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Sample records for passive gene-environment correlation

  1. Childhood Temperament: Passive Gene-Environment Correlation, Gene-Environment Interaction, and the Hidden Importance of the Family Environment

    PubMed Central

    Lemery-Chalfant, Kathryn; Kao, Karen; Swann, Gregory; Goldsmith, H. Hill

    2013-01-01

    Biological parents pass on genotypes to their children, as well as provide home environments that correlate with their genotypes; thus, the association between the home environment and children's temperament can be genetically (i.e. passive gene-environment correlation) or environmentally mediated. Furthermore, family environments may suppress or facilitate the heritability of children's temperament (i.e. gene-environment interaction). The sample comprised 807 twin pairs (M age = 7.93 years) from the longitudinal Wisconsin Twin Project. Important passive gene-environment correlations emerged, such that home environments were less chaotic for children with high Effortful Control, and this association was genetically mediated. Children with high Extraversion/Surgency experienced more chaotic home environments, and this correlation was also genetically mediated. In addition, heritability of children's temperament was moderated by home environments, such that Effortful Control and Extraversion/Surgency were more heritable in chaotic homes, and Negative Affectivity was more heritable under crowded or unsafe home conditions. Modeling multiple types of gene-environment interplay uncovered the complex role of genetic factors and the hidden importance of the family environment for children's temperament and development more generally. PMID:23398752

  2. Disentangling Gene-Environment Correlations and Interactions on Adolescent Depressive Symptoms

    ERIC Educational Resources Information Center

    Lau, Jennifer Y. F.; Eley, Thalia C.

    2008-01-01

    Background: Genetic risks for depression may be expressed through greater exposure towards environmental stressors (gene-environment correlation, rGE) and increased susceptibility to these stressors (gene-environment interaction, G x E). While these effects are often studied independently, evidence supports their co-occurrence on depression.…

  3. Evidence of reactive gene-environment correlation in preschoolers' prosocial play with unfamiliar peers.

    PubMed

    DiLalla, Lisabeth Fisher; Bersted, Kyle; John, Sufna Gheyara

    2015-10-01

    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 behaviors in young children. This study of 126 twin and sibling pairs examined 5-year-old preschool children's positive behaviors (prosocial and easy-going) while playing freely with an unfamiliar, same-age, same-sex peer. Children were randomly paired, allowing us to rule out passive (parent-influenced environment) and active (child-driven peer choices) gene-environment correlations as potential influences on the results. We found evidence of reactive gene-environment correlation, demonstrating that children who are genetically more likely to act prosocially and to be temperamentally outgoing appear to evoke more prosocial and easy-going behaviors from an unfamiliar peer. We also found that both dominant genetic and nonshared environmental factors were significant influences on preschoolers' prosocial play behaviors, but that neither genetic nor shared environmental factors were significant for easy-going play behaviors. These findings shed important light on influences of prosocial behaviors in preschoolers. Via inherited tendencies, preschool children's positive behaviors evoke similar positive behaviors from their play peers. Given that prosocial behaviors are preludes to a large range of important socially appropriate behaviors, prosocial children should be encouraged to interact with their peers to potentially create a more positive atmosphere within social contexts. PMID:26372295

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

    ERIC Educational Resources Information Center

    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…

  5. Effects of the Family Environment: Gene-Environment Interaction and Passive Gene-Environment Correlation

    ERIC Educational Resources Information Center

    Price, Thomas S.; Jaffee, Sara R.

    2008-01-01

    The classical twin study provides a useful resource for testing hypotheses about how the family environment influences children's development, including how genes can influence sensitivity to environmental effects. However, existing statistical models do not account for the possibility that children can inherit exposure to family environments…

  6. The genetics of music accomplishment: evidence for gene-environment correlation and interaction.

    PubMed

    Hambrick, David Z; Tucker-Drob, Elliot M

    2015-02-01

    Theories of skilled performance that emphasize training history, such as K. Anders Ericsson and colleagues' deliberate-practice theory, have received a great deal of recent attention in both the scientific literature and the popular press. Twin studies, however, have demonstrated evidence for moderate-to-strong genetic influences on skilled performance. Focusing on musical accomplishment in a sample of over 800 pairs of twins, we found evidence for gene-environment correlation, in the form of a genetic effect on music practice. However, only about one quarter of the genetic effect on music accomplishment was explained by this genetic effect on music practice, suggesting that genetically influenced factors other than practice contribute to individual differences in music accomplishment. We also found evidence for gene-environment interaction, such that genetic effects on music accomplishment were most pronounced among those engaging in music practice, suggesting that genetic potentials for skilled performance are most fully expressed and fostered by practice. PMID:24957535

  7. Early respiratory infections: the role of passive smoking in gene-environment interaction.

    PubMed

    Brescianini, Sonia; Fagnani, Corrado; Aquilini, Elisabetta; Annesi-Maesano, Isabella; Stazi, Maria A

    2016-06-01

    This study aims to: (i) estimate genetic and environmental components of four early respiratory diseases and (ii) test if these components are modified by parental smoking exposure. Study subjects were 2068 Italian twins aged 3-17. We performed biometric modeling under the assumptions of the twin design. For bronchitis and bronchiolitis, variance was mostly explained by shared environment, with no modification effect by parental smoking. For pneumonia and wheezy bronchitis, shared environmental component was larger among passive smokers, while genetic component was predominant among non-smokers. In the etiology of pneumonia and wheezy bronchitis, parental smoking could be a major familial factor. PMID:27013548

  8. Local Area Disadvantage and Gambling Involvement and Disorder: Evidence for Gene-Environment Correlation and Interaction

    PubMed Central

    Slutske, Wendy S.; Deutsch, Arielle R.; Statham, Dixie B.; Martin, Nicholas G.

    2015-01-01

    Previous research has demonstrated that local area characteristics (such as disadvantage and gambling outlet density) and genetic risk factors are associated with gambling involvement and disordered gambling. These two lines of research were brought together in the present study by examining the extent to which genetic contributions to individual differences in gambling involvement and disorder contributed to being exposed to, and were also accentuated by, local area disadvantage. Participants were members of the national community-based Australian Twin Registry who completed a telephone interview in which the past-year frequency of gambling and symptoms of disordered gambling were assessed. Indicators of local area disadvantage were based on census data matched to the participants' postal codes. Univariate biometric model-fitting revealed that exposure to area disadvantage was partially explained by genetic factors. Bivariate biometric model-fitting was conducted to examine the evidence for gene-environment interaction while accounting for gene-environment correlation. These analyses demonstrated that: (a) a small portion of the genetic propensity to gamble was explained by moving to or remaining in a disadvantaged area, and (b) the remaining genetic and unique environmental variation in the frequency of participating in electronic machine gambling (among men and women) and symptoms of disordered gambling (among women) was greater in more disadvantaged localities. As the gambling industry continues to grow, it will be important to take into account the multiple contexts in which problematic gambling behavior can emerge -- from genes to geography -- as well as the ways in which such contexts may interact with each other. PMID:26147321

  9. Gene-environment correlation linking aggression and peer victimization: do classroom behavioral norms matter?

    PubMed

    Brendgen, Mara; Girard, Alain; Vitaro, Frank; Dionne, Ginette; Boivin, Michel

    2015-01-01

    Using a genetically informed design based on 197 Monozygotic and Dizygotic twin pairs assessed in grade 4, this study examined 1) whether, in line with a gene-environment correlation (rGE), a genetic disposition for physical aggression or relational aggression puts children at risk of being victimized by their classmates, and 2) whether this rGE is moderated by classroom injunctive norm salience in regard to physical or relational aggression. Physical aggression and relational aggression, as well as injunctive classroom norm salience in regard to these behaviors, were measured via peer nominations. Peer victimization was measured via self-reports. Multi-Level Mixed modeling revealed that children with a genetic disposition for either aggressive behavior are at higher risk of being victimized by their peers only when classroom norms are unfavourable toward such behaviors. However, when classroom injunctive norms favor aggressive behaviors, a genetic disposition for physical or relational aggression may actually protect children against peer victimization. These results lend further support to the notion that bullying interventions must include the larger peer context instead of a sole focus on victims and bullies. PMID:25723009

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

    ERIC Educational Resources Information Center

    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'…

  11. A latent variable approach to study gene-environment interactions in the presence of multiple correlated exposures

    PubMed Central

    Kang, Shan; Mukherjee, Bhramar

    2015-01-01

    Summary Many existing cohort studies initially designed to investigate disease risk as a function of environmental exposures have collected genomic data in recent years with the objective of testing for gene-environment interaction (G × E) effects. In environmental epidemiology, interest in G × E arises primarily after a significant effect of the environmental exposure has been documented. Cohort studies often collect rich exposure data, as a result, assessing G × E effects in the presence of multiple exposure markers further increases the burden of multiple testing, an issue already present in both genetic and environment health studies. Latent variable (LV) models have been used in environmental epidemiology to reduce dimensionality of the exposure data, gain power by reducing multiplicity issues via condensing exposure data, and avoid collinearity problems due to presence of multiple correlated exposures. We extend the LV framework to characterize gene-environment interaction in presence of multiple correlated exposures and genotype categories. Further, similar to what has been done in case-control G × E studies, we use the assumption of gene-environment (G-E) independence to boost the power of tests for interaction. The consequences of making this assumption, or the issue of how to explicitly model G-E association has not been previously investigated in LV models. We postulate a hierarchy of assumptions about the LV model regarding the different forms of G-E dependence and show that making such assumptions may influence inferential results on the G, E, and G × E parameters. We implement a class of shrinkage estimators to data adaptively trade-off between the most restrictive to most flexible form of G-E dependence assumption and note that such class of compromise estimators can serve as a benchmark of model adequacy in LV models. We demonstrate the methods with an example from the Early Life Exposures in Mexico City to Neuro-Toxicants (ELEMENT) study of

  12. Temperament and peer problems from early to middle childhood: Gene-environment correlations with negative emotionality and sociability.

    PubMed

    Hasenfratz, Liat; Benish-Weisman, Maya; Steinberg, Tami; Knafo-Noam, Ariel

    2015-11-01

    Based in a transactional framework in which children's own characteristics and the social environment influence each other to produce individual differences in social adjustment, we investigated relationships between children's peer problems and their temperamental characteristics, using a longitudinal and genetically informed study of 939 pairs of Israeli twins followed from early to middle childhood (ages 3, 5, and 6.5). Peer problems were moderately stable within children over time, such that children who appeared to have more peer problems at age 3 tended to have also more peer problems at age 6.5. Children's temperament accounted for 10%-22% of the variance in their peer problems measured at the same age and for 2%-7% of the variance longitudinally. It is important that genetic factors accounted for the association between temperament and peer problems and were in line with a gene-environment correlation process, providing support for the proposal that biologically predisposed characteristics, particularly negative emotionality and sociability, have an influence on children's early experiences of peer problems. The results highlight the need for early and continuous interventions that are specifically tailored to address the interpersonal difficulties of children with particular temperamental profiles. PMID:26439064

  13. Passive rGE or developmental gene-environment cascade? An investigation of the role of xenobiotic metabolism genes in the association between smoke exposure during pregnancy and child birth weight

    PubMed Central

    Marceau, Kristine; Palmer, Rohan H.C.; Neiderhiser, Jenae M.; Smith, Taylor F.; McGeary, John E.; Knopik, Valerie S.

    2016-01-01

    There is considerable evidence that smoke exposure during pregnancy (SDP) environmentally influences birth weight after controlling for genetic influences and maternal characteristics. However, maternal smoking during pregnancy – the behavior that leads to smoke exposure during pregnancy – is also genetically-influenced, indicating the potential role of passive gene-environment correlation. An alternative to passive gene-SDP correlation is a cascading effect whereby maternal and child genetic influences are causally linked to prenatal exposures, which then have an ‘environmental’ effect on the development of the child’s biology and behavior. We describe and demonstrate a conceptual framework for disentangling passive rGE from this cascading GE effect using a systems-based polygenic scoring approach comprised of genes shown to be important in the xenobiotic (substances foreign to the body) metabolism pathway. Data were drawn from 5,044 families from the Avon Longitudinal Study of Parents and Children with information on maternal SDP, birth weight, and genetic polymorphisms in the xenobiotic pathway. Within a k-fold cross-validation approach (k=5), we created weighted maternal and child polygenic scores using 18 polymorphisms from 10 genes that have been implicated in the xenobiotic metabolism pathway. Mothers and children shared variation in xenobiotic metabolism genes. Amongst mothers who smoked during pregnancy, neither maternal nor child xenobiotic metabolism polygenic scores were associated with a higher likelihood of smoke exposure during pregnancy, or the severity of smoke exposure during pregnancy (and therefore, neither proposed mechanism was supported), or with child birth weight. SDP was consistently associated with lower child birth weight controlling for the polygenic scores, maternal educational attainment, social class, psychiatric problems, and age. Limitations of the study design and the potential of the framework using other designs are

  14. Passive rGE or Developmental Gene-Environment Cascade? An Investigation of the Role of Xenobiotic Metabolism Genes in the Association Between Smoke Exposure During Pregnancy and Child Birth Weight.

    PubMed

    Marceau, Kristine; Palmer, Rohan H C; Neiderhiser, Jenae M; Smith, Taylor F; McGeary, John E; Knopik, Valerie S

    2016-05-01

    There is considerable evidence that smoke exposure during pregnancy (SDP) environmentally influences birth weight after controlling for genetic influences and maternal characteristics. However, maternal smoking during pregnancy-the behavior that leads to smoke exposure during pregnancy-is also genetically-influenced, indicating the potential role of passive gene-environment correlation. An alternative to passive gene-SDP correlation is a cascading effect whereby maternal and child genetic influences are causally linked to prenatal exposures, which then have an 'environmental' effect on the development of the child's biology and behavior. We describe and demonstrate a conceptual framework for disentangling passive rGE from this cascading GE effect using a systems-based polygenic scoring approach comprised of genes shown to be important in the xenobiotic (substances foreign to the body) metabolism pathway. Data were drawn from 5044 families from the Avon Longitudinal Study of Parents and Children with information on maternal SDP, birth weight, and genetic polymorphisms in the xenobiotic pathway. Within a k-fold cross-validation approach (k = 5), we created weighted maternal and child polygenic scores using 18 polymorphisms from 10 genes that have been implicated in the xenobiotic metabolism pathway. Mothers and children shared variation in xenobiotic metabolism genes. Amongst mothers who smoked during pregnancy, neither maternal nor child xenobiotic metabolism polygenic scores were associated with a higher likelihood of smoke exposure during pregnancy, or the severity of smoke exposure during pregnancy (and therefore, neither proposed mechanism was supported), or with child birth weight. SDP was consistently associated with lower child birth weight controlling for the polygenic scores, maternal educational attainment, social class, psychiatric problems, and age. Limitations of the study design and the potential of the framework using other designs are discussed

  15. 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

    ERIC Educational Resources Information Center

    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…

  16. Child-evoked maternal negativity from 9 to 27 months: evidence of gene-environment correlation and its moderation by marital distress

    PubMed Central

    Fearon, R.M. Pasco; Reiss, David; Leve, Leslie D.; Shaw, Daniel S.; Scaramella, Laura V.; Ganiban, Jody M.; Neiderhiser, Jenae M.

    2014-01-01

    Past research has documented pervasive genetic influences on emotional and behavioral disturbance across the lifespan and on liability to adult psychiatric disorder. Increasingly, interest is turning to mechanisms of gene-environment interplay in attempting to understand the earliest manifestations of genetic risk. We report findings from a prospective adoption study, which aimed to test the role of evocative gene-environment correlation in early development. 561 infants adopted at birth were studied between 9 and 27 months with their adoptive parents and birth mothers. Birth mother psychiatric diagnoses and symptoms scales were used as indicators of genetic influence, and multiple self-report measures were used to index adoptive mother parental negativity. We hypothesized that birth parent psychopathology would be associated with greater adoptive parent negativity, and that such evocative effects would be amplified under conditions of high family adversity. The findings suggested that genetic factors linked to birth mother externalizing psychopathology may evoke negative reactions in adoptive mothers in the first year of life, but primarily when the adoptive family environment was characterized by marital problems. The observed maternal negativity mediated the effects of genetic risk on child adjustment at 27 months. The results underline the importance of genetically-influenced evocative processes in early development. PMID:25216383

  17. Child-evoked maternal negativity from 9 to 27 months: Evidence of gene-environment correlation and its moderation by marital distress.

    PubMed

    Fearon, R M Pasco; Reiss, David; Leve, Leslie D; Shaw, Daniel S; Scaramella, Laura V; Ganiban, Jody M; Neiderhiser, Jenae M

    2015-11-01

    Past research has documented pervasive genetic influences on emotional and behavioral disturbance across the life span and on liability to adult psychiatric disorder. Increasingly, interest is turning to mechanisms of gene-environment interplay in attempting to understand the earliest manifestations of genetic risk. We report findings from a prospective adoption study, which aimed to test the role of evocative gene-environment correlation in early development. Included in the study were 561 infants adopted at birth and studied between 9 and 27 months, along with their adoptive parents and birth mothers. Birth mother psychiatric diagnoses and symptoms scales were used as indicators of genetic influence, and multiple self-report measures were used to index adoptive mother parental negativity. We hypothesized that birth mother psychopathology would be associated with greater adoptive parent negativity and that such evocative effects would be amplified under conditions of high adoptive family adversity. The findings suggested that genetic factors associated with birth mother externalizing psychopathology may evoke negative reactions in adoptive mothers in the first year of life, but only when the adoptive family environment is characterized by marital problems. Maternal negativity mediated the effects of genetic risk on child adjustment at 27 months. The results underscore the importance of genetically influenced evocative processes in early development. PMID:25216383

  18. Correlation between lidar-derived intensity and passive optical imagery

    NASA Astrophysics Data System (ADS)

    Metcalf, Jeremy P.; Kim, Angela M.; Kruse, Fred A.; Olsen, Richard C.

    2014-06-01

    When LiDAR data are collected, the intensity information is recorded for each return, and can be used to produce an image resembling those acquired by passive imaging sensors. This research evaluated LiDAR intensity data to determine its potential for use as baseline imagery where optical imagery are unavailable. Two airborne LiDAR datasets collected at different point densities and laser wavelengths were gridded and compared with optical imagery. Optech Orion C200 laser data were compared with a corresponding 1541 nm spectral band from the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS). Optech ALTM Gemini LiDAR data collected at 1064 nm were compared to the WorldView-2 (WV-2) 949 - 1043 nm NIR2 band. Intensity images were georegistered and spatially resampled to match the optical data. The Pearson Product Moment correlation coefficient was calculated between datasets to determine similarity. Comparison for the full LiDAR datasets yielded correlation coefficients of approximately 0.5. Because LiDAR returns from vegetation are known to be highly variable, a Normalized Difference Vegetation Index (NDVI) was calculated utilizing the optical imagery, and intensity and optical imagery were separated into vegetation and nonvegetation categories. Comparison of the LiDAR intensity for non-vegetated areas to the optical imagery yielded coefficients greater than 0.9. These results demonstrate that LiDAR intensity data may be useful in substituting for optical imagery where only LiDAR is available.

  19. Genes, Environment, and Human Behavior.

    ERIC Educational Resources Information Center

    Bloom, Mark V.; Cutter, Mary Ann; Davidson, Ronald; Dougherty, Michael J.; Drexler, Edward; Gelernter, Joel; McCullough, Laurence B.; McInerney, Joseph D.; Murray, Jeffrey C.; Vogler, George P.; Zola, John

    This curriculum module explores genes, environment, and human behavior. This book provides materials to teach about the nature and methods of studying human behavior, raise some of the ethical and public policy dilemmas emerging from the Human Genome Project, and provide professional development for teachers. An extensive Teacher Background…

  20. Gene-Environment Interplay in Twin Models.

    PubMed

    Verhulst, Brad; Hatemi, Peter K

    2013-07-01

    In this article, we respond to Shultziner's critique that argues that identical twins are more alike not because of genetic similarity, but because they select into more similar environments and respond to stimuli in comparable ways, and that these effects bias twin model estimates to such an extent that they are invalid. The essay further argues that the theory and methods that undergird twin models, as well as the empirical studies which rely upon them, are unaware of these potential biases. We correct this and other misunderstandings in the essay and find that gene-environment (GE) interplay is a well-articulated concept in behavior genetics and political science, operationalized as gene-environment correlation and gene-environment interaction. Both are incorporated into interpretations of the classical twin design (CTD) and estimated in numerous empirical studies through extensions of the CTD. We then conduct simulations to quantify the influence of GE interplay on estimates from the CTD. Due to the criticism's mischaracterization of the CTD and GE interplay, combined with the absence of any empirical evidence to counter what is presented in the extant literature and this article, we conclude that the critique does not enhance our understanding of the processes that drive political traits, genetic or otherwise. PMID:24808718

  1. Gene-Environment Interplay in Twin Models

    PubMed Central

    Hatemi, Peter K.

