex interplay of genetic and environmental factors. Although the study of gene-environment interactions (G×E) has been an active area of research, little is reported about the known findings in the literature. To examine the state of the science in G×E research in cancer, we performed a systematic review of published literature using gene-environment or pharmacogenomic flags from two curated databases of genetic association studies, the Human Genome Epidemiology (HuGE) literature finder and Cancer Genome-Wide Association and Meta Analyses Database (CancerGAMAdb), from January 1, 2001, to January 31, 2011. A supplemental search using HuGE was conducted for articles published from February 1, 2011, to April 11, 2013. A 25% sample of the supplemental publications was reviewed. A total of 3,019 articles were identified in the original search. From these articles, 243 articles were determined to be relevant based on inclusion criteria (more than 3,500 interactions). From the supplemental search (1,400 articles identified), 29 additional relevant articles (1,370 interactions) were included. The majority of publications in both searches examined G×E in colon, rectal, or colorectal; breast; or lung cancer. Specific interactions examined most frequently included environmental factors categorized as energy balance (e.g., body mass index, diet), exogenous (e.g., oral contraceptives) and endogenous hormones (e.g., menopausal status), chemical environment (e.g., grilled meats), and lifestyle (e.g., smoking, alcohol intake). In both searches, the majority of interactions examined were using loci from candidate genes studies and none of the studies were genome-wide interaction studies (GEWIS). The most commonly reported measure was the interaction P-value, of which a sizable number of P-values were considered statistically significant (i.e., article is a U.S. Government work and is in the public domain in the USA.

  14. Potential role of gene-environment interactions in ion transport mechanisms in the etiology of renal cell cancer

    Science.gov (United States)

    Deckers, Ivette A. G.; van den Brandt, Piet A.; van Engeland, Manon; van Schooten, Frederik J.; Godschalk, Roger W. L.; Keszei, András P.; Hogervorst, Janneke G. F.; Schouten, Leo J.

    2016-01-01

    We investigated the ion transport mechanism (ITM) in renal cell cancer (RCC) etiology using gene-environment interactions between candidate single nucleotide polymorphisms (SNPs) and associated environmental factors, including dietary intakes of sodium, potassium and fluid, hypertension and diuretic medication. A literature-based selection of 13 SNPs in ten ITM genes were successfully genotyped in toenail DNA of 3,048 subcohort members and 419 RCC cases from the Netherlands Cohort Study. Diet and lifestyle were measured with baseline questionnaires. Cox regression analyses were conducted for main effects and gene-environment interactions. ADD1_rs4961 was significantly associated with RCC risk, showing a Hazard Ratio (HR) of 1.24 (95% confidence intervals (CI): 1.01–1.53) for the GT + TT (versus GG) genotype. Four of 65 tested gene-environment interactions were statistically significant. Three of these interactions clustered in SLC9A3_rs4957061, including the ones with fluid and potassium intake, and diuretic medication. For fluid intake, the RCC risk was significantly lower for high versus low intake in participants with the CC genotype (HR(95% CI): 0.47(0.26–0.86)), but not for the CT + TT genotype (P-interaction = 0.002). None of the main genetic effects and gene-environment interactions remained significant after adjustment for multiple testing. Data do not support the general hypothesis that the ITM is a disease mechanism in RCC etiology. PMID:27686058

  15. A Fast Multiple-Kernel Method With Applications to Detect Gene-Environment Interaction.

    Science.gov (United States)

    Marceau, Rachel; Lu, Wenbin; Holloway, Shannon; Sale, Michèle M; Worrall, Bradford B; Williams, Stephen R; Hsu, Fang-Chi; Tzeng, Jung-Ying

    2015-09-01

    Kernel machine (KM) models are a powerful tool for exploring associations between sets of genetic variants and complex traits. Although most KM methods use a single kernel function to assess the marginal effect of a variable set, KM analyses involving multiple kernels have become increasingly popular. Multikernel analysis allows researchers to study more complex problems, such as assessing gene-gene or gene-environment interactions, incorporating variance-component based methods for population substructure into rare-variant association testing, and assessing the conditional effects of a variable set adjusting for other variable sets. The KM framework is robust, powerful, and provides efficient dimension reduction for multifactor analyses, but requires the estimation of high dimensional nuisance parameters. Traditional estimation techniques, including regularization and the "expectation-maximization (EM)" algorithm, have a large computational cost and are not scalable to large sample sizes needed for rare variant analysis. Therefore, under the context of gene-environment interaction, we propose a computationally efficient and statistically rigorous "fastKM" algorithm for multikernel analysis that is based on a low-rank approximation to the nuisance effect kernel matrices. Our algorithm is applicable to various trait types (e.g., continuous, binary, and survival traits) and can be implemented using any existing single-kernel analysis software. Through extensive simulation studies, we show that our algorithm has similar performance to an EM-based KM approach for quantitative traits while running much faster. We also apply our method to the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, examining gene-by-vitamin effects on recurrent stroke risk and gene-by-age effects on change in homocysteine level.

  16. Gene-environment interactions in Leber hereditary optic neuropathy.

    Science.gov (United States)

    Kirkman, Matthew Anthony; Yu-Wai-Man, Patrick; Korsten, Alex; Leonhardt, Miriam; Dimitriadis, Konstantin; De Coo, Ireneaus F; Klopstock, Thomas; Chinnery, Patrick Francis

    2009-09-01

    Leber hereditary optic neuropathy (LHON) is a genetic disorder primarily due to mutations of mitochondrial DNA (mtDNA). Environmental factors are thought to precipitate the visual failure and explain the marked incomplete penetrance of LHON, but previous small studies have failed to confirm this to be the case. LHON has no treatment, so identifying environmental triggers is the key to disease prevention, whilst potentially revealing new mechanisms amenable to therapeutic manipulation. To address this issue, we conducted a large, multicentre epidemiological study of 196 affected and 206 unaffected carriers from 125 LHON pedigrees known to harbour one of the three primary pathogenic mtDNA mutations: m.3460G>A, m.11778G>A and m.14484T>C. A comprehensive history of exposure to smoking, alcohol and other putative environmental insults was collected using a structured questionnaire. We identified a strong and consistent association between visual loss and smoking, independent of gender and alcohol intake, leading to a clinical penetrance of 93% in men who smoked. There was a trend towards increased visual failure with alcohol, but only with a heavy intake. Based on these findings, asymptomatic carriers of a LHON mtDNA mutation should be strongly advised not to smoke and to moderate their alcohol intake.

  17. Behavior of QQ-plots and genomic control in studies of gene-environment interaction.

    Directory of Open Access Journals (Sweden)

    Arend Voorman

    Full Text Available Genome-wide association studies of gene-environment interaction (GxE GWAS are becoming popular. As with main effects GWAS, quantile-quantile plots (QQ-plots and Genomic Control are being used to assess and correct for population substructure. However, in G x E work these approaches can be seriously misleading, as we illustrate; QQ-plots may give strong indications of substructure when absolutely none is present. Using simulation and theory, we show how and why spurious QQ-plot inflation occurs in G x E GWAS, and how this differs from main-effects analyses. We also explain how simple adjustments to standard regression-based methods used in G x E GWAS can alleviate this problem.

  18. Case-control studies of gene-environment interaction: Bayesian design and analysis.

    Science.gov (United States)

    Mukherjee, Bhramar; Ahn, Jaeil; Gruber, Stephen B; Ghosh, Malay; Chatterjee, Nilanjan

    2010-09-01

    With increasing frequency, epidemiologic studies are addressing hypotheses regarding gene-environment interaction. In many well-studied candidate genes and for standard dietary and behavioral epidemiologic exposures, there is often substantial prior information available that may be used to analyze current data as well as for designing a new study. In this article, first, we propose a proper full Bayesian approach for analyzing studies of gene-environment interaction. The Bayesian approach provides a natural way to incorporate uncertainties around the assumption of gene-environment independence, often used in such an analysis. We then consider Bayesian sample size determination criteria for both estimation and hypothesis testing regarding the multiplicative gene-environment interaction parameter. We illustrate our proposed methods using data from a large ongoing case-control study of colorectal cancer investigating the interaction of N-acetyl transferase type 2 (NAT2) with smoking and red meat consumption. We use the existing data to elicit a design prior and show how to use this information in allocating cases and controls in planning a future study that investigates the same interaction parameters. The Bayesian design and analysis strategies are compared with their corresponding frequentist counterparts.

  19. Gene-environment interactions in early life and adulthood : implications for cocaine intake

    NARCIS (Netherlands)

    Veen, Rixt van der

    2008-01-01

    The objective of the research described in this thesis was to demonstrate the role of gene-environment interactions in the emergence of individual differences in cocaine use. For this purpose we used two inbred mouse strains, the C57Bl/6 (C57) and DBA/2 (DBA), which are known to differ in drug-intak

  20. Gene-Environment Interactions in Genome-Wide Association Studies: Current Approaches and New Directions

    Science.gov (United States)

    Winham, Stacey J.; Biernacka, Joanna M.

    2013-01-01

    Background: Complex psychiatric traits have long been thought to be the result of a combination of genetic and environmental factors, and gene-environment interactions are thought to play a crucial role in behavioral phenotypes and the susceptibility and progression of psychiatric disorders. Candidate gene studies to investigate hypothesized…

  1. Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions

    DEFF Research Database (Denmark)

    Schoeps, Anja; Rudolph, Anja; Seibold, Petra

    2014-01-01

    Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,47...

  2. A maximum likelihood method for studying gene-environment interactions under conditional independence of genotype and exposure.

    Science.gov (United States)

    Cheng, K F

    2006-09-30

    Given the biomedical interest in gene-environment interactions along with the difficulties inherent in gathering genetic data from controls, epidemiologists need methodologies that can increase precision of estimating interactions while minimizing the genotyping of controls. To achieve this purpose, many epidemiologists suggested that one can use case-only design. In this paper, we present a maximum likelihood method for making inference about gene-environment interactions using case-only data. The probability of disease development is described by a logistic risk model. Thus the interactions are model parameters measuring the departure of joint effects of exposure and genotype from multiplicative odds ratios. We extend the typical inference method derived under the assumption of independence between genotype and exposure to that under a more general assumption of conditional independence. Our maximum likelihood method can be applied to analyse both categorical and continuous environmental factors, and generalized to make inference about gene-gene-environment interactions. Moreover, the application of this method can be reduced to simply fitting a multinomial logistic model when we have case-only data. As a consequence, the maximum likelihood estimates of interactions and likelihood ratio tests for hypotheses concerning interactions can be easily computed. The methodology is illustrated through an example based on a study about the joint effects of XRCC1 polymorphisms and smoking on bladder cancer. We also give two simulation studies to show that the proposed method is reliable in finite sample situation.

  3. Perinatal Gene-Gene and Gene-Environment Interactions on IgE Production and Asthma Development

    Directory of Open Access Journals (Sweden)

    Jen-Chieh Chang

    2012-01-01

    Full Text Available Atopic asthma is a complex disease associated with IgE-mediated immune reactions. Numerous genome-wide studies identified more than 100 genes in 22 chromosomes associated with atopic asthma, and different genetic backgrounds in different environments could modulate susceptibility to atopic asthma. Current knowledge emphasizes the effect of tobacco smoke on the development of childhood asthma. This suggests that asthma, although heritable, is significantly affected by gene-gene and gene-environment interactions. Evidence has recently shown that molecular mechanism of a complex disease may be limited to not only DNA sequence differences, but also gene-environmental interactions for epigenetic difference. This paper reviews and summarizes how gene-gene and gene-environment interactions affect IgE production and the development of atopic asthma in prenatal and childhood stages. Based on the mechanisms responsible for perinatal gene-environment interactions on IgE production and development of asthma, we formulate several potential strategies to prevent the development of asthma in the perinatal stage.

  4. Advances in adult asthma diagnosis and treatment in 2012: potential therapeutics and gene-environment interactions.

    Science.gov (United States)

    Apter, Andrea J

    2013-01-01

    In the Journal of Allergy and Clinical Immunology in 2012, research reports related to asthma in adults clustered around mechanisms of disease, with a special focus on their potential for informing new therapies. There was also consideration of the effect of the environment on health from pollution, climate change, and epigenetic influences, underlining the importance of understanding gene-environment interactions in the pathogenesis of asthma and response to treatment.

  5. A methodology to establish a database to study gene environment interactions for childhood asthma

    Directory of Open Access Journals (Sweden)

    McCormick Jonathan

    2010-12-01

    Full Text Available Abstract Background Gene-environment interactions are likely to explain some of the heterogeneity in childhood asthma. Here, we describe the methodology and experiences in establishing a database for childhood asthma designed to study gene-environment interactions (PAGES - Paediatric Asthma Gene Environment Study. Methods Children with asthma and under the care of a respiratory paediatrician are being recruited from 15 hospitals between 2008 and 2011. An asthma questionnaire is completed and returned by post. At a routine clinic visit saliva is collected for DNA extraction. Detailed phenotyping in a proportion of children includes spirometry, bronchodilator response (BDR, skin prick reactivity, exhaled nitric oxide and salivary cotinine. Dietary and quality of life questionnaires are completed. Data are entered onto a purpose-built database. Results To date 1045 children have been invited to participate and data collected in 501 (48%. The mean age (SD of participants is 8.6 (3.9 years, 57% male. DNA has been collected in 436 children. Spirometry has been obtained in 172 children, mean % predicted (SD FEV1 97% (15 and median (IQR BDR is 5% (2, 9. There were differences in age, socioeconomic status, severity and %FEV1 between the different centres (p≤0.024. Reasons for non-participation included parents not having time to take part, children not attending clinics and, in a small proportion, refusal to take part. Conclusions It is feasible to establish a national database to study gene-environment interactions within an asthmatic paediatric population; there are barriers to participation and some different characteristics in individuals recruited from different centres. Recruitment to our study continues and is anticipated to extend current understanding of asthma heterogeneity.

  6. Detecting gene-environment interactions in human birth defects: Study designs and statistical methods.

    Science.gov (United States)

    Tai, Caroline G; Graff, Rebecca E; Liu, Jinghua; Passarelli, Michael N; Mefford, Joel A; Shaw, Gary M; Hoffmann, Thomas J; Witte, John S

    2015-08-01

    The National Birth Defects Prevention Study (NBDPS) contains a wealth of information on affected and unaffected family triads, and thus provides numerous opportunities to study gene-environment interactions (G×E) in the etiology of birth defect outcomes. Depending on the research objective, several analytic options exist to estimate G×E effects that use varying combinations of individuals drawn from available triads. In this study, we discuss important considerations in the collection of genetic data and environmental exposures. We will also present several population- and family-based approaches that can be applied to data from the NBDPS including case-control, case-only, family-based trio, and maternal versus fetal effects. For each, we describe the data requirements, applicable statistical methods, advantages, and disadvantages. A range of approaches can be used to evaluate potentially important G×E effects in the NBDPS. Investigators should be aware of the limitations inherent to each approach when choosing a study design and interpreting results. © 2015 Wiley Periodicals, Inc.

  7. Gene-Environment Interactions in Stress Response Contribute Additively to a Genotype-Environment Interaction.

    Directory of Open Access Journals (Sweden)

    Takeshi Matsui

    2016-07-01

    Full Text Available How combinations of gene-environment interactions collectively give rise to genotype-environment interactions is not fully understood. To shed light on this problem, we genetically dissected an environment-specific poor growth phenotype in a cross of two budding yeast strains. This phenotype is detectable when certain segregants are grown on ethanol at 37°C ('E37', a condition that differs from the standard culturing environment in both its carbon source (ethanol as opposed to glucose and temperature (37°C as opposed to 30°C. Using recurrent backcrossing with phenotypic selection, we identified 16 contributing loci. To examine how these loci interact with each other and the environment, we focused on a subset of four loci that together can lead to poor growth in E37. We measured the growth of all 16 haploid combinations of alleles at these loci in all four possible combinations of carbon source (ethanol or glucose and temperature (30 or 37°C in a nearly isogenic population. This revealed that the four loci act in an almost entirely additive manner in E37. However, we also found that these loci have weaker effects when only carbon source or temperature is altered, suggesting that their effect magnitudes depend on the severity of environmental perturbation. Consistent with such a possibility, cloning of three causal genes identified factors that have unrelated functions in stress response. Thus, our results indicate that polymorphisms in stress response can show effects that are intensified by environmental stress, thereby resulting in major genotype-environment interactions when multiple of these variants co-occur.

  8. Community-Based Participatory Research and Gene-Environment Interaction Methodologies Addressing Environmental Justice among Migrant and Seasonal Farmworker Women and Children in Texas: "From Mother to Child Project"

    Science.gov (United States)

    Hernández-Valero, María A; Herrera, Angelica P; Zahm, Sheila H; Jones, Lovell A

    2007-05-01

    The "From Mother to Child Project" is a molecular epidemiological study that employs a community- based participatory research (CBPR) approach and gene-environment interaction research to address environmental justice in migrant and seasonal farmworker (MSF) women and children of Mexican origin home-based in Baytown and La Joya, Texas. This paper presents the background and rationale for the study and describes the study design and methodology. Preliminary data showed that MSF women and children in Texas have measurable levels of pesticides in their blood and urine, some of which were banned in the United States decades ago and are possible human carcinogens. Polymorphisms in genes involved in chemical detoxification and DNA repair have been associated with susceptibility to genetic damage and cancer development in populations exposed to environmental toxins. The "From Mother to Child Project" is testing three hypotheses: (1) MSF women and children who are occupationally exposed to pesticides are at higher risk for DNA damage than are non-exposed women and children. (2) Both, the extent of pesticide exposure and type of polymorphisms in chemical detoxification and DNA repair genes contribute to the extent of DNA damage observed in study participants. (3) The mutagenic potency levels measured in the organic compounds extracted from the urine and serum of study participants will correlate with the total concentrations of pesticides and with the measured DNA damage in study participants. The study will enroll 800 participants: 200 MSF mother-child pairs; 200 children (one per family) whose parents have never worked in agriculture, matched with the MSF children by ethnicity, age ± 2 years, gender, and city of residence; and these children's mothers. Personal interviews with the mothers are used to gather data for both mothers and children on sociodemographic characteristics; pesticide exposure at work and home; medical and reproductive history; dietary assessment, and

  9. Genome-wide gene-environment interactions on quantitative traits using family data.

    Science.gov (United States)

    Sitlani, Colleen M; Dupuis, Josée; Rice, Kenneth M; Sun, Fangui; Pitsillides, Achilleas N; Cupples, L Adrienne; Psaty, Bruce M

    2016-07-01

    Gene-environment interactions may provide a mechanism for targeting interventions to those individuals who would gain the most benefit from them. Searching for interactions agnostically on a genome-wide scale requires large sample sizes, often achieved through collaboration among multiple studies in a consortium. Family studies can contribute to consortia, but to do so they must account for correlation within families by using specialized analytic methods. In this paper, we investigate the performance of methods that account for within-family correlation, in the context of gene-environment interactions with binary exposures and quantitative outcomes. We simulate both cross-sectional and longitudinal measurements, and analyze the simulated data taking family structure into account, via generalized estimating equations (GEE) and linear mixed-effects models. With sufficient exposure prevalence and correct model specification, all methods perform well. However, when models are misspecified, mixed modeling approaches have seriously inflated type I error rates. GEE methods with robust variance estimates are less sensitive to model misspecification; however, when exposures are infrequent, GEE methods require modifications to preserve type I error rate. We illustrate the practical use of these methods by evaluating gene-drug interactions on fasting glucose levels in data from the Framingham Heart Study, a cohort that includes related individuals.

  10. Gene-environment interactions in early life and adulthood: implications for cocaine intake

    OpenAIRE

    van der Veen, Rixt

    2008-01-01

    The objective of the research described in this thesis was to demonstrate the role of gene-environment interactions in the emergence of individual differences in cocaine use. For this purpose we used two inbred mouse strains, the C57Bl/6 (C57) and DBA/2 (DBA), which are known to differ in drug-intake and to be differentially sensitive to several stressors. We studied the impact of early life experiences (long-term influence) as well as a later life psychosocial stressor (short-term influence)...

  11. Bisphenol-A and Female Infertility: A Possible Role of Gene-Environment Interactions

    Directory of Open Access Journals (Sweden)

    Xiaona Huo

    2015-09-01

    Full Text Available Background: Bisphenol-A (BPA is widely used and ubiquitous in the environment. Animal studies indicate that BPA affects reproduction, however, the gene-environment interaction mechanism(s involved in this association remains unclear. We performed a literature review to summarize the evidence on this topic. Methods: A comprehensive search was conducted in PubMed using as keywords BPA, gene, infertility and female reproduction. Full-text articles in both human and animals published in English prior to December 2014 were selected. Results: Evidence shows that BPA can interfere with endocrine function of hypothalamic-pituitary axis, such as by changing gonadotropin-releasing hormones (GnRH secretion in hypothalamus and promoting pituitary proliferation. Such actions affect puberty, ovulation and may even result in infertility. Ovary, uterus and other reproductive organs are also targets of BPA. BPA exposure impairs the structure and functions of female reproductive system in different times of life cycle and may contribute to infertility. Both epidemiological and experimental evidences demonstrate that BPA affects reproduction-related gene expression and epigenetic modification that are closely associated with infertility. The detrimental effects on reproduction may be lifelong and transgenerational. Conclusions: Evidence on gene-environment interactions, especially from human studies, is still limited. Further research on this topic is warranted.

  12. Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    L. Chouliaras

    2010-01-01

    Full Text Available The etiology of the sporadic form of Alzheimer's disease (AD remains largely unknown. Recent evidence has suggested that gene-environment interactions (GxE may play a crucial role in its development and progression. Whereas various susceptibility loci have been identified, like the apolipoprotein E4 allele, these cannot fully explain the increasing prevalence of AD observed with aging. In addition to such genetic risk factors, various environmental factors have been proposed to alter the risk of developing AD as well as to affect the rate of cognitive decline in AD patients. Nevertheless, aside from the independent effects of genetic and environmental risk factors, their synergistic participation in increasing the risk of developing AD has been sparsely investigated, even though evidence points towards such a direction. Advances in the genetic manipulation of mice, modeling various aspects of the AD pathology, have provided an excellent tool to dissect the effects of genes, environment, and their interactions. In this paper we present several environmental factors implicated in the etiology of AD that have been tested in transgenic animal models of the disease. The focus lies on the concept of GxE and its importance in a multifactorial disease like AD. Additionally, possible mediating mechanisms and future challenges are discussed.

  13. Environmental and gene-environment interactions and risk of rheumatoid arthritis

    Science.gov (United States)

    Karlson, Elizabeth W.; Deane, Kevin

    2012-01-01

    Multiple environmental factors including hormones, dietary factors, infections and exposure to tobacco smoke as well as gene-environment interactions have been associated with increased risk for rheumatoid arthritis (RA). Importantly, the growing understanding of the prolonged period prior to the first onset of symptoms of RA suggests that these environmental and genetic factors are likely acting to drive the development of RA-related autoimmunity long before the appearance of the first joint symptoms and clinical findings that are characteristic of RA. Herein we will review these factors and interactions, especially those that have been investigated in a prospective fashion prior to the symptomatic onset of RA. We will also discuss how these factors may be explored in future study to further the understanding of the pathogenesis of RA, and ultimately perhaps develop preventive measures for this disease. PMID:22819092

  14. The role of gene-environment interactions in the development of food allergy.

    Science.gov (United States)

    Neeland, Melanie R; Martino, David J; Allen, Katrina J

    2015-01-01

    The rates of IgE-mediated food allergy have increased globally, particularly in developed countries. The rising incidence is occurring more rapidly than changes to the genome sequence would allow, suggesting that environmental exposures that alter the immune response play an important role. Genetic factors may also be used to predict an increased predisposition to these environmental risk factors, giving rise to the concept of gene-environment interactions, whereby differential risk of environmental exposures is mediated through the genome. Increasing evidence also suggests a role for epigenetic mechanisms, which are sensitive to environmental exposures, in the development of food allergy. This paper discusses the current state of knowledge regarding the environmental and genetic risk factors for food allergy and how environmental exposures may interact with immune genes to modify disease risk or outcome.

  15. MAOA genotype, social exclusion and aggression: an experimental test of a gene-environment interaction.

    Science.gov (United States)

    Gallardo-Pujol, D; Andrés-Pueyo, A; Maydeu-Olivares, A

    2013-02-01

    In 2002, Caspi and colleagues provided the first epidemiological evidence that genotype may moderate individuals' responses to environmental determinants. However, in a correlational study great care must be taken to ensure the proper estimation of the causal relationship. Here, a randomized experiment was performed to test the hypothesis that the MAOA gene promoter polymorphism (MAOA-LPR) interacts with environmental adversity in determining aggressive behavior using laboratory analogs of real-life conditions. A sample of 57 Caucasian male students of Catalan and Spanish origin was recruited at the University of Barcelona. Ostracism, or social exclusion, was induced as environmental adversity using the Cyberball software. Laboratory aggression was assessed with the Point Subtraction Aggression Paradigm (PSAP), which was used as an analog of antisocial behavior. We also measured aggressiveness by means of the reduced version of the Aggression Questionnaire. The MAOA-LPR polymorphism showed a significant effect on the number of aggressive responses in the PSAP (F(1,53) = 4.63, P = 0.03, partial η(2) = 0.08), as well as social exclusion (F(1,53) = 8.03, P = 0.01, partial η(2) = 0.13). Most notably, however, we found that the MAOA-LPR polymorphism interacts significantly with social exclusion in order to provoke aggressive behavior (F(1,53) = 4.42, P = 0.04, partial η(2) = 0.08), remarkably, the low-activity allele of the MAOA-LPR polymorphism carriers in the ostracized group show significantly higher aggression scores than the rest. Our results support the notion that gene-environment interactions can be successfully reproduced within a laboratory using analogs and an appropriate design. We provide guidelines to test gene-environment interactions hypotheses under controlled, experimental settings.

  16. Key Considerations and Methods in the Study of Gene-Environment Interactions.

    Science.gov (United States)

    Simon, Paul H G; Sylvestre, Marie-Pierre; Tremblay, Johanne; Hamet, Pavel

    2016-08-01

    With increased involvement of genetic data in most epidemiological investigations, gene-environment (G × E) interactions now stand as a topic, which must be meticulously assessed and thoroughly understood. The level, mode, and outcomes of interactions between environmental factors and genetic traits have the capacity to modulate disease risk. These must, therefore, be carefully evaluated as they have the potential to offer novel insights on the "missing heritability problem", reaching beyond our current limitations. First, we review a definition of G × E interactions. We then explore how concepts such as the early manifestation of the genetic components of a disease, the heterogeneity of complex traits, the clear definition of epidemiological strata, and the effect of varying physiological conditions can affect our capacity to detect (or miss) G × E interactions. Lastly, we discuss the shortfalls of regression models to study G × E interactions and how other methods such as the ReliefF algorithm, pattern recognition methods, or the LASSO (Least Absolute Shrinkage and Selection Operator) method can enable us to more adequately model G × E interactions. Overall, we present the elements to consider and a path to follow when studying genetic determinants of disease in order to uncover potential G × E interactions.

  17. The heritable basis of gene-environment interactions in cardiometabolic traits.

    Science.gov (United States)

    Poveda, Alaitz; Chen, Yan; Brändström, Anders; Engberg, Elisabeth; Hallmans, Göran; Johansson, Ingegerd; Renström, Frida; Kurbasic, Azra; Franks, Paul W

    2017-03-01

    Little is known about the heritable basis of gene-environment interactions in humans. We therefore screened multiple cardiometabolic traits to assess the probability that they are influenced by genotype-environment interactions. Fourteen established environmental risk exposures and 11 cardiometabolic traits were analysed in the VIKING study, a cohort of 16,430 Swedish adults from 1682 extended pedigrees with available detailed genealogical, phenotypic and demographic information, using a maximum likelihood variance decomposition method in Sequential Oligogenic Linkage Analysis Routines software. All cardiometabolic traits had statistically significant heritability estimates, with narrow-sense heritabilities (h (2)) ranging from 24% to 47%. Genotype-environment interactions were detected for age and sex (for the majority of traits), physical activity (for triacylglycerols, 2 h glucose and diastolic BP), smoking (for weight), alcohol intake (for weight, BMI and 2 h glucose) and diet pattern (for weight, BMI, glycaemic traits and systolic BP). Genotype-age interactions for weight and systolic BP, genotype-sex interactions for BMI and triacylglycerols and genotype-alcohol intake interactions for weight remained significant after multiple test correction. Age, sex and alcohol intake are likely to be major modifiers of genetic effects for a range of cardiometabolic traits. This information may prove valuable for studies that seek to identify specific loci that modify the effects of lifestyle in cardiometabolic disease.

  18. Gene-environment interactions in psychopathology throughout early childhood: a systematic review.

    Science.gov (United States)

    Pinto, Raquel Q; Soares, Isabel; Carvalho-Correia, Eduarda; Mesquita, Ana R

    2015-12-01

    Up to 20% of children and adolescents worldwide suffer from mental health problems. Epidemiological studies have shown that some of these problems are already present at an early age. The recognition that psychopathology is a result of an interaction between individual experiences and genetic characteristics has led to an increase in the number of studies using a gene-environment approach (G×E). However, to date, there has been no systematic review of G×E studies on psychopathology in the first 6 years of life. Following a literature search and a selection process, 14 studies were identified and most (n=12) of the studies found at least one significant G×E effect. This review provides a systematic characterization of the published G×E studies, providing insights into the neurobiological and environmental determinants involved in the etiology of children's psychopathology.

  19. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

    DEFF Research Database (Denmark)

    Nickels, Stefan; Truong, Thérèse; Hein, Rebecca

    2013-01-01

    ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4)). Overall...

  20. The heritability of personality is not always 50%: gene-environment interactions and correlations between personality and parenting.

    Science.gov (United States)

    Krueger, Robert F; South, Susan; Johnson, Wendy; Iacono, William

    2008-12-01

    Twin studies of personality are consistent in attributing approximately half of the variance in personality to genetic effects, with the remaining variance attributed to environments that make people within the same families different. Such conclusions, however, are based on quantitative models of human individual differences that estimate genetic and environmental contributions as constants for entire populations. Recent advances in statistical modeling allow for the possibility of estimating genetic and environmental contributions contingent on other variables, allowing the quantification of phenomena that have traditionally been characterized as gene-environment interaction and correlation. We applied these newer models to understand how adolescents' descriptions of their relationships with their parents might change or moderate the impact of genetic and environmental factors on personality. We documented notable moderation in the domains of positive and negative emotionality, with parental relationships acting both to enhance and diminish both genetic and environmental effects. We discuss how genetic and environmental contributions to personality might be more richly conceptualized as dynamic systems of gene-environment interplay--systems that are not captured by classical concepts, such as the overall heritability of personality.

  1. Gene-environment interaction effects on lung function- a genome-wide association study within the Framingham heart study

    Science.gov (United States)

    2013-01-01

    Background Previous studies in occupational exposure and lung function have focused only on the main effect of occupational exposure or genetics on lung function. Some disease-susceptible genes may be missed due to their low marginal effects, despite potential involvement in the disease process through interactions with the environment. Through comprehensive genome-wide gene-environment interaction studies, we can uncover these susceptibility genes. Our objective in this study was to explore gene by occupational exposure interaction effects on lung function using both the individual SNPs approach and the genetic network approach. Methods The study population comprised the Offspring Cohort and the Third Generation from the Framingham Heart Study. We used forced expiratory volume in one second (FEV1) and ratio of FEV1 to forced vital capacity (FVC) as outcomes. Occupational exposures were classified using a population-specific job exposure matrix. We performed genome-wide gene-environment interaction analysis, using the Affymetrix 550 K mapping array for genotyping. A linear regression-based generalized estimating equation was applied to account for within-family relatedness. Network analysis was conducted using results from single-nucleotide polymorphism (SNP)-level analyses and from gene expression study results. Results There were 4,785 participants in total. SNP-level analysis and network analysis identified SNP rs9931086 (Pinteraction =1.16 × 10-7) in gene SLC38A8, which may significantly modify the effects of occupational exposure on FEV1. Genes identified from the network analysis included CTLA-4, HDAC, and PPAR-alpha. Conclusions Our study implies that SNP rs9931086 in SLC38A8 and genes CTLA-4, HDAC, and PPAR-alpha, which are related to inflammatory processes, may modify the effect of occupational exposure on lung function. PMID:24289273

  2. Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: A GWAS data analysis

    Science.gov (United States)

    Tang, Hongwei; Wei, Peng; Duell, Eric J.; Risch, Harvey A.; Olson, Sara H.; Bueno-de-Mesquita, H. Bas; Gallinger, Steven; Holly, Elizabeth A.; Petersen, Gloria M.; Bracci, Paige M.; McWilliams, Robert R.; Jenab, Mazda; Riboli, Elio; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Kaaks, Rudolf; Trichopoulos, Dimitrios; Panico, Salvatore; Sund, Malin; Peeters, Petra H.M; Khaw, Kay-Tee; Amos, Christopher I; Li, Donghui

    2013-01-01

    Background Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level. Methods Using GWAS genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study of 2,028 cases and 2,109 controls to examine gene-obesity and gene-diabetes interactions in relation to pancreatic cancer risk by employing the likelihood ratio test (LRT) nested in logistic regression models and Ingenuity Pathway Analysis (IPA). Results After adjusting for multiple comparisons, a significant interaction of the chemokine signaling pathway with obesity (P = 3.29 × 10−6) and a near significant interaction of calcium signaling pathway with diabetes (P = 1.57 × 10−4) in modifying the risk of pancreatic cancer was observed. These findings were supported by results from IPA analysis of the top genes with nominal interactions. The major contributing genes to the two top pathways include GNGT2, RELA, TIAM1 and GNAS. None of the individual genes or SNPs except one SNP remained significant after adjusting for multiple testing. Notably, SNP rs10818684 of the PTGS1 gene showed an interaction with diabetes (P = 7.91 × 10−7) at a false discovery rate of 6%. Conclusions Genetic variations in inflammatory response and insulin resistance may affect the risk of obesity and diabetes-related pancreatic cancer. These observations should be replicated in additional large datasets. Impact Gene-environment interaction analysis may provide new insights into the genetic susceptibility and molecular mechanisms of obesity- and diabetes-related pancreatic cancer. PMID:24136929

  3. Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis.

    Science.gov (United States)

    Tang, Hongwei; Wei, Peng; Duell, Eric J; Risch, Harvey A; Olson, Sara H; Bueno-de-Mesquita, H Bas; Gallinger, Steven; Holly, Elizabeth A; Petersen, Gloria M; Bracci, Paige M; McWilliams, Robert R; Jenab, Mazda; Riboli, Elio; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Kaaks, Rudolf; Trichopoulos, Dimitrios; Panico, Salvatore; Sund, Malin; Peeters, Petra H M; Khaw, Kay-Tee; Amos, Christopher I; Li, Donghui

    2014-01-01

    Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level. Using genome-wide association studies (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study of 2,028 cases and 2,109 controls to examine gene-obesity and gene-diabetes interactions in relation to pancreatic cancer risk by using the likelihood-ratio test nested in logistic regression models and Ingenuity Pathway Analysis (IPA). After adjusting for multiple comparisons, a significant interaction of the chemokine signaling pathway with obesity (P = 3.29 × 10(-6)) and a near significant interaction of calcium signaling pathway with diabetes (P = 1.57 × 10(-4)) in modifying the risk of pancreatic cancer were observed. These findings were supported by results from IPA analysis of the top genes with nominal interactions. The major contributing genes to the two top pathways include GNGT2, RELA, TIAM1, and GNAS. None of the individual genes or single-nucleotide polymorphism (SNP) except one SNP remained significant after adjusting for multiple testing. Notably, SNP rs10818684 of the PTGS1 gene showed an interaction with diabetes (P = 7.91 × 10(-7)) at a false discovery rate of 6%. Genetic variations in inflammatory response and insulin resistance may affect the risk of obesity- and diabetes-related pancreatic cancer. These observations should be replicated in additional large datasets. A gene-environment interaction analysis may provide new insights into the genetic susceptibility and molecular mechanisms of obesity- and diabetes-related pancreatic cancer.

  4. Population stratification bias in the case-only study for gene-environment interactions.

    Science.gov (United States)

    Wang, Liang-Yi; Lee, Wen-Chung

    2008-07-15

    The case-only study is a convenient approach and provides increased statistical efficiency in detecting gene-environment interactions. The validity of a case-only study hinges on one well-recognized assumption: The susceptibility genotypes and the environmental exposures of interest are independent in the population. Otherwise, the study will be biased. The authors show that hidden stratification in the study population could also ruin a case-only study. They derive the formulas for population stratification bias. The bias involves three terms: 1) the coefficient of variation of the exposure prevalence odds, 2) the coefficient of variation of the genotype frequency odds, and 3) the correlation coefficient between the exposure prevalence odds and the genotype frequency odds. The authors perform simulation to investigate the magnitude of bias over a wide range of realistic scenarios. It is found that the estimated interaction effect is frequently biased by more than 5%. For a rarer gene and a rarer exposure, the bias becomes even larger (>30%). Because of the potentially large bias, researchers conducting case-only studies should use the boundary formula presented in this paper to make more prudent interpretations of their results, or they should use stratified analysis or a modeling approach to adjust for population stratification bias in their studies.

  5. Leveraging gene-environment interactions and endotypes for asthma gene discovery.

    Science.gov (United States)

    Bønnelykke, Klaus; Ober, Carole

    2016-03-01

    Asthma is a heterogeneous clinical syndrome that includes subtypes of disease with different underlying causes and disease mechanisms. Asthma is caused by a complex interaction between genes and environmental exposures; early-life exposures in particular play an important role. Asthma is also heritable, and a number of susceptibility variants have been discovered in genome-wide association studies, although the known risk alleles explain only a small proportion of the heritability. In this review, we present evidence supporting the hypothesis that focusing on more specific asthma phenotypes, such as childhood asthma with severe exacerbations, and on relevant exposures that are involved in gene-environment interactions (GEIs), such as rhinovirus infections, will improve detection of asthma genes and our understanding of the underlying mechanisms. We will discuss the challenges of considering GEIs and the advantages of studying responses to asthma-associated exposures in clinical birth cohorts, as well as in cell models of GEIs, to dissect the context-specific nature of genotypic risks, to prioritize variants in genome-wide association studies, and to identify pathways involved in pathogenesis in subgroups of patients. We propose that such approaches, in spite of their many challenges, present great opportunities for better understanding of asthma pathogenesis and heterogeneity and, ultimately, for improving prevention and treatment of disease.

  6. Testing gene-environment interaction in large-scale case-control association studies: possible choices and comparisons.

    Science.gov (United States)

    Mukherjee, Bhramar; Ahn, Jaeil; Gruber, Stephen B; Chatterjee, Nilanjan

    2012-02-01

    Several methods for screening gene-environment interaction have recently been proposed that address the issue of using gene-environment independence in a data-adaptive way. In this report, the authors present a comparative simulation study of power and type I error properties of 3 classes of procedures: 1) the standard 1-step case-control method; 2) the case-only method that requires an assumption of gene-environment independence for the underlying population; and 3) a variety of hybrid methods, including empirical-Bayes, 2-step, and model averaging, that aim at gaining power by exploiting the assumption of gene-environment independence and yet can protect against false positives when the independence assumption is violated. These studies suggest that, although the case-only method generally has maximum power, it has the potential to create substantial false positives in large-scale studies even when a small fraction of markers are associated with the exposure under study in the underlying population. All the hybrid methods perform well in protecting against such false positives and yet can retain substantial power advantages over standard case-control tests. The authors conclude that, for future genome-wide scans for gene-environment interactions, major power gain is possible by using alternatives to standard case-control analysis. Whether a case-only type scan or one of the hybrid methods should be used depends on the strength and direction of gene-environment interaction and association, the level of tolerance for false positives, and the nature of replication strategies.

  7. Rethinking expertise: A multifactorial gene-environment interaction model of expert performance.

    Science.gov (United States)

    Ullén, Fredrik; Hambrick, David Zachary; Mosing, Miriam Anna

    2016-04-01

    Scientific interest in expertise-superior performance within a specific domain-has a long history in psychology. Although there is a broad consensus that a long period of practice is essential for expertise, a long-standing controversy in the field concerns the importance of other variables such as cognitive abilities and genetic factors. According to the influential deliberate practice theory, expert performance is essentially limited by a single variable: the amount of deliberate practice an individual has accumulated. Here, we provide a review of the literature on deliberate practice, expert performance, and its neural correlates. A particular emphasis is on recent studies indicating that expertise is related to numerous traits other than practice as well as genetic factors. We argue that deliberate practice theory is unable to account for major recent findings relating to expertise and expert performance, and propose an alternative multifactorial gene-environment interaction model of expertise, which provides an adequate explanation for the available empirical data and may serve as a useful framework for future empirical and theoretical work on expert performance.

  8. Education and alcohol use: A study of gene-environment interaction in young adulthood.

    Science.gov (United States)

    Barr, Peter B; Salvatore, Jessica E; Maes, Hermine; Aliev, Fazil; Latvala, Antti; Viken, Richard; Rose, Richard J; Kaprio, Jaakko; Dick, Danielle M

    2016-08-01

    The consequences of heavy alcohol use remain a serious public health problem. Consistent evidence has demonstrated that both genetic and social influences contribute to alcohol use. Research on gene-environment interaction (GxE) has also demonstrated that these social and genetic influences do not act independently. Instead, certain environmental contexts may limit or exacerbate an underlying genetic predisposition. However, much of the work on GxE and alcohol use has focused on adolescence and less is known about the important environmental contexts in young adulthood. Using data from the young adult wave of the Finnish Twin Study, FinnTwin12 (N = 3402), we used biometric twin modeling to test whether education moderated genetic risk for alcohol use as assessed by drinking frequency and intoxication frequency. Education is important because it offers greater access to personal resources and helps determine one's position in the broader stratification system. Results from the twin models show that education did not moderate genetic variance components and that genetic risk was constant across levels of education. Instead, education moderated environmental variance so that under conditions of low education, environmental influences explained more of the variation in alcohol use outcomes. The implications and limitations of these results are discussed.

  9. Shame and Guilt-Proneness in Adolescents: Gene-Environment Interactions.

    Directory of Open Access Journals (Sweden)

    Aurora Szentágotai-Tătar

    Full Text Available Rooted in people's preoccupation with how they are perceived and evaluated, shame and guilt are self-conscious emotions that play adaptive roles in social behavior, but can also contribute to psychopathology when dysregulated. Shame and guilt-proneness develop during childhood and adolescence, and are influenced by genetic and environmental factors that are little known to date. This study investigated the effects of early traumatic events and functional polymorphisms in the brain-derived neurotrophic factor (BDNF gene and the serotonin transporter gene promoter (5-HTTLPR on shame and guilt in adolescents. A sample of N = 271 healthy adolescents between 14 and 17 years of age filled in measures of early traumatic events and proneness to shame and guilt, and were genotyped for the BDNF Val66Met and 5-HTTLPR polymorphisms. Results of moderator analyses indicated that trauma intensity was positively associated with guilt-proneness only in carriers of the low-expressing Met allele of BDNF Val66Met. This is the first study that identifies a gene-environment interaction that significantly contributes to guilt proneness in adolescents, with potential implications for developmental psychopathology.

  10. Shame and Guilt-Proneness in Adolescents: Gene-Environment Interactions.

    Science.gov (United States)

    Szentágotai-Tătar, Aurora; Chiș, Adina; Vulturar, Romana; Dobrean, Anca; Cândea, Diana Mirela; Miu, Andrei C

    2015-01-01

    Rooted in people's preoccupation with how they are perceived and evaluated, shame and guilt are self-conscious emotions that play adaptive roles in social behavior, but can also contribute to psychopathology when dysregulated. Shame and guilt-proneness develop during childhood and adolescence, and are influenced by genetic and environmental factors that are little known to date. This study investigated the effects of early traumatic events and functional polymorphisms in the brain-derived neurotrophic factor (BDNF) gene and the serotonin transporter gene promoter (5-HTTLPR) on shame and guilt in adolescents. A sample of N = 271 healthy adolescents between 14 and 17 years of age filled in measures of early traumatic events and proneness to shame and guilt, and were genotyped for the BDNF Val66Met and 5-HTTLPR polymorphisms. Results of moderator analyses indicated that trauma intensity was positively associated with guilt-proneness only in carriers of the low-expressing Met allele of BDNF Val66Met. This is the first study that identifies a gene-environment interaction that significantly contributes to guilt proneness in adolescents, with potential implications for developmental psychopathology.

  11. Environmental factors as modulators of neurodegeneration: insights from gene-environment interactions in Huntington's disease.

    Science.gov (United States)

    Mo, Christina; Hannan, Anthony J; Renoir, Thibault

    2015-05-01

    Unlike many other neurodegenerative diseases with established gene-environment interactions, Huntington's disease (HD) is viewed as a disorder governed by genetics. The cause of the disease is a highly penetrant tandem repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. In the year 2000, a pioneering study showed that the disease could be delayed in transgenic mice by enriched housing conditions. This review describes subsequent human and preclinical studies identifying environmental modulation of motor, cognitive, affective and other symptoms found in HD. Alongside the behavioral observations we also discuss potential mechanisms and the relevance to other neurodegenerative disorders, including Alzheimer's and Parkinson's disease. In mouse models of HD, increased sensorimotor and cognitive stimulation can delay or ameliorate various endophenotypes. Potential mechanisms include increased trophic support, synaptic plasticity, adult neurogenesis, and other forms of experience-dependent cellular plasticity. Subsequent clinical investigations support a role for lifetime activity levels in modulating the onset and progression of HD. Stress can accelerate memory and olfactory deficits and exacerbate cellular dysfunctions in HD mice. In the absence of effective treatments to slow the course of HD, environmental interventions offer feasible approaches to delay the disease, however further preclinical and human studies are needed in order to generate clinical recommendations. Environmental interventions could be combined with future pharmacological therapies and stimulate the identification of enviromimetics, drugs which mimic or enhance the beneficial effects of cognitive stimulation and physical activity.

  12. Cognitive endophenotypes, gene-environment interactions and experience-dependent plasticity in animal models of schizophrenia.

    Science.gov (United States)

    Burrows, Emma L; Hannan, Anthony J

    2016-04-01

    Schizophrenia is a devastating brain disorder caused by a complex and heterogeneous combination of genetic and environmental factors. In order to develop effective new strategies to prevent and treat schizophrenia, valid animal models are required which accurately model the disorder, and ideally provide construct, face and predictive validity. The cognitive deficits in schizophrenia represent some of the most debilitating symptoms and are also currently the most poorly treated. Therefore it is crucial that animal models are able to capture the cognitive dysfunction that characterizes schizophrenia, as well as the negative and psychotic symptoms. The genomes of mice have, prior to the recent gene-editing revolution, proven the most easily manipulable of mammalian laboratory species, and hence most genetic targeting has been performed using mouse models. Importantly, when key environmental factors of relevance to schizophrenia are experimentally manipulated, dramatic changes in the phenotypes of these animal models are often observed. We will review recent studies in rodent models which provide insight into gene-environment interactions in schizophrenia. We will focus specifically on environmental factors which modulate levels of experience-dependent plasticity, including environmental enrichment, cognitive stimulation, physical activity and stress. The insights provided by this research will not only help refine the establishment of optimally valid animal models which facilitate development of novel therapeutics, but will also provide insight into the pathogenesis of schizophrenia, thus identifying molecular and cellular targets for future preclinical and clinical investigations.

  13. Drug metabolism and liver disease: a drug-gene-environment interaction.

    Science.gov (United States)

    Zgheib, Nathalie K; Branch, Robert A

    2017-02-01

    Despite the central role of the liver in drug metabolism, surprisingly there is lack of certainty in anticipating the extent of modification of the clearance of a given drug in a given patient. The intent of this review is to provide a conceptual framework in considering the impact of liver disease on drug disposition and reciprocally the impact of drug disposition on liver disease. It is proposed that improved understanding of the situation is gained by considering the issue as a special example of a drug-gene-environment interaction. This requires an integration of knowledge of the drug's properties, knowledge of the gene products involved in its metabolism, and knowledge of the pathophysiology of its disposition. This will enhance the level of predictability of drug disposition and toxicity for a drug of interest in an individual patient. It is our contention that advances in pharmacology, pharmacogenomics, and hepatology, together with concerted interests in the academic, regulatory, and pharmaceutical industry communities provide an ideal immediate environment to move from a qualitative reactive approach to quantitative proactive approach in individualizing patient therapy in liver disease.

  14. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations.

    Science.gov (United States)

    van Os, Jim; Rutten, Bart P; Myin-Germeys, Inez; Delespaul, Philippe; Viechtbauer, Wolfgang; van Zelst, Catherine; Bruggeman, Richard; Reininghaus, Ulrich; Morgan, Craig; Murray, Robin M; Di Forti, Marta; McGuire, Philip; Valmaggia, Lucia R; Kempton, Matthew J; Gayer-Anderson, Charlotte; Hubbard, Kathryn; Beards, Stephanie; Stilo, Simona A; Onyejiaka, Adanna; Bourque, Francois; Modinos, Gemma; Tognin, Stefania; Calem, Maria; O'Donovan, Michael C; Owen, Michael J; Holmans, Peter; Williams, Nigel; Craddock, Nicholas; Richards, Alexander; Humphreys, Isla; Meyer-Lindenberg, Andreas; Leweke, F Markus; Tost, Heike; Akdeniz, Ceren; Rohleder, Cathrin; Bumb, J Malte; Schwarz, Emanuel; Alptekin, Köksal; Üçok, Alp; Saka, Meram Can; Atbaşoğlu, E Cem; Gülöksüz, Sinan; Gumus-Akay, Guvem; Cihan, Burçin; Karadağ, Hasan; Soygür, Haldan; Cankurtaran, Eylem Şahin; Ulusoy, Semra; Akdede, Berna; Binbay, Tolga; Ayer, Ahmet; Noyan, Handan; Karadayı, Gülşah; Akturan, Elçin; Ulaş, Halis; Arango, Celso; Parellada, Mara; Bernardo, Miguel; Sanjuán, Julio; Bobes, Julio; Arrojo, Manuel; Santos, Jose Luis; Cuadrado, Pedro; Rodríguez Solano, José Juan; Carracedo, Angel; García Bernardo, Enrique; Roldán, Laura; López, Gonzalo; Cabrera, Bibiana; Cruz, Sabrina; Díaz Mesa, Eva Ma; Pouso, María; Jiménez, Estela; Sánchez, Teresa; Rapado, Marta; González, Emiliano; Martínez, Covadonga; Sánchez, Emilio; Olmeda, Ma Soledad; de Haan, Lieuwe; Velthorst, Eva; van der Gaag, Mark; Selten, Jean-Paul; van Dam, Daniella; van der Ven, Elsje; van der Meer, Floor; Messchaert, Elles; Kraan, Tamar; Burger, Nadine; Leboyer, Marion; Szoke, Andrei; Schürhoff, Franck; Llorca, Pierre-Michel; Jamain, Stéphane; Tortelli, Andrea; Frijda, Flora; Vilain, Jeanne; Galliot, Anne-Marie; Baudin, Grégoire; Ferchiou, Aziz; Richard, Jean-Romain; Bulzacka, Ewa; Charpeaud, Thomas; Tronche, Anne-Marie; De Hert, Marc; van Winkel, Ruud; Decoster, Jeroen; Derom, Catherine; Thiery, Evert; Stefanis, Nikos C; Sachs, Gabriele; Aschauer, Harald; Lasser, Iris; Winklbaur, Bernadette; Schlögelhofer, Monika; Riecher-Rössler, Anita; Borgwardt, Stefan; Walter, Anna; Harrisberger, Fabienne; Smieskova, Renata; Rapp, Charlotte; Ittig, Sarah; Soguel-dit-Piquard, Fabienne; Studerus, Erich; Klosterkötter, Joachim; Ruhrmann, Stephan; Paruch, Julia; Julkowski, Dominika; Hilboll, Desiree; Sham, Pak C; Cherny, Stacey S; Chen, Eric Y H; Campbell, Desmond D; Li, Miaoxin; Romeo-Casabona, Carlos María; Emaldi Cirión, Aitziber; Urruela Mora, Asier; Jones, Peter; Kirkbride, James; Cannon, Mary; Rujescu, Dan; Tarricone, Ilaria; Berardi, Domenico; Bonora, Elena; Seri, Marco; Marcacci, Thomas; Chiri, Luigi; Chierzi, Federico; Storbini, Viviana; Braca, Mauro; Minenna, Maria Gabriella; Donegani, Ivonne; Fioritti, Angelo; La Barbera, Daniele; La Cascia, Caterina Erika; Mulè, Alice; Sideli, Lucia; Sartorio, Rachele; Ferraro, Laura; Tripoli, Giada; Seminerio, Fabio; Marinaro, Anna Maria; McGorry, Patrick; Nelson, Barnaby; Amminger, G Paul; Pantelis, Christos; Menezes, Paulo R; Del-Ben, Cristina M; Gallo Tenan, Silvia H; Shuhama, Rosana; Ruggeri, Mirella; Tosato, Sarah; Lasalvia, Antonio; Bonetto, Chiara; Ira, Elisa; Nordentoft, Merete; Krebs, Marie-Odile; Barrantes-Vidal, Neus; Cristóbal, Paula; Kwapil, Thomas R; Brietzke, Elisa; Bressan, Rodrigo A; Gadelha, Ary; Maric, Nadja P; Andric, Sanja; Mihaljevic, Marina; Mirjanic, Tijana

    2014-07-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.

  15. Gene-Environment Interaction in Externalizing Problems among Adolescents: Evidence from the Pelotas 1993 Birth Cohort Study

    Science.gov (United States)

    Kieling, Christian; Hutz, Mara H.; Genro, Julia P.; Polanczyk, Guilherme V.; Anselmi, Luciana; Camey, Suzi; Hallal, Pedro C.; Barros, Fernando C.; Victora, Cesar G.; Menezes, Ana M. B.; Rohde, Luis Augusto

    2013-01-01

    Background: The study of gene-environment interactions (G by E) is one of the most promising strategies to uncover the origins of mental disorders. Replication of initial findings, however, is essential because there is a strong possibility of publication bias in the literature. In addition, there is a scarcity of research on the topic originated…

  16. Sample size requirements for indirect association studies of gene-environment interactions (G x E).

    Science.gov (United States)

    Hein, Rebecca; Beckmann, Lars; Chang-Claude, Jenny

    2008-04-01

    Association studies accounting for gene-environment interactions (G x E) may be useful for detecting genetic effects. Although current technology enables very dense marker spacing in genetic association studies, the true disease variants may not be genotyped. Thus, causal genes are searched for by indirect association using genetic markers in linkage disequilibrium (LD) with the true disease variants. Sample sizes needed to detect G x E effects in indirect case-control association studies depend on the true genetic main effects, disease allele frequencies, whether marker and disease allele frequencies match, LD between loci, main effects and prevalence of environmental exposures, and the magnitude of interactions. We explored variables influencing sample sizes needed to detect G x E, compared these sample sizes with those required to detect genetic marginal effects, and provide an algorithm for power and sample size estimations. Required sample sizes may be heavily inflated if LD between marker and disease loci decreases. More than 10,000 case-control pairs may be required to detect G x E. However, given weak true genetic main effects, moderate prevalence of environmental exposures, as well as strong interactions, G x E effects may be detected with smaller sample sizes than those needed for the detection of genetic marginal effects. Moreover, in this scenario, rare disease variants may only be detectable when G x E is included in the analyses. Thus, the analysis of G x E appears to be an attractive option for the detection of weak genetic main effects of rare variants that may not be detectable in the analysis of genetic marginal effects only.

  17. Metabolic syndrome, diabetes and atherosclerosis: Influence of gene-environment interaction

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    Andreassi, Maria Grazia, E-mail: andreas@ifc.cnr.it [CNR Institute of Clinical Physiology, G. Pasquinucci Hospital, Via Aurelia Sud, Massa (Italy)

    2009-07-10

    Despite remarkable progress in diagnosis and understanding of risk factors, cardiovascular disease (CVD) remains still the leading cause of morbidity and mortality in the world's developed countries. The metabolic syndrome, a cluster of risk factors (visceral obesity, insulin resistance, dyslipidaemia, and hypertension), is increasingly being recognized as a new risk factor for type 2 diabetes and atherosclerotic cardiovascular disease. Nevertheless, there is wide variation in both the occurrence of disease and age of onset, even in individuals who display very similar risk profiles. There is now compelling evidence that a complex interplay between genetic determinants and environmental factors (still largely unknown) is the reason for this large inter-individual variation in disease susceptibility. The purpose of the present review is to describe the current status of our knowledge concerning the gene-environment interactions potentially implicated in the pathogenesis of metabolic syndrome, diabetes and cardiovascular disease. It focuses predominantly on studies of genes (peroxisome proliferator-activated receptor-gamma, alcohol dehydrogenase type 1C, apolipoprotein E, glutathione S-transferases T1 and M1) that are known to be modified by dietary and lifestyle habits (fat diet, intake of alcohol and smoking habit). It also describes the limited current understanding of the role of genetic variants of xenobiotic metabolizing enzymes and their interactions with environmental toxicants. Additional studies are needed in order to clarify whether inter-individual differences in detoxification of environmental toxicants may have an essential role in the development of CVD and contribute to the emerging field of 'environmental cardiology'. Such knowledge may be particularly relevant for improving cardiovascular risk stratification and conceiving the development of 'personalized intervention program'.

  18. Gene-environment interaction between the oxytocin receptor (OXTR) gene and parenting behaviour on children's theory of mind.

    Science.gov (United States)

    Wade, Mark; Hoffmann, Thomas J; Jenkins, Jennifer M

    2015-12-01

    Theory of mind (ToM) is the ability to interpret and understand human behaviour by representing the mental states of others. Like many human capacities, ToM is thought to develop through both complex biological and socialization mechanisms. However, no study has examined the joint effect of genetic and environmental influences on ToM. This study examined how variability in the oxytocin receptor gene (OXTR) and parenting behavior--two widely studied factors in ToM development-interacted to predict ToM in pre-school-aged children. Participants were 301 children who were part of an ongoing longitudinal birth cohort study. ToM was assessed at age 4.5 using a previously validated scale. Parenting was assessed through observations of mothers' cognitively sensitive behaviours. Using a family-based association design, it was suggestive that a particular variant (rs11131149) interacted with maternal cognitive sensitivity on children's ToM (P = 0.019). More copies of the major allele were associated with higher ToM as a function of increasing cognitive sensitivity. A sizeable 26% of the variability in ToM was accounted for by this interaction. This study provides the first empirical evidence of gene-environment interactions on ToM, supporting the notion that genetic factors may be modulated by potent environmental influences early in development.