    2013-01-01

    In this article, we respond to Shultziner’s critique that argues that identical twins are more alike not because of genetic similarity, but because they select into more similar environments and respond to stimuli in comparable ways, and that these effects bias twin model estimates to such an extent that they are invalid. The essay further argues that the theory and methods that undergird twin models, as well as the empirical studies which rely upon them, are unaware of these potential biases. We correct this and other misunderstandings in the essay and find that gene-environment (GE) interplay is a well-articulated concept in behavior genetics and political science, operationalized as gene-environment correlation and gene-environment interaction. Both are incorporated into interpretations of the classical twin design (CTD) and estimated in numerous empirical studies through extensions of the CTD. We then conduct simulations to quantify the influence of GE interplay on estimates from the CTD. Due to the criticism’s mischaracterization of the CTD and GE interplay, combined with the absence of any empirical evidence to counter what is presented in the extant literature and this article, we conclude that the critique does not enhance our understanding of the processes that drive political traits, genetic or otherwise. PMID:24808718

  2. Coherent averaging of the passive fathometer response using short correlation time.

    PubMed

    Traer, James; Gerstoft, Peter

    2011-12-01

    The passive fathometer algorithm was applied to data from two drifting array experiments in the Mediterranean, Boundary 2003 and 2004. The passive fathometer response was computed with correlation times from 0.34 to 90 s and, for correlation times less than a few seconds, the observed signal-to-noise ratio (SNR) agrees with a 1D model of SNR of the passive fathometer response in an ideal waveguide. In the 2004 experiment, the fathometer response showed the array depth varied periodically with an amplitude of 1 m and a period of 7 s consistent with wave driven motion of the array. This introduced a destructive interference, which prevents the SNR growing with increasing correlation time. A peak-tracking algorithm applied to the fathometer response of experimental data was used to remove this motion allowing the coherent passive fathometer response to be averaged over several minutes without destructive interference. Multirate adaptive beamforming, using 90 s correlation time to form adaptive steer vectors which were applied to 0.34 s data snapshots, increases the SNR of the passive fathometer response. PMID:22225020

  3. Benefits of Time Correlation Measurements for Passive Screening

    NASA Astrophysics Data System (ADS)

    Murer, David; Blackie, Douglas; Peerani, Paolo

    2014-02-01

    The “FLASH Portals Project” is a collaboration between Arktis Radiation Detectors Ltd (CH), the Atomic Weapons Establishment (UK), and the Joint Research Centre (European Commission), supported by the Technical Support Working Group (TSWG). The program's goal was to develop and demonstrate a technology to detect shielded special nuclear materials (SNM) more efficiently and less ambiguously by exploiting time correlation. This study presents experimental results of a two-sided portal monitor equipped with in total 16 4He fast neutron detectors as well as four polyvinyltoluene (PVT) plastic scintillators. All detectors have been synchronized to nanosecond precision, thereby allowing the resolution of time correlations from timescales of tens of microseconds (such as (n, γ) reactions) down to prompt fission correlations directly. Our results demonstrate that such correlations can be detected in a typical radiation portal monitor (RPM) geometry and within operationally acceptable time scales, and that exploiting these signatures significantly improves the performance of the RPM compared to neutron counting. Furthermore, the results show that some time structure remains even in the presence of heavy shielding, thus significantly improving the sensitivity of the detection system to shielded SNM.

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

    ERIC Educational Resources Information Center

    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…

  5. Feasibility of Passive Tomography of Extended Defects Using Ambient Elastic Noise Correlation

    NASA Astrophysics Data System (ADS)

    Druet, Tom; Chapuis, Bastien; Moulin, Emmanuel

    Using guided waves in structural health monitoring seems interesting because of their capability to propagate over long distances. This paper shows that tomography algorithms using guided waves in plate-like structures and cross-correlation of ambient noise can be combined to process the passive tomography of a structure. This can make a very robust and low power SHM system. An active tomography image has been performed with a time-of-flight tomography algorithm using experimental data produced by piezoelectric transducers. Comparison between active signals and passive signals which come from cross-correlation of ambient noise produced by compressed air sprayed on an aluminum plate shows that it is possible to detect time-of-flight passively.

  6. Passive elastography: shear-wave tomography from physiological-noise correlation in soft tissues.

    PubMed

    Gallot, Thomas; Catheline, Stefan; Roux, Philippe; Brum, Javier; Benech, Nicolas; Negreira, Carlos

    2011-06-01

    Inspired by seismic-noise correlation and time reversal, a shear-wave tomography of soft tissues using an ultrafast ultrasonic scanner is presented here. Free from the need for controlled shear-wave sources, this passive elastography is based on Green's function retrieval and takes advantage of the permanent physiological noise of the human body. PMID:21693392

  7. Simulation of GPR passive interferometry using cross-correlation for LNAPL model monitoring application

    NASA Astrophysics Data System (ADS)

    Li, Jing; Zeng, Zhaofa; Slob, Evert; Chen, Xiong; Liu, Fengshan

    2014-12-01

    Passive interferometry technology is based on the relation between the reflection and the transmission responses of the subsurface. The transmission response can be received at surface in the presence of the ambient noise source in the subsurface with the cross-correlation (CC) or multidimensional deconvolution methods. We investigate the feasibility of electromagnetic (EM) wave passive interferometry with CC method. We design a 2-D finite-difference time domain (FDTD) algorithm to simulate the long-duration ground penetrating radar (GPR) measurements with random distribution of passive EM sources. The noise sources have random duration time, waveform and spatial distribution. We test the FDTD GPR passive interferometry code with above source characteristics and apply the method to light non-aqueous phase liquid (LNAPL) monitoring. Based on the model simulation data, by using common midpoint velocity analysis and normal move out correction to process the interferometry retrieve record, we can accurately obtain the dynamic changing characteristics of the target's permittivity. The LNAPL dynamic leakage model can be imaged as well. The synthetic results demonstrate that the GPR passive interferometry is feasible in subsurface LNAPL monitoring. Our work provides a foundation for a passive interferometry field application using GPR.

  8. The Correlation of Active and Passive Microwave Outputs for the Skylab S-193 Sensor

    NASA Technical Reports Server (NTRS)

    Krishen, K.

    1976-01-01

    This paper presents the results of the correlation analysis of the Skylab S-193 13.9 GHz Radiometer/Scatterometer data. Computer analysis of the S-193 data shows more than 50 percent of the radiometer and scatterometer data are uncorrelated. The correlation coefficients computed for the data gathered over various ground scenes indicates the desirability of using both active and passive sensors for the determination of various Earth phenomena.

  9. The correlation of active and passive microwave data for the Skylab S-193 sensor

    NASA Technical Reports Server (NTRS)

    Krishen, Kumar

    1993-01-01

    This paper presents the results of the correlation analysis of the Skylab S-193 13.9 GHz Radiometer/Scatterometer data. Computer analysis of the S-193 data shows more than 50 percent of the radiometer and scatterometer data are uncorrelated. The correlation coefficients computed for the data gathered over various ground scenes indicates the desirability of using both active and passive sensors for the determination of various Earth phenomena.

  10. Passive localization in the deep ocean based on cross-correlation function matching.

    PubMed

    Lei, Zhixiong; Yang, Kunde; Ma, Yuanliang

    2016-06-01

    Passive localization of a sound source in the deep ocean is investigated in this study. The source can be localized by taking advantage of a cross-correlation function matching technique. When a two-sensor vertical array is used in the deep ocean, two types of side lobe curves appear in the ambiguity surface of the localization. The side lobe curves are analytically expressed and they are then used as indicators of the localization result instead of the scanning point with the maximum power. Simulation and experiment demonstrate the performance of the proposed passive localization method. PMID:27369172

  11. Anisotropic Turbulent Advection of a Passive Vector Field: Effects of the Finite Correlation Time

    NASA Astrophysics Data System (ADS)

    Antonov, N. V.; Gulitskiy, N. M.

    2016-02-01

    The turbulent passive advection under the environment (velocity) field with finite correlation time is studied. Inertial-range asymptotic behavior of a vector (e.g., magnetic) field, passively advected by a strongly anisotropic turbulent flow, is investigated by means of the field theoretic renormalization group and the operator product expansion. The advecting velocity field is Gaussian, with finite correlation time and prescribed pair correlation function. The inertial-range behavior of the model is described by two regimes (the limits of vanishing or infinite correlation time) that correspond to nontrivial fixed points of the RG equations and depend on the relation between the exponents in the energy energy spectrum ɛ ∝ k⊥1-ξ and the dispersion law ω ∝ k⊥2-η . The corresponding anomalous exponents are associated with the critical dimensions of tensor composite operators built solely of the passive vector field itself. In contrast to the well-known isotropic Kraichnan model, where various correlation functions exhibit anomalous scaling behavior with infinite sets of anomalous exponents, here the dependence on the integral turbulence scale L has a logarithmic behavior: instead of power-like corrections to ordinary scaling, determined by naive (canonical) dimensions, the anomalies manifest themselves as polynomials of logarithms of L. Due to the presence of the anisotropy in the model, all multiloop diagrams are equal to zero, thus this result is exact.

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

    ERIC Educational Resources Information Center

    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…

  13. Gene-Environment Processes Linking Aggression, Peer Victimization, and the Teacher-Child Relationship

    ERIC Educational Resources Information Center

    Brendgen, Mara; Boivin, Michel; Dionne, Ginette; Barker, Edward D.; Vitaro, Frank; Girard, Alain; Tremblay, Richard; Perusse, Daniel

    2011-01-01

    Aggressive behavior in middle childhood is at least partly explained by genetic factors. Nevertheless, estimations of simple effects ignore possible gene-environment interactions (G x E) or gene-environment correlations (rGE) in the etiology of aggression. The present study aimed to simultaneously test for G x E and rGE processes between…

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

    ERIC Educational Resources Information Center

    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…

  15. Active-passive correlation spectroscopy - A new technique for identifying ocean color algorithm spectral regions

    NASA Technical Reports Server (NTRS)

    Hoge, F. E.; Swift, R. N.

    1986-01-01

    A new active-passive airborne data correlation technique has been developed which allows the validation of existing in-water oceoan color algorithms and the rapid search, identification, and evaluation of new sensor band locations and algorithm wavelength intervals. Thus far, applied only in conjunction with the spectral curvature algorithm (SCA), the active-passive correlation spectroscopy (APCS) technique shows that (1) the usual 490-nm (center-band) chlorophyll SCA could satisfactorily be placed anywhere within the nominal 460-510-nm interval, and (2) two other spectral regions, 645-660 and 680-695 nm, show considerable promise for chlorophyll pigment measurement. Additionally, the APCS method reveals potentially useful wavelength regions (at 600 and about 670 nm) of very low chlorophyll-in-water spectral curvature into which accessory pigment algorithms for phycoerythrin might be carefully positioned. In combination, the APCS and SCA methods strongly suggest that significant information content resides within the seemingly featureless ocean color spectrum.

  16. Passive dispersion analysis on a sea dike using cross-correlations and beamforming

    NASA Astrophysics Data System (ADS)

    Le Feuvre, Mathieu; Joubert, Anaëlle; Leparoux, Donatienne; Côte, Philippe

    2014-05-01

    In order to passively infer the velocities of surface waves beneath a receiver array, we propose to apply beamforming on cross-correlated noise records. We test the method with synthetic signals generated for a variety of array geometries and noise distributions. We show that the use of cross-correlations cleans the dispersion diagram that would be obtained from a phase-shift analysis alone, by resolving ambiguities between the location of noise sources and the wave velocities. In particular, when nearby noise sources are present, accurate dispersion curves can be inferred from arrays possessing poor azimuthal coverages. This passive method is therefore appropriate for the monitoring of stiffness at the civil-engineering scale, where multiple isolated noise sources may be present and where the field geometry does not always allow to deploy circular arrays. We apply the method to field data obtained from a linear array installed on top of a sea dike. The seismic noise, recorded at high tide during 8 minutes, is essentially generated by impacts of sea waves. In contrast to a phase-shift analysis performed on the noise itself, we show that the use of cross-correlations allow to infer a dispersion curve consistent with an active hammer-shot measurement, in a larger frequency band, ranging from 5 to 55 Hz. This result opens the possibility of following passively the mechanical evolution of embankments on a daily basis.

  17. Millimeter-wave passive components of correlation radiometers for polarization measurements

    NASA Astrophysics Data System (ADS)

    Peverini, Oscar A.; Tascone, Riccardo; Virone, Giuseppe; Baralis, Massimo; Olivieri, Augusto; Orta, Renato

    2004-10-01

    In this paper the millimeter-wave passive components developed for the Ka-band Bar-SPOrt (Balloon-borne Radiometer for Sky Polarization Observatory) correlation radiometer are described. Comparison between numerical and experimental results are reported for all the building blocks of the radiometer: marker injector, polarizer, ortho-mode transducer, filtering sections and correlation unit. Due to the very low level of the polarized sky emission to be measured, all the components were designed and manufactured in order to achieve a very high level of sensitivity.

  18. Active Flexion in Weight Bearing Better Correlates with Functional Outcomes of Total Knee Arthroplasty than Passive Flexion

    PubMed Central

    Song, Young Dong; Jain, Nimash; Kang, Yeon Gwi; Kim, Tae Yune

    2016-01-01

    Purpose Correlations between maximum flexion and functional outcomes in total knee arthroplasty (TKA) patients are reportedly weak. We investigated whether there are differences between passive maximum flexion in nonweight bearing and other types of maximum flexion and whether the type of maximum flexion correlates with functional outcomes. Materials and Methods A total of 210 patients (359 knees) underwent preoperative evaluation and postoperative follow-up evaluations (6, 12, and 24 months) for the assessment of clinical outcomes including maximum knee flexion. Maximum flexion was measured under five conditions: passive nonweight bearing, passive weight bearing, active nonweight bearing, and active weight bearing with or without arm support. Data were analyzed for relationships between passive maximum flexion in nonweight bearing by Pearson correlation analyses, and a variance comparison between measurement techniques via paired t test. Results We observed substantial differences between passive maximum flexion in nonweight bearing and the other four maximum flexion types. At all time points, passive maximum flexion in nonweight bearing correlated poorly with active maximum flexion in weight bearing with or without arm support. Active maximum flexion in weight bearing better correlated with functional outcomes than the other maximum flexion types. Conclusions Our study suggests active maximum flexion in weight bearing should be reported together with passive maximum flexion in nonweight bearing in research on the knee motion arc after TKA. PMID:27274468

  19. Multi-channel analysis of passive surface waves based on cross-correlations

    NASA Astrophysics Data System (ADS)

    Cheng, F.; Xia, J.; Xu, Z.; Hu, Y.

    2015-12-01

    Traditional active seismic survey can no longer be properly applied in highly populated urban areas due to restrictions in modern civilian life styles. Passive seismic methods, however, have gained much more attention from the engineering geophysics community because of their environmental friendly and deeper investigation depth. Due to extracting signal from noise has never been as comfortable as that in active seismic survey, how to make it more efficiently and accurately has been emphasized. We propose a multi-channel analysis of passive surface waves (MAPW) based on long noise sequences cross-correlations to meet the demand for increasing investigation depth by acquiring surface-wave data at a relative low-frequency range (1 Hz ≤ f ≤ 10 Hz) in urban areas. We utilize seismic interferometry to produce common virtual source gathers from one-hour-long noise records and do dispersion measurements by using the classic passive multi-channel analysis of surface waves (PMASW). We used synthetic tests to demonstrate the advantages of MAPW for various noise distributions. Results show that our method has the superiority of maximizing the analysis accuracy. Finally, we used two field data applications to demonstrate the advantages of our MAPW over the classic PMASW on isolating azimuth of the predominant noise sources and the effectivity of combined survey of active multi-channel analysis of surface waves (MASW) and MAPW. We suggest, for the field operation using MAPW, that a parallel receiver line which is close to a main road or river, if any, with one or two hours noise observation will be an effective means for an unbiased dispersion image. Keywords: passive seismic method, MAPW, MASW, cross-correlation, directional noise source, spatial-aliasing effects, inversion

  20. Biological Implications of Gene-Environment Interaction

    ERIC Educational Resources Information Center

    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…

  1. Why study gene-environment interactions?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    PURPOSE OF REVIEW: We examine the reasons for investigating gene-environment interactions and address recent reports evaluating interactions between genes and environmental modulators in relation to cardiovascular disease and its common risk factors. RECENT FINDINGS: Studies focusing on smoking, phy...

  2. Gene-environment interactions in sarcoidosis

    PubMed Central

    Culver, Daniel A.; Newman, Lee S.; Kavuru, Mani S.

    2007-01-01

    Susceptibility to most human diseases is polygenic, with complex interactions between functional polymorphisms of single genes governing disease incidence, phenotype, or both. In this context, the contribution of any discrete gene is generally modest for a single individual, but may confer substantial attributable risk on a population level. Environmental exposure can modify the effects of a polymorphism, either by providing a necessary substrate for development of human disease or because the effects of a given exposure modulate the effects of the gene. In several diseases, genetic polymorphisms have been shown to be context-dependent, i.e. the effects of a genetic variant are realized only in the setting of a relevant exposure. Since sarcoidosis susceptibility is dependent on both genetic and environmental modifiers, the study of gene-environment interactions may yield important pathogenetic information and will likely be crucial for uncovering the range of genetic susceptibility loci. However, the complexity of these relationships implies that investigations of gene-environment interactions will require the study of large cohorts with carefully-defined exposures and similar clinical phenotypes. A general principle is that the study of gene-environment interactions requires a sample size at least several-fold greater than for either factor alone. To date, the presence of environmental modifiers has been demonstrated for one sarcoidosis susceptibility locus, HLA-DQB1, in African-American families. This article reviews general considerations obtaining for the study of gene-environment interactions in sarcoidosis. It also describes the limited current understanding of the role of environmental influences on sarcoidosis susceptibility genes. PMID:17560304

  3. Correlation between density and oxidation temperature for pyrolytic-gas passivated ultrathin silicon oxide films

    NASA Astrophysics Data System (ADS)

    Yamada, Hiroshi

    2004-01-01

    Pyrolytic-gas passivation (PGP) with a small amount nitrogen gas enhances the breakdown reliability of silicon oxide gate films. To clarify the reliability retention of the PGP-grown films oxidized at low temperature, densities (ρox's) of the 3.5-6.5-nm-thick PGP-grown films on Si(100) oxidized at 700-900 °C were investigated. Since ρox's correlate well with the reliability and are useful as an index of the intrinsic structural characteristics of the films. Moreover, changes in ρox and nitrogen content corresponding to oxidation temperature are similar to those in breakdown reliability and interface state density (Dit), respectively. In addition, ρox's of the 700 °C-grown PGP films do not deteriorate as much when compared with those of the films grown by normal ultradry oxidation at 800 °C and their Dit's are less than about 6×1010/eV cm2. This suggests that PGP probably improves the reliability by generating the higher-ρox microscopic structure with few Si dangling bonds and effective passivation. .

  4. Gene-environment interactions on growth trajectories.

    PubMed

    Wang, Shuang; Xiong, Wei; Ma, Weiping; Chanock, Stephen; Jedrychowski, Wieslaw; Wu, Rongling; Perera, Frederica P

    2012-04-01

    It has been suggested that children with larger brains tend to perform better on IQ tests or cognitive function tests. Prenatal head growth and head growth in infancy are two crucial periods for subsequent intelligence. Studies have shown that environmental exposure to air pollutants during pregnancy is associated with fetal growth reduction, developmental delay, and reduced IQ. Meanwhile, genetic polymorphisms may modify the effect of environment on head growth. However, studies on gene-environment or gene-gene interactions on growth trajectories have been quite limited partly due to the difficulty to quantitatively measure interactions on growth trajectories. Moreover, it is known that assessing the significance of gene-environment or gene-gene interactions on cross-sectional outcomes empirically using the permutation procedures may bring substantial errors in the tests. We proposed a score that quantitatively measures interactions on growth trajectories and developed an algorithm with a parametric bootstrap procedure to empirically assess the significance of the interactions on growth trajectories under the likelihood framework. We also derived a Wald statistic to test for interactions on growth trajectories and compared it to the proposed parametric bootstrap procedure. Through extensive simulation studies, we demonstrated the feasibility and power of the proposed testing procedures. We applied our method to a real dataset with head circumference measures from birth to age 7 on a cohort currently being conducted by the Columbia Center for Children's Environmental Health (CCCEH) in Krakow, Poland, and identified several significant gene-environment interactions on head circumference growth trajectories. PMID:22311237

  5. Gene-environment interplay and psychopathology: multiple varieties but real effects.

    PubMed

    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 focus on variations in heritability according to environmental circumstances. Third, we discuss what is known about gene-environment correlations. Finally, we assess concepts and findings on the interaction between specific identified genes and specific measured environmental risks. In order to provide an understanding of what may be involved in gene-environment interplay, we begin our presentation with a brief historical review of prevailing views about the role of genetic and environmental factors in the causation of mental disorders, and we provide a simplified account of some of the key features of how genes 'work'. PMID:16492258

  6. Spatial dependence of correlation functions in the decay problem for a passive scalar in a large-scale velocity field

    SciTech Connect

    Vergeles, S. S.

    2006-04-15

    Statistical characteristics of a passive scalar advected by a turbulent velocity field are considered in the decay problem with a low scalar diffusivity {kappa} (large Prandtl number v/{kappa}, where v is kinematic viscosity). A regime in which the scalar correlation length remains smaller than the velocity correlation length is analyzed. The equal-time correlation functions of the scalar field are found to vary according to power laws and have angular singularities reflecting locally layered distribution of the scalar in space.

  7. The Role of Individual Correlates and Class Norms in Defending and Passive Bystanding Behavior in Bullying: A Multilevel Analysis

    ERIC Educational Resources Information Center

    Pozzoli, Tiziana; Gini, Gianluca; Vieno, Alessio

    2012-01-01

    This study investigates possible individual and class correlates of defending and passive bystanding behavior in bullying, in a sample of 1,825 Italian primary school (mean age = 10 years 1 month) and middle school (mean age = 13 years 2 months) students. The findings of a series of multilevel regression models show that both individual (e.g.,…

  8. Passive correlation ranging of a geostationary satellite using DVB-S payload signals.

    NASA Astrophysics Data System (ADS)

    Shakun, Leonid; Shulga, Alexandr; Sybiryakova, Yevgeniya; Bushuev, Felix; Kaliuzhnyi, Mykola; Bezrukovs, Vladislavs; Moskalenko, Sergiy; Kulishenko, Vladislav; Balagura, Oleg

    2016-07-01

    Passive correlation ranging (PaCoRa) for geostationary satellites is now considered as an alternate to tone-ranging (https://artes.esa.int/search/node/PaCoRa). The PaCoRa method has been employed in the Research Institute "Nikolaev astronomical observatory" since the first experiment in August 2011 with two stations spatially separated on 150 km. The PaCoRa has been considered as an independent method for tracking the future Ukrainian geostationary satellite "Lybid'. Now a radio engineering complex (RC) for passive ranging consists of five spatially separated stations of receiving digital satellite television and a data processing center located in Mykolaiv. The stations are located in Kyiv, Kharkiv, Mukacheve, Mykolaiv (Ukraine) and in Ventspils (Latvia). Each station has identical equipment. The equipment allows making synchronous recording of fragments of the DVB-S signal from the quadrature detector output of a satellite television receiver. The fragments are recorded every second. Synchronization of the stations is performed using GPS receivers. Samples of the complex signal obtained in this way are archived and are sent to the data processing center over the Internet. Here the time differences of arrival (TDOA) for pairs of the stations are determined as a result of correlation processing of received signals. The values of the TDOA that measured every second are used for orbit determination (OD) of the satellite. The results of orbit determination of the geostationary telecommunication satellite "Eutelsat-13B" (13º East) obtained during about four months of observations in 2015 are presented in the report. The TDOA and OD accuracies are also given. Single-measurement error (1 sigma) of the TDOA is equal about 8.7 ns for all pairs of the stations. Standard deviations and average values of the residuals between the observed TDOA and the TDOA computed using the orbit elements obtained from optical measurements are estimated for the pairs Kharkiv-Mykolaiv and

  9. Gene-environment interactions in esophageal cancer.

    PubMed

    Matejcic, Marco; Iqbal Parker, M

    2015-01-01

    Esophageal cancer (EC) is one of the most common malignancies in low- and medium-income countries and represents a disease of public health importance because of its poor prognosis and high mortality rate in these regions. The striking variation in the prevalence of EC among different ethnic groups suggests a significant contribution of population-specific environmental and dietary factors to susceptibility to the disease. Although individuals within a demarcated geographical area are exposed to the same environment and share similar dietary habits, not all of them will develop the disease; thus genetic susceptibility to environmental risk factors may play a key role in the development of EC. A wide range of xenobiotic-metabolizing enzymes are responsible for the metabolism of carcinogens introduced via the diet or inhaled from the environment. Such dietary or environmental carcinogens can bind to DNA, resulting in mutations that may lead to carcinogenesis. Genes involved in the biosynthesis of these enzymes are all subject to genetic polymorphisms that can lead to altered expression or activity of the encoded proteins. Genetic polymorphisms may, therefore, act as molecular biomarkers that can provide important predictive information about carcinogenesis. The aim of this review is to discuss our current knowledge on the genetic risk factors associated with the development of EC in different populations; it addresses mainly the topics of genetic polymorphisms, gene-environment interactions, and carcinogenesis. We have reviewed the published data on genetic polymorphisms of enzymes involved in the metabolism of xenobiotics and discuss some of the potential gene-environment interactions underlying esophageal carcinogenesis. The main enzymes discussed in this review are the glutathione S-transferases (GSTs), N-acetyltransferases (NATs), cytochrome P450s (CYPs), sulfotransferases (SULTs), UDP-glucuronosyltransferases (UGTs), and epoxide hydrolases (EHs), all of which

  10. Temperature Knowledge and Model Correlation for the Soil Moisture Active and Passive (SMAP) Reflector Mesh

    NASA Technical Reports Server (NTRS)

    Mikhaylov, Rebecca; Dawson, Douglas; Kwack, Eug

    2014-01-01

    NASA's Earth observing Soil Moisture Active & Passive (SMAP) Mission is scheduled to launch in November 2014 into a 685 km near-polar, sun synchronous orbit. SMAP will provide comprehensive global mapping measurements of soil moisture and freeze/thaw state in order to enhance understanding of the processes that link the water, energy, and carbon cycles. The primary objectives of SMAP are to improve worldwide weather and flood forecasting, enhance climate prediction, and refine drought and agriculture monitoring during its 3 year mission. The SMAP instrument architecture incorporates an L-band radar and an L-band radiometer which share a common feed horn and parabolic mesh reflector. The instrument rotates about the nadir axis at approximately 15 rpm, thereby providing a conically scanning wide swath antenna beam that is capable of achieving global coverage within 3 days. In order to make the necessary precise surface emission measurements from space, a temperature knowledge of 60 deg C for the mesh reflector is required. In order to show compliance, a thermal vacuum test was conducted using a portable solar simulator to illuminate a non flight, but flight-like test article through the quartz window of the vacuum chamber. The molybdenum wire of the antenna mesh is too fine to accommodate thermal sensors for direct temperature measurements. Instead, the mesh temperature was inferred from resistance measurements made during the test. The test article was rotated to five separate angles between 10 deg and 90 deg via chamber breaks to simulate the maximum expected on-orbit solar loading during the mission. The resistance measurements were converted to temperature via a resistance versus temperature calibration plot that was constructed from data collected in a separate calibration test. A simple thermal model of two different representations of the mesh (plate and torus) was created to correlate the mesh temperature predictions to within 60 deg C. The on-orbit mesh

  11. Passive Leg Raising Correlates with Future Exercise Capacity after Coronary Revascularization

    PubMed Central

    Huang, Shu-Chun; Wong, May-Kuen; Lin, Pyng-Jing; Tsai, Feng-Chun; Wen, Ming-Shien; Kuo, Chi-Tai; Hsu, Chih-Chin; Wang, Jong-Shyan

    2015-01-01

    Hemodynamic properties affected by the passive leg raise test (PLRT) reflect cardiac pumping efficiency. In the present study, we aimed to further explore whether PLRT predicts exercise intolerance/capacity following coronary revascularization. Following coronary bypass/percutaneous coronary intervention, 120 inpatients underwent a PLRT and a cardiopulmonary exercise test (CPET) 2–12 days during post-surgery hospitalization and 3–5 weeks after hospital discharge. The PLRT included head-up, leg raise, and supine rest postures. The end point of the first CPET during admission was the supra-ventilatory anaerobic threshold, whereas that during the second CPET in the outpatient stage was maximal performance. Bio-reactance-based non-invasive cardiac output monitoring was employed during PLRT to measure real-time stroke volume and cardiac output. A correlation matrix showed that stroke volume during leg raise (SVLR) during the first PLRT was positively correlated (R = 0.653) with the anaerobic threshold during the first CPET. When exercise intolerance was defined as an anaerobic threshold < 3 metabolic equivalents, SVLR / body weight had an area under curve value of 0.822, with sensitivity of 0.954, specificity of 0.593, and cut-off value of 1504·10-3mL/kg (positive predictive value 0.72; negative predictive value 0.92). Additionally, cardiac output during leg raise (COLR) during the first PLRT was related to peak oxygen consumption during the second CPET (R = 0.678). When poor aerobic fitness was defined as peak oxygen consumption < 5 metabolic equivalents, COLR / body weight had an area under curve value of 0.814, with sensitivity of 0.781, specificity of 0.773, and a cut-off value of 68.3 mL/min/kg (positive predictive value 0.83; negative predictive value 0.71). Therefore, we conclude that PLRT during hospitalization has a good screening and predictive power for exercise intolerance/capacity in inpatients and early outpatients following coronary revascularization

  12. Passive Leg Raising Correlates with Future Exercise Capacity after Coronary Revascularization.

    PubMed

    Huang, Shu-Chun; Wong, May-Kuen; Lin, Pyng-Jing; Tsai, Feng-Chun; Wen, Ming-Shien; Kuo, Chi-Tai; Hsu, Chih-Chin; Wang, Jong-Shyan

    2015-01-01

    Hemodynamic properties affected by the passive leg raise test (PLRT) reflect cardiac pumping efficiency. In the present study, we aimed to further explore whether PLRT predicts exercise intolerance/capacity following coronary revascularization. Following coronary bypass/percutaneous coronary intervention, 120 inpatients underwent a PLRT and a cardiopulmonary exercise test (CPET) 2-12 days during post-surgery hospitalization and 3-5 weeks after hospital discharge. The PLRT included head-up, leg raise, and supine rest postures. The end point of the first CPET during admission was the supra-ventilatory anaerobic threshold, whereas that during the second CPET in the outpatient stage was maximal performance. Bio-reactance-based non-invasive cardiac output monitoring was employed during PLRT to measure real-time stroke volume and cardiac output. A correlation matrix showed that stroke volume during leg raise (SVLR) during the first PLRT was positively correlated (R = 0.653) with the anaerobic threshold during the first CPET. When exercise intolerance was defined as an anaerobic threshold < 3 metabolic equivalents, SVLR / body weight had an area under curve value of 0.822, with sensitivity of 0.954, specificity of 0.593, and cut-off value of 1504·10-3mL/kg (positive predictive value 0.72; negative predictive value 0.92). Additionally, cardiac output during leg raise (COLR) during the first PLRT was related to peak oxygen consumption during the second CPET (R = 0.678). When poor aerobic fitness was defined as peak oxygen consumption < 5 metabolic equivalents, COLR / body weight had an area under curve value of 0.814, with sensitivity of 0.781, specificity of 0.773, and a cut-off value of 68.3 mL/min/kg (positive predictive value 0.83; negative predictive value 0.71). Therefore, we conclude that PLRT during hospitalization has a good screening and predictive power for exercise intolerance/capacity in inpatients and early outpatients following coronary revascularization

  13. An automated cross-correlation based event detection technique and its application to surface passive data set

    USGS Publications Warehouse

    Forghani-Arani, Farnoush; Behura, Jyoti; Haines, Seth S.; Batzle, Mike

    2013-01-01

    In studies on heavy oil, shale reservoirs, tight gas and enhanced geothermal systems, the use of surface passive seismic data to monitor induced microseismicity due to the fluid flow in the subsurface is becoming more common. However, in most studies passive seismic records contain days and months of data and manually analysing the data can be expensive and inaccurate. Moreover, in the presence of noise, detecting the arrival of weak microseismic events becomes challenging. Hence, the use of an automated, accurate and computationally fast technique for event detection in passive seismic data is essential. The conventional automatic event identification algorithm computes a running-window energy ratio of the short-term average to the long-term average of the passive seismic data for each trace. We show that for the common case of a low signal-to-noise ratio in surface passive records, the conventional method is not sufficiently effective at event identification. Here, we extend the conventional algorithm by introducing a technique that is based on the cross-correlation of the energy ratios computed by the conventional method. With our technique we can measure the similarities amongst the computed energy ratios at different traces. Our approach is successful at improving the detectability of events with a low signal-to-noise ratio that are not detectable with the conventional algorithm. Also, our algorithm has the advantage to identify if an event is common to all stations (a regional event) or to a limited number of stations (a local event). We provide examples of applying our technique to synthetic data and a field surface passive data set recorded at a geothermal site.

  14. [Interhemisphere asymmetry of hippocampus and neocortex in correlates of active and passive behavioural strategy in negative emotional situations].

    PubMed

    Pavlova, I V; Rysakova, M P; Ziablintseva, E A

    2010-12-01

    The interhemisphere interaction of neurons in bilateral derivations from parietal and sensomotor areas of neocortex and the area CA1 of hippocampus were studied in rabbits with active and passive behavioural strategy in the open field by plotting histograms of crosscorrelation. In passive animals, there was asymmetry in bilateral neuronal interaction: with right-sided dominance in the neocortex and with left-sided that--in the hippocampus. On the contrary, in active rabbits, the left-sided dominance was observed in the neocortex, and the lateralization was not revealed in the hippocampus. The brain laterality was reflected in motor asymmetry of animals in preferring left or right turns in the open field. Passive rabbits made relatively more left turns, and the active animals--right turns. Systemic administration of agonist GABA(B) receptors phenibut decreased behavioural responses to emotional stimuli and eliminated interhemisphere asymmetry observed usually in negative emotional situations. Thus the interhemisphere asymmetry of the neocortex and hippocampus is correlated with individual typological characteristics of animals and reflects the readiness to preferential forms of behavioural responses in active and passive rabbits. PMID:21473104

  15. Gene-environment interactions in ocular diseases.

    PubMed

    Sacca, S C; Bolognesi, C; Battistella, A; Bagnis, A; Izzotti, A

    2009-07-10

    Degenerative ocular diseases are widespread in the population and represent a major cause of reversible and irreversible blindness. Scientific evidences have been accumulating supporting the role of genotoxic damage and gene environment interactions in the pathogenesis of these diseases mainly including glaucoma, age-related macular degeneration, and cataract. Glaucoma, in its degenerative form, is characterized by the degeneration of the trabecular meshwork, the tissue of the anterior chamber of the eye devoted to aqueous-humour outflow. Such a degenerative process results in intra-ocular pressure increase and progressive damage of optic nerve head. Oxidative stress and DNA damage play an important role in inducing the degeneration of these well differentiated target tissues in which DNA damage results in a progressive cell loss. Macular degeneration is a common age-related disease affecting the central regions of the retina inducing progressive accumulation of oxidized lipoproteins and neovascularization. Environmental genotoxic risk factors include diet, light, and cigarette smoke paralleled by individual susceptibility as determined by adverse genetic assets. Cataract is a progressive opacity of the crystalline lens resulting from molecular damages induced by various risk factors including UV-containing light. This disease has been related to a failure in antioxidant defences. Experimental study provides evidence that cataract patients possess higher basal level of DNA damage, as evaluated by Comet test, in lymphocytes than controls. This finding is paralleled by the higher susceptibility to oxidative stress observed in the same patients. These novel experimental data further support the role of DNA damage as a main factor contributing to cataract onset. In conclusion, the examined degenerative ocular diseases recognise environmental risk factors often displaying genotoxic attitudes. Whenever these factors target individuals who are susceptible due their

  16. Gene-Environment Interactions in Human Disease: Nuisance or Opportunity?

    PubMed Central

    Ober, Carole; Vercelli, Donata

    2010-01-01

    Many environmental risk factors for common, complex human diseases have been revealed by epidemiologic studies, but how genotypes at specific loci modulate individual responses to environmental risk factors is largely unknown. Gene-environment interactions will be missed in genome-wide association studies and may account for some of the ‘missing heritability’ for these diseases. In this review, we focus on asthma as a model disease for studying gene-environment interactions because of relatively large numbers of candidate gene-environment interactions with asthma risk in the literature. Identifying these interactions using genome-wide approaches poses formidable methodological problems and elucidating molecular mechanisms for these interactions has been challenging. We suggest that studying gene-environment interactions in animal models, while more tractable, is not likely to shed light on the genetic architecture of human diseases. Lastly, we propose avenues for future studies to find gene-environment interactions. PMID:21216485

  17. Parametric exponentially correlated surface emission model for L-band passive microwave soil moisture retrieval

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Surface soil moisture is an important parameter in hydrology and climate investigations. Current and future satellite missions with L-band passive microwave radiometers can provide valuable information for monitoring the global soil moisture. A factor that can play a significant role in the modeling...

  18. Comparison of eye-safe solid state laser DIAL with passive gas filter correlation measurements from aircraft and spacecraft

    NASA Astrophysics Data System (ADS)

    Hess, Robert V.; Staton, Leo D.; Wallio, H. Andrew; Wang, Liang-Guo

    1992-07-01

    Differential Absorption Lidar (DIAL) using solid state Ti:sapphire lasers finds current application in the NASA/LASE Project for H2O vapor measurements in the approximately = 0.820 micron region for the lower and mid-troposphere and in potential future applications in planned measurements of the approximately = 0.940 micron region where both strong and weak absorption lines enables measurements throughout the troposphere and lower stratosphere. The challenge exists to perform measurements in the eye-safe greater than 1.5 micron region. A comparison between DIAL and passive Gas Filter Correlation Radiometer (GFCR) measurements is made. The essence of the differences in signal to noise ratio for DIAL and passive GFCR measurements is examined. The state of the art of lasers and optical parametric oscillators (OPO's) is discussed.

  19. The role of individual correlates and class norms in defending and passive bystanding behavior in bullying: a multilevel analysis.

    PubMed

    Pozzoli, Tiziana; Gini, Gianluca; Vieno, Alessio

    2012-11-01

    This study investigates possible individual and class correlates of defending and passive bystanding behavior in bullying, in a sample of 1,825 Italian primary school (mean age=10 years 1 month) and middle school (mean age=13 years 2 months) students. The findings of a series of multilevel regression models show that both individual (e.g., provictim attitudes and perceived peer pressure for intervention) and class characteristics (e.g., class provictim attitudes, peer injunctive norms, and descriptive norms) help explain defending and passive bystanding behavior in bullying. These results significantly expand previous findings in this field, by demonstrating the need for a social-ecological approach to the study of the different aspects of bullying. Implications for antibullying programs are discussed. PMID:22880944

  20. Comparison of eye-safe solid state laser DIAL with passive gas filter correlation measurements from aircraft and spacecraft

    NASA Technical Reports Server (NTRS)

    Hess, Robert V.; Staton, Leo D.; Wallio, H. Andrew; Wang, Liang-Guo

    1992-01-01

    Differential Absorption Lidar (DIAL) using solid state Ti:sapphire lasers finds current application in the NASA/LASE Project for H2O vapor measurements in the approximately = 0.820 micron region for the lower and mid-troposphere and in potential future applications in planned measurements of the approximately = 0.940 micron region where both strong and weak absorption lines enables measurements throughout the troposphere and lower stratosphere. The challenge exists to perform measurements in the eye-safe greater than 1.5 micron region. A comparison between DIAL and passive Gas Filter Correlation Radiometer (GFCR) measurements is made. The essence of the differences in signal to noise ratio for DIAL and passive GFCR measurements is examined. The state of the art of lasers and optical parametric oscillators (OPO's) is discussed.

  1. Passive multi-channel analysis of surface waves with cross-correlations and beamforming. Application to a sea dike

    NASA Astrophysics Data System (ADS)

    Le Feuvre, M.; Joubert, A.; Leparoux, D.; Côte, P.

    2015-03-01

    We introduce the use of cross-correlations in the passive multi-channel analysis of surface waves (MASW), and report an improvement in the determination of subsurface shear velocities from ambient seismic noise. Velocities are measured from phase-shifts that are also related to the source location. Consequently, the accuracy with which velocities can be inferred depends on the ability of the array to locate noise sources. The computation of cross-correlations for each receiver pair allows increasing the effective spatial sampling of the array. For this reason, we show that beamforming is more efficient with cross-correlated signals. Consequently, MASW performed with cross-correlations produces a dispersion diagram where aliasing is reduced and signal-to-noise ratio increased. The proposed method is validated with synthetic records. It is then applied on passive recordings obtained on top of a sea dike at high tide, where sea waves were acting as continuous seismic sources. Surface wave velocities that favorably compare with hammer shot measurements are inferred.