  19. DISC1 mouse models as a tool to decipher gene-environment interactions in psychiatric disorders

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    Tyler eCash-Padgett

    2013-09-01

    Full Text Available DISC1 was discovered in a Scottish pedigree in which a chromosomal translocation that breaks this gene segregates with psychiatric disorders, mainly depression and schizophrenia. Linkage and association studies in diverse populations support DISC1 as a susceptibility gene to a variety of neuropsychiatric disorders. Many Disc1 mouse models have been generated to study its neuronal functions. These mouse models display variable phenotypes, some of them relevant to schizophrenia, others to depression.The Disc1 mouse models are popular genetic models for studying gene-environment interactions in schizophrenia. Five different Disc1 models have been combined with environmental factors. The environmental stressors employed can be classified as either early immune activation or later social paradigms. These studies cover major time points along the neurodevelopmental trajectory: prenatal, early postnatal, adolescence, and adulthood. Various combinations of molecular, anatomical and behavioral methods have been used to assess the outcomes. Additionally, three of the studies sought to rescue the resulting abnormalities.Here we provide background on the environmental paradigms used, summarize the results of these studies combining Disc1 mouse models with environmental stressors and discuss what we can learn and how to proceed. A major question is how the genetic and environmental factors determine which psychiatric disorder will be clinically manifested. To address this we can take advantage of the many Disc1 models available and expose them to the same environmental stressor. The complementary experiment would be to expose the same model to different environmental stressors. DISC1 is an ideal gene for this approach, since in the Scottish pedigree the same chromosomal translocation results in different psychiatric conditions.

  20. G x E: a NIAAA workshop on gene-environment interactions.

    Science.gov (United States)

    Gunzerath, Lorraine; Goldman, David

    2003-03-01

    The National Institute on Alcohol Abuse and Alcoholism (NIAAA) sponsored a May 2002 workshop on gene-environment interaction (G x E) research to identify potential roadblocks to further research and to propose solutions to those roadblocks, to optimize investigative opportunities and multidisciplinary or multi-institution collaborations, and to explore ways that NIAAA can facilitate G x E studies. Sessions included panels on animal models; phenotypes; genetic findings in humans; study designs and analytical methods; and assessment of environmental risk. Key among the identified challenges to progress in G x E research were issues of study design and sampling strategies; logistic and methodological costs and constraints; availability and understanding of data analysis techniques; potential stigmatization of study populations; and organizational/bureaucratic structures that are inadequate to address the unique needs of large-scale, multicenter, longitudinal projects. Participants proposed a series of recommendations to address these issues. Session coordinators included: Gayle Boyd, Kendall Bryant, Page Chiapella, Vivian Faden, David Goldman, and Antonio Noronha. Session participants included: Laura Almasy, Henri Begleiter, Raul Caetano, Bruce Dudek, Mary Dufour, Cindy Ehlers, Mary-Anne Enoch, Joel Gelernter, David Goldman, Bridget Grant, Lorraine Gunzerath, Deborah Hasin, Andrew Heath, Victor Hesselbrock, J. Dee Higley, Shirley Hill, Kerry Jang, Raynard S. Kington, Rick Kittles, George Koob, Kenneth Leonard, Ting-Kai Li, Jeffrey Long, William McBride, Matthew McGue, Kathleen Merikangas, Tamara Phillips, Bernice Porjesz, Carol Prescott, Theodore Reich, John Rice, Richard Rose, Charmaine Royal, Arnold Sameroff, Marc Schuckit, Kenneth Sher, Renee Sieving, Robert Taylor, Michael Windle, and Robert Zucker.

  1. I just ran a thousand analyses: benefits of multiple testing in understanding equivocal evidence on gene-environment interactions.

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    Vera E Heininga

    Full Text Available In psychiatric genetics research, the volume of ambivalent findings on gene-environment interactions (G x E is growing at an accelerating pace. In response to the surging suspicions of systematic distortion, we challenge the notion of chance capitalization as a possible contributor. Beyond qualifying multiple testing as a mere methodological issue that, if uncorrected, leads to chance capitalization, we advance towards illustrating the potential benefits of multiple tests in understanding equivocal evidence in genetics literature.We focused on the interaction between the serotonin-transporter-linked promotor region (5-HTTLPR and childhood adversities with regard to depression. After testing 2160 interactions with all relevant measures available within the Dutch population study of adolescents TRAILS, we calculated percentages of significant (p < .05 effects for several subsets of regressions. Using chance capitalization (i.e. overall significance rate of 5% alpha and randomly distributed findings as a competing hypothesis, we expected more significant effects in the subsets of regressions involving: 1 interview-based instead of questionnaire-based measures; 2 abuse instead of milder childhood adversities; and 3 early instead of later adversities. Furthermore, we expected equal significance percentages across 4 male and female subsamples, and 5 various genotypic models of 5-HTTLPR.We found differences in the percentages of significant interactions among the subsets of analyses, including those regarding sex-specific subsamples and genetic modeling, but often in unexpected directions. Overall, the percentage of significant interactions was 7.9% which is only slightly above the 5% that might be expected based on chance.Taken together, multiple testing provides a novel approach to better understand equivocal evidence on G x E, showing that methodological differences across studies are a likely reason for heterogeneity in findings - but chance

  2. The Association between Gene-Environment Interactions and Diseases Involving the Human GST Superfamily with SNP Variants

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    Antoinesha L. Hollman

    2016-03-01

    Full Text Available Exposure to environmental hazards has been associated with diseases in humans. The identification of single nucleotide polymorphisms (SNPs in human populations exposed to different environmental hazards, is vital for detecting the genetic risks of some important human diseases. Several studies in this field have been conducted on glutathione S-transferases (GSTs, a phase II detoxification superfamily, to investigate its role in the occurrence of diseases. Human GSTs consist of cytosolic and microsomal superfamilies that are further divided into subfamilies. Based on scientific search engines and a review of the literature, we have found a large amount of published articles on human GST super- and subfamilies that have greatly assisted in our efforts to examine their role in health and disease. Because of its polymorphic variations in relation to environmental hazards such as air pollutants, cigarette smoke, pesticides, heavy metals, carcinogens, pharmaceutical drugs, and xenobiotics, GST is considered as a significant biomarker. This review examines the studies on gene-environment interactions related to various diseases with respect to single nucleotide polymorphisms (SNPs found in the GST superfamily. Overall, it can be concluded that interactions between GST genes and environmental factors play an important role in human diseases.

  3. Genetic risk for violent behavior and environmental exposure to disadvantage and violent crime: the case for gene-environment interaction.

    Science.gov (United States)

    Barnes, J C; Jacobs, Bruce A

    2013-01-01

    Despite mounds of evidence to suggest that neighborhood structural factors predict violent behavior, almost no attention has been given to how these influences work synergistically (i.e., interact) with an individual's genetic propensity toward violent behavior. Indeed, two streams of research have, heretofore, flowed independently of one another. On one hand, criminologists have underscored the importance of neighborhood context in the etiology of violence. On the other hand, behavioral geneticists have argued that individual-level genetic propensities are important for understanding violence. The current study seeks to integrate these two compatible frameworks by exploring gene-environment interactions (GxE). Two GxEs were examined and supported by the data (i.e., the National Longitudinal Study of Adolescent Health). Using a scale of genetic risk based on three dopamine genes, the analysis revealed that genetic risk had a greater influence on violent behavior when the individual was also exposed to neighborhood disadvantage or when the individual was exposed to higher violent crime rates. The relevance of these findings for criminological theorizing was considered.

  4. NEXT-GENERATION ANALYSIS OF CATARACTS: DETERMINING KNOWLEDGE DRIVEN GENE-GENE INTERACTIONS USING BIOFILTER, AND GENE-ENVIRONMENT INTERACTIONS USING THE PHENX TOOLKIT*

    Science.gov (United States)

    Pendergrass, Sarah A.; Verma, Shefali S.; Holzinger, Emily R.; Moore, Carrie B.; Wallace, John; Dudek, Scott M.; Huggins, Wayne; Kitchner, Terrie; Waudby, Carol; Berg, Richard; McCarty, Catherine A.; Ritchie, Marylyn D.

    2013-01-01

    and gene-environment interactions beyond GWAS, and that the EHR based approach provides an additional source of data for seeking these advanced explanatory models of the etiology of complex disease/outcome such as cataracts. PMID:23424120

  5. Detection of Epistatic and Gene-Environment Interactions Underlying Three Quality Traits in Rice Using High-Throughput Genome-Wide Data

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    Haiming Xu

    2015-01-01

    Full Text Available With development of sequencing technology, dense single nucleotide polymorphisms (SNPs have been available, enabling uncovering genetic architecture of complex traits by genome-wide association study (GWAS. However, the current GWAS strategy usually ignores epistatic and gene-environment interactions due to absence of appropriate methodology and heavy computational burden. This study proposed a new GWAS strategy by combining the graphics processing unit- (GPU- based generalized multifactor dimensionality reduction (GMDR algorithm with mixed linear model approach. The reliability and efficiency of the analytical methods were verified through Monte Carlo simulations, suggesting that a population size of nearly 150 recombinant inbred lines (RILs had a reasonable resolution for the scenarios considered. Further, a GWAS was conducted with the above two-step strategy to investigate the additive, epistatic, and gene-environment associations between 701,867 SNPs and three important quality traits, gelatinization temperature, amylose content, and gel consistency, in a RIL population with 138 individuals derived from super-hybrid rice Xieyou9308 in two environments. Four significant SNPs were identified with additive, epistatic, and gene-environment interaction effects. Our study showed that the mixed linear model approach combining with the GPU-based GMDR algorithm is a feasible strategy for implementing GWAS to uncover genetic architecture of crop complex traits.

  6. The challenge of causal inference in gene-environment interaction research: leveraging research designs from the social sciences.

    Science.gov (United States)

    Fletcher, Jason M; Conley, Dalton

    2013-10-01

    The integration of genetics and the social sciences will lead to a more complex understanding of the articulation between social and biological processes, although the empirical difficulties inherent in this integration are large. One key challenge is the implications of moving "outside the lab" and away from the experimental tools available for research with model organisms. Social science research methods used to examine human behavior in nonexperimental, real-world settings to date have not been fully taken advantage of during this disciplinary integration, especially in the form of gene-environment interaction research. This article outlines and provides examples of several prominent research designs that should be used in gene-environment research and highlights a key benefit to geneticists of working with social scientists.

  7. Vulnerability or Sensitivity to the Environment? Methodological Issues, Trends, and Recommendations in Gene-Environment Interactions Research in Human Behavior.

    Science.gov (United States)

    Leighton, Caroline; Botto, Alberto; Silva, Jaime R; Jiménez, Juan Pablo; Luyten, Patrick

    2017-01-01

    Research on the potential role of gene-environment interactions (GxE) in explaining vulnerability to psychopathology in humans has witnessed a shift from a diathesis-stress perspective to differential susceptibility approaches. This paper critically reviews methodological issues and trends in this body of research. Databases were screened for studies of GxE in the prediction of personality traits, behavior, and mental health disorders in humans published between January 2002 and January 2015. In total, 315 papers were included. Results showed that 34 candidate genes have been included in GxE studies. Independent of the type of environment studied (early or recent life events, positive or negative environments), about 67-83% of studies have reported significant GxE interactions, which is consistent with a social susceptibility model. The percentage of positive results does not seem to differ depending on the gene studied, although publication bias might be involved. However, the number of positive findings differs depending on the population studied (i.e., young adults vs. older adults). Methodological considerations limit the ability to draw strong conclusions, particularly as almost 90% (n = 283/315) of published papers are based on samples from North America and Europe, and about 70% of published studies (219/315) are based on samples that were also used in other reports. At the same time, there are clear indications of methodological improvements over time, as is shown by a significant increase in longitudinal and experimental studies as well as in improved minimum genotyping. Recommendations for future research, such as minimum quality assessment of genes and environmental factors, specifying theoretical models guiding the study, and taking into account of cultural, ethnic, and lifetime perspectives, are formulated.

  8. Gene-Gene-Environment Interactions of Serotonin Transporter, Monoamine Oxidase A and Childhood Maltreatment Predict Aggressive Behavior in Chinese Adolescents

    Science.gov (United States)

    Zhang, Yun; Ming, Qing-sen; Yi, Jin-yao; Wang, Xiang; Chai, Qiao-lian; Yao, Shu-qiao

    2017-01-01

    Gene-environment interactions that moderate aggressive behavior have been identified independently in the serotonin transporter (5-HTT) gene and monoamine oxidase A gene (MAOA). The aim of the present study was to investigate epistasis interactions between MAOA-variable number tandem repeat (VNTR), 5-HTTlinked polymorphism (LPR) and child abuse and the effects of these on aggressive tendencies in a group of otherwise healthy adolescents. A group of 546 Chinese male adolescents completed the Child Trauma Questionnaire and Youth self-report of the Child Behavior Checklist. Buccal cells were collected for DNA analysis. The effects of childhood abuse, MAOA-VNTR, 5-HTTLPR genotypes and their interactive gene-gene-environmental effects on aggressive behavior were analyzed using a linear regression model. The effect of child maltreatment was significant, and a three-way interaction among MAOA-VNTR, 5-HTTLPR and sexual abuse (SA) relating to aggressive behaviors was identified. Chinese male adolescents with high expression of the MAOA-VNTR allele and 5-HTTLPR “SS” genotype exhibited the highest aggression tendencies with an increase in SA during childhood. The findings reported support aggression being a complex behavior involving the synergistic effects of gene-gene-environment interactions. PMID:28203149

  9. Epigenetic genes and emotional reactivity to daily life events: a multi-step gene-environment interaction study.

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    Ehsan Pishva

    Full Text Available Recent human and animal studies suggest that epigenetic mechanisms mediate the impact of environment on development of mental disorders. Therefore, we hypothesized that polymorphisms in epigenetic-regulatory genes impact stress-induced emotional changes. A multi-step, multi-sample gene-environment interaction analysis was conducted to test whether 31 single nucleotide polymorphisms (SNPs in epigenetic-regulatory genes, i.e. three DNA methyltransferase genes DNMT1, DNMT3A, DNMT3B, and methylenetetrahydrofolate reductase (MTHFR, moderate emotional responses to stressful and pleasant stimuli in daily life as measured by Experience Sampling Methodology (ESM. In the first step, main and interactive effects were tested in a sample of 112 healthy individuals. Significant associations in this discovery sample were then investigated in a population-based sample of 434 individuals for replication. SNPs showing significant effects in both the discovery and replication samples were subsequently tested in three other samples of: (i 85 unaffected siblings of patients with psychosis, (ii 110 patients with psychotic disorders, and iii 126 patients with a history of major depressive disorder. Multilevel linear regression analyses showed no significant association between SNPs and negative affect or positive affect. No SNPs moderated the effect of pleasant stimuli on positive affect. Three SNPs of DNMT3A (rs11683424, rs1465764, rs1465825 and 1 SNP of MTHFR (rs1801131 moderated the effect of stressful events on negative affect. Only rs11683424 of DNMT3A showed consistent directions of effect in the majority of the 5 samples. These data provide the first evidence that emotional responses to daily life stressors may be moderated by genetic variation in the genes involved in the epigenetic machinery.

  10. Semiparametric Bayesian analysis of gene-environment interactions with error in measurement of environmental covariates and missing genetic data.

    Science.gov (United States)

    Lobach, Iryna; Mallick, Bani; Carroll, Raymond J

    2011-01-01

    Case-control studies are widely used to detect gene-environment interactions in the etiology of complex diseases. Many variables that are of interest to biomedical researchers are difficult to measure on an individual level, e.g. nutrient intake, cigarette smoking exposure, long-term toxic exposure. Measurement error causes bias in parameter estimates, thus masking key features of data and leading to loss of power and spurious/masked associations. We develop a Bayesian methodology for analysis of case-control studies for the case when measurement error is present in an environmental covariate and the genetic variable has missing data. This approach offers several advantages. It allows prior information to enter the model to make estimation and inference more precise. The environmental covariates measured exactly are modeled completely nonparametrically. Further, information about the probability of disease can be incorporated in the estimation procedure to improve quality of parameter estimates, what cannot be done in conventional case-control studies. A unique feature of the procedure under investigation is that the analysis is based on a pseudo-likelihood function therefore conventional Bayesian techniques may not be technically correct. We propose an approach using Markov Chain Monte Carlo sampling as well as a computationally simple method based on an asymptotic posterior distribution. Simulation experiments demonstrated that our method produced parameter estimates that are nearly unbiased even for small sample sizes. An application of our method is illustrated using a population-based case-control study of the association between calcium intake with the risk of colorectal adenoma development.

  11. Gene-environment interactions: key to unraveling the mystery of Parkinson's disease.

    Science.gov (United States)

    Gao, Hui-Ming; Hong, Jau-Shyong

    2011-06-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease. The gradual, irreversible loss of dopamine neurons in the substantia nigra is the signature lesion of PD. Clinical symptoms of PD become apparent when 50-60% of nigral dopamine neurons are lost. PD progresses insidiously for 5-7 years (preclinical period) and then continues to worsen even under the symptomatic treatment. To determine what triggers the disease onset and what drives the chronic, self-propelling neurodegenerative process becomes critical and urgent, since lack of such knowledge impedes the discovery of effective treatments to retard PD progression. At present, available therapeutics only temporarily relieve PD symptoms. While the identification of causative gene defects in familial PD uncovers important genetic influences in this disease, the majority of PD cases are sporadic and idiopathic. The current consensus suggests that PD develops from multiple risk factors including aging, genetic predisposition, and environmental exposure. Here, we briefly review research on the genetic and environmental causes of PD. We also summarize very recent genome-wide association studies on risk gene polymorphisms in the emergence of PD. We highlight the new converging evidence on gene-environment interplay in the development of PD with an emphasis on newly developed multiple-hit PD models involving both genetic lesions and environmental triggers.

  12. Gene-Environment Interactions Target Mitogen-activated Protein 3 Kinase 1 (MAP3K1) Signaling in Eyelid Morphogenesis*

    Science.gov (United States)

    Mongan, Maureen; Meng, Qinghang; Wang, Jingjing; Kao, Winston W.-Y.; Puga, Alvaro; Xia, Ying

    2015-01-01

    Gene-environment interactions determine the biological outcomes through mechanisms that are poorly understood. Mouse embryonic eyelid closure is a well defined model to study the genetic control of developmental programs. Using this model, we investigated how exposure to dioxin-like environmental pollutants modifies the genetic risk of developmental abnormalities. Our studies reveal that mitogen-activated protein 3 kinase 1 (MAP3K1) signaling is a focal point of gene-environment cross-talk. Dioxin exposure, acting through the aryl hydrocarbon receptor (AHR), blocked eyelid closure in genetic mutants in which MAP3K1 signaling was attenuated but did not disturb this developmental program in either wild type or mutant mice with attenuated epidermal growth factor receptor or WNT signaling. Exposure also markedly inhibited c-Jun phosphorylation in Map3k1+/− embryonic eyelid epithelium, suggesting that dioxin-induced AHR pathways can synergize with gene mutations to inhibit MAP3K1 signaling. Our studies uncover a novel mechanism through which the dioxin-AHR axis interacts with the MAP3K1 signaling pathways during fetal development and provide strong empirical evidence that specific gene alterations can increase the risk of developmental abnormalities driven by environmental pollutant exposure. PMID:26109068

  13. Allowing for population stratification in case-only studies of gene-environment interaction, using genomic control.

    Science.gov (United States)

    Yadav, Pankaj; Freitag-Wolf, Sandra; Lieb, Wolfgang; Dempfle, Astrid; Krawczak, Michael

    2015-10-01

    Gene-environment interactions (G × E) have attracted considerable research interest in the past owing to their scientific and public health implications, but powerful statistical methods are required to successfully track down G × E, particularly at a genome-wide level. Previously, a case-only (CO) design has been proposed as a means to identify G × E with greater efficiency than traditional case-control or cohort studies. However, as with genotype-phenotype association studies themselves, hidden population stratification (PS) can impact the validity of G × E studies using a CO design. Since this problem has been subject to little research to date, we used comprehensive simulation to systematically assess the type I error rate, power and effect size bias of CO studies of G × E in the presence of PS. Three types of PS were considered, namely genetic-only (PSG), environment-only (PSE), and joint genetic and environmental stratification (PSGE). Our results reveal that the type I error rate of an unadjusted Wald test, appropriate for the CO design, would be close to its nominal level (0.05 in our study) as long as PS involves only one interaction partner (i.e., either PSG or PSE). In contrast, if the study population is stratified with respect to both G and E (i.e., if there is PSGE), then the type I error rate is seriously inflated and estimates of the underlying G × E interaction are biased. Comparison of CO to a family-based case-parents design confirmed that the latter is more robust against PSGE, as expected. However, case-parent trios may be particularly unsuitable for G × E studies in view of the fact that they require genotype data from parents and that many diseases with an environmental component are likely to be of late onset. An alternative approach to adjusting for PS is principal component analysis (PCA), which has been widely used for this very purpose in past genome-wide association studies (GWAS). However, resolving genetic PS properly by PCA

  14. Multiple Gene-Environment Interactions on the Angiogenesis Gene-Pathway Impact Rectal Cancer Risk and Survival

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    Noha Sharafeldin

    2017-09-01

    Full Text Available Characterization of gene-environment interactions (GEIs in cancer is limited. We aimed at identifying GEIs in rectal cancer focusing on a relevant biologic process involving the angiogenesis pathway and relevant environmental exposures: cigarette smoking, alcohol consumption, and animal protein intake. We analyzed data from 747 rectal cancer cases and 956 controls from the Diet, Activity and Lifestyle as a Risk Factor for Rectal Cancer study. We applied a 3-step analysis approach: first, we searched for interactions among single nucleotide polymorphisms on the pathway genes; second, we searched for interactions among the genes, both steps using Logic regression; third, we examined the GEIs significant at the 5% level using logistic regression for cancer risk and Cox proportional hazards models for survival. Permutation-based test was used for multiple testing adjustment. We identified 8 significant GEIs associated with risk among 6 genes adjusting for multiple testing: TNF (OR = 1.85, 95% CI: 1.10, 3.11, TLR4 (OR = 2.34, 95% CI: 1.38, 3.98, and EGR2 (OR = 2.23, 95% CI: 1.04, 4.78 with smoking; IGF1R (OR = 1.69, 95% CI: 1.04, 2.72, TLR4 (OR = 2.10, 95% CI: 1.22, 3.60 and EGR2 (OR = 2.12, 95% CI: 1.01, 4.46 with alcohol; and PDGFB (OR = 1.75, 95% CI: 1.04, 2.92 and MMP1 (OR = 2.44, 95% CI: 1.24, 4.81 with protein. Five GEIs were associated with survival at the 5% significance level but not after multiple testing adjustment: CXCR1 (HR = 2.06, 95% CI: 1.13, 3.75 with smoking; and KDR (HR = 4.36, 95% CI: 1.62, 11.73, TLR2 (HR = 9.06, 95% CI: 1.14, 72.11, EGR2 (HR = 2.45, 95% CI: 1.42, 4.22, and EGFR (HR = 6.33, 95% CI: 1.95, 20.54 with protein. GEIs between angiogenesis genes and smoking, alcohol, and animal protein impact rectal cancer risk. Our results support the importance of considering the biologic hypothesis to characterize GEIs associated with cancer outcomes.

  15. Tests for gene-environment interaction from case-control data: a novel study of type I error, power and designs.

    Science.gov (United States)

    Mukherjee, Bhramar; Ahn, Jaeil; Gruber, Stephen B; Rennert, Gad; Moreno, Victor; Chatterjee, Nilanjan

    2008-11-01

    To evaluate the risk of a disease associated with the joint effects of genetic susceptibility and environmental exposures, epidemiologic researchers often test for non-multiplicative gene-environment effects from case-control studies. In this article, we present a comparative study of four alternative tests for interactions: (i) the standard case-control method; (ii) the case-only method, which requires an assumption of gene-environment independence for the underlying population; (iii) a two-step method that decides between the case-only and case-control estimators depending on a statistical test for the gene-environment independence assumption and (iv) a novel empirical-Bayes (EB) method that combines the case-control and case-only estimators depending on the sample size and strength of the gene-environment association in the data. We evaluate the methods in terms of integrated Type I error and power, averaged with respect to varying scenarios for gene-environment association that are likely to appear in practice. These unique studies suggest that the novel EB procedure overall is a promising approach for detection of gene-environment interactions from case-control studies. In particular, the EB procedure, unlike the case-only or two-step methods, can closely maintain a desired Type I error under realistic scenarios of gene-environment dependence and yet can be substantially more powerful than the traditional case-control analysis when the gene-environment independence assumption is satisfied, exactly or approximately. Our studies also reveal potential utility of some non-traditional case-control designs that samples controls at a smaller rate than the cases. Apart from the simulation studies, we also illustrate the different methods by analyzing interactions of two commonly studied genes, N-acetyl transferase type 2 and glutathione s-transferase M1, with smoking and dietary exposures, in a large case-control study of colorectal cancer.

  16. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors.

    Science.gov (United States)

    Nickels, Stefan; Truong, Thérèse; Hein, Rebecca; Stevens, Kristen; Buck, Katharina; Behrens, Sabine; Eilber, Ursula; Schmidt, Martina; Häberle, Lothar; Vrieling, Alina; Gaudet, Mia; Figueroa, Jonine; Schoof, Nils; Spurdle, Amanda B; Rudolph, Anja; Fasching, Peter A; Hopper, John L; Makalic, Enes; Schmidt, Daniel F; Southey, Melissa C; Beckmann, Matthias W; Ekici, Arif B; Fletcher, Olivia; Gibson, Lorna; Silva, Isabel dos Santos; Peto, Julian; Humphreys, Manjeet K; Wang, Jean; Cordina-Duverger, Emilie; Menegaux, Florence; Nordestgaard, Børge G; Bojesen, Stig E; Lanng, Charlotte; Anton-Culver, Hoda; Ziogas, Argyrios; Bernstein, Leslie; Clarke, Christina A; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Brauch, Hiltrud; Brüning, Thomas; Harth, Volker; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Lambrechts, Diether; Smeets, Dominiek; Neven, Patrick; Paridaens, Robert; Flesch-Janys, Dieter; Obi, Nadia; Wang-Gohrke, Shan; Couch, Fergus J; Olson, Janet E; Vachon, Celine M; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Offit, Kenneth; John, Esther M; Miron, Alexander; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Chanock, Stephen J; Lissowska, Jolanta; Liu, Jianjun; Cox, Angela; Cramp, Helen; Connley, Dan; Balasubramanian, Sabapathy; Dunning, Alison M; Shah, Mitul; Trentham-Dietz, Amy; Newcomb, Polly; Titus, Linda; Egan, Kathleen; Cahoon, Elizabeth K; Rajaraman, Preetha; Sigurdson, Alice J; Doody, Michele M; Guénel, Pascal; Pharoah, Paul D P; Schmidt, Marjanka K; Hall, Per; Easton, Doug F; Garcia-Closas, Montserrat; Milne, Roger L; Chang-Claude, Jenny

    2013-01-01

    Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of environmental risk factors.

  17. Gene Environment Interaction: A Trigger Point of Developing Polyglandular Autoimmunity in A Minor Girl from Rural India

    Directory of Open Access Journals (Sweden)

    Dastidar Rinini

    2017-05-01

    Full Text Available A six-year-old girl from rural Bengal was admitted in our hospital with complaints of thirst, frequent micturition, pain in abdomen and constipation. Polyglandular endocrinopathies were identified in the girl thorough clinical and biochemical examination. Hashimoto’s thyroiditis along with Type 1 diabetes mellitus made her a candidate of Polyglandular Autoimmune disease type IIIA. Patient’s history revealed that she was on cow milk since birth. Presence of high risk alleles for T1DM HLA DQA1*0101-DQB1*0302 and DQA1*0301-DQB1*0501 in the girl was disclosed by genetic study. The effect of environmental factors along with genetic susceptibility might contribute to the aggravation and early expression of these rare autoimmune diseases in this girl. This could be a classic example of gene environment interaction in case of unexplained endocrinopathies

  18. Gene, environment, and brain-gut interactions in irritable bowel syndrome.

    Science.gov (United States)

    Fukudo, Shin; Kanazawa, Motoyori

    2011-04-01

    The genetic predisposition and influence of environment may underlie in the pathogenesis and/or pathophysiology of irritable bowel syndrome (IBS). This phenomenon, gene x environment interaction together with brain-gut interactions is emerging area to be clarified in IBS research. Earlier studies focused on candidate genes of neurotransmitters, cytokines, and growth factors. Among them, some studies but not all studies revealed association between phenotypes of IBS and 5-hydroxytryptamine (5-HT)-related genes, noradrenaline-related genes, and cytokine genes. Recent prospective cohort study showed that genes encoding immune and adhesion molecules were associated with post-infectious etiology of IBS. Psychosocial stressors and intraluminal factors especially microbiota are keys to develop IBS. IBS patients may have abnormal gut microbiota as well as increased organic acids. IBS is disorder that relates to brain-gut interactions, emotional dysregulation, and illness behaviors. Brain imaging with or without combination of visceral stimulation enables us to depict the detailed information of brain-gut interactions. In IBS patients, thalamus, insula, anterior cingulate cortex, amygdala, and brainstem were more activated in response to visceral stimulation than controls. Corticotropin-releasing hormone and 5-HT are the candidate substances which regulate exaggerated brain-gut response. In conclusion, gene x environment interaction together with brain-gut interactions may play crucial roles in IBS development. Further fundamental research on this issue is warranted.

  19. Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity

    Science.gov (United States)

    Bouret, Sebastien; Levin, Barry E.; Ozanne, Susan E.

    2015-01-01

    Obesity and type 2 diabetes mellitus (T2DM) often occur together and affect a growing number of individuals in both the developed and developing worlds. Both are associated with a number of other serious illnesses that lead to increased rates of mortality. There is likely a polygenic mode of inheritance underlying both disorders, but it has become increasingly clear that the pre- and postnatal environments play critical roles in pushing predisposed individuals over the edge into a disease state. This review focuses on the many genetic and environmental variables that interact to cause predisposed individuals to become obese and diabetic. The brain and its interactions with the external and internal environment are a major focus given the prominent role these interactions play in the regulation of energy and glucose homeostasis in health and disease. PMID:25540138

  20. Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity, and Hormone-Related Risk Factors.

    Science.gov (United States)

    Usset, Joseph L; Raghavan, Rama; Tyrer, Jonathan P; McGuire, Valerie; Sieh, Weiva; Webb, Penelope; Chang-Claude, Jenny; Rudolph, Anja; Anton-Culver, Hoda; Berchuck, Andrew; Brinton, Louise; Cunningham, Julie M; DeFazio, Anna; Doherty, Jennifer A; Edwards, Robert P; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Goodman, Marc T; Høgdall, Estrid; Jensen, Allan; Johnatty, Sharon E; Kiemeney, Lambertus A; Kjaer, Susanne K; Larson, Melissa C; Lurie, Galina; Massuger, Leon; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Pike, Malcolm C; Ramus, Susan J; Rossing, Mary Anne; Rothstein, Joseph; Song, Honglin; Thompson, Pamela J; van den Berg, David J; Vierkant, Robert A; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wilkens, Lynne R; Wu, Anna H; Yang, Hannah; Pearce, Celeste Leigh; Schildkraut, Joellen M; Pharoah, Paul; Goode, Ellen L; Fridley, Brooke L

    2016-05-01

    Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene-environment interactions related to hormone-related risk factors could differ between obese and non-obese women. We considered interactions between 11,441 SNPs within 80 candidate genes related to hormone biosynthesis and metabolism and insulin-like growth factors with six hormone-related factors (oral contraceptive use, parity, endometriosis, tubal ligation, hormone replacement therapy, and estrogen use) and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case-control studies (6,247 cases; 10,379 controls). Histotype-specific analyses were also completed. SNPs in the following candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology = all, P = 4.9 × 10(-6)) and ESR1 (rs12661437, endometriosis, histology = all, P = 1.5 × 10(-5)). The most notable obesity-gene-hormone risk factor interaction was within INSR (rs113759408, parity, histology = endometrioid, P = 8.8 × 10(-6)). We have demonstrated the feasibility of assessing multifactor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2 Future work is needed to develop powerful statistical methods able to detect these complex interactions. Assessment of multifactor interaction is feasible, and, here, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility. Cancer Epidemiol Biomarkers Prev; 25(5); 780-90. ©2016 AACR. ©2016 American Association for Cancer Research.

  1. Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk

    DEFF Research Database (Denmark)

    Usset, Joseph L; Raghavan, Rama; Tyrer, Jonathan P

    2016-01-01

    , parity, histology = endometrioid, P = 8.8 × 10(-6)). CONCLUSIONS: We have demonstrated the feasibility of assessing multifactor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2...

  2. The Behavioural Phenotype of Smith-Magenis Syndrome: Evidence for a Gene-Environment Interaction

    Science.gov (United States)

    Taylor, L.; Oliver, C.

    2008-01-01

    Background: Behaviour problems and a preference for adult contact are reported to be prominent in the phenotype of Smith-Magenis syndrome. In this study we examined the relationship between social interactions and self-injurious and aggressive/disruptive behaviour in Smith-Magenis syndrome to explore potential operant reinforcement of problem…

  3. Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits

    DEFF Research Database (Denmark)

    Dashti, Hassan S; Follis, Jack L; Smith, Caren E;

    2015-01-01

    , MTNR1B-rs10830963, NR1D1-rs2314339) and cardiometabolic traits (fasting glucose [FG], HOMA-insulin resistance, BMI, waist circumference, and HDL-cholesterol) to facilitate personalized recommendations. RESEARCH DESIGN AND METHODS: We conducted inverse-variance weighted, fixed-effect meta......-analyses of results of adjusted associations and interactions between dietary intake/sleep duration and selected variants on cardiometabolic traits from 15 cohort studies including up to 28,190 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium....... RESULTS: We observed significant associations between relative macronutrient intakes and glycemic traits and short sleep duration (traits. No interactions were evident after accounting for multiple comparisons. However, we observed...

  4. Gene-Environment Interactions in the Development of Complex Disease Phenotypes

    Directory of Open Access Journals (Sweden)

    Kenneth Olden

    2008-03-01

    Full Text Available The lack of knowledge about the earliest events in disease development is due to the multi-factorial nature of disease risk. This information gap is the consequence of the lack of appreciation for the fact that most diseases arise from the complex interactions between genes and the environment as a function of the age or stage of development of the individual. Whether an environmental exposure causes illness or not is dependent on the efficiency of the so-called “environmental response machinery” (i.e., the complex of metabolic pathways that can modulate response to environmental perturbations that one has inherited. Thus, elucidating the causes of most chronic diseases will require an understanding of both the genetic and environmental contribution to their etiology. Unfortunately, the exploration of the relationship between genes and the environment has been hampered in the past by the limited knowledge of the human genome, and by the inclination of scientists to study disease development using experimental models that consider exposure to a single environmental agent. Rarely in the past were interactions between multiple genes or between genes and environmental agents considered in studies of human disease etiology. The most critical issue is how to relate exposure-disease association studies to pathways and mechanisms. To understand how genes and environmental factors interact to perturb biological pathways to cause injury or disease, scientists will need tools with the capacity to monitor the global expression of thousands of genes, proteins and metabolites simultaneously. The generation of such data in multiple species can be used to identify conserved and functionally significant genes and pathways involved in geneenvironment interactions. Ultimately, it is this knowledge that will be used to guide agencies such as the U.S. Department of Health and Human Services in decisions regarding biomedical research funding

  5. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors.

    Directory of Open Access Journals (Sweden)

    Stefan Nickels

    Full Text Available Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6 and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4. Overall, the per-allele odds ratio (95% confidence interval for LSP1-rs3817198 was 1.08 (1.01-1.16 in nulliparous women and ranged from 1.03 (0.96-1.10 in parous women with one birth to 1.26 (1.16-1.37 in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98 in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85 in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5, with a per-allele OR of 1.14 (1.11-1.17 in parous women and 0.98 (0.92-1.05 in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

  6. Gene-environment interactions in cancer epidemiology: a National Cancer Institute Think Tank report.

    Science.gov (United States)

    Hutter, Carolyn M; Mechanic, Leah E; Chatterjee, Nilanjan; Kraft, Peter; Gillanders, Elizabeth M

    2013-11-01

    Cancer risk is determined by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified hundreds of common (minor allele frequency [MAF] > 0.05) and less common (0.01 cancer epidemiology, and (3) opportunities for developing novel study designs and analysis tools. This report summarizes the Think Tank discussion, with a focus on contemporary approaches to the analysis of G × E interactions. Selecting the appropriate methods requires first identifying the relevant scientific question and rationale, with an important distinction made between analyses aiming to characterize the joint effects of putative or established genetic and environmental factors and analyses aiming to discover novel risk factors or novel interaction effects. Other discussion items include measurement error, statistical power, significance, and replication. Additional designs, exposure assessments, and analytical approaches need to be considered as we move from the current small number of success stories to a fuller understanding of the interplay of genetic and environmental factors. © 2013 WILEY PERIODICALS, INC.

  7. Does Parental Divorce Moderate the Heritability of Body Dissatisfaction? An Extension of Previous Gene-Environment Interaction Effects

    Science.gov (United States)

    O’Connor, Shannon M.; Klump, Kelly L.; VanHuysse, Jessica L.; McGue, Matt; Iacono, William

    2015-01-01

    Objective Previous research suggests that parental divorce moderates genetic influences on body dissatisfaction. Specifically, the heritability of body dissatisfaction is higher in children of divorced versus intact families, suggesting possible gene-environment interaction effects. However, prior research is limited to a single, self-report measure of body dissatisfaction. The primary aim of the present study was to examine whether these findings extend to a different dimension of body dissatisfaction, body image perceptions. Method Participants were 1,534 female twins from the Minnesota Twin Family Study, ages 16–20 years. The Body Rating Scale (BRS) was used to assess body image perceptions. Results Although BRS scores were heritable in twins from divorced and intact families, the heritability estimates in the divorced group were not significantly greater than estimates in the intact group. However, there were differences in nonshared environmental effects, where the magnitude of these environmental influences was larger in the divorced as compared to the intact families. Discussion Different dimensions of body dissatisfaction (i.e., negative self-evaluation versus body image perceptions) may interact with environmental risk, such as parental divorce, in discrete ways. Future research should examine this possibility and explore differential gene x environment interactions using diverse measures. PMID:26314278

  8. Gli2 gene-environment interactions contribute to the etiological complexity of holoprosencephaly: evidence from a mouse model

    Directory of Open Access Journals (Sweden)

    Galen W. Heyne

    2016-11-01

    Full Text Available Holoprosencephaly (HPE is a common and severe human developmental abnormality marked by malformations of the forebrain and face. Although several genetic mutations have been linked to HPE, phenotypic outcomes range dramatically, and most cases cannot be attributed to a specific cause. Gene-environment interaction has been invoked as a premise to explain the etiological complexity of HPE, but identification of interacting factors has been extremely limited. Here, we demonstrate that mutations in Gli2, which encodes a Hedgehog pathway transcription factor, can cause or predispose to HPE depending upon gene dosage. On the C57BL/6J background, homozygous GLI2 loss of function results in the characteristic brain and facial features seen in severe human HPE, including midfacial hypoplasia, hypotelorism and medial forebrain deficiency with loss of ventral neurospecification. Although normally indistinguishable from wild-type littermates, we demonstrate that mice with single-allele Gli2 mutations exhibit increased penetrance and severity of HPE in response to low-dose teratogen exposure. This genetic predisposition is associated with a Gli2 dosage-dependent attenuation of Hedgehog ligand responsiveness at the cellular level. In addition to revealing a causative role for GLI2 in HPE genesis, these studies demonstrate a mechanism by which normally silent genetic and environmental factors can interact to produce severe outcomes. Taken together, these findings provide a framework for the understanding of the extreme phenotypic variability observed in humans carrying GLI2 mutations and a paradigm for reducing the incidence of this morbid birth defect.

  9. Gli2 gene-environment interactions contribute to the etiological complexity of holoprosencephaly: evidence from a mouse model

    Science.gov (United States)

    Heyne, Galen W.; Everson, Joshua L.; Ansen-Wilson, Lydia J.; Melberg, Cal G.; Fink, Dustin M.; Parins, Kia F.; Doroodchi, Padydeh; Ulschmid, Caden M.

    2016-01-01

    ABSTRACT Holoprosencephaly (HPE) is a common and severe human developmental abnormality marked by malformations of the forebrain and face. Although several genetic mutations have been linked to HPE, phenotypic outcomes range dramatically, and most cases cannot be attributed to a specific cause. Gene-environment interaction has been invoked as a premise to explain the etiological complexity of HPE, but identification of interacting factors has been extremely limited. Here, we demonstrate that mutations in Gli2, which encodes a Hedgehog pathway transcription factor, can cause or predispose to HPE depending upon gene dosage. On the C57BL/6J background, homozygous GLI2 loss of function results in the characteristic brain and facial features seen in severe human HPE, including midfacial hypoplasia, hypotelorism and medial forebrain deficiency with loss of ventral neurospecification. Although normally indistinguishable from wild-type littermates, we demonstrate that mice with single-allele Gli2 mutations exhibit increased penetrance and severity of HPE in response to low-dose teratogen exposure. This genetic predisposition is associated with a Gli2 dosage-dependent attenuation of Hedgehog ligand responsiveness at the cellular level. In addition to revealing a causative role for GLI2 in HPE genesis, these studies demonstrate a mechanism by which normally silent genetic and environmental factors can interact to produce severe outcomes. Taken together, these findings provide a framework for the understanding of the extreme phenotypic variability observed in humans carrying GLI2 mutations and a paradigm for reducing the incidence of this morbid birth defect. PMID:27585885

  10. Gene-Environment Interactions in Preventive Medicine: Current Status and Expectations for the Future.

    Science.gov (United States)

    Narimatsu, Hiroto

    2017-01-30

    The progression of many common disorders involves a complex interplay of multiple factors, including numerous different genes and environmental factors. Gene-environmental cohort studies focus on the identification of risk factors that cannot be discovered by conventional epidemiological methodologies. Such epidemiological methodologies preclude precise predictions, because the exact risk factors can be revealed only after detailed analyses of the interactions among multiple factors, that is, between genes and environmental factors. To date, these cohort studies have reported some promising results. However, the findings do not yet have sufficient clinical significance for the development of precise, personalized preventive medicine. Especially, some promising preliminary studies have been conducted in terms of the prevention of obesity. Large-scale validation studies of those preliminary studies, using a prospective cohort design and long follow-ups, will produce useful and practical evidence for the development of preventive medicine in the future.

  11. Gene-environment interaction in the onset of eczema in infancy

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Simpson, Angela; Palmer, Colin N A

    2008-01-01

    BACKGROUND: Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether...... there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema. METHODS AND FINDINGS: We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort...... in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27-4.00, p...

  12. Gene - environment interaction in programming hippocampal plasticity: focus on adult neurogenesis

    Directory of Open Access Journals (Sweden)

    Muriel eKoehl

    2015-08-01

    Full Text Available Interactions between genes and environment are a critical feature of development and both contribute to shape individuality. They are at the chore of vulnerability / resiliency for mental illnesses. During the early postnatal period, several brain structures involved in cognitive and emotional processing, such as the hippocampus, still develop and it is likely that interferences with this neuronal development, which is genetically determined, might lead to long-lasting structural and functional consequences and increase the risk of developing psychopathology. One particular target is adult neurogenesis, which is involved in the regulation of cognitive and emotional processes. Insights into the dynamic interplay between genes and environmental factors in setting up individual rates of neurogenesis have come from laboratory studies exploring experience-dependent changes in adult neurogenesis as a function of individual’s genetic makeup. These studies have implications for our understanding of the mechanisms regulating adult neurogenesis, which could constitute a link between environmental challenges and psychopathology.

  13. Gene-gene and gene-environment interactions in prostate, breast and colorectal cancer

    DEFF Research Database (Denmark)

    Kopp, Tine Iskov

    transporters and IL-10 in relation to CRC. Paper V illustrated that genetic variations in CYP19A1 predicts circulating sex-hormone levels in postmenopausal women, and that alcohol intake affects female sex-hormone concentrations in the blood. However, it was not possible to put PPARγ and the aromatase...... single-gene mutations due to their low frequency in the general population. Overall, the contribution from hereditary factors to the causation of BC is only 27%, whereas genetics contributes to 35% and 42% for CRC and PC, respectively. Additionally, immigrations studies point to environmental factors......, such as alcohol consumption, smoking, obesity, inflammation and high meat intake; whereas other factors protect against cancer, such as high intake of dietary fibre, fruits and vegetables, and physical activity. Investigating the interactions between genetic variations and environmental factors, such as dietary...

  14. Progress in the epidemiological understanding of gene-environment interactions in major diseases: cancer.

    Science.gov (United States)

    Clavel, Jacqueline

    2007-04-01

    Cancer epidemiology has undergone marked development since the 1950s. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking on the occurrence of lung, larynx, and bladder cancer. Major chemical, physical, and biological carcinogenic agents have been identified in the working environment and in the overall environment. The chain of events from environmental exposures to cancer requires hundreds of polymorphic genes coding for proteins involved in the transport and metabolism of xenobiotics, or in repair, or in an immune or inflammatory response. The multifactorial and multistage characteristics of cancer create the theoretical conditions for statistical interactions that have been exceptionally detected. Over the last two decades, a considerable mass of data has been generated, mostly addressing the interactions between smoking and xenobiotic-metabolizing enzymes in smoking-related cancers. They were sometimes considered disappointing, but they actually brought a lot of information and raised many methodological issues. In parallel, the number of polymorphisms that can be considered candidate per function increased so much that multiple testing has become a major issue, and genome wide-screening approaches have more and more gained in interest. Facing the resulting complexity, some instruments are being set up: our studies are now equipped with carefully sampled biological collections, high-throughput genotyping systems are becoming available, work on statistical methodologies is ongoing, bioinformatics databases are growing larger and access to them is becoming simpler; international consortiums are being organized. The roles of environmental and genetic factors are being jointly elucidated. The basic rules of epidemiology, which are demanding with respect to sampling, with respect to the histological and molecular criteria for cancer classification, with respect to the evaluation of environmental exposures

  15. Gene-environment interactions and intermediate phenotypes: early trauma and depression

    Directory of Open Access Journals (Sweden)

    Orla eHornung

    2014-02-01

    Full Text Available This review focuses on current research developments in the study of Gene x ELS interactions and depression. It serves as a snapshot report of the most recent findings in this dynamic and complex field of research. After several years of investigating and characterizing the specific role of early life stress within the pathogenesis of depression and linking these findings to neurobiological changes of the brain, especially the stress response system, the latest findings highlight the role of genetic factors that increase vulnerability or, likewise, promote resilience to depression after childhood trauma. Considering intermediate phenotypes has further increased our understanding of the complex relationship between early trauma and depression. Recent findings with regard to epigenetic changes resulting from adverse environmental events during childhood promote current aspirations to identify specific target areas for prevention and treatment schemes regarding the long-term impact of early life stress. Taken together, latest findings have underscored the essential role of genotypes and epigenetic processes within the development of depression after childhood trauma, thereby building the basis for future research and clinical interventions.

  16. Degenerative periodontal-diseases and oral osteonecrosis: The role of gene-environment interactions

    Energy Technology Data Exchange (ETDEWEB)

    Baldi, D. [Department of Medical, Biophysical, and Dentistry Sciences and Technologies, University of Genoa (Italy); Izzotti, A. [Department of Health Sciences, University of Genoa, Via A. Pastore 1 (Italy); Bonica, P.; Pera, P. [Department of Medical, Biophysical, and Dentistry Sciences and Technologies, University of Genoa (Italy); Pulliero, A., E-mail: alessandra.pulliero@unige.it [Department of Health Sciences, University of Genoa, Via A. Pastore 1 (Italy)

    2009-07-10

    Chronic-degenerative dentistry diseases, including periodontal diseases and oral osteonecrosis, are widespread in human populations and represent a significant problem for public health. These diseases result from pathogenic mechanisms created by the interaction between environmental genotoxic risk-factors and genetic assets conferring individual susceptibility. Osteonecrosis occurs in subjects undergoing exposure to high doses of DNA-damaging agents for chemo- and radiotherapy of neoplastic diseases. In susceptible patients, ionizing radiation and biphosphonate-chemotherapy induce severe, progressive, and irreversible degeneration of facial bones, resulting in avascular necrosis of the jaw. This may also occur in patients receiving biphosphonate for osteoporosis therapy. Periodontal diseases include chronic, aggressive, and necrotizing periodontitis, often resulting in severe alteration of periodontal tissues and tooth loss. Cigarette smoking and chronic inflammation caused by specific bacteria are the main risk factors for periodontitis. Oxidative damage plays a fundamental pathogenic role, as established by detection of mitochondrial DNA damage in the gingival tissue of patients with periodontitis. Endogenous risk factors in dental diseases include polymorphisms for metabolic enzymes such as glutathione transferases M1 and T1, N-acetyl transferase 2, and CYP 1A1. Other genetic polymorphisms that confer susceptibility to dentistry diseases affect genes encoding metalloproteases (involved in periodontal tissue remodeling and degradation), cytokines (involved in inflammation), prothrombin, and DNA repair activities. These findings provide evidence that dentistry diseases are related to risk factors associated with environmental mutagenesis. This issue warrants future investigations aimed at improving oral health and preventing oral degenerative diseases using molecular and experimental approaches currently utilized in mutagenicity studies.

  17. Three Approaches to Modeling Gene-Environment Interactions in Longitudinal Family Data: Gene-Smoking Interactions in Blood Pressure.

    Science.gov (United States)

    Basson, Jacob; Sung, Yun Ju; de Las Fuentes, Lisa; Schwander, Karen L; Vazquez, Ana; Rao, Dabeeru C

    2016-01-01

    Blood pressure (BP) has been shown to be substantially heritable, yet identified genetic variants explain only a small fraction of the heritability. Gene-smoking interactions have detected novel BP loci in cross-sectional family data. Longitudinal family data are available and have additional promise to identify BP loci. However, this type of data presents unique analysis challenges. Although several methods for analyzing longitudinal family data are available, which method is the most appropriate and under what conditions has not been fully studied. Using data from three clinic visits from the Framingham Heart Study, we performed association analysis accounting for gene-smoking interactions in BP at 31,203 markers on chromosome 22. We evaluated three different modeling frameworks: generalized estimating equations (GEE), hierarchical linear modeling, and pedigree-based mixed modeling. The three models performed somewhat comparably, with multiple overlaps in the most strongly associated loci from each model. Loci with the greatest significance were more strongly supported in the longitudinal analyses than in any of the component single-visit analyses. The pedigree-based mixed model was more conservative, with less inflation in the variant main effect and greater deflation in the gene-smoking interactions. The GEE, but not the other two models, resulted in substantial inflation in the tail of the distribution when variants with minor allele frequency familial and longitudinal data. © 2015 WILEY PERIODICALS, INC.

  18. Gene-environment interaction from international cohorts: impact on development and evolution of occupational and environmental lung and airway disease.

    Science.gov (United States)

    Gaffney, Adam; Christiani, David C

    2015-06-01

    Environmental and occupational pulmonary diseases impose a substantial burden of morbidity and mortality on the global population. However, it has been long observed that only some of those who are exposed to pulmonary toxicants go on to develop disease; increasingly, it is being recognized that genetic differences may underlie some of this person-to-person variability. Studies performed throughout the globe are demonstrating important gene-environment interactions for diseases as diverse as chronic beryllium disease, coal workers' pneumoconiosis, silicosis, asbestosis, byssinosis, occupational asthma, and pollution-associated asthma. These findings have, in many instances, elucidated the pathogenesis of these highly complex diseases. At the same time, however, translation of this research into clinical practice has, for good reasons, proceeded slowly. No genetic test has yet emerged with sufficiently robust operating characteristics to be clearly useful or practicable in an occupational or environmental setting. In addition, occupational genetic testing raises serious ethical and policy concerns. Therefore, the primary objective must remain ensuring that the workplace and the environment are safe for all.

  19. Nrf2 regulates gene-environment interactions in an animal model of intrauterine inflammation: Implications for preterm birth and prematurity

    Science.gov (United States)

    Sussan, Thomas E.; Sudini, Kuladeep; Talbot, C. Conover; Wang, Xiaobin; Wills-Karp, Marsha; Burd, Irina; Biswal, Shyam

    2017-01-01

    Preterm birth (PTB) is the leading cause of neonatal mortality, and surviving infants are at increased risk for lifelong disabilities. Intrauterine inflammation is an etiological factor that drives PTB, and oxidative stress is associated with PTB. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and inflammatory stress. Here, we used the established mouse model of intrauterine inflammation-induced PTB to determine whether Nrf2 is a modifier of susceptibility to PTB and prematurity-related morbidity and mortality in the offspring. We determined that Nr2-deficient (Nrf2−/−) mice exhibited a greater sensitivity to intrauterine inflammation, as indicated by decreased time to delivery, reduced birthweight, and 100% mortality. Placentas from preterm Nrf2−/− mice showed elevated levels of markers of inflammation, oxidative stress, and cell death, and transcriptomic analysis identified numerous key signaling pathways that were differentially expressed between wild-type (WT) and Nrf2−/− mice in both preterm and control samples. Thus, Nrf2 could be a critical factor for gene-environment interactions that may determine susceptibility to PTB. Further studies are needed to determine if Nrf2 is a viable therapeutic target in women who are at risk for PTB and associated complications in the affected offspring. PMID:28071748

  20. Genetic gating of human fear learning and extinction: possible implications for gene-environment interaction in anxiety disorder.

    Science.gov (United States)

    Lonsdorf, Tina B; Weike, Almut I; Nikamo, Pernilla; Schalling, Martin; Hamm, Alfons O; Ohman, Arne

    2009-02-01

    Pavlovian fear conditioning is a widely used model of the acquisition and extinction of fear. Neural findings suggest that the amygdala is the core structure for fear acquisition, whereas prefrontal cortical areas are given pivotal roles in fear extinction. Forty-eight volunteers participated in a fear-conditioning experiment, which used fear potentiation of the startle reflex as the primary measure to investigate the effect of two genetic polymorphisms (5-HTTLPR and COMTval158met) on conditioning and extinction of fear. The 5-HTTLPR polymorphism, located in the serotonin transporter gene, is associated with amygdala reactivity and neuroticism, whereas the COMTval158met polymorphism, which is located in the gene coding for catechol-O-methyltransferase (COMT), a dopamine-degrading enzyme, affects prefrontal executive functions. Our results show that only carriers of the 5-HTTLPR s allele exhibited conditioned startle potentiation, whereas carriers of the COMT met/met genotype failed to extinguish conditioned fear. These results may have interesting implications for understanding gene-environment interactions in the development and treatment of anxiety disorders.

  1. Estimating genetic effect sizes under joint disease-endophenotype models in presence of gene-environment interactions

    Directory of Open Access Journals (Sweden)

    Alexandre eBureau

    2015-07-01

    Full Text Available Effects of genetic variants on the risk of complex diseases estimated from association studies are typically small. Nonetheless, variants may have important effects in presence of specific levels of environmental exposures, and when a trait related to the disease (endophenotype is either normal or impaired. We propose polytomous and transition models to represent the relationship between disease, endophenotype, genotype and environmental exposure in family studies. Model coefficients were estimated using generalized estimating equations and were used to derive gene-environment interaction effects and genotype effects at specific levels of exposure. In a simulation study, estimates of the effect of a genetic variant were substantially higher when both an endophenotype and an environmental exposure modifying the variant effect were taken into account, particularly under transition models, compared to the alternative of ignoring the endophenotype. Illustration of the proposed modeling with the metabolic syndrome, abdominal obesity, physical activity and polymorphisms in the NOX3 gene in the Quebec Family Study revealed that the positive association of the A allele of rs1375713 with the metabolic syndrome at high levels of physical activity was only detectable in subjects without abdominal obesity, illustrating the importance of taking into account the abdominal obesity endophenotype in this analysis.

  2. Evaluation of two methods for assessing gene-environment interactions using data from the Danish case-control study of facial clefts

    DEFF Research Database (Denmark)

    Etheredge, Analee J; Christensen, Kaare; Del Junco, Deborah

    2005-01-01

    BACKGROUND: Epidemiological investigations have begun to consider gene-environment (GE) interactions as potential risk factors for many diseases, including several different birth defects. However, traditional methodological approaches for the analysis of case-control data tend to have low power...

  3. Gene environment interaction in urinary bladder cancer with special reference to organochlorine pesticide: a case control study.

    Science.gov (United States)

    Sharma, Tusha; Jain, Smita; Verma, Ankur; Sharma, Nivedita; Gupta, Sanjay; Arora, Vinod Kumar; Dev Banerjee, Basu

    2013-01-01

    Urinary bladder cancer (UBC) is a common disease worldwide with a higher incidence rate in developed countries. Organochlorine pesticides (OCPs), potent endocrine disrupters, are found to be associated with several cancers such as prostate, breast, bladder, etc. Glutathione S-transferase (GST) is a polymorphic supergene family involved in the detoxification of numerous environmental toxins including OCPs. The present study was carried out in UBC subjects (n=50) and healthy control subjects (n=50) with an aim to determine the role of GSTM1 and GSTT1 polymorphism and its implication on the OCP detoxification or bioaccumulation which may increase the risk of UBC in humans. This study was also designed to identify the "gene-environment interaction" specifically between gene polymorphism in xenobiotic metabolizing genetic enzyme(s) and blood OCP levels. GSTM1/GSTT1 gene polymorphism was analysed by using multiplex PCR. OCPs levels in whole blood were estimated by Gas chromatography equipped with electron capture detector. The results demonstrated a significant (p^{-}/GSTT1^{-} (null) genotype in UBC cases without interfering the distribution of other GSTT1/GSTM1 genotypes. The blood levels of alpha (α), Beta (β), Gamma (γ), total - Hexachlorcyclohexane (HCH) and para-para - dichlorodiphenyltrichloroetane (p,p'-DDT) were found to be significantly (pcases as compared to controls. Multiple regression analysis revealed a significant interaction between β-HCH and GSTM1^{-} genotype (p^{-} genotype (penvironment interaction" may play a key role in increasing the risk for UBC in individuals who are genetically more susceptible due to presence of GSTM1/GSTT1 null deletion during their routine encounter with or exposure to OCPs.

  4. Gene-environment interaction in progression of AMD: the CFH gene, smoking and exposure to chronic infection.

    Science.gov (United States)

    Baird, Paul N; Robman, Luba D; Richardson, Andrea J; Dimitrov, Peter N; Tikellis, Gabriella; McCarty, Catherine A; Guymer, Robyn H

    2008-05-01

    A number of risk factors including the complement factor H (CFH) gene, smoking and Chlamydia pneumoniae have been associated with age-related macular degeneration (AMD). However, the mechanisms underlying how these risk factors might be involved in disease progression and disease aetiology is poorly understood. A cohort series of 233 individuals followed for AMD progression over a mean period of 7 years underwent a full eye examination, blood was taken for DNA and antibody titre and individuals completed a standard medical and general questionnaire. Y402H variants of the CFH gene were assessed with disease progression as well as examination of interaction between Y402H variants and smoking and Y402H variants and the pathogen C. pneumoniae. The CC risk genotype of Y402H was significantly associated with increased AMD progression [odds ratio (OR) 2.43, 95% confidence interval (95% CI) 1.07-5.49] as was smoking (OR 2.28, 95% CI 1.26-4.12). However, the risk of progression was greatly increased to almost 12-fold (OR 11.8, 95% CI 2.1-65.8) when, in addition to having the C risk allele, subjects also presented with the upper tertile of antibodies to the bacterial pathogen C. pneumoniae compared with those with the T allele of Y402H and the lowest antibody tertile. This demonstrates for the first time the existence of a gene environment-interaction between pathogenic load of C. pneumoniae and the CFH gene in the aetiology of AMD.

  5. Culture as a mediator of gene-environment interaction: Cultural consonance, childhood adversity, a 2A serotonin receptor polymorphism, and depression in urban Brazil.

    Science.gov (United States)

    Dressler, William W; Balieiro, Mauro C; Ferreira de Araújo, Luiza; Silva, Wilson A; Ernesto Dos Santos, José

    2016-07-01

    Research on gene-environment interaction was facilitated by breakthroughs in molecular biology in the late 20th century, especially in the study of mental health. There is a reliable interaction between candidate genes for depression and childhood adversity in relation to mental health outcomes. The aim of this paper is to explore the role of culture in this process in an urban community in Brazil. The specific cultural factor examined is cultural consonance, or the degree to which individuals are able to successfully incorporate salient cultural models into their own beliefs and behaviors. It was hypothesized that cultural consonance in family life would mediate the interaction of genotype and childhood adversity. In a study of 402 adult Brazilians from diverse socioeconomic backgrounds, conducted from 2011 to 2014, the interaction of reported childhood adversity and a polymorphism in the 2A serotonin receptor was associated with higher depressive symptoms. Further analysis showed that the gene-environment interaction was mediated by cultural consonance in family life, and that these effects were more pronounced in lower social class neighborhoods. The findings reinforce the role of the serotonergic system in the regulation of stress response and learning and memory, and how these processes in turn interact with environmental events and circumstances. Furthermore, these results suggest that gene-environment interaction models should incorporate a wider range of environmental experience and more complex pathways to better understand how genes and the environment combine to influence mental health outcomes.

  6. Estimating risks and relative risks in case-base studies under the assumptions of gene-environment independence and Hardy-Weinberg equilibrium.

    Science.gov (United States)

    Chui, Tina Tsz-Ting; Lee, Wen-Chung

    2014-01-01

    Many diseases result from the interactions between genes and the environment. An efficient method has been proposed for a case-control study to estimate the genetic and environmental main effects and their interactions, which exploits the assumptions of gene-environment independence and Hardy-Weinberg equilibrium. To estimate the absolute and relative risks, one needs to resort to an alternative design: the case-base study. In this paper, the authors show how to analyze a case-base study under the above dual assumptions. This approach is based on a conditional logistic regression of case-counterfactual controls matched data. It can be easily fitted with readily available statistical packages. When the dual assumptions are met, the method is approximately unbiased and has adequate coverage probabilities for confidence intervals. It also results in smaller variances and shorter confidence intervals as compared with a previous method for a case-base study which imposes neither assumption.

  7. Research Review: Gene-Environment Interaction Research in Youth Depression--A Systematic Review with Recommendations for Future Research

    Science.gov (United States)

    Dunn, Erin C.; Uddin, Monica; Subramanian, S. V.; Smoller, Jordan W.; Galea, Sandro; Koenen, Karestan C.

    2011-01-01

    Background: Depression is a major public health problem among youth, currently estimated to affect as many as 9% of US children and adolescents. The recognition that both genes (nature) and environments (nurture) are important for understanding the etiology of depression has led to a rapid growth in research exploring gene-environment interactions…

  8. Research Review: Gene-Environment Interaction Research in Youth Depression--A Systematic Review with Recommendations for Future Research

    Science.gov (United States)

    Dunn, Erin C.; Uddin, Monica; Subramanian, S. V.; Smoller, Jordan W.; Galea, Sandro; Koenen, Karestan C.

    2011-01-01

    Background: Depression is a major public health problem among youth, currently estimated to affect as many as 9% of US children and adolescents. The recognition that both genes (nature) and environments (nurture) are important for understanding the etiology of depression has led to a rapid growth in research exploring gene-environment interactions…

  9. Epigenetic Genes and Emotional Reactivity to Daily Life Events : A Multi-Step Gene-Environment Interaction Study

    NARCIS (Netherlands)

    Pishva, Ehsan; Drukker, Marjan; Viechtbauer, Wolfgang; Decoster, Jeroen; Collip, Dina; van Winkel, Ruud; Wichers, Marieke; Jacobs, Nele; Thiery, Evert; Derom, Catherine; Geschwind, Nicole; van den Hove, Daniel; Lataster, Tineke; Myin-Germeys, Inez; van Os, Jim; Rutten, Bart P. F.; Kenis, Gunter

    2014-01-01

    Recent human and animal studies suggest that epigenetic mechanisms mediate the impact of environment on development of mental disorders. Therefore, we hypothesized that polymorphisms in epigenetic-regulatory genes impact stress-induced emotional changes. A multi-step, multi-sample gene-environment i

  10. Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer.

    Directory of Open Access Journals (Sweden)

    Rakhshan Ihsan

    SULT1A1 Arg213His and EPHX1 Tyr113His in smokers and SULT1A1 Arg213His with GSTP1 Ile105Val and CYP1A1*2C in nonsmokers. These results identified distinct gene-gene and gene environment interactions in smokers and non-smokers, which confirms the importance of multifactorial interaction in risk assessment of lung cancer.

  11. The Interacting Effect of the BDNF Val66Met Polymorphism and Stressful Life Events on Adolescent Depression Is Not an Artifact of Gene-Environment Correlation: Evidence from a Longitudinal Twin Study

    Science.gov (United States)

    Chen, Jie; Li, Xinying; McGue, Matt

    2013-01-01

    Background: Confounding introduced by gene-environment correlation (rGE) may prevent one from observing a true gene-environment interaction (G × E) effect on psychopathology. The present study investigated the interacting effect of the BDNF Val66Met polymorphism and stressful life events (SLEs) on adolescent depression while controlling for the…

  12. Assessing gene-environment interaction effects of FTO, MC4R and lifestyle factors on obesity using an extreme phenotype sampling design: Results from the HUNT study.

    Science.gov (United States)

    Bjørnland, Thea; Langaas, Mette; Grill, Valdemar; Mostad, Ingrid Løvold

    2017-01-01

    Our aim was to assess the influence of age, gender and lifestyle factors on the effect of the obesity-promoting alleles of FTO and MCR4. The HUNT study comprises health information on the population of Nord-Trøndelag county, Norway. Extreme phenotype participants (gender-wise lower and upper quartiles of waist-hip-ratio and BMI ≥ 35 kg/m2) in the third survey, HUNT3 (2006-08), were genotyped for the single-nucleotide polymorphisms rs9939609 (FTO) and rs17782313 (MC4R); 25686 participants were successfully genotyped. Extreme sampling was chosen to increase power to detect genetic and gene-environment effects on waist-hip-ratio and BMI. Statistical inference was based on linear regression models and a missing-covariate likelihood approach for the extreme phenotype sampling design. Environmental factors were physical activity, diet (artificially sweetened beverages) and smoking. Longitudinal analysis was performed using material from HUNT2 (1995-97). Cross-sectional and longitudinal genetic effects indicated stronger genetic associations with obesity in young than in old, as well as differences between women and men. We observed larger genetic effects among physically inactive compared to active individuals. This interaction was age-dependent and seen mainly in 20-40 year olds. We observed a greater FTO effect among men with a regular intake of artificially sweetened beverages, compared to non-drinkers. Interaction analysis of smoking was mainly inconclusive. In a large all-adult and area-based population survey the effects of obesity-promoting minor-alleles of FTO and MCR4, and interactions with life style factors are age- and gender-related. These findings appear relevant when designing individualized treatment for and prophylaxis against obesity.

  13. The immunogenetics of narcolepsy associated with A(H1N1)pdm09 vaccination (Pandemrix) supports a potent gene-environment interaction.

    Science.gov (United States)

    Bomfim, I L; Lamb, F; Fink, K; Szakács, A; Silveira, A; Franzén, L; Azhary, V; Maeurer, M; Feltelius, N; Darin, N; Hallböök, T; Arnheim-Dahlström, L; Kockum, I; Olsson, T

    2017-03-01

    The influenza A(H1N1)pdm09 vaccination campaign from 2009 to 2010 was associated with a sudden increase in the incidence of narcolepsy in several countries. Narcolepsy with cataplexy is strongly associated with the human leukocyte antigen (HLA) class II DQB1*06:02 allele, and protective associations with the DQB1*06:03 allele have been reported. Several non-HLA gene loci are also associated, such as common variants of the T-cell receptor-α (TRA), the purinergic receptor P2RY11, cathepsin H (CTSH) and TNFSF4/OX40L/CD252. In this retrospective multicenter study, we investigated if these predisposing gene loci were also involved in vaccination-associated narcolepsy. We compared HLA- along with single-nucleotide polymorphism genotypes for non-HLA regions between 42 Pandemrix-vaccinated narcolepsy cases and 1990 population-based controls. The class II gene loci associations supported previous findings. Nominal association (P-value<0.05) with TRA as well as suggestive (P-value<0.1) associations with P2RY11 and CTSH were found. These associations suggest a very strong gene-environment interaction, in which the influenza A(H1N1)pdm09 strain or Pandemrix vaccine can act as potent environmental triggers.

  14. Replication and meta-analysis of the gene-environment interaction between body mass index and the interleukin-6 promoter polymorphism with higher insulin resistance.

    Science.gov (United States)

    Underwood, Patricia C; Chamarthi, Bindu; Williams, Jonathan S; Sun, Bei; Vaidya, Anand; Raby, Benjamin A; Lasky-Su, Jessica; Hopkins, Paul N; Adler, Gail K; Williams, Gordon H

    2012-05-01

    Insulin resistance (IR) is a complex disorder caused by an interplay of both genetic and environmental factors. Recent studies identified a significant interaction between body mass index (BMI) and the rs1800795 polymorphism of the interleukin-6 gene that influences both IR and onset of type 2 diabetes mellitus, with obese individuals homozygous for the C allele demonstrating the highest level of IR and greatest risk for type 2 diabetes mellitus. Replication of a gene-environment interaction is important to confirm the validity of the initial finding and extend the generalizability of the results to other populations. Thus, the objective of this study was to replicate this gene-environment interaction on IR in a hypertensive population and perform a meta-analysis with prior published results. The replication analysis was performed using white individuals with hypertension from the Hypertensive Pathotype cohort (N = 311), genotyped for rs1800795. Phenotype studies were conducted after participants consumed 2 diets--high sodium (200 mmol/d) and low sodium (10 mmol/d)--for 7 days each. Measurements for plasma glucose, insulin, and interleukin-6 were obtained after 8 hours of fasting. Insulin resistance was characterized by the homeostatic model assessment (HOMA-IR). In Hypertensive Pathotype, BMI was a significant effect modifier of the relationship between rs1800795 and HOMA-IR; higher BMI was associated with higher HOMA-IR among homozygote CC individuals when compared with major allele G carriers (P = .003). Furthermore, the meta-analysis in 1028 individuals confirmed the result, demonstrating the same significant interaction between rs1800795 and BMI on HOMA-IR (P = 1.05 × 10(-6)). This rare replication of a gene-environment interaction extends the generalizability of the results to hypertension while highlighting this polymorphism as a marker of IR in obese individuals.

  15. Gene environment interaction in periphery and brain converge to modulate behavioral outcomes: Insights from the SP1 transient early in life interference rat model

    Science.gov (United States)

    Asor, Eyal; Ben-Shachar, Dorit

    2016-01-01

    It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages. The present article reviews the main theoretical and practical concepts in the research of gene environment interaction, emphasizing the need for models simulating real life complexity. We review a novel approach to study gene environment interaction in which a brief post-natal interference with the expression of multiple genes, by hindering the activity of the ubiquitous transcription factor specificity protein 1 (Sp1) is followed by later-in-life exposure of rats to stress. Finally, this review discusses the role of peripheral processes in behavioral responses, with the Sp1 model as one example demonstrating how specific behavioral patterns are linked to modulations in both peripheral and central physiological processes. We suggest that models, which take into account the tripartite reciprocal interaction between the central nervous system, peripheral systems and environmental stimuli will advance our understanding of the complexity of behavior. PMID:27679768

  16. A systematic gene-gene and gene-environment interaction analysis of DNA repair genes XRCC1, XRCC2, XRCC3, XRCC4, and oral cancer risk.

    Science.gov (United States)

    Yang, Cheng-Hong; Lin, Yu-Da; Yen, Ching-Yui; Chuang, Li-Yeh; Chang, Hsueh-Wei

    2015-04-01

    Oral cancer is the sixth most common cancer worldwide with a high mortality rate. Biomarkers that anticipate susceptibility, prognosis, or response to treatments are much needed. Oral cancer is a polygenic disease involving complex interactions among genetic and environmental factors, which require multifaceted analyses. Here, we examined in a dataset of 103 oral cancer cases and 98 controls from Taiwan the association between oral cancer risk and the DNA repair genes X-ray repair cross-complementing group (XRCCs) 1-4, and the environmental factors of smoking, alcohol drinking, and betel quid (BQ) chewing. We employed logistic regression, multifactor dimensionality reduction (MDR), and hierarchical interaction graphs for analyzing gene-gene (G×G) and gene-environment (G×E) interactions. We identified a significantly elevated risk of the XRCC2 rs2040639 heterozygous variant among smokers [adjusted odds ratio (OR) 3.7, 95% confidence interval (CI)=1.1-12.1] and alcohol drinkers [adjusted OR=5.7, 95% CI=1.4-23.2]. The best two-factor based G×G interaction of oral cancer included the XRCC1 rs1799782 and XRCC2 rs2040639 [OR=3.13, 95% CI=1.66-6.13]. For the G×E interaction, the estimated OR of oral cancer for two (drinking-BQ chewing), three (XRCC1-XRCC2-BQ chewing), four (XRCC1-XRCC2-age-BQ chewing), and five factors (XRCC1-XRCC2-age-drinking-BQ chewing) were 32.9 [95% CI=14.1-76.9], 31.0 [95% CI=14.0-64.7], 49.8 [95% CI=21.0-117.7] and 82.9 [95% CI=31.0-221.5], respectively. Taken together, the genotypes of XRCC1 rs1799782 and XRCC2 rs2040639 DNA repair genes appear to be significantly associated with oral cancer. These were enhanced by exposure to certain environmental factors. The observations presented here warrant further research in larger study samples to examine their relevance for routine clinical care in oncology.

  17. Rigorous tests of gene-environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression.

    Science.gov (United States)

    LoParo, Devon; Johansson, Ada; Walum, Hasse; Westberg, Lars; Santtila, Pekka; Waldman, Irwin

    2016-07-01

    Naturalistic studies of gene-environment interactions (G X E) have been plagued by several limitations, including difficulty isolating specific environmental risk factors from other correlated aspects of the environment, gene-environment correlation (rGE ), and the use of a single genetic variant to represent the influence of a gene. We present results from 235 Finnish young men in two lab studies of aggression and alcohol challenge that attempt to redress these limitations of the extant G X E literature. Specifically, we use a latent variable modeling approach in an attempt to more fully account for genetic variation across the oxytocin receptor gene (OXTR) and to robustly test its main effects on aggression and its interaction with alcohol exposure. We also modeled aggression as a latent variable comprising various indices, including the average and maximum levels of aggression, the earliest trial on which aggression was expressed, and the proportion of trials on which the minimum and maximum levels of aggression were expressed. The best fitting model for the genetic variation across OXTR included six factors derived from an exploratory factor analysis, roughly corresponding to six haplotype blocks. Aggression levels were higher on trials in which participants were administered alcohol, won, or were provoked. There was a significant main effect of OXTR on aggression across studies after controlling for covariates. The interaction of OXTR and alcohol was also significant across studies, such that OXTR had stronger effects on aggression in the alcohol administration condition. © 2015 Wiley Periodicals, Inc.

  18. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

    DEFF Research Database (Denmark)

    Shungin, Dmitry; Deng, Wei Q; Varga, Tibor V

    2017-01-01

    variance effects (Pv), G×E interaction effects (with smoking and physical activity), and marginal genetic effects (Pm). Correlations between Pv and Pm were stronger for SNPs with established marginal effects (Spearman's ρ = 0.401 for triglycerides, and ρ = 0.236 for BMI) compared to all SNPs. When Pv...... (Pbinomial = 8.63×10-9 and 8.52×10-7 for SNP × smoking and SNP × physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for G×E, and variance-based prioritization can be used to identify them....

  19. The oxytocin receptor gene (OXTR in relation to state levels of loneliness in adolescence: evidence for micro-level gene-environment interactions.

    Directory of Open Access Journals (Sweden)

    Eeske van Roekel

    Full Text Available Previous research has shown that the rs53576 variant of the oxytocin receptor gene (OXTR is associated with trait levels of loneliness, but results are inconsistent. The aim of the present study is to examine micro-level effects of the OXTR rs53576 variant on state levels of loneliness in early adolescents. In addition, gene-environment interactions are examined between this OXTR variant and positive and negative perceptions of company. Data were collected in 278 adolescents (58% girls, by means of the Experience Sampling Method (ESM. Sampling periods consisted of six days with nine assessments per day. A relation was found between the OXTR rs53576 variant and state loneliness, in girls only. Girls carrying an A allele had higher levels of state loneliness than girls carrying the GG genotype. In addition, adolescents with an A allele were more affected by negative perceptions of company than GG carriers, on weekend days only. No significant gene-environment interactions were found with positive company. Adolescents carrying an A allele were more susceptible to negative environments during weekend days than GG carriers. Our findings emphasize the importance of operationalizing the phenotype and the environment accurately.

  20. The oxytocin receptor gene (OXTR) in relation to state levels of loneliness in adolescence: evidence for micro-level gene-environment interactions.

    Science.gov (United States)

    van Roekel, Eeske; Verhagen, Maaike; Scholte, Ron H J; Kleinjan, Marloes; Goossens, Luc; Engels, Rutger C M E

    2013-01-01

    Previous research has shown that the rs53576 variant of the oxytocin receptor gene (OXTR) is associated with trait levels of loneliness, but results are inconsistent. The aim of the present study is to examine micro-level effects of the OXTR rs53576 variant on state levels of loneliness in early adolescents. In addition, gene-environment interactions are examined between this OXTR variant and positive and negative perceptions of company. Data were collected in 278 adolescents (58% girls), by means of the Experience Sampling Method (ESM). Sampling periods consisted of six days with nine assessments per day. A relation was found between the OXTR rs53576 variant and state loneliness, in girls only. Girls carrying an A allele had higher levels of state loneliness than girls carrying the GG genotype. In addition, adolescents with an A allele were more affected by negative perceptions of company than GG carriers, on weekend days only. No significant gene-environment interactions were found with positive company. Adolescents carrying an A allele were more susceptible to negative environments during weekend days than GG carriers. Our findings emphasize the importance of operationalizing the phenotype and the environment accurately.

  1. Multivariate dimensionality reduction approaches to identify gene-gene and gene-environment interactions underlying multiple complex traits.

    Directory of Open Access Journals (Sweden)

    Hai-Ming Xu

    Full Text Available The elusive but ubiquitous multifactor interactions represent a stumbling block that urgently needs to be removed in searching for determinants involved in human complex diseases. The dimensionality reduction approaches are a promising tool for this task. Many complex diseases exhibit composite syndromes required to be measured in a cluster of clinical traits with varying correlations and/or are inherently longitudinal in nature (changing over time and measured dynamically at multiple time points. A multivariate approach for detecting interactions is thus greatly needed on the purposes of handling a multifaceted phenotype and longitudinal data, as well as improving statistical power for multiple significance testing via a two-stage testing procedure that involves a multivariate analysis for grouped phenotypes followed by univariate analysis for the phenotypes in the significant group(s. In this article, we propose a multivariate extension of generalized multifactor dimensionality reduction (GMDR based on multivariate generalized linear, multivariate quasi-likelihood and generalized estimating equations models. Simulations and real data analysis for the cohort from the Study of Addiction: Genetics and Environment are performed to investigate the properties and performance of the proposed method, as compared with the univariate method. The results suggest that the proposed multivariate GMDR substantially boosts statistical power.

  2. An update on the rotenone models of Parkinson's disease: their ability to reproduce the features of clinical disease and model gene-environment interactions.

    Science.gov (United States)

    Johnson, Michaela E; Bobrovskaya, Larisa

    2015-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by two major neuropathological hallmarks: the degeneration of dopaminergic neurons in the substantia nigra (SN) and the presence of Lewy bodies in the surviving SN neurons, as well as other regions of the central and peripheral nervous system. Animal models have been invaluable tools for investigating the underlying mechanisms of the pathogenesis of PD and testing new potential symptomatic, neuroprotective and neurorestorative therapies. However, the usefulness of these models is dependent on how precisely they replicate the features of clinical PD with some studies now employing combined gene-environment models to replicate more of the affected pathways. The rotenone model of PD has become of great interest following the seminal paper by the Greenamyre group in 2000 (Betarbet et al., 2000). This paper reported for the first time that systemic rotenone was able to reproduce the two pathological hallmarks of PD as well as certain parkinsonian motor deficits. Since 2000, many research groups have actively used the rotenone model worldwide. This paper will review rotenone models, focusing upon their ability to reproduce the two pathological hallmarks of PD, motor deficits, extranigral pathology and non-motor symptoms. We will also summarize the recent advances in neuroprotective therapies, focusing on those that investigated non-motor symptoms and review rotenone models used in combination with PD genetic models to investigate gene-environment interactions.

  3. Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer

    National Research Council Canada - National Science Library

    Ihsan, Rakhshan; Chauhan, Pradeep Singh; Mishra, Ashwani Kumar; Yadav, Dhirendra Singh; Kaushal, Mishi; Sharma, Jagannath Dev; Zomawia, Eric; Verma, Yogesh; Kapur, Sujala; Saxena, Sunita

    2011-01-01

    ...) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors...

  4. Multiple Analytical Approaches Reveal Distinct Gene-Environment Interactions in Smokers and Non Smokers in Lung Cancer: e29431

    National Research Council Canada - National Science Library

    Rakhshan Ihsan; Pradeep Singh Chauhan; Ashwani Kumar Mishra; Dhirendra Singh Yadav; Mishi Kaushal; Jagannath Dev Sharma; Eric Zomawia; Yogesh Verma; Sujala Kapur; Sunita Saxena

    2011-01-01

    ...) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors...

  5. Gene-environment interactions in multiple sclerosis: Innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway

    DEFF Research Database (Denmark)

    Christensen, Tove; Petersen, Thor; Thiel, Steffen

    2007-01-01

    Aspects of gene-environment interactions in multiple sclerosis (MS) were analysed in serum samples from 46 MS families (25 sporadic MS cases and 42 familial MS cases): antibodies to the MS-associated human endogenous retrovirus HERV-H, and levels of three components in the innate pathogen......-associated molecular pattern recognition: mannan-binding lectin (MBL), and MASP-2 and MASP-3. For representative MS families, we also determined herpesvirus serology for HSV-1, VZV, and EBV; and tissue typed for HLA-B, and HLA DR and DQ. In MS, a significant correlation between elevated immune reactivity to HERV-H Env......-H and the antiviral immune response may play a role in MS development, and also underline the tenuous nature of specific genetic contributions to this complex disease....

  6. Gene-environment interactions in multiple sclerosis: innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway

    DEFF Research Database (Denmark)

    Christensen, Tove; Petersen, Thor; Thiel, Steffen

    2006-01-01

    Aspects of gene-environment interactions in multiple sclerosis (MS) were analysed in serum samples from 46 MS families (25 sporadic MS cases and 42 familial MS cases): antibodies to the MS-associated human endogenous retrovirus HERV-H, and levels of three components in the innate pathogen......-associated molecular pattern recognition: mannan-binding lectin (MBL), and MASP-2 and MASP-3. For representative MS families, we also determined herpesvirus serology for HSV-1, VZV, and EBV; and tissue typed for HLA-B, and HLA DR and DQ. In MS, a significant correlation between elevated immune reactivity to HERV-H Env...... immune response may play a role in MS development, and also underline the tenuous nature of specific genetic contributions to this complex disease. Udgivelsesdato: 2007-Feb...

  7. The STANISLAS Cohort: a 10-year follow-up of supposed healthy families. Gene-environment interactions, reference values and evaluation of biomarkers in prevention of cardiovascular diseases.

    Science.gov (United States)

    Visvikis-Siest, Sophie; Siest, Gérard

    2008-01-01

    The description of this familial longitudinal cohort was published in this journal 10 years ago, in 1998. To date, 117 publications on the STANISLAS Cohort (SC) have appeared, corresponding to five main categories of results: familial resemblance and heritability; genetics and gene-environment interactions; mRNA and proteins as gene products; reference values and biological variations of proteins; and finally preventive medicine and prepathological epidemiological data. More than 600 data values on demographic and laboratory data have been collected on each individual taking part out of the 1006 families at the beginning and for all three recruitments. Serum and plasma are stored in liquid nitrogen for all participants for all three recruitments. DNA has been extracted from all participants and mRNA from 357 families. They are stored at -80 degrees C. Owing to the SC study, heritability and many gene-environment interactions have been described. The expression of 166 genes related to cardiovascular diseases was measured in peripheral blood mononuclear cells RNA. Reference values for proteins and vitamins have been established in addition to reference values for the carotid and femoral intima media thickness in adults and children. The data obtained contribute to a better understanding of the relation between the studied polymorphisms (161 polymorphic sites) and health, and predisposition to obesity, high blood pressure and metabolic syndrome. To the best of our knowledge, the SC study is internationally the only longitudinal family cohort of subjects who are presumed to be healthy, which enables the study of the chain DNA-RNA-proteins.

  8. Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors.

    Science.gov (United States)

    Rudolph, Anja; Milne, Roger L; Truong, Thérèse; Knight, Julia A; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dunning, Alison M; Shah, Mitul; Munday, Hannah R; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S; Olson, Janet; Vachon, Celine M; Hallberg, Emily; Castelao, J Esteban; Carracedo, Angel; Torres, Maria; Li, Jingmei; Humphreys, Keith; Cordina-Duverger, Emilie; Menegaux, Florence; Flyger, Henrik; Nordestgaard, Børge G; Nielsen, Sune F; Yesilyurt, Betul T; Floris, Giuseppe; Leunen, Karin; Engelhardt, Ellen G; Broeks, Annegien; Rutgers, Emiel J; Glendon, Gord; Mulligan, Anna Marie; Cross, Simon; Reed, Malcolm; Gonzalez-Neira, Anna; Arias Perez, José Ignacio; Provenzano, Elena; Apicella, Carmel; Southey, Melissa C; Spurdle, Amanda; Häberle, Lothar; Beckmann, Matthias W; Ekici, Arif B; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; McLean, Catriona; Baglietto, Laura; Chanock, Stephen J; Lissowska, Jolanta; Sherman, Mark E; Brüning, Thomas; Hamann, Ute; Ko, Yon-Dschun; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M; Mannermaa, Arto; Swerdlow, Anthony; Giles, Graham G; Brenner, Hermann; Fasching, Peter A; Chenevix-Trench, Georgia; Hopper, John; Benítez, Javier; Cox, Angela; Andrulis, Irene L; Lambrechts, Diether; Gago-Dominguez, Manuela; Couch, Fergus; Czene, Kamila; Bojesen, Stig E; Easton, Doug F; Schmidt, Marjanka K; Guénel, Pascal; Hall, Per; Pharoah, Paul D P; Garcia-Closas, Montserrat; Chang-Claude, Jenny

    2015-03-15

    A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint ) factors and the observed potential interactions require confirmation in independent studies.

  9. A comparison of case-control and case-only designs to investigate gene-environment interactions using breast cancer data.

    Science.gov (United States)

    Hassanzadeh, Jafar; Moradzadeh, Rahmatollah; Rajaee Fard, Abdolreza; Tahmasebi, Sedigheh; Golmohammadi, Parvaneh

    2012-06-01

    The traditional methods of studying the gene-environment interactions need a control group. However, the selection of an appropriate control group has been associated with problems. Therefore, new methods, such as case-only design, have been created to study such interactions. The objective of this study was to compare the case-only and case-control designs using data from patients with breast cancer. The interaction of genetic and environmental factor as well as the ratio of control to population odds ratio was calculated for case-only (300 patients with breast cancer) and case-control (300 cases of breast cancer and 300 matched controls) designs. The confidence intervals and -2log likelihood in all variables in case-only design was smaller than those in the matched case-control design. In case-only design, the standard errors of some variables such as age at menarche, the first delivery at the age of 35 yrs and more or no delivery, the history of having live birth, use of oral contraception pills, breastfeeding history were less than those in the matched case-control design. The findings indicate that the case-only design is an efficient method to investigate the interaction of genetic and environmental factors.

  10. A Comparison of Case-Control and Case-Only Designs to Investigate Gene-Environment Interactions Using Breast Cancer Data

    Directory of Open Access Journals (Sweden)

    Jafar Hassanzadeh

    2012-06-01

    Full Text Available Background: The traditional methods of studying the gene-environment interactions need a control group. However, the selection of an appropriate control group has been associated with problems. Therefore, new methods, such as case-only design, have been created to study such interactions. The objective of this study was to compare the case-only and case-control designs using data from patients with breast cancer.Methods: The interaction of genetic and environmental factor as well as the ratio of control to population odds ratio was calculated for case-only (300 patients with breast cancer and case-control (300 cases of breast cancer and 300 matched controls designs. Results: The confidence intervals and -2log likelihood in all variables in case-only design was smaller than those in the matched case-control design. In case-only design, the standard errors of some variables such as age at menarche, the first delivery at the age of 35 yrs and more or no delivery, the history of having live birth, use of oral contraception pills, breastfeeding history were less than those in the matched case-control design. Conclusion: The findings indicate that the case-only design is an efficient method to investigate the interaction of genetic and environmental factors.

  11. An investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

    Science.gov (United States)

    Rudolph, Anja; Milne, Roger L.; Truong, Thérèse; Knight, Julia A.; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Munday, Hannah R.; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Olson, Janet; Vachon, Celine M.; Hallberg, Emily; Castelao, J. Esteban; Carracedo, Angel; Torres, Maria; Li, Jingmei; Humphreys, Keith; Cordina-Duverger, Emilie; Menegaux, Florence; Flyger, Henrik; Nordestgaard, Børge G.; Nielsen, Sune F.; Yesilyurt, Betul T.; Floris, Giuseppe; Leunen, Karin; Engelhardt, Ellen G.; Broeks, Annegien; Rutgers, Emiel J.; Glendon, Gord; Mulligan, Anna Marie; Cross, Simon; Reed, Malcolm; Gonzalez-Neira, Anna; Perez, José Ignacio Arias; Provenzano, Elena; Apicella, Carmel; Southey, Melissa C.; Spurdle, Amanda; Investigators, kConFab; Group, AOCS; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; McLean, Catriona; Baglietto, Laura; Chanock, Stephen J.; Lissowska, Jolanta; Sherman, Mark E.; Brüning, Thomas; Hamann, Ute; Ko, Yon-Dschun; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Mannermaa, Arto; Swerdlow, Anthony; Giles, Graham G.; Brenner, Hermann; Fasching, Peter A.; Chenevix-Trench, Georgia; Hopper, John; Benítez, Javier; Cox, Angela; Andrulis, Irene L.; Lambrechts, Diether; Gago-Dominguez, Manuela; Couch, Fergus; Czene, Kamila; Bojesen, Stig E.; Easton, Doug F.; Schmidt, Marjanka K.; Guénel, Pascal; Hall, Per; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Chang-Claude, Jenny

    2014-01-01

    A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint) <1.1×10−3. None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170cm (OR=1.22, p=0.017), but inversely associated with ER-negative BC risk in women <160cm (OR=0.83, p=0.039, pint=1.9×10−4). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR=0.85, p=2.0×10−4), and absent in women who had had just one (OR=0.96, p=0.19, pint = 6.1×10−4). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR=0.93, p=2.8×10−5), but no association was observed in current smokers (OR=1.07, p=0.14, pint = 3.4×10−4). In conclusion, recently identified breast cancer susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies. PMID:25227710

  12. Dopamine transporter DAT and receptor DRD2 variants affect risk of lethal cocaine abuse: a gene-gene-environment interaction.

    Science.gov (United States)

    Sullivan, D; Pinsonneault, J K; Papp, A C; Zhu, H; Lemeshow, S; Mash, D C; Sadee, W

    2013-01-22

    Epistatic gene-gene interactions could contribute to the heritability of complex multigenic disorders, but few examples have been reported. Here, we focus on the role of aberrant dopaminergic signaling, involving the dopamine transporter DAT, a cocaine target, and the dopamine D2 receptor, which physically interacts with DAT. Splicing polymorphism rs2283265 of DRD2, encoding D2 receptors, were shown to confer risk of cocaine overdose/death (odds ratio ∼3) in subjects and controls from the Miami Dade County Brain Bank.(1) Risk of cocaine-related death attributable to the minor allele of rs2283265 was significantly enhanced to OR=7.5 (P=0.0008) in homozygous carriers of the main 6-repeat allele of DAT rs3836790, a regulatory VNTR in intron8 lacking significant effect itself. In contrast, carriers of the minor 5-repeat DAT allele showed no significant risk (OR=1.1, P=0.84). DAT rs3836790 and DRD2 rs2283265 also interacted by modulating DAT protein activity in the ventral putamen of cocaine abusers. In high-linkage disequilibrium with the VNTR, DAT rs6347 in exon9 yielded similar results. Assessing the impact of DAT alone, a rare DAT haplotype formed by the minor alleles of rs3836790 and rs27072, a regulatory DAT variant in the 3'-UTR, occurred in nearly one-third of the cocaine abusers but was absent in African American controls, apparently conferring strong risk. These results demonstrate gene-gene-drug interaction affecting risk of fatal cocaine intoxication.

  13. Neuregulin 1: a prime candidate for research into gene-environment interactions in schizophrenia? Insights from genetic rodent models

    Directory of Open Access Journals (Sweden)

    Tim eKarl

    2013-08-01

    Full Text Available Schizophrenia is a multi-factorial disease characterized by a high heritability and environmental risk factors. In recent years, an increasing number of researchers worldwide have started investigating the ‘two-hit hypothesis’ of schizophrenia predicting that genetic and environmental risk factors (GxE interactively cause the development of the disorder. This work is starting to produce valuable new animal models and reveal novel insights into the pathophysiology of schizophrenia. This mini review will focus on recent advancements in the field made by challenging mutant and transgenic rodent models for the schizophrenia candidate gene neuregulin 1 (NRG1 with particular environmental factors. It will outline results obtained from mouse and rat models for various Nrg1 isoforms/isoform types (e.g. transmembrane domain Nrg1, Type II Nrg1, which have been exposed to different forms of stress (acute versus chronic, restraint versus social and housing conditions (standard laboratory versus minimally enriched housing. These studies suggest Nrg1 as a prime candidate for GxE interactions in schizophrenia rodent models and that the use of rodent models will enable a better understanding of GxE interactions and the underlying mechanisms.

  14. The Influence of Gene-Environment Interactions on Alcohol Consumption and Alcohol Use Disorders: A Comprehensive Review

    Science.gov (United States)

    Young-Wolff, Kelly C.; Enoch, Mary-Anne; Prescott, Carol A.

    2011-01-01

    Since 2005, a rapidly expanding literature has evaluated whether environmental factors such as socio-cultural context and environmental adversity interact with genetic influences on drinking behaviors. This article critically reviews empirical research on alcohol-related genotype-environment interactions (GxE) and provides a contextual framework for understanding how genetic factors combine with (or are shaped by) environmental influences to influence the development of drinking behaviors and alcohol use disorders. Collectively, evidence from twin, adoption, and molecular genetic studies indicates that the degree of importance of genetic influences on risk for drinking outcomes can vary in different populations and under different environmental circumstances. However, methodological limitations and lack of consistent replications in this literature make it difficult to draw firm conclusions regarding the nature and effect size of alcohol-related GxE. On the basis of this review, we describe several methodological challenges as they relate to current research on GxE in drinking behaviors and provide recommendations to aid future research. PMID:21530476

  15. Classification and Clustering Methods for Multiple Environmental Factors in Gene-Environment Interaction: Application to the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Ko, Yi-An; Mukherjee, Bhramar; Smith, Jennifer A; Kardia, Sharon L R; Allison, Matthew; Diez Roux, Ana V

    2016-11-01

    There has been an increased interest in identifying gene-environment interaction (G × E) in the context of multiple environmental exposures. Most G × E studies analyze one exposure at a time, but we are exposed to multiple exposures in reality. Efficient analysis strategies for complex G × E with multiple environmental factors in a single model are still lacking. Using the data from the Multiethnic Study of Atherosclerosis, we illustrate a two-step approach for modeling G × E with multiple environmental factors. First, we utilize common clustering and classification strategies (e.g., k-means, latent class analysis, classification and regression trees, Bayesian clustering using Dirichlet Process) to define subgroups corresponding to distinct environmental exposure profiles. Second, we illustrate the use of an additive main effects and multiplicative interaction model, instead of the conventional saturated interaction model using product terms of factors, to study G × E with the data-driven exposure subgroups defined in the first step. We demonstrate useful analytical approaches to translate multiple environmental exposures into one summary class. These tools not only allow researchers to consider several environmental exposures in G × E analysis but also provide some insight into how genes modify the effect of a comprehensive exposure profile instead of examining effect modification for each exposure in isolation.

  16. Influence of 5-HTT variation, childhood trauma and self-efficacy on anxiety traits: a gene-environment-coping interaction study.

    Science.gov (United States)

    Schiele, Miriam A; Ziegler, Christiane; Holitschke, Karoline; Schartner, Christoph; Schmidt, Brigitte; Weber, Heike; Reif, Andreas; Romanos, Marcel; Pauli, Paul; Zwanzger, Peter; Deckert, Jürgen; Domschke, Katharina

    2016-08-01

    Environmental vulnerability factors such as adverse childhood experiences in interaction with genetic risk variants, e.g., the serotonin transporter gene linked polymorphic region (5-HTTLPR), are assumed to play a role in the development of anxiety and affective disorders. However, positive influences such as general self-efficacy (GSE) may exert a compensatory effect on genetic disposition, environmental adversity, and anxiety traits. We, thus, assessed childhood trauma (Childhood Trauma Questionnaire, CTQ) and GSE in 678 adults genotyped for 5-HTTLPR/rs25531 and their interaction on agoraphobic cognitions (Agoraphobic Cognitions Questionnaire, ACQ), social anxiety (Liebowitz Social Anxiety Scale, LSAS), and trait anxiety (State-Trait Anxiety Inventory, STAI-T). The relationship between anxiety traits and childhood trauma was moderated by self-efficacy in 5-HTTLPR/rs25531 LALA genotype carriers: LALA probands maltreated as children showed high anxiety scores when self-efficacy was low, but low anxiety scores in the presence of high self-efficacy despite childhood maltreatment. Our results extend previous findings regarding anxiety-related traits showing an interactive relationship between 5-HTT genotype and adverse childhood experiences by suggesting coping-related measures to function as an additional dimension buffering the effects of a gene-environment risk constellation. Given that anxiety disorders manifest already early in childhood, this insight could contribute to the improvement of psychotherapeutic interventions by including measures strengthening self-efficacy and inform early targeted preventive interventions in at-risk populations, particularly within the crucial time window of childhood and adolescence.

  17. Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

    DEFF Research Database (Denmark)

    Rudolph, Anja; Milne, Roger L; Truong, Thérèse

    2015-01-01

    A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estro......A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated...... with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage...

  18. Gene-environment Interactions in Human Health: Case Studies and Strategies for developing new paradigms and research methodologies

    Directory of Open Access Journals (Sweden)

    Fatimah L.C. Jackson

    2014-08-01

    Full Text Available The synergistic effects of genes and the environment on health are explored in three case studies: adult lactase persistence, autism spectrum disorders, and the metabolic syndrome, providing examples of the interactive complexities underlying these phenotypes. Since the phenotypes are the initial targets of evolutionary processes, understanding the specific environmental contexts of the genetic, epigenetic, and proteomic changes associated with these phenotypes is essential in predicting their health implications. Robust databases must be developed on the local scale to deconstruct both the population substructure and the unique components of the environment that stimulate geographically-specific changes in gene expression patterns. To produce these databases and make valid predictions, new, locally-focused and information-dense models are needed that incorporate data on evolutionary ecology, environmental complexity, local geographic patterns of gene expression, and population substructure.

  19. Linkages between Children's and Their Friends' Social and Physical Aggression: Evidence for a Gene-Environment Interaction?

    Science.gov (United States)

    Brendgen, Mara; Boivin, Michel; Vitaro, Frank; Bukowski, William M.; Dionne, Ginette; Tremblay, Richard E.; Perusse, Daniel

    2008-01-01

    Based on a sample of 406 seven-year-old twins, this study examined whether exposure to friends' social or physical aggression, respectively, moderates the effect of heritability on children's own social and physical aggression. Univariate analyses showed that children's own social and physical aggression were significantly explained by genetic…

  20. Linkages between Children's and Their Friends' Social and Physical Aggression: Evidence for a Gene-Environment Interaction?

    Science.gov (United States)

    Brendgen, Mara; Boivin, Michel; Vitaro, Frank; Bukowski, William M.; Dionne, Ginette; Tremblay, Richard E.; Perusse, Daniel

    2008-01-01

    Based on a sample of 406 seven-year-old twins, this study examined whether exposure to friends' social or physical aggression, respectively, moderates the effect of heritability on children's own social and physical aggression. Univariate analyses showed that children's own social and physical aggression were significantly explained by genetic…

  1. Gene-environment interactions in male reproductive health: special reference to the aryl hydrocarbon receptor signaling pathway

    Directory of Open Access Journals (Sweden)

    Leon J S Brokken

    2014-02-01

    Full Text Available Over the last few decades, there have been numerous reports of adverse effects on the reproductive health of wildlife and laboratory animals caused by exposure to endocrine disrupting chemicals (EDCs. The increasing trends in human male reproductive disorders and the mounting evidence for causative environmental factors have therefore sparked growing interest in the health threat posed to humans by EDCs, which are substances in our food, environment and consumer items that interfere with hormone action, biosynthesis or metabolism, resulting in disrupted tissue homeostasis or reproductive function. The mechanisms of EDCs involve a wide array of actions and pathways. Examples include the estrogenic, androgenic, thyroid and retinoid pathways, in which the EDCs may act directly as agonists or antagonists, or indirectly via other nuclear receptors. Dioxins and dioxin-like EDCs exert their biological and toxicological actions through activation of the aryl hydrocarbon-receptor, which besides inducing transcription of detoxifying enzymes also regulates transcriptional activity of other nuclear receptors. There is increasing evidence that genetic predispositions may modify the susceptibility to adverse effects of toxic chemicals. In this review, potential consequences of hereditary predisposition and EDCs are discussed, with a special focus on the currently available publications on interactions between dioxin and androgen signaling.

  2. Gene-environment interaction during early development in the heterozygous reeler mouse: clues for modelling of major neurobehavioral syndromes.

    Science.gov (United States)

    Laviola, Giovanni; Ognibene, Elisa; Romano, Emilia; Adriani, Walter; Keller, Flavio

    2009-04-01

    Autism and schizophrenia are multifactorial disorders with increasing prevalence in the young population. Among candidate molecules, reelin (RELN) is a protein of the extracellular matrix playing a key role in brain development and synaptic plasticity. The heterozygous (HZ) reeler mouse provides a model for studying the role of reelin deficiency for the onset of these syndromes. We investigated whether early indices of neurobehavioral disorders can be identified in the infant reeler, and whether the consequences of ontogenetic adverse experiences may question or support the suitability of this model. A first study focused on the link between early exposure to Chlorpyryfos and its enduring neurobehavioral consequences. Our data are interesting in view of recently discovered cholinergic abnormalities in autism and schizophrenia, and may suggest new avenues for early pharmacological intervention. In a second study, we analyzed the consequences of repeated maternal separation early in ontogeny. The results provide evidence of how unusual stress early in development are converted into altered behavior in some, but not all, individuals depending on gender and genetic background. A third study aimed to verify the reliability of the model at critical age windows. Data suggest reduced anxiety, increased impulsivity and disinhibition, and altered pain threshold in response to morphine for HZ, supporting a differential organization of brain dopaminergic, serotonergic and opioid systems in this genotype. In conclusion, HZ exhibited a complex behavioral and psycho-pharmacological phenotype, and differential responsivity to ontogenetic adverse conditions. HZ may be used to disentangle interactions between genetic vulnerability and environmental factors. Such an approach could help to model the pathogenesis of neurodevelopmental psychiatric diseases.

  3. Cross-cultural gene- environment interactions in depression, post-traumatic stress disorder, and the cortisol awakening response: FKBP5 polymorphisms and childhood trauma in South Asia.

    Science.gov (United States)

    Kohrt, Brandon A; Worthman, Carol M; Ressler, Kerry J; Mercer, Kristina B; Upadhaya, Nawaraj; Koirala, Suraj; Nepal, Mahendra K; Sharma, Vidya Dev; Binder, Elisabeth B

    2015-01-01

    Despite increased attention to global mental health, psychiatric genetic research has been dominated by studies in high-income countries, especially with populations of European descent. The objective of this study was to assess single nucleotide polymorphisms (SNPs) in the FKBP5 gene in a population living in South Asia. Among adults in Nepal, depression was assessed with the Beck Depression Inventory (BDI), post-traumatic stress disorder (PTSD) with the PTSD Checklist-Civilian Version (PCL-C), and childhood maltreatment with the Childhood Trauma Questionnaire (CTQ). FKBP5 SNPs were genotyped for 682 participants. Cortisol awakening response (CAR) was assessed in a subsample of 118 participants over 3 days. The FKBP5 tag-SNP rs9296158 showed a main effect on depressive symptoms (p = 0.03). Interaction of rs9296158 and childhood maltreatment predicted adult depressive symptoms (p = 0.02) but not PTSD. Childhood maltreatment associated with endocrine response in individuals homozygous for the A allele, demonstrated by a negative CAR and overall hypocortisolaemia in the rs9296158 AA genotype and childhood maltreatment group (p depression but not PTSD. Gene-environment studies should take differences in prevalence and cultural significance of phenotypes and exposures into account when interpreting cross-cultural findings.

  4. Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions.

    Science.gov (United States)

    D'Amelio, M; Ricci, I; Sacco, R; Liu, X; D'Agruma, L; Muscarella, L A; Guarnieri, V; Militerni, R; Bravaccio, C; Elia, M; Schneider, C; Melmed, R; Trillo, S; Pascucci, T; Puglisi-Allegra, S; Reichelt, K-L; Macciardi, F; Holden, J J A; Persico, A M

    2005-11-01

    Organophosphates (OPs) are routinely used as pesticides in agriculture and as insecticides within the household. Our prior work on Reelin and APOE delineated a gene-environment interactive model of autism pathogenesis, whereby genetically vulnerable individuals prenatally exposed to OPs during critical periods in neurodevelopment could undergo altered neuronal migration, resulting in an autistic syndrome. Since household use of OPs is far greater in the USA than in Italy, this model was predicted to hold validity in North America, but not in Europe. Here, we indirectly test this hypothesis by assessing linkage/association between autism and variants of the paraoxonase gene (PON1) encoding paraoxonase, the enzyme responsible for OP detoxification. Three functional single nucleotide polymorphisms, PON1 C-108T, L55M, and Q192R, were assessed in 177 Italian and 107 Caucasian-American complete trios with primary autistic probands. As predicted, Caucasian-American and not Italian families display a significant association between autism and PON1 variants less active in vitro on the OP diazinon (R192), according to case-control contrasts (Q192R: chi2=6.33, 1 df, Pautism pathogenesis in a sizable subgroup of North American individuals.

  5. A genome-wide association and gene-environment interaction study for serum triglycerides levels in a healthy Chinese male population.

    Science.gov (United States)

    Tan, Aihua; Sun, Jielin; Xia, Ning; Qin, Xue; Hu, Yanling; Zhang, Shijun; Tao, Sha; Gao, Yong; Yang, Xiaobo; Zhang, Haiying; Kim, Seong-Tae; Peng, Tao; Lin, Xiaoling; Li, Li; Mo, Linjian; Liang, Zhengjia; Shi, Deyi; Huang, Zhang; Huang, Xianghua; Liu, Ming; Ding, Qiang; Trent, Jeffrey M; Zheng, S Lilly; Mo, Zengnan; Xu, Jianfeng

    2012-04-01

    Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10(-26) and 1.41 × 10(-9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10(-5)). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10(-10)), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10(-8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.

  6. Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate.

    Directory of Open Access Journals (Sweden)

    Tao Wu

    Full Text Available Nonsyndromic cleft palate (CP is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester. When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10(-6interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10(-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10(-7 and P = 1.98×10(-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP.

  7. Organochlorine Pesticides Exposure and Bladder Cancer: Evaluation from a Gene-Environment Perspective in a Hospital-Based Case-Control Study in the Canary Islands (Spain).

    Science.gov (United States)

    Boada, L D; Henríquez-Hernández, L A; Zumbado, M; Almeida-González, M; Álvarez-León, E E; Navarro, P; Luzardo, O P

    2016-01-01

    The incidence of bladder cancer has increased significantly since the 1950s. Pesticide exposure has been linked with increasing bladder cancer incidence, although the evidence is inconclusive. However, most epidemiological studies did not evaluate the potential role played by the organochlorine pesticides, the most widely used pesticides in Western countries from the 1940s to the 1970s. Organochlorine pesticides were banned in the late 1970s because of their persistence in the environment and their carcinogenic and mutagenic effects. Organochlorine pesticides were employed in huge amounts in the Spanish archipelago of the Canary Islands; the authors, therefore, evaluated the role played by organochlorine pesticides exposure on bladder cancer. Serum levels of the most prevalent organochlorine pesticides used in the agriculture of these Islands (dichlorodiphenyltrichloroethane [p,p'-DDT], and its metabolites dichlorodiphenyldichloroethylene [p,p'-DDE] and dichlorodiphenyldichloroethane [p,p'-DDD], hexachlorobenzene, hexachlorocyclohexane isomers, aldrin, dieldrin, endrin, heptachlor, cis-chlordane, trans-chlordane, α- and β-endosulfan, endosulfan sulfate, methoxychlor, and mirex) were measured in 140 bladder cancer cases and 206 controls. GST-M1 and GST-T1 gene polymorphisms were genotyped by polymerase chain reaction (PCR)-based methods. These results showed that serum levels of organochlorine pesticides did not increase bladder cancer risk. On the contrary, total burden of hexachlorocyclohexanes was found to be negatively associated to bladder cancer (odds ratio [OR] = 0.929, 95% confidence interval [CI]: 0.865-0.997; P = .041). This effect disappeared when the distribution of the gluthathione S-transferase polymorphisms was introduced in the statistical model. These results indicate that organochlorine pesticides are not a risk factor for bladder cancer. However, these findings provide additional evidence of gene-environment interactions for organochlorine

  8. Cytochrome P450 1B1, a new keystone in gene-environment interactions related to human head and neck cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Thier, R. [Dept. Physiology and Pharmacology, Univ. of Queensland, St. Lucia, Qld. (Australia); Bruening, T. [Berufsgenossenschaftliches Forschungsinstitut fuer Arbeitsmedizin (BGFA), Bochum (Germany); Roos, P.H.; Bolt, H.M. [Inst. fuer Arbeitsphysiologie an der Univ. Dortmund (IfADo), Dortmund (Germany)

    2002-06-01

    Alcohol consumption and tobacco smoking are major causes of head and neck cancers, and regional differences point to the importance of research into gene-environment interactions. Much interest has been focused on polymorphisms of CYP1A1 and of GSTM1 and GSTT1, but a number of studies have not demonstrated significant effects. This has mostly been ascribed to small sample sizes. In general, the impact of polymorphisms of metabolic enzymes appears inconsistent, with some reports of weak-to-moderate associations, and with other of no elevation of risks. The classical cytochrome P450 isoenzyme considered for metabolic activation of polycyclic aromatic hydrocarbons (PAH) is CYP1A1. A new member of CYP1 family, CYP1B1, was cloned in 1994, currently representing the only member of the CYP1B subfamily. A number of single nucleotide polymorphisms of the CYP1B1 gene have been reported. The amino acid substitutions Val432Leu (CYP1B1*3) and Asn453Ser (CYP1B1*4), located in the heme binding domain of CYP1B1, appear as likely candidates to be linked with biological effects. CYP1B1 activates a wide range of PAH, aromatic and heterocyclic amines. Very recently, the CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squamous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has pointed to interactive effects. This provides new molecular evidence that tobacco smoke-specific compounds relevant to head and neck carcinogenesis are metabolically activated through CYP1B1 and is consistent with a major pathogenetic relevance of PAH as ingredients of tobacco smoke. (orig.)

  9. Quantitative gene-gene and gene-environment mapping for leaf shape variation using tree-based models

    Science.gov (United States)

    Leaf shape traits have long been a focus of many disciplines, but searching for complex genetic and environmental interactive mechanisms regulating leaf shape variation has not yet been well developed. The question of the respective roles of gene and environment and how they interplay to modulate l...

  10. Genetic susceptibility on CagA-interacting molecules and gene-environment interaction with phytoestrogens: a putative risk factor for gastric cancer.

    Directory of Open Access Journals (Sweden)

    Jae Jeong Yang

    Full Text Available OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2 are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone were measured using the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively. Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05. CONCLUSIONS: Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk.

  11. Breast cancer risk, fungicide exposure and CYP1A1*2A gene-environment interactions in a province-wide case control study in Prince Edward Island, Canada.

    Science.gov (United States)

    Ashley-Martin, Jillian; VanLeeuwen, John; Cribb, Alastair; Andreou, Pantelis; Guernsey, Judith Read

    2012-05-01

    Scientific certainty regarding environmental toxin-related etiologies of breast cancer, particularly among women with genetic polymorphisms in estrogen metabolizing enzymes, is lacking. Fungicides have been recognized for their carcinogenic potential, yet there is a paucity of epidemiological studies examining the health risks of these agents. The association between agricultural fungicide exposure and breast cancer risk was examined in a secondary analysis of a province-wide breast cancer case-control study in Prince Edward Island (PEI) Canada. Specific objectives were: (1) to derive and examine the level of association between estimated fungicide exposures, and breast cancer risk among women in PEI; and (2) to assess the potential for gene-environment interactions between fungicide exposure and a CYP1A1 polymorphism in cases versus controls. After 1:3 matching of 207 cases to 621 controls by age, family history of breast cancer and menopausal status, fungicide exposure was not significantly associated with an increased risk of breast cancer (OR = 0.74; 95% CI: 0.46-1.17). Moreover, no statistically significant interactions between fungicide exposure and CYP1A1*2A were observed. Gene-environment interactions were identified. Though interpretations of findings are challenged by uncertainty of exposure assignment and small sample sizes, this study does provide grounds for further research.

  12. Gene-environment effects on hippocampal neurodevelopment

    DEFF Research Database (Denmark)

    Rosenthal, Eva Helga

    Mental disorders like schizophrenia and autism put a heavy load on today’s societies, creating a steady call for revealing underlying disease mechanisms and the development of effective treatments. The etiology of major psychiatric illnesses is complex involving gene by environment susceptibility...... factors. Hence, a deeper understanding is needed of how cortical neurodevelopmental deficiencies can arise from such gene-environment interactions. The convergence of genetic and environmental risk factors is a recent field of research. It is now clear that disease, infection and stress factors may...

  13. Gene-environment interaction affects substance P and neurokinin A in the entorhinal cortex and periaqueductal grey in a genetic animal model of depression: implications for the pathophysiology of depression

    DEFF Research Database (Denmark)

    Husum, Henriette; Wörtwein, Gitta; Andersson, Weronika

    2008-01-01

    of the congenitally 'depressed' Flinders Sensitive Line (FSL) compared to the Flinders Resistant Line (FRL) control rats. It is also known that environmental stress may affect brain levels of tachykinins. In view of these results we decided to superimpose maternal deprivation, an early life environmental stressor......, onto the genetically predisposed 'depressed' FSL rats and the FRL control rats and use this paradigm as a model of gene-environment interaction. The adult animals were sacrificed, adrenal glands and brains dissected out and SP-, NKA- and CRH-LI levels were determined in ten discrete brain regions....... Maternal deprivation led to a marked increase in SP-LI and NKA-LI levels in the periaqueductal grey (PAG) and entorhinal cortex of the 'depressed' FSL strain while it had no significant effect in the FRL controls. Furthermore, specific strain differences in peptide-LI content were confirmed. No difference...

  14. Gene-environment and gene-gene interactions of specific MTHFR, MTR and CBS gene variants in relation to homocysteine in black South Africans.

    Science.gov (United States)

    Nienaber-Rousseau, Cornelie; Ellis, Suria M; Moss, Sarah J; Melse-Boonstra, Alida; Towers, G Wayne

    2013-11-01

    The methylenetetrahydrofolate reductase (MTHFR), cystathione-β-synthase (CBS) and methionine synthase (MTR) genes interact with each other and the environment. These interactions could influence homocysteine (Hcy) and diseases contingent thereon. We determined single nucleotide polymorphisms (SNPs) within these genes, their relationships and interactions with total Hcy concentrations within black South Africans to address the increased prevalence of diseases associated with Hcy. The MTHFR 677 TT and MTR 2756 AA genotypes were associated with higher Hcy concentrations (16.6 and 10.1 μmol/L; pCBS genotypes did not influence Hcy. We demonstrated interactions between the area of residence and the CBS T833C/844ins68 genotypes (p=0.005) so that when harboring the wildtype allele, rural subjects had significantly higher Hcy than their urban counterparts, but when hosting the variant allele the environment made no difference to Hcy. Between the CBS T833C/844ins68 or G9276A and MTHFR C677T genotypes, there were two-way interactions (p=0.003 and=0.004, respectively), with regard to Hcy. Subjects harboring the MTHFR 677 TT genotype in combination with the CBS 833 TT/homozygous 844 non-insert or the MTHFR 677 TT genotype in combination with the CBS 9276 GA/GG displayed higher Hcy concentrations. Therefore, some of the investigated genotypes affected Hcy; residential area changed the way in which the CBS T833C/844ins68 SNPs influenced Hcy concentrations highlighting the importance of environmental factors; and gene-gene interactions allude to epistatic effects. © 2013 Elsevier B.V. All rights reserved.