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

    ERIC Educational Resources Information Center

    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…

  3. Correlation between Abortion and Infertility among Nonsmoking Women with a History of Passive Smoking in Childhood and Adolescence

    PubMed Central

    Amirkhani, Jila; Yadollah-Damavandi, Soheila; Mirlohi, Seyed Mohammad-Javad; Nasiri, Seyede Mahnaz; Parsa, Yekta

    2014-01-01

    The aim of this study is to evaluate the correlation of exposing to the cigarette smoke in childhood and adolescence with infertility and abortion in women. This case-control study evaluated 178 women who had been attended to at the Amir-al-Momenin Hospital in Tehran in 2012-2013. Seventy-eight women with chief complaint of abortion, infertility, and missed abortion and 100 healthy women were considered as case and control groups, respectively. The tool was a questionnaire with two parts. In the first part demographic information was gathered and in the second part the information regarding the history of passive smoking in childhood and adolescence period, abortion, and infertility was gathered. The mean age in case and control groups was 26.24 ± 3.1 and 27.3 ± 4.2 years, respectively. The mean body mass index (BMI) was 25.74 ± 1.38 Kg/m2. Abortion rates among passive smoker and nonpassive smoker patients were statistically significant (P = 0.036). Based on findings of this study, the experience of being a passive smoker in childhood and adolescence in women will increase the risk of abortion and infertility in the future, which could be the reason to encourage the society to step back from smoking cigarettes. PMID:25763404

  4. Gene-environment contributions to young adult sexual partnering.

    PubMed

    Halpern, Carolyn T; Kaestle, Christine E; Guo, Guang; Hallfors, Denise D

    2007-08-01

    To date, there has been relatively little work on gene-environment contributions to human sexuality, especially molecular analyses examining the potential contributions of specific polymorphisms in conjunction with life experiences. Using Wave III data from 717 heterozygous young adult sibling pairs included in the National Longitudinal Study of Adolescent Health, this article examined the combined contributions of attendance at religious services and three genetic polymorphisms (in the dopamine D4 receptor [DRD4]), dopamine D2 receptor [DRD2]), and the serotonin transporter promoter [5HTT]) to sensation seeking, a personality construct related to sexual behavior, and the number of vaginal sex partners participants had in the year before interview. Data analyses used an Allison mixed model approach to account for population stratification and correlated observations. DRD4 was unrelated to sensation seeking and to the number of sex partners in tests of both main effects and in interaction with religious attendance. Contrary to hypothesis, presence of the A1 DRD2 allele was associated with having had fewer sex partners in the past year. Associations between the 5HTT allele and sex partners varied by religious attendance, but again the patterns of associations were contrary to hypothesized relationships and were small in magnitude. These findings underscore the necessity of using more comprehensive multiple gene-multiple life experience approaches to investigations of complex behaviors such as sexual patterns. PMID:17186131

  5. The nature of nurture: disentangling passive genotype-environment correlation from family relationship influences on children's externalizing problems.

    PubMed

    Harold, Gordon T; Leve, Leslie D; Elam, Kit K; Thapar, Anita; Neiderhiser, Jenae M; Natsuaki, Misaki N; Shaw, Daniel S; Reiss, David

    2013-02-01

    The relationship between interparental conflict, hostile parenting, and children's externalizing problems is well established. Few studies, however, have examined the pattern of association underlying this constellation of family and child level variables while controlling for the possible confounding presence of passive genotype-environment correlation. Using the attributes of 2 genetically sensitive research designs, the present study examined associations among interparental conflict, parent-to-child hostility, and children's externalizing problems among genetically related and genetically unrelated mother-child and father-child groupings. Analyses were conducted separately by parent gender, thereby allowing examination of the relative role of the mother-child and father-child relationships on children's behavioral outcomes. Path analyses revealed that for both genetically related and genetically unrelated parents and children, indirect associations were apparent from interparental conflict to child externalizing problems through mother-to-child and father-to-child hostility. Associations between interparental conflict and parent-to-child hostility across genetically related and genetically unrelated parent-child groupings were significantly stronger for fathers compared to mothers. Results are discussed with respect to the role of passive genotype-environment correlation as a possible confounding influence in interpreting research findings from previous studies conducted in this area. Implications for intervention programs focusing on family process influences on child externalizing problems are also considered. PMID:23421830

  6. Passive advection of a vector field: Anisotropy, finite correlation time, exact solution, and logarithmic corrections to ordinary scaling.

    PubMed

    Antonov, N V; Gulitskiy, N M

    2015-10-01

    In this work we study the generalization of the problem considered in [Phys. Rev. E 91, 013002 (2015)] to the case of finite correlation time of the environment (velocity) field. The model describes a vector (e.g., magnetic) field, passively advected by a strongly anisotropic turbulent flow. Inertial-range asymptotic behavior is studied by means of the field theoretic renormalization group and the operator product expansion. The advecting velocity field is Gaussian, with finite correlation time and preassigned pair correlation function. Due to the presence of distinguished direction n, all the multiloop diagrams in this model vanish, so that the results obtained are exact. The inertial-range behavior of the model is described by two regimes (the limits of vanishing or infinite correlation time) that correspond to the two nontrivial fixed points of the RG equations. Their stability depends on the relation between the exponents in the energy spectrum E∝k(⊥)(1-ξ) and the dispersion law ω∝k(⊥)(2-η). In contrast to the well-known isotropic Kraichnan's model, where various correlation functions exhibit anomalous scaling behavior with infinite sets of anomalous exponents, here the corrections to ordinary scaling are polynomials of logarithms of the integral turbulence scale L. PMID:26565343

  7. Passive advection of a vector field: Anisotropy, finite correlation time, exact solution, and logarithmic corrections to ordinary scaling

    NASA Astrophysics Data System (ADS)

    Antonov, N. V.; Gulitskiy, N. M.

    2015-10-01

    In this work we study the generalization of the problem considered in [Phys. Rev. E 91, 013002 (2015), 10.1103/PhysRevE.91.013002] to the case of finite correlation time of the environment (velocity) field. The model describes a vector (e.g., magnetic) field, passively advected by a strongly anisotropic turbulent flow. Inertial-range asymptotic behavior is studied by means of the field theoretic renormalization group and the operator product expansion. The advecting velocity field is Gaussian, with finite correlation time and preassigned pair correlation function. Due to the presence of distinguished direction n , all the multiloop diagrams in this model vanish, so that the results obtained are exact. The inertial-range behavior of the model is described by two regimes (the limits of vanishing or infinite correlation time) that correspond to the two nontrivial fixed points of the RG equations. Their stability depends on the relation between the exponents in the energy spectrum E ∝k⊥1 -ξ and the dispersion law ω ∝k⊥2 -η . In contrast to the well-known isotropic Kraichnan's model, where various correlation functions exhibit anomalous scaling behavior with infinite sets of anomalous exponents, here the corrections to ordinary scaling are polynomials of logarithms of the integral turbulence scale L .

  8. MAOA, maltreatment, and gene-environment interaction predicting children's mental health: new evidence and a meta-analysis.

    PubMed

    Kim-Cohen, J; Caspi, A; Taylor, A; Williams, B; Newcombe, R; Craig, I W; Moffitt, T E

    2006-10-01

    Previous research on adults has shown that a functional polymorphism in the promoter region of the monoamine oxidase A (MAOA) gene moderates the impact of childhood maltreatment on risk for developing antisocial behavior. Thus far, attempts to replicate this finding have been mixed. The current study (i) presents new data investigating this finding in a sample of 975 seven-year-old boys, and (ii) evaluates the extant data by conducting a meta-analysis of published findings. We replicated the original finding by showing that the MAOA polymorphism moderates the development of psychopathology after exposure to physical abuse, we extended the finding to childhood closer in time to the maltreatment experience, and we ruled-out the possibility of a spurious finding by accounting for passive and evocative gene-environment correlation. Moreover, meta-analysis demonstrated that across studies, the association between maltreatment and mental health problems is significantly stronger in the group of males with the genotype conferring low vs high MAOA activity. These findings provide the strongest evidence to date suggesting that the MAOA gene influences vulnerability to environmental stress, and that this biological process can be initiated early in life. PMID:16801953

  9. Correlation between electronic and corrosion properties of the passive oxide film on nitinol.

    PubMed

    Katić, Jozefina; Metikoš-Huković, Mirjana

    2014-01-01

    The oxide film (TiO(2)) was formed on Nitinol potentiostatically in an acetic acid solution. Deep understanding of electronic properties of this film is needed to predict long-term corrosion properties of Nitinol implant material in simulated body fluid conditions. The capacitance measurements were performed under depletion conditions to study electronic (semiconducting) properties. The space charge, formed at the solid|liquid interface, creates the barrier for the corrosion processes in aggressive (bio)environment. According to the results of electrochemical impedance spectroscopy (EIS) and Mott-Schottky analysis (MS), the passive film on Nitinol behaves as amorphous highly-doped n-type semiconductor. The values of electronic structure parameters (the flat-band potential, E(fb) and the carrier (donor) density, N(D)) were corrected for frequency dispersion. PMID:25125118

  10. Stress and behavior in streptozotocin diabetic rats: biochemical correlates of passive avoidance learning.

    PubMed

    Bellush, L L; Rowland, N E

    1989-02-01

    Retention of one-trial passive avoidance training was compared in diabetic and nondiabetic rats. Also compared were corticosterone concentrations associated with both training and retention testing, catecholamine excretion related to training, and regional brain catecholamine concentrations accompanying retention testing. Diabetic rats showed significantly better retention for the task than did nondiabetic rats. Associated with retention differences, diabetic rats had higher epinephrine excretion and nondiabetic rats had lower excretion after footshock training relative to baseline measures. Norepinephrine excretion was elevated in diabetics both in baseline measurement and during the 24 hr following footshock training. No differences were found in baseline or stimulated corticosterone concentration between diabetic and nondiabetic rats. Diabetic rats had higher concentrations of norepinephrine (NE) and dopamine (DA) and lower 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratios in hypothalamus and higher NE in brain stem and amygdala than did nondiabetics, although both diabetic and nondiabetic rats had reduced DA and NE following retention testing. The results indicate that there are biochemical alterations in diabetes that may have important behavioral impact. PMID:2522305

  11. Calibration of Passive Microwave Polarimeters that Use Hybrid Coupler-Based Correlators

    NASA Technical Reports Server (NTRS)

    Piepmeier, J. R.

    2003-01-01

    Four calibration algorithms are studied for microwave polarimeters that use hybrid coupler-based correlators: 1) conventional two-look of hot and cold sources, 2) three looks of hot and cold source combinations, 3) two-look with correlated source, and 4) four-look combining methods 2 and 3. The systematic errors are found to depend on the polarimeter component parameters and accuracy of calibration noise temperatures. A case study radiometer in four different remote sensing scenarios was considered in light of these results. Applications for Ocean surface salinity, Ocean surface winds, and soil moisture were found to be sensitive to different systematic errors. Finally, a standard uncertainty analysis was performed on the four-look calibration algorithm, which was found to be most sensitive to the correlated calibration source.

  12. Gene-environment interaction and risk of breast cancer.

    PubMed

    Rudolph, Anja; Chang-Claude, Jenny; Schmidt, Marjanka K

    2016-01-19

    Hereditary, genetic factors as well as lifestyle and environmental factors, for example, parity and body mass index, predict breast cancer development. Gene-environment interaction studies may help to identify subgroups of women at high-risk of breast cancer and can be leveraged to discover new genetic risk factors. A few interesting results in studies including over 30,000 breast cancer cases and healthy controls indicate that such interactions exist. Explorative gene-environment interaction studies aiming to identify new genetic or environmental factors are scarce and still underpowered. Gene-environment interactions might be stronger for rare genetic variants, but data are lacking. Ongoing initiatives to genotype larger sample sets in combination with comprehensive epidemiologic databases will provide further opportunities to study gene-environment interactions in breast cancer. However, based on the available evidence, we conclude that associations between the common genetic variants known today and breast cancer risk are only weakly modified by environmental factors, if at all. PMID:26757262

  13. Correlations between short-term mobile monitoring and long-term passive sampler measurements of traffic-related air pollution

    NASA Astrophysics Data System (ADS)

    Riley, Erin A.; Schaal, LaNae; Sasakura, Miyoko; Crampton, Robert; Gould, Timothy R.; Hartin, Kris; Sheppard, Lianne; Larson, Timothy; Simpson, Christopher D.; Yost, Michael G.

    2016-05-01

    Mobile monitoring has provided a means for broad spatial measurements of air pollutants that are otherwise impractical to measure with multiple fixed site sampling strategies. However, the larger the mobile monitoring route the less temporally dense measurements become, which may limit the usefulness of short-term mobile monitoring for applications that require long-term averages. To investigate the stationarity of short-term mobile monitoring measurements, we calculated long term medians derived from a mobile monitoring campaign that also employed 2-week integrated passive sampler detectors (PSD) for NOx, Ozone, and nine volatile organic compounds at 43 intersections distributed across the entire city of Baltimore, MD. This is one of the largest mobile monitoring campaigns in terms of spatial extent undertaken at this time. The mobile platform made repeat measurements every third day at each intersection for 6-10 min at a resolution of 10 s. In two-week periods in both summer and winter seasons, each site was visited 3-4 times, and a temporal adjustment was applied to each dataset. We present the correlations between eight species measured using mobile monitoring and the 2-week PSD data and observe correlations between mobile NOx measurements and PSD NOx measurements in both summer and winter (Pearson's r = 0.84 and 0.48, respectively). The summer season exhibited the strongest correlations between multiple pollutants, whereas the winter had comparatively few statistically significant correlations. In the summer CO was correlated with PSD pentanes (r = 0.81), and PSD NOx was correlated with mobile measurements of black carbon (r = 0.83), two ultrafine particle count measures (r = 0.8), and intermodal (1-3 μm) particle counts (r = 0.73). Principal Component Analysis of the combined PSD and mobile monitoring data revealed multipollutant features consistent with light duty vehicle traffic, diesel exhaust and crankcase blow by. These features were more

  14. Correlations between short-term mobile monitoring and long-term passive sampler measurements of traffic-related air pollution

    NASA Astrophysics Data System (ADS)

    Riley, Erin A.; Schaal, LaNae; Sasakura, Miyoko; Crampton, Robert; Gould, Timothy R.; Hartin, Kris; Sheppard, Lianne; Larson, Timothy; Simpson, Christopher D.; Yost, Michael G.

    2016-05-01

    Mobile monitoring has provided a means for broad spatial measurements of air pollutants that are otherwise impractical to measure with multiple fixed site sampling strategies. However, the larger the mobile monitoring route the less temporally dense measurements become, which may limit the usefulness of short-term mobile monitoring for applications that require long-term averages. To investigate the stationarity of short-term mobile monitoring measurements, we calculated long term medians derived from a mobile monitoring campaign that also employed 2-week integrated passive sampler detectors (PSD) for NOx, Ozone, and nine volatile organic compounds at 43 intersections distributed across the entire city of Baltimore, MD. This is one of the largest mobile monitoring campaigns in terms of spatial extent undertaken at this time. The mobile platform made repeat measurements every third day at each intersection for 6-10 min at a resolution of 10 s. In two-week periods in both summer and winter seasons, each site was visited 3-4 times, and a temporal adjustment was applied to each dataset. We present the correlations between eight species measured using mobile monitoring and the 2-week PSD data and observe correlations between mobile NOx measurements and PSD NOx measurements in both summer and winter (Pearson's r = 0.84 and 0.48, respectively). The summer season exhibited the strongest correlations between multiple pollutants, whereas the winter had comparatively few statistically significant correlations. In the summer CO was correlated with PSD pentanes (r = 0.81), and PSD NOx was correlated with mobile measurements of black carbon (r = 0.83), two ultrafine particle count measures (r = 0.8), and intermodal (1-3 μm) particle counts (r = 0.73). Principal Component Analysis of the combined PSD and mobile monitoring data revealed multipollutant features consistent with light duty vehicle traffic, diesel exhaust and crankcase blow by. These features were more consistent

  15. Development of phytotoxicity indexes and their correlation with ecotoxicological, stability and physicochemical parameters during passive composting of poultry manure.

    PubMed

    Young, Brian Jonathan; Rizzo, Pedro Federico; Riera, Nicolás Iván; Torre, Virginia Della; López, Valeria Alejandra; Molina, Cecilia Denisse; Fernández, Florencia Estefanía; Crespo, Diana Cristina; Barrena, Raquel; Komilis, Dimitrios; Sánchez, Antoni

    2016-08-01

    Both raw and composted poultry manure is applied as soil amendment. The aims of this study were: (1) to develop phytotoxicity indexes for organic wastes and composts, and (2) to assess the correlation among phytotoxicity indexes, ecotoxicological endpoints and stability and physicochemical parameters during passive composting of poultry manure. Six 2-m(3) composting piles were constructed and four parameter groups (physicochemical and microbiological parameters, ecotoxicological endpoints, and biological activity) were determined at four sampling times during 92days. Extracts were used to carry out acute toxicity tests on Daphnia magna, Lactuca sativa and Raphanus sativus. Composting decreased average toxicity 22.8% for the 3 species and D. magna was the most sensitive species. The static respiration index decreased from 1.12 to 0.46mgO2gOMh(-1) whilst organic matter reduced by 64.1% at the end of the process. Escherichia coli colonies remained higher than values recommended by international guidelines. The D. magna immobilization test allowed the assessment of possible leachate or run-off toxicity. The new phytotoxicity indexes (RGIC0.8 and GIC80%), proposed in this study, as well as salinity, proved to be good maturity indicators. Hence, these phytotoxicity indexes could be implemented in monitoring strategies as useful ecotoxicological tools. Multivariate analyses demonstrated positive correlations between ecotoxicological endpoints (low toxicity) and biological activity (stability). These two parameter groups were associated at the final sampling time and showed negative correlations with several physicochemical parameters (organic and inorganic contents). The final poultry manure compost was rendered stable, but immature and, thus, unsuitable for soil amending. PMID:27185192

  16. Understanding risk for psychopathology through imaging gene-environment interactions

    PubMed Central

    Hyde, Luke W.; Bogdan, Ryan; Hariri, Ahmad R.