  15. The Dopamine Receptor D4 7-Repeat Allele and Prenatal Smoking in ADHD-Affected Children and Their Unaffected Siblings: No Gene-Environment Interaction

    Science.gov (United States)

    Altink, Marieke E.; Arias-Vasquez, Alejandro; Franke, Barbara; Slaats-Willemse, Dorine I. E.; Buschgens, Cathelijne J. M.; Rommelse, Nanda N. J.; Fliers, Ellen A.; Anney, Richard; Brookes, Keeley-Joanne; Chen, Wai; Gill, Michael; Mulligan, Aisling; Sonuga-Barke, Edmund; Thompson, Margaret; Sergeant, Joseph A.; Faraone, Stephen V.; Asherson, Philip; Buitelaar, Jan K.

    2008-01-01

    Background: The dopamine receptor D4 ("DRD4") 7-repeat allele and maternal smoking during pregnancy are both considered as risk factors in the aetiology of attention deficit hyperactivity disorder (ADHD), but few studies have been conducted on their interactive effects in causing ADHD. The purpose of this study is to examine the gene by…

  16. HTR1B, ADIPOR1, PPARGC1A, and CYP19A1 and Obesity in a Cohort of Caucasians and African Americans: An Evaluation of Gene-Environment Interactions and Candidate Genes

    Science.gov (United States)

    Edwards, Todd L.; Velez Edwards, Digna R.; Villegas, Raquel; Cohen, Sarah S.; Buchowski, Maciej S.; Fowke, Jay H.; Schlundt, David; Long, Ji Rong; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou; Hargreaves, Margaret K.; Jeffrey, Smith; Williams, Scott M.; Signorello, Lisa B.; Blot, William J.; Matthews, Charles E.

    2012-01-01

    The World Health Organization estimates that the number of obese and overweight adults has increased to 1.6 billion, with concomitant increases in comorbidity. While genetic factors for obesity have been extensively studied in Caucasians, fewer studies have investigated genetic determinants of body mass index (BMI; weight (kg)/height (m)2) in African Americans. A total of 38 genes and 1,086 single nucleotide polymorphisms (SNPs) in African Americans (n = 1,173) and 897 SNPs in Caucasians (n = 1,165) were examined in the Southern Community Cohort Study (2002–2009) for associations with BMI and gene × environment interactions. A statistically significant association with BMI survived correction for multiple testing at rs4140535 (β = −0.04, 95% confidence interval: −0.06, −0.02; P = 5.76 × 10−5) in African Americans but not in Caucasians. Gene-environment interactions were observed with cigarette smoking and a SNP in ADIPOR1 in African Americans, as well as between a different SNP in ADIPOR1 and physical activity in Caucasians. A SNP in PPARGC1A interacted with alcohol consumption in African Americans, and a different SNP in PPARGC1A was nominally associated in Caucasians. A SNP in CYP19A1 interacted with dietary energy intake in African Americans, and another SNP in CYP191A had an independent association with BMI in Caucasians. PMID:22106445

  17. Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure.

    Directory of Open Access Journals (Sweden)

    Hans Bisgaard

    2008-06-01

    Full Text Available BACKGROUND: Loss-of-function variants in the gene encoding filaggrin (FLG are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites in relation to the development of eczema. METHODS AND FINDINGS: We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379, FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27-4.00, p = 0.005, with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79-32.60, p < 0.0001; dog exposure was moderately protective (HR 0.49, 95% CI 0.24-1.01, p = 0.05, but not related to FLG genotype. In Manchester (n = 503 an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13-3.36, p = 0.02. In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35-10.81, p = 0.01, with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16-2.20, p = 0.43. Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation. CONCLUSIONS: We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4 and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially

  18. Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee.

    Science.gov (United States)

    Hamza, Taye H; Chen, Honglei; Hill-Burns, Erin M; Rhodes, Shannon L; Montimurro, Jennifer; Kay, Denise M; Tenesa, Albert; Kusel, Victoria I; Sheehan, Patricia; Eaaswarkhanth, Muthukrishnan; Yearout, Dora; Samii, Ali; Roberts, John W; Agarwal, Pinky; Bordelon, Yvette; Park, Yikyung; Wang, Liyong; Gao, Jianjun; Vance, Jeffery M; Kendler, Kenneth S; Bacanu, Silviu-Alin; Scott, William K; Ritz, Beate; Nutt, John; Factor, Stewart A; Zabetian, Cyrus P; Payami, Haydeh

    2011-08-01

    Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P(2df) = 10(-6), GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10(-7)) but not in light coffee-drinkers. The a priori Replication hypothesis that "Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers" was confirmed: OR(Replication) = 0.59, P(Replication) = 10(-3); OR(Pooled) = 0.51, P(Pooled) = 7×10(-8). Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10(-3)), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10(-13)). Imputation revealed a block of SNPs that achieved P(2df)coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify

  19. Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson's Disease Modifier Gene via Interaction with Coffee

    Science.gov (United States)

    Hamza, Taye H.; Chen, Honglei; Hill-Burns, Erin M.; Rhodes, Shannon L.; Montimurro, Jennifer; Kay, Denise M.; Tenesa, Albert; Kusel, Victoria I.; Sheehan, Patricia; Eaaswarkhanth, Muthukrishnan; Yearout, Dora; Samii, Ali; Roberts, John W.; Agarwal, Pinky; Bordelon, Yvette; Park, Yikyung; Wang, Liyong; Gao, Jianjun; Vance, Jeffery M.; Kendler, Kenneth S.; Bacanu, Silviu-Alin; Scott, William K.; Ritz, Beate; Nutt, John; Factor, Stewart A.; Zabetian, Cyrus P.; Payami, Haydeh

    2011-01-01

    Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P2df = 10−6, GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10−7) but not in light coffee-drinkers. The a priori Replication hypothesis that “Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers” was confirmed: ORReplication = 0.59, PReplication = 10−3; ORPooled = 0.51, PPooled = 7×10−8. Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10−3), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10−13). Imputation revealed a block of SNPs that achieved P2dfcoffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that

  20. [Gene-environment interaction for the HIF1-A 1772C>T polymorphisms and cigarette smoking increase susceptibility to abdominal aortic aneurysm].

    Science.gov (United States)

    Strauss, Ewa; Waliszewski, Krzysztof; Oszkinis, Grzegorz; Staniszewski, Ryszard

    2012-01-01

    Pathological changes in the vascular vessels, such as the presence of atherosclerotic plaques or aneurysmal dilatations, are associated with the local conditions of ischemial/hypoxia. Polymorphisms in the HIF1A gene, encoding an oxygen-regulated HIF-1 subunit (HIF-1a), determine inter-individual variability in vascular response to hypoxia. Stimulation of selected pathways, related to this response (i.e. angiogenesis) is impaired by cigarette smoke exposure. In this work, we examined the associations between 1772C>T polymorphism (rs11549465) located in the coding region of HIF1A gene (Pro582-Ser), smoking and the occurrence of abdominal aortic aneurysm (AAA). Moreover, the relations of these factors with the presence of peripheral arterial disease (PAD) in patients with AAA were studied. The case-control study was designed, in which a group of 1060 Caucasian subjects: 535 AAA patients and 525 controls, was analyzed. Data regarding smoking status were collected using questionnaire. Past and current smokers were analyzed together. In the group of 220 AAA subjects the coexistence of PAD was characterized. HIF-1A genotypes were assessed by PCR-RFLP method. Genetic-environmental interactions were examined by a two-by-four tables. In these analyzes, logistic regression models were used to adjusting for the relevant covariates. The frequency of HIF1A 1772T allele in AAA group (0,067) was similar to that observed in the control group (0,070). In the analyses of genetic-environmental interactions was observed that the co-occurrence of HIF1A 1772CT and TT genotypes and exposure to tobacco smoke has a strong multiplicative effect on the susceptibility to the AAA development. The age and gender adjusted odds ratios (ORs) were: 7,6 for smoking alone (p<0,0001); 0,65 for 1772CT and TT genotypes alone (p=0,3) and 14,4for smoking plus 1772CT and TT genotypes (p<0,0001). The proportion of smokers carrying 1772T allele was higher among patients with advanced form of PAD (femoro

  1. The influence of gene-environment interactions on GHR and IGF-1 expression and their association with growth in brook charr, Salvelinus fontinalis (Mitchill

    Directory of Open Access Journals (Sweden)

    Blier Pierre

    2007-12-01

    Full Text Available Abstract Background Quantitative reaction norm theory proposes that genotype-by-environment interaction (GxE results from inter-individual differences of expression in adaptive suites of genes in distinct environments. However, environmental norms for actual gene suites are poorly documented. In this study, we investigated the effects of GxE interactions on levels of gene transcription and growth by documenting the impact of rearing environment (freshwater vs. saltwater, sex and genotypic (low vs. high estimated breeding value EBV effects on the transcription level of insulin-like growth factor (IGF-1 and growth hormone receptor (GHR in brook charr (Salvelinus fontinalis. Results Males grew faster than females (μ♀ = 1.20 ± 0.07 g·d-1, μ♂ = 1.46 ± 0.06 g·d-1 and high-EBV fish faster than low-EBV fish (μLOW = 0.97 ± 0.05 g·d-1, μHIGH = 1.58 ± 0.07 g·d-1; p FW = 1.52 ± 0.07 g·d-1, μSW = 1.15 ± 0.06 g·d-1, yet GHR mRNA transcription level was significantly higher in saltwater than in freshwater (μSW = 0.85 ± 0.05, μFW = 0.61 ± 0.05. The ratio of actual growth to units in assayed mRNA ('individual transcript efficiency', iTE; g·d-1·u-1 also differed among EBV groups (μLOW = 2.0 ± 0.24 g·d-1·u-1; μHIGH = 3.7 ± 0.24 g·d-1·u-1 and environments (μSW = 2.0 ± 0.25 g·d-1·u-1; μFW = 3.7 ± 0.25 g·d-1·u-1 for GHR. Males had a lower iTE for GHR than females (μ♂ = 2.4 ± 0.29 g·d-1·u-1; μ♀ = 3.1 ± 0.23 g·d-1·u-1. There was no difference in IGF-1 transcription level between environments (p > 0.7 or EBV groups (p > 0.15 but the level of IGF-1 was four times higher in males than females (μ♂ = 2.4 ± 0.11, μ♀ = 0.58 ± 0.09; p ♂ = 1.3 ± 0.59 g·d-1·u-1; μ♀ = 3.9 ± 0.47 g·d-1·u-1, salinities (μSW = 2.3 ± 0.52 g·d-1·u-1; μFW = 3.7 ± 0.53 g·d-1·u-1 and EBV-groups (μLOW = 2.4 ± 0.49 g·d-1·u-1; μHIGH = 3.8 ± 0.49 g·d-1·u-1. Interaction between EBV-group and environment was detected for

  2. Replication of a gene-environment interaction Via Multimodel inference: additive-genetic variance in adolescents' general cognitive ability increases with family-of-origin socioeconomic status.

    Science.gov (United States)

    Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

    2015-03-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES-an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research.

  3. Gene environment interactions in bipolar disorder.

    Science.gov (United States)

    Pregelj, Peter

    2011-09-01

    It has been estimated that the heritable component of bipolar disorder ranges between 80 and 90%. However, even genome-wide association studies explain only a fraction of phenotypic variability not resolving the problem of "lost heritability". Although direct evidence for epigenetic dysfunction in bipolar disorder is still limited, methodological technologies in epigenomic profiling have advanced, offering even single cell analysing and resolving the problem of cell heterogeneity in epigenetics research. Gene overlapping with other mental disorders represents another problem in identifying potential susceptibility genes in bipolar disorder. Better understanding of the interplay between multiple environmental and genetic factors involved in the patogenesis of bipolar disorder could provide relevant information for treatment of patients with this complex disorder. Future studies on the role of these factors in psychopathological conditions, subphenotypes and endophenotypes may greatly benefit by using more precise clinical data and a combined approach with multiple research tools incorporated into a single study.

  4. Identifying Gene-Environment Interactions in Schizophrenia

    DEFF Research Database (Denmark)

    van Os, Jim; Rutten, Bart P; Myin-Germeys, Inez

    2014-01-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual...... of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap...

  5. Gene-Environment Interplay between Number of Friends and Prosocial Leadership Behavior in Children

    Science.gov (United States)

    Rivizzigno, Alessandra S.; Brendgen, Mara; Feng, Bei; Vitaro, Frank; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2014-01-01

    Enriched environments may moderate the effect of genetic factors on prosocial leadership (gene-environment interaction, G × E). However, positive environmental experiences may also themselves be influenced by a genetic disposition for prosocial leadership (gene-environment correlation, rGE). Relating these processes to friendships, the present…

  6. Gene-Environment Interplay between Peer Rejection and Depressive Behavior in Children

    Science.gov (United States)

    Brendgen, Mara; Vitaro, Frank; Boivin, Michel; Girard, Alain; Bukowski, William M.; Dionne, Ginette; Tremblay, Richard E.; Perusse, Daniel

    2009-01-01

    Background: Genetic risk for depressive behavior may increase the likelihood of exposure to environmental stressors (gene-environment correlation, rGE). By the same token, exposure to environmental stressors may moderate the effect of genes on depressive behavior (gene-environment interaction, GxE). Relating these processes to a peer-related…

  7. Gene-Environment Interplay between Number of Friends and Prosocial Leadership Behavior in Children

    Science.gov (United States)

    Rivizzigno, Alessandra S.; Brendgen, Mara; Feng, Bei; Vitaro, Frank; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2014-01-01

    Enriched environments may moderate the effect of genetic factors on prosocial leadership (gene-environment interaction, G × E). However, positive environmental experiences may also themselves be influenced by a genetic disposition for prosocial leadership (gene-environment correlation, rGE). Relating these processes to friendships, the present…

  8. Gene-Environment Interplay between Peer Rejection and Depressive Behavior in Children

    Science.gov (United States)

    Brendgen, Mara; Vitaro, Frank; Boivin, Michel; Girard, Alain; Bukowski, William M.; Dionne, Ginette; Tremblay, Richard E.; Perusse, Daniel

    2009-01-01

    Background: Genetic risk for depressive behavior may increase the likelihood of exposure to environmental stressors (gene-environment correlation, rGE). By the same token, exposure to environmental stressors may moderate the effect of genes on depressive behavior (gene-environment interaction, GxE). Relating these processes to a peer-related…

  9. Vision-based interaction

    CERN Document Server

    Turk, Matthew

    2013-01-01

    In its early years, the field of computer vision was largely motivated by researchers seeking computational models of biological vision and solutions to practical problems in manufacturing, defense, and medicine. For the past two decades or so, there has been an increasing interest in computer vision as an input modality in the context of human-computer interaction. Such vision-based interaction can endow interactive systems with visual capabilities similar to those important to human-human interaction, in order to perceive non-verbal cues and incorporate this information in applications such

  10. Gene-Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood

    DEFF Research Database (Denmark)

    Reynolds, Chandra A; Gatz, Margaret; Christensen, Kaare

    2016-01-01

    Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body m...

  11. When chocolate seeking becomes compulsion: gene-environment interplay.

    Directory of Open Access Journals (Sweden)

    Enrico Patrono

    Full Text Available Eating disorders appear to be caused by a complex interaction between environmental and genetic factors, and compulsive eating in response to adverse circumstances characterizes many eating disorders.We compared compulsion-like eating in the form of conditioned suppression of palatable food-seeking in adverse situations in stressed C57BL/6J and DBA/2J mice, two well-characterized inbred strains, to determine the influence of gene-environment interplay on this behavioral phenotype. Moreover, we tested the hypothesis that low accumbal D2 receptor (R availability is a genetic risk factor of food compulsion-like behavior and that environmental conditions that induce compulsive eating alter D2R expression in the striatum. To this end, we measured D1R and D2R expression in the striatum and D1R, D2R and α1R levels in the medial prefrontal cortex, respectively, by western blot.Exposure to environmental conditions induces compulsion-like eating behavior, depending on genetic background. This behavioral pattern is linked to decreased availability of accumbal D2R. Moreover, exposure to certain environmental conditions upregulates D2R and downregulates α1R in the striatum and medial prefrontal cortex, respectively, of compulsive animals. These findings confirm the function of gene-environment interplay in the manifestation of compulsive eating and support the hypothesis that low accumbal D2R availability is a "constitutive" genetic risk factor for compulsion-like eating behavior. Finally, D2R upregulation and α1R downregulation in the striatum and medial prefrontal cortex, respectively, are potential neuroadaptive responses that parallel the shift from motivated to compulsive eating.

  12. When Chocolate Seeking Becomes Compulsion: Gene-Environment Interplay

    Science.gov (United States)

    Patella, Loris; Andolina, Diego; Valzania, Alessandro; Latagliata, Emanuele Claudio; Felsani, Armando; Pompili, Assunta; Gasbarri, Antonella; Puglisi-Allegra, Stefano; Ventura, Rossella

    2015-01-01

    Background Eating disorders appear to be caused by a complex interaction between environmental and genetic factors, and compulsive eating in response to adverse circumstances characterizes many eating disorders. Materials and Methods We compared compulsion-like eating in the form of conditioned suppression of palatable food-seeking in adverse situations in stressed C57BL/6J and DBA/2J mice, two well-characterized inbred strains, to determine the influence of gene-environment interplay on this behavioral phenotype. Moreover, we tested the hypothesis that low accumbal D2 receptor (R) availability is a genetic risk factor of food compulsion-like behavior and that environmental conditions that induce compulsive eating alter D2R expression in the striatum. To this end, we measured D1R and D2R expression in the striatum and D1R, D2R and α1R levels in the medial prefrontal cortex, respectively, by western blot. Results Exposure to environmental conditions induces compulsion-like eating behavior, depending on genetic background. This behavioral pattern is linked to decreased availability of accumbal D2R. Moreover, exposure to certain environmental conditions upregulates D2R and downregulates α1R in the striatum and medial prefrontal cortex, respectively, of compulsive animals. These findings confirm the function of gene-environment interplay in the manifestation of compulsive eating and support the hypothesis that low accumbal D2R availability is a “constitutive” genetic risk factor for compulsion-like eating behavior. Finally, D2R upregulation and α1R downregulation in the striatum and medial prefrontal cortex, respectively, are potential neuroadaptive responses that parallel the shift from motivated to compulsive eating. PMID:25781028

  13. Gene-Environment Interplay in the Link of Friends' and Nonfriends' Behaviors with Children's Social Reticence in a Competitive Situation

    Science.gov (United States)

    Guimond, Fanny-Alexandra; Brendgen, Mara; Vitaro, Frank; Forget-Dubois, Nadine; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2014-01-01

    This study used a genetically informed design to assess the effects of friends' and nonfriends' reticent and dominant behaviors on children's observed social reticence in a competitive situation. Potential gene-environment correlations (rGE) and gene-environment interactions (GxE) in the link between (a) friends' and…

  14. Gene-Environment Correlation Underlying the Association between Parental Negativity and Adolescent Externalizing Problems

    Science.gov (United States)

    Marceau, Kristine; Horwitz, Briana N.; Narusyte, Jurgita; Ganiban, Jody M.; Spotts, Erica L.; Reiss, David; Neiderhiser, Jenae M.

    2013-01-01

    Studies of adolescent or parent-based twins suggest that gene-environment correlation (rGE) is an important mechanism underlying parent-adolescent relationships. However, information on how parents' and children's genes and environments influence correlated parent "and" child behaviors is needed to distinguish types of rGE. The…

  15. Gene-Environment Correlation Underlying the Association between Parental Negativity and Adolescent Externalizing Problems

    Science.gov (United States)

    Marceau, Kristine; Horwitz, Briana N.; Narusyte, Jurgita; Ganiban, Jody M.; Spotts, Erica L.; Reiss, David; Neiderhiser, Jenae M.

    2013-01-01

    Studies of adolescent or parent-based twins suggest that gene-environment correlation (rGE) is an important mechanism underlying parent-adolescent relationships. However, information on how parents' and children's genes and environments influence correlated parent "and" child behaviors is needed to distinguish types of rGE. The present…

  16. Gene-environment interaction and male reproductive function

    DEFF Research Database (Denmark)

    Axelsson, Jonatan; Bonde, Jens Peter; Giwercman, Yvonne L;

    2010-01-01

    As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between...... that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism...... of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity...

  17. Gene-environment interactions in Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    M.A. Kirkman; P. Yu-Wai-Man (Patrick); A. Korsten (Alex); M. Leonhardt (Miriam); K. Dimitriadis (Konstantin); I.F.M. de Coo (René); T. Klopstock (Thomas); P.F. Chinnery

    2009-01-01

    textabstractLeber hereditary optic neuropathy (LHON) is a genetic disorder primarily due to mutations of mitochondrial DNA (mtDNA). Environmental factors are thought to precipitate the visual failure and explain the marked incomplete penetrance of LHON, but previous small studies have failed to conf

  18. Gene-Environment Interplay, Family Relationships, and Child Adjustment

    Science.gov (United States)

    Horwitz, Briana N.; Neiderhiser, Jenae M.

    2011-01-01

    This paper reviews behavioral genetic research from the past decade that has moved beyond simply studying the independent influences of genes and environments. The studies considered in this review have instead focused on understanding gene-environment interplay, including genotype-environment correlation (rGE) and genotype x environment…

  19. Gene-Environment Interplay, Family Relationships, and Child Adjustment

    Science.gov (United States)

    Horwitz, Briana N.; Neiderhiser, Jenae M.

    2011-01-01

    This paper reviews behavioral genetic research from the past decade that has moved beyond simply studying the independent influences of genes and environments. The studies considered in this review have instead focused on understanding gene-environment interplay, including genotype-environment correlation (rGE) and genotype x environment…

  20. Interactive example-based hatching

    NARCIS (Netherlands)

    Gerl, Moritz; Isenberg, Tobias

    2013-01-01

    We present an approach for interactively generating pen-and-ink hatching renderings based on hand-drawn examples. We aim to overcome the regular and synthetic appearance of the results of existing methods by incorporating human virtuosity and illustration skills in the computer generation of such

  1. Gene-environment correlations in the stress-depression relationship.

    Science.gov (United States)

    Schnittker, Jason

    2010-09-01

    A critical feature of the social stress model is the apparent relationship between stress and depression. Although many studies have demonstrated a connection between the two, the relationship may be contaminated by genes affecting both stress and depression. Using a sample of identical and fraternal twins, this study explores genetic influences on depression and assorted sources of stress while explicitly estimating, and thereby controlling for, gene-environment correlations. I consider both stress and depression in a fine-grained fashion. For the former, the study explores assorted sources of stress, including health and disability, family, unemployment, discrimination, and perceived neighborhood safety, as gene-environment correlations may be stronger for some forms of stress than others. For the latter, the study explores both depressive symptoms and major depressive disorders, as each may entail a different epidemiological process, especially with respect to genes. The results reveal that most, but not all, measures of stress have moderate heritabilities, suggesting that genes influence exposure to the environment in a broad fashion. Yet, despite this, the relationship between stress and depression is generally robust to gene-environment correlations. There are some notable exceptions. For example, allowing for gene-environment correlations, marital conflict is generally unrelated to depression. Moreover, gene-environment correlations are generally stronger for major depression than for depressive symptoms, encouraging further elaboration of the distinction between the onset of depression and its recurrence, especially in the context of genes. These exceptions do not put limits on environmental influence, but do suggest that genes operate in a complex life-course fashion.

  2. Kernel Approach for Modeling Interaction Effects in Genetic Association Studies of Complex Quantitative Traits.

    Science.gov (United States)

    Broadaway, K Alaine; Duncan, Richard; Conneely, Karen N; Almli, Lynn M; Bradley, Bekh; Ressler, Kerry J; Epstein, Michael P

    2015-07-01

    The etiology of complex traits likely involves the effects of genetic and environmental factors, along with complicated interaction effects between them. Consequently, there has been interest in applying genetic association tests of complex traits that account for potential modification of the genetic effect in the presence of an environmental factor. One can perform such an analysis using a joint test of gene and gene-environment interaction. An optimal joint test would be one that remains powerful under a variety of models ranging from those of strong gene-environment interaction effect to those of little or no gene-environment interaction effect. To fill this demand, we have extended a kernel machine based approach for association mapping of multiple SNPs to consider joint tests of gene and gene-environment interaction. The kernel-based approach for joint testing is promising, because it incorporates linkage disequilibrium information from multiple SNPs simultaneously in analysis and permits flexible modeling of interaction effects. Using simulated data, we show that our kernel machine approach typically outperforms the traditional joint test under strong gene-environment interaction models and further outperforms the traditional main-effect association test under models of weak or no gene-environment interaction effects. We illustrate our test using genome-wide association data from the Grady Trauma Project, a cohort of highly traumatized, at-risk individuals, which has previously been investigated for interaction effects. © 2015 WILEY PERIODICALS, INC.

  3. Child dopamine active transporter 1 genotype and parenting: evidence for evocative gene-environment correlations.

    Science.gov (United States)

    Hayden, Elizabeth P; Hanna, Brigitte; Sheikh, Haroon I; Laptook, Rebecca S; Kim, Jiyon; Singh, Shiva M; Klein, Daniel N

    2013-02-01

    The dopamine active transporter 1 (DAT1) gene is implicated in psychopathology risk. Although the processes by which this gene exerts its effects on risk are poorly understood, a small body of research suggests that the DAT1 gene influences early emerging negative emotionality, a marker of children's psychopathology risk. As child negative emotionality evokes negative parenting practices, the DAT1 gene may also play a role in gene-environment correlations. To test this model, children (N = 365) were genotyped for the DAT1 gene and participated in standardized parent-child interaction tasks with their primary caregiver. The DAT1 gene 9-repeat variant was associated with child negative affect expressed toward the parent during parent-child interactions, and parents of children with a 9-repeat allele exhibited more hostility and lower guidance/engagement than parents of children without a 9-repeat allele. These gene-environment associations were partially mediated by child negative affect toward the parent. The findings implicate a specific polymorphism in eliciting negative parenting, suggesting that evocative associations play a role in elevating children's risk for emotional trajectories toward psychopathology risk.

  4. Results-Based Interaction Design

    Science.gov (United States)

    Weiss, Meredith

    2008-01-01

    Interaction design is a user-centered approach to development in which users and their goals are the driving force behind a project's design. Interaction design principles are fundamental to the design and implementation of effective websites, but they are not sufficient. This article argues that, to reach its full potential, a website should also…

  5. Activity-Based Collaboration for Interactive Spaces

    DEFF Research Database (Denmark)

    Bardram, Jakob Eyvind; Esbensen, Morten; Tabard, Aurélien

    2017-01-01

    Activity-based computing (ABC) is a conceptual and technological framework for designing interactive systems that offers a better mapping between the activities people conduct and the digital entities they use. In ABC, rather than interacting directly with lower-level technical entities like file......LabBench [2, 3]. The chapter discusses the benefits of activity-based collaboration support for these interactive spaces, while also discussing limitations and challenges to be addressed in further research....

  6. Cognitive neurorehabilitation based on interactive video technology

    OpenAIRE

    Martinez Moreno, Jose Maria; Solana Sánchez, Javier; R. Sánchez; González Palmero, S.; Sánchez González, Patricia; Gómez Pérez, C.; Morell Vilaseca, Marc; Cáceres Taladriz, César; Roig Rovira, Teresa; Tormos Muñoz, Josep M.; Gómez Aguilera, Enrique J.

    2013-01-01

    Cognitive impairment is the main cause of disability in developed societies. New interactive technologies help therapists in neurorehabilitation in order to increase patients’ autonomy and quality of life. This work proposes Interactive Video (IV) as a technology to develop cognitive rehabilitation tasks based on Activities of Daily Living (ADL). ADL cognitive task has been developed and integrated with eye-tracking technology for task interaction and patients’ performance monitoring....

  7. Interactive Reliability-Based Optimal Design

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Thoft-Christensen, Palle; Siemaszko, A.

    1994-01-01

    Interactive design/optimization of large, complex structural systems is considered. The objective function is assumed to model the expected costs. The constraints are reliability-based and/or related to deterministic code requirements. Solution of this optimization problem is divided in four main...... be used in interactive optimization....

  8. Gene-Environment Interplay and Psychopathology: Multiple Varieties but Real Effects

    Science.gov (United States)

    Rutter, Michael; Moffitt, Terrie E.; Caspi, Avshalom

    2006-01-01

    Gene-environment interplay is a general term that covers several divergent concepts with different meanings and different implications. In this review, we evaluate research evidence on four varieties of gene-environment interplay. First, we consider epigenetic mechanisms by which environmental influences alter the effects of genes. Second, we…

  9. Spatial interactions in agent-based modeling

    CERN Document Server

    Ausloos, Marcel; Merlone, Ugo

    2014-01-01

    Agent Based Modeling (ABM) has become a widespread approach to model complex interactions. In this chapter after briefly summarizing some features of ABM the different approaches in modeling spatial interactions are discussed. It is stressed that agents can interact either indirectly through a shared environment and/or directly with each other. In such an approach, higher-order variables such as commodity prices, population dynamics or even institutions, are not exogenously specified but instead are seen as the results of interactions. It is highlighted in the chapter that the understanding of patterns emerging from such spatial interaction between agents is a key problem as much as their description through analytical or simulation means. The chapter reviews different approaches for modeling agents' behavior, taking into account either explicit spatial (lattice based) structures or networks. Some emphasis is placed on recent ABM as applied to the description of the dynamics of the geographical distribution o...

  10. Movement-based Interaction in Camera Spaces

    DEFF Research Database (Denmark)

    Eriksson, Eva; Riisgaard Hansen, Thomas; Lykke-Olesen, Andreas

    2006-01-01

    In this paper we present three concepts that address movement-based interaction using camera tracking. Based on our work with several movement-based projects we present four selected applications, and use these applications to leverage our discussion, and to describe our three main concepts space......, relations, and feedback. We see these as central for describing and analysing movement-based systems using camera tracking and we show how these three concepts can be used to analyse other camera tracking applications....

  11. Evidence-Based Interactive Management of Change

    Directory of Open Access Journals (Sweden)

    Albert Fleischmann

    2011-06-01

    Full Text Available Evidence-based interactive management of change means hands-on experience of modified work processes, given evidence of change. For this kind of pro-active organizational development support we use an organisational process memory and a communication-based representation technique for role-specific and task-oriented process execution. Both are effective means for organizations becoming agile through interactively modelling the business at the process level and re-constructing or re-arranging process representations according to various needs. The tool allows experiencing role-specific workflows, as the communication-based refinement of work models allows for executable process specifications. When presenting the interactive processes to individuals involved in the business processes, changes can be explored interactively in a context-sensitive way before re-implementing business processes and information systems. The tool is based on a service-oriented architecture and a flexible representation scheme comprising the exchange of message between actors, business objects and actors (roles. The interactive execution of workflows does not only enable the individual reorganization of work but also changes at the level of the entire organization due to the represented interactions.

  12. An interactive segmentation method based on superpixel

    DEFF Research Database (Denmark)

    Yang, Shu; Zhu, Yaping; Wu, Xiaoyu

    2015-01-01

    This paper proposes an interactive image-segmentation method which is based on superpixel. To achieve fast segmentation, the method is used to establish a Graphcut model using superpixels as nodes, and a new energy function is proposed. Experimental results demonstrate that the authors' method has...... excellent performance in terms of segmentation accuracy and computation efficiency compared with other segmentation algorithm based on pixels....

  13. Gene-gene, gene-environment, gene-nutrient interactionsand single nucleotide polymorphisms of inflammatorycytokines

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Inflammation plays a significant role in the etiologyof type 2 diabetes mellitus (T2DM). The rise in thepro-inflammatory cytokines is the essential step inglucotoxicity and lipotoxicity induced mitochondrialinjury, oxidative stress and beta cell apoptosis inT2DM. Among the recognized markers are interleukin(IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha(TNF-α), C-reactive protein, resistin, adiponectin, tissueplasminogen activator, fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strongenvironmental influence; exhibiting a polygenic modeof inheritance. Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatorycytokines have been reported as a riskfor T2DM. Not all the SNPs have been confirmed byunifying results in different studies and wide variationshave been reported in various ethnic groups. Theinter-ethnic variations can be explained by the factthat gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions. Thisreview highlights the impact of these interactions ondetermining the role of single nucleotide polymorphismof IL-6, TNF-α, resistin and adiponectin in pathogenesisof T2DM.

  14. Evocative gene-environment correlation in the mother-child relationship: a twin study of interpersonal processes.

    Science.gov (United States)

    Klahr, Ashlea M; Thomas, Katherine M; Hopwood, Christopher J; Klump, Kelly L; Burt, S Alexandra

    2013-02-01

    The behavior genetic literature suggests that genetically influenced characteristics of the child elicit specific behaviors from the parent. However, little is known about the processes by which genetically influenced child characteristics evoke parental responses. Interpersonal theory provides a useful framework for identifying reciprocal behavioral processes between children and mothers. The theory posits that, at any given moment, interpersonal behavior varies along the orthogonal dimensions of warmth and control and that the interpersonal behavior of one individual tends to elicit corresponding or contrasting behavior from the other (i.e., warmth elicits warmth, whereas control elicits submission). The current study thus examined these dimensions of interpersonal behavior as they relate to the parent-child relationship in 546 twin families. A computer joystick was used to rate videos of mother-child interactions in real time, yielding information on mother and child levels of warmth and control throughout the interaction. Analyses indicated that maternal control, but not maternal warmth, was influenced by evocative gene-environment correlational processes, such that genetic influences on maternal control and child control were largely overlapping. Moreover, these common genetic influences were present both cross-sectionally and over the course of the interaction. Such findings not only confirm the presence of evocative gene-environment correlational processes in the mother-child relationship but also illuminate at least one of the specific interpersonal behaviors that underlie this evocative process.

  15. Evolutionary algorithm based configuration interaction approach

    CERN Document Server

    Chakraborty, Rahul

    2016-01-01

    A stochastic configuration interaction method based on evolutionary algorithm is designed as an affordable approximation to full configuration interaction (FCI). The algorithm comprises of initiation, propagation and termination steps, where the propagation step is performed with cloning, mutation and cross-over, taking inspiration from genetic algorithm. We have tested its accuracy in 1D Hubbard problem and a molecular system (symmetric bond breaking of water molecule). We have tested two different fitness functions based on energy of the determinants and the CI coefficients of determinants. We find that the absolute value of CI coefficients is a more suitable fitness function when combined with a fixed selection scheme.

  16. INTERACTION OF COPPER BASED PRESERVATIVES WITH WOOD

    Directory of Open Access Journals (Sweden)

    Ali Temiz

    2004-11-01

    Full Text Available Copper is highly toxic to fungi and the element is widely used in many preservative formulations over 50 years. The interactions of wood and copper-based preservatives impact both the performance and the environment aspects of treated wood. Copper might be present in treated wood as coppercellulose complex, copper-lignin complex, and crystalline or amorphous inorganic/organic copper compounds. In this review; it was aimed to investigate the interactions of wood and copper-based preservatives, Copper Adsorpsion factors and copper forms in treated wood

  17. Paired Comparisons-based Interactive Differential Evolution

    CERN Document Server

    Takagi, Hideyuki

    2009-01-01

    We propose Interactive Differential Evolution (IDE) based on paired comparisons for reducing user fatigue and evaluate its convergence speed in comparison with Interactive Genetic Algorithms (IGA) and tournament IGA. User interface and convergence performance are two big keys for reducing Interactive Evolutionary Computation (IEC) user fatigue. Unlike IGA and conventional IDE, users of the proposed IDE and tournament IGA do not need to compare whole individuals each other but compare pairs of individuals, which largely decreases user fatigue. In this paper, we design a pseudo-IEC user and evaluate another factor, IEC convergence performance, using IEC simulators and show that our proposed IDE converges significantly faster than IGA and tournament IGA, i.e. our proposed one is superior to others from both user interface and convergence performance points of view.

  18. Interactive analysis of geodata based intelligence

    Science.gov (United States)

    Wagner, Boris; Eck, Ralf; Unmüessig, Gabriel; Peinsipp-Byma, Elisabeth

    2016-05-01

    When a spatiotemporal events happens, multi-source intelligence data is gathered to understand the problem, and strategies for solving the problem are investigated. The difficulties arising from handling spatial and temporal intelligence data represent the main problem. The map might be the bridge to visualize the data and to get the most understand model for all stakeholders. For the analysis of geodata based intelligence data, a software was developed as a working environment that combines geodata with optimized ergonomics. The interaction with the common operational picture (COP) is so essentially facilitated. The composition of the COP is based on geodata services, which are normalized by international standards of the Open Geospatial Consortium (OGC). The basic geodata are combined with intelligence data from images (IMINT) and humans (HUMINT), stored in a NATO Coalition Shared Data Server (CSD). These intelligence data can be combined with further information sources, i.e., live sensors. As a result a COP is generated and an interaction suitable for the specific workspace is added. This allows the users to work interactively with the COP, i.e., searching with an on board CSD client for suitable intelligence data and integrate them into the COP. Furthermore, users can enrich the scenario with findings out of the data of interactive live sensors and add data from other sources. This allows intelligence services to contribute effectively to the process by what military and disaster management are organized.

  19. ECCE Toolkit: Prototyping Sensor-Based Interaction

    Science.gov (United States)

    Bellucci, Andrea; Aedo, Ignacio; Díaz, Paloma

    2017-01-01

    Building and exploring physical user interfaces requires high technical skills and hours of specialized work. The behavior of multiple devices with heterogeneous input/output channels and connectivity has to be programmed in a context where not only the software interface matters, but also the hardware components are critical (e.g., sensors and actuators). Prototyping physical interaction is hindered by the challenges of: (1) programming interactions among physical sensors/actuators and digital interfaces; (2) implementing functionality for different platforms in different programming languages; and (3) building custom electronic-incorporated objects. We present ECCE (Entities, Components, Couplings and Ecosystems), a toolkit for non-programmers that copes with these issues by abstracting from low-level implementations, thus lowering the complexity of prototyping small-scale, sensor-based physical interfaces to support the design process. A user evaluation provides insights and use cases of the kind of applications that can be developed with the toolkit. PMID:28241502

  20. ECCE Toolkit: Prototyping Sensor-Based Interaction.

    Science.gov (United States)

    Bellucci, Andrea; Aedo, Ignacio; Díaz, Paloma

    2017-02-23

    Building and exploring physical user interfaces requires high technical skills and hours of specialized work. The behavior of multiple devices with heterogeneous input/output channels and connectivity has to be programmed in a context where not only the software interface matters, but also the hardware components are critical (e.g., sensors and actuators). Prototyping physical interaction is hindered by the challenges of: (1) programming interactions among physical sensors/actuators and digital interfaces; (2) implementing functionality for different platforms in different programming languages; and (3) building custom electronic-incorporated objects. We present ECCE (Entities, Components, Couplings and Ecosystems), a toolkit for non-programmers that copes with these issues by abstracting from low-level implementations, thus lowering the complexity of prototyping small-scale, sensor-based physical interfaces to support the design process. A user evaluation provides insights and use cases of the kind of applications that can be developed with the toolkit.

  1. ECCE Toolkit: Prototyping Sensor-Based Interaction

    Directory of Open Access Journals (Sweden)

    Andrea Bellucci

    2017-02-01

    Full Text Available Building and exploring physical user interfaces requires high technical skills and hours of specialized work. The behavior of multiple devices with heterogeneous input/output channels and connectivity has to be programmed in a context where not only the software interface matters, but also the hardware components are critical (e.g., sensors and actuators. Prototyping physical interaction is hindered by the challenges of: (1 programming interactions among physical sensors/actuators and digital interfaces; (2 implementing functionality for different platforms in different programming languages; and (3 building custom electronic-incorporated objects. We present ECCE (Entities, Components, Couplings and Ecosystems, a toolkit for non-programmers that copes with these issues by abstracting from low-level implementations, thus lowering the complexity of prototyping small-scale, sensor-based physical interfaces to support the design process. A user evaluation provides insights and use cases of the kind of applications that can be developed with the toolkit.

  2. Interactive early warning technique based on SVDD

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    After reviewing current researches on early warning,it is found that"bad" data of some systems is not easy to obtain,which makes methods proposed by these researches unsuitable for monitored systems.An interactive early warning technique based on SVDD(support vector data description)is proposed to adopt"good" data as samples to overcome the difficulty in obtaining the"bad"data.The process consists of two parts:(1)A hypersphere is fitted on"good"data using SVDD.If the data object are outside the hypersphere,it would be taken as"suspicious";(2)A group of experts would decide whether the suspicious data is"bad"or"good",early warning messages would be issued according to the decisions.And the detailed process of implementation is proposed.At last,an experiment based on data of a macroeconomic system is conducted to verify the proposed technique.

  3. The Gene, Environment Association Studies consortium (GENEVA): maximizing the knowledge obtained from GWAS by collaboration across studies of multiple conditions.

    Science.gov (United States)

    Cornelis, Marilyn C; Agrawal, Arpana; Cole, John W; Hansel, Nadia N; Barnes, Kathleen C; Beaty, Terri H; Bennett, Siiri N; Bierut, Laura J; Boerwinkle, Eric; Doheny, Kimberly F; Feenstra, Bjarke; Feingold, Eleanor; Fornage, Myriam; Haiman, Christopher A; Harris, Emily L; Hayes, M Geoffrey; Heit, John A; Hu, Frank B; Kang, Jae H; Laurie, Cathy C; Ling, Hua; Manolio, Teri A; Marazita, Mary L; Mathias, Rasika A; Mirel, Daniel B; Paschall, Justin; Pasquale, Louis R; Pugh, Elizabeth W; Rice, John P; Udren, Jenna; van Dam, Rob M; Wang, Xiaojing; Wiggs, Janey L; Williams, Kayleen; Yu, Kai

    2010-05-01

    Genome-wide association studies (GWAS) have emerged as powerful means for identifying genetic loci related to complex diseases. However, the role of environment and its potential to interact with key loci has not been adequately addressed in most GWAS. Networks of collaborative studies involving different study populations and multiple phenotypes provide a powerful approach for addressing the challenges in analysis and interpretation shared across studies. The Gene, Environment Association Studies (GENEVA) consortium was initiated to: identify genetic variants related to complex diseases; identify variations in gene-trait associations related to environmental exposures; and ensure rapid sharing of data through the database of Genotypes and Phenotypes. GENEVA consists of several academic institutions, including a coordinating center, two genotyping centers and 14 independently designed studies of various phenotypes, as well as several Institutes and Centers of the National Institutes of Health led by the National Human Genome Research Institute. Minimum detectable effect sizes include relative risks ranging from 1.24 to 1.57 and proportions of variance explained ranging from 0.0097 to 0.02. Given the large number of research participants (N>80,000), an important feature of GENEVA is harmonization of common variables, which allow analyses of additional traits. Environmental exposure information available from most studies also enables testing of gene-environment interactions. Facilitated by its sizeable infrastructure for promoting collaboration, GENEVA has established a unified framework for genotyping, data quality control, analysis and interpretation. By maximizing knowledge obtained through collaborative GWAS incorporating environmental exposure information, GENEVA aims to enhance our understanding of disease etiology, potentially identifying opportunities for intervention.

  4. Gene-Environment Interplay in Internalizing Disorders: Consistent Findings across Six Environmental Risk Factors

    Science.gov (United States)

    Hicks, Brian M.; Dirago, Ana C.; Iacono, William G.; McGue, Matt

    2009-01-01

    Background: Behavior genetic methods can help to elucidate gene-environment (G-E) interplay in the development of internalizing (INT) disorders (i.e., major depression and anxiety disorders). To date, however, no study has conducted a comprehensive analysis examining multiple environmental risk factors with the purpose of delineating general…

  5. Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

    Science.gov (United States)

    2007-06-01

    taking any oral contraceptives and then resumed, ask questions D1- D2 again) D2 . Name of the oral contraceptive D3 . Age of first use D4. Duration...June 2007). “The multipotent influence of Vitamin D on breast cancer risk”. D.R. Marshall (PI), primary submitter with Dr. Alecia Malin-Fair (PI), co...Portion Size 170. Pepper 1 2 3 4 5 171. Chili/Hot 1 2 3 4 5 172. Salt 1 2 3 4 5 173. Vitamins and Supplements 1 2 3 4 5 174. Others 1 2 3 4 5

  6. Identifying Gene-Environment Interactions in Schizophrenia : Contemporary Challenges for Integrated, Large-scale Investigations

    NARCIS (Netherlands)

    van Os, Jim; Rutten, Bart P.; Myin-Germeys, Inez; Delespaul, Philippe; Viechtbauer, Wolfgang; van Zelst, Catherine; Bruggeman, Richard; Reininghaus, Ulrich; Morgan, Craig; Murray, Robin M.; Di Forti, Marta; McGuire, Philip; Valmaggia, Lucia R.; Kempton, Matthew J.; Gayer-Anderson, Charlotte; Hubbard, Kathryn; Beards, Stephanie; Stilo, Simona A.; Onyejiaka, Adanna; Bourque, Francois; Modinos, Gemma; Tognin, Stefania; Calem, Maria; O'Donovan, Michael C.; Owen, Michael J.; Holmans, Peter; Williams, Nigel; Craddock, Nicholas; Richards, Alexander; Humphreys, Isla; Meyer-Lindenberg, Andreas; Leweke, F. Markus; Tost, Heike; Akdeniz, Ceren; Rohleder, Cathrin; Bumb, J. Malte; Schwarz, Emanuel; Alptekin, Koksal; Ucok, Alp; Saka, Meram Can; Atbasoglu, E. Cem; Guloksuz, Sinan; Gumus-Akay, Guvem; Cihan, Burin; Karadag, Hasan; Soygur, Haldan; Cankurtaran, Eylem Sahin; Ulusoy, Semra; Akdede, Berna; Binbay, Tolga; Ayer, Ahmet; Noyan, Handan; Karadayi, Gulsah; Akturan, Elin; Ulas, Halis; Arango, Celso; Parellada, Mara; Bernardo, Miguel; Sanjuan, Julio; Bobes, Julio; Arrojo, Manuel; Luis Santos, Jose; Cuadrado, Pedro; Rodriguez Solano, Jose Juan; Carracedo, Angel; Garcia Bernardo, Enrique; Roldan, Laura; Lopez, Gonzalo; Cabrera, Bibiana; Cruz, Sabrina; Diaz Mesa, Eva Ma; Pouso, Maria; Jimenez, Estela; Sanchez, Teresa; Rapado, Marta; Gonzalez, Emiliano; Martinez, Covadonga; Sanchez, Emilio; Soledad Olmeda, Ma; de Haan, Lieuwe; Velthorst, Eva; van der Gaag, Mark; Selten, Jean-Paul; van Dam, Daniella; van der Ven, Elsje; van der Meer, Floor; Messchaert, Elles; Kraan, Tamar; Burger, Nadine; Leboyer, Marion; Szoke, Andrei; Schurhoff, Franck; Llorca, Pierre-Michel; Jamain, Stephane; Tortelli, Andrea; Frijda, Flora; Vilain, Jeanne; Galliot, Anne-Marie; Baudin, Gregoire; Ferchiou, Aziz; Richard, Jean-Romain; Bulzacka, Ewa; Charpeaud, Thomas; Tronche, Anne-Marie; De Hert, Marc; van Winkel, Ruud; Decoster, Jeroen; Derom, Catherine; Thiery, Evert; Stefanis, Nikos C.; Sachs, Gabriele; Aschauer, Harald; Lasser, Iris; Winklbaur, Bernadette; Schlogelhofer, Monika; Riecher-Rossler, Anita; Borgwardt, Stefan; Walter, Anna; Harrisberger, Fabienne; Smieskova, Renata; Rapp, Charlotte; Ittig, Sarah; Soguel-Dit-Piquard, Fabienne; Studerus, Erich; Klosterkotter, Joachim; Ruhrmann, Stephan; Paruch, Julia; Julkowski, Dominika; Hilboll, Desiree; Sham, Pak C.; Cherny, Stacey S.; Chen, Eric Y. H.; Campbell, Desmond D.; Li, Miaoxin; Maria Romeo-Casabona, Carlos; Emaldi Cirion, Aitziber; Urruela Mora, Asier; Jones, Peter; Kirkbride, James; Cannon, Mary; Rujescu, Dan; Tarricone, Ilaria; Berardi, Domenico; Bonora, Elena; Seri, Marco; Marcacci, Thomas; Chiri, Luigi; Chierzi, Federico; Storbini, Viviana; Braca, Mauro; Minenna, Maria Gabriella; Donegani, Ivonne; Fioritti, Angelo; La Barbera, Daniele; La Cascia, Caterina Erika; Mule, Alice; Sideli, Lucia; Sartorio, Rachele; Ferraro, Laura; Tripoli, Giada; Seminerio, Fabio; Marinaro, Anna Maria; McGorry, Patrick; Nelson, Barnaby; Amminger, G. Paul; Pantelis, Christos; Menezes, Paulo R.; Del-Ben, Cristina M.; Tenan, Silvia H. Gallo; Shuhama, Rosana; Ruggeri, Mirella; Tosato, Sarah; Lasalvia, Antonio; Bonetto, Chiara; Ira, Elisa; Nordentoft, Merete; Krebs, Marie-Odile; Barrantes-Vidal, Neus; Cristobal, Paula; Kwapil, Thomas R.; Brietzke, Elisa; Bressan, Rodrigo A.; Gadelha, Ary; Maric, Nadja P.; Andric, Sanja; Mihaljevic, Marina; Mirjanic, Tijana

    2014-01-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular

  7. Gene-environment interactions and the impact on obesity and lipid profile phenotypes

    Science.gov (United States)

    Sequencing the human genome provided the data, human intellectual capital and technology, particularly in terms of infrastructure and methodologies, to begin discovering genes involved in a wide range of human diseases and afflictions. This has led to a resurgence in genetics with the advent of geno...

  8. Gene-Environment Interaction and Breast Cancer on Long Island, NY

    Science.gov (United States)

    2008-05-01

    multiethnic pregnancy cohort. Am J Epidemiol. 2007 Jun 15;165(12):1397-404. Sagiv SK, Gaudet MM, Eng SM, Abrahamson PE, Shantakumar S, Teitelbaum SL...Gammon MD. Preeclampsia, pregnancy -related hypertension, and breast cancer risk. Am J Epidemiol. 2007 May 1;165(9):1007-14. • Invited Presentation...potential hormonal activity, can have beneficial health effects including lowering the risk of breast cancer and osteoporosis (Branca and Lorenzetti, 2005

  9. Gene-gene and gene-environment interactions in prostate, breast and colorectal cancer

    OpenAIRE

    Kopp, Tine Iskov; Vogel, Ulla Birgitte; Nellemann, Christine; Ravn-Haren, Gitte; Tjønneland, Anne

    2015-01-01

    Cancer incidensen i Vesten er steget stødt de sidste 50 år. For tre af de mest prævalente cancer typer i Danmark, prostata-, bryst- og kolorektal cancer, er kun en lille del (1-15%) af incidensen forårsaget af højpenetrans enkelt-genmutationer pga. deres lave frekvens i populationen. Generelt set bidrager nedarvede faktorer til årsagsforhold for bryst cancer kun med 27%, hvorimod genetik bidrager med 35% og 42% for henholdsvis kolorektal- og prostata cancer. Derudover indikerer immigrationsst...

  10. Childhood problem behavior and parental divorce: evidence for gene-environment interaction

    NARCIS (Netherlands)

    S.C.C. Robbers (Sylvana); F.V.A. van Oort (Floor); A.C. Huizink (Anja); F.C. Verhulst (Frank); C.E.M. van Beijsterveldt (Toos); D.I. Boomsma (Dorret); M. Bartels (Meike)

    2012-01-01

    textabstractObjective: The importance of genetic and environmental influences on children's behavioral and emotional problems may vary as a function of environmental exposure. We previously reported that 12-year-olds with divorced parents showed more internalizing and externalizing problems than

  11. Shame and Guilt-Proneness in Adolescents: Gene-Environment Interactions

    OpenAIRE

    Aurora Szentágotai-Tătar; Adina Chiș; Romana Vulturar; Anca Dobrean; Diana Mirela Cândea; Andrei C Miu

    2015-01-01

    Rooted in people's preoccupation with how they are perceived and evaluated, shame and guilt are self-conscious emotions that play adaptive roles in social behavior, but can also contribute to psychopathology when dysregulated. Shame and guilt-proneness develop during childhood and adolescence, and are influenced by genetic and environmental factors that are little known to date. This study investigated the effects of early traumatic events and functional polymorphisms in the brain-derived neu...

  12. Linking Genes to Cardiovascular Diseases: Gene Action and Gene-Environment Interactions.

    Science.gov (United States)

    Pasipoularides, Ares

    2015-12-01

    A unique myocardial characteristic is its ability to grow/remodel in order to adapt; this is determined partly by genes and partly by the environment and the milieu intérieur. In the "post-genomic" era, a need is emerging to elucidate the physiologic functions of myocardial genes, as well as potential adaptive and maladaptive modulations induced by environmental/epigenetic factors. Genome sequencing and analysis advances have become exponential lately, with escalation of our knowledge concerning sometimes controversial genetic underpinnings of cardiovascular diseases. Current technologies can identify candidate genes variously involved in diverse normal/abnormal morphomechanical phenotypes, and offer insights into multiple genetic factors implicated in complex cardiovascular syndromes. The expression profiles of thousands of genes are regularly ascertained under diverse conditions. Global analyses of gene expression levels are useful for cataloging genes and correlated phenotypes, and for elucidating the role of genes in maladies. Comparative expression of gene networks coupled to complex disorders can contribute insights as to how "modifier genes" influence the expressed phenotypes. Increasingly, a more comprehensive and detailed systematic understanding of genetic abnormalities underlying, for example, various genetic cardiomyopathies is emerging. Implementing genomic findings in cardiology practice may well lead directly to better diagnosing and therapeutics. There is currently evolving a strong appreciation for the value of studying gene anomalies, and doing so in a non-disjointed, cohesive manner. However, it is challenging for many-practitioners and investigators-to comprehend, interpret, and utilize the clinically increasingly accessible and affordable cardiovascular genomics studies. This survey addresses the need for fundamental understanding in this vital area.

  13. Gene-environment interactions and obesity: recent developments and future directions

    OpenAIRE

    Huang, Tao; Hu, Frank B

    2015-01-01

    Obesity, a major public health concern, is a multifactorial disease caused by both environmental and genetic factors. Although recent genome-wide association studies have identified many loci related to obesity or body mass index, the identified variants explain only a small proportion of the heritability of obesity. Better understanding of the interplay between genetic and environmental factors is the basis for developing effective personalized obesity prevention and management strategies. T...

  14. Identifying Gene-Environment Interactions in Schizophrenia : Contemporary Challenges for Integrated, Large-scale Investigations

    NARCIS (Netherlands)

    van Os, Jim; Rutten, Bart P.; Myin-Germeys, Inez; Delespaul, Philippe; Viechtbauer, Wolfgang; van Zelst, Catherine; Bruggeman, Richard; Reininghaus, Ulrich; Morgan, Craig; Murray, Robin M.; Di Forti, Marta; McGuire, Philip; Valmaggia, Lucia R.; Kempton, Matthew J.; Gayer-Anderson, Charlotte; Hubbard, Kathryn; Beards, Stephanie; Stilo, Simona A.; Onyejiaka, Adanna; Bourque, Francois; Modinos, Gemma; Tognin, Stefania; Calem, Maria; O'Donovan, Michael C.; Owen, Michael J.; Holmans, Peter; Williams, Nigel; Craddock, Nicholas; Richards, Alexander; Humphreys, Isla; Meyer-Lindenberg, Andreas; Leweke, F. Markus; Tost, Heike; Akdeniz, Ceren; Rohleder, Cathrin; Bumb, J. Malte; Schwarz, Emanuel; Alptekin, Koksal; Ucok, Alp; Saka, Meram Can; Atbasoglu, E. Cem; Guloksuz, Sinan; Gumus-Akay, Guvem; Cihan, Burin; Karadag, Hasan; Soygur, Haldan; Cankurtaran, Eylem Sahin; Ulusoy, Semra; Akdede, Berna; Binbay, Tolga; Ayer, Ahmet; Noyan, Handan; Karadayi, Gulsah; Akturan, Elin; Ulas, Halis; Arango, Celso; Parellada, Mara; Bernardo, Miguel; Sanjuan, Julio; Bobes, Julio; Arrojo, Manuel; Luis Santos, Jose; Cuadrado, Pedro; Rodriguez Solano, Jose Juan; Carracedo, Angel; Garcia Bernardo, Enrique; Roldan, Laura; Lopez, Gonzalo; Cabrera, Bibiana; Cruz, Sabrina; Diaz Mesa, Eva Ma; Pouso, Maria; Jimenez, Estela; Sanchez, Teresa; Rapado, Marta; Gonzalez, Emiliano; Martinez, Covadonga; Sanchez, Emilio; Soledad Olmeda, Ma; de Haan, Lieuwe; Velthorst, Eva; van der Gaag, Mark; Selten, Jean-Paul; van Dam, Daniella; van der Ven, Elsje; van der Meer, Floor; Messchaert, Elles; Kraan, Tamar; Burger, Nadine; Leboyer, Marion; Szoke, Andrei; Schurhoff, Franck; Llorca, Pierre-Michel; Jamain, Stephane; Tortelli, Andrea; Frijda, Flora; Vilain, Jeanne; Galliot, Anne-Marie; Baudin, Gregoire; Ferchiou, Aziz; Richard, Jean-Romain; Bulzacka, Ewa; Charpeaud, Thomas; Tronche, Anne-Marie; De Hert, Marc; van Winkel, Ruud; Decoster, Jeroen; Derom, Catherine; Thiery, Evert; Stefanis, Nikos C.; Sachs, Gabriele; Aschauer, Harald; Lasser, Iris; Winklbaur, Bernadette; Schlogelhofer, Monika; Riecher-Rossler, Anita; Borgwardt, Stefan; Walter, Anna; Harrisberger, Fabienne; Smieskova, Renata; Rapp, Charlotte; Ittig, Sarah; Soguel-Dit-Piquard, Fabienne; Studerus, Erich; Klosterkotter, Joachim; Ruhrmann, Stephan; Paruch, Julia; Julkowski, Dominika; Hilboll, Desiree; Sham, Pak C.; Cherny, Stacey S.; Chen, Eric Y. H.; Campbell, Desmond D.; Li, Miaoxin; Maria Romeo-Casabona, Carlos; Emaldi Cirion, Aitziber; Urruela Mora, Asier; Jones, Peter; Kirkbride, James; Cannon, Mary; Rujescu, Dan; Tarricone, Ilaria; Berardi, Domenico; Bonora, Elena; Seri, Marco; Marcacci, Thomas; Chiri, Luigi; Chierzi, Federico; Storbini, Viviana; Braca, Mauro; Minenna, Maria Gabriella; Donegani, Ivonne; Fioritti, Angelo; La Barbera, Daniele; La Cascia, Caterina Erika; Mule, Alice; Sideli, Lucia; Sartorio, Rachele; Ferraro, Laura; Tripoli, Giada; Seminerio, Fabio; Marinaro, Anna Maria; McGorry, Patrick; Nelson, Barnaby; Amminger, G. Paul; Pantelis, Christos; Menezes, Paulo R.; Del-Ben, Cristina M.; Tenan, Silvia H. Gallo; Shuhama, Rosana; Ruggeri, Mirella; Tosato, Sarah; Lasalvia, Antonio; Bonetto, Chiara; Ira, Elisa; Nordentoft, Merete; Krebs, Marie-Odile; Barrantes-Vidal, Neus; Cristobal, Paula; Kwapil, Thomas R.; Brietzke, Elisa; Bressan, Rodrigo A.; Gadelha, Ary; Maric, Nadja P.; Andric, Sanja; Mihaljevic, Marina; Mirjanic, Tijana

    2014-01-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular

  15. Gene Environment Interactions in Women With Breast and Secondary Lung Cancer

    Science.gov (United States)

    2006-07-01

    Komorowski,J., Bell,A.K., Downie ,I., Mooney,J., Verbeke,C., Bellamy,C., and Keith,W.N. (2005) Markers of adenocarcinoma characteristic of the site of...sensitivity. Am.J.Clin.Pathol., 123, 9-12. 107. Esteller,M., Corn ,P.G., Baylin,S.B., and Herman,J.G. (2001) A gene hypermethylation profile of human

  16. Coronary heart disease risk : family history and gene-environment interaction

    NARCIS (Netherlands)

    Boer, J.