    2011-01-01

    Examining the interplay of genes, experience, and the brain is critical to understanding psychopathology. We review the recent gene-environment interaction (GxE) and imaging genetics literature with the goal of developing models to bridge these approaches within single imaging gene-environment interaction (IGxE) studies. We explore challenges inherent in both GxE and imaging genetics and highlight studies that address these limitations. In specifying IGxE models, we examine statistical methods for combining these approaches, and explore plausible biological mechanisms (e.g., epigenetics) through which these conditional mechanisms can be understood. Finally, we discuss the potential contribution that IGxE studies can make to understanding psychopathology and developing more personalized and effective prevention and treatment. PMID:21839667

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

    PubMed

    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. PMID:26626313

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

    PubMed

    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. PMID:27503943

  19. Confluence of Genes, Environment, Development, and Behavior in a Post-GWAS World

    PubMed Central

    Vrieze, Scott I.; Iacono, William G.; McGue, Matt

    2012-01-01

    This article serves to outline a research paradigm to investigate main effects and interactions of genes, environment, and development on behavior and psychiatric illness. We provide a historical context for candidate gene studies and genome-wide association studies, including benefits, limitations, and expected payoff. Using substance use and abuse as our driving example, we then turn to the importance of etiological psychological theory in guiding genetic, environmental, and developmental research, as well as the utility of refined phenotypic measures, such as endophenotypes, in the pursuit of etiological understanding and focused tests of genetic and environmental associations. Phenotypic measurement has received considerable attention and is informed by psychometrics, while the environment remains relatively poorly measured and is often confounded with genetic effects (i.e., gene-environment correlation). Genetically-informed designs which—thanks to ever cheaper genotyping—are no longer are limited to twin and adoption studies, are required to understand environmental influences. Finally, we outline the vast amount of individual differences in structural genomic variation, most of which remains to be leveraged in genetic association tests. While the genetic data can be burdensomely massive (tens of millions of variants per person), we argue that improved understanding of genomic structure and function will provide investigators with new tools to test specific a priori hypotheses derived from etiological psychological theory, much like current candidate gene research, but with less confusion and more payoff than candidate gene research has to date. PMID:23062291

  20. Confluence of genes, environment, development, and behavior in a post Genome-Wide Association Study world.

    PubMed

    Vrieze, Scott I; Iacono, William G; McGue, Matt

    2012-11-01

    This article serves to outline a research paradigm to investigate main effects and interactions of genes, environment, and development on behavior and psychiatric illness. We provide a historical context for candidate gene studies and genome-wide association studies, including benefits, limitations, and expected payoffs. Using substance use and abuse as our driving example, we then turn to the importance of etiological psychological theory in guiding genetic, environmental, and developmental research, as well as the utility of refined phenotypic measures, such as endophenotypes, in the pursuit of etiological understanding and focused tests of genetic and environmental associations. Phenotypic measurement has received considerable attention in the history of psychology and is informed by psychometrics, whereas the environment remains relatively poorly measured and is often confounded with genetic effects (i.e., gene-environment correlation). Genetically informed designs, which are no longer limited to twin and adoption studies thanks to ever-cheaper genotyping, are required to understand environmental influences. Finally, we outline the vast amount of individual difference in structural genomic variation, most of which remains to be leveraged in genetic association tests. Although the genetic data can be massive and burdensome (tens of millions of variants per person), we argue that improved understanding of genomic structure and function will provide investigators with new tools to test specific a priori hypotheses derived from etiological psychological theory, much like current candidate gene research but with less confusion and more payoff than candidate gene research has to date. PMID:23062291

  1. Psychosocial and Environmental Correlates of Walking, Cycling, Public Transport and Passive Transport to Various Destinations in Flemish Older Adolescents

    PubMed Central

    Verhoeven, Hannah; Simons, Dorien; Van Dyck, Delfien; Van Cauwenberg, Jelle; Clarys, Peter; De Bourdeaudhuij, Ilse; de Geus, Bas; Vandelanotte, Corneel; Deforche, Benedicte

    2016-01-01

    Background Active transport is a convenient way to incorporate physical activity in adolescents’ daily life. The present study aimed to investigate which psychosocial and environmental factors are associated with walking, cycling, public transport (train, tram, bus, metro) and passive transport (car, motorcycle, moped) over short distances (maximum eight kilometres) among older adolescents (17–18 years), to school and to other destinations. Methods 562 older adolescents completed an online questionnaire assessing socio-demographic variables, psychosocial variables, environmental variables and transport to school/other destinations. Zero-inflated negative binomial regression models were performed. Results More social modelling and a higher residential density were positively associated with walking to school and walking to other destinations, respectively. Regarding cycling, higher self-efficacy and a higher social norm were positively associated with cycling to school and to other destinations. Regarding public transport, a higher social norm, more social modelling of siblings and/or friends, more social support and a higher land use mix access were positively related to public transport to school and to other destinations, whereas a greater distance to school only related positively to public transport to school. Regarding passive transport, more social support and more perceived benefits were positively associated with passive transport to school and to other destinations. Perceiving less walking and cycling facilities at school was positively related to passive transport to school only, and more social modelling was positively related to passive transport to other destinations. Conclusions Overall, psychosocial variables seemed to be more important than environmental variables across the four transport modes. Social norm, social modelling and social support were the most consistent psychosocial factors which indicates that it is important to target both

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

    PubMed

    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. PMID:25773632

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

    PubMed Central

    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

  4. Correlation between carrier mobility of pentacene thin-film transistor and surface passivation of its gate dielectric

    SciTech Connect

    Cheng, Kam Ho; Tang, Wing Man; Deng, L. F.; Leung, C. H.; Lai, P. T.; Che Chiming

    2008-12-01

    The carrier mobility of pentacene thin-film transistor is studied by passivating the surface of its SiO{sub 2} gate dielectric in NH{sub 3} at different temperatures, namely, 900, 1000, 1100, and 1150 deg. C. Measurements demonstrate that the higher the annealing temperature, the higher the carrier mobility of the OTFT is. The device annealed at 1150 deg. C has a field-effect mobility of 0.74 cm{sup 2}/V s, which is 35% higher than that of the device annealed at 900 deg. C. Energy-dispersive x-ray analysis, scanning-electron microscopy, and atomic-force microscopy show that the higher carrier mobility should be due to more nitrogen incorporated at the gate-dielectric surface which results in more passivated dielectric surface and larger pentacene grains for carrier transport.

  5. A penalized robust semiparametric approach for gene-environment interactions.

    PubMed

    Wu, Cen; Shi, Xingjie; Cui, Yuehua; Ma, Shuangge

    2015-12-30

    In genetic and genomic studies, gene-environment (G×E) interactions have important implications. Some of the existing G×E interaction methods are limited by analyzing a small number of G factors at a time, by assuming linear effects of E factors, by assuming no data contamination, and by adopting ineffective selection techniques. In this study, we propose a new approach for identifying important G×E interactions. It jointly models the effects of all E and G factors and their interactions. A partially linear varying coefficient model is adopted to accommodate possible nonlinear effects of E factors. A rank-based loss function is used to accommodate possible data contamination. Penalization, which has been extensively used with high-dimensional data, is adopted for selection. The proposed penalized estimation approach can automatically determine if a G factor has an interaction with an E factor, main effect but not interaction, or no effect at all. The proposed approach can be effectively realized using a coordinate descent algorithm. Simulation shows that it has satisfactory performance and outperforms several competing alternatives. The proposed approach is used to analyze a lung cancer study with gene expression measurements and clinical variables. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26239060

  6. Candidate Gene-Environment Interaction Research: Reflections and Recommendations

    PubMed Central

    Dick, Danielle M.; Agrawal, Arpana; Keller, Matthew C.; Adkins, Amy; Aliev, Fazil; Monroe, Scott; Hewitt, John K.; Kendler, Kenneth S.; Sher, Kenneth J.

    2014-01-01

    Studying how genetic predispositions come together with environmental factors to contribute to complex behavioral outcomes has great potential for advancing our understanding of the development of psychopathology. It represents a clear theoretical advance over studying these factors in isolation. However, research at the intersection of multiple fields creates many challenges. We review several reasons why the rapidly expanding candidate gene-environment interaction (cGxE) literature should be considered with a degree of caution. We discuss lessons learned about candidate gene main effects from the evolving genetics literature and how these inform the study of cGxE. We review the importance of the measurement of the gene and environment of interest in cGxE studies. We discuss statistical concerns with modeling cGxE that are frequently overlooked. And we review other challenges that have likely contributed to the cGxE literature being difficult to interpret, including low power and publication bias. Many of these issues are similar to other concerns about research integrity (e.g., high false positive rates) that have received increasing attention in the social sciences. We provide recommendations for rigorous research practices for cGxE studies that we believe will advance its potential to contribute more robustly to the understanding of complex behavioral phenotypes. PMID:25620996

  7. BPD'S INTERPERSONAL HYPERSENSITIVITY PHENOTYPE: A GENE-ENVIRONMENT-DEVELOPMENTAL MODEL

    PubMed Central

    Gunderson, John G.; Lyons-Ruth, Karlen

    2008-01-01

    This paper explores the development of BPD as it might emerge in the child's early interpersonal reactions and how such reactions might evolve into the interpersonal pattern that typifies BPD. It begins to bridge the relevant bodies of clinical literature on the borderline's prototypic interpersonal problems with the concurrently expanding relevant literature on early child development. We will start by considering how a psychobiological disposition to BPD is likely to include a constitutional diathesis for relational reactivity, that is, for hypersensitivity to interpersonal stressors. Data relevant to this disposition's manifestations in adult clinical samples and to its heritability and neurobiology will be reviewed. We then consider how such a psychobiological disposition for interpersonal reactivity might contribute to the development of a disorganized-ambivalent form of attachment, noting especially the likely contributions of both the predisposed child and of parents who are themselves predisposed to maladaptive responses, leading to an escalation of problematic transactions. Evidence concerning both the genetics and the developmental pathways associated with disorganized attachments will be considered. Emerging links between such developmental pathways and adult BPD will be described, in particular the potential appearance by early- to middle-childhood of controlling-caregiving or controlling-punitive interpersonal strategies. Some implications from this gene-environment interactional theory for a better developmental understanding of BPD's etiology are discussed. PMID:18312121

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

    SciTech Connect

    Hwang, S.J.; Beaty, T.H.; Panny, S.

    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.

  9. Gene-Environment Interplay between Parent-Child Relationship Problems and Externalizing Disorders in Adolescence and Young Adulthood

    PubMed Central

    Samek, Diana R.; Hicks, Brian M.; Keyes, Margaret A.; Bailey, Jennifer; McGue, Matt; Iacono, William G.

    2014-01-01

    Background Previous studies have shown that genetic risk for externalizing (EXT) disorders is greater in the context of adverse family environments during adolescence, but it is unclear whether these effects are long-lasting. The current study evaluated developmental changes in gene-environment interplay in the concurrent and prospective associations between parent-child relationship problems and EXT at ages 18 and 25. Method The sample included 1,382 twin pairs (48% male) from the Minnesota Twin Family Study, participating in assessments at ages 18 (M = 17.8 years, SD = 0.69) and 25 (M = 25.0 years, SD = 0.90). Perceptions of parent-child relationship problems were assessed using questionnaires. Structured interviews were used to assess symptoms of adult antisocial behavior and nicotine, alcohol, and illicit drug dependence. Results We detected a gene-environment interaction at age 18, such that the genetic influence on EXT was greater in the context of more parent-child relationship problems. This moderation effect was not present at age 25, nor did parent-relationship problems at age 18 moderate genetic influence on EXT at age 25. Rather, common genetic influences accounted for this longitudinal association. Conclusions Gene-environment interaction evident in the relationship between adolescent parent-child relationship problems and EXT is both proximal and developmentally limited. Common genetic influence, rather than a gene-environment interaction, accounts for the long-term association between parent-child relationship problems at age 18 and EXT at age 25. These results are consistent with a relatively pervasive importance of gene-environmental correlation in the transition from late adolescence to young adulthood. PMID:25066478

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

    PubMed

    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. PMID:23067570

  11. Gene-Gene and Gene-Environment Interactions in Ulcerative Colitis

    PubMed Central

    Wang, Ming-Hsi; Fiocchi, Claudio; Zhu, Xiaofeng; Ripke, Stephan; Kamboh, M. Ilyas; Rebert, Nancy; Duerr, Richard H.; Achkar, Jean-Paul

    2014-01-01

    Genome-wide association studies (GWAS) have identified at least 133 ulcerative colitis (UC) associated loci. The role of genetic factors in clinical practice is not clearly defined. The relevance of genetic variants to disease pathogenesis is still uncertain because of not characterized gene-gene and gene-environment interactions. We examined the predictive value of combining the 133 UC risk loci with genetic interactions in an ongoing inflammatory bowel disease (IBD) GWAS. The Wellcome Trust Case-Control Consortium (WTCCC) IBD GWAS was used as a replication cohort. We applied logic regression (LR), a novel adaptive regression methodology, to search for high order interactions. Exploratory genotype correlations with UC sub-phenotypes (extent of disease, need of surgery, age of onset, extra-intestinal manifestations and primary sclerosing cholangitis (PSC)) were conducted. The combination of 133 UC loci yielded good UC risk predictability (area under the curve [AUC] of 0.86). A higher cumulative allele score predicted higher UC risk. Through LR, several lines of evidence for genetic interactions were identified and successfully replicated in the WTCCC cohort. The genetic interactions combined with the gene-smoking interaction significantly improved predictability in the model (AUC, from 0.86 to 0.89, P=3.26E-05). Explained UC variance increased from 37% to 42% after adding the interaction terms. A within case analysis found suggested genetic association with PSC. Our study demonstrates that the LR methodology allows the identification and replication of high order genetic interactions in UC GWAS datasets. UC risk can be predicted by a 133 loci and improved by adding gene-gene and gene-environment interactions. PMID:24241240

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

    PubMed Central

    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 < 0.05). There was a significant gene × sleep duration interaction effect on depressive symptoms (a'c = 0.23, SE = 0.08, P < 0.05), with the interaction occurring on genetic influences that are common to both 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 (< 7 h/night) or high (≥ 9 h/night) range, increased genetic influence on depressive symptoms was observed, particularly at 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

  13. Investigations of Passive Seismic Body-Wave Interferometry Using Noise Auto-correlations for Crustal and Upper Mantle Structure

    NASA Astrophysics Data System (ADS)

    Oren, C.; Nowack, R. L.

    2015-12-01

    It is known that the positive lags of the auto-correlation for the seismic transmission response of a layered medium correspond to the reflection seismogram (Claerbout, 1968). In this study, we investigate the use of ambient seismic noise recorded at selected broadband USArray EarthScope Transportable Array (TA) stations to obtain effective reflection seismograms for frequencies up to 1 Hz. The goal is to determine the most suitable parameters used for the processing of ambient seismic noise for the identification of crustal and upper mantle reflections and to minimize unwanted artifacts in the noise correlations. In order to best retrieve the body-wave components of the Green's function beneath a station, a number of processing steps are required. We first remove the instrument response and apply a temporal normalization to remove the effects of the most energetic sources. Next we implement spectral whitening. We test several operators for the spectral whitening where the undulations of the power spectrum are related to the strengths of later arrivals in the auto-correlation. Different filters are then applied to the auto-correlation functions, including Gaussian and zero phase Butterworth filters, in order to reduce the effect of side lobes. Hourly auto-correlations are then stacked for up to one year. On the final stack, Automatic Gain Control (AGC) is applied to equalize the correlation amplitudes in the time domain. The robustness of the resulting ambient noise auto-correlation is first tested on selected TA stations in Nevada, where we are able to identify PmP and SmS arrivals similar to those found by Tibuleac and von Seggern (2012). We then investigate noise auto-correlations applied to selected USArray TA stations in the central US.

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

    ERIC Educational Resources Information Center

    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…

  15. Electrophysiological Correlates of the Threshold to Detection of Passive Motion: An Investigation in Professional Volleyball Athletes with and without Atrophy of the Infraspinatus Muscle

    PubMed Central

    Salles, José Inácio; Cossich, Victor Rodrigues Amaral; Amaral, Marcus Vinicius; Monteiro, Martim T.; Cagy, Maurício; Motta, Geraldo; Velasques, Bruna; Piedade, Roberto; Ribeiro, Pedro

    2013-01-01

    The goal of the present study is to compare the electrophysiological correlates of the threshold to detection of passive motion (TTDPM) among three groups: healthy individuals (control group), professional volleyball athletes with atrophy of the infraspinatus muscle on the dominant side, and athletes with no shoulder pathologies. More specifically, the study aims at assessing the effects of infraspinatus muscle atrophy on the cortical representation of the TTDPM. A proprioception testing device (PTD) was used to measure the TTDPM. The device passively moved the shoulder and participants were instructed to respond as soon as movement was detected (TTDPM) by pressing a button switch. Response latency was established as the delay between the stimulus (movement) and the response (button press). Electroencephalographic (EEG) and electromyographic (EMG) activities were recorded simultaneously. An analysis of variance (ANOVA) and subsequent post hoc tests indicated a significant difference in latency between the group of athletes without the atrophy when compared both to the group of athletes with the atrophy and to the control group. Furthermore, distinct patterns of cortical activity were observed in the three experimental groups. The results suggest that systematically trained motor abilities, as well as the atrophy of the infraspinatus muscle, change the cortical representation of the different stages of proprioceptive information processing and, ultimately, the cortical representation of the TTDPM. PMID:23484136

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

    PubMed

    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

  17. Can Clouds Dance? Neural Correlates of Passive Conceptual Expansion Using a Metaphor Processing Task: Implications for Creative Cognition

    ERIC Educational Resources Information Center

    Rutter, Barbara; Kroger, Soren; Stark, Rudolf; Schweckendiek, Jan; Windmann, Sabine; Hermann, Christiane; Abraham, Anna

    2012-01-01

    Creativity has emerged in the focus of neurocognitive research in the past decade. However, a heterogeneous pattern of brain areas has been implicated as underpinning the neural correlates of creativity. One explanation for these divergent findings lies in the fact that creativity is not usually investigated in terms of its many underlying…

  18. Meconium Nicotine and Metabolites by Liquid Chromatography–Tandem Mass Spectrometry: Differentiation of Passive and Nonexposure and Correlation with Neonatal Outcome Measures

    PubMed Central

    Gray, Teresa R.; Magri, Raquel; Shakleya, Diaa M.; Huestis, Marilyn A.

    2011-01-01

    BACKGROUND Meconium analysis is a diagnostically sensitive and objective alternative to maternal self-report for detecting prenatal tobacco exposure. Nicotine and metabolite disposition in meconium is poorly characterized, and correlation of analytes’ concentrations with neonatal outcomes is unexplored. Our objectives were to quantify nicotine, cotinine, trans-3′-hydroxycotinine (OH-cotinine), nornicotine, norcotinine, and glucuronide concentrations in meconium, identify the best biomarkers of in utero tobacco exposure, compare meconium concentrations of tobacco-exposed and nonexposed neonates, and investigate concentration–outcome relationships. METHODS We quantified concentrations of nicotine and 4 metabolites with and without hydrolysis simultaneously in meconium from tobacco-exposed and nonexposed neonates by liquid chromatography–tandem mass spectrometry. We compared meconium concentrations to birth weight, length, head circumference, gestational age, and 1- and 5-min Apgar scores. RESULTS Nicotine, cotinine, and OH-cotinine were the most prevalent and abundant meconium tobacco biomarkers and were found in higher concentrations in tobacco-exposed neonates. Whereas cotinine and OH-cotinine are glucuronide bound, performing the lengthy and costly enzymatic hydrolysis identified only 1 additional positive specimen. Unconjugated nicotine, cotinine, or OH-cotinine meconium concentration >10 ng/g most accurately discriminated active from passive and nonexposed neonates. There was no significant correlation between quantitative nicotine and metabolite meconium results and neonatal outcomes, although presence of a nicotine biomarker predicted decreased head circumference. CONCLUSIONS Unconjugated nicotine, cotinine, and OH-cotinine should be analyzed in meconium to detect in utero tobacco exposure, as approximately 25% of positive specimens did not contain cotinine. Immunoassay testing monitoring cotinine only would underestimate the prevalence of prenatal

  19. Evidence of Reactive Gene-Environment Correlation in Preschoolers' Prosocial Play with Unfamiliar Peers

    ERIC Educational Resources Information Center

    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…

  20. Gene-Environment Interactions Between Depressive Symptoms and Smoking Quantity.

    PubMed

    Keskitalo-Vuokko, Kaisu; Korhonen, Tellervo; Kaprio, Jaakko

    2016-08-01

    We investigated genetic and environmental correlations and gene by environment interactions (GxE) between depressive symptoms measured by the Beck Depression Inventory (BDI) and quantity smoked measured by number of cigarettes smoked per day (CPD) using quantitative genetic modeling. The population-based sample consisted of 12,063 twin individuals from the Finnish Twin Cohort Study. Bivariate Cholesky decomposition revealed that the phenotypic correlation (r = 0.09) between BDI and CPD was explained by shared genetic (r g = 0.18) and environmental (r e = 0.08) factors. GxE models incorporating moderator effects were built by using CPD as trait and BDI as moderator and vice versa. The importance of the genetic variance component increased with increasing moderator value in both models. Thus, the influence of genetic effects on variance of smoking quantity was enhanced in individuals with elevated depression score and vice versa; the genetic effects on depression variance were potentiated among heavy smokers. In conclusion, shared genetic and environmental factors as well as GxE underlie the association of smoking with depression. PMID:27161145

  1. Powerful Set-Based Gene-Environment Interaction Testing Framework for Complex Diseases.

    PubMed

    Jiao, Shuo; Peters, Ulrike; Berndt, Sonja; Bézieau, Stéphane; Brenner, Hermann; Campbell, Peter T; Chan, Andrew T; Chang-Claude, Jenny; Lemire, Mathieu; Newcomb, Polly A; Potter, John D; Slattery, Martha L; Woods, Michael O; Hsu, Li

    2015-12-01

    Identification of gene-environment interaction (G × E) is important in understanding the etiology of complex diseases. Based on our previously developed Set Based gene EnviRonment InterAction test (SBERIA), in this paper we propose a powerful framework for enhanced set-based G × E testing (eSBERIA). The major challenge of signal aggregation within a set is how to tell signals from noise. eSBERIA tackles this challenge by adaptively aggregating the interaction signals within a set weighted by the strength of the marginal and correlation screening signals. eSBERIA then combines the screening-informed aggregate test with a variance component test to account for the residual signals. Additionally, we develop a case-only extension for eSBERIA (coSBERIA) and an existing set-based method, which boosts the power not only by exploiting the G-E independence assumption but also by avoiding the need to specify main effects for a large number of variants in the set. Through extensive simulation, we show that coSBERIA and eSBERIA are considerably more powerful than existing methods within the case-only and the case-control method categories across a wide range of scenarios. We conduct a genome-wide G × E search by applying our methods to Illumina HumanExome Beadchip data of 10,446 colorectal cancer cases and 10,191 controls and identify two novel interactions between nonsteroidal anti-inflammatory drugs (NSAIDs) and MINK1 and PTCHD3. PMID:26095235

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

    PubMed Central

    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. This article reviews recent advances in identifying gene-environment interactions related to obesity and describes epidemiological designs and newly developed statistical approaches to characterizing and discovering gene-environment interactions on obesity risk. PMID:25951849

  3. Commentary: Gene-Environment Interplay in the Context of Genetics, Epigenetics, and Gene Expression.

    ERIC Educational Resources Information Center

    Kramer, Douglas A.

    2005-01-01

    Objective: To comment on the article in this issue of the Journal by Professor Michael Rutter, "Environmentally Mediated Risks for Psychopathology: Research Strategies and Findings," in the context of current research findings on gene-environment interaction, epigenetics, and gene expression. Method: Animal and human studies are reviewed that…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  6. Confirmatory and Competitive Evaluation of Alternative Gene-Environment Interaction Hypotheses

    ERIC Educational Resources Information Center

    Belsky, Jay; Pluess, Michael; Widaman, Keith F.

    2013-01-01

    Background: Most gene-environment interaction (GXE) research, though based on clear, vulnerability-oriented hypotheses, is carried out using exploratory rather than hypothesis-informed statistical tests, limiting power and making formal evaluation of competing GXE propositions difficult. Method: We present and illustrate a new regression technique…

  7. How Gene-Environment Interaction Affects Children's Anxious and Fearful Behavior. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This brief reports on the study "Evidence for a Gene-Environment Interaction in Predicting Behavioral Inhibition in Middle Childhood" (N. A. Fox, K E. Nichols, H. A. Henderson, K. Rubin, L. Schmidt, D. Hamer, M. Ernst, and D. S.…

  8. A Platform for the Remote Conduct of Gene-Environment Interaction Studies

    PubMed Central

    Gallacher, John; Collins, Rory; Elliott, Paul; Palmer, Stephen; Burton, Paul; Mitchell, Clive; John, Gareth; Lyons, Ronan

    2013-01-01

    Background Gene-environment interaction studies offer the prospect of robust causal inference through both gene identification and instrumental variable approaches. As such they are a major and much needed development. However, conducting these studies using traditional methods, which require direct participant contact, is resource intensive. The ability to conduct gene-environment interaction studies remotely would reduce costs and increase capacity. Aim To develop a platform for the remote conduct of gene-environment interaction studies. Methods A random sample of 15,000 men and women aged 50+ years and living in Cardiff, South Wales, of whom 6,012 were estimated to have internet connectivity, were mailed inviting them to visit a web-site to join a study of successful ageing. Online consent was obtained for questionnaire completion, cognitive testing, re-contact, record linkage and genotyping. Cognitive testing was conducted using the Cardiff Cognitive Battery. Bio-sampling was randomised to blood spot, buccal cell or no request. Results A heterogeneous sample of 663 (4.5% of mailed sample and 11% of internet connected sample) men and women (47% female) aged 50–87 years (median = 61 yrs) from diverse backgrounds (representing the full range of deprivation scores) was recruited. Bio-samples were donated by 70% of those agreeing to do so. Self report questionnaires and cognitive tests showed comparable distributions to those collected using face-to-face methods. Record linkage was achieved for 99.9% of participants. Conclusion This study has demonstrated that remote methods are suitable for the conduct of gene-environment interaction studies. Up-scaling these methods provides the opportunity to increase capacity for large-scale gene-environment interaction studies. PMID:23349852

  9. Passive Accelerometer

    NASA Technical Reports Server (NTRS)

    Naumann, Robert J.; Baugher, Charles; Alexander, Iwan

    1992-01-01

    Motion of ball in liquid indicates acceleration. Passive accelerometer measures small accelerations along cylindrical axis. Principle of operation based on Stokes' law. Provides accurate measurements of small quasi-steady accelerations. Additional advantage, automatically integrates out unwanted higher-frequency components of acceleration.

  10. Gene-Environment Interactions in Cancer Epidemiology: A National Cancer Institute Think Tank Report

    PubMed Central

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

    2014-01-01

    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 (0.01gene-environment interactions, into epidemiologic studies of cancer. To help address these questions, and to better inform research priorities and allocation of resources, the National Cancer Institute sponsored a “Gene-Environment Think Tank” on January 10th–011th, 2012. The objective of the Think Tank was to facilitate discussions on: 1) the state of the science; 2) the goals of gene-environment interaction studies in 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 gene-environment 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. PMID:24123198

  11. Genetics, environment, and gene-environment interactions in the development of systemic rheumatic diseases

    PubMed Central

    Sparks, Jeffrey A.; Costenbader, Karen H.

    2014-01-01

    Understanding disease susceptibility factors and gene-environment interactions may offer valuable insights into the biological mechanisms for the etiology of rheumatic diseases. Defining the contributions of genetic and environmental factors to the pathogenesis of rheumatic diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS), may have important implications for understanding risk prediction, pathogenic mechanisms, cellular pathways, drug discovery, and prevention strategies. However, rheumatic diseases offer distinct challenges to researchers due to heterogeneity in disease phenotypes, low disease incidence, and geographic variation in both genetic and environmental factors. Emerging research areas, including epigenetics, metabolomics, and the microbiome, may provide additional links between genetic and environmental risk factors in rheumatic disease pathogenesis. This article reviews the methods used to establish genetic and environmental risk factors and to study gene-environment interactions in rheumatic diseases and provides specific examples of successes and challenges for identifying gene-environment interactions in RA, SLE, and AS. Finally, we describe how emerging research strategies may build upon previous discoveries as well as future challenges. PMID:25437282

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

    PubMed

    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. PMID:26250573

  13. Gene-Environment Interaction Effects of Peer Deviance, Parental Knowledge and Stressful Life Events on Adolescent Alcohol Use

    PubMed Central

    Cooke, Megan E.; Meyers, Jacquelyn L.; Latvala, Antti; Korhonen, Tellervo; Rose, Richard J.; Kaprio, Jaakko; Salvatore, Jessica E.; Dick, Danielle M.

    2016-01-01

    The purpose of this study was to address two methodological issues that have called into question whether previously reported gene-environment interaction (GxE) effects for adolescent alcohol use are “real.” These issues are (1) the potential correlation between the environmental moderator and the outcome across twins and (2) non-linear transformations of the behavioral outcome. Three environments that have been previously reported on (peer deviance, parental knowledge, and potentially stressful life events) were examined here. For each moderator (peer deviance, parental knowledge, and potentially stressful life events), a series of models was fit to both a raw and transformed measure of monthly adolescent alcohol use in a sample that included 825 DZ and 803 MZ twin pairs. The results showed that the moderating effect of peer deviance was robust to transformation, and that although the significance of moderating effects of parental knowledge and potentially stressful life events were dependent on the scale of the adolescent alcohol use outcome, the overall results were consistent across transformation. In addition, the findings did not vary across statistical models. The consistency of the peer deviance results and the shift of the parental knowledge and potentially stressful life events results between trending and significant, shed some light on why previous findings for certain moderators have been inconsistent and emphasize the importance of considering both methodological issues and previous findings when conducting and interpreting GxE analyses. PMID:26290350

  14. From 'omics' to complex disease: a systems biology approach to gene-environment interactions in cancer

    PubMed Central

    2010-01-01

    Background Cancer is a complex disease that involves a sequence of gene-environment interactions in a progressive process that cannot occur without dysfunction in multiple systems, including DNA repair, apoptotic and immune functions. Epigenetic mechanisms, responding to numerous internal and external cues in a dynamic ongoing exchange, play a key role in mediating environmental influences on gene expression and tumor development. Hypothesis The hypothesis put forth in this paper addresses the limited success of treatment outcomes in clinical oncology. It states that improvement in treatment efficacy requires a new paradigm that focuses on reversing systemic dysfunction and tailoring treatments to specific stages in the process. It requires moving from a reductionist framework of seeking to destroy aberrant cells and pathways to a transdisciplinary systems biology approach aimed at reversing multiple levels of dysfunction. Conclusion Because there are many biological pathways and multiple epigenetic influences working simultaneously in the expression of cancer phenotypes, studying individual components in isolation does not allow an adequate understanding of phenotypic expression. A systems biology approach using new modeling techniques and nonlinear mathematics is needed to investigate gene-environment interactions and improve treatment efficacy. A broader array of study designs will also be required, including prospective molecular epidemiology, immune competent animal models and in vitro/in vivo translational research that more accurately reflects the complex process of tumor initiation and progression. PMID:20420667

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

    PubMed Central

    Chouliaras, L.; Sierksma, A. S. R.; Kenis, G.; Prickaerts, J.; Lemmens, M. A. M.; Brasnjevic, I.; van Donkelaar, E. L.; Martinez-Martinez, P.; Losen, M.; De Baets, M. H.; Kholod, N.; van Leeuwen, F.; Hof, P. R.; van Os, J.; Steinbusch, H. W. M.; van den Hove, D. L. A.; Rutten, B. P. F.

    2010-01-01

    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. PMID:20953364

  16. Enhancing the gene-environment interaction framework through a quasi-experimental research design: evidence from differential responses to September 11.

    PubMed

    Fletcher, Jason M

    2014-01-01

    This article uses a gene-environment interaction framework to examine the differential responses to an objective external stressor based on genetic variation in the production of depressive symptoms. This article advances the literature by utilizing a quasi-experimental environmental exposure design, as well as a regression discontinuity design, to control for seasonal trends, which limit the potential for gene-environment correlation and allow stronger causal claims. Replications are attempted for two prominent genes (5-HTT and MAOA), and three additional genes are explored (DRD2, DRD4, and DAT1). This article provides evidence of a main effect of 9/11 on reports of feelings of sadness and fails to replicate a common finding of interaction using 5-HTT but does show support for interaction with MAOA in men. It also provides new evidence that variation in the DRD4 gene modifies an individual's response to the exposure, with individuals with no 7-repeats found to have a muted response. PMID:24784984

  17. Composition of incipient passivating layers on heat-rejecting aluminum in carboxylate- and silicate-inhibited coolants: Correlation with ASTM D 4340 weight losses

    SciTech Connect

    Wagner, F.T.; Moylan, T.E.; Simko, S.J.; Militello, M.C.

    1999-08-01

    X-ray photoelectron spectroscopy identified compositional differences between passivating layers initially formed in carboxylated coolants, in silicated coolants, and in a mixture thereof on well-controlled 319 aluminum surfaces under heat-rejecting conditions. The layer formed in silicated coolant was primarily silica, while that in carboxylated coolant was primarily hydrated alumina. Competition between inhibitor packages when carboxylated coolant was contaminated from the start with low levels of silicated coolant produced films which were not simply patchwise mixtures of the pure-coolant film types. The surface analytical results aid the interpretation of subtle differences in weight losses under the ASTM Standard Test Method for Corrosion of Cast Aluminum Alloys in Engine Coolants Under Heat-Rejecting Conditions (D 4340) in carboxylated versus silicated coolants that became more pronounced when testing was carried out at a vehicle-like 50% coolant concentration. Results from time-resolved D4340 measurements and from a two-step cleaning procedure further contribute towards proper evaluation of D4340 weight losses in the different coolant types.

  18. Gene-Environment Interactions, Folate Metabolism and the Embryonic Nervous System

    PubMed Central

    Ross, M. Elizabeth

    2010-01-01

    Formation of brain and spinal cord requires the successful closure of neural ectoderm into an embryonic neural tube. Defects in this process result in anencephaly or spina bifida, which together constitute a leading cause of mortality and morbidity in children, affecting all ethnic and socioeconomic groups. The subject of intensive research for decades, neural tube defects (NTDs) are understood to arise from complex interactions of genes and environmental conditions, though systems-level details are still elusive. Despite the variety of underlying causes, a single intervention, folic acid supplementation given in the first gestational month can measurably reduce the occurrence of NTDs in a population. Evidence for and the scope of gene-environment interactions in the genesis of NTDs are discussed. A systems-based approach is now possible toward studies of genetic and environmental influences underlying NTDs that will enable the assessment of individual risk and personalized optimization of prevention. PMID:20836042

  19. Externalizing Disorders and Environmental Risk: Mechanisms of Gene-Environment Interplay and Strategies for Intervention

    PubMed Central

    Samek, Diana R.; Hicks, Brian M.

    2014-01-01

    Summary Though heritable, externalizing disorders have a number of robust associations with several environmental risk factors, including family, school, and peer contexts. To account for these associations, we integrate a behavioral genetic perspective with principles of a developmental cascade theory of antisocial behavior. The major environmental contexts associated with child externalizing problems are reviewed, as are the processes of gene-environment interplay underlying these associations. Throughout, we discuss implications for prevention and intervention. Three major approaches designed to reduce child externalizing behavior are reviewed. Prevention and intervention programs appear to be most successful when they target individuals or communities most at risk for developing externalizing disorders, rather than applied universally. We end by commenting on areas in need of additional research concerning environmental influences on persistent externalizing behaviors. PMID:25485087

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

    PubMed

    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. PMID:26357960

  1. Putting the Genome in Context: Gene-Environment Interactions in Type 2 Diabetes.

    PubMed

    Franks, Paul W; Paré, Guillaume

    2016-07-01

    The genome is often the conduit through which environmental exposures convey their effects on health and disease. Whilst not all diseases act by directly perturbing the genome, the phenotypic responses are often genetically determined. Hence, whilst diseases are often defined has having differing degrees of genetic determination, genetic and environmental factors are, with few exceptions, inseparable features of most diseases, not least type 2 diabetes. It follows that to optimize diabetes, prevention and treatment will require that the etiological roles of genetic and environmental risk factors be jointly considered. As we discuss here, studies focused on quantifying gene-environment and gene-treatment interactions are gathering momentum and may eventually yield data that helps guide health-related choices and medical interventions for type 2 diabetes and other complex diseases. PMID:27155607

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

    PubMed Central

    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

  3. Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease

    PubMed Central

    Chou, Vivian P.; Ko, Novie; Holman, Theodore R.; Manning-Boğ, Amy B.

    2014-01-01

    Lipoxygenase (LOX) activity has been implicated in neurodegenerative disorders such as Alzheimer's disease, but its effects in Parkinson's disease (PD) pathogenesis are less understood. Gene-environment interaction models have utility in unmasking the impact of specific cellular pathways in toxicity that may not be observed using a solely genetic or toxicant disease model alone. To evaluate if distinct LOX isozymes selectively contribute to PD-related neurodegeneration, transgenic (i.e. 5-LOX and 12/15-LOX deficient) mice can be challenged with a toxin that mimics cell injury and death in the disorder. Here we describe the use of a neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces a nigrostriatal lesion to elucidate the distinct contributions of LOX isozymes to neurodegeneration related to PD. The use of MPTP in mouse, and nonhuman primate, is well-established to recapitulate the nigrostriatal damage in PD. The extent of MPTP-induced lesioning is measured by HPLC analysis of dopamine and its metabolites and semi-quantitative Western blot analysis of striatum for tyrosine hydroxylase (TH), the rate-limiting enzyme for the synthesis of dopamine. To assess inflammatory markers, which may demonstrate LOX isozyme-selective sensitivity, glial fibrillary acidic protein (GFAP) and Iba-1 immunohistochemistry are performed on brain sections containing substantia nigra, and GFAP Western blot analysis is performed on striatal homogenates. This experimental approach can provide novel insights into gene-environment interactions underlying nigrostriatal degeneration and PD. PMID:24430802

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

    PubMed

    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. PMID:26139508

  5. 2D Raman correlation analysis of formation mechanism of passivating film on overcharged LiCoO2 electrode with additive system

    NASA Astrophysics Data System (ADS)

    Park, Yeonju; Shin, Su Hyun; Lee, Sung Man; Kim, Sung Phil; Choi, Hyun Chul; Jung, Young Mee

    2014-07-01

    The effect of vinylene carbonate (VC) as solid electrolyte interface (SEI)-forming additive on the electrochemical performance of the LiCoO2 cathode was investigated by galvanostatic charge-discharge testing as well as Raman and 2D correlation spectroscopy. It was found that VC-containing electrolyte has a positive effect on capacity fading. An analysis of the 2D Raman correlation spectra suggested that even though the same SEI components (i.e., Co3O4 and Li2O) are produced on the cathode surface, the electrochemical reaction kinetics in the cathode/electrolyte interface differ according to the non-use or use of VC: in the latter case, formation of the SEI components is delayed.

  6. Passive solar technology

    SciTech Connect

    Watson, D

    1981-04-01

    The present status of passive solar technology is summarized, including passive solar heating, cooling and daylighting. The key roles of the passive solar system designer and of innovation in the building industry are described. After definitions of passive design and a summary of passive design principles are given, performance and costs of passive solar technology are discussed. Passive energy design concepts or methods are then considered in the context of the overall process by which building decisions are made to achieve the integration of new techniques into conventional design. (LEW).

  7. Fundamental studies of passivity and passivity breakdown

    SciTech Connect

    Macdonald, D.D.; Urquidi-Macdonald, M.; Song, H.; Biaggio-Rocha, S.; Searson, P.

    1991-11-01

    This report summarizes the findings of our fundamental research program on passivity and passivity breakdown. During the past three and one half years in this program (including the three year incrementally-funded grant prior to the present grant), we developed and experimentally tested various physical models for the growth and breakdown of passive films on metal surfaces. These models belong to a general class termed point defects models'' (PDMs), in which the growth and breakdown of passive films are described in terms of the movement of anion and cation vacancies.

  8. CardioGxE, a catalog of gene-environment interactions for cardiometabolic traits

    PubMed Central

    2014-01-01

    Background Genetic understanding of complex traits has developed immensely over the past decade but remains hampered by incomplete descriptions of contribution to phenotypic variance. Gene-environment (GxE) interactions are one of these contributors and in the guise of diet and physical activity are important modulators of cardiometabolic phenotypes and ensuing diseases. Results We mined the scientific literature to collect GxE interactions from 386 publications for blood lipids, glycemic traits, obesity anthropometrics, vascular measures, inflammation and metabolic syndrome, and introduce CardioGxE, a gene-environment interaction resource. We then analyzed the genes and SNPs supporting cardiometabolic GxEs in order to demonstrate utility of GxE SNPs and to discern characteristics of these important genetic variants. We were able to draw many observations from our extensive analysis of GxEs. 1) The CardioGxE SNPs showed little overlap with variants identified by main effect GWAS, indicating the importance of environmental interactions with genetic factors on cardiometabolic traits. 2) These GxE SNPs were enriched in adaptation to climatic and geographical features, with implications on energy homeostasis and response to physical activity. 3) Comparison to gene networks responding to plasma cholesterol-lowering or regression of atherosclerotic plaques showed that GxE genes have a greater role in those responses, particularly through high-energy diets and fat intake, than do GWAS-identified genes for the same traits. Other aspects of the CardioGxE dataset were explored. Conclusions Overall, we demonstrate that SNPs supporting cardiometabolic GxE interactions often exhibit transcriptional effects or are under positive selection. Still, not all such SNPs can be assigned potential functional or regulatory roles often because data are lacking in specific cell types or from treatments that approximate the environmental factor of the GxE. With research on metabolic related

  9. Estimating primaries from passive seismic data

    NASA Astrophysics Data System (ADS)

    Cheng, Hao; Wang, De-Li; Feng, Fei; Zhu, Heng

    2015-12-01

    Passive seismic sources can generally be divided into transient sources and noise sources. Noise sources are particularly the continuous, random small bursts, like background noise. The virtual-shot gathers obtained by the traditional cross-correlation algorithm from passive seismic data not only contain primaries, but also include surface-related multiples. Through estimating primaries by sparse inversion, we can directly obtain primaries from passive seismic data activated by transient sources, which are free of surface-related multiples. The problem of estimating primaries from passive seismic data activated by noise sources has not been discussed to date. First, by introducing the optimisation problem via the L1-norm constraint, this paper makes the traditional method of estimating primaries by sparse inversion from passive seismic data activated by transient sources improved, which overcomes the time-window problem. During the sparse inversion, the sparsifying transform, S = C2⊗W, is introduced. In the sparsifying-transform domain, the transformed data is more sparse, so the solution becomes more accurate. Second, this paper proposes estimating primaries from passive seismic data activated by noise sources. In the case of the sparse assumption not holding, we use the least-squares method based on the principle of minimum energy to estimate primaries from passive seismic data using the noise sources. Finally, we compare the primaries estimated from passive seismic data using transient sources and noise sources and analyse the characteristics of the estimated primaries obtained from two passive seismic data.

  10. Gene-Environment Interactions across Development: Exploring DRD2 Genotype and Prenatal Smoking Effects on Self-Regulation

    ERIC Educational Resources Information Center

    Wiebe, Sandra A.; Espy, Kimberly Andrews; Stopp, Christian; Respass, Jennifer; Stewart, Peter; Jameson, Travis R.; Gilbert, David G.; Huggenvik, Jodi I.