    1999-01-01

    The first part of this thesis describes research into lifestyle, genetic, and biological factors that may underlie the increased risk for coronary heart disease (CHD) in individuals with a family history of this disorder. The second part of this thesis describes whether levels of plasma lipids and l

  17. Respiratory effects of endotoxin exposure : Individual susceptibility and gene-environment interactions

    NARCIS (Netherlands)

    Smit, L.A.|info:eu-repo/dai/nl/311470882

    2008-01-01

    Endotoxins are cell wall components of Gram-negative bacteria that occur commonly on plants and plant products and as gut commensals. A large variability in airborne endotoxin exposure levels has been measured in a range of agricultural and other occupational environments. Inhalation of endotoxins m

  18. Respiratory effects of endotoxin exposure : Individual susceptibility and gene-environment interactions

    NARCIS (Netherlands)

    Smit, L.A.

    2008-01-01

    Endotoxins are cell wall components of Gram-negative bacteria that occur commonly on plants and plant products and as gut commensals. A large variability in airborne endotoxin exposure levels has been measured in a range of agricultural and other occupational environments. Inhalation of endotoxins m

  19. Childhood problem behavior and parental divorce: evidence for gene-environment interaction

    NARCIS (Netherlands)

    S.C.C. Robbers (Sylvana); F.V.A. van Oort (Floor); A.C. Huizink (Anja); F.C. Verhulst (Frank); C.E.M. van Beijsterveldt (Toos); D.I. Boomsma (Dorret); M. Bartels (Meike)

    2012-01-01

    textabstractObjective: The importance of genetic and environmental influences on children's behavioral and emotional problems may vary as a function of environmental exposure. We previously reported that 12-year-olds with divorced parents showed more internalizing and externalizing problems than chi

  20. Gene-environment interplay in the link of friends' and nonfriends' behaviors with children's social reticence in a competitive situation.

    Science.gov (United States)

    Guimond, Fanny-Alexandra; Brendgen, Mara; Vitaro, Frank; Forget-Dubois, Nadine; Dionne, Ginette; Tremblay, Richard E; Boivin, Michel

    2014-03-01

    This study used a genetically informed design to assess the effects of friends' and nonfriends' reticent and dominant behaviors on children's observed social reticence in a competitive situation. Potential gene-environment correlations (rGE) and gene-environment interactions (GxE) in the link between (a) friends' and nonfriends' behaviors and (b) children's social reticence were examined. The sample comprised 466 twin children (i.e., the target children), each of whom was assessed in kindergarten together with a same-sex friend and two nonfriend classmates of either sex. Multilevel regression analyses revealed that children with a genetic disposition for social reticence showed more reticent behavior in the competitive situation and were more likely to affiliate with reticent friends (i.e., rGE). Moreover, a higher level of children's reticent behavior was predicted by their friends' higher social reticence (particularly for girls) and their friends' higher social dominance, independently of children's genetic disposition. Children's social reticence was also predicted by their nonfriends' behaviors. Specifically, children were less reticent when male nonfriends showed high levels of social reticence in the competitive situation, and this was particularly true for children with a genetic disposition for social reticence (i.e., GxE). Moreover, children genetically vulnerable for social reticence seemed to foster dominant behavior in their female nonfriend peers (i.e., rGE). In turn, male nonfriends seemed to be more dominant as soon as the target children were reticent, even if the target children did not have a stable genetic disposition for this behavior.

  1. Interacting with Stroke-Based Rendering on a Wall Display

    NARCIS (Netherlands)

    Grubert, Jens; Hanckock, Mark; Carpendale, Sheelagh; Tse, Edward; Isenberg, Tobias

    2007-01-01

    We introduce two new interaction techniques for creating and interacting with non-photorealistic images using stroke-based rendering. We provide bimanual control of a large interactive canvas through both remote pointing and direct touch. Remote pointing allows people to sit and interact at a distan

  2. Interacting with Stroke-Based Rendering on a Wall Display

    NARCIS (Netherlands)

    Grubert, Jens; Hanckock, Mark; Carpendale, Sheelagh; Tse, Edward; Isenberg, Tobias

    2007-01-01

    We introduce two new interaction techniques for creating and interacting with non-photorealistic images using stroke-based rendering. We provide bimanual control of a large interactive canvas through both remote pointing and direct touch. Remote pointing allows people to sit and interact at a

  3. Modeling, Designing, and Implementing an Avatar-based Interactive Map

    National Research Council Canada - National Science Library

    Stefan Andrei; Milin Joshi; Chandrakant Rudani; Ankur Shah; Bharatkumar Tejwani

    2016-01-01

    ...), has probably the highest level of interaction with the user. This article describes an innovative technique for designing an avatar-based virtual interactive map for the Lamar University Campus, which will entail the buildings...

  4. A review of gene-environment correlations and their implications for autism: a conceptual model.

    Science.gov (United States)

    Meek, Shantel E; Lemery-Chalfant, Kathryn; Jahromi, Laudan B; Valiente, Carlos

    2013-07-01

    A conceptual model is proposed that explains how gene-environment correlations and the multiplier effect function in the context of social development in individuals with autism. The review discusses the current state of autism genetic research, including its challenges, such as the genetic and phenotypic heterogeneity of the disorder, and its limitations, such as the lack of interdisciplinary work between geneticists and social scientists. We discuss literature on gene-environment correlations in the context of social development and draw implications for individuals with autism. The review expands upon genes, behaviors, types of environmental exposure, and exogenous variables relevant to social development in individuals on the autism spectrum, and explains these factors in the context of the conceptual model to provide a more in-depth understanding of how the effects of certain genetic variants can be multiplied by the environment to cause largely phenotypic individual differences. Using the knowledge gathered from gene-environment correlations and the multiplier effect, we outline novel intervention directions and implications.

  5. Designing Software-Based Interactive Installations

    DEFF Research Database (Denmark)

    Andreasen, Troels; Juul, Niels Christian; Rosendahl, Mads

    2014-01-01

    What. This chapter focuses on software engineering principles with specific emphasis on interactive installations providing embodied, tangible, and immersive experiences for the user. Such installations may deliver light, image, sound, and movement through actuators and may provide interaction...... installations and support the description of the approach with a single case- a bumper car competition. Why. To some extent, standard techniques for software development can be adapted for interactive installations. However, there is a need to emphasize the unique aspects of installations, bringing tangible...... architecture as well as esthetic experience, artistic expression, and leisure aspects into focus. The approach presented here has this intended purpose. Where. Building on experience from conventional software development and with inspiration from interaction design and creative programming, this chapter...

  6. Genetic interaction mapping with microfluidic-based single cell sequencing

    Science.gov (United States)

    Haliburton, John R.; Shao, Wenjun; Deutschbauer, Adam; Arkin, Adam; Abate, Adam R.

    2017-01-01

    Genetic interaction mapping is useful for understanding the molecular basis of cellular decision making, but elucidating interactions genome-wide is challenging due to the massive number of gene combinations that must be tested. Here, we demonstrate a simple approach to thoroughly map genetic interactions in bacteria using microfluidic-based single cell sequencing. Using single cell PCR in droplets, we link distinct genetic information into single DNA sequences that can be decoded by next generation sequencing. Our approach is scalable and theoretically enables the pooling of entire interaction libraries to interrogate multiple pairwise genetic interactions in a single culture. The speed, ease, and low-cost of our approach makes genetic interaction mapping viable for routine characterization, allowing the interaction network to be used as a universal read out for a variety of biology experiments, and for the elucidation of interaction networks in non-model organisms. PMID:28170417

  7. Repetition-based Interactive Facade Modeling

    KAUST Repository

    AlHalawani, Sawsan

    2012-07-01

    Modeling and reconstruction of urban environments has gained researchers attention throughout the past few years. It spreads in a variety of directions across multiple disciplines such as image processing, computer graphics and computer vision as well as in architecture, geoscience and remote sensing. Having a virtual world of our real cities is very attractive in various directions such as entertainment, engineering, governments among many others. In this thesis, we address the problem of processing a single fa cade image to acquire useful information that can be utilized to manipulate the fa cade and generate variations of fa cade images which can be later used for buildings\\' texturing. Typical fa cade structures exhibit a rectilinear distribution where in windows and other elements are organized in a grid of horizontal and vertical repetitions of similar patterns. In the firt part of this thesis, we propose an efficient algorithm that exploits information obtained from a single image to identify the distribution grid of the dominant elements i.e. windows. This detection method is initially assisted with the user marking the dominant window followed by an automatic process for identifying its repeated instances which are used to define the structure grid. Given the distribution grid, we allow the user to interactively manipulate the fa cade by adding, deleting, resizing or repositioning the windows in order to generate new fa cade structures. Having the utility for the interactive fa cade is very valuable to create fa cade variations and generate new textures for building models. Ultimately, there is a wide range of interesting possibilities of interactions to be explored.

  8. Gene-Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood: Is APOE a Variability Gene?

    Science.gov (United States)

    Reynolds, Chandra A; Gatz, Margaret; Christensen, Kaare; Christiansen, Lene; Dahl Aslan, Anna K; Kaprio, Jaakko; Korhonen, Tellervo; Kremen, William S; Krueger, Robert; McGue, Matt; Neiderhiser, Jenae M; Pedersen, Nancy L

    2016-01-01

    Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a 'variability gene' across these measures and whether it partly represents the 'G' in G×E effects. In all three domains, G×E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable-with both increasing and decreasing age-cohort trends-for different cognitive measures. Results also suggested that APOE may represent a 'variability gene' for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE.

  9. Physically-based interactive Schlieren flow visualization

    Energy Technology Data Exchange (ETDEWEB)

    Mccormick, Patrick S [Los Alamos National Laboratory; Brownlee, Carson S [Los Alamos National Laboratory; Pegoraro, Vincent [UNIV OF UTAH; Shankar, Siddharth [UNIV OF UTAH; Hansen, Charles D [UNIV OF UTAH

    2009-01-01

    Understanding fluid flow is a difficult problem and of increasing importance as computational fluid dynamics produces an abundance of simulation data. Experimental flow analysis has employed techniques such as shadowgraph and schlieren imaging for centuries which allow empirical observation of inhomogeneous flows. Shadowgraphs provide an intuitive way of looking at small changes in flow dynamics through caustic effects while schlieren cutoffs introduce an intensity gradation for observing large scale directional changes in the flow. The combination of these shading effects provides an informative global analysis of overall fluid flow. Computational solutions for these methods have proven too complex until recently due to the fundamental physical interaction of light refracting through the flow field. In this paper, we introduce a novel method to simulate the refraction of light to generate synthetic shadowgraphs and schlieren images of time-varying scalar fields derived from computational fluid dynamics (CFD) data. Our method computes physically accurate schlieren and shadowgraph images at interactive rates by utilizing a combination of GPGPU programming, acceleration methods, and data-dependent probabilistic schlieren cutoffs. Results comparing this method to previous schlieren approximations are presented.

  10. Telling interactive stories: A practice-based investigation into new media interactive storytelling

    OpenAIRE

    Atkinson, Sarah

    2009-01-01

    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University. Telling Interactive Stories is a practice-based thesis, which theoretically and practically probes the field of digital fictional interactive storytelling. The submission takes the form of the interactive cinema installation Crossed Lines together with a written element of the thesis which interrogates historical, contextual, theoretical, technical and critical aspects of the field of inte...

  11. 3-D interactive physically based micro world

    Science.gov (United States)

    Waters, Keith; Wang, SerKuang

    1990-08-01

    This paper describes an approach to synthetic three-dimensional object manipulation using three different haptic I/O devices in a virtual workspace on a graphics superworkstation. The devices involve the operator in unique mode8 of interaction that require positioning a six degree-of-freedom sensor, applying torques to a static ball, or creating interpreted hand ge8tures. With these devices, the user can select, rotate and deposit synthetic virtual objects in the micro world. The micro world is an "artificial reality" in which elementary physical forces of gravity, volume preservation, collision, and external user input may be applied. The techniques developed overcome some of the difficulties experienced with two-dimensional input devices in a three-dimensional space. Furthermore, the ability of the user to continuous modify physical constraints while observing the results in real-time facilitates data interpretation tasks.

  12. Adaptive Game Level Creation through Rank-based Interactive Evolution

    DEFF Research Database (Denmark)

    Liapis, Antonios; Martínez, Héctor Pérez; Togelius, Julian

    2013-01-01

    This paper introduces Rank-based Interactive Evolution (RIE) which is an alternative to interactive evolution driven by computational models of user preferences to generate personalized content. In RIE, the computational models are adapted to the preferences of users which, in turn, are used as f...

  13. An agent-based architecture for multimodal interaction

    NARCIS (Netherlands)

    Jonker, C.M.; Treur, J.; Wijngaards, W.C.A.

    2001-01-01

    In this paper, an executable generic process model is proposed for combined verbal and non-verbal communication processes and their interaction. The agent-based architecture can be used to create multimodal interaction. The generic process model has been designed, implemented and used to simulate

  14. On Interactive Teaching Model of Translation Course Based on Wechat

    Science.gov (United States)

    Lin, Wang

    2017-01-01

    Constructivism is a theory related to knowledge and learning, focusing on learners' subjective initiative, based on which the interactive approach has been proved to play a crucial role in language learning. Accordingly, the interactive approach can also be applied to translation teaching since translation itself is a bilingual transformational…

  15. A Usability Study of Interactive Web-Based Modules

    Science.gov (United States)

    Girard, Tulay; Pinar, Musa

    2011-01-01

    This research advances the understanding of the usability of marketing case study modules in the area of interactive web-based technologies through the assignment of seven interactive case modules in a Principles of Marketing course. The case modules were provided for marketing students by the publisher, McGraw Hill Irwin, of the…

  16. Identity-based Encryption with Non-Interactive Opening

    Institute of Scientific and Technical Information of China (English)

    FAN Jia; TANG Xiao-hu; KANG Li; LU Xian-hui

    2008-01-01

    An identity-based encryption (IBE) was studied with non-interactively opening property that the plain text of a ciphertext can be revealed without affecting the security of the encryption system.Two kinds of non-interactive opening properties for IBE schemes were defined along with a concrete scheme in each case.

  17. An agent-based architecture for multimodal interaction

    NARCIS (Netherlands)

    Jonker, C.M.; Treur, J.; Wijngaards, W.C.A.

    2001-01-01

    In this paper, an executable generic process model is proposed for combined verbal and non-verbal communication processes and their interaction. The agent-based architecture can be used to create multimodal interaction. The generic process model has been designed, implemented and used to simulate di

  18. Helium-3 Microscopic Optical Model Potential Based on Skyrme Interaction

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>The helium-3 microscopic optical potential is obtained by Green function method through nuclear matter approximation and local density approximation based on the effective Skyrme interaction. The reaction cross

  19. Interactive Excel-Based Gantt Chart Schedule Builder

    National Research Council Canada - National Science Library

    2017-01-01

    .... In this paper, we present an interactive Excel-based Gantt Chart Schedule builder that enables students to experiment with building schedules for different single and parallel machine problem examples...

  20. EyeScreen: A Vision-Based Gesture Interaction System

    Institute of Scientific and Technical Information of China (English)

    LI Shan-qing; XU Yi-hua; JIA Yun-de

    2007-01-01

    EyeScreen is a vision-based interaction system which provides a natural gesture interface for human-computer interaction (HCI) by tracking human fingers and recognizing gestures. Multi-view video images are captured by two cameras facing a computer screen, which can be used to detect clicking actions of a fingertip and improve the recognition rate. The system enables users to directly interact with rendered objects on the screen. Robustness of the system has been verified by extensive experiments with different user scenarios. EyeScreen can be used in many applications such as intelligent interaction and digital entertainment.

  1. Multiquadric Spline-Based Interactive Segmentation of Vascular Networks.

    Science.gov (United States)

    Meena, Sachin; Surya Prasath, V B; Kassim, Yasmin M; Maude, Richard J; Glinskii, Olga V; Glinsky, Vladislav V; Huxley, Virginia H; Palaniappan, Kannappan

    2016-08-01

    Commonly used drawing tools for interactive image segmentation and labeling include active contours or boundaries, scribbles, rectangles and other shapes. Thin vessel shapes in images of vascular networks are difficult to segment using automatic or interactive methods. This paper introduces the novel use of a sparse set of user-defined seed points (supervised labels) for precisely, quickly and robustly segmenting complex biomedical images. A multiquadric spline-based binary classifier is proposed as a unique approach for interactive segmentation using as features color values and the location of seed points. Epifluorescence imagery of the dura mater microvasculature are difficult to segment for quantitative applications due to challenging tissue preparation, imaging conditions, and thin, faint structures. Experimental results based on twenty epifluorescence images is used to illustrate the benefits of using a set of seed points to obtain fast and accurate interactive segmentation compared to four interactive and automatic segmentation approaches.

  2. Interactive Internet Based Pendulum for Learning Mechatronics

    Science.gov (United States)

    Sethson, Magnus R.

    2003-01-01

    This paper describes an Internet based remote experimental setup of a double lined pendulum mechanism for students experiments at the M. Sc. Level. Some of the first year experience using this web-based setup in classes is referred. In most of the courses given at the division of mechanical engineering systems at Linkoeping Institute of Technology we provide experimental setups to enhance the teaching Of M.Sc. students. Many of these experimental setups involve mechatronical systems. Disciplines like fluid power, electronics, and mechanics and also software technologies are used in each experiment. As our campus has recently been split into two different cities some new concepts for distance learning have been studied. The one described here tries to implement remotely controlled mechatronic setups for teaching basic programming of real-time operating systems and analysis of the dynamics of mechanical systems. The students control the regulators for the pendulum through a web interface and get measurement results and a movie back through their email. The present setup uses a double linked pendulum that is controlled by a DC-motor and monitored through both camera and angular position sensors. All software needed is hosted on a double-processor PC running the RedHat 7.1. distribution complemented with real-time scheduling using DIAPM-RTAI 1.7. The Internet site is presented to the students using PHP, Apache and MySQL. All of the used software originates from the open source domain. The experience from integrating these technologies and security issues is discussed together with the web-camera interface. One of the important experiences from this project so far is the need for a good visual feedback. This is both in terms of video speed but also in resolution. It has been noticed that when the students makes misstates and wants to search the failure they want clear, large images with high resolution to support their personal believes in the cause of the failure. Even

  3. Individual versus Interactive Task-Based Performance through Voice-Based Computer-Mediated Communication

    Science.gov (United States)

    Granena, Gisela

    2016-01-01

    Interaction is a necessary condition for second language (L2) learning (Long, 1980, 1996). Research in computer-mediated communication has shown that interaction opportunities make learners pay attention to form in a variety of ways that promote L2 learning. This research has mostly investigated text-based rather than voice-based interaction. The…

  4. Gallium based low-interaction anions

    Science.gov (United States)

    King, Wayne A.; Kubas, Gregory J.

    2000-01-01

    The present invention provides: a composition of the formula M.sup.+x (Ga(Y).sub.4.sup.-).sub.x where M is a metal selected from the group consisting of lithium, sodium, potassium, cesium, calcium, strontium, thallium, and silver, x is an integer selected from the group consisting of 1 or 2, each Y is a ligand selected from the group consisting of aryl, alkyl, hydride and halide with the proviso that at least one Y is a ligand selected from the group consisting of aryl, alkyl and halide; a composition of the formula (R).sub.x Q.sup.+ Ga(Y).sub.4.sup.- where Q is selected from the group consisting of carbon, nitrogen, sulfur, phosphorus and oxygen, each R is a ligand selected from the group consisting of alkyl, aryl, and hydrogen, x is an integer selected from the group consisting of 3 and 4 depending upon Q, and each Y is a ligand selected from the group consisting of aryl, alkyl, hydride and halide with the proviso that at least one Y is a ligand selected from the group consisting of aryl, alkyl and halide; an ionic polymerization catalyst composition including an active cationic portion and a gallium based weakly coordinating anion; and bridged anion species of the formula M.sup.+x.sub.y [X(Ga(Y.sub.3).sub.z ].sup.-y.sub.x where M is a metal selected from the group consisting of lithium, sodium, potassium, magnesium, cesium, calcium, strontium, thallium, and silver, x is an integer selected from the group consisting of 1 or 2, X is a bridging group between two gallium atoms, y is an integer selected from the group consisting 1 and 2, z is an integer of at least 2, each Y is a ligand selected from the group consisting of aryl, alkyl, hydride and halide with the proviso that at least one Y is a ligand selected from the group consisting of aryl, alkyl and halide.

  5. Modeling, Designing, and Implementing an Avatar-based Interactive Map

    Directory of Open Access Journals (Sweden)

    Stefan Andrei

    2016-03-01

    Full Text Available Designing interactive maps has always been a challenge due to the geographical complexity of the earth’s landscape and the difficulty of resolving details to a high resolution. In the past decade or so, one of the most impressive map-based software application, the Global Positioning System (GPS, has probably the highest level of interaction with the user. This article describes an innovative technique for designing an avatar-based virtual interactive map for the Lamar University Campus, which will entail the buildings’ exterior as well as their interiors. Many universities provide 2D or 3D maps and even interactive maps. However, these maps do not provide a complete interaction with the user. To the best of our knowledge, this project is the first avatar-based interaction game that allows 100% interaction with the user. This work provides tremendous help to the freshman students and visitors of Lamar University. As an important marketing tool, the main objective is to get better visibility of the campus worldwide and to increase the number of students attending Lamar University.

  6. An Interactive Tool for Creating Multi-Agent Systems and Interactive Agent-based Games

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop; Pagliarini, Luigi

    2011-01-01

    Utilizing principles from parallel and distributed processing combined with inspiration from modular robotics, we developed the modular interactive tiles. As an educational tool, the modular interactive tiles facilitate the learning of multi-agent systems and interactive agent-based games....... The modular and physical property of the tiles provides students with hands-on experience in exploring the theoretical aspects underlying multi-agent systems which often appear as challenging to students. By changing the representation of the cognitive challenging aspects of multi-agent systems education...

  7. Theoretical analysis of noncanonical base pairing interactions in RNA molecules

    Indian Academy of Sciences (India)

    Dhananjay Bhattacharyya; Siv Chand Koripella; Abhijit Mitra; Vijay Babu Rajendran; Bhabdyuti Sinha

    2007-08-01

    Noncanonical base pairs in RNA have strong structural and functional implications but are currently not considered for secondary structure predictions. We present results of comparative ab initio studies of stabilities and interaction energies for the three standard and 24 selected unusual RNA base pairs reported in the literature. Hydrogen added models of isolated base pairs, with heavy atoms frozen in their ‘away from equilibrium’ geometries, built from coordinates extracted from NDB, were geometry optimized using HF/6-31G** basis set, both before and after unfreezing the heavy atoms. Interaction energies, including BSSE and deformation energy corrections, were calculated, compared with respective single point MP2 energies, and correlated with occurrence frequencies and with types and geometries of hydrogen bonding interactions. Systems having two or more N-H…O/N hydrogen bonds had reasonable interaction energies which correlated well with respective occurrence frequencies and highlighted the possibility of some of them playing important roles in improved secondary structure prediction methods. Several of the remaining base pairs with one N-H…O/N and/or one C-H…O/N interactions respectively, had poor interaction energies and negligible occurrences. High geometry variations on optimization of some of these were suggestive of their conformational switch like characteristics.

  8. Interactive Coherence-Based Façade Modeling

    KAUST Repository

    Musialski, Przemyslaw

    2012-05-01

    We propose a novel interactive framework for modeling building facades from images. Our method is based on the notion of coherence-based editing which allows exploiting partial symmetries across the facade at any level of detail. The proposed workflow mixes manual interaction with automatic splitting and grouping operations based on unsupervised cluster analysis. In contrast to previous work, our approach leads to detailed 3d geometric models with up to several thousand regions per facade. We compare our modeling scheme to others and evaluate our approach in a user study with an experienced user and several novice users.

  9. Movement-based interaction in camera spaces: a conceptual framework

    DEFF Research Database (Denmark)

    Eriksson, Eva; Hansen, Thomas Riisgaard; Lykke-Olesen, Andreas

    2007-01-01

    In this paper we present three concepts that address movement-based interaction using camera tracking. Based on our work with several movementbased projects we present four selected applications, and use these applications to leverage our discussion, and to describe our three main concepts space,...

  10. Interacting with Visual Poems through AR-Based Digital Artwork

    Science.gov (United States)

    Lin, Hao-Chiang Koong; Hsieh, Min-Chai; Liu, Eric Zhi-Feng; Chuang, Tsung-Yen

    2012-01-01

    In this study, an AR-based digital artwork called "Mind Log" was designed and evaluated. The augmented reality technique was employed to create digital artwork that would present interactive poems. A digital poem was generated via the interplay between a video film and a text-based poem. This artwork was created following a rigorous design flow,…

  11. Learner Attention to Form in ACCESS Task-Based Interaction

    Science.gov (United States)

    Dao, Phung; Iwashita, Noriko; Gatbonton, Elizabeth

    2017-01-01

    This study explored the potential effects of communicative tasks developed using a reformulation of a task-based language teaching called Automatization in Communicative Contexts of Essential Speech Sequences (ACCESS) that includes automatization of language elements as one of its goals on learner attention to form in task-based interaction. The…

  12. Interactive Multimedia Synchronization Model Based on Petri Nets

    Institute of Scientific and Technical Information of China (English)

    WANG Zhiqiang; PENG Xiaogang; JI Zhen

    2007-01-01

    The multimedia synchronization is used to coordinate the timing of each multimedia object in the multimedia system.After studying different multimedia synchronization systems that have been published, an Interactive Synchronization multimedia based on Petri Nets model (ISPN) is proposed in this paper. The system is capable of describing the dynamic timing actions of multimedia objects vividly as well as controlling them interactively to maintain the system level synchronization balance.

  13. Adaptive Game Level Creation through Rank-based Interactive Evolution

    DEFF Research Database (Denmark)

    Liapis, Antonios; Martínez, Héctor Pérez; Togelius, Julian

    2013-01-01

    as fitness functions for the optimization of the generated content. The preference models are built via ranking-based preference learning, while the content is generated via evolutionary search. The proposed method is evaluated on the creation of strategy game maps, and its performance is tested using...... artificial agents. Results suggest that RIE is both faster and more robust than standard interactive evolution and outperforms other state-of-the-art interactive evolution approaches....

  14. RNA-RNA interaction prediction based on multiple sequence alignments

    CERN Document Server

    Li, Andrew X; Qin, Jing; Reidys, Christian M

    2010-01-01

    Recently, $O(N^6)$ time and $O(N^4)$ space dynamic programming algorithms have become available that compute the partition function of RNA-RNA interaction complexes for pairs of RNA sequences. These algorithms and the biological requirement of more reliable interactions motivate to utilize the additional information contained in multiple sequence alignments and to generalize the above framework to the partition function and base pairing probabilities for multiple sequence alignments.

  15. ACID-BASE INTERACTIONS BETWEEN POLYMERS AND FILLERS

    Institute of Scientific and Technical Information of China (English)

    WANG Qingguo; CHEN Fute; HUANG Yuanfu; ZHOU Qingli

    1987-01-01

    Inverse gas chromatography(IGC) and Fourier-transform infrared (FT-IR) techniques were applied to determining the relative acid-base strength of polymers and coupling agents. The acid-base characteristics of fillers such as CaCO3 could be altered by treatment with different coupling agents. It was shown that some mechanical properties of filled polymers were obviously associated with acid-base interactions between polymers and fillers.

  16. Cyberpsychology: a human-interaction perspective based on cognitive modeling.

    Science.gov (United States)

    Emond, Bruno; West, Robert L

    2003-10-01

    This paper argues for the relevance of cognitive modeling and cognitive architectures to cyberpsychology. From a human-computer interaction point of view, cognitive modeling can have benefits both for theory and model building, and for the design and evaluation of sociotechnical systems usability. Cognitive modeling research applied to human-computer interaction has two complimentary objectives: (1) to develop theories and computational models of human interactive behavior with information and collaborative technologies, and (2) to use the computational models as building blocks for the design, implementation, and evaluation of interactive technologies. From the perspective of building theories and models, cognitive modeling offers the possibility to anchor cyberpsychology theories and models into cognitive architectures. From the perspective of the design and evaluation of socio-technical systems, cognitive models can provide the basis for simulated users, which can play an important role in usability testing. As an example of application of cognitive modeling to technology design, the paper presents a simulation of interactive behavior with five different adaptive menu algorithms: random, fixed, stacked, frequency based, and activation based. Results of the simulation indicate that fixed menu positions seem to offer the best support for classification like tasks such as filing e-mails. This research is part of the Human-Computer Interaction, and the Broadband Visual Communication research programs at the National Research Council of Canada, in collaboration with the Carleton Cognitive Modeling Lab at Carleton University.

  17. Links between Friends' Physical Aggression and Adolescents' Physical Aggression: What Happens If Gene-Environment Correlations are Controlled?

    Science.gov (United States)

    Vitaro, Frank; Brendgen, Mara; Girard, Alain; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2016-01-01

    Exposure to deviant friends has been found to be a powerful source of influence on children's and adolescents' aggressive behavior. However, the contribution of deviant friends may have been overestimated because of a possible non-accounted gene-environment correlation (rGE). In this study, we used a cross-lagged design to test whether friends'…

  18. Assessing Bacterial Interactions Using Carbohydrate-Based Microarrays

    Directory of Open Access Journals (Sweden)

    Andrea Flannery

    2015-12-01

    Full Text Available Carbohydrates play a crucial role in host-microorganism interactions and many host glycoconjugates are receptors or co-receptors for microbial binding. Host glycosylation varies with species and location in the body, and this contributes to species specificity and tropism of commensal and pathogenic bacteria. Additionally, bacterial glycosylation is often the first bacterial molecular species encountered and responded to by the host system. Accordingly, characterising and identifying the exact structures involved in these critical interactions is an important priority in deciphering microbial pathogenesis. Carbohydrate-based microarray platforms have been an underused tool for screening bacterial interactions with specific carbohydrate structures, but they are growing in popularity in recent years. In this review, we discuss carbohydrate-based microarrays that have been profiled with whole bacteria, recombinantly expressed adhesins or serum antibodies. Three main types of carbohydrate-based microarray platform are considered; (i conventional carbohydrate or glycan microarrays; (ii whole mucin microarrays; and (iii microarrays constructed from bacterial polysaccharides or their components. Determining the nature of the interactions between bacteria and host can help clarify the molecular mechanisms of carbohydrate-mediated interactions in microbial pathogenesis, infectious disease and host immune response and may lead to new strategies to boost therapeutic treatments.

  19. Online approach to feature interaction problems in middleware based system

    Institute of Scientific and Technical Information of China (English)

    HUANG Gang; LIU XuanZhe; MEI Hong

    2008-01-01

    As a popular infrastructure for distributed systems running on the Internet, middle-ware has to support much more diverse and complex interactions for coping with the drastically increasing demand on information technology and the extremely open and dynamic nature of the Internet. These supporting mechanisms facilitate the development, deployment, and integration of distributed systems, as well as increase the occasions for distributed systems to interact in an undesired way. The undesired interactions may cause serious problems, such as quality violation, function loss, and even system crash. In this paper, the problem is studied from the perspective of the feature interaction problem (FIP) in telecom, and an online ap-proach to the detection and solution on runtime systems is proposed. Based on a classification of middleware enabled interactions, the existence of FIP in middle-ware based systems is illustrated by four real cases and a conceptual comparison between middleware based systems and telecom systems. After that, runtime soft-ware architecture is employed to facilitate the online detection and solution of FIP. The approach is demonstrated on J2EE (Java 2 Platform Enterprise Edition) and applied to detect and resolve all of the four real cases.

  20. The Design of Tools for Sketching Sensor-Based Interaction

    DEFF Research Database (Denmark)

    Brynskov, Martin; Lunding, Rasmus; Vestergaard, Lasse Steenbock

    2012-01-01

    In this paper we motivate, present, and give an initial evaluation of DUL Radio, a small wireless toolkit for sketching sensor-based interaction. In the motivation, we discuss the purpose of this specific platform, which aims to balance ease-of-use (learning, setup, initialization), size, speed......, flexibility and cost, aimed at wearable and ultra-mobile prototyping where fast reaction is needed (e.g. in controlling sound), and we discuss the general issues facing this category of embodied interaction design tools. We then present the platform in more detail, both regarding hard- ware and software....... In the brief evaluation, we present our initial experiences with the platform both in design projects and in teaching. We conclude that DUL Radio does seem to be a relatively easy-to-use tool for sketching sensor-based interaction compared to other solutions, but that there are many ways to improve it. Target...

  1. Computer-Based Interaction Analysis with DEGREE Revisited

    Science.gov (United States)

    Barros, B.; Verdejo, M. F.

    2016-01-01

    We review our research with "DEGREE" and analyse how our work has impacted the collaborative learning community since 2000. Our research is framed within the context of computer-based interaction analysis and the development of computer-supported collaborative learning (CSCL) tools. We identify some aspects of our work which have been…

  2. Interactions between acid- and base-functionalized surfaces

    NARCIS (Netherlands)

    Giesbers, M.; Kleijn, J.M.; Cohen Stuart, M.A.

    2002-01-01

    In this paper we present an AFM force study on interactions between chemically modified surfaces. Surfaces with terminal groups of either NH2 or COOH were obtained by chemisorption of a silane-based compound (3-amino-propyltriethoxysilane) on silica or a thiol compound (11-mercapto undecanoic acid)

  3. Observations on Experience and Flow in Movement-Based Interaction

    NARCIS (Netherlands)

    Nijholt, Anton; Pasch, Marco; Dijk, van Betsy; Reidsma, Dennis; Heylen, Dirk; England, David

    2011-01-01

    Movement-based interfaces assume that their users move. Users have to perform exercises, they have to dance, they have to golf or football, or they want to train particular bodily skills. Many examples of those interfaces exist, sometimes asking for subtle interaction between user and interface and

  4. Map-based mobile services design, interaction and usability

    CERN Document Server

    Meng, Liqiu; Winter, Stephan; Popovich, Vasily

    2008-01-01

    This book reports the newest research and technical achievements on the following theme blocks: Design of mobile map services and its constraints; Typology and usability of mobile map services; Visualization solutions on small displays for time-critical tasks; Mobile map users; Interaction and adaptation in mobile environments; and Applications of map-based mobile services.

  5. Base flow and exhaust plume interaction. Part 1: Experimental study

    NARCIS (Netherlands)

    Schoones, M.M.J.; Bannink, W.J.

    1998-01-01

    An experimental study of the flow field along an axi-symmetric body with a single operating exhaust nozzle has been performed in the scope of an investigation on base flow-jet plume interactions. The structure of under-expanded jets in a co-flowing supersonic free stream was described using analytic

  6. Assessing protein-protein interactions based on the semantic similarity of interacting proteins.

    Science.gov (United States)

    Cui, Guangyu; Kim, Byungmin; Alguwaizani, Saud; Han, Kyungsook

    2015-01-01

    The Gene Ontology (GO) has been used in estimating the semantic similarity of proteins since it has the largest and reliable vocabulary of gene products and characteristics. We developed a new method which can assess Protein-Protein Interactions (PPI) using the branching factor and information content of the common ancestor of interacting proteins in the GO hierarchy. We performed a comparative evaluation of the measure with other GO-based similarity measures and evaluation results showed that our method outperformed others in most GO domains.

  7. An Interactive Multimedia Based Instruction in Experimental Modelling

    DEFF Research Database (Denmark)

    Knudsen, Morten; Nielsen, J.N.; Østergaard, J.

    1997-01-01

    A CD-ROM based interactive multimedia instruction in experimental modelling for Danish Engineering School teachers is described. The content is based on a new sensitivity approach for direct estimation of physical parameters in linear and nonlinear dynamic systems. The presentation is inspired...... of Solomans=s inventory of learning styles. To enhance active learning and motivation by real life problems, the simulation tool Matlab is integrated in the authoring program Medi8or....

  8. Why does parental language input style predict child language development? A twin study of gene-environment correlation.

    Science.gov (United States)

    Dale, Philip S; Tosto, Maria Grazia; Hayiou-Thomas, Marianna E; Plomin, Robert

    2015-01-01

    There are well-established correlations between parental input style and child language development, which have typically been interpreted as evidence that the input style causes, or influences the rate of, changes in child language. We present evidence from a large twin study (TEDS; 8395 pairs for this report) that there are also likely to be both child-to-parent effects and shared genetic effects on parent and child. Self-reported parental language style at child age 3 and age 4 was aggregated into an 'informal language stimulation' factor and a 'corrective feedback' factor at each age; the former was positively correlated with child language concurrently and longitudinally at 3, 4, and 4.5 years, whereas the latter was weakly and negatively correlated. Both parental input factors were moderately heritable, as was child language. Longitudinal bivariate analysis showed that the correlation between the language stimulation factor and child language was significantly and moderately due to shared genes. There is some suggestive evidence from longitudinal phenotypic analysis that the prediction from parental language stimulation to child language includes both evocative and passive gene-environment correlation, with the latter playing a larger role. The reader will understand why correlations between parental language and rate of child language are by themselves ambiguous, and how twin studies can clarify the relationship. The reader will also understand that, based on the present study, at least two aspects of parental language style - informal language stimulation and corrective feedback - have substantial genetic influence, and that for informal language stimulation, a substantial portion of the prediction to child language represents the effect of shared genes on both parent and child. It will also be appreciated that these basic research findings do not imply that parental language input style is unimportant or that interventions cannot be effective. Copyright

  9. Protein-protein interaction based on pairwise similarity

    Directory of Open Access Journals (Sweden)

    Zaki Nazar

    2009-05-01

    Full Text Available Abstract Background Protein-protein interaction (PPI is essential to most biological processes. Abnormal interactions may have implications in a number of neurological syndromes. Given that the association and dissociation of protein molecules is crucial, computational tools capable of effectively identifying PPI are desirable. In this paper, we propose a simple yet effective method to detect PPI based on pairwise similarity and using only the primary structure of the protein. The PPI based on Pairwise Similarity (PPI-PS method consists of a representation of each protein sequence by a vector of pairwise similarities against large subsequences of amino acids created by a shifting window which passes over concatenated protein training sequences. Each coordinate of this vector is typically the E-value of the Smith-Waterman score. These vectors are then used to compute the kernel matrix which will be exploited in conjunction with support vector machines. Results To assess the ability of the proposed method to recognize the difference between "interacted" and "non-interacted" proteins pairs, we applied it on different datasets from the available yeast saccharomyces cerevisiae protein interaction. The proposed method achieved reasonable improvement over the existing state-of-the-art methods for PPI prediction. Conclusion Pairwise similarity score provides a relevant measure of similarity between protein sequences. This similarity incorporates biological knowledge about proteins and it is extremely powerful when combined with support vector machine to predict PPI.

  10. Traffic and Driving Simulator Based on Architecture of Interactive Motion.

    Science.gov (United States)

    Paz, Alexander; Veeramisti, Naveen; Khaddar, Romesh; de la Fuente-Mella, Hanns; Modorcea, Luiza

    2015-01-01

    This study proposes an architecture for an interactive motion-based traffic simulation environment. In order to enhance modeling realism involving actual human beings, the proposed architecture integrates multiple types of simulation, including: (i) motion-based driving simulation, (ii) pedestrian simulation, (iii) motorcycling and bicycling simulation, and (iv) traffic flow simulation. The architecture has been designed to enable the simulation of the entire network; as a result, the actual driver, pedestrian, and bike rider can navigate anywhere in the system. In addition, the background traffic interacts with the actual human beings. This is accomplished by using a hybrid mesomicroscopic traffic flow simulation modeling approach. The mesoscopic traffic flow simulation model loads the results of a user equilibrium traffic assignment solution and propagates the corresponding traffic through the entire system. The microscopic traffic flow simulation model provides background traffic around the vicinities where actual human beings are navigating the system. The two traffic flow simulation models interact continuously to update system conditions based on the interactions between actual humans and the fully simulated entities. Implementation efforts are currently in progress and some preliminary tests of individual components have been conducted. The implementation of the proposed architecture faces significant challenges ranging from multiplatform and multilanguage integration to multievent communication and coordination.

  11. Traffic and Driving Simulator Based on Architecture of Interactive Motion

    Directory of Open Access Journals (Sweden)

    Alexander Paz

    2015-01-01

    Full Text Available This study proposes an architecture for an interactive motion-based traffic simulation environment. In order to enhance modeling realism involving actual human beings, the proposed architecture integrates multiple types of simulation, including: (i motion-based driving simulation, (ii pedestrian simulation, (iii motorcycling and bicycling simulation, and (iv traffic flow simulation. The architecture has been designed to enable the simulation of the entire network; as a result, the actual driver, pedestrian, and bike rider can navigate anywhere in the system. In addition, the background traffic interacts with the actual human beings. This is accomplished by using a hybrid mesomicroscopic traffic flow simulation modeling approach. The mesoscopic traffic flow simulation model loads the results of a user equilibrium traffic assignment solution and propagates the corresponding traffic through the entire system. The microscopic traffic flow simulation model provides background traffic around the vicinities where actual human beings are navigating the system. The two traffic flow simulation models interact continuously to update system conditions based on the interactions between actual humans and the fully simulated entities. Implementation efforts are currently in progress and some preliminary tests of individual components have been conducted. The implementation of the proposed architecture faces significant challenges ranging from multiplatform and multilanguage integration to multievent communication and coordination.

  12. WAVE: Interactive Wave-based Sound Propagation for Virtual Environments.

    Science.gov (United States)

    Mehra, Ravish; Rungta, Atul; Golas, Abhinav; Ming Lin; Manocha, Dinesh

    2015-04-01

    We present an interactive wave-based sound propagation system that generates accurate, realistic sound in virtual environments for dynamic (moving) sources and listeners. We propose a novel algorithm to accurately solve the wave equation for dynamic sources and listeners using a combination of precomputation techniques and GPU-based runtime evaluation. Our system can handle large environments typically used in VR applications, compute spatial sound corresponding to listener's motion (including head tracking) and handle both omnidirectional and directional sources, all at interactive rates. As compared to prior wave-based techniques applied to large scenes with moving sources, we observe significant improvement in runtime memory. The overall sound-propagation and rendering system has been integrated with the Half-Life 2 game engine, Oculus-Rift head-mounted display, and the Xbox game controller to enable users to experience high-quality acoustic effects (e.g., amplification, diffraction low-passing, high-order scattering) and spatial audio, based on their interactions in the VR application. We provide the results of preliminary user evaluations, conducted to study the impact of wave-based acoustic effects and spatial audio on users' navigation performance in virtual environments.

  13. Web-based Interactive Landform Simulation Model - Grand Canyon

    Science.gov (United States)

    Luo, W.; Pelletier, J. D.; Duffin, K.; Ormand, C. J.; Hung, W.; Iverson, E. A.; Shernoff, D.; Zhai, X.; Chowdary, A.

    2013-12-01

    Earth science educators need interactive tools to engage and enable students to better understand how Earth systems work over geologic time scales. The evolution of landforms is ripe for interactive, inquiry-based learning exercises because landforms exist all around us. The Web-based Interactive Landform Simulation Model - Grand Canyon (WILSIM-GC, http://serc.carleton.edu/landform/) is a continuation and upgrade of the simple cellular automata (CA) rule-based model (WILSIM-CA, http://www.niu.edu/landform/) that can be accessed from anywhere with an Internet connection. Major improvements in WILSIM-GC include adopting a physically based model and the latest Java technology. The physically based model is incorporated to illustrate the fluvial processes involved in land-sculpting pertaining to the development and evolution of one of the most famous landforms on Earth: the Grand Canyon. It is hoped that this focus on a famous and specific landscape will attract greater student interest and provide opportunities for students to learn not only how different processes interact to form the landform we observe today, but also how models and data are used together to enhance our understanding of the processes involved. The latest development in Java technology (such as Java OpenGL for access to ubiquitous fast graphics hardware, Trusted Applet for file input and output, and multithreaded ability to take advantage of modern multi-core CPUs) are incorporated into building WILSIM-GC and active, standards-aligned curricula materials guided by educational psychology theory on science learning will be developed to accompany the model. This project is funded NSF-TUES program.

  14. Deep-Learning-Based Drug-Target Interaction Prediction.

    Science.gov (United States)

    Wen, Ming; Zhang, Zhimin; Niu, Shaoyu; Sha, Haozhi; Yang, Ruihan; Yun, Yonghuan; Lu, Hongmei

    2017-03-13

    Identifying interactions between known drugs and targets is a major challenge in drug repositioning. In silico prediction of drug-target interaction (DTI) can speed up the expensive and time-consuming experimental work by providing the most potent DTIs. In silico prediction of DTI can also provide insights about the potential drug-drug interaction and promote the exploration of drug side effects. Traditionally, the performance of DTI prediction depends heavily on the descriptors used to represent the drugs and the target proteins. In this paper, to accurately predict new DTIs between approved drugs and targets without separating the targets into different classes, we developed a deep-learning-based algorithmic framework named DeepDTIs. It first abstracts representations from raw input descriptors using unsupervised pretraining and then applies known label pairs of interaction to build a classification model. Compared with other methods, it is found that DeepDTIs reaches or outperforms other state-of-the-art methods. The DeepDTIs can be further used to predict whether a new drug targets to some existing targets or whether a new target interacts with some existing drugs.

  15. An Opinion Interactive Model Based on Individual Persuasiveness.

    Science.gov (United States)

    Zhou, Xin; Chen, Bin; Liu, Liang; Ma, Liang; Qiu, Xiaogang

    2015-01-01

    In order to study the formation process of group opinion in real life, we put forward a new opinion interactive model based on Deffuant model and its improved models in this paper because current models of opinion dynamics lack considering individual persuasiveness. Our model has following advantages: firstly persuasiveness is added to individual's attributes reflecting the importance of persuasiveness, which means that all the individuals are different from others; secondly probability is introduced in the course of interaction which simulates the uncertainty of interaction. In Monte Carlo simulation experiments, sensitivity analysis including the influence of randomness, initial persuasiveness distribution, and number of individuals is studied at first; what comes next is that the range of common opinion based on the initial persuasiveness distribution can be predicted. Simulation experiment results show that when the initial values of agents are fixed, no matter how many times independently replicated experiments, the common opinion will converge at a certain point; however the number of iterations will not always be the same; the range of common opinion can be predicted when initial distribution of opinion and persuasiveness are given. As a result, this model can reflect and interpret some phenomena of opinion interaction in realistic society.

  16. Violent Interaction Detection in Video Based on Deep Learning

    Science.gov (United States)

    Zhou, Peipei; Ding, Qinghai; Luo, Haibo; Hou, Xinglin

    2017-06-01

    Violent interaction detection is of vital importance in some video surveillance scenarios like railway stations, prisons or psychiatric centres. Existing vision-based methods are mainly based on hand-crafted features such as statistic features between motion regions, leading to a poor adaptability to another dataset. En lightened by the development of convolutional networks on common activity recognition, we construct a FightNet to represent the complicated visual violence interaction. In this paper, a new input modality, image acceleration field is proposed to better extract the motion attributes. Firstly, each video is framed as RGB images. Secondly, optical flow field is computed using the consecutive frames and acceleration field is obtained according to the optical flow field. Thirdly, the FightNet is trained with three kinds of input modalities, i.e., RGB images for spatial networks, optical flow images and acceleration images for temporal networks. By fusing results from different inputs, we conclude whether a video tells a violent event or not. To provide researchers a common ground for comparison, we have collected a violent interaction dataset (VID), containing 2314 videos with 1077 fight ones and 1237 no-fight ones. By comparison with other algorithms, experimental results demonstrate that the proposed model for violent interaction detection shows higher accuracy and better robustness.

  17. An Integrated Approach for Creating Service-Based Interactive Applications

    Science.gov (United States)

    Feldmann, Marius; Janeiro, Jordan; Nestler, Tobias; Hübsch, Gerald; Jugel, Uwe; Preussner, André; Schill, Alexander

    While the implementation of business logic and business processes based on service-oriented architectures is well-understood and covered by existing development approaches, integrated concepts that empower users to exploit the Internet of Services to create complex interactive applications are missing. In this paper, we present an integrated approach that fills this gap. Our approach builds upon service annotations that add meta-information related to user interface generation, service dependencies, and service composition to existing service descriptions. Services can be composed visually to complex interactive applications based on these annotations without the need to write any code. The application code is generated completely from the service composition description. Our approach is able to support heterogeneous target environments ranging from client/server architectures to mobile platforms.

  18. Elementary Quantum Gates Based on Intrinsic Interaction Hamiltonian

    Institute of Scientific and Technical Information of China (English)

    CHEN Jing; YU Chang-Shui; SONG He-Shan

    2006-01-01

    A kind of new operators, the generalized pseudo-spin operators are introduced and a universal intrinsic Hamiltonian of two-qubit interaction is studied in terms of the generalized pseudo-spin operators. A fundamental quantum gate U(θ) is constructed based on the universal Hamiltonian and shown that the roles of the new quantum gate U(θ) is equivalent, functionally, to the joint operation of Hadamard and C-Not gates.

  19. A Moving Human Tracking Approach Based on Semantic Interaction

    Institute of Scientific and Technical Information of China (English)

    ZHOU Ning; FANG Bao-hong; SUN Fu-liang

    2007-01-01

    In order to deal with partical occlusion, a semantic interaction based moving human tracking approach is put forward. Firstly human is modeled as moving blobs which are described as blob descriptions. Then moving blobs are updated and verified by projecting these descriptions. The approach exploits improved fast gauss transform and chooses source and target samples to reduce compute cost. Multi-moving human can be tracked simply and part occlusion can be done well.

  20. Spreadsheet‐based interactive modules for control education

    OpenAIRE

    2010-01-01

    In the last few years, spreadsheets have become a popular computational tool and a powerful platform for performing engineering calculations. The simplicity of spreadsheet programming in addition to their plotting capabilities, and other provided utilities, make them a powerful didactic tool. This paper describes the development of interactive tools based on Excel spreadsheets for basic control education. The motivation for developing these tools was to give students special learning modules ...

  1. Improved physical stability of amorphous state through acid base interactions.

    Science.gov (United States)

    Telang, Chitra; Mujumdar, Siddharthya; Mathew, Michael

    2009-06-01

    To investigate role of specific interactions in aiding formation and stabilization of amorphous state in ternary and binary dispersions of a weakly acidic drug. Indomethacin (IMC), meglumine (MU), and polyvinyl pyrollidone (PVP) were the model drug, base, and polymer, respectively. Dispersions were prepared using solvent evaporation. Physical mixtures were cryogenically coground. XRPD, PLM, DSC, TGA, and FTIR were used for characterization. MU has a high crystallization tendency and is characterized by a low T(g) (17 degrees C). IMC crystallization was inhibited in ternary dispersion with MU compared to IMC/PVP alone. An amorphous state formed readily even in coground mixtures. Spectroscopic data are indicative of an IMC-MU amorphous salt and supports solid-state proton transfer. IMC-MU salt displays a low T(g) approximately 50 degrees C, but is more physically stable than IMC, which in molecular mixtures with MU, resisted crystallization even when present in stoichiometric excess of base. This is likely due to a disrupted local structure of amorphous IMC due to specific interactions. IMC showed improved physical stability on incorporating MU in polymer, in spite of low T(g) of the base indicating that chemical interactions play a dominant role in physical stabilization. Salt formation could be induced thermally and mechanically.

  2. Delegateable signatures based on non-interactive witness indistinguishable and non-interactive witness hiding proofs

    Institute of Scientific and Technical Information of China (English)

    TANG ChunMing; PEI DingYi; WANG XiaoFeng; LIU ZhuoJun

    2008-01-01

    A delegateable signature scheme (DSS) which was first introduced by Barak is mainly based on the non-interactive zero-knowledge proof (NIZK) for preventing the signing verifier from telling which witness (i.e., restricted subset) is being used. However, the scheme is not significantly efficient due to the difficulty of constructing NIZK. We first show that a non-Interactive witness indistinguishable (NIWI) proof sys-tern and a non-interactive witness hiding (NIWH) proof system are easier and more efficient proof models than NIZK in some cases. Furthermore, the witnesses em-ployed in these two protocols (NIWI and NIWT) cannot also be distinguished by the verifiers. Combined with the Σ-protocol, we then construct NlWl and NIWH proofs for any NP statement under the existence of one-way functions and show that each proof is different from those under the existence of trapdoor permutations. Finally, based on our NIWI and NIWH proofs, we construct delegateable signature schemes under the existence of one-way functions, which are more efficient than Barak's scheme under the existence of trapdoor permutations.

  3. Role of exchange interaction in nitrogen vacancy center based magnetometry

    Science.gov (United States)

    Ho, Cong Son; Tan, Seng Ghee; Jalil, Mansoor B. A.; Chen, Zilong; Krivitsky, Leonid A.

    2016-12-01

    We propose a multilayer device comprising a thin-film-based ferromagnetic heterostructure (FMH) deposited on a diamond layer doped with nitrogen vacancy centers (NVC's). We find that when the NVC's are in close proximity (1-2 nm) to the FMH, the exchange energy is comparable to, and may even surpass, the magnetostatic interaction energy. This calls forth the need to consider and utilize both effects in magnetometry based on NVC's in diamond. As the distance between the FMH and NVC is decreased to the subnanometer scale, the exponential increase in the exchange energy suggests spintronic applications of NVC's beyond magnetometry, such as detection of spin Hall effect or spin currents.

  4. Quantification of Aromaticity Based on Interaction Coordinates: A New Proposal.

    Science.gov (United States)

    Pandey, Sarvesh Kumar; Manogaran, Dhivya; Manogaran, Sadasivam; Schaefer, Henry F

    2016-05-12

    Attempts to establish degrees of aromaticity in molecules are legion. In the present study, we begin with a fictitious fragment arising from only those atoms contributing to the aromatic ring and having a force field projected from the original system. For example, in benzene, we adopt a fictitious C6 fragment with a force field projected from the full benzene force field. When one bond or angle is stretched and kept fixed, followed by a partial optimization for all other internal coordinates, structures change from their respective equilibria. These changes are the responses of all other internal coordinates for constraining the bond or angle by unit displacements and relaxing the forces on all other internal coordinates. The "interaction coordinate" derived from the redundant internal coordinate compliance constants measures how a bond (its electron density) responds for constrained optimization when another bond or angle is stretched by a specified unit (its electron density is perturbed by a finite amount). The sum of interaction coordinates (responses) of all bonded neighbors for all internal coordinates of the fictitious fragment is a measure of the strength of the σ and π electron interactions leading to aromatic stability. This sum, based on interaction coordinates, appears to be successful as an aromaticity index for a range of chemical systems. Since the concept involves analyzing a fragment rather than the whole molecule, this idea is more general and is likely to lead to new insights.

  5. An interactive tutorial-based training technique for vertebral morphometry.

    Science.gov (United States)

    Gardner, J C; von Ingersleben, G; Heyano, S L; Chesnut, C H

    2001-01-01

    The purpose of this work was to develop a computer-based procedure for training technologists in vertebral morphometry. The utility of the resulting interactive, tutorial based training method was evaluated in this study. The training program was composed of four steps: (1) review of an online tutorial, (2) review of analyzed spine images, (3) practice in fiducial point placement and (4) testing. During testing, vertebral heights were measured from digital, lateral spine images containing osteoporotic fractures. Inter-observer measurement precision was compared between research technicians, and between technologists and radiologist. The technologists participating in this study had no prior experience in vertebral morphometry. Following completion of the online training program, good inter-observer measurement precision was seen between technologists, showing mean coefficients of variation of 2.33% for anterior, 2.87% for central and 2.65% for posterior vertebral heights. Comparisons between the technicians and radiologist ranged from 2.19% to 3.18%. Slightly better precision values were seen with height measurements compared with height ratios, and with unfractured compared with fractured vertebral bodies. The findings of this study indicate that self-directed, tutorial-based training for spine image analyses is effective, resulting in good inter-observer measurement precision. The interactive tutorial-based approach provides standardized training methods and assures consistency of instructional technique over time.

  6. The Design of Tools for Sketching Sensor-Based Interaction

    DEFF Research Database (Denmark)

    Brynskov, Martin; Lunding, Rasmus; Vestergaard, Lasse Steenbock

    2012-01-01

    , flexibility and cost, aimed at wearable and ultra-mobile prototyping where fast reaction is needed (e.g. in controlling sound), and we discuss the general issues facing this category of embodied interaction design tools. We then present the platform in more detail, both regarding hard- ware and software....... In the brief evaluation, we present our initial experiences with the platform both in design projects and in teaching. We conclude that DUL Radio does seem to be a relatively easy-to-use tool for sketching sensor-based interaction compared to other solutions, but that there are many ways to improve it. Target...... users include designers, students, artists etc. with minimal programming and hardware skills, but this paper adresses the issues with designing the tools, which includes technical details....

  7. Gesture Interaction Browser-Based 3D Molecular Viewer.

    Science.gov (United States)

    Virag, Ioan; Stoicu-Tivadar, Lăcrămioara; Crişan-Vida, Mihaela

    2016-01-01

    The paper presents an open source system that allows the user to interact with a 3D molecular viewer using associated hand gestures for rotating, scaling and panning the rendered model. The novelty of this approach is that the entire application is browser-based and doesn't require installation of third party plug-ins or additional software components in order to visualize the supported chemical file formats. This kind of solution is suitable for instruction of users in less IT oriented environments, like medicine or chemistry. For rendering various molecular geometries our team used GLmol (a molecular viewer written in JavaScript). The interaction with the 3D models is made with Leap Motion controller that allows real-time tracking of the user's hand gestures. The first results confirmed that the resulting application leads to a better way of understanding various types of translational bioinformatics related problems in both biomedical research and education.

  8. Interactive cell segmentation based on phase contrast optics.

    Science.gov (United States)

    Su, Hang; Su, Zhou; Zheng, Shibao; Yang, Hua; Wei, Sha

    2014-01-01

    Cell segmentation in phase contrast microscopy images lays a crucial foundation for numerous subsequent computer-aided cell image analysis, but it encounters many unsolved challenges due to image qualities and artifacts caused by phase contrast optics. Addressing the unsolved challenges, the authors propose an interactive cell segmentation scheme over phase retardation features. After partitioning the images into phase homogeneous atoms, human annotations are propagated to unlabeled atoms over an affinity graph that is learned based on discrimination analysis. Then, an active query strategy is proposed for which the most informative unlabeled atom is selected for annotation, which is also propagated to the other unlabeled atoms. Cell segmentation converges to quality results after several rounds of interactions involving both the user's intentions and characteristics of image features. Experimental results demonstrate that cells with different optical properties are well segmented via the proposed approach.

  9. Point based interactive image segmentation using multiquadrics splines

    Science.gov (United States)

    Meena, Sachin; Duraisamy, Prakash; Palniappan, Kannappan; Seetharaman, Guna

    2017-05-01

    Multiquadrics (MQ) are radial basis spline function that can provide an efficient interpolation of data points located in a high dimensional space. MQ were developed by Hardy to approximate geographical surfaces and terrain modelling. In this paper we frame the task of interactive image segmentation as a semi-supervised interpolation where an interpolating function learned from the user provided seed points is used to predict the labels of unlabeled pixel and the spline function used in the semi-supervised interpolation is MQ. This semi-supervised interpolation framework has a nice closed form solution which along with the fact that MQ is a radial basis spline function lead to a very fast interactive image segmentation process. Quantitative and qualitative results on the standard datasets show that MQ outperforms other regression based methods, GEBS, Ridge Regression and Logistic Regression, and popular methods like Graph Cut,4 Random Walk and Random Forest.6

  10. The "Wedding-Ring": An agent-based marriage model based on social interaction

    Directory of Open Access Journals (Sweden)

    Alexia Prskawetz

    2007-08-01

    Full Text Available In this paper we develop an agent-based marriage model based on social interaction. We build an population of interacting agents whose chances of marrying depend on the availability of partners, and whose willingness to marry depends on the share of relevant others in their social network who are already married. We then let the typical aggregate age pattern of marriage emerge from the bottom-up. The results of our simulation show that micro-level hypotheses founded on existing theory and evidence on social interaction can reproduce age-at-marriage patterns with both realistic shape and realistic micro-level dynamics.

  11. Chronic and Acute Stress, Gender, and Serotonin Transporter Gene-Environment Interactions Predicting Depression Symptoms in Youth

    Science.gov (United States)

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Hazel, Nicholas A.; Najman, Jake M.

    2010-01-01

    Background: Many recent studies of serotonin transporter gene by environment effects predicting depression have used stress assessments with undefined or poor psychometric methods, possibly contributing to wide variation in findings. The present study attempted to distinguish between effects of acute and chronic stress to predict depressive…

  12. Neuronal connectivity as a convergent target of gene-environment interactions that confer risk for Autism Spectrum Disorders

    OpenAIRE

    Stamou, Marianna; Streifel, Karin M.; Goines, Paula E; Pamela J Lein

    2012-01-01

    Evidence implicates environmental factors in the pathogenesis of Autism Spectrum Disorders (ASD). However, the identity of specific environmental chemicals that influence ASD risk, severity or treatment outcome remains elusive. The impact of any given environmental exposure likely varies across a population according to individual genetic substrates, and this increases the difficulty of identifying clear associations between exposure and ASD diagnoses. Heritable genetic vulnerabilities may am...

  13. Gene/Environment Interaction in Atherosclerosis: An Example of Clinical Medicine as Seen from the Evolutionary Perspective

    Directory of Open Access Journals (Sweden)

    Gerhard Mertens

    2010-01-01

    The chronic multifactorial disease of atherosclerosis clearly illustrates the Darwinian paradigm. Recent research, combining the effects of genes and environment, has provided surprising clues to the pathogenesis of this major public health problem. This example makes a strong case for recognizing evolution biology as a basic science for medicine.

  14. The Dopamine D2 Receptor Gene, Perceived Parental Support, and Adolescent Loneliness: Longitudinal Evidence for Gene-Environment Interactions

    Science.gov (United States)

    van Roekel, Eeske; Goossens, Luc; Scholte, Ron H. J.; Engels, Rutger C. M. E.; Verhagen, Maaike

    2011-01-01

    Background: Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine-related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Methods: Associations among the DRD2, sex, parental support,…

  15. Exploration of gene-environment interactions, maternal effects and parent of origin effects in the etiology of hypospadias

    NARCIS (Netherlands)

    Zanden, L.F.M. van der; Galesloot, T.E.; Feitz, W.F.J.; Brouwers, M.M.; Shi, M.; Knoers, N.V.; Franke, B.; Roeleveld, N.; Rooij, I.A.L.M. van

    2012-01-01

    PURPOSE: Hypospadias is a common congenital malformation of the male external genitalia. Association studies for single nucleotide polymorphisms in genes encoding steroid 5alpha-reductase, estrogen receptors 1 and 2, and activating transcription factor 3 have been equivocal. We examined whether nonr

  16. The Dopamine D2 Receptor Gene, Perceived Parental Support, and Adolescent Loneliness: Longitudinal Evidence for Gene-Environment Interactions

    Science.gov (United States)

    van Roekel, Eeske; Goossens, Luc; Scholte, Ron H. J.; Engels, Rutger C. M. E.; Verhagen, Maaike

    2011-01-01

    Background: Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine-related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Methods: Associations among the DRD2, sex, parental support,…

  17. Physical activity, diet and gene-environment interactions in relation to body mass index and waist circumference

    DEFF Research Database (Denmark)

    Karnehed, Nina; Tynelius, Per; Heitmann, Berit L

    2006-01-01

    OBJECTIVE: The aim of the present study was to examine the relationships between genetic susceptibility to obesity, physical activity (PA), dietary fibre, sugar and fat intakes and 4-year changes in body mass index (BMI) and attained waist circumference (WC) in a cohort of 287 monozygotic and 189...

  18. An investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

    OpenAIRE

    Rudolph, Anja; Roger L Milne; Truong, Thérèse; Knight, Julia A.; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Munday, Hannah R.; Darabi, Hatef

    2014-01-01

    A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC.

  19. Underlying Mechanisms of Gene-Environment Interactions in Externalizing Behavior: A Systematic Review and Search for Theoretical Mechanisms

    NARCIS (Netherlands)

    Weeland, J.; Overbeek, G.; Orobio de Castro, B.; Matthys, W.

    2015-01-01

    Over the last decade, several candidate genes (i.e., MAOA, DRD4, DRD2, DAT1, 5-HTTLPR, and COMT) have been extensively studied as potential moderators of the detrimental effects of postnatal family adversity on child externalizing behaviors, such as aggression and conduct disorder. Many studies on s

  20. An investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

    OpenAIRE

    Rudolph, Anja; Milne, Roger L; Truong, Thérèse; Knight, Julia A; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Alison M Dunning; Shah, Mitul; Munday, Hannah R.; Darabi, Hatef

    2014-01-01

    A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC.

  1. Elucidating Interactions between DMSO and Chelate-Based Ionic Liquids.

    Science.gov (United States)

    Chen, Hang; Wang, Xinyu; Yao, Jia; Chen, Kexian; Guo, Yan; Zhang, Pengfei; Li, Haoran

    2015-12-21

    The C-D bond stretching vibrations of deuterated dimethyl sulfoxide ([D6 ]DMSO) and the C2 -H bond stretching vibrations of 1,1,1,5,5,5-hexafluoropentane-2,4-dione (hfac) ligand in anion are chosen as probes to elucidate the solvent-solute interaction between chelate-based ionic liquids (ILs) and DMSO by vibrational spectroscopic studies. The indirect effect from the interaction of the adjacent S=O functional group of DMSO with the cation [C10 mim](+) and anion [Mn(hfac)3 ](-) of the ILs leads to the blue-shift of the C-D stretching vibrations of DMSO. The C2 -H bond stretching vibrations in hfac ligand is closely related to the ionic hydrogen bond strength between the cation and anion of chelate-based ILs. EPR studies reveal that the crystal field of the central metal is kept when the chelate-based ILs are in different microstructure environment in the solution.

  2. Research on Goods and the Ship Interaction Based on ADAMS

    Directory of Open Access Journals (Sweden)

    Song Fangzhen

    2017-01-01

    Full Text Available The equivalent method of the relative movement goods on board is discussed in details. This method is to establish dynamic model based on moving trajectory of gravity-center for goods and to take rigid body geometric model with the trajectory as constraints in ADAMS. The difference of simulation methods for the different goods in carrier rolling is compared. The interact of relative moving objects with bulk carrier is discussed by using the ADAMS model. It is verified that the ballast water can maintain the ship’s stability by means of the ADAMS model.

  3. A prototype system based on visual interactive SDM called VGC

    Science.gov (United States)

    Jia, Zelu; Liu, Yaolin; Liu, Yanfang

    2009-10-01

    In many application domains, data is collected and referenced by its geo-spatial location. Spatial data mining, or the discovery of interesting patterns in such databases, is an important capability in the development of database systems. Spatial data mining recently emerges from a number of real applications, such as real-estate marketing, urban planning, weather forecasting, medical image analysis, road traffic accident analysis, etc. It demands for efficient solutions for many new, expensive, and complicated problems. For spatial data mining of large data sets to be effective, it is also important to include humans in the data exploration process and combine their flexibility, creativity, and general knowledge with the enormous storage capacity and computational power of today's computers. Visual spatial data mining applies human visual perception to the exploration of large data sets. Presenting data in an interactive, graphical form often fosters new insights, encouraging the information and validation of new hypotheses to the end of better problem-solving and gaining deeper domain knowledge. In this paper a visual interactive spatial data mining prototype system (visual geo-classify) based on VC++6.0 and MapObject2.0 are designed and developed, the basic algorithms of the spatial data mining is used decision tree and Bayesian networks, and data classify are used training and learning and the integration of the two to realize. The result indicates it's a practical and extensible visual interactive spatial data mining tool.

  4. INTERACTING MULTIPLE MODEL ALGORITHM BASED ON JOINT LIKELIHOOD ESTIMATION

    Institute of Scientific and Technical Information of China (English)

    Sun Jie; Jiang Chaoshu; Chen Zhuming; Zhang Wei

    2011-01-01

    A novel approach is proposed for the estimation of likelihood on Interacting Multiple-Model (IMM) filter.In this approach,the actual innovation,based on a mismatched model,can be formulated as sum of the theoretical innovation based on a matched model and the distance between matched and mismatched models,whose probability distributions are known.The joint likelihood of innovation sequence can be estimated by convolution of the two known probability density functions.The likelihood of tracking models can be calculated by conditional probability formula.Compared with the conventional likelihood estimation method,the proposed method improves the estimation accuracy of likelihood and robustness of IMM,especially when maneuver occurs.

  5. Agent Based Modeling of Human Gut Microbiome Interactions and Perturbations.

    Directory of Open Access Journals (Sweden)

    Tatiana Shashkova

    Full Text Available Intestinal microbiota plays an important role in the human health. It is involved in the digestion and protects the host against external pathogens. Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes.In this work we report an agent-based model of interactions between two bacterial species and between species and the gut. The model is based on reactions describing bacterial fermentation of polysaccharides to acetate and propionate and fermentation of acetate to butyrate. Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. Bacterial species are known to mutate and acquire resistance to the antibiotics. The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery.The model confirms a hypothesis of feedbacks mechanisms necessity for providing functionality and stability of the system after disturbance. High fraction of bacterial community was shown to mutate during antibiotic treatment, though sensitive strains could become dominating after recovery. The recovery of sensitive strains is explained by fitness cost of the resistance. The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms. Visual version of the model shows that spatial

  6. Comparing Four Touch-Based Interaction Techniques for an Image-Based Audience Response System

    NARCIS (Netherlands)

    Jorritsma, Wiard; Prins, Jonatan T.; van Ooijen, Peter M. A.

    2015-01-01

    This study aimed to determine the most appropriate touch-based interaction technique for I2Vote, an image-based audience response system for radiology education in which users need to accurately mark a target on a medical image. Four plausible techniques were identified: land-on, take-off, zoom-poin

  7. Hamiltonian multiplex interaction based on excitons effect in semiconductor QCs

    Directory of Open Access Journals (Sweden)

    Arezu Jahanshir

    2014-11-01

    Full Text Available The subject of modern technology has been the focus of extensive theoretical investigations in semiconducting nanostructures which we know as quantum dots (QCs. The possibility of monitoring and controlling the properties of QCs attracted considerable attention to these objects, as an important basic system in future technology. So, the quantum-mechanical effects play a significant role in the description of the formation mechanism QCs, determination of mass spectrum, binding energy and other characteristics. Based on QFT and by using oscillator representation method (ORM and operator product expansion technique developed in QFT, we study the properties of electron-hole QDs, determine mass spectrum and peruse spin-spin interactions in exciton system and its multiple pair systems. This method has applications to calculate the binding energy of exciton system in ground and excited states with semi-nuclear structure in semiconductor QCs or cold atomic few-body systems and develop the general calculation’s theory of few-body systems based on the Coulomb interaction between particles by forming excitonic pairs in semiconductor QCs. We investigate the binding energy of exciton bound states. It is shown that fermion particles have a very small mass, and after bonding together by dynamically force, constituent particles become massive, which is analogous to what happens in QCD.

  8. The Use of a Web-Based Classroom Interaction System in Introductory Physics Classes

    Science.gov (United States)

    Corpuz, Edgar D.; Corpuz, Ma. Aileen A.; Rosalez, Rolando

    2010-10-01

    A web-based interaction system was used in algebra-based and calculus-based physics classes to enhance students' classroom interaction. The interactive teaching approach primarily incorporated elements of Mazur's Peer Instruction and Interactive Lecture Demonstration. In our implementation, students used personal digital assistants (PDAs) to interact with their instructor during lecture and classroom demonstration. In this paper, we document the perceptions and attitudes of algebra-based and calculus-based physics students towards the interactive teaching approach and likewise present data on how this approach affected students' performance on the Force Concept Inventory (FCI).

  9. CIVILITY: cloud based interactive visualization of tractography brain connectome

    Science.gov (United States)

    Puechmaille, Danaële; Styner, Martin; Prieto, Juan C.

    2017-03-01

    Cloud based Interactive Visualization of Tractography Brain Connectome (CIVILITY) is an interactive visualization tool of brain connectome in the cloud. This application submits tasks to remote computing grids were the CIVILITY-tractography pipeline is deployed. The application will list the running tasks for the user and once a task is completed the brain connectome is visualized using Hierarchical Edge Bundling. The analysis pipeline uses FSL tools (bedpostx and probtrackx2) to generate a triangular matrix indicating the connectivity strength between different regions in the brain. This work is motivated by medical applications in which expensive computational tasks such as brain connectivity is needed and to provide a state of the art visualization tool of Brain Connectome. This work does not contribute any novelty with respect to the visualization methodology, is rather a new resource for the neuroimaging community. This work is submitted to the SPIE Biomedical Applications in Molecular, Structural, and Functional Imaging conference. The source code of this application is available in NITRC∗

  10. Interactive Web-based tutorials for teaching digital electronics

    Science.gov (United States)

    Bailey, Donald G.

    2000-10-01

    With a wide range of student abilities in a class, it is difficult to effectively teach and stimulate all students. A series of web based tutorials was designed to help weaker students and stretch the stronger students. The tutorials consist of a series of HTML web pages with embedded Java applets. This combination is particularly powerful for providing interactive demonstrations because any textual content may be easily provided within the web page. The applet is able to be a compete working program that dynamically illustrates the concept, or provides a working environment for the student to experiment and work through their solution. The applet is dynamic, and responds to the student through both mouse clicks and keyboard entry. These allow the student to adjust parameters, make selections, and affect the way the program is run or information is displayed. Such interaction allows each applet to provide a mini demonstration or experiment to help the student understand a particular concept or technique. The approach taken is illustrated with a tutorial that dynamically shows the relationships between a truth table, Karnaugh amp, logic circuit and Boolean algebra representations of a logic function, and dramatically illustrates the effect of minimization on the resultant circuit. Use of the tutorial has resulted in significant benefits, particularly with weaker students.

  11. Coordinate Descent Based Hierarchical Interactive Lasso Penalized Logistic Regression and Its Application to Classification Problems

    Directory of Open Access Journals (Sweden)

    Jin-Jia Wang

    2014-01-01

    Full Text Available We present the hierarchical interactive lasso penalized logistic regression using the coordinate descent algorithm based on the hierarchy theory and variables interactions. We define the interaction model based on the geometric algebra and hierarchical constraint conditions and then use the coordinate descent algorithm to solve for the coefficients of the hierarchical interactive lasso model. We provide the results of some experiments based on UCI datasets, Madelon datasets from NIPS2003, and daily activities of the elder. The experimental results show that the variable interactions and hierarchy contribute significantly to the classification. The hierarchical interactive lasso has the advantages of the lasso and interactive lasso.

  12. Interactive brain shift compensation using GPU based programming

    Science.gov (United States)

    van der Steen, Sander; Noordmans, Herke Jan; Verdaasdonk, Rudolf

    2009-02-01

    Processing large images files or real-time video streams requires intense computational power. Driven by the gaming industry, the processing power of graphic process units (GPUs) has increased significantly. With the pixel shader model 4.0 the GPU can be used for image processing 10x faster than the CPU. Dedicated software was developed to deform 3D MR and CT image sets for real-time brain shift correction during navigated neurosurgery using landmarks or cortical surface traces defined by the navigation pointer. Feedback was given using orthogonal slices and an interactively raytraced 3D brain image. GPU based programming enables real-time processing of high definition image datasets and various applications can be developed in medicine, optics and image sciences.

  13. An Interactive Web-based Environment using Human Companion

    Directory of Open Access Journals (Sweden)

    Tahar Bouhadada

    2006-01-01

    Full Text Available This paper describes the architecture of an Interactive Learning Environment (ILE on internet using companions, one of which is a human and geographically distant from the learning site. The achieved system rests on a 3-tier customer/server architecture (customer, web server, data and applications server where human and software actors can communicate via the internet and use the DTL learning strategy. It contains five main actors: a tutor actor in charge to guide the learner; a system actor whose role is to manage and to control the accesses to the system; a teacher actor in charge of the management and the updating of the different bases; a learner actor who represents the main actor of the system for whom is dedicated the teaching. Also, a learning companion actor whose role can be sometimes as an assistant, and other times as a troublemaker.

  14. Evolving effective behaviours to interact with tag-based populations

    Science.gov (United States)

    Yucel, Osman; Crawford, Chad; Sen, Sandip

    2015-07-01

    Tags and other characteristics, externally perceptible features that are consistent among groups of animals or humans, can be used by others to determine appropriate response strategies in societies. This usage of tags can be extended to artificial environments, where agents can significantly reduce cognitive effort spent on appropriate strategy choice and behaviour selection by reusing strategies for interacting with new partners based on their tags. Strategy selection mechanisms developed based on this idea have successfully evolved stable cooperation in games such as the Prisoner's Dilemma game but relies upon payoff sharing and matching methods that limit the applicability of the tag framework. Our goal is to develop a general classification and behaviour selection approach based on the tag framework. We propose and evaluate alternative tag matching and adaptation schemes for a new, incoming individual to select appropriate behaviour against any population member of an existing, stable society. Our proposed approach allows agents to evolve both the optimal tag for the environment as well as appropriate strategies for existing agent groups. We show that these mechanisms will allow for robust selection of optimal strategies by agents entering a stable society and analyse the various environments where this approach is effective.

  15. Progress in EEG-Based Brain Robot Interaction Systems

    Directory of Open Access Journals (Sweden)

    Xiaoqian Mao

    2017-01-01

    Full Text Available The most popular noninvasive Brain Robot Interaction (BRI technology uses the electroencephalogram- (EEG- based Brain Computer Interface (BCI, to serve as an additional communication channel, for robot control via brainwaves. This technology is promising for elderly or disabled patient assistance with daily life. The key issue of a BRI system is to identify human mental activities, by decoding brainwaves, acquired with an EEG device. Compared with other BCI applications, such as word speller, the development of these applications may be more challenging since control of robot systems via brainwaves must consider surrounding environment feedback in real-time, robot mechanical kinematics, and dynamics, as well as robot control architecture and behavior. This article reviews the major techniques needed for developing BRI systems. In this review article, we first briefly introduce the background and development of mind-controlled robot technologies. Second, we discuss the EEG-based brain signal models with respect to generating principles, evoking mechanisms, and experimental paradigms. Subsequently, we review in detail commonly used methods for decoding brain signals, namely, preprocessing, feature extraction, and feature classification, and summarize several typical application examples. Next, we describe a few BRI applications, including wheelchairs, manipulators, drones, and humanoid robots with respect to synchronous and asynchronous BCI-based techniques. Finally, we address some existing problems and challenges with future BRI techniques.

  16. Mixed Reality-based Interactive Technology for Aircraft Cabin Assembly

    Institute of Scientific and Technical Information of China (English)

    LI Shiqi; PENG Tao; WANG Junfeng; XU Chi

    2009-01-01

    Due to the narrowness of space and the complexity of structure, the assembly of aircraft cabin has become one of the major bottlenecks in the whole manufacturing process. To solve the problem, at the beginning of aircraft design, the different stages of the lifecycle of aircraft must be thought about, which include the trial manufacture, assembly, maintenance, recycling and destruction of the product. Recently, thanks to the development of the virtual reality and augmented reality, some low-cost and fast solutions are found for the product assembly. This paper presents a mixed reality-based interactive technology for the aircraft cabin assembly, which can enhance the efficiency of the assemblage in a virtual environment in terms of vision, information and operation. In the mixed reality-based assembly environment, the physical scene can be obtained by a camera and then generated by a computer. The virtual parts, the features of visual assembly, the navigation information, the physical parts and the physical assembly environment will be mixed and presented in the same assembly scene. The mixed or the augmented information will provide some assembling information as a detailed assembly instruction in the mixed reality-based assembly environment. Constraint proxy and its match rules help to reconstruct and visualize the restriction relationship among different parts, and to avoid the complex calculation of constraint's match. Finally, a desktop prototype system of virtual assembly has been built to assist the assembly verification and training with the virtual hand.

  17. Progress in EEG-Based Brain Robot Interaction Systems

    Science.gov (United States)

    Li, Mengfan; Niu, Linwei; Xian, Bin; Zeng, Ming; Chen, Genshe

    2017-01-01

    The most popular noninvasive Brain Robot Interaction (BRI) technology uses the electroencephalogram- (EEG-) based Brain Computer Interface (BCI), to serve as an additional communication channel, for robot control via brainwaves. This technology is promising for elderly or disabled patient assistance with daily life. The key issue of a BRI system is to identify human mental activities, by decoding brainwaves, acquired with an EEG device. Compared with other BCI applications, such as word speller, the development of these applications may be more challenging since control of robot systems via brainwaves must consider surrounding environment feedback in real-time, robot mechanical kinematics, and dynamics, as well as robot control architecture and behavior. This article reviews the major techniques needed for developing BRI systems. In this review article, we first briefly introduce the background and development of mind-controlled robot technologies. Second, we discuss the EEG-based brain signal models with respect to generating principles, evoking mechanisms, and experimental paradigms. Subsequently, we review in detail commonly used methods for decoding brain signals, namely, preprocessing, feature extraction, and feature classification, and summarize several typical application examples. Next, we describe a few BRI applications, including wheelchairs, manipulators, drones, and humanoid robots with respect to synchronous and asynchronous BCI-based techniques. Finally, we address some existing problems and challenges with future BRI techniques. PMID:28484488

  18. Evidence of Reactive Gene-Environment Correlation in Preschoolers' Prosocial Play with Unfamiliar Peers

    Science.gov (United States)

    DiLalla, Lisabeth Fisher; Bersted, Kyle; John, Sufna Gheyara

    2015-01-01

    The development of prosocial behaviors during the preschool years is essential for children's positive interactions with peers in school and other social situations. Although there is some evidence of genetic influences on prosocial behaviors, very little is known about how genes and environment, independently and in concert, affect prosocial…

  19. Interaction Pattern Analysis in cMOOCs Based on the Connectivist Interaction and Engagement Framework

    Science.gov (United States)

    Wang, Zhijun; Anderson, Terry; Chen, Li; Barbera, Elena

    2017-01-01

    Connectivist learning is interaction-centered learning. A framework describing interaction and cognitive engagement in connectivist learning was constructed using logical reasoning techniques. The framework and analysis was designed to help researchers and learning designers understand and adapt the characteristics and principles of interaction in…

  20. A Comparison of Interaction in AV-based and Internet-based Distance Courses

    Directory of Open Access Journals (Sweden)

    Melodee Landis

    2001-04-01

    Full Text Available At the center of the debate over the viability of distance education is whether the newer electronic technologies can offer enough interaction to maintain quality learner outcomes and critical mass. Two of the most commonly used forms of distance education are 1 two-way, fully interactive audio-video classrooms and 2 on-line instruction through the Internet or Worldwide Web. This study used qualitative methods to compare and contrast the interaction that occurred in distance learning courses offered via each medium. The research process confirmed findings that there were fundamental differences in the interaction that occurred in the two environments. On-line interaction is so profoundly different than interaction in the traditional and AV-based class room that it appears instructors and students will need a substantial period of adjustment to feel comfortable with it and to fully appreciate its value. It appears that, as distance teaching and learning moves to a “mixed media” approach to teaching and learning, how interaction is handled with each of the media may be important to the success of a distance program.

  1. Interactive model evaluation tool based on IPython notebook

    Science.gov (United States)

    Balemans, Sophie; Van Hoey, Stijn; Nopens, Ingmar; Seuntjes, Piet

    2015-04-01

    In hydrological modelling, some kind of parameter optimization is mostly performed. This can be the selection of a single best parameter set, a split in behavioural and non-behavioural parameter sets based on a selected threshold or a posterior parameter distribution derived with a formal Bayesian approach. The selection of the criterion to measure the goodness of fit (likelihood or any objective function) is an essential step in all of these methodologies and will affect the final selected parameter subset. Moreover, the discriminative power of the objective function is also dependent from the time period used. In practice, the optimization process is an iterative procedure. As such, in the course of the modelling process, an increasing amount of simulations is performed. However, the information carried by these simulation outputs is not always fully exploited. In this respect, we developed and present an interactive environment that enables the user to intuitively evaluate the model performance. The aim is to explore the parameter space graphically and to visualize the impact of the selected objective function on model behaviour. First, a set of model simulation results is loaded along with the corresponding parameter sets and a data set of the same variable as the model outcome (mostly discharge). The ranges of the loaded parameter sets define the parameter space. A selection of the two parameters visualised can be made by the user. Furthermore, an objective function and a time period of interest need to be selected. Based on this information, a two-dimensional parameter response surface is created, which actually just shows a scatter plot of the parameter combinations and assigns a color scale corresponding with the goodness of fit of each parameter combination. Finally, a slider is available to change the color mapping of the points. Actually, the slider provides a threshold to exclude non behaviour parameter sets and the color scale is only attributed to the

  2. Real-time retrieval for case-based reasoning in interactive multiagent-based simulations

    CERN Document Server

    De Loor, Pierre; Pierre, Chevaillier; 10.1016/j.eswa.2010.10.048

    2011-01-01

    The aim of this paper is to present the principles and results about case-based reasoning adapted to real- time interactive simulations, more precisely concerning retrieval mechanisms. The article begins by introducing the constraints involved in interactive multiagent-based simulations. The second section pre- sents a framework stemming from case-based reasoning by autonomous agents. Each agent uses a case base of local situations and, from this base, it can choose an action in order to interact with other auton- omous agents or users' avatars. We illustrate this framework with an example dedicated to the study of dynamic situations in football. We then go on to address the difficulties of conducting such simulations in real-time and propose a model for case and for case base. Using generic agents and adequate case base structure associated with a dedicated recall algorithm, we improve retrieval performance under time pressure compared to classic CBR techniques. We present some results relating to the perfor...

  3. Enhancing food engineering education with interactive web-based simulations

    Directory of Open Access Journals (Sweden)

    Alexandros Koulouris

    2015-04-01

    Full Text Available In the traditional deductive approach in teaching any engineering topic, teachers would first expose students to the derivation of the equations that govern the behavior of a physical system and then demonstrate the use of equations through a limited number of textbook examples. This methodology, however, is rarely adequate to unmask the cause-effect and quantitative relationships between the system variables that the equations embody. Web-based simulation, which is the integration of simulation and internet technologies, has the potential to enhance the learning experience by offering an interactive and easily accessible platform for quick and effortless experimentation with physical phenomena.This paper presents the design and development of a web-based platform for teaching basic food engineering phenomena to food technology students. The platform contains a variety of modules (“virtual experiments” covering the topics of mass and energy balances, fluid mechanics and heat transfer. In this paper, the design and development of three modules for mass balances and heat transfer is presented. Each webpage representing an educational module has the following features: visualization of the studied phenomenon through graphs, charts or videos, computation through a mathematical model and experimentation.  The student is allowed to edit key parameters of the phenomenon and observe the effect of these changes on the outputs. Experimentation can be done in a free or guided fashion with a set of prefabricated examples that students can run and self-test their knowledge by answering multiple-choice questions.

  4. Magnetic interactions in martensitic Ni-Mn based Heusler systems

    Energy Technology Data Exchange (ETDEWEB)

    Aksoy, Seda

    2010-04-22

    In this work, magnetic, magnetocaloric and structural properties are investigated in Ni-Mn-based martensitic Heusler alloys with the aim to tailor these properties as well as to understand in detail the magnetic interactions in the various crystallographic states of these alloys. We choose Ni{sub 50}Mn{sub 34}In{sub 16} as a prototype which undergoes a martensitic transformation and exhibits field-induced strain and the inverse magnetocaloric effect. Using the structural phase diagram of martensitic Ni-Mn-based Heusler alloys, we substitute gallium and tin for indium to carry these effects systematically closer to room temperature by shifting the martensitic transformation. A magneto-calorimeter is designed and built to measure adiabatically the magnetocaloric effect in these alloys. The temperature dependence of strain under an external magnetic field is studied in Ni{sub 50}Mn{sub 50-x}Z{sub x} (Z: Ga, Sn, In and Sb) and Ni{sub 50}Mn{sub 34}In{sub 16-x}Z{sub x} (Z: Ga and Sn). An argument based on the effect of the applied magnetic field on martensite nucleation is adopted to extract information on the direction of the magnetization easy axis in the martensitic unit cell in Heusler alloys. Parallel to these studies, the structure in the presence of an external field is also studied by powder neutron diffraction. It is demonstrated that martensite nucleation is influenced by cooling the sample under a magnetic field such that the austenite phase is arrested within the martensitic state. The magnetic interactions in Ni{sub 50}Mn{sub 37}Sn{sub 13} and Ni{sub 50}Mn{sub 40}Sb{sub 10} are characterized by using neutron polarization analysis. Below the martensitic transformation temperature, M{sub s}, an antiferromagnetically correlated state is found. Ferromagnetic resonance experiments are carried out on Ni{sub 50}Mn{sub 37}Sn{sub 13} and Ni{sub 50}Mn{sub 34}In{sub 16} to gain more detailed information on the nature of the magnetic interactions. The experimental

  5. Study on the Strategies of Distance Learning Support Services Based on Effective Interaction

    Institute of Scientific and Technical Information of China (English)

    王文琳; 靳桂阳

    2014-01-01

    The paper firstly analyzes the problems of distance learning interaction in order to clarify the significance of implement-ing effective interaction. Then it puts forward the learning support services strategies based on effective interaction, which means to design strategies from the perspective of effective interaction to improve the effect of distance learning.

  6. User-Based Interaction for Content-Based Image Retrieval by Mining User Navigation Patterns.

    Directory of Open Access Journals (Sweden)

    A. Srinagesh

    2013-09-01

    Full Text Available In Internet, Multimedia and Image Databases image searching is a necessity. Content-Based Image Retrieval (CBIR is an approach for image retrieval. With User interaction included in CBIR with Relevance Feedback (RF techniques, the results are obtained by giving more number of iterative feedbacks for large databases is not an efficient method for real- time applications. So, we propose a new approach which converges rapidly and can aptly be called as Navigation Pattern-Based Relevance Feedback (NPRF with User-based interaction mode. We combined NPRF with RF techniques with three concepts viz., query Re-weighting (QR, Query Expansion (QEX and Query Point Movement (QPM. By using, these three techniques efficient results are obtained by giving a small number of feedbacks. The efficiency of the proposed method with results is proved by calculating Precision, Recall and Evaluation measures.

  7. Sensing Landscape History with an Interactive Location Based Service

    Directory of Open Access Journals (Sweden)

    Paul Roncken

    2009-09-01

    Full Text Available This paper introduces the STEAD approach for interpreting data acquired by a “human sensor”, who uses an informal interactive location-based service (iLBS to sense cultural-historic facts and anecdotes of, and in the landscape. This user-generated data is collected outdoors and in situ. The approach consists of four related facets (who, what, where, when. Three of the four facets are discussed and illustrated by user generated data collected during a Dutch survey in 2008. These data represent the personal cultural-historic knowledge and anecdotes of 150 people using a customized iLBS for experiencing the cultural history of a landscape. The “who” facet shows three dominant mentality groups (cosmopolitans, modern materialists and post modern hedonists that generated user content. The “what” facet focuses on three subject types of pictures and four picture framing classes. Pictures of the place type showed to be dominant and foreground framing class was slightly favourite. The “where” facet is explored via density, distribution, and distance of the pictures made. The illustrations of the facets indirectly show the role of the “human sensor” with respect to the domain of interest. The STEAD approach needs further development of the when-facet and of the relations between the four facets. Finally the results of the approach may support data archives of iLBS applications.

  8. Physical punishment and childhood aggression: the role of gender and gene-environment interplay.

    Science.gov (United States)

    Boutwell, Brian B; Franklin, Cortney A; Barnes, J C; Beaver, Kevin M

    2011-01-01

    A large body of research has linked spanking with a range of adverse outcomes in children, including aggression, psychopathology, and criminal involvement. Despite evidence concerning the association of spanking with antisocial behavior, not all children who are spanked develop antisocial traits. Given the heterogeneous effects of spanking on behavior, it is possible that a third variable may condition the influence of corporal punishment on child development. We test this possibility using data drawn from a nationally representative dataset of twin siblings. Our findings suggest that genetic risk factors condition the effects of spanking on antisocial behavior. Moreover, our results provide evidence that the interaction between genetic risk factors and corporal punishment may be particularly salient for males.

  9. Movement-based interaction applied to physical rehabilitation therapies.

    Science.gov (United States)

    Garrido Navarro, Juan Enrique; Ruiz Penichet, Victor Manuel; Lozano Pérez, María Dolores

    2014-12-09

    Health care environments are continuously improving conditions, especially regarding the use of current technology. In the field of rehabilitation, the use of video games and related technology has helped to develop new rehabilitation procedures. Patients are able to work on their disabilities through new processes that are more motivating and entertaining. However, these patients are required to leave their home environment to complete their rehabilitation programs. The focus of our research interests is on finding a solution to eliminate the need for patients to interrupt their daily routines to attend rehabilitation therapy. We have developed an innovative system that allows patients with a balance disorder to perform a specific rehabilitation exercise at home. Additionally, the system features an assistive tool to complement the work of physiotherapists. Medical staff are thus provided with a system that avoids the need for them to be present during the exercise in specific cases in which patients are under suitable supervision. A movement-based interaction device was used to achieve a reliable system for monitoring rehabilitation exercises performed at home. The system accurately utilizes parameters previously defined by the specialist for correct performance of the exercise. Accordingly, the system gives instructions and corrects the patient's actions. The data generated during the session are collected for assessment by the specialist to adapt the difficulty of the exercise to the patient's progress. The evaluation of the system was conducted by two experts in balance disorder rehabilitation. They were required to verify the effectiveness of the system, and they also facilitated the simulation of real patient behavior. They used the system freely for a period of time and provided interesting and optimistic feedback. First, they evaluated the system as a tool for real-life rehabilitation therapy. Second, their interaction with the system allowed us to obtain

  10. Natural Interaction Based Online Military Boxing Learning System

    Science.gov (United States)

    Yang, Chenglei; Wang, Lu; Sun, Bing; Yin, Xu; Wang, Xiaoting; Liu, Li; Lu, Lin

    2013-01-01

    Military boxing, a kind of Chinese martial arts, is widespread and health beneficial. In this paper, the authors introduce a military boxing learning system realized by 3D motion capture, Web3D and 3D interactive technologies. The interactions with the system are natural and intuitive. Users can observe and learn the details of each action of the…

  11. Natural Interaction Based Online Military Boxing Learning System

    Science.gov (United States)

    Yang, Chenglei; Wang, Lu; Sun, Bing; Yin, Xu; Wang, Xiaoting; Liu, Li; Lu, Lin

    2013-01-01

    Military boxing, a kind of Chinese martial arts, is widespread and health beneficial. In this paper, the authors introduce a military boxing learning system realized by 3D motion capture, Web3D and 3D interactive technologies. The interactions with the system are natural and intuitive. Users can observe and learn the details of each action of the…

  12. Eye-based head gestures for interaction in the car

    DEFF Research Database (Denmark)

    Mardanbeigi, Diako; Witzner Hansen, Dan

    2013-01-01

    that can be used as an alternative input in the multimodal interaction context. Two approaches are described for using this method for interaction with objects inside or outside the car. Some application examples are described where the discrete or continuous head movements in combination with the driver......’s visual attention can be used for controlling the objects inside the car....

  13. Atomic interaction mechanism for designing the interface of W/Zr-based bulk metallic glass composites

    OpenAIRE

    Li, Z K; Fu, H. M.; Sha, P. F.; Zhu, Z. W.; A. M. Wang; Li, H.; Zhang, H. W.; Zhang, H. F.; Hu, Z. Q.

    2015-01-01

    The interaction between active element Zr and W damages the W fibers and the interface and decreases the mechanical properties, especially the tensile strength of the W fibers reinforced Zr-based bulk metallic glass composites (BMGCs). From the viewpoint of atomic interaction, the W-Zr interaction can be restrained by adding minor elements that have stronger interaction with W into the alloy. The calculation about atomic interaction energy indicates that Ta and Nb preferred to segregate on th...

  14. Study on Distance Learning Support Services Strategy Based on Effective Interaction

    Institute of Scientific and Technical Information of China (English)

    王文琳; 靳桂阳

    2014-01-01

    Achieving effective interaction can the students get good learning results, and enhance the quality of distance learning. The paper firstly analyzes the research on distance learning support services and the problems of distance learning interaction in or-der to clarify the significance of implementing effective interaction. Then it puts forward the learning support services strategies based on effective interaction, which means to promote distance learning interaction and enhance the students' self-learning abili-ty.

  15. Web-Based Interactions Support for Information Systems

    Directory of Open Access Journals (Sweden)

    Youcef Baghdadi

    2002-01-01

    Full Text Available Work organization, business innovation and IT have enhanced the distributed nature enterprise information systems. Information systems today are made up of subsystems running on heterogeneous IT platforms with varying implementations of business objects and processes increasing the dual risks of (i inconsistency of business objects views and (ii inefficiency of processes. This paper frames this problem as lack of representation and implementation of interactions among the subsystems and external sources. It proposes an interaction support system to make interactions an explicit element of the Enterprise Information System like data and operations. It describes a solution where the interaction elements are encapsulated into a separate subsystem and located in a web server to be used by other subsystems to exchange and share data and to perform processes with complete transparency. We argue that such Interaction Support System may provide global, unified and consistent view of business objects and synergy of processes.

  16. The Autism Birth Cohort: a paradigm for gene-environment-timing research.

    Science.gov (United States)

    Stoltenberg, C; Schjølberg, S; Bresnahan, M; Hornig, M; Hirtz, D; Dahl, C; Lie, K K; Reichborn-Kjennerud, T; Schreuder, P; Alsaker, E; Øyen, A-S; Magnus, P; Surén, P; Susser, E; Lipkin, W I

    2010-07-01

    The reported prevalence of autism spectrum disorders (ASDs) has increased by 5- to 10-fold over the past 20 years. Whether ASDs are truly more frequent is controversial; nonetheless, the burden is profound in human and economic terms. Although autism is among the most heritable of mental disorders, its pathogenesis remains obscure. Environmental factors are proposed; however, none is implicated. Furthermore, there are no biomarkers to screen for ASD or risk of ASD. The Autism Birth Cohort (ABC) was initiated to analyze gene x environment x timing interactions and enable early diagnosis. It uses a large, unselected birth cohort in which cases are prospectively ascertained through population screening. Samples collected serially through pregnancy and childhood include parental blood, maternal urine, cord blood, milk teeth and rectal swabs. More than 107,000 children are continuously screened through questionnaires, referral, and a national registry. Cases are compared with a control group from the same cohort in a 'nested case-control' design. Early screening and diagnostic assessments and re-assessments are designed to provide a rich view of longitudinal trajectory. Genetic, proteomic, immunologic, metagenomic and microbiological tools will be used to exploit unique biological samples. The ABC is a paradigm for analyzing the role of genetic and environmental factors in complex disorders.

  17. Research on Gene-Environment Interplay in the Era of "Big Data".

    Science.gov (United States)

    Heath, Andrew C; Lessov-Schlaggar, Christina N; Lian, Min; Miller, Ruth; Duncan, Alexis E; Madden, Pamela A F

    2016-09-01

    Successful identification of genetic risk factors in genomewide association studies typically has depended on meta-analyses combining data from large numbers of studies involving tens or hundreds of thousands of participants. This poses a challenge for research on Gene × Environment interaction (G × E) effects, where characterization of environmental exposures is quite limited in most studies and often varies idiosyncratically between studies. Yet the importance of environmental exposures in the etiology of many disorders-and especially alcohol, tobacco, and drug use disorders-is undeniable. We discuss the potential for "big-data" approaches (e.g., aggregating data from state databases) to generate consistent measures of neighborhood environment across multiple studies, requiring only information about residential address (or ideally residential history) to make progress in G × E analyses. Big-data approaches may also help address limits to the generalizability of existing research literature, such as those that arise because of the limited numbers of severely alcohol-dependent mothers represented in prospective research studies.

  18. A Mobile, Map-Based Tasking Interface for Human-Robot Interaction

    Science.gov (United States)

    2010-12-01

    the one of the fastest but least accurate methods of interaction (Muratore, 1987; Ahlström and Lenman, 1987; Karat et al., 1986) . However, these...claims of Muratore (1987); Ahlström and Lenman (1987); and Karat et al. (1986) which state that touch-based interaction is faster, but less accurate...interaction versus mouse-based interaction were also compared. Once again, the claimes of Muratore (1987); Ahlström and Lenman (1987); and Karat et al

  19. Expectation-driven interaction: a model based on Luhmann's contingency approach

    CERN Document Server

    Barber, M J; Buchinger, E; Cessac, B; Streit, L; Blanchard, Ph.

    2006-01-01

    We introduce an agent-based model of interaction, drawing on the contingency approach from Luhmann's theory of social systems. The agent interactions are defined by the exchange of distinct messages. Message selection is based on the history of the interaction and developed within the confines of the problem of double contingency. We examine interaction strategies in the light of the message-exchange description using analytical and computational methods.

  20. Interaction Junk: User Interaction-Based Evaluation of Visual Analytic Systems

    Energy Technology Data Exchange (ETDEWEB)

    Endert, Alexander; North, Chris

    2012-10-14

    With the growing need for visualization to aid users in understanding large, complex datasets, the ability for users to interact and explore these datasets is critical. As visual analytic systems have advanced to leverage powerful computational models and data analytics capabilities, the modes by which users engage and interact with the information are limited. Often, users are taxed with directly manipulating parameters of these models through traditional GUIs (e.g., using sliders to directly manipulate the value of a parameter). However, the purpose of user interaction in visual analytic systems is to enable visual data exploration – where users can focus on their task, as opposed to the tool or system. As a result, users can engage freely in data exploration and decision-making, for the purpose of gaining insight. In this position paper, we discuss how evaluating visual analytic systems can be approached through user interaction analysis, where the goal is to minimize the cognitive translation between the visual metaphor and the mode of interaction (i.e., reducing the “Interactionjunk”). We motivate this concept through a discussion of traditional GUIs used in visual analytics for direct manipulation of model parameters, and the importance of designing interactions the support visual data exploration.

  1. Apparatus and method for determining microscale interactions based on compressive sensors such as crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    McAdams, Harley; AlQuraishi, Mohammed

    2015-04-21

    Techniques for determining values for a metric of microscale interactions include determining a mesoscale metric for a plurality of mesoscale interaction types, wherein a value of the mesoscale metric for each mesoscale interaction type is based on a corresponding function of values of the microscale metric for the plurality of the microscale interaction types. A plurality of observations that indicate the values of the mesoscale metric are determined for the plurality of mesoscale interaction types. Values of the microscale metric are determined for the plurality of microscale interaction types based on the plurality of observations and the corresponding functions and compressed sensing.

  2. Agent based models for wealth distribution with preference in interaction

    CERN Document Server

    Goswami, Sanchari

    2014-01-01

    We propose a set of conservative models in which agents exchange wealth with a preference in the choice of interacting agents in different ways. The common feature in all the models is that the temporary values of financial status of agents is a deciding factor for interaction. Other factors which may play important role are past interactions and wealth possessed by individuals. Wealth distribution, network properties and activity are the main quantities which have been studied. Evidence of phase transitions and other interesting features are presented. The results show that certain observations of real economic system can be reproduced by the models.

  3. Support for Dynamic Service Composition with Role-Based Interaction Model

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper aims to present a role-based interaction model for dynamic service composition in Grid environments. Assigning roles to a service means to associate with it capabilities that describes all the operations the service intends to perform. When all of the services can be recognized by their roles, the appropriate services can be selected. Based on the interaction policy, a role-based interaction model not only facilitates access control, but also offers flexible interaction mechanism for adapting service-oriented applications. This interaction model adopts programmable reactive tuple space to facilitate context-dependent coordination.

  4. A reliability measure of protein-protein interactions and a reliability measure-based search engine.

    Science.gov (United States)

    Park, Byungkyu; Han, Kyungsook

    2010-02-01

    Many methods developed for estimating the reliability of protein-protein interactions are based on the topology of protein-protein interaction networks. This paper describes a new reliability measure for protein-protein interactions, which does not rely on the topology of protein interaction networks, but expresses biological information on functional roles, sub-cellular localisations and protein classes as a scoring schema. The new measure is useful for filtering many spurious interactions, as well as for estimating the reliability of protein interaction data. In particular, the reliability measure can be used to search protein-protein interactions with the desired reliability in databases. The reliability-based search engine is available at http://yeast.hpid.org. We believe this is the first search engine for interacting proteins, which is made available to public. The search engine and the reliability measure of protein interactions should provide useful information for determining proteins to focus on.

  5. Pendaphonics: A Tangible Pendulum-based Sonic Interaction Experience

    DEFF Research Database (Denmark)

    Overholt, Daniel; Hansen, Anne-Marie S.; Burleson, Winslow

    2009-01-01

    , presents a strategy for the design and evaluation of a low-cost, flexible, distributed system for public interaction and performance in a large scale tangible system. Pendaphonics has been installed in a public new media arts space, where over 200 people experienced the initial opening of the environment......, and is now active within five different research university interaction laboratories. This paper presents the development process and findings from observations and evaluation of Pendaphonics’ users and the social interaction patterns among performers and members of the public. In particular, the repeated...... along with descriptions of the broad potential of this system as a compositional and choreographic tool, an educational exhibit and classroom manipulative, and as an interface that facilitates playful interaction, exploration, discovery and creativity....

  6. IoT Based Human-Building Interaction

    DEFF Research Database (Denmark)

    Fürst, Jonathan

    2017-01-01

    Our interactions with built environments are increasingly augmented with digital capabilities. Smart appliances coupled with Building Management Systems (BMS) promise to increase occupant comfort and to reduce energy consumption through automated control and personalized services. However, it is ...

  7. Mobile gaze-based screen interaction in 3D environments

    DEFF Research Database (Denmark)

    Mardanbeigi, Diako; Witzner Hansen, Dan

    2011-01-01

    Head-mounted eye trackers can be used for mobile interaction as well as gaze estimation purposes. This paper presents a method that enables the user to interact with any planar digital display in a 3D environment using a head-mounted eye tracker. An effective method for identifying the screens...... in the field of view of the user is also presented which can be applied in a general scenario in which multiple users can interact with multiple screens. A particular application of using this technique is implemented in a home environment with two big screens and a mobile phone. In this application a user...... was able to interact with these screens using a wireless head-mounted eye tracker....

  8. Interactive Rendering For Projection-Based Augmented Reality Displays

    OpenAIRE

    Bimber, Oliver

    2002-01-01

    The rapid advances in computing and communications are dramatically changing all aspects of our lives. In particular, sophisticated 3D visualization, display, and interaction technologies are being used to complement our familiar physical world with computer-generated augmentations. These new interaction and display techniques are expected to make our work, learning, and leisure environments vastly more efficient and appealing. Within different application areas, variants of these technologie...

  9. Working with interpreters: an interactive Web-based learning module.

    Science.gov (United States)

    Kalet, Adina; Gany, Francesca; Senter, Lindsay

    2002-09-01

    Medical students are presented with unique challenges when they care for patients with limited English proficiency. Students must learn a complex set of skills needed to care for patients across cultural and language barriers and to understand the impact of their own attitudes and beliefs about caring for these patients. We developed and piloted a multimedia interactive Web-based module aimed at teaching students effective strategies for working with interpreters and diverse patient populations, and at raising their awareness of important legal, ethical, and cultural issues. First the learner completes a 37-multiple-choice-question (MCQ) pre-test that assesses attitudes, factual knowledge, and ability to analyze written clinical scenarios relevant to the module's content. Learners are then shown a series of professionally produced video vignettes, which reflect diverse patient populations, interpreters, and effectiveness of interpretation strategies (e.g., a Russian-speaking woman with chest pain whose daughter interprets, a medical student interpreting for a Chinese-speaking man using herbal medication, a Haitian woman told of an abnormal mammogram through a trained simultaneous interpreter). In each case, learners submit short answers to on-screen questions analyzing the effectiveness of the interpretation strategies demonstrated. Immediate feedback is given comparing student responses with those of experts. At any time during the module, the learners may view video commentary by legal, ethics, and cultural experts, or access a glossary and Web site links. Students conclude the module by again taking the MCQ test. A final screen compares their pre- and post-MCQ test responses and shows best answers, allowing them to assess their learning. The learners also complete a survey, providing personal cultural information and feedback on the module. All 160 first-year medical students completed the module and evaluated its effectiveness this year. On average, students

  10. Acid-base interactions in microbial adhesion to hexadecane and chloroform

    NARCIS (Netherlands)

    Bos, R; Busscher, HJ; Geertsema-Doornbusch, GI; Van Der Mei, HC; Mittal, KL

    2000-01-01

    Acid-base interactions play an important role in adhesion, including microbial adhesion to surfaces. Qualitatively acid-base interactions in microbial adhesion can be demonstrated by comparing adhesion to hexadecane (a negatively charged interface in aqueous solutions, unable to exert acid-base inte

  11. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested...

  12. Magnet-based Around Device Interaction for Playful Music Composition and Gaming

    NARCIS (Netherlands)

    El Ali, A.; Ketabdar, H.

    2013-01-01

    Around Device Interaction (ADI) has expanded the interaction space on mobile devices to allow 3D gesture interaction around the device. In this paper, the authors look specifically at magnet-based ADI and its applied use in a playful, music-related context. Using three musical applications developed

  13. ESL Students' Interaction in Second Life: Task-Based Synchronous Computer-Mediated Communication

    Science.gov (United States)

    Jee, Min Jung

    2010-01-01

    The purpose of the present study was to explore ESL students' interactions in task-based synchronous computer-mediated communication (SCMC) in Second Life, a virtual environment by which users can interact through representational figures. I investigated Low-Intermediate and High-Intermediate ESL students' interaction patterns before, during, and…

  14. Social network extraction and analysis based on multimodal dyadic interaction.

    Science.gov (United States)

    Escalera, Sergio; Baró, Xavier; Vitrià, Jordi; Radeva, Petia; Raducanu, Bogdan

    2012-01-01

    Social interactions are a very important component in people's lives. Social network analysis has become a common technique used to model and quantify the properties of social interactions. In this paper, we propose an integrated framework to explore the characteristics of a social network extracted from multimodal dyadic interactions. For our study, we used a set of videos belonging to New York Times' Blogging Heads opinion blog. The Social Network is represented as an oriented graph, whose directed links are determined by the Influence Model. The links' weights are a measure of the "influence" a person has over the other. The states of the Influence Model encode automatically extracted audio/visual features from our videos using state-of-the art algorithms. Our results are reported in terms of accuracy of audio/visual data fusion for speaker segmentation and centrality measures used to characterize the extracted social network.

  15. Social Network Extraction and Analysis Based on Multimodal Dyadic Interaction

    Directory of Open Access Journals (Sweden)

    Bogdan Raducanu

    2012-02-01

    Full Text Available Social interactions are a very important component in people’s lives. Social network analysis has become a common technique used to model and quantify the properties of social interactions. In this paper, we propose an integrated framework to explore the characteristics of a social network extracted from multimodal dyadic interactions. For our study, we used a set of videos belonging to New York Times’ Blogging Heads opinion blog. The Social Network is represented as an oriented graph, whose directed links are determined by the Influence Model. The links’ weights are a measure of the “influence” a person has over the other. The states of the Influence Model encode automatically extracted audio/visual features from our videos using state-of-the art algorithms. Our results are reported in terms of accuracy of audio/visual data fusion for speaker segmentation and centrality measures used to characterize the extracted social network.

  16. Molecular microenvironments: Solvent interactions with nucleic acid bases and ions

    Science.gov (United States)

    Macelroy, R. D.; Pohorille, A.

    1986-01-01

    The possibility of reconstructing plausible sequences of events in prebiotic molecular evolution is limited by the lack of fossil remains. However, with hindsight, one goal of molecular evolution was obvious: the development of molecular systems that became constituents of living systems. By understanding the interactions among molecules that are likely to have been present in the prebiotic environment, and that could have served as components in protobiotic molecular systems, plausible evolutionary sequences can be suggested. When stable aggregations of molecules form, a net decrease in free energy is observed in the system. Such changes occur when solvent molecules interact among themselves, as well as when they interact with organic species. A significant decrease in free energy, in systems of solvent and organic molecules, is due to entropy changes in the solvent. Entropy-driven interactioins played a major role in the organization of prebiotic systems, and understanding the energetics of them is essential to understanding molecular evolution.

  17. Situated dialog in speech-based human-computer interaction

    CERN Document Server

    Raux, Antoine; Lane, Ian; Misu, Teruhisa

    2016-01-01

    This book provides a survey of the state-of-the-art in the practical implementation of Spoken Dialog Systems for applications in everyday settings. It includes contributions on key topics in situated dialog interaction from a number of leading researchers and offers a broad spectrum of perspectives on research and development in the area. In particular, it presents applications in robotics, knowledge access and communication and covers the following topics: dialog for interacting with robots; language understanding and generation; dialog architectures and modeling; core technologies; and the analysis of human discourse and interaction. The contributions are adapted and expanded contributions from the 2014 International Workshop on Spoken Dialog Systems (IWSDS 2014), where researchers and developers from industry and academia alike met to discuss and compare their implementation experiences, analyses and empirical findings.

  18. Interactive, Computer-Based Training Program for Radiological Workers

    Energy Technology Data Exchange (ETDEWEB)

    Trinoskey, P.A.; Camacho, P.I.; Wells, L.

    2000-01-18

    Lawrence Livermore National Laboratory (LLNL) is redesigning its Computer-Based Training (CBT) program for radiological workers. The redesign represents a major effort to produce a single, highly interactive and flexible CBT program that will meet the training needs of a wide range of radiological workers--from researchers and x-ray operators to individuals working in tritium, uranium, plutonium, and accelerator facilities. The new CBT program addresses the broad diversity of backgrounds found at a national laboratory. When a training audience is homogeneous in terms of education level and type of work performed, it is difficult to duplicate the effectiveness of a flexible, technically competent instructor who can tailor a course to the express needs and concerns of a course's participants. Unfortunately, such homogeneity is rare. At LLNL, they have a diverse workforce engaged in a wide range of radiological activities, from the fairly common to the quite exotic. As a result, the Laboratory must offer a wide variety of radiological worker courses. These include a general contamination-control course in addition to radioactive-material-handling courses for both low-level laboratory (i.e., bench-top) activities as well as high-level work in tritium, uranium, and plutonium facilities. They also offer training courses for employees who work with radiation-generating devices--x-ray, accelerator, and E-beam operators, for instance. However, even with the number and variety of courses the Laboratory offers, they are constrained by the diversity of backgrounds (i.e., knowledge and experience) of those to be trained. Moreover, time constraints often preclude in-depth coverage of site- and/or task-specific details. In response to this situation, several years ago LLNL began moving toward computer-based training for radiological workers. Today, that CBT effort includes a general radiological safety course developed by the Department of Energy's Hanford facility and

  19. Interactive Image Segmentation Framework Based On Control Theory.

    Science.gov (United States)

    Zhu, Liangjia; Kolesov, Ivan; Karasev, Peter; Tannenbaum, Allen

    2015-02-21

    Segmentation of anatomical structures in medical imagery is a key step in a variety of clinical applications. Designing a generic, automated method that works for various structures and imaging modalities is a daunting task. Instead of proposing a new specific segmentation algorithm, in this paper, we present a general design principle on how to integrate user interactions from the perspective of control theory. In this formulation, Lyapunov stability analysis is employed to design and analyze an interactive segmentation system. The effectiveness and robustness of the proposed method are demonstrated.