    2009-01-01

    Genetic factors dynamically interact with both pre- and postnatal environmental influences to shape development. Considerable attention has been devoted to gene-environment interactions (G x E) on important outcomes (A. Caspi & T. E. Moffitt, 2006). It is also important to consider the possibility that these G x E effects may vary across…

  11. A database of gene-environment interactions pertaining to blood lipid traits, cardiovascular disease and type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As the role of the environment – diet, exercise, alcohol and tobacco use and sleep among others – is accorded a more prominent role in modifying the relationship between genetic variants and clinical measures of disease, consideration of gene-environment (GxE) interactions is a must. To facilitate i...

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  14. Gene-environment interactions in common mental disorders: an update and strategy for a genome-wide search.

    PubMed

    Uher, Rudolf

    2014-01-01

    A decade of research has demonstrated the explanatory potential of interplay between genetic variants and environmental factors in the development of common mental disorders. Initial findings have undergone tests of replicability and specificity. Some gene-environment interactions have been confirmed, some have not replicated and yet other turned out to be more specific than initially thought. Specific and complementary roles of genetic factors have been delineated: a common functional length polymorphism in the serotonin transporter gene (5-HTTLPR) moderated the effect of childhood maltreatment on chronic depression in adulthood, but did not substantially influence the effects of adult stressful life events on the onset of new depressive episodes; in contrast, a common functional polymorphism in the brain-derived neurotrophic factor gene (BDNF) moderated the effect of stressful life events in adulthood in triggering new depressive episodes, but did not influence the effects of childhood maltreatment. Molecular mechanisms underlying gene-environment interactions are being uncovered, including DNA methylation and other epigenetic modifications. New gene-environment interactions continue to be reported, still largely from hypothesis-driven research. Statistical and biological prioritization strategies are proposed to facilitate a systematic discovery of novel gene-environment interactions in genome-wide analyses. PMID:24323294

  15. Bayesian Variable Selection for Hierarchical Gene-Environment and Gene-Gene Interactions

    PubMed Central

    Liu, Changlu; Ma, Jianzhong; Amos, Christopher I.

    2014-01-01

    We propose a Bayesian hierarchical mixture model framework that allows us to investigate the genetic and environmental effects, gene by gene interactions and gene by environment interactions in the same model. Our approach incorporates the natural hierarchical structure between the main effects and interaction effects into a mixture model, such that our methods tend to remove the irrelevant interaction effects more effectively, resulting in more robust and parsimonious models. We consider both strong and weak hierarchical models. For a strong hierarchical model, both of the main effects between interacting factors must be present for the interactions to be considered in the model development, while for a weak hierarchical model, only one of the two main effects is required to be present for the interaction to be evaluated. Our simulation results show that the proposed strong and weak hierarchical mixture models work well in controlling false positive rates and provide a powerful approach for identifying the predisposing effects and interactions in gene-environment interaction studies, in comparison with the naive model that does not impose this hierarchical constraint in most of the scenarios simulated. We illustrated our approach using data for lung cancer and cutaneous melanoma. PMID:25154630

  16. Gene-Environment Interplay in the Association between Pubertal Timing and Delinquency in Adolescent Girls

    PubMed Central

    Harden, K. Paige; Mendle, Jane

    2014-01-01

    Early pubertal timing places girls at elevated risk for a breadth of negative outcomes, including involvement in delinquent behavior. While previous developmental research has emphasized the unique social challenges faced by early maturing girls, this relation is complicated by genetic influences for both delinquent behavior and pubertal timing, which are seldom controlled for in existing research. The current study uses genetically informed data on 924 female-female twin and sibling pairs drawn from the National Longitudinal Study of Adolescent Health to (1) disentangle biological versus environmental mechanisms for the effects of early pubertal timing and (2) test for gene-environment interactions. Results indicate that early pubertal timing influences girls’ delinquency through a complex interplay between biological risk and environmental experiences. Genes related to earlier age at menarche and higher perceived development significantly predict increased involvement in both non-violent and violent delinquency. Moreover, after accounting for this genetic association between pubertal timing and delinquency, the impact of non-shared environmental influences on delinquency are significantly moderated by pubertal timing, such that the non-shared environment is most important among early maturing girls. This interaction effect is particularly evident for non-violent delinquency. Overall, results suggest early maturing girls are vulnerable to an interaction between genetic and environmental risks for delinquent behavior. PMID:21668078

  17. A unified set-based test with adaptive filtering for gene-environment interaction analyses.

    PubMed

    Liu, Qianying; Chen, Lin S; Nicolae, Dan L; Pierce, Brandon L

    2016-06-01

    In genome-wide gene-environment interaction (GxE) studies, a common strategy to improve power is to first conduct a filtering test and retain only the SNPs that pass the filtering in the subsequent GxE analyses. Inspired by two-stage tests and gene-based tests in GxE analysis, we consider the general problem of jointly testing a set of parameters when only a few are truly from the alternative hypothesis and when filtering information is available. We propose a unified set-based test that simultaneously considers filtering on individual parameters and testing on the set. We derive the exact distribution and approximate the power function of the proposed unified statistic in simplified settings, and use them to adaptively calculate the optimal filtering threshold for each set. In the context of gene-based GxE analysis, we show that although the empirical power function may be affected by many factors, the optimal filtering threshold corresponding to the peak of the power curve primarily depends on the size of the gene. We further propose a resampling algorithm to calculate P-values for each gene given the estimated optimal filtering threshold. The performance of the method is evaluated in simulation studies and illustrated via a genome-wide gene-gender interaction analysis using pancreatic cancer genome-wide association data. PMID:26496228

  18. Gene-environment interactions in asthma and allergic diseases: challenges and perspectives.

    PubMed

    Kauffmann, Francine; Demenais, Florence

    2012-12-01

    The concept of gene-environment (GxE) interactions has dramatically evolved in the last century and has now become a central theme in studies that assess the causes of human disease. Despite the numerous efforts to discover genes associated in asthma and allergy through various approaches, including the recent genome-wide association studies, investigation of GxE interactions has been mainly limited to candidate genes, candidate environmental exposures, or both. This review discusses the various strategies from hypothesis-driven strategies to the full agnostic search of GxE interactions with an illustration from recently published articles. Challenges raised by each piece of the puzzle (ie, phenotype, environment, gene, and analysis of GxE interaction) are put forward, and tentative solutions are proposed. New perspectives to integrate various types of data generated by new sequencing technologies and to progress toward a systems biology approach of disease are outlined. The future of a molecular network-based approach of disease to which GxE interactions are related requires space for innovative and multidisciplinary research. Assembling the various parts of a puzzle in a complex system could well occur in a way that might not necessarily follow the rules of logic. PMID:23195523

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

    PubMed

    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. PMID:27367897

  20. A unified set-based test with adaptive filtering for gene-environment interaction analyses

    PubMed Central

    Liu, Qianying; Chen, Lin S.; Nicolae, Dan L.; Pierce, Brandon L.

    2015-01-01

    Summary In genome-wide gene-environment interaction (GxE) studies, a common strategy to improve power is to first conduct a filtering test and retain only the SNPs that pass the filtering in the subsequent GxE analyses. Inspired by two-stage tests and gene-based tests in GxE analysis, we consider the general problem of jointly testing a set of parameters when only a few are truly from the alternative hypothesis and when filtering information is available. We propose a unified set-based test that simultaneously considers filtering on individual parameters and testing on the set. We derive the exact distribution and approximate the power function of the proposed unified statistic in simplified settings, and use them to adaptively calculate the optimal filtering threshold for each set. In the context of gene-based GxE analysis, we show that although the empirical power function may be affected by many factors, the optimal filtering threshold corresponding to the peak of the power curve primarily depends on the size of the gene. We further propose a resampling algorithm to calculate p-values for each gene given the estimated optimal filtering threshold. The performance of the method is evaluated in simulation studies and illustrated via a genome-wide gene-gender interaction analysis using pancreatic cancer genome-wide association data. PMID:26496228

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

    PubMed

    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. PMID:26230319

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

    PubMed

    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. PMID:26687973

  3. The Influence of Gene-Gene and Gene-Environment Interactions on the Risk of Asbestosis

    PubMed Central

    Franko, A.; Dolžan, V.; Arnerić, N.; Dodič-Fikfak, M.

    2013-01-01

    This study investigated the influence of gene-gene and gene-environment interactions on the risk of developing asbestosis. The study comprised 262 cases with asbestosis and 265 controls with no asbestos-related disease previously studied for MnSOD, ECSOD, CAT, GSTT1, GSTM1, GSTP1, and iNOS polymorphisms. Data on cumulative asbestos and smoking were available for all subjects. To assess gene-gene and gene-environmental interactions, logistic regression was used. The associations between MnSOD Ala −9Val polymorphism and the risk of asbestosis and between iNOS genotypes and asbestosis were modified by CAT –262 C > T polymorphism (P = 0.038; P = 0.031). A strong interaction was found between GSTM1-null polymorphism and smoking (P = 0.007), iNOS (CCTTT)n polymorphism and smoking (P = 0.054), and between iNOS (CCTTT)n polymorphism and cumulative asbestos exposure (P = 0.037). The findings of this study suggest that the interactions between different genotypes, genotypes and smoking, and between genotypes and asbestos exposure have an important influence on the development of asbestosis and should be seriously considered in future research on occupational/environmental asbestos-related diseases. PMID:23984360

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

    PubMed

    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. PMID:27037711

  5. Methods for Investigating Gene-Environment Interactions in Candidate Pathway and Genome-Wide Association Studies

    PubMed Central

    Thomas, Duncan

    2010-01-01

    Despite the considerable enthusiasm about the yield of novel and replicated discoveries of genetic associations from the new generation of genome-wide association studies (GWAS), the proportion of the heritability of most complex diseases that have been studied to date remains small. Some of this “dark matter” could be due to gene-environment (G×E) interactions or more complex pathways involving multiple genes and exposures. We review the basic epidemiologic study design and statistical analysis approaches to studying G×E interactions individually and then consider more comprehensive approaches to studying entire pathways or GWAS data. In addition to the usual issues in genetic association studies, particular care is needed in exposure assessment and very large sample sizes are required. Although hypothesis-driven pathway-based and “agnostic” GWAS approaches are generally viewed as opposite poles, we suggest that the two can be usefully married using hierarchical modeling strategies that exploit external pathway knowledge in mining genome-wide data. PMID:20070199

  6. Genes, environment, and individual differences in responding to treatment for depression.

    PubMed

    Uher, Rudolf

    2011-01-01

    A principal weakness of evidence-based psychiatry is that it does not account for the individual variability in therapeutic response among individuals with the same diagnosis. The aim of personalized psychiatry is to remediate this shortcoming and to use predictors to select treatment that is most likely to be beneficial for an individual. This article reviews the evidence that genetic variation, environmental exposures, and gene-environment interactions shape mental illness and influence treatment outcomes, with a primary focus on depression. Several genetic polymorphisms have been identified that influence the outcome of specific treatments, but the strength and generalizability of such influences are not sufficient to justify personalized prescribing. Environmental exposures in early life, such as childhood maltreatment, exert long-lasting influences that are moderated by inherited genetic variation and mediated through stable epigenetic mechanisms such as tissue- and gene-specific DNA methylation. Pharmacological and psychological treatments act on and against the background of genetic disposition, with epigenetic annotation resulting from previous experiences. Research in animal models suggests the possibility that epigenetic interventions may modify the impact of environmental stressors on mental health. Gaps in evidence are identified that need to be bridged before knowledge about cause can inform cure in personalized psychiatry. PMID:21631158

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

    PubMed

    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. PMID:24860087

  8. Heavy metals, organic solvents, and multiple sclerosis: An exploratory look at gene-environment interactions.

    PubMed

    Napier, Melanie D; Poole, Charles; Satten, Glen A; Ashley-Koch, Allison; Marrie, Ruth Ann; Williamson, Dhelia M

    2016-01-01

    Exposure to heavy metals and organic solvents are potential etiologic factors for multiple sclerosis (MS), but their interaction with MS-associated genes is under-studied. The authors explored the relationship between environmental exposure to lead, mercury, and solvents and 58 single-nucleotide polymorphisms (SNPs) in MS-associated genes. Data from a population-based case-control study of 217 prevalent MS cases and 496 age-, race-, gender-, and geographically matched controls were used to fit conditional logistic regression models of the association between the chemical, gene, and MS, adjusting for education and ancestry. MS cases were more likely than controls to report lead (odds ratio [OR] = 2.03; 95% confidence interval [CI]: 1.07, 3.86) and mercury exposure (OR = 2.06; 95% CI: 1.08, 3.91). Findings of potential gene-environment interactions between SNPs in TNF-α, TNF-β, TCA-β, VDR, MBP, and APOE, and lead, mercury, or solvents should be considered cautiously due to limited sample size. PMID:25137520

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

    PubMed Central

    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 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. PMID:24860087

  10. [Gene-environment-interaction of ODD and Conduct Disorder Versus "Anethic Psychopathy"].

    PubMed

    Schepker, Renate; Schmeck, Klaus; Kölch, Michael; Schepker, Klaus

    2015-01-01

    Gene-environment-interaction of ODD and Conduct Disorder Versus »Anethic Psychopathy«. In 1934, Kramer and von der Leyen demonstrated in a sophisticated longitudinal study with eleven conduct disordered and neglected children labelled as »anethic psychopaths« that »anethic traits« subsided in a favourable educational setting. Sound prognoses, due to the diversity of environmental factors, were found to be impossible. On the contrary they stated that negative labelling led to an affirmation of a negative prognosis. In theory, they supposed a genetic predisposition resulting in a heightened sensitivity to the environment. This early theory of epigenetics radically contradicted the Nazi dogma of hereditability and ostracism and the selection procedures in mainstream psychiatry at that time. The debate ended with von der Leyen's suicide and the prohibition of medical work and publication towards Kramer. Even after the end of the Nazi policy of »eradication of the socially debased«, this early theory was not taken on again, nor dignified. PMID:25968413

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

    PubMed Central

    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. PMID:26230319

  12. Gene environment interaction studies in depression and suicidal behavior: An update.

    PubMed

    Mandelli, Laura; Serretti, Alessandro

    2013-12-01

    Increasing evidence supports the involvement of both heritable and environmental risk factors in major depression (MD) and suicidal behavior (SB). Studies investigating gene-environment interaction (G × E) may be useful for elucidating the role of biological mechanisms in the risk for mental disorders. In the present paper, we review the literature regarding the interaction between genes modulating brain functions and stressful life events in the etiology of MD and SB and discuss their potential added benefit compared to genetic studies only. Within the context of G × E investigation, thus far, only a few reliable results have been obtained, although some genes have consistently shown interactive effects with environmental risk in MD and, to a lesser extent, in SB. Further investigation is required to disentangle the direct and mediated effects that are common or specific to MD and SB. Since traditional G × E studies overall suffer from important methodological limitations, further effort is required to develop novel methodological strategies with an interdisciplinary approach. PMID:23886513

  13. Passive solar design handbook. Volume 3: Passive solar design analysis

    NASA Astrophysics Data System (ADS)

    Jones, R. W.; Bascomb, J. D.; Kosiewicz, C. E.; Lazarus, G. S.; McFarland, R. D.; Wray, W. O.

    1982-07-01

    Simple analytical methods concerning the design of passive solar heating systems are presented with an emphasis on the average annual heating energy consumption. Key terminology and methods are reviewed. The solar load ratio (SLR) is defined, and its relationship to analysis methods is reviewed. The annual calculation, or Load Collector Ratio (LCR) method, is outlined. Sensitivity data are discussed. Information is presented on balancing conservation and passive solar strategies in building design. Detailed analysis data are presented for direct gain and sunspace systems, and details of the systems are described. Key design parameters are discussed in terms of their impact on annual heating performance of the building. These are the sensitivity data. The SLR correlations for the respective system types are described. The monthly calculation, or SLR method, based on the SLR correlations, is reviewed. Performance data are given for 9 direct gain systems and 15 water wall and 42 Trombe wall systems.

  14. Fundamental studies on passivity and passivity breakdown

    SciTech Connect

    Macdonald, D.D.; Urquidi-Macdonald, M.

    1993-06-01

    Using photoelectrochemical impedance and admittance spectroscopies, a fundamental and quantitative understanding of the mechanisms for the growth and breakdown of passive films on metal and alloy surfaces in contact with aqueous environments is being developed. A point defect model has been extended to explain the breakdown of passive films, leading to pitting and crack growth and thus development of damage due to localized corrosion.

  15. Tropospheric Passive Remote Sensing

    NASA Technical Reports Server (NTRS)

    Keafer, L. S., Jr. (Editor)

    1982-01-01

    The long term role of airborne/spaceborne passive remote sensing systems for tropospheric air quality research and the identification of technology advances required to improve the performance of passive remote sensing systems were discussed.

  16. Passive storage technologies

    NASA Astrophysics Data System (ADS)

    Kittel, P.

    1984-04-01

    Advances in storage technology and how passive techniques could be applied to the storage of propellants at the space station are described. The devices considered are passive orbital disconnect struts, cooled shield optimization, liftweight shields and catalytic converters.

  17. Passive storage technologies

    NASA Technical Reports Server (NTRS)

    Kittel, P.

    1984-01-01

    Advances in storage technology and how passive techniques could be applied to the storage of propellants at the space station are described. The devices considered are passive orbital disconnect struts, cooled shield optimization, liftweight shields and catalytic converters.

  18. Interlanguage Passive Construction

    ERIC Educational Resources Information Center

    Simargool, Nirada

    2008-01-01

    Because the appearance of the passive construction varies cross linguistically, differences exist in the interlanguage (IL) passives attempted by learners of English. One such difference is the widely studied IL pseudo passive, as in "*new cars must keep inside" produced by Chinese speakers. The belief that this is a reflection of L1 language…

  19. A Nonlinear Model for Gene-Based Gene-Environment Interaction.

    PubMed

    Sa, Jian; Liu, Xu; He, Tao; Liu, Guifen; Cui, Yuehua

    2016-01-01

    A vast amount of literature has confirmed the role of gene-environment (G×E) interaction in the etiology of complex human diseases. Traditional methods are predominantly focused on the analysis of interaction between a single nucleotide polymorphism (SNP) and an environmental variable. Given that genes are the functional units, it is crucial to understand how gene effects (rather than single SNP effects) are influenced by an environmental variable to affect disease risk. Motivated by the increasing awareness of the power of gene-based association analysis over single variant based approach, in this work, we proposed a sparse principle component regression (sPCR) model to understand the gene-based G×E interaction effect on complex disease. We first extracted the sparse principal components for SNPs in a gene, then the effect of each principal component was modeled by a varying-coefficient (VC) model. The model can jointly model variants in a gene in which their effects are nonlinearly influenced by an environmental variable. In addition, the varying-coefficient sPCR (VC-sPCR) model has nice interpretation property since the sparsity on the principal component loadings can tell the relative importance of the corresponding SNPs in each component. We applied our method to a human birth weight dataset in Thai population. We analyzed 12,005 genes across 22 chromosomes and found one significant interaction effect using the Bonferroni correction method and one suggestive interaction. The model performance was further evaluated through simulation studies. Our model provides a system approach to evaluate gene-based G×E interaction. PMID:27271617

  20. Genome-wide analysis of gestational gene-environment interactions in the developing kidney

    PubMed Central

    Yan, Lei; Yao, Xiao; Bachvarov, Dimcho; Saifudeen, Zubaida

    2014-01-01

    The G protein-coupled bradykinin B2 receptor (Bdkrb2) plays an important role in regulation of blood pressure under conditions of excess salt intake. Our previous work has shown that Bdkrb2 also plays a developmental role since Bdkrb2−/− embryos, but not their wild-type or heterozygous littermates, are prone to renal dysgenesis in response to gestational high salt intake. Although impaired terminal differentiation and apoptosis are consistent findings in the Bdkrb2−/− mutant kidneys, the developmental pathways downstream of gene-environment interactions leading to the renal phenotype remain unknown. Here, we performed genome-wide transcriptional profiling on embryonic kidneys from salt-stressed Bdkrb2+/+ and Bdkrb2−/− embryos. The results reveal significant alterations in key pathways regulating Wnt signaling, apoptosis, embryonic development, and cell-matrix interactions. In silico analysis reveal that nearly 12% of differentially regulated genes harbor one or more Pax2 DNA-binding sites in their promoter region. Further analysis shows that metanephric kidneys of salt-stressed Bdkrb2−/− have a significant downregulation of Pax2 gene expression. This was corroborated in Bdkrb2−/−;Pax2GFP+/tg mice, demonstrating that Pax2 transcriptional activity is significantly repressed by gestational salt-Bdkrb2 interactions. We conclude that gestational gene (Bdkrb2) and environment (salt) interactions cooperate to impact gene expression programs in the developing kidney. Suppression of Pax2 likely contributes to the defects in epithelial survival, growth, and differentiation in salt-stressed BdkrB2−/− mice. PMID:25005792

  1. A Nonlinear Model for Gene-Based Gene-Environment Interaction

    PubMed Central

    Sa, Jian; Liu, Xu; He, Tao; Liu, Guifen; Cui, Yuehua

    2016-01-01

    A vast amount of literature has confirmed the role of gene-environment (G×E) interaction in the etiology of complex human diseases. Traditional methods are predominantly focused on the analysis of interaction between a single nucleotide polymorphism (SNP) and an environmental variable. Given that genes are the functional units, it is crucial to understand how gene effects (rather than single SNP effects) are influenced by an environmental variable to affect disease risk. Motivated by the increasing awareness of the power of gene-based association analysis over single variant based approach, in this work, we proposed a sparse principle component regression (sPCR) model to understand the gene-based G×E interaction effect on complex disease. We first extracted the sparse principal components for SNPs in a gene, then the effect of each principal component was modeled by a varying-coefficient (VC) model. The model can jointly model variants in a gene in which their effects are nonlinearly influenced by an environmental variable. In addition, the varying-coefficient sPCR (VC-sPCR) model has nice interpretation property since the sparsity on the principal component loadings can tell the relative importance of the corresponding SNPs in each component. We applied our method to a human birth weight dataset in Thai population. We analyzed 12,005 genes across 22 chromosomes and found one significant interaction effect using the Bonferroni correction method and one suggestive interaction. The model performance was further evaluated through simulation studies. Our model provides a system approach to evaluate gene-based G×E interaction. PMID:27271617

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

    PubMed Central

    Matsui, Takeshi; Ehrenreich, Ian M.