  20. Approximation scheme based on effective interactions for stochastic gene regulation

    CERN Document Server

    Ohkubo, Jun

    2010-01-01

    Since gene regulatory systems contain sometimes only a small number of molecules, these systems are not described well by macroscopic rate equations; a master equation approach is needed for such cases. We develop an approximation scheme for dealing with the stochasticity of the gene regulatory systems. Using an effective interaction concept, original master equations can be reduced to simpler master equations, which can be solved analytically. We apply the approximation scheme to self-regulating systems with monomer or dimer interactions, and a two-gene system with an exclusive switch. The approximation scheme can recover bistability of the exclusive switch adequately.

  1. An Agent Interaction Based Method for Nonlinear Process Plan Scheduling

    Institute of Scientific and Technical Information of China (English)

    GAO Qinglu; WU Bo; GUO Guang

    2006-01-01

    This article puts forward a scheduling method for nonlinear process plan shop floor. Task allocation and load balance are realized by bidding mechanism. Though the agent interaction process, the execution of tasks is determined and the coherence of manufacturing decision is verified. The employment of heuristic index can help to optimize the system performance.

  2. Vizic: Jupyter-based interactive visualization tool for astronomical catalogs

    Science.gov (United States)

    Yu, Weixiang; Carrasco-Kind, Matias; Brunner, Robert J.

    2017-01-01

    Vizic is a Python visualization library that builds the connection between images and catalogs through an interactive map of the sky region. The software visualizes catalog data over a custom background canvas using the shape, size and orientation of each object in the catalog and displays interactive and customizable objects in the map. Property values such as redshift and magnitude can be used to filter or apply colormaps, and objects can be selected for further analysis through standard Python functions from inside a Jupyter notebook. Vizic allows custom overlays to be appended dynamically on top of the sky map; included are Voronoi, Delaunay, Minimum Spanning Tree and HEALPix layers, which are helpful for visualizing large-scale structure. Overlays can be generated, added or removed dynamically with one line of code. Catalog data is kept in a non-relational database. The Jupyter Notebook allows the user to create scripts to analyze and plot the data selected/displayed in the interactive map, making Vizic a powerful and flexible interactive analysis tool. Vizic be used for data inspection, clustering analysis, galaxy alignment studies, outlier identification or simply large-scale visualizations.

  3. Referring Expression Generation in Interaction: A Graph-based perspective

    NARCIS (Netherlands)

    Krahmer, E.J.; Goudbeek, M.B.; Theune, M.; Stent, Amanda; Bangalore, Srinivas

    2014-01-01

    An informative and comprehensive overview of the state-of-the-art in natural language generation (NLG) for interactive systems, this guide serves to introduce graduate students and new researchers to the field of natural language processing and artificial intelligence, while inspiring them with idea

  4. Physics-Based Visual Characterization of Molecular Interaction Forces.

    Science.gov (United States)

    Hermosilla, Pedro; Estrada, Jorge; Guallar, Victor; Ropinski, Timo; Vinacua, Alvar; Vazquez, Pere-Pau

    2017-01-01

    Molecular simulations are used in many areas of biotechnology, such as drug design and enzyme engineering. Despite the development of automatic computational protocols, analysis of molecular interactions is still a major aspect where human comprehension and intuition are key to accelerate, analyze, and propose modifications to the molecule of interest. Most visualization algorithms help the users by providing an accurate depiction of the spatial arrangement: the atoms involved in inter-molecular contacts. There are few tools that provide visual information on the forces governing molecular docking. However, these tools, commonly restricted to close interaction between atoms, do not consider whole simulation paths, long-range distances and, importantly, do not provide visual cues for a quick and intuitive comprehension of the energy functions (modeling intermolecular interactions) involved. In this paper, we propose visualizations designed to enable the characterization of interaction forces by taking into account several relevant variables such as molecule-ligand distance and the energy function, which is essential to understand binding affinities. We put emphasis on mapping molecular docking paths obtained from Molecular Dynamics or Monte Carlo simulations, and provide time-dependent visualizations for different energy components and particle resolutions: atoms, groups or residues. The presented visualizations have the potential to support domain experts in a more efficient drug or enzyme design process.

  5. Externalizing behaviors in preadolescents: familial risk to externalizing behaviors, prenatal and perinatal risks, and their interactions.

    NARCIS (Netherlands)

    Buschgens, C.J.M.; Swinkels, S.H.N.; Aken, M.A. van; Ormel, J.; Verhulst, F.C.; Buitelaar, J.K.

    2009-01-01

    BACKGROUND: Accumulating evidence indicates that there is a rich and varied interplay between persons and their environments, which strongly suggests that this involves gene-environment correlations and interactions. We investigated whether familial risk (FR) to externalizing behaviors and prenatal

  6. 3did: a catalog of domain-based interactions of known three-dimensional structure.

    Science.gov (United States)

    Mosca, Roberto; Céol, Arnaud; Stein, Amelie; Olivella, Roger; Aloy, Patrick

    2014-01-01

    The database of 3D interacting domains (3did, available online for browsing and bulk download at http://3did.irbbarcelona.org) is a catalog of protein-protein interactions for which a high-resolution 3D structure is known. 3did collects and classifies all structural templates of domain-domain interactions in the Protein Data Bank, providing molecular details for such interactions. The current version also includes a pipeline for the discovery and annotation of novel domain-motif interactions. For every interaction, 3did identifies and groups different binding modes by clustering similar interfaces into 'interaction topologies'. By maintaining a constantly updated collection of domain-based structural interaction templates, 3did is a reference source of information for the structural characterization of protein interaction networks. 3did is updated every 6 months.

  7. Interactive web-based Earth visualization telling the earth science story.

    Science.gov (United States)

    Stein, C.

    2006-12-01

    Interactive earth visualization applications provide a new level of understanding of complex spatial and time based environmental information. GeoFusion's earth visualization tools provide a web-based platform for sharing results of scientific research. One hundred years of predicted sea ice coverage is animated on an interactive globe in a web page. Watershed visualization comes alive with interactive control of terrain, map, satellite, and digital raster graph layers. Animating NASA's Blue Marble Next Generation half kilometer monthly datasets becomes a background for discussing yearly earth cycles. GeoFusion's tools are used for creating custom museum and web-based applications that engage users in an interactive exploration of environmental phenomena.

  8. A secure mobile phone-based interactive logon in Windows

    OpenAIRE

    Bodriagov, Oleksandr

    2010-01-01

    Password-based logon schemes have many security weaknesses. Smart card and biometric based authentication solutions are available as a replacement for standard password-based schemes for security sensitive environments. However, the cost of deployment and maintenance of these systems is quite high. On the other hand, mobile network operators have a huge base of deployed smart cards that can be reused to provide authentication in other areas significantly reducing costs. This master s thesis ...

  9. Muscle Quality and Myosteatosis: Novel Associations With Mortality Risk: The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.

    Science.gov (United States)

    Reinders, Ilse; Murphy, Rachel A; Brouwer, Ingeborg A; Visser, Marjolein; Launer, Lenore; Siggeirsdottir, Kristin; Eiriksdottir, Gudny; Gudnason, Vilmundur; Jonsson, Palmi V; Lang, Thomas F; Harris, Tamara B

    2016-01-01

    Muscle composition may affect mortality risk, but prior studies have been limited to specific samples or less precise determination of muscle composition. We evaluated associations of thigh muscle composition, determined using computed tomography imaging, and knee extension strength with mortality risk among 4,824 participants aged 76.4 (standard deviation (SD), 5.5) years from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study (2002-2006). Cox proportional hazards models were used to estimate hazard ratios. After 8.8 years of follow-up, there were 1,942 deaths. For men, each SD-increment increase in muscle lean area, muscle quality, and strength was associated with lower mortality risk, with decreases ranging between 11% and 22%. Each SD-increment increase in intermuscular adipose tissue and intramuscular adipose tissue was associated with higher mortality risk (hazard ratio (HR) = 1.13 (95% confidence interval (CI): 1.06, 1.22) and HR = 1.23 (95% CI: 1.15, 1.30), respectively). For women, each SD-increment increase in muscle lean area, muscle quality, and strength was associated with lower mortality risk, with decreases ranging between 12% and 19%. Greater intramuscular adipose tissue was associated with an 8% higher mortality risk (HR = 1.08, 95% CI: 1.01, 1.16). This study shows that muscle composition is associated with mortality risk. These results also show the importance of improving muscle strength and area and lowering muscle adipose tissue infiltration.

  10. The Influence of Major Life Events on Economic Attitudes in a World of Gene-Environment Interplay

    Science.gov (United States)

    Hatemi, Peter K.

    2014-01-01

    The role of “genes” on political attitudes has gained attention across disciplines. However, person-specific experiences have yet to be incorporated into models that consider genetic influences. Relying on a gene-environment interplay approach, this study explicates how life-events, such as losing one’s job or suffering a financial loss, influence economic policy attitudes. The results indicate genetic and environmental variance on support for unions, immigration, capitalism, socialism and property tax is moderated by financial risks. Changes in the magnitude of genetic influences, however, are temporary. After two years, the phenotypic effects of the life events remain on most attitudes, but changes in the sources of individual differences do not. Univariate twin models that estimate the independent contributions of genes and environment on the variation of attitudes appear to provide robust baseline indicators of sources of individual differences. These estimates, however, are not event or day specific. In this way, genetic influences add stability, while environment cues change, and this process is continually updated. PMID:24860199

  11. Marker-Based Embodied Interaction for Handheld Augmented Reality Games

    Directory of Open Access Journals (Sweden)

    Michael Rohs

    2007-05-01

    Full Text Available This article deals with embodied user interfaces for handheld augmented reality games, which consist of both physical and virtual components. We have developed a number of spatial interaction techniques that optically capture the device’s movement and orientation relative to a visual marker. Such physical interactions in 3D space enable manipulative control of mobile games. In addition to acting as a physical controller that recognizes multiple game-dependent gestures, the mobile device augments the camera view with graphical overlays. We describe three game prototypes that use ubiquitous product packaging and other passive media as backgrounds for handheld augmentation. The prototypes can be realized on widely available off-the-shelf hardware and require only minimal setup and infrastructure support.

  12. Nanoelectromechanical Heat Engine Based on Electron-Electron Interaction

    Science.gov (United States)

    Vikström, A.; Eriksson, A. M.; Kulinich, S. I.; Gorelik, L. Y.

    2016-12-01

    We theoretically show that a nanoelectromechanical system can be mechanically actuated by a heat flow through it via an electron-electron interaction. In contrast to most known actuation mechanisms in similar systems, this new mechanism does not involve an electronic current nor external ac fields. Instead, the mechanism relies on deflection-dependent tunneling rates and a heat flow which is mediated by an electron-electron interaction while an electronic current through the device is prohibited by, for instance, a spin-valve effect. Therefore, the system resembles a nanoelectromechanical heat engine. We derive a criterion for the mechanical instability and estimate the amplitude of the resulting self-sustained oscillations. Estimations show that the suggested phenomenon can be studied using available experimental techniques.

  13. Java-based Interactive Illustrations for Studio Physics

    Science.gov (United States)

    Malak, Michael; Wilson, Jack

    1997-04-01

    We have written a series of interactive demonstrations and simulations for introductory Electricity and Magnetism. These programs are written in the Java (TM) language and are delivered via the World-Wide Web to students either in the classroom or at home. The combination of such interactive illustrations with the Web's hypermedia capability is of significant value in the creation of network-distributable useful courseware. We are using these applets at Rensselaer and are evaluating their effectiveness as components of the instruction of Studio Physics II (Introduction to Electricity and Magnetism). Two of the applets allow the student to explore two-dimensional electric and magnetic fields by drawing field lines and equipotentials, evaluating divergence and curl, and calculating loop and surface integrals for Maxwell's laws. Another applet illustrates Snell's law of refraction, and another is an optical bench with movable lenses and a movable object.

  14. A Jupyter-based Interactive Visualization Tool for Astronomical Catalogs

    Science.gov (United States)

    Yu, Weixiang; Carrasco Kind, Matias; Brunner, Robert

    2017-01-01

    The ever-growing datasets in observational astronomy have challenged scientists in many aspects, including an efficient and interactive data exploration and visualization. Many tools have been developed to confront this challenge. However, they usually focus on displaying the actual images or focus on visualizing patterns within catalogs. Here we present Vizic, a Python visualization library that builds the connection between images and catalogs through an interactive map of the sky region. Vizic visualizes catalog data over a custom background canvas using the shape, size and orientation of each object in the catalog. The displayed objects in the map are highly interactive and customizable comparing to those in the observation images. These objects can be filtered by or colored by their property values, such as redshift and/or magnitude or can be sub-selected using a lasso-like tool. In addition, Vizic also allows custom overlays to be appended dynamically on top of the image. We have implemented a minimum spanning tree overlay and a Voronoi diagram overlay. Both overlays can be generated, added or removed with just a click of a button. All the data is kept in a non relational database, and the interfaces were developed in JavaScript and Python to work on Jupyter notebooks which allows to create custom widgets, user generated scripts to analyze and plot the data selected/displayed in the interactive map.Vizic can be adopted in variety of exercises, for example, data inspection, clustering analysis, galaxy alignment studies or public data release for large surveys.

  15. Structuring Task-based Interaction through Collaborative Learning Techniques (2)

    Institute of Scientific and Technical Information of China (English)

    William Littlewood

    2004-01-01

    @@ Techniques for collaborative learning In this section the focus will move from broad strategies to specific techniques (often also called "structures") through which the strategies can be realized. It gives a selection of techniques which have proved (in my own experience as well as that of others) particularly useful in pro-viding contexts for practice, exploration and /or interaction in the second language classroom.

  16. An Interactive Narrative Architecture Based on Filmmaking Theory

    OpenAIRE

    Seif El-Nasr, Magy

    2004-01-01

    Designing and developing an interactive narrative experience includes development of story content as well as a visual composition plan for visually realizing the story content. Theatre directors, filmmakers, and animators have emphasized the importance of visual design. Choices of character placements, lighting configuration, and camera movements, have been documented by designers to have direct impact on communicating the narrative, evoking emotions and moods, and engaging viewers. Many res...

  17. TopoAngler: Interactive Topology-based Extraction of Fishes.

    Science.gov (United States)

    Bock, Alexander; Doraiswamy, Harish; Summers, Adam; Silva, Claudio

    2017-08-29

    We present TopoAngler, a visualization framework that enables an interactive user-guided segmentation of fishes contained in a micro-CT scan. The inherent noise in the CT scan coupled with the often disconnected (and sometimes broken) skeletal structure of fishes makes an automatic segmentation of the volume impractical. To overcome this, our framework combines techniques from computational topology with an interactive visual interface, enabling the human-in-the-loop to effectively extract fishes from the volume. In the first step, the join tree of the input is used to create a hierarchical segmentation of the volume. Through the use of linked views, the visual interface then allows users to interactively explore this hierarchy, and gather parts of individual fishes into a coherent sub-volume, thus reconstructing entire fishes. Our framework was primarily developed for its application to CT scans of fishes, generated as part of the ScanAllFish project, through close collaboration with their lead scientist. However, we expect it to also be applicable in other biological applications where a single dataset contains multiple specimen; a common routine that is now widely followed in laboratories to increase throughput of expensive CT scanners.

  18. Model-based description of environment interaction for mobile robots

    Science.gov (United States)

    Borghi, Giuseppe; Ferrari, Carlo; Pagello, Enrico; Vianello, Marco

    1999-01-01

    We consider a mobile robot that attempts to accomplish a task by reaching a given goal, and interacts with its environment through a finite set of actions and observations. The interaction between robot and environment is modeled by Partially Observable Markov Decision Processes (POMDP). The robot takes its decisions in presence of uncertainty about the current state, by maximizing its reward gained during interactions with the environment. It is able to self-locate into the environment by collecting actions and perception histories during the navigation. To make the state estimation more reliable, we introduce an additional information in the model without adding new states and without discretizing the considered measures. Thus, we associate to the state transition probabilities also a continuous metric given through the mean and the variance of some significant sensor measurements suitable to be kept under continuous form, such as odometric measurements, showing that also such unreliable data can supply a great deal of information to the robot. The overall control system of the robot is structured as a two-levels layered architecture, where the low level implements several collision avoidance algorithms, while the upper level takes care of the navigation problem. In this paper, we concentrate on how to use POMDP models at the upper level.

  19. Predicting Drugs Side Effects Based on Chemical-Chemical Interactions and Protein-Chemical Interactions

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2013-01-01

    Full Text Available A drug side effect is an undesirable effect which occurs in addition to the intended therapeutic effect of the drug. The unexpected side effects that many patients suffer from are the major causes of large-scale drug withdrawal. To address the problem, it is highly demanded by pharmaceutical industries to develop computational methods for predicting the side effects of drugs. In this study, a novel computational method was developed to predict the side effects of drug compounds by hybridizing the chemical-chemical and protein-chemical interactions. Compared to most of the previous works, our method can rank the potential side effects for any query drug according to their predicted level of risk. A training dataset and test datasets were constructed from the benchmark dataset that contains 835 drug compounds to evaluate the method. By a jackknife test on the training dataset, the 1st order prediction accuracy was 86.30%, while it was 89.16% on the test dataset. It is expected that the new method may become a useful tool for drug design, and that the findings obtained by hybridizing various interactions in a network system may provide useful insights for conducting in-depth pharmacological research as well, particularly at the level of systems biomedicine.

  20. Interactions

    DEFF Research Database (Denmark)

    The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists...... such as Lorentz and Einstein as well as mathematicians such as Poincare, Minkowski, Hilbert and Weyl contributed to this development. They created the new physical theories and the mathematical disciplines that play such paramount roles in their mathematical formulations. These physicists and mathematicians were...

  1. Discovering Pair-Wise Genetic Interactions: An Information Theory-Based Approach

    Science.gov (United States)

    Ignac, Tomasz M.; Skupin, Alexander; Sakhanenko, Nikita A.; Galas, David J.

    2014-01-01

    Phenotypic variation, including that which underlies health and disease in humans, results in part from multiple interactions among both genetic variation and environmental factors. While diseases or phenotypes caused by single gene variants can be identified by established association methods and family-based approaches, complex phenotypic traits resulting from multi-gene interactions remain very difficult to characterize. Here we describe a new method based on information theory, and demonstrate how it improves on previous approaches to identifying genetic interactions, including both synthetic and modifier kinds of interactions. We apply our measure, called interaction distance, to previously analyzed data sets of yeast sporulation efficiency, lipid related mouse data and several human disease models to characterize the method. We show how the interaction distance can reveal novel gene interaction candidates in experimental and simulated data sets, and outperforms other measures in several circumstances. The method also allows us to optimize case/control sample composition for clinical studies. PMID:24670935

  2. Prediction of Protein-Protein Interaction Sites Based on Naive Bayes Classifier

    Directory of Open Access Journals (Sweden)

    Haijiang Geng

    2015-01-01

    Full Text Available Protein functions through interactions with other proteins and biomolecules and these interactions occur on the so-called interface residues of the protein sequences. Identifying interface residues makes us better understand the biological mechanism of protein interaction. Meanwhile, information about the interface residues contributes to the understanding of metabolic, signal transduction networks and indicates directions in drug designing. In recent years, researchers have focused on developing new computational methods for predicting protein interface residues. Here we creatively used a 181-dimension protein sequence feature vector as input to the Naive Bayes Classifier- (NBC- based method to predict interaction sites in protein-protein complexes interaction. The prediction of interaction sites in protein interactions is regarded as an amino acid residue binary classification problem by applying NBC with protein sequence features. Independent test results suggested that Naive Bayes Classifier-based method with the protein sequence features as input vectors performed well.

  3. Carotid arterial stiffness and risk of incident cerebral microbleeds in older people: the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study.

    Science.gov (United States)

    Ding, Jie; Mitchell, Gary F; Bots, Michiel L; Sigurdsson, Sigurdur; Harris, Tamara B; Garcia, Melissa; Eiriksdottir, Gudny; van Buchem, Mark A; Gudnason, Vilmundur; Launer, Lenore J

    2015-08-01

    Age and high blood pressure are major risk factors for cerebral microbleeds (CMBs). However, the underlying mechanisms remain unclear and arterial stiffness may be important. We investigated whether carotid arterial stiffness is associated with incidence and location of CMBs. In the prospective, population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik study, 2512 participants aged 66 to 93 years underwent a baseline brain MRI examination and carotid ultrasound in 2002 to 2006 and returned for a repeat brain MRI in 2007 to 2011. Common carotid arterial stiffness was assessed using a standardized protocol and expressed as carotid arterial strain, distensibility coefficient, and Young elastic modulus. Modified Poisson regression was applied to relate carotid arterial stiffness parameters to CMB incidence. During a mean follow-up of 5.2 years, 463 people (18.4%) developed new CMBs, of whom 292 had CMBs restricted to lobar regions and 171 had CMBs in a deep or infratentorial region. After adjusting for age, sex, and follow-up interval, arterial stiffness measures were associated with incident CMBs (risk ratio per SD decrease in carotid arterial strain, 1.11 [95% confidence interval, 1.01-1.21]; per SD decrease in natural log-transformed distensibility coefficient, 1.14 [1.05-1.24]; and per SD increase in natural log-transformed Young elastic modulus, 1.13 [1.04-1.23]). These measures were also significantly associated with incident deep CMBs (1.18 [1.02-1.37]; 1.24 [1.08-1.42]; and 1.23 [1.07-1.42]) but not with lobar CMBs. When further adjusted for blood pressure and other baseline vascular risk factors, carotid plaque, prevalent CMBs, subcortical infarcts, and white matter hyperintensities, the associations persisted. Our findings support the hypothesis that localized increases in carotid arterial stiffness may contribute to the development of CMBs, especially in a deep location attributable to hypertension. © 2015 American Heart Association, Inc.

  4. Aerosol-cirrus interactions: a number based phenomenon at all?

    Directory of Open Access Journals (Sweden)

    M. Seifert

    2004-01-01

    Full Text Available In situ measurements of the partitioning of aerosol particles within cirrus clouds were used to investigate aerosol-cloud interactions in ice clouds. The number density of interstitial aerosol particles (non-activated particles in between the cirrus crystals was compared to the number density of cirrus crystal residuals. The data was obtained during the two INCA (Interhemispheric Differences in Cirrus Properties from Anthropogenic Emissions campaigns, performed in the Southern Hemisphere (SH and Northern Hemisphere (NH midlatitudes. Different aerosol-cirrus interactions can be linked to the different stages of the cirrus lifecycle. Cloud formation is linked to positive correlations between the number density of interstitial aerosol (Nint and crystal residuals (Ncvi, whereas the correlations are smaller or even negative in a dissolving cloud. Unlike warm clouds, where the number density of cloud droplets is positively related to the aerosol number density, we observed a rather complex relationship when expressing Ncvi as a function of Nint for forming clouds. The data sets are similar in that they both show local maxima in the Nint range 100 to 200cm, where the SH- maximum is shifted towards the higher value. For lower number densities Nint and Ncvi are positively related. The slopes emerging from the data suggest that a tenfold increase in the aerosol number density corresponds to a 3 to 4 times increase in the crystal number density. As Nint increases beyond the ca. 100 to 200cm, the mean crystal number density decreases at about the same rate for both data sets. For much higher aerosol number densities, only present in the NH data set, the mean Ncvi remains low. The situation for dissolving clouds allows us to offer two possible, but at this point only speculative, alternative interactions between aerosols and cirrus: evaporating clouds might be associated with a source of aerosol particles, or air pollution (high aerosol number density might

  5. Task-Based Learning: The Interaction between Tasks and Learners.

    Science.gov (United States)

    Murphy, Jacky

    2003-01-01

    Investigates the relationship between tasks and learners in task-based learning. Findings suggest that manipulation of task characteristics and conditions may not achieve the intended pedagogic outcomes, and that new ways are needed to focus learners' attention of form without sacrificing the meaning-driven principles of task-based learning.…

  6. Comprehensive characterization of molecular interactions based on nanomechanics.

    Directory of Open Access Journals (Sweden)

    Murali Krishna Ghatkesar

    Full Text Available Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6 Da adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions.

  7. Child second language interaction in science-based tasks

    Science.gov (United States)

    McPhail, Cynthia Leigh

    While quasi-experimental in design, this study utilized qualitative data collection and analysis methods to examine the questions of whether students' speech act behavior and language use would vary by linguistic grouping. Second grade Puerto Rican native speakers of Spanish, and native English speakers completed sets of paired, hands-on, science activities. Children were paired in two linguistic groupings: heterogeneous (English native speaker/non-native speaker), and homogeneous (English non-native speaker/non-native speaker, or English native speaker/native speaker). Speech acts and use of target and native language in the two linguistic groupings were compared. Interviews with both the students and their teachers provided further understanding of the speech act behavior. Most prior research has dealt with university level adults learning English. Previous research that has dealt with children and second language interaction has often focused on teacher talk directed to the children, and no child/child interaction studies have attempted to control for variables such as linguistic grouping. Results indicated that linguistically heterogeneous groupings led to higher percentages of English use for non-native speakers. Homogeneous grouping led to higher percentages of native Spanish use. English native speakers' speech act behavior remained consistent in terms of dominance or passivity of behavior regardless of linguistic grouping, but there is the possibility that non-English speakers may behave in a slightly more passive manner when in heterogeneous grouping.

  8. Sculpting Mountains: Interactive Terrain Modeling Based on Subsurface Geology.

    Science.gov (United States)

    Cordonnier, Guillaume; Cani, Marie-Paule; Benes, Bedrich; Braun, Jean; Galin, Eric

    2017-03-29

    Most mountain ranges are formed by the compression and folding of colliding tectonic plates. Subduction of one plate causes large-scale asymmetry while their layered composition (or stratigraphy) explains the multi-scale folded strata observed on real terrains. We introduce a novel interactive modeling technique to generate visually plausible, large scale terrains that capture these phenomena. Our method draws on both geological knowledge for consistency and on sculpting systems for user interaction. The user is provided hands-on control on the shape and motion of tectonic plates, represented using a new geologically-inspired model for the Earth crust. The model captures their volume preserving and complex folding behaviors under collision, causing mountains to grow. It generates a volumetric uplift map representing the growth rate of subsurface layers. Erosion and uplift movement are jointly simulated to generate the terrain. The stratigraphy allows us to render folded strata on eroded cliffs. We validated the usability of our sculpting interface through a user study, and compare the visual consistency of the earth crust model with geological simulation results and real terrains.

  9. Direct measurement of acid-base interaction energy at solid interfaces.

    Science.gov (United States)

    Kurian, Anish; Prasad, Shishir; Dhinojwala, Ali

    2010-12-07

    We have studied acid-base interactions at solid-liquid and solid-solid interfaces using interface-sensitive sum frequency generation (SFG) spectroscopy. The shift of the sapphire hydroxyl peak in contact with several polar and nonpolar liquids and polymers was used to determine the interaction energy. The trend in the interaction energies cannot be explained by measuring only water contact angles. Molecular rearrangements at the sapphire interface, to maximize the interaction of the acid-base groups, play a dominant role, and these effects are not accounted for in the current theoretical models. These results provide important insights into understanding adhesion, friction, and wetting on solid interfaces.

  10. A global test for gene-gene interactions based on random matrix theory.

    Science.gov (United States)

    Frost, H Robert; Amos, Christopher I; Moore, Jason H

    2016-12-01

    Statistical interactions between markers of genetic variation, or gene-gene interactions, are believed to play an important role in the etiology of many multifactorial diseases and other complex phenotypes. Unfortunately, detecting gene-gene interactions is extremely challenging due to the large number of potential interactions and ambiguity regarding marker coding and interaction scale. For many data sets, there is insufficient statistical power to evaluate all candidate gene-gene interactions. In these cases, a global test for gene-gene interactions may be the best option. Global tests have much greater power relative to multiple individual interaction tests and can be used on subsets of the markers as an initial filter prior to testing for specific interactions. In this paper, we describe a novel global test for gene-gene interactions, the global epistasis test (GET), that is based on results from random matrix theory. As we show via simulation studies based on previously proposed models for common diseases including rheumatoid arthritis, type 2 diabetes, and breast cancer, our proposed GET method has superior performance characteristics relative to existing global gene-gene interaction tests. A glaucoma GWAS data set is used to demonstrate the practical utility of the GET method.

  11. A global test for gene‐gene interactions based on random matrix theory

    Science.gov (United States)

    Amos, Christopher I.; Moore, Jason H.

    2016-01-01

    ABSTRACT Statistical interactions between markers of genetic variation, or gene‐gene interactions, are believed to play an important role in the etiology of many multifactorial diseases and other complex phenotypes. Unfortunately, detecting gene‐gene interactions is extremely challenging due to the large number of potential interactions and ambiguity regarding marker coding and interaction scale. For many data sets, there is insufficient statistical power to evaluate all candidate gene‐gene interactions. In these cases, a global test for gene‐gene interactions may be the best option. Global tests have much greater power relative to multiple individual interaction tests and can be used on subsets of the markers as an initial filter prior to testing for specific interactions. In this paper, we describe a novel global test for gene‐gene interactions, the global epistasis test (GET), that is based on results from random matrix theory. As we show via simulation studies based on previously proposed models for common diseases including rheumatoid arthritis, type 2 diabetes, and breast cancer, our proposed GET method has superior performance characteristics relative to existing global gene‐gene interaction tests. A glaucoma GWAS data set is used to demonstrate the practical utility of the GET method. PMID:27386793

  12. KINECTWheels: wheelchair-accessible motion-based game interaction

    OpenAIRE

    Gerling, Kathrin M; Kalyn, Michael R.; Mandryk, Regan L.

    2013-01-01

    The increasing popularity of full-body motion-based video games creates new challenges for game accessibility research. Many games strongly focus on able-bodied persons and require players to move around freely. To address this problem, we introduce KINECTWheels, a toolkit that facilitates the integration of wheelchair-based game input. Our library can help game designers to integrate wheelchair input at the development stage, and it can be configured to trigger keystroke events to make off-t...

  13. Counting statistics for genetic switches based on effective interaction approximation

    Science.gov (United States)

    Ohkubo, Jun

    2012-09-01

    Applicability of counting statistics for a system with an infinite number of states is investigated. The counting statistics has been studied a lot for a system with a finite number of states. While it is possible to use the scheme in order to count specific transitions in a system with an infinite number of states in principle, we have non-closed equations in general. A simple genetic switch can be described by a master equation with an infinite number of states, and we use the counting statistics in order to count the number of transitions from inactive to active states in the gene. To avoid having the non-closed equations, an effective interaction approximation is employed. As a result, it is shown that the switching problem can be treated as a simple two-state model approximately, which immediately indicates that the switching obeys non-Poisson statistics.

  14. Nonreciprocity and magnetic-free isolation based on optomechanical interactions

    CERN Document Server

    Ruesink, Freek; Alù, Andrea; Verhagen, Ewold

    2016-01-01

    Photonic nonreciprocal components, such as isolators and circulators, provide highly desirable functionalities for optical circuitry. This motivates the active investigation of mechanisms that break reciprocity, and pose alternatives to magneto-optic effects in on-chip systems. In this work, we use optomechanical interactions to strongly break reciprocity in a compact system. We derive minimal requirements to create nonreciprocity in a wide class of systems that couple two optical modes to a mechanical mode, highlighting the importance of optically biasing the modes at a controlled phase difference. We realize these principles in a silica microtoroid optomechanical resonator and use quantitative heterodyne spectroscopy to demonstrate up to 10 dB optical isolation at telecom wavelengths. We show that nonreciprocal transmission is preserved for nondegenerate modes, and demonstrate nonreciprocal parametric amplification. These results open a route to exploiting various nonreciprocal effects in optomechanical sys...

  15. Nonreciprocity and magnetic-free isolation based on optomechanical interactions

    Science.gov (United States)

    Ruesink, Freek; Miri, Mohammad-Ali; Alù, Andrea; Verhagen, Ewold

    2016-11-01

    Nonreciprocal components, such as isolators and circulators, provide highly desirable functionalities for optical circuitry. This motivates the active investigation of mechanisms that break reciprocity, and pose alternatives to magneto-optic effects in on-chip systems. In this work, we use optomechanical interactions to strongly break reciprocity in a compact system. We derive minimal requirements to create nonreciprocity in a wide class of systems that couple two optical modes to a mechanical mode, highlighting the importance of optically biasing the modes at a controlled phase difference. We realize these principles in a silica microtoroid optomechanical resonator and use quantitative heterodyne spectroscopy to demonstrate up to 10 dB optical isolation at telecom wavelengths. We show that nonreciprocal transmission is preserved for nondegenerate modes, and demonstrate nonreciprocal parametric amplification. These results open a route to exploiting various nonreciprocal effects in optomechanical systems in different electromagnetic and mechanical frequency regimes, including optomechanical metamaterials with topologically non-trivial properties.

  16. Self-Healing Supramolecular Hydrogels Based on Reversible Physical Interactions

    Directory of Open Access Journals (Sweden)

    Satu Strandman

    2016-04-01

    Full Text Available Dynamic and reversible polymer networks capable of self-healing, i.e., restoring their mechanical properties after deformation and failure, are gaining increasing research interest, as there is a continuous need towards extending the lifetime and improving the safety and performance of materials particularly in biomedical applications. Hydrogels are versatile materials that may allow self-healing through a variety of covalent and non-covalent bonding strategies. The structural recovery of physical gels has long been a topic of interest in soft materials physics and various supramolecular interactions can induce this kind of recovery. This review highlights the non-covalent strategies of building self-repairing hydrogels and the characterization of their mechanical properties. Potential applications and future prospects of these materials are also discussed.

  17. Counting statistics for genetic switches based on effective interaction approximation

    CERN Document Server

    Ohkubo, Jun

    2012-01-01

    Applicability of counting statistics for a system with an infinite number of states is investigated. The counting statistics has been studied a lot for a system with a finite number of states. While it is possible to use the scheme in order to count specific transitions in a system with an infinite number of states in principle, we have non-closed equations in general. A simple genetic switch can be described by a master equation with an infinite number of states, and we use the counting statistics in order to count the number of transitions from inactive to active states in the gene. To avoid to have the non-closed equations, an effective interaction approximation is employed. As a result, it is shown that the switching problem can be treated as a simple two-state model approximately, which immediately indicates that the switching obeys non-Poisson statistics.

  18. EWS based visual and interactive simulator for plant engineering

    Energy Technology Data Exchange (ETDEWEB)

    Ohtsuka, Shiroh [Toshiba Corp. (Japan). Isogo Nuclear Engineering Center; Tanaka, Kazuma; Yoshikawa, Eiji [Toshiba Corp. (Japan). Nuclear Engineering Lab.

    1994-12-31

    The `Plant Engineering Visual and Interactive Simulator (PLEVIS)` is a realtime plant engineering simulator and runs on a general-purpose desk-top engineering workstation with a high-resolution bit-mapped display. PLEVIS is unique in that simulation models are integrated with a control/interlock model editor. PLEVIS can be used in a wide variety of applications, some of which are: (1) Design and modification studies of a control and interlock system, (2) Plant response evaluation for plant start-up testing and troubleshooting, (3) Transient recognition and mitigation studies, and (4) Familiarization with the plant process and control/ interlock system concept. The basic features of PLEVIS in order to realize the above applications are described in the presentation. (1 ref., 6 figs.).

  19. Inquiry and groups: student interactions in cooperative inquiry-based science

    Science.gov (United States)

    Woods-McConney, Amanda; Wosnitza, Marold; Sturrock, Keryn L.

    2016-03-01

    Science education research has recommended cooperative inquiry based science in the primary science context for more than two decades but after more than 20 years, student achievement in science has not substantially improved. This study, through direct observation and analysis, investigated content-related student interactions in an authentic inquiry based primary science class setting. Thirty-one upper primary students were videotaped working in cooperative inquiry based science activities. Cooperative talk and negotiation of the science content was analysed to identify any high-level group interactions. The data show that while all groups have incidences of high-level content-related group interactions, the frequency and duration of these interactions were limited. No specific pattern of preceding events was identified and no episodes of high-level content-related group interactions were immediately preceded by the teacher's interactions with the groups. This in situ study demonstrated that even without any kind of scaffolding, specific skills in knowing how to implement cooperative inquiry based science, high-level content-related group interactions did occur very briefly. Support for teachers to develop their knowledge and skills in facilitating cooperative inquiry based science learning is warranted to ensure that high-level content-related group interactions and the associated conceptual learning are not left to chance in science classrooms.

  20. Atomic interaction mechanism for designing the interface of W/Zr-based bulk metallic glass composites

    Science.gov (United States)

    Li, Z. K.; Fu, H. M.; Sha, P. F.; Zhu, Z. W.; Wang, A. M.; Li, H.; Zhang, H. W.; Zhang, H. F.; Hu, Z. Q.

    2015-03-01

    The interaction between active element Zr and W damages the W fibers and the interface and decreases the mechanical properties, especially the tensile strength of the W fibers reinforced Zr-based bulk metallic glass composites (BMGCs). From the viewpoint of atomic interaction, the W-Zr interaction can be restrained by adding minor elements that have stronger interaction with W into the alloy. The calculation about atomic interaction energy indicates that Ta and Nb preferred to segregate on the W substrate surface. Sessile drop experiment proves the prediction and corresponding in-situ coating appears at the interface. Besides, the atomic interaction mechanism was proven to be effective in many other systems by the sessile drop technique. Considering the interfacial morphology, Nb was added into the alloy to fabricate W/Zr-based BMGCs. As expected, the Nb addition effectively suppressed the W-Zr reaction and damage to W fibers. Both the compressive and tensile properties are improved obviously.

  1. Dynamic Communication of Humanoid Robot with Multiple People Based on Interaction Distance

    Science.gov (United States)

    Tasaki, Tsuyoshi; Matsumoto, Shohei; Ohba, Hayato; Yamamoto, Shunichi; Toda, Mitsuhiko; Komatani, Kazunori; Ogata, Tetsuya; Okuno, Hiroshi G.

    Research on human-robot interaction is getting an increasing amount of attention. Since most research has dealt with communication between one robot and one person, quite few researchers have studied communication between a robot and multiple people. This paper presents a method that enables robots to communicate with multiple people using the ``selection priority of the interactive partner'' based on the concept of Proxemics. In this method, a robot changes active sensory-motor modalities based on the interaction distance between itself and a person. Our method was implemented into a humanoid robot, SIG2. SIG2 has various sensory-motor modalities to interact with humans. A demonstration of SIG2 showed that our method selected an appropriate interaction partner during interaction with multiple people.

  2. Literature Mining and Ontology based Analysis of Host-Brucella Gene-Gene Interaction Network.

    Science.gov (United States)

    Karadeniz, İlknur; Hur, Junguk; He, Yongqun; Özgür, Arzucan

    2015-01-01

    Brucella is an intracellular bacterium that causes chronic brucellosis in humans and various mammals. The identification of host-Brucella interaction is crucial to understand host immunity against Brucella infection and Brucella pathogenesis against host immune responses. Most of the information about the inter-species interactions between host and Brucella genes is only available in the text of the scientific publications. Many text-mining systems for extracting gene and protein interactions have been proposed. However, only a few of them have been designed by considering the peculiarities of host-pathogen interactions. In this paper, we used a text mining approach for extracting host-Brucella gene-gene interactions from the abstracts of articles in PubMed. The gene-gene interactions here represent the interactions between genes and/or gene products (e.g., proteins). The SciMiner tool, originally designed for detecting mammalian gene/protein names in text, was extended to identify host and Brucella gene/protein names in the abstracts. Next, sentence-level and abstract-level co-occurrence based approaches, as well as sentence-level machine learning based methods, originally designed for extracting intra-species gene interactions, were utilized to extract the interactions among the identified host and Brucella genes. The extracted interactions were manually evaluated. A total of 46 host-Brucella gene interactions were identified and represented as an interaction network. Twenty four of these interactions were identified from sentence-level processing. Twenty two additional interactions were identified when abstract-level processing was performed. The Interaction Network Ontology (INO) was used to represent the identified interaction types at a hierarchical ontology structure. Ontological modeling of specific gene-gene interactions demonstrates that host-pathogen gene-gene interactions occur at experimental conditions which can be ontologically represented. Our

  3. Ontology-based literature mining of E. coli vaccine-associated gene interaction networks.

    Science.gov (United States)

    Hur, Junguk; Özgür, Arzucan; He, Yongqun

    2017-03-14

    Pathogenic Escherichia coli infections cause various diseases in humans and many animal species. However, with extensive E. coli vaccine research, we are still unable to fully protect ourselves against E. coli infections. To more rational development of effective and safe E. coli vaccine, it is important to better understand E. coli vaccine-associated gene interaction networks. In this study, we first extended the Vaccine Ontology (VO) to semantically represent various E. coli vaccines and genes used in the vaccine development. We also normalized E. coli gene names compiled from the annotations of various E. coli strains using a pan-genome-based annotation strategy. The Interaction Network Ontology (INO) includes a hierarchy of various interaction-related keywords useful for literature mining. Using VO, INO, and normalized E. coli gene names, we applied an ontology-based SciMiner literature mining strategy to mine all PubMed abstracts and retrieve E. coli vaccine-associated E. coli gene interactions. Four centrality metrics (i.e., degree, eigenvector, closeness, and betweenness) were calculated for identifying highly ranked genes and interaction types. Using vaccine-related PubMed abstracts, our study identified 11,350 sentences that contain 88 unique INO interactions types and 1,781 unique E. coli genes. Each sentence contained at least one interaction type and two unique E. coli genes. An E. coli gene interaction network of genes and INO interaction types was created. From this big network, a sub-network consisting of 5 E. coli vaccine genes, including carA, carB, fimH, fepA, and vat, and 62 other E. coli genes, and 25 INO interaction types was identified. While many interaction types represent direct interactions between two indicated genes, our study has also shown that many of these retrieved interaction types are indirect in that the two genes participated in the specified interaction process in a required but indirect process. Our centrality analysis of

  4. FEATURES OF USE INTERACTIVE TASKS IN MODERN MEANS OF COMPUTER-BASED TRAINING

    Directory of Open Access Journals (Sweden)

    Victoria V. Bova

    2014-01-01

    Full Text Available The article considers the problem of automated generation of interactive activities for learning software. This problem is relevant, since at the present stage of development of computer-based training systems can be traced need to build a tool that allows to implement various types of test and the training tasks on the basis of technologies of interactivity. We propose a tool to create dynamic tasks, enhance student’s interactivity with the system. 

  5. Protein complex prediction based on k-connected subgraphs in protein interaction network

    OpenAIRE

    Habibi Mahnaz; Eslahchi Changiz; Wong Limsoon

    2010-01-01

    Abstract Background Protein complexes play an important role in cellular mechanisms. Recently, several methods have been presented to predict protein complexes in a protein interaction network. In these methods, a protein complex is predicted as a dense subgraph of protein interactions. However, interactions data are incomplete and a protein complex does not have to be a complete or dense subgraph. Results We propose a more appropriate protein complex prediction method, CFA, that is based on ...

  6. Interactive Reliability-Based Optimization of Structural Systems

    DEFF Research Database (Denmark)

    Pedersen, Claus

    In order to introduce the basic concepts within the field of reliability-based structural optimization problems, this chapter is devoted to a brief outline of the basic theories. Therefore, this chapter is of a more formal nature and used as a basis for the remaining parts of the thesis. In secti...

  7. Vehicle-based interactive management with multi-agent approach

    Directory of Open Access Journals (Sweden)

    Yee Ming Chen

    2009-09-01

    Full Text Available Under the energy crisis and global warming, mass transportation becomes more important than before. The disadvantages of mass transportation, plus the high flexibility and efficiency of taxi and with the revolution of technology, electric-taxi is the better transportation choice for metropolis. On the other hand, among the many taxi service types, dial-a-ride (DAR service system is the better way for passenger and taxi. However the electricity replenishing of electric-taxi is the biggest shortage and constraint for DAR operation system. In order to more effectively manage the electric-taxi DAR operation system and the lots of disadvantages of physical system and observe the behaviors and interactions of simulation system, multi-agent simulation technique is the most suitable simulation technique. Finally, we use virtual data as the input of simulation system and analyze the simulation result. We successfully obtain two performance measures: average waiting time and service rate. Result shows the average waiting time is only 3.93 seconds and the service rate (total transport passenger number / total passenger number is 37.073%. So these two performance measures can support us to make management decisions. The multiagent oriented model put forward in this article is the subject of an application intended in the long term to supervise the user information system of an urban transport network.

  8. A Fast Goal Recognition Technique Based on Interaction Estimates

    Science.gov (United States)

    E-Martin, Yolanda; R-Moreno, Maria D.; Smith, David E.

    2015-01-01

    Goal Recognition is the task of inferring an actor's goals given some or all of the actor's observed actions. There is considerable interest in Goal Recognition for use in intelligent personal assistants, smart environments, intelligent tutoring systems, and monitoring user's needs. In much of this work, the actor's observed actions are compared against a generated library of plans. Recent work by Ramirez and Geffner makes use of AI planning to determine how closely a sequence of observed actions matches plans for each possible goal. For each goal, this is done by comparing the cost of a plan for that goal with the cost of a plan for that goal that includes the observed actions. This approach yields useful rankings, but is impractical for real-time goal recognition in large domains because of the computational expense of constructing plans for each possible goal. In this paper, we introduce an approach that propagates cost and interaction information in a plan graph, and uses this information to estimate goal probabilities. We show that this approach is much faster, but still yields high quality results.

  9. A sparse matrix based full-configuration interaction algorithm.

    Science.gov (United States)

    Rolik, Zoltán; Szabados, Agnes; Surján, Péter R

    2008-04-14

    We present an algorithm related to the full-configuration interaction (FCI) method that makes complete use of the sparse nature of the coefficient vector representing the many-electron wave function in a determinantal basis. Main achievements of the presented sparse FCI (SFCI) algorithm are (i) development of an iteration procedure that avoids the storage of FCI size vectors; (ii) development of an efficient algorithm to evaluate the effect of the Hamiltonian when both the initial and the product vectors are sparse. As a result of point (i) large disk operations can be skipped which otherwise may be a bottleneck of the procedure. At point (ii) we progress by adopting the implementation of the linear transformation by Olsen et al. [J. Chem Phys. 89, 2185 (1988)] for the sparse case, getting the algorithm applicable to larger systems and faster at the same time. The error of a SFCI calculation depends only on the dropout thresholds for the sparse vectors, and can be tuned by controlling the amount of system memory passed to the procedure. The algorithm permits to perform FCI calculations on single node workstations for systems previously accessible only by supercomputers.

  10. Experimental perspectives for systems based on long-range interactions

    CERN Document Server

    Bachelard, Romain; De Buyl, Pierre; Staniscia, F; Cataliotti, F S; De Ninno, G; Fanelli, Duccio; Piovella, Nicola

    2010-01-01

    The possibility of observing phenomena peculiar to long-range interactions, and more specifically in the so-called Quasi-Stationary State (QSS) regime is investigated within the framework of two devices, namely the Free-Electron Laser (FEL) and the Collective Atomic Recoil Laser (CARL). The QSS dynamics has been mostly studied using the Hamiltonian Mean-Field (HMF) toy model, demonstrating in particular the presence of first versus second order phase transitions from magnetized to unmagnetized regimes in the case of HMF. Here, we give evidence of the strong connections between the HMF model and the dynamics of the two mentioned devices, and we discuss the perspectives to observe some specific QSS features experimentally. In particular, a dynamical analog of the phase transition is present in the FEL and in the CARL in its conservative regime. Regarding the dissipative CARL, a formal link is established with the HMF model. For both FEL and CARL, calculations are performed with reference to existing experimenta...

  11. iDoRNA: An Interacting Domain-based Tool for Designing RNA-RNA Interaction Systems

    Directory of Open Access Journals (Sweden)

    Jittrawan Thaiprasit

    2016-03-01

    Full Text Available RNA-RNA interactions play a crucial role in gene regulation in living organisms. They have gained increasing interest in the field of synthetic biology because of their potential applications in medicine and biotechnology. However, few novel regulators based on RNA-RNA interactions with desired structures and functions have been developed due to the challenges of developing design tools. Recently, we proposed a novel tool, called iDoDe, for designing RNA-RNA interacting sequences by first decomposing RNA structures into interacting domains and then designing each domain using a stochastic algorithm. However, iDoDe did not provide an optimal solution because it still lacks a mechanism to optimize the design. In this work, we have further developed the tool by incorporating a genetic algorithm (GA to find an RNA solution with maximized structural similarity and minimized hybridized RNA energy, and renamed the tool iDoRNA. A set of suitable parameters for the genetic algorithm were determined and found to be a weighting factor of 0.7, a crossover rate of 0.9, a mutation rate of 0.1, and the number of individuals per population set to 8. We demonstrated the performance of iDoRNA in comparison with iDoDe by using six RNA-RNA interaction models. It was found that iDoRNA could efficiently generate all models of interacting RNAs with far more accuracy and required far less computational time than iDoDe. Moreover, we compared the design performance of our tool against existing design tools using forty-four RNA-RNA interaction models. The results showed that the performance of iDoRNA is better than RiboMaker when considering the ensemble defect, the fitness score and computation time usage. However, it appears that iDoRNA is outperformed by NUPACK and RNAiFold 2.0 when considering the ensemble defect. Nevertheless, iDoRNA can still be an useful alternative tool for designing novel RNA-RNA interactions in synthetic biology research. The source code of i

  12. Base pairing in RNA structures: A computational analysis of structural aspects and interaction energies

    Indian Academy of Sciences (India)

    Purshotam Sharma; Abhijit Mitra; Sitansh Sharma; Harjinder Singh

    2007-09-01

    The base pairing patterns in RNA structures are more versatile and completely different as compared to DNA. We present here results of ab-initio studies of structures and interaction energies of eight selected RNA base pairs reported in literature. Interaction energies, including BSSE correction, of hydrogen added crystal geometries of base pairs have been calculated at the HF/6-31G∗∗ level. The structures and interaction energies of the base pairs in the crystal geometry are compared with those obtained after optimization of the base pairs. We find that the base pairs become more planar on full optimization. No change in the hydrogen bonding pattern is seen. It is expected that the inclusion of appropriate considerations of many of these aspects of RNA base pairing would significantly improve the accuracy of RNA secondary structure prediction.

  13. Rydberg-interaction-based quantum gates free from blockade error

    CERN Document Server

    Shi, Xiao-Feng

    2016-01-01

    Accurate quantum gates are basic elements for building quantum computers. There has been great interest in designing quantum gates by using blockade effect of Rydberg atoms recently. The fidelity and operation speed of these gates, however, are fundamentally limited by the blockade error. Here we propose another type of quantum gates, which are based on Rydberg blockade effect, yet free from any blockade error. In contrast to the `blocking' method in previous schemes, we use Rydberg energy shift to realise a rational generalised Rabi frequency so that a novel $\\pi$ phase for one input state of the gate emerges. This leads to an accurate Rydberg-blockade based two-qubit quantum gate that can operate in a $0.1\\mu s$ timescale or faster thanks to that it operates by a Rabi frequency which is comparable to the blockade shift.

  14. A Framework for Agent-based Human Interaction Support

    Directory of Open Access Journals (Sweden)

    Axel Bürkle

    2008-10-01

    Full Text Available In this paper we describe an agent-based infrastructure for multimodal perceptual systems which aims at developing and realizing computer services that are delivered to humans in an implicit and unobtrusive way. The framework presented here supports the implementation of human-centric context-aware applications providing non-obtrusive assistance to participants in events such as meetings, lectures, conferences and presentations taking place in indoor "smart spaces". We emphasize on the design and implementation of an agent-based framework that supports "pluggable" service logic in the sense that the service developer can concentrate on coding the service logic independently of the underlying middleware. Furthermore, we give an example of the architecture's ability to support the cooperation of multiple services in a meeting scenario using an intelligent connector service and a semantic web oriented travel service.

  15. A Knowledge Based Interactive System for Complex Product Design

    Science.gov (United States)

    Gayretli, Ahmet

    This research presents a new Artificial Intelligence (AI) based product development approach for integrating mechanical design with electronic design to improve design and manufacture of electromechanical products by avoiding design conflicts in the early stages of the design process. The proposed approach has been implemented in a Delphi based environment integrated with a CAD system. The system assists designers from different disciplines in evaluating complex systems as far as parts relation, potential effects on each other, conflict management, costs, weight and physical constraints are concerned in the early design stages. This helps the designers to avoid design iterations leading to longer lead-time, hence increased cost. The developed system enables to rapidly develop and evaluate new complex products and add new functions to the existing products within given constraints.

  16. iCaCoT: Interactive camera-based coaching and training

    NARCIS (Netherlands)

    D'Acunto, L.; Redi, J.A.; Niamut, O.A.

    2015-01-01

    This paper reports on the evaluation of the concept of interactive camera-based coaching and training (iCaCoT), which focuses on using interactive video navigation for coaching and training purposes. The iCaCoT concept leverages tiled streaming technology, which allows users to navigate freely throu

  17. SEAsite: Web-based Interactive Learning Resources for Southeast Asian Languages and Cultures.

    Science.gov (United States)

    Henry, George; Zerwekh, Robert

    2002-01-01

    Discusses SEAsite, a Web-based interactive learning resource site for Southeast Asian Languages (Indonesian, Tagalog, Thai., Khmer, Lao, Burmese, and Vietnamese). Its language learning materials feature second language script support, streaming audio, pictures, and interactive exercise types that allow learners to test their understanding.…

  18. Virtual-Reality-Based Social Interaction Training for Children with High-Functioning Autism

    Science.gov (United States)

    Ke, Fengfeng; Im, Tami

    2013-01-01

    Employing the multiple-baseline across-subjects design, the authors examined the implementation and potential effect of a virtual-reality-based social interaction program on the interaction and communication performance of children with high functioning autism. The data were collected via behavior observation and analysis, questionnaires, and…

  19. Managing Mutual Orientation in the Absence of Physical Copresence: Multiparty Voice-Based Chat Room Interaction

    Science.gov (United States)

    Jenks, Christopher Joseph; Brandt, Adam

    2013-01-01

    This study investigates the interactional work involved in ratifying mutual participation in online, multiparty, voice-based chat rooms. The purpose of this article is to provide a preliminary sketch of how talk and participation is managed in a spoken communication environment that comprises interactants who are not physically copresent but are…

  20. Virtual-Reality-Based Social Interaction Training for Children with High-Functioning Autism

    Science.gov (United States)

    Ke, Fengfeng; Im, Tami

    2013-01-01

    Employing the multiple-baseline across-subjects design, the authors examined the implementation and potential effect of a virtual-reality-based social interaction program on the interaction and communication performance of children with high functioning autism. The data were collected via behavior observation and analysis, questionnaires, and…

  1. iCaCoT - Interactive Camera-based Coaching and Training

    NARCIS (Netherlands)

    D’Acunto, L.; Redi, J.; Niamut, O.A.

    2015-01-01

    This paper reports on the evaluation of the concept of interactive camera-based coaching and training (iCaCoT), which focuses on using interactive video navigation for coaching and training purposes. The iCaCoT concept leverages tiled streaming technology, which allows users to navigate freely

  2. A cell-based method for screening RNA-protein interactions: identification of constitutive transport element-interacting proteins.

    Directory of Open Access Journals (Sweden)

    Robert L Nakamura

    Full Text Available We have developed a mammalian cell-based screening platform to identify proteins that assemble into RNA-protein complexes. Based on Tat-mediated activation of the HIV LTR, proteins that interact with an RNA target elicit expression of a GFP reporter and are captured by fluorescence activated cell sorting. This "Tat-hybrid" screening platform was used to identify proteins that interact with the Mason Pfizer monkey virus (MPMV constitutive transport element (CTE, a structured RNA hairpin that mediates the transport of unspliced viral mRNAs from the nucleus to the cytoplasm. Several hnRNP-like proteins, including hnRNP A1, were identified and shown to interact with the CTE with selectivity in the reporter system comparable to Tap, a known CTE-binding protein. In vitro gel shift and pull-down assays showed that hnRNP A1 is able to form a complex with the CTE and Tap and that the RGG domain of hnRNP A1 mediates binding to Tap. These results suggest that hnRNP-like proteins may be part of larger export-competent RNA-protein complexes and that the RGG domains of these proteins play an important role in directing these binding events. The results also demonstrate the utility of the screening platform for identifying and characterizing new components of RNA-protein complexes.

  3. Thioarsenides: A case for long-range Lewis acid-base-directed van der Waals interactions

    Energy Technology Data Exchange (ETDEWEB)

    Gibbs, Gerald V.; Wallace, Adam F.; Downs, R. T.; Ross, Nancy L.; Cox, David F.; Rosso, Kevin M.

    2011-04-01

    Electron density distributions, bond paths, Laplacian and local energy density properties have been calculated for a number of As4Sn (n = 3,4,5) thioarsenide molecular crystals. On the basis of the distributions, the intramolecular As-S and As-As interactions classify as shared bonded interactions and the intermolecular As-S, As-As and S-S interactions classify as closed-shell van der Waals bonded interactions. The bulk of the intermolecular As-S bond paths link regions of locally concentrated electron density (Lewis base regions) with aligned regions of locally depleted electron density (Lewis acid regions) on adjacent molecules. The paths are comparable with intermolecular paths reported for several other molecular crystals that link aligned Lewis base and acid regions in a key-lock fashion, interactions that classified as long range Lewis acid-base directed van der Waals interactions. As the bulk of the intermolecular As-S bond paths (~70%) link Lewis acid-base regions on adjacent molecules, it appears that molecules adopt an arrangement that maximizes the number of As-S Lewis acid-base intermolecular bonded interactions. The maximization of the number of Lewis acid-base interactions appears to be connected with the close-packed array adopted by molecules: distorted cubic close-packed arrays are adopted for alacránite, pararealgar, uzonite, realgar and β-AsS and the distorted hexagonal close-packed arrays adopted by α- and β-dimorphite. A growth mechanism is proposed for thioarsenide molecular crystals from aqueous species that maximizes the number of long range Lewis acid-base vdW As-S bonded interactions with the resulting directed bond paths structuralizing the molecules as a molecular crystal.

  4. A toy model for weak interaction based on condensed gauge bosons

    CERN Document Server

    Kohyama, Hiroaki

    2016-01-01

    We construct a toy model for weak interaction based on the assumption that gauge bosons form condensates. We then discuss the model predictions calculated from the effective Feynman rules which are derived through computing the effective action.

  5. Design and implementation of an interactive web-based near real-time forest monitoring system

    NARCIS (Netherlands)

    Pratihast, Arun Kumar; Vries, de Ben; Avitabile, Valerio; Bruin, De Sytze; Herold, Martin; Bergsma, Aldo

    2016-01-01

    This paper describes an interactive web-based near real-time (NRT) forest monitoring system using four levels of geographic information services: 1) the acquisition of continuous data streams from satellite and community-based monitoring using mobile devices, 2) NRT forest disturbance detection base

  6. Development of Novel Random Network Theory-Based Approaches to Identify Network Interactions among Nitrifying Bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Cindy

    2015-07-17

    The interactions among different microbial populations in a community could play more important roles in determining ecosystem functioning than species numbers and their abundances, but very little is known about such network interactions at a community level. The goal of this project is to develop novel framework approaches and associated software tools to characterize the network interactions in microbial communities based on high throughput, large scale high-throughput metagenomics data and apply these approaches to understand the impacts of environmental changes (e.g., climate change, contamination) on network interactions among different nitrifying populations and associated microbial communities.

  7. Grandmaster: Interactive text-based analytics of social media

    Energy Technology Data Exchange (ETDEWEB)

    Fabian, Nathan D.; Davis, Warren Leon,; Raybourn, Elaine M.; Lakkaraju, Kiran; Whetzel, Jonathan

    2015-11-01

    People use social media resources like Twitter, Facebook, forums etc. to share and discuss various activities or topics. By aggregating topic trends across many individuals using these services, we seek to construct a richer profile of a person’s activities and interests as well as provide a broader context of those activities. This profile may then be used in a variety of ways to understand groups as a collection of interests and affinities and an individual’s participation in those groups. Our approach considers that much of these data will be unstructured, free-form text. By analyzing free-form text directly, we may be able to gain an implicit grouping of individuals with shared interests based on shared conversation, and not on explicit social software linking them. In this paper, we discuss a proof-of-concept application called Grandmaster built to pull short sections of text, a person’s comments or Twitter posts, together by analysis and visualization to allow a gestalt understanding of the full collection of all individuals: how groups are similar and how they differ, based on their text inputs.

  8. Promoting oral interaction in large groups through task-based learning

    OpenAIRE

    Forero Rocha, Yolima

    2009-01-01

    This research project attempts to show the way a group of five teachers used task-based learning with a group of 50 seventh graders to improve oral interaction. The students belonged to Isabel II School. They took an active part in the implementation of tasks and were asked to answer two questionnaires. Some English classes were observed and recorded; finally, an evaluation was taken by students to test their improvement. Key words: Task-based learning, oral interaction, large groups, hig...

  9. Do interactions speak louder than words? Dialogic reading of an interactive tablet-based e-book with children between 16 months and three years of age

    DEFF Research Database (Denmark)

    Knoche, Hendrik; Rasmussen, Niklas Ammitzbøl; Boldreel, Kasper

    2014-01-01

    the effect of interactive elements on speech production of 12 children between the ages of 16 and 33 months when engaged in individual dialogic reading sessions with a tablet-based e-book. Interaction with interactive elements did not reduce the children’s responses to dialogic reading prompts. Spontaneous...

  10. Interactions between DNA purinic bases and amodiaquine: A theoretical approach

    Directory of Open Access Journals (Sweden)

    Valdemar Lacerda Júnior

    2010-06-01

    Full Text Available We study theoretically the amodiaquine-adenine and amodiaquine-guanine adducts formation using Density Functional Theory (B3LYP and the 6-31G(d basis set for the geometry optimizations and 6-31+G(d,p for the analysis of the global indexes: electrophilicity (w, electronic chemical potential (m, hardness (h and softness (S, based in the Frontier Molecular Orbital Theory – FMO. Local softness for nucleophilic reaction (sk+ sites over guanine was evaluated using Fukui function (f k. We also evaluated the guanine Electrostatic Potential (EP values using the (MSK charge scheme. The theoretical calculations had demonstrated that the amodiaquine has greater electronic affinity for the guanine, with irreversible formation of the amodiaquine-guanine adduct, as reported before on a previous experimental work.

  11. Single-photon absorber based on strongly interacting Rydberg atoms

    CERN Document Server

    Tresp, Christoph; Mirgorodskiy, Ivan; Gorniaczyk, Hannes; Paris-Mandoki, Asaf; Hofferberth, Sebastian

    2016-01-01

    Removing exactly one photon from an arbitrary input pulse is an elementary operation in quantum optics and enables applications in quantum information processing and quantum simulation. Here we demonstrate a deterministic single-photon absorber based on the saturation of an optically thick free-space medium by a single photon due to Rydberg blockade. Single-photon subtraction adds a new component to the Rydberg quantum optics toolbox, which already contains photonic logic building-blocks such as single-photon sources, switches, transistors, and conditional $\\pi$-phase shifts. Our approach is scalable to multiple cascaded absorbers, essential for preparation of non-classical light states for quantum information and metrology applications, and, in combination with the single-photon transistor, high-fidelity number-resolved photon detection.

  12. CaseWorld™: Interactive, media rich, multidisciplinary case based learning.

    Science.gov (United States)

    Gillham, David; Tucker, Katie; Parker, Steve; Wright, Victoria; Kargillis, Christina

    2015-11-01

    Nurse educators are challenged to keep up with highly specialised clinical practice, emerging research evidence, regulation requirements and rapidly changing information technology while teaching very large numbers of diverse students in a resource constrained environment. This complex setting provides the context for the CaseWorld project, which aims to simulate those aspects of clinical practice that can be represented by e-learning. This paper describes the development, implementation and evaluation of CaseWorld, a simulated learning environment that supports case based learning. CaseWorld provides nursing students with the opportunity to view unfolding authentic cases presented in a rich multimedia context. The first round of comprehensive summative evaluation of CaseWorld is discussed in the context of earlier formative evaluation, reference group input and strategies for integration of CaseWorld with subject content. This discussion highlights the unique approach taken in this project that involved simultaneous prototype development and large scale implementation, thereby necessitating strong emphasis on staff development, uptake and engagement. The lessons learned provide an interesting basis for further discussion of broad content sharing across disciplines and universities, and the contribution that local innovations can make to global education advancement. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  13. Interactive object modelling based on piecewise planar surface patches.

    Science.gov (United States)

    Prankl, Johann; Zillich, Michael; Vincze, Markus

    2013-06-01

    Detecting elements such as planes in 3D is essential to describe objects for applications such as robotics and augmented reality. While plane estimation is well studied, table-top scenes exhibit a large number of planes and methods often lock onto a dominant plane or do not estimate 3D object structure but only homographies of individual planes. In this paper we introduce MDL to the problem of incrementally detecting multiple planar patches in a scene using tracked interest points in image sequences. Planar patches are reconstructed and stored in a keyframe-based graph structure. In case different motions occur, separate object hypotheses are modelled from currently visible patches and patches seen in previous frames. We evaluate our approach on a standard data set published by the Visual Geometry Group at the University of Oxford [24] and on our own data set containing table-top scenes. Results indicate that our approach significantly improves over the state-of-the-art algorithms.

  14. Interactive object modelling based on piecewise planar surface patches☆

    Science.gov (United States)

    Prankl, Johann; Zillich, Michael; Vincze, Markus

    2013-01-01

    Detecting elements such as planes in 3D is essential to describe objects for applications such as robotics and augmented reality. While plane estimation is well studied, table-top scenes exhibit a large number of planes and methods often lock onto a dominant plane or do not estimate 3D object structure but only homographies of individual planes. In this paper we introduce MDL to the problem of incrementally detecting multiple planar patches in a scene using tracked interest points in image sequences. Planar patches are reconstructed and stored in a keyframe-based graph structure. In case different motions occur, separate object hypotheses are modelled from currently visible patches and patches seen in previous frames. We evaluate our approach on a standard data set published by the Visual Geometry Group at the University of Oxford [24] and on our own data set containing table-top scenes. Results indicate that our approach significantly improves over the state-of-the-art algorithms. PMID:24511219

  15. PPI-IRO: A two-stage method for protein-protein interaction extraction based on interaction relation ontology

    KAUST Repository

    Li, Chuanxi

    2014-01-01

    Mining Protein-Protein Interactions (PPIs) from the fast-growing biomedical literature resources has been proven as an effective approach for the identifi cation of biological regulatory networks. This paper presents a novel method based on the idea of Interaction Relation Ontology (IRO), which specifi es and organises words of various proteins interaction relationships. Our method is a two-stage PPI extraction method. At fi rst, IRO is applied in a binary classifi er to determine whether sentences contain a relation or not. Then, IRO is taken to guide PPI extraction by building sentence dependency parse tree. Comprehensive and quantitative evaluations and detailed analyses are used to demonstrate the signifi cant performance of IRO on relation sentences classifi cation and PPI extraction. Our PPI extraction method yielded a recall of around 80% and 90% and an F1 of around 54% and 66% on corpora of AIMed and Bioinfer, respectively, which are superior to most existing extraction methods. Copyright © 2014 Inderscience Enterprises Ltd.

  16. Method of predicting Splice Sites based on signal interactions

    Directory of Open Access Journals (Sweden)

    Deogun Jitender S

    2006-04-01

    Full Text Available Abstract Background Predicting and proper ranking of canonical splice sites (SSs is a challenging problem in bioinformatics and machine learning communities. Any progress in SSs recognition will lead to better understanding of splicing mechanism. We introduce several new approaches of combining a priori knowledge for improved SS detection. First, we design our new Bayesian SS sensor based on oligonucleotide counting. To further enhance prediction quality, we applied our new de novo motif detection tool MHMMotif to intronic ends and exons. We combine elements found with sensor information using Naive Bayesian Network, as implemented in our new tool SpliceScan. Results According to our tests, the Bayesian sensor outperforms the contemporary Maximum Entropy sensor for 5' SS detection. We report a number of putative Exonic (ESE and Intronic (ISE Splicing Enhancers found by MHMMotif tool. T-test statistics on mouse/rat intronic alignments indicates, that detected elements are on average more conserved as compared to other oligos, which supports our assumption of their functional importance. The tool has been shown to outperform the SpliceView, GeneSplicer, NNSplice, Genio and NetUTR tools for the test set of human genes. SpliceScan outperforms all contemporary ab initio gene structural prediction tools on the set of 5' UTR gene fragments. Conclusion Designed methods have many attractive properties, compared to existing approaches. Bayesian sensor, MHMMotif program and SpliceScan tools are freely available on our web site. Reviewers This article was reviewed by Manyuan Long, Arcady Mushegian and Mikhail Gelfand.

  17. 4.1 Web-based interactive learning programmes.

    Science.gov (United States)

    Nattestad, Anders; Attstrom, Rolf; Mattheos, Nikos; Ramseier, Christoph; Canegallo, Lorenza; Eaton, Ken; Feeney, Luke; Goffin, Guy; Markovska, Neda; Maixner, William; Persson, Rutger; Reynolds, Patricia; Ruotoistenmaki, Juha; Schittek, Martin; Spohn, Eric; Sudzina, Mike

    2002-01-01

    In the future, the training of competent dentists will need to take advantage of up-to-date digital technologies and learning practices. In order to accomplish this, the following goals should be considered: i) the design of 'customizable' web-based curriculum matrices that accommodate the training philosophies and resources of individual dental schools; ii) the development of digital instructional modules that can be incorporated or downloaded into specific parts of a curriculum; iii) the establishment of an e-consortium, which provides peer view and guidance in the design of teaching modules, and which is responsible for the storage, maintenance, and distribution of teaching modules within the consortium; iv) the development of central human and physical resources at each dental school to enable the seamless delivery of instructional modules in a variety of learning environments; and v) the assessment and provision of ICT training to students and faculty with respect to the use of computers and related digital technologies and educational software programmes. These goals should lead to the creation of a 'virtual dental school'. Within this project summative and formative evaluations should be performed during both the production and development of teaching material (e-learning material) and the learning process. During the learning process the following aspects should be measured and evaluated: i) students' behaviour; and ii) effectiveness, retention and the transfer of e-learned material into the clinical situation. To obtain evidence of the efficacy of e-learning material a certain amount of research has to be done in the near future. It is suggested that all parameters currently known have to be implemented during the development of a learning programme. Previous workers have evaluated the following elements with e-learning: i) planning, ii) programming and technical development, iii) learning behaviours, iv) learning outcomes of both the programme and the

  18. A point-based rendering approach for real-time interaction on mobile devices

    Institute of Scientific and Technical Information of China (English)

    LIANG XiaoHui; ZHAO QinPing; HE ZhiYing; XIE Ke; LIU YuBo

    2009-01-01

    Mobile device is an Important interactive platform. Due to the limitation of computation, memory, display area and energy, how to realize the efficient and real-time interaction of 3D models based on mobile devices is an important research topic. Considering features of mobile devices, this paper adopts remote rendering mode and point models, and then, proposes a transmission and rendering approach that could interact in real time. First, improved simplification algorithm based on MLS and display resolution of mobile devices is proposed. Then, a hierarchy selection of point models and a QoS transmission control strategy are given based on interest area of operator, interest degree of object in the virtual environment and rendering error. They can save the energy consumption. Finally, the rendering and interaction of point models are completed on mobile devices. The experiments show that our method is efficient.

  19. An interactive game-based shoulder wheel system for rehabilitation

    Directory of Open Access Journals (Sweden)

    Chou LW

    2012-11-01

    Full Text Available Chun-Ming Chang,1,* Yen-Ching Chang,2,3 Hsiao-Yun Chang,4 Li-Wei Chou5,6,* 1Department of Applied Informatics and Multimedia, Asia University, Taichung, Taiwan; 2Department of Medical Informatics, Chung Shan Medical University, Taichung, Taiwan; 3Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan; 4Department of Biotechnology, Asia University, Taichung, Taiwan; 5Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 6School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan*These authors contributed equally to this workBackground: Increases in the aging population and in the number of accidents have resulted in more people suffering from physical impairments or disabilities. Rehabilitation therapy thus attracts greater attention as a means of helping patients recover and return to a normal life. With the extremely long and tedious nature of traditional rehabilitation, patients are reluctant to continue the entire process, thus the expected effects of the therapy cannot be obtained. Games are well known to help patients improve their concentration and shift their attention away from the discomfort of their injuries during rehabilitation. Thus, incorporating game technology into a rehabilitation program may be a promising approach.Methods: In this study, a gaming system used for shoulder rehabilitation was developed. The mechanical parts and electric circuits were integrated to mimic the functionalities of a shoulder wheel. Several games were also designed to suit the rehabilitation needs of the patients based on the age and gender differences among the individual users, enabling individuals to undergo the rehabilitation process by playing games. Two surveys were conducted to evaluate the satisfaction of the participants regarding the gaming system.Results: The results of the online survey among a larger population

  20. Cardiac and Carotid Markers Link With Accelerated Brain Atrophy: The AGES-Reykjavik Study (Age, Gene/Environment Susceptibility-Reykjavik).

    Science.gov (United States)

    Sabayan, Behnam; van Buchem, Mark A; Sigurdsson, Sigurdur; Zhang, Qian; Meirelles, Osorio; Harris, Tamara B; Gudnason, Vilmundur; Arai, Andrew E; Launer, Lenore J

    2016-11-01

    Pathologies in the heart-brain axis might, independently or in combination, accelerate the process of brain parenchymal loss. We aimed to investigate the association of serum N-terminal brain natriuretic peptide (NT-proBNP), as a marker of cardiac dysfunction, and carotid intima media thickness (CIMT), as a marker of carotid atherosclerosis burden, with structural brain changes. In the longitudinal population-based AGES-Reykjavik study (Age, Gene/Environment Susceptibility-Reykjavik), we included 2430 subjects (mean age, 74.6 years; 41.4% men) with baseline data on NT-proBNP and CITM (assessed by ultrasound imaging). Participants underwent a high-resolution brain magnetic resonance imaging at baseline and 5 years later to assess total brain (TBV), gray matter, and white matter volumes. Each unit higher log-transformed NT-proBNP was associated with 3.6 mL (95% confidence interval [CI], -6.0 to -1.1) decline in TBV and 3.5 mL (95% CI, -5.7 to -1.3) decline in gray matter volume. Likewise, each millimeter higher CIMT was associated with 10.8 mL (95% CI, -17.3 to -4.2) decline in TBV and 8.6 mL (95% CI, -14.4 to -2.8) decline in gray matter volume. There was no association between NT-proBNP and CIMT and changes in white matter volume. Compared with participants with low NT-proBNP and CIMT, participants with both high NT-proBNP and CIMT had 3.8 mL (95% CI, -6.0 to -1.6) greater decline in their TBV and 4 mL (95% CI, -6.0 to -2.0) greater decline in GMW. These associations were independent of sociodemographic and cardiovascular factors. Older subjects with both cardiac dysfunction and carotid atherosclerosis are at an increased risk for brain parenchymal loss. Accumulated pathologies in the heart-brain axis might accelerate brain atrophy. © 2016 American Heart Association, Inc.

  1. Risk Factors Associated With Incident Cerebral Microbleeds According to Location in Older People: The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.

    Science.gov (United States)

    Ding, Jie; Sigurdsson, Sigurdur; Garcia, Melissa; Phillips, Caroline L; Eiriksdottir, Gudny; Gudnason, Vilmundur; van Buchem, Mark A; Launer, Lenore J

    2015-06-01

    The spatial distribution of cerebral microbleeds (CMBs), which are asymptomatic precursors of intracerebral hemorrhage, reflects specific underlying microvascular abnormalities of cerebral amyloid angiopathy (lobar structures) and hypertensive vasculopathy (deep brain structures). Relatively little is known about the occurrence of and modifiable risk factors for developing CMBs, especially in a lobar location, in the general population of older people. To investigate whether lifestyle and lipid factors predict new CMBs in relation to their anatomic location. We enrolled 2635 individuals aged 66 to 93 years from the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study in a brain imaging study. Participants underwent a baseline magnetic resonance imaging (MRI) examination of the brain from September 1, 2002, through February 28, 2006, and returned for a second MRI examination from April 1, 2007, through September 30, 2011. Lifestyle and lipid factors assessed at baseline included smoking, alcohol consumption, body mass index, and serum levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides. Incident CMBs detected on MRIs, which were further categorized as exclusively lobar or as deep. During a mean follow-up of 5.2 years, 486 people (18.4%) developed new CMBs, of whom 308 had lobar CMBs only and 178 had deep CMBs. In the multivariate logarithm-binomial regression model adjusted for baseline cardiovascular risk factors, including blood pressure, antihypertensive use, prevalent CMBs, and markers of cerebral ischemic small-vessel disease, heavy alcohol consumption (vs light to moderate consumption; relative risk [RR], 2.94 [95% CI, 1.23-7.01]) was associated with incident CMBs in a deep location. Baseline underweight (vs normal weight; RR, 2.41 [95% CI, 1.21-4.80]), current smoking (RR, 1.47 [95% CI, 1.11-1.94]), an elevated serum level of high-density lipoprotein cholesterol (RR per 1-SD increase, 1.13 [95

  2. The Interactions between Imidazolium-Based Ionic Liquids and Stable Nitroxide Radical Species: A Theoretical Study.

    Science.gov (United States)

    Zhang, Shaoze; Wang, Guimin; Lu, Yunxiang; Zhu, Weiliang; Peng, Changjun; Liu, Honglai

    2016-08-01

    In this work, the interactions between imidazolium-based ionic liquids and some stable radicals based on 2,2,6,6-tetramethylpiperidine-1-yloxyl (TEMPO) have been systematically investigated using density functional theory calculations at the level of M06-2x. Several different substitutions, such as hydrogen bonding formation substituent (OH) and ionic substituents (N(CH3)3(+) and OSO3(-)), are presented at the 4-position of the spin probe, which leads to additional hydrogen bonds or ionic interactions between these substitutions and ionic liquids. The interactions in the systems of the radicals containing ionic substitutions with ionic liquids are predicted much stronger than those in the systems of neutral radicals, resulting in a significant reduction of the mobility of ionic radicals in ionic liquids. To further understand the nature of these interactions, the natural bond order, atoms in molecules, noncovalent interaction index, electron density difference, energy decomposition analysis, and charge decomposition analysis schemes were employed. The additional ionic interactions between ionic radicals and counterions in ionic liquids are dominantly contributed from the electrostatic term, while the orbital interaction plays a major role in other interactions. The results reported herein are important to understand radical processes in ionic liquids and will be very useful in the design of task-specific ionic liquids to make the processes more efficient.

  3. Cursive word recognition based on interactive activation and early visual processing models.

    Science.gov (United States)

    Ruiz-Pinales, Jose; Jaime-Rivas, Rene; Lecolinet, Eric; Castro-Bleda, Maria Jose

    2008-10-01

    We present an off-line cursive word recognition system based completely on neural networks: reading models and models of early visual processing. The first stage (normalization) preprocesses the input image in order to reduce letter position uncertainty; the second stage (feature extraction) is based on the feedforward model of orientation selectivity; the third stage (letter pre-recognition) is based on a convolutional neural network, and the last stage (word recognition) is based on the interactive activation model.

  4. Sub-Synchronous Interaction Analysis between DFIG Based Wind Farm and Series Compensated Network

    DEFF Research Database (Denmark)

    Wang, Yun; Wu, Qiuwei; Kang, Shaoli

    2016-01-01

    This paper analyzes the sub-synchronous interaction (SSI) phenomenon between the doubly fed induction generator (DFIG) based wind farm (WF) and the series capacitor compensated network. The possible types of SSI in the DFIG based WF are studied. The factors influencing the SSI of DFIG based WF...... are investigated. The large signal stability and small signal stability of the DFIG based WF with different series compensation (SC) level and wind speed are simulated and compared....

  5. Protein-protein interactions prediction based on iterative clique extension with gene ontology filtering.

    Science.gov (United States)

    Yang, Lei; Tang, Xianglong

    2014-01-01

    Cliques (maximal complete subnets) in protein-protein interaction (PPI) network are an important resource used to analyze protein complexes and functional modules. Clique-based methods of predicting PPI complement the data defection from biological experiments. However, clique-based predicting methods only depend on the topology of network. The false-positive and false-negative interactions in a network usually interfere with prediction. Therefore, we propose a method combining clique-based method of prediction and gene ontology (GO) annotations to overcome the shortcoming and improve the accuracy of predictions. According to different GO correcting rules, we generate two predicted interaction sets which guarantee the quality and quantity of predicted protein interactions. The proposed method is applied to the PPI network from the Database of Interacting Proteins (DIP) and most of the predicted interactions are verified by another biological database, BioGRID. The predicted protein interactions are appended to the original protein network, which leads to clique extension and shows the significance of biological meaning.

  6. Protein-Protein Interactions Prediction Based on Iterative Clique Extension with Gene Ontology Filtering

    Directory of Open Access Journals (Sweden)

    Lei Yang

    2014-01-01

    Full Text Available Cliques (maximal complete subnets in protein-protein interaction (PPI network are an important resource used to analyze protein complexes and functional modules. Clique-based methods of predicting PPI complement the data defection from biological experiments. However, clique-based predicting methods only depend on the topology of network. The false-positive and false-negative interactions in a network usually interfere with prediction. Therefore, we propose a method combining clique-based method of prediction and gene ontology (GO annotations to overcome the shortcoming and improve the accuracy of predictions. According to different GO correcting rules, we generate two predicted interaction sets which guarantee the quality and quantity of predicted protein interactions. The proposed method is applied to the PPI network from the Database of Interacting Proteins (DIP and most of the predicted interactions are verified by another biological database, BioGRID. The predicted protein interactions are appended to the original protein network, which leads to clique extension and shows the significance of biological meaning.

  7. Simplified method to predict mutual interactions of human transcription factors based on their primary structure

    KAUST Repository

    Schmeier, Sebastian

    2011-07-05

    Background: Physical interactions between transcription factors (TFs) are necessary for forming regulatory protein complexes and thus play a crucial role in gene regulation. Currently, knowledge about the mechanisms of these TF interactions is incomplete and the number of known TF interactions is limited. Computational prediction of such interactions can help identify potential new TF interactions as well as contribute to better understanding the complex machinery involved in gene regulation. Methodology: We propose here such a method for the prediction of TF interactions. The method uses only the primary sequence information of the interacting TFs, resulting in a much greater simplicity of the prediction algorithm. Through an advanced feature selection process, we determined a subset of 97 model features that constitute the optimized model in the subset we considered. The model, based on quadratic discriminant analysis, achieves a prediction accuracy of 85.39% on a blind set of interactions. This result is achieved despite the selection for the negative data set of only those TF from the same type of proteins, i.e. TFs that function in the same cellular compartment (nucleus) and in the same type of molecular process (transcription initiation). Such selection poses significant challenges for developing models with high specificity, but at the same time better reflects real-world problems. Conclusions: The performance of our predictor compares well to those of much more complex approaches for predicting TF and general protein-protein interactions, particularly when taking the reduced complexity of model utilisation into account. © 2011 Schmeier et al.

  8. Shrinkage Estimators for Robust and Efficient Inference in Haplotype-Based Case-Control Studies

    KAUST Repository

    Chen, Yi-Hau

    2009-03-01

    Case-control association studies often aim to investigate the role of genes and gene-environment interactions in terms of the underlying haplotypes (i.e., the combinations of alleles at multiple genetic loci along chromosomal regions). The goal of this article is to develop robust but efficient approaches to the estimation of disease odds-ratio parameters associated with haplotypes and haplotype-environment interactions. We consider "shrinkage" estimation techniques that can adaptively relax the model assumptions of Hardy-Weinberg-Equilibrium and gene-environment independence required by recently proposed efficient "retrospective" methods. Our proposal involves first development of a novel retrospective approach to the analysis of case-control data, one that is robust to the nature of the gene-environment distribution in the underlying population. Next, it involves shrinkage of the robust retrospective estimator toward a more precise, but model-dependent, retrospective estimator using novel empirical Bayes and penalized regression techniques. Methods for variance estimation are proposed based on asymptotic theories. Simulations and two data examples illustrate both the robustness and efficiency of the proposed methods.

  9. Dynamic Multicast Grouping Approach in HLA-Based Distributed Interactive Simulation

    Institute of Scientific and Technical Information of China (English)

    DAI Zhong-jian; HOU Chao-zhen

    2005-01-01

    In order to improve the efficiency of data distributed management service in distributed interactive simulation based on high level architecture (HLA) and to reduce the network traffic and save the system resource, the approaches of multicast grouping in HLA-based distributed interactive simulation are discussed. Then a new dynamic multicast grouping approach is proposed. This approach is based on the current publication and subscription region in the process of simulation. The results of simulation experiment show that this approach can significantly reduce the message overhead and use fewer multicast groups.

  10. Collaborative Scaffolding in Online Task-Based Voice Interactions between Advanced Learners

    Science.gov (United States)

    Kenning, Marie-Madeleine

    2010-01-01

    This paper reports some of the findings of a distinctive innovative use of audio-conferencing involving a population (campus-based advanced learners) and a type of application (task-based language learning) that have received little attention to date: the use of Wimba Voice Tools to provide additional opportunities for spoken interactions between…

  11. Twenty weeks of home-based interactive training of children with cerebral palsy improves functional abilities

    DEFF Research Database (Denmark)

    Lorentzen, Jakob; Greve, Line Z; Kliim-Due, Mette

    2015-01-01

    BACKGROUND: Home-based training is becoming ever more important with increasing demands on the public health systems. We investigated whether individualized and supervised interactive home-based training delivered through the internet improves functional abilities in children with cerebral palsy...

  12. Whole Language versus Code-Based Skills and Interactional Patterns in Singapore's Early Literacy Program

    Science.gov (United States)

    Vaish, Viniti

    2014-01-01

    This paper analyzes whole language and code-based skills approaches in early literacy and the specific patterns of interaction present in both approaches. Nineteen hours of video data were coded to analyze the nature of whole language versus code-based skills instruction and document the allocation of time spent on each approach in a reading…

  13. Reciprocity in computer-human interaction: source-based, norm-based, and affect-based explanations.

    Science.gov (United States)

    Lee, Seungcheol Austin; Liang, Yuhua Jake

    2015-04-01

    Individuals often apply social rules when they interact with computers, and this is known as the Computers Are Social Actors (CASA) effect. Following previous work, one approach to understand the mechanism responsible for CASA is to utilize computer agents and have the agents attempt to gain human compliance (e.g., completing a pattern recognition task). The current study focuses on three key factors frequently cited to influence traditional notions of compliance: evaluations toward the source (competence and warmth), normative influence (reciprocity), and affective influence (mood). Structural equation modeling assessed the effects of these factors on human compliance with computer request. The final model shows that norm-based influence (reciprocity) increased the likelihood of compliance, while evaluations toward the computer agent did not significantly influence compliance.

  14. A Study of User's Performance and Satisfaction on the Web Based Photo Annotation with Speech Interaction

    CERN Document Server

    Ramlan, Siti Azura

    2010-01-01

    This paper reports on empirical evaluation study of users' performance and satisfaction with prototype of Web Based speech photo annotation with speech interaction. Participants involved consist of Johor Bahru citizens from various background. They have completed two parts of annotation task; part A involving PhotoASys; photo annotation system with proposed speech interaction and part B involving Microsoft Microsoft Vista Speech Interaction style. They have completed eight tasks for each part including system login and selection of album and photos. Users' performance was recorded using computer screen recording software. Data were captured on the task completion time and subjective satisfaction. Participants need to complete a questionnaire on the subjective satisfaction when the task was completed. The performance data show the comparison between proposed speech interaction and Microsoft Vista Speech interaction applied in photo annotation system, PhotoASys. On average, the reduction in annotation performan...

  15. A Framework for Spatial Interaction Analysis Based on Large-Scale Mobile Phone Data

    Directory of Open Access Journals (Sweden)

    Weifeng Li

    2014-01-01

    Full Text Available The overall understanding of spatial interaction and the exact knowledge of its dynamic evolution are required in the urban planning and transportation planning. This study aimed to analyze the spatial interaction based on the large-scale mobile phone data. The newly arisen mass dataset required a new methodology which was compatible with its peculiar characteristics. A three-stage framework was proposed in this paper, including data preprocessing, critical activity identification, and spatial interaction measurement. The proposed framework introduced the frequent pattern mining and measured the spatial interaction by the obtained association. A case study of three communities in Shanghai was carried out as verification of proposed method and demonstration of its practical application. The spatial interaction patterns and the representative features proved the rationality of the proposed framework.

  16. MAS C-Terminal Tail Interacting Proteins Identified by Mass Spectrometry- Based Proteomic Approach.

    Science.gov (United States)

    Tirupula, Kalyan C; Zhang, Dongmei; Osbourne, Appledene; Chatterjee, Arunachal; Desnoyer, Russ; Willard, Belinda; Karnik, Sadashiva S

    2015-01-01

    Propagation of signals from G protein-coupled receptors (GPCRs) in cells is primarily mediated by protein-protein interactions. MAS is a GPCR that was initially discovered as an oncogene and is now known to play an important role in cardiovascular physiology. Current literature suggests that MAS interacts with common heterotrimeric G-proteins, but MAS interaction with proteins which might mediate G protein-independent or atypical signaling is unknown. In this study we hypothesized that MAS C-terminal tail (Ct) is a major determinant of receptor-scaffold protein interactions mediating MAS signaling. Mass-spectrometry based proteomic analysis was used to comprehensively identify the proteins that interact with MAS Ct comprising the PDZ-binding motif (PDZ-BM). We identified both PDZ and non-PDZ proteins from human embryonic kidney cell line, mouse atrial cardiomyocyte cell line and human heart tissue to interact specifically with MAS Ct. For the first time our study provides a panel of PDZ and other proteins that potentially interact with MAS with high significance. A 'cardiac-specific finger print' of MAS interacting PDZ proteins was identified which includes DLG1, MAGI1 and SNTA. Cell based experiments with wild-type and mutant MAS lacking the PDZ-BM validated MAS interaction with PDZ proteins DLG1 and TJP2. Bioinformatics analysis suggested well-known multi-protein scaffold complexes involved in nitric oxide signaling (NOS), cell-cell signaling of neuromuscular junctions, synapses and epithelial cells. Majority of these protein hits were predicted to be part of disease categories comprising cancers and malignant tumors. We propose a 'MAS-signalosome' model to stimulate further research in understanding the molecular mechanism of MAS function. Identifying hierarchy of interactions of 'signalosome' components with MAS will be a necessary step in future to fully understand the physiological and pathological functions of this enigmatic receptor.

  17. Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.

    Directory of Open Access Journals (Sweden)

    Ming-Wei Su

    Full Text Available BACKGROUND: The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 single-nucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1, the gene coding interleukin-4 receptor alpha chain (IL4Ra and the gene coding insulin induced gene 2 (INSIG2 on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83% with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2, signal transducer and activator of transcription 6 (STAT6. We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest that GSTP1, INSIG2 and IL4Ra may influence the lifetime asthma susceptibility through gene-gene interactions in schoolchildren. Home dampness combined with each one of the genes STAT6, IL13 and ADRB2 could raise the asthma risk.

  18. Proteome-wide prediction of self-interacting proteins based on multiple properties.

    Science.gov (United States)

    Liu, Zhongyang; Guo, Feifei; Zhang, Jiyang; Wang, Jian; Lu, Liang; Li, Dong; He, Fuchu

    2013-06-01

    Self-interacting proteins, whose two or more copies can interact with each other, play important roles in cellular functions and the evolution of protein interaction networks (PINs). Knowing whether a protein can self-interact can contribute to and sometimes is crucial for the elucidation of its functions. Previous related research has mainly focused on the structures and functions of specific self-interacting proteins, whereas knowledge on their overall properties is limited. Meanwhile, the two current most common high throughput protein interaction assays have limited ability to detect self-interactions because of biological artifacts and design limitations, whereas the bioinformatic prediction method of self-interacting proteins is lacking. This study aims to systematically study and predict self-interacting proteins from an overall perspective. We find that compared with other proteins the self-interacting proteins in the structural aspect contain more domains; in the evolutionary aspect they tend to be conserved and ancient; in the functional aspect they are significantly enriched with enzyme genes, housekeeping genes, and drug targets, and in the topological aspect tend to occupy important positions in PINs. Furthermore, based on these features, after feature selection, we use logistic regression to integrate six representative features, including Gene Ontology term, domain, paralogous interactor, enzyme, model organism self-interacting protein, and betweenness centrality in the PIN, to develop a proteome-wide prediction model of self-interacting proteins. Using 5-fold cross-validation and an independent test, this model shows good performance. Finally, the prediction model is developed into a user-friendly web service SLIPPER (SeLf-Interacting Protein PrEdictoR). Users may submit a list of proteins, and then SLIPPER will return the probability_scores measuring their possibility to be self-interacting proteins and various related annotation information. This

  19. Updated solution to the solar neutrino problem based on non-standard neutrino interactions

    CERN Document Server

    Guzzo, M M; Nunokawa, H

    2001-01-01

    We present an updated version of the solution to the solar neutrino problem based on non-standard flavor changing neutrino interactions (FCNI) and non-universal flavor diagonal neutrino interactions (FDNI). We find a good fit not only to the total rates measured by all solar neutrino experiments but also to the day-night and seasonal variations of the event rate, as well as the recoil electron energy spectrum measured by the SuperKamiokande collaboration.

  20. Study of high-speed interaction processes between fluoropolymer projectiles and aluminum-based targets

    Institute of Scientific and Technical Information of China (English)

    Evgeny A. KHMELNIKOV; Alexey V. STYROV; Konstantin V. SMAGIN; Natalia S. KRAVCHENKO; Valery L. RUDENKO; Vladimir I. FALALEEV; Sergey S. SOKOLOV; Artem V. SVIDINSKY; Natalia F. SVIDINSKAYA

    2015-01-01

    The experimental results and numerical modeling of penetration process of fluoropolymer projectiles in aluminum-based targets are pre-sented. Analysis of mathematical models for interaction of elastoplastic projectile and target without taking additional energy released during interaction of fluoropolymer and aluminum into consideration is carried out. Energy fraction which is spent effectively on the increase in cavity volume is determined. The experimental and calculated results of penetration by combined and inert projectiles are compared.

  1. Photoswitchable Adsorption in Metal-Organic Frameworks Based on Polar Guest-Host Interactions.

    Science.gov (United States)

    Wang, Zhengbang; Grosjean, Sylvain; Bräse, Stefan; Heinke, Lars

    2015-12-21

    Reversible remote-controlled switching of the properties of nanoporous metal-organic frameworks (MOFs) is enabled by incorporating photoswitchable azobenzene. The interaction of the host material with different guest molecules, which is crucial for all applications, is precisely studied using thin MOF films of the type Cu2 (BDC)2 (AzoBipyB). A molecule-specific effect of the photoswitching, based on dipole-dipole interactions, is found.

  2. A Q-based integrating interaction framework system for multi-agent coordination

    Institute of Scientific and Technical Information of China (English)

    WANG Zhen-jie; SHENG Huan-ye; XIAO Zheng-guang

    2005-01-01

    Interaction is one of the crucial features of multi-agent systems, in which there are two kinds of interaction: agent-to-agent and human-to-agent. In order to unify the two kinds of interaction while designing multiagent systems, this paper introduces Q language-a scenario description language for designing interaction among agents and humans. Based on Q, we propose an integrating interaction framework system for multi-agent coordination, in which Q scenarios are used to uniformly describe both kinds of interactions. Being in accordance to the characteristics of Q language, the Q-based framework makes the interaction process open and easily understood by the users. Additionally, it makes specific applications of multi-agent systems easy to be established by application designers. By applying agent negotiation in agent-mediated e-commerce and agent cooperation in interoperable information query on the Semantic Web, we illustrate how the presented framework for multi-agent coordination is implemented in concrete applications. At the same time, these two different applications also demonstrate usability of the presented framework and verify validity of Q language.

  3. A New Framework of Human Interaction Recognition Based on Multiple Stage Probability Fusion

    Directory of Open Access Journals (Sweden)

    Xiaofei Ji

    2017-06-01

    Full Text Available Visual-based human interactive behavior recognition is a challenging research topic in computer vision. There exist some important problems in the current interaction recognition algorithms, such as very complex feature representation and inaccurate feature extraction induced by wrong human body segmentation. In order to solve these problems, a novel human interaction recognition method based on multiple stage probability fusion is proposed in this paper. According to the human body’s contact in interaction as a cut-off point, the process of the interaction can be divided into three stages: start stage, execution stage and end stage. Two persons’ motions are respectively extracted and recognizes in the start stage and the finish stage when there is no contact between those persons. The two persons’ motion is extracted as a whole and recognized in the execution stage. In the recognition process, the final recognition results are obtained by the weighted fusing these probabilities in different stages. The proposed method not only simplifies the extraction and representation of features, but also avoids the wrong feature extraction caused by occlusion. Experiment results on the UT-interaction dataset demonstrated that the proposed method results in a better performance than other recent interaction recognition methods.

  4. Web-based interactive visualization in a Grid-enabled neuroimaging application using HTML5.

    Science.gov (United States)

    Siewert, René; Specovius, Svenja; Wu, Jie; Krefting, Dagmar

    2012-01-01

    Interactive visualization and correction of intermediate results are required in many medical image analysis pipelines. To allow certain interaction in the remote execution of compute- and data-intensive applications, new features of HTML5 are used. They allow for transparent integration of user interaction into Grid- or Cloud-enabled scientific workflows. Both 2D and 3D visualization and data manipulation can be performed through a scientific gateway without the need to install specific software or web browser plugins. The possibilities of web-based visualization are presented along the FreeSurfer-pipeline, a popular compute- and data-intensive software tool for quantitative neuroimaging.

  5. Tele-Immersive Interaction with Intelligent Virtual Agents Based on Real-Time 3D Modeling

    Directory of Open Access Journals (Sweden)

    Shujun Zhang

    2012-02-01

    Full Text Available To enable intelligent agents interacting smoothly with human users, researchers have been deploying novel interaction modalities (e.g. non-verbal cue, vision and touch in addition to agents’ conversational skills. Models of multi-modality interaction can enhance agents’ real-time perception, cognition and reaction towards the user. In this paper we report a novel tele-immersive interaction system developed using real-time 3D modelling techniques. In such system user’s full body is reconstructed using multi-view cameras and CUDA based visual hull reconstruction algorithm. User’s mesh model is then loaded into a virtual environment for interacting with an autonomous agent. Technical details and initial results of the system are illustrated in this paper. Following that a novel interaction scenario is proposed which links the virtual agent with a remote physical robot who takes the role of mediating interactions between two geographically separated users. Finally we discuss in depth the implications of such human-agent interaction and possible future improvements and directions.

  6. Plant-based antimicrobial studies--methods and approaches to study the interaction between natural products.

    Science.gov (United States)

    van Vuuren, Sandy; Viljoen, Alvaro

    2011-07-01

    The therapeutic value of synergistic interactions has been known since antiquity, and many different cultural healing systems still rely on this principle in the belief that combination therapy may enhance efficacy. This paper intends to provide an overview, from an antimicrobial perspective, on the research undertaken and interactive principles involved in pharmacognosy studies. Methods used to determine antimicrobial interactions include basic combination studies, the sum of the fractional inhibitory concentration index (ΣFIC), isobole interpretations, and death kinetic (time-kill) assays. The various interactions are discussed with reference to molecules, different plant parts or fractions, different plant species, and combinations with nonbotanical antimicrobial agents. It is recommended for future development in the field of phytosynergy that consideration should be given to the selection criteria for the two inhibitors. A more conservative approach should be adopted when classifying synergy. When examining interactions in plant-based studies, antagonistic interactions should not be ignored. Combinations involving more than two test samples should be examined where applicable, and very importantly, the mechanism of action of synergistic interactions should be given precedence. It is encouraging to observe the upsurge in papers exploring the complex interactions of medicinal plants, and undoubtedly this will become increasingly important in our continued quest to understand the mechanism of action of phytotherapy. The scientific validation of efficacious antimicrobial combinations could lead to patentable entities making research in the field of phytosynergy not only academically rewarding but also commercially relevant.

  7. Poultry production: a model for developing interactive Internet-based distance education.

    Science.gov (United States)

    Emmert, J L; Shortridge, A M; Sexton, S L

    2003-05-01

    Over the last several decades, many poultry science programs have merged with other departments, but the poultry industry has undergone tremendous expansion worldwide, leading to a growing instructional void with regard to poultry production information. The objective of this project was to address the demand for information by developing two Web-based poultry production courses that cover management of broilers, turkeys, breeders, and layers. The Internet was chosen as the platform because it is asynchronous and may be accessed from any connected site around the world. To be effective, web-based courseware must be theoretically grounded and interactive, but university-level web-based distance education courses often fail to meet these standards. During courseware development, the impact of instructional techniques and technologies on interactivity and learning outcomes was explored. A content expert, an instructional designer, and a graphic artist carefully reviewed a variety of instructional techniques to increase interactivity. Concept mapping was chosen because it has been shown to be a superior learning tool for enhancing the exchange of ideas and knowledge between instructors, students, and content. A unique instructional interface was established that includes threaded e-mail discussion, thought questions, animation, hypertext, rollover interactions, video clips, and concept mapping exercises. Results indicate that the integration of concept mapping into web-based learning environments successfully increased interactivity and learning outcomes.

  8. Predicting domain-domain interaction based on domain profiles with feature selection and support vector machines

    Directory of Open Access Journals (Sweden)

    Liao Li

    2010-10-01

    Full Text Available Abstract Background Protein-protein interaction (PPI plays essential roles in cellular functions. The cost, time and other limitations associated with the current experimental methods have motivated the development of computational methods for predicting PPIs. As protein interactions generally occur via domains instead of the whole molecules, predicting domain-domain interaction (DDI is an important step toward PPI prediction. Computational methods developed so far have utilized information from various sources at different levels, from primary sequences, to molecular structures, to evolutionary profiles. Results In this paper, we propose a computational method to predict DDI using support vector machines (SVMs, based on domains represented as interaction profile hidden Markov models (ipHMM where interacting residues in domains are explicitly modeled according to the three dimensional structural information available at the Protein Data Bank (PDB. Features about the domains are extracted first as the Fisher scores derived from the ipHMM and then selected using singular value decomposition (SVD. Domain pairs are represented by concatenating their selected feature vectors, and classified by a support vector machine trained on these feature vectors. The method is tested by leave-one-out cross validation experiments with a set of interacting protein pairs adopted from the 3DID database. The prediction accuracy has shown significant improvement as compared to InterPreTS (Interaction Prediction through Tertiary Structure, an existing method for PPI prediction that also uses the sequences and complexes of known 3D structure. Conclusions We show that domain-domain interaction prediction can be significantly enhanced by exploiting information inherent in the domain profiles via feature selection based on Fisher scores, singular value decomposition and supervised learning based on support vector machines. Datasets and source code are freely available on

  9. Prediction of oncogenic interactions and cancer-related signaling networks based on network topology.

    Science.gov (United States)

    Acencio, Marcio Luis; Bovolenta, Luiz Augusto; Camilo, Esther; Lemke, Ney

    2013-01-01

    Cancer has been increasingly recognized as a systems biology disease since many investigators have demonstrated that this malignant phenotype emerges from abnormal protein-protein, regulatory and metabolic interactions induced by simultaneous structural and regulatory changes in multiple genes and pathways. Therefore, the identification of oncogenic interactions and cancer-related signaling networks is crucial for better understanding cancer. As experimental techniques for determining such interactions and signaling networks are labor-intensive and time-consuming, the development of a computational approach capable to accomplish this task would be of great value. For this purpose, we present here a novel computational approach based on network topology and machine learning capable to predict oncogenic interactions and extract relevant cancer-related signaling subnetworks from an integrated network of human genes interactions (INHGI). This approach, called graph2sig, is twofold: first, it assigns oncogenic scores to all interactions in the INHGI and then these oncogenic scores are used as edge weights to extract oncogenic signaling subnetworks from INHGI. Regarding the prediction of oncogenic interactions, we showed that graph2sig is able to recover 89% of known oncogenic interactions with a precision of 77%. Moreover, the interactions that received high oncogenic scores are enriched in genes for which mutations have been causally implicated in cancer. We also demonstrated that graph2sig is potentially useful in extracting oncogenic signaling subnetworks: more than 80% of constructed subnetworks contain more than 50% of original interactions in their corresponding oncogenic linear pathways present in the KEGG PATHWAY database. In addition, the potential oncogenic signaling subnetworks discovered by graph2sig are supported by experimental evidence. Taken together, these results suggest that graph2sig can be a useful tool for investigators involved in cancer research

  10. Prediction of oncogenic interactions and cancer-related signaling networks based on network topology.

    Directory of Open Access Journals (Sweden)

    Marcio Luis Acencio

    Full Text Available Cancer has been increasingly recognized as a systems biology disease since many investigators have demonstrated that this malignant phenotype emerges from abnormal protein-protein, regulatory and metabolic interactions induced by simultaneous structural and regulatory changes in multiple genes and pathways. Therefore, the identification of oncogenic interactions and cancer-related signaling networks is crucial for better understanding cancer. As experimental techniques for determining such interactions and signaling networks are labor-intensive and time-consuming, the development of a computational approach capable to accomplish this task would be of great value. For this purpose, we present here a novel computational approach based on network topology and machine learning capable to predict oncogenic interactions and extract relevant cancer-related signaling subnetworks from an integrated network of human genes interactions (INHGI. This approach, called graph2sig, is twofold: first, it assigns oncogenic scores to all interactions in the INHGI and then these oncogenic scores are used as edge weights to extract oncogenic signaling subnetworks from INHGI. Regarding the prediction of oncogenic interactions, we showed that graph2sig is able to recover 89% of known oncogenic interactions with a precision of 77%. Moreover, the interactions that received high oncogenic scores are enriched in genes for which mutations have been causally implicated in cancer. We also demonstrated that graph2sig is potentially useful in extracting oncogenic signaling subnetworks: more than 80% of constructed subnetworks contain more than 50% of original interactions in their corresponding oncogenic linear pathways present in the KEGG PATHWAY database. In addition, the potential oncogenic signaling subnetworks discovered by graph2sig are supported by experimental evidence. Taken together, these results suggest that graph2sig can be a useful tool for investigators involved

  11. A hybrid configuration interaction treatment based on seniority number and excitation schemes

    Energy Technology Data Exchange (ETDEWEB)

    Alcoba, Diego R.; Capuzzi, Pablo [Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and Instituto de Física de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad Universitaria, 1428 Buenos Aires (Argentina); Torre, Alicia; Lain, Luis, E-mail: qfplapel@lg.ehu.es [Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco, Apdo. 644 E-48080 Bilbao (Spain); Oña, Ofelia B. [Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas, Universidad Nacional de La Plata, CCT La Plata, Consejo Nacional de Investigaciones Científicas y Técnicas, Diag. 113 y 64 (S/N), Sucursal 4, CC 16, 1900 La Plata (Argentina); Van Raemdonck, Mario; Bultinck, Patrick [Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281 (S3), 9000 Gent (Belgium); Van Neck, Dimitri [Center for Molecular Modelling, Ghent University, Technologiepark 903, 9052 Zwijnaarde (Belgium)

    2014-12-28

    We present a configuration interaction method in which the Hamiltonian of an N-electron system is projected on Slater determinants selected according to the seniority-number criterion along with the traditional excitation-based procedure. This proposed method is especially useful to describe systems which exhibit dynamic (weak) correlation at determined geometric arrangements (where the excitation-based procedure is more suitable) but show static (strong) correlation at other arrangements (where the seniority-number technique is preferred). The hybrid method amends the shortcomings of both individual determinant selection procedures, yielding correct shapes of potential energy curves with results closer to those provided by the full configuration interaction method.

  12. Specular Andreev reflection in graphene-based superconducting junction with substate-induced spin orbit interaction

    Science.gov (United States)

    Bai, Chunxu; Yang, Yanling

    2016-08-01

    Based on the Dirac-Bogoliubov-de Gennes equation, the chirality-resolved transport properties through a ballistic graphene-based superconducting heterojunction with both the Rashba and the Dresselhaus spin orbit interaction have been investigated. Our results show that, in contrast to the retro-Andreev reflection suppressed by the spin orbit interaction (SOI), the specular Andreev reflection (SAR) can be enhanced largely by the SOI. Moreover, the Fabry-Perot interferences in the barrier region lead to the oscillating feature of the tunneling conductance. It is anticipated to apply the qualitative different results to diagnose the SAR in single layer graphene in the presence of both kinds of the SOI.

  13. Efficient fold-change detection based on protein-protein interactions.

    Science.gov (United States)

    Buijsman, W; Sheinman, M

    2014-02-01

    Various biological sensory systems exhibit a response to a relative change of the stimulus, often referred to as fold-change detection. In the past few years, fold-change detecting mechanisms, based on transcriptional networks, have been proposed. Here we present a fold-change detecting mechanism, based on protein-protein interactions, consisting of two interacting proteins. This mechanism does not consume chemical energy and is not subject to transcriptional and translational noise, in contrast to previously proposed mechanisms. We show by analytical and numerical calculations that the mechanism is robust and can have a fast, precise, and efficient response for parameters that are relevant to eukaryotic cells.

  14. Efficient fold-change detection based on protein-protein interactions

    Science.gov (United States)

    Buijsman, W.; Sheinman, M.

    2014-02-01

    Various biological sensory systems exhibit a response to a relative change of the stimulus, often referred to as fold-change detection. In the past few years, fold-change detecting mechanisms, based on transcriptional networks, have been proposed. Here we present a fold-change detecting mechanism, based on protein-protein interactions, consisting of two interacting proteins. This mechanism does not consume chemical energy and is not subject to transcriptional and translational noise, in contrast to previously proposed mechanisms. We show by analytical and numerical calculations that the mechanism is robust and can have a fast, precise, and efficient response for parameters that are relevant to eukaryotic cells.

  15. Stacking interaction in metal complexes with compositions of DNA and heteroaromatic N-bases

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The current development in the intramolecular aromatic-ring stacking i nteractions in the complexes with compositions of DNA and heteroaromatic N-bases has been reviewed to a great extent, especially the significant contributions i n several important systems about ternary mixed-ligand complexes, including nucl eotide-metal ion-po- lyaromatic amine, amino acid-metal ion-polyaromatic amine, nucleotide-metal ion-pyridine-like aromatic amine, nucleotide-metal ion-amino ac id, nucleotide-metal ion-nucleic acid base, nucleic acid base-metal ion, and the important factors affecting the intramolecular aromatic-ring stacking interacti ons in the complexes. Based on the study of stacking interaction in the complexe s, the mechanism of interaction between DNA molecules and complexes of heteroaro matic N-bases has been established, which is crucial for the design and synthesi s of the complexes acting as molecular devices of DNA.

  16. Theoretical Studies on the Intermolecular Interactions of Potentially Primordial Base-Pair Analogues

    Energy Technology Data Exchange (ETDEWEB)

    Leszczynski, Jerzy [Computational Center for Molecular Structure and Interactions, Jackson, MS; Sponer, Judit [Academy of Sciences of the Czech Republic; Sponer, Jiri [Academy of Sciences of the Czech Republic; Sumpter, Bobby G [ORNL; Fuentes-Cabrera, Miguel A [ORNL; Vazquez-Mayagoitia, Alvaro [ORNL

    2010-01-01

    Recent experimental studies on the Watson Crick type base pairing of triazine and aminopyrimidine derivatives suggest that acid/base properties of the constituent bases might be related to the duplex stabilities measured in solution. Herein we use high-level quantum chemical calculations and molecular dynamics simulations to evaluate the base pairing and stacking interactions of seven selected base pairs, which are common in that they are stabilized by two NH O hydrogen bonds separated by one NH N hydrogen bond. We show that neither the base pairing nor the base stacking interaction energies correlate with the reported pKa data of the bases and the melting points of the duplexes. This suggests that the experimentally observed correlation between the melting point data of the duplexes and the pKa values of the constituent bases is not rooted in the intrinsic base pairing and stacking properties. The physical chemistry origin of the observed experimental correlation thus remains unexplained and requires further investigations. In addition, since our calculations are carried out with extrapolation to the complete basis set of atomic orbitals and with inclusion of higher electron correlation effects, they provide reference data for stacking and base pairing energies of non-natural bases.

  17. Limitations of a metabolic network-based reverse ecology method for inferring host-pathogen interactions.

    Science.gov (United States)

    Takemoto, Kazuhiro; Aie, Kazuki

    2017-05-25

    Host-pathogen interactions are important in a wide range of research fields. Given the importance of metabolic crosstalk between hosts and pathogens, a metabolic network-based reverse ecology method was proposed to infer these interactions. However, the validity of this method remains unclear because of the various explanations presented and the influence of potentially confounding factors that have thus far been neglected. We re-evaluated the importance of the reverse ecology method for evaluating host-pathogen interactions while statistically controlling for confounding effects using oxygen requirement, genome, metabolic network, and phylogeny data. Our data analyses showed that host-pathogen interactions were more strongly influenced by genome size, primary network parameters (e.g., number of edges), oxygen requirement, and phylogeny than the reserve ecology-based measures. These results indicate the limitations of the reverse ecology method; however, they do not discount the importance of adopting reverse ecology approaches altogether. Rather, we highlight the need for developing more suitable methods for inferring host-pathogen interactions and conducting more careful examinations of the relationships between metabolic networks and host-pathogen interactions.

  18. Reputation-Based Conditional Interaction Supports Cooperation in Well-Mixed Prisoner’s Dilemmas

    Science.gov (United States)

    Chen, Xiaojie; Schick, Alana; Doebeli, Michael; Blachford, Alistair; Wang, Long

    2012-01-01

    In the well-mixed prisoner’s dilemma game, individuals are typically assumed to have no choice about whether to interact with other individuals in the population. In this paper, we instead consider reputation-based conditional interaction and its consequences for the evolution of cooperation. Each individual has a tolerance range, and only interacts with other individuals whose reputation lies within its tolerance range in a chosen sample of the population. Reputation contains information about the number of interaction partners an individual has just cooperated with. We find that the introduction of conditional interaction promotes cooperation in well-mixed populations, and there exist moderate tolerance ranges for which this effect is maximized. For a given tolerance range, there is a critical cost-to-benefit ratio below which cooperation can be promoted. Interestingly, we find that if cooperation evolves, different cooperators’ interaction clusters are typically maintained in the population, each around a different reputation level. We further investigate some properties of these cooperators’ clusters. Moreover, we examine the effects of the sample number on the evolution of cooperation. Our results highlight the importance of the detailed consideration of modes of interaction for the evolution of cooperation in well-mixed populations. PMID:22615761

  19. Physics-based scoring of protein-ligand interactions: explicit polarizability, quantum mechanics and free energies.

    Science.gov (United States)

    Bryce, Richard A

    2011-04-01

    The ability to accurately predict the interaction of a ligand with its receptor is a key limitation in computer-aided drug design approaches such as virtual screening and de novo design. In this article, we examine current strategies for a physics-based approach to scoring of protein-ligand affinity, as well as outlining recent developments in force fields and quantum chemical techniques. We also consider advances in the development and application of simulation-based free energy methods to study protein-ligand interactions. Fuelled by recent advances in computational algorithms and hardware, there is the opportunity for increased integration of physics-based scoring approaches at earlier stages in computationally guided drug discovery. Specifically, we envisage increased use of implicit solvent models and simulation-based scoring methods as tools for computing the affinities of large virtual ligand libraries. Approaches based on end point simulations and reference potentials allow the application of more advanced potential energy functions to prediction of protein-ligand binding affinities. Comprehensive evaluation of polarizable force fields and quantum mechanical (QM)/molecular mechanical and QM methods in scoring of protein-ligand interactions is required, particularly in their ability to address challenging targets such as metalloproteins and other proteins that make highly polar interactions. Finally, we anticipate increasingly quantitative free energy perturbation and thermodynamic integration methods that are practical for optimization of hits obtained from screened ligand libraries.

  20. DEVELOPMENT OF INTERACTIVE E-BOOK BASED ON CHEMICAL REPRESENTATION REFER TO CURRICULUM 2013

    Directory of Open Access Journals (Sweden)

    L. Tania

    2015-11-01

    Full Text Available This research aimed to develop an interactive e-book based representations of chemistry; describes the characteristics of the interactive e-book developed; the teachers responses in content suitability with curriculum and graphics aspects; and student responses in readibility aspects. The method used was research and development. The characteristics of interactive e-book: it was developed referring to the core competencies (KI and basic competence (KD in the curriculum 2013, allowed active interaction between students and e-book, completed with pictures, animations or videos in three levels of the chemical representation. Teachers’ responses to the content suitability and graphic aspects were very good with the percentage of each 98.46% and 97.5%. The students’ responses in readibility aspects was very good with percentage of 88.5%.