    2016-01-01

    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. PMID:27437938

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

    PubMed

    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. PMID:12658122

  4. Identification of New Genetic Susceptibility Loci for Breast Cancer Through Consideration of Gene-Environment Interactions

    PubMed Central

    Schoeps, Anja; Rudolph, Anja; Seibold, Petra; Dunning, Alison M.; Milne, Roger L.; Bojesen, Stig E.; Swerdlow, Anthony; Andrulis, Irene; Brenner, Hermann; Behrens, Sabine; Orr, Nicholas; Jones, Michael; Ashworth, Alan; Li, Jingmei; Cramp, Helen; Connley, Dan; Czene, Kamila; Darabi, Hatef; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Knight, Julia; Glendon, Gord; Mulligan, Anna M.; Dumont, Martine; Severi, Gianluca; Baglietto, Laura; Olson, Janet; Vachon, Celine; Purrington, Kristen; Moisse, Matthieu; Neven, Patrick; Wildiers, Hans; Spurdle, Amanda; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Hamann, Ute; Ko, Yon-Dschun; Dieffenbach, Aida K.; Arndt, Volker; Stegmaier, Christa; Malats, Núria; Arias Perez, JoséI.; Benítez, Javier; Flyger, Henrik; Nordestgaard, Børge G.; Truong, Théresè; Cordina-Duverger, Emilie; Menegaux, Florence; Silva, Isabel dos Santos; Fletcher, Olivia; Johnson, Nichola; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Braaf, Linde; Atsma, Femke; van den Broek, Alexandra J.; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Cox, Angela; Simard, Jacques; Giles, Graham G.; Lambrechts, Diether; Mannermaa, Arto; Brauch, Hiltrud; Guénel, Pascal; Peto, Julian; Fasching, Peter A.; Hopper, John; Flesch-Janys, Dieter; Couch, Fergus; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Schmidt, Marjanka K.; Hall, Per; Easton, Douglas F.; Chang-Claude, Jenny

    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 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10−07), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m2 (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m2 or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10−05). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci. PMID:24248812

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

    PubMed Central

    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

  6. The First Pilot Genome-Wide Gene-Environment Study of Depression in the Japanese Population.

    PubMed

    Otowa, Takeshi; Kawamura, Yoshiya; Tsutsumi, Akizumi; Kawakami, Norito; Kan, Chiemi; Shimada, Takafumi; Umekage, Tadashi; Kasai, Kiyoto; Tokunaga, Katsushi; Sasaki, Tsukasa

    2016-01-01

    Stressful events have been identified as a risk factor for depression. Although gene-environment (G × E) interaction in a limited number of candidate genes has been explored, no genome-wide search has been reported. The aim of the present study is to identify genes that influence the association of stressful events with depression. Therefore, we performed a genome-wide G × E interaction analysis in the Japanese population. A genome-wide screen with 320 subjects was performed using the Affymetrix Genome-Wide Human Array 6.0. Stressful life events were assessed using the Social Readjustment Rating Scale (SRRS) and depression symptoms were assessed with self-rating questionnaires using the Center for Epidemiologic Studies Depression (CES-D) scale. The p values for interactions between single nucleotide polymorphisms (SNPs) and stressful events were calculated using the linear regression model adjusted for sex and age. After quality control of genotype data, a total of 534,848 SNPs on autosomal chromosomes were further analyzed. Although none surpassed the level of the genome-wide significance, a marginal significant association of interaction between SRRS and rs10510057 with depression were found (p = 4.5 × 10-8). The SNP is located on 10q26 near Regulators of G-protein signaling 10 (RGS10), which encodes a regulatory molecule involved in stress response. When we investigated a similar G × E interaction between depression (K6 scale) and work-related stress in an independent sample (n = 439), a significant G × E effect on depression was observed (p = 0.015). Our findings suggest that rs10510057, interacting with stressors, may be involved in depression risk. Incorporating G × E interaction into GWAS can contribute to find susceptibility locus that are potentially missed by conventional GWAS. PMID:27529621

  7. Detecting Gene-Environment Interactions for a Quantitative Trait in a Genome-Wide Association Study.

    PubMed

    Zhang, Pingye; Lewinger, Juan Pablo; Conti, David; Morrison, John L; Gauderman, W James

    2016-07-01

    A genome-wide association study (GWAS) typically is focused on detecting marginal genetic effects. However, many complex traits are likely to be the result of the interplay of genes and environmental factors. These SNPs may have a weak marginal effect and thus unlikely to be detected from a scan of marginal effects, but may be detectable in a gene-environment (G × E) interaction analysis. However, a genome-wide interaction scan (GWIS) using a standard test of G × E interaction is known to have low power, particularly when one corrects for testing multiple SNPs. Two 2-step methods for GWIS have been previously proposed, aimed at improving efficiency by prioritizing SNPs most likely to be involved in a G × E interaction using a screening step. For a quantitative trait, these include a method that screens on marginal effects [Kooperberg and Leblanc, 2008] and a method that screens on variance heterogeneity by genotype [Paré et al., 2010] In this paper, we show that the Paré et al. approach has an inflated false-positive rate in the presence of an environmental marginal effect, and we propose an alternative that remains valid. We also propose a novel 2-step approach that combines the two screening approaches, and provide simulations demonstrating that the new method can outperform other GWIS approaches. Application of this method to a G × Hispanic-ethnicity scan for childhood lung function reveals a SNP near the MARCO locus that was not identified by previous marginal-effect scans. PMID:27230133

  8. The developmental origins of externalizing behavioral problems: parental disengagement and the role of gene-environment interplay.

    PubMed

    Boutwell, Brian B; Beaver, Kevin M; Barnes, James C; Vaske, Jamie

    2012-05-30

    A line of research has revealed that the influence of genes on behavioral development is closely tied to environmental experiences. Known as gene-environment interaction, research in this area is beginning to reveal that variation in parenting behaviors may moderate genetic influences on antisocial behaviors in children. Despite growing interest in gene-environment interaction research, little evidence exists concerning the role of maternal disengagement in the conditioning of genetic influences on childhood behavioral problems. The current study is intended to address this gap in the literature by analyzing a sample of twin pairs drawn from the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B). Analysis of the ECLS-B provided evidence that maternal disengagement moderates genetic influences on the development of externalizing problems. PMID:22421070

  9. Toward a 3D model of human brain development for studying gene/environment interactions

    PubMed Central

    2013-01-01

    This project aims to establish and characterize an in vitro model of the developing human brain for the purpose of testing drugs and chemicals. To accurately assess risk, a model needs to recapitulate the complex interactions between different types of glial cells and neurons in a three-dimensional platform. Moreover, human cells are preferred over cells from rodents to eliminate cross-species differences in sensitivity to chemicals. Previously, we established conditions to culture rat primary cells as three-dimensional aggregates, which will be humanized and evaluated here with induced pluripotent stem cells (iPSCs). The use of iPSCs allows us to address gene/environment interactions as well as the potential of chemicals to interfere with epigenetic mechanisms. Additionally, iPSCs afford us the opportunity to study the effect of chemicals during very early stages of brain development. It is well recognized that assays for testing toxicity in the developing brain must consider differences in sensitivity and susceptibility that arise depending on the time of exposure. This model will reflect critical developmental processes such as proliferation, differentiation, lineage specification, migration, axonal growth, dendritic arborization and synaptogenesis, which will probably display differences in sensitivity to different types of chemicals. Functional endpoints will evaluate the complex cell-to-cell interactions that are affected in neurodevelopment through chemical perturbation, and the efficacy of drug intervention to prevent or reverse phenotypes. The model described is designed to assess developmental neurotoxicity effects on unique processes occurring during human brain development by leveraging human iPSCs from diverse genetic backgrounds, which can be differentiated into different cell types of the central nervous system. Our goal is to demonstrate the feasibility of the personalized model using iPSCs derived from individuals with neurodevelopmental disorders

  10. Characterization of gene-environment interactions for colorectal cancer susceptibility loci

    PubMed Central

    Hutter, Carolyn M.; Chang-Claude, Jenny; Slattery, Martha L.; Pflugeisen, Bethann M.; Lin, Yi; Duggan, David; Nan, Hongmei; Lemire, Mathieu; Rangrej, Jagadish; Figueiredo, Jane C.; Jiao, Shuo; Harrison, Tabitha A.; Liu, Yan; Chen, Lin S.; Stelling, Deanna L.; Warnick, Greg S.; Hoffmeister, Michael; Küry, Sébastien; Fuchs, Charles S.; Giovannucci, Edward; Hazra, Aditi; Kraft, Peter; Hunter, David J.; Gallinger, Steven; Zanke, Brent W.; Brenner, Hermann; Frank, Bernd; Ma, Jing; Ulrich, Cornelia M.; White, Emily; Newcomb, Polly A.; Kooperberg, Charles; LaCroix, Andrea Z.; Prentice, Ross L.; Jackson, Rebecca D.; Schoen, Robert E.; Chanock, Stephen J.; Berndt, Sonja I.; Hayes, Richard B.; Caan, Bette J.; Potter, John D.; Hsu, Li; Bézieau, Stéphane; Chan, Andrew T.; Hudson, Thomas J.; Peters, Ulrike

    2012-01-01

    Genome-wide association studies (GWAS) have identified over a dozen loci associated with colorectal cancer (CRC) risk. Here we examined potential effect-modification between single nucleotide polymorphisms (SNPs) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case-control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23); rs6983267 at 8q24 (MYC); rs10795668 at 10p14 (FLJ3802842); rs3802842 at11q23 (LOC120376); rs4444235 at 14q22.2 (BMP4); rs4779584 at15q13 (GREM1); rs9929218 at16q22.1 (CDH1); rs4939827 at18q21 (SMAD7); rs10411210 at19q13.1 (RHPN2); and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/non-steroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene-environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal p-interaction =1.3×10–4; adjusted p-value 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS appears to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption. PMID:22367214

  11. Correlation of serum IgG concentration in foals and refractometry index of the dam's pre- and post-parturient colostrums: an assessment for failure of passive transfer in foals.

    PubMed

    Korosue, Kenji; Murase, Harutaka; Sato, Fumio; Ishimaru, Mutsuki; Kotoyori, Yasumitsu; Nambo, Yasuo

    2012-11-01

    The object of this study was to evaluate the usefulness of measuring the differences in the values of the serum total protein (DVSTP) concentration of foals and the refractometry index (DVRI) of the milk of dams before and after nursing of the colostrum for assessing failure of passive transfer (FPT) in foals. Serum samples from 31 foals were collected before the first nursing and other 1 to 6 times between 4 and 24 hr after birth. Paired colostrum and milk samples were collected from 14 of their dams at the same time. Serum samples were analyzed for IgG concentration using a single radial immunodiffusion (SRID) test (98 samples) and total protein concentration using a temperature-compensating refractometer (98 samples). Colostrum and milk samples were analyzed for refractometry index (RI) using a Brix refractometer (71 samples). DVSTP concentration and DVRI were significantly correlated with serum IgG concentration. The negative predictive values (NPVs) of DVSTP concentration for detecting serum IgG concentrations<400 mg/dl and<800 mg/dl were 98.2% and 91.3% when the cutoff value is set to 0.4 mg/dl and 0.8 mg/dl, respectively. Furthermore, the NPVs of DVRI for detecting serum IgG concentrations<400 mg/dl and<800 mg/dl were 97.3% and 96.3% when the cutoff value is set to 6% and 10%, respectively. The results suggest that measurement of DVRI is useful in assessing FPT as an initial "stall-side" screening test, because it is easy, inexpensive to perform and allows for rapid interpretation. PMID:22785030

  12. A model of gene-gene and gene-environment interactions and its implications for targeting environmental interventions by genotype

    PubMed Central

    Wallace, Helen M

    2006-01-01

    Background The potential public health benefits of targeting environmental interventions by genotype depend on the environmental and genetic contributions to the variance of common diseases, and the magnitude of any gene-environment interaction. In the absence of prior knowledge of all risk factors, twin, family and environmental data may help to define the potential limits of these benefits in a given population. However, a general methodology to analyze twin data is required because of the potential importance of gene-gene interactions (epistasis), gene-environment interactions, and conditions that break the 'equal environments' assumption for monozygotic and dizygotic twins. Method A new model for gene-gene and gene-environment interactions is developed that abandons the assumptions of the classical twin study, including Fisher's (1918) assumption that genes act as risk factors for common traits in a manner necessarily dominated by an additive polygenic term. Provided there are no confounders, the model can be used to implement a top-down approach to quantifying the potential utility of genetic prediction and prevention, using twin, family and environmental data. The results describe a solution space for each disease or trait, which may or may not include the classical twin study result. Each point in the solution space corresponds to a different model of genotypic risk and gene-environment interaction. Conclusion The results show that the potential for reducing the incidence of common diseases using environmental interventions targeted by genotype may be limited, except in special cases. The model also confirms that the importance of an individual's genotype in determining their risk of complex diseases tends to be exaggerated by the classical twin studies method, owing to the 'equal environments' assumption and the assumption of no gene-environment interaction. In addition, if phenotypes are genetically robust, because of epistasis, a largely environmental

  13. Passive magnetic bearing configurations

    DOEpatents

    Post, Richard F.

    2011-01-25

    A journal bearing provides vertical and radial stability to a rotor of a passive magnetic bearing system when the rotor is not rotating and when it is rotating. In the passive magnetic bearing system, the rotor has a vertical axis of rotation. Without the journal bearing, the rotor is vertically and radially unstable when stationary, and is vertically stable and radially unstable when rotating.

  14. Passive solar construction handbook

    SciTech Connect

    Levy, E.; Evans, D.; Gardstein, C.

    1981-08-01

    Many of the basic elements of passive solar design are reviewed. The unique design constraints presented in passive homes are introduced and many of the salient issues influencing design decisions are described briefly. Passive solar construction is described for each passive system type: direct gain, thermal storage wall, attached sunspace, thermal storage roof, and convective loop. For each system type, important design and construction issues are discussed and case studies illustrating designed and built examples of the system type are presented. Construction details are given and construction and thermal performance information is given for the materials used in collector components, storage components, and control components. Included are glazing materials, framing systems, caulking and sealants, concrete masonry, concrete, brick, shading, reflectors, and insulators. The Load Collector Ratio method for estimating passive system performance is appended, and other analysis methods are briefly summarized. (LEW)

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

    PubMed Central

    Lobach, Iryna; Fan, Ruzong

    2015-01-01

    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 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. PMID:26180529

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

    PubMed Central

    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

  17. High-throughput phenotypic profiling of gene-environment interactions by quantitative growth curve analysis in Saccharomyces cerevisiae.

    PubMed

    Weiss, Andrew; Delproposto, James; Giroux, Craig N

    2004-04-01

    Cell-based assays are widely used in high-throughput screening to determine the effects of toxicants and drugs on their biological targets. To enable a functional genomics modeling of gene-environment interactions, quantitative assays are required both for gene expression and for the phenotypic responses to environmental challenge. To address this need, we describe an automated high-throughput methodology that provides phenotypic profiling of the cellular responses to environmental stress in Saccharomyces cerevisiae. Standardized assay conditions enable the use of a single metric value to quantify yeast microculture growth curves. This assay format allows precise control of both genetic and environmental determinants of the cellular responses to oxidative stress, a common mechanism of environmental insult. These yeast-cell-based assays are validated with hydrogen peroxide, a simple direct-acting oxidant. Phenotypic profiling of the oxidative stress response of a yap1 mutant strain demonstrates the mechanistic analysis of genetic susceptibility to oxidative stress. As a proof of concept for analysis of more complex gene-environment interactions, we describe a combinatorial assay design for phenotypic profiling of the cellular responses to tert-butyl hydroperoxide, a complex oxidant that is actively metabolized by its target cells. Thus, the yeast microculture assay format supports comprehensive applications in toxicogenomics. PMID:15033507

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

    PubMed

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

    2015-08-01

    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

  19. Optimum mix of passive and active control of space structures

    NASA Technical Reports Server (NTRS)

    Rogers, Lynn; Richards, Ken

    1987-01-01

    The objective of this research was to test vibration suppression (settling time and jitter) of a large space structure (LSS) characterized by low frequency high global vibration modes. Five percent passive damping in a large truss was analyzed, tested and correlated. A representative system article re-target analysis shows that modest levels of passive damping dramatically reduce the control energy required. LSS must incorporate passive damping from the outset. The LSS system performance will not be met by either active or passive damping alone.

  20. Immunizations: Active vs. Passive

    MedlinePlus

    ... they’ve been exposed. For example, the passive rabies immunization (rabies immune globulin) is commonly used after a certain ... of your pediatrician. There may be variations in treatment that your pediatrician may recommend based on individual ...

  1. Hood River Passive House

    SciTech Connect

    Hales, D.

    2013-03-01

    The Hood River Passive Project was developed by Root Design Build of Hood River Oregon using the Passive House Planning Package (PHPP) to meet all of the requirements for certification under the European Passive House standards. The Passive House design approach has been gaining momentum among residential designers for custom homes and BEopt modeling indicates that these designs may actually exceed the goal of the U.S. Department of Energy's (DOE) Building America program to reduce home energy use by 30%-50% (compared to 2009 energy codes for new homes). This report documents the short term test results of the Shift House and compares the results of PHPP and BEopt modeling of the project.

  2. Use of the Twin Design to Examine Evocative Gene-Environment Effects within a Conversational Context

    PubMed Central

    DeThorne, Laura Segebart; Hart, Sara Ann

    2010-01-01

    The purpose of this study was to highlight the role of twin designs in understanding children’s conversational interactions. Specifically, we (a) attempted to replicate the findings of genetic effects on children’s conversational language use reported in DeThorne et al. (2008), and (b) examined whether the language used by examiners in their conversation with twins reflected differences in the children’s genetic similarity. Behavioral genetic analyses included intraclass correlations and model fitting procedures applied to 514 same-sex twins (202 MZ, 294 DZ, 10 unknown zygosity) from the Western Reserve Reading Project (Petrill, Deater-Deckard, Thompson, DeThorne, & Schatschneider, 2006). Analyses focused on child and examiner measures of talkativeness, average utterance length, vocabulary diversity, and grammatical complexity from a fifteen-minute conversational exchange. Substantial genetic effects on children’s conversational language measures replicated results from DeThorne et al. (2008) using an expanded sample. However, no familiality was reflected in the examiner language measures. Modest phenotypic correlations between child and examiner language measures suggested that differences in examiner language use may elicit differences in child language use, but evidence of evocative rGE in which genetic differences across children evoke differences in examiner language use, was not found. The discussion focuses on a comparison of findings to previous studies and implications for future research. PMID:22102850

  3. Gene Environment Risk Assessment and Colorectal Cancer Screening in an Average Risk Population: A Randomized, Controlled Trial

    PubMed Central

    Weinberg, David S.; Myers, Ronald E.; Keenan, Eileen; Ruth, Karen; Sifri, Randa; Ziring, Barry; Ross, Eric; Manne, Sharon L.

    2015-01-01

    Background New methods are needed to improve health behaviors such as adherence to colorectal cancer (CRC) screening. There is increasing availability of personalized genetic information to inform medical decisions. It is not known if such information motivates behavioral change. Objective To determine, in average risk persons, if individualized gene-environment risk assessment about CRC susceptibility improves adherence to screening. Design Two-arm, randomized, controlled trial Setting Four medical school affiliated primary care practices Patients 783 patients at average risk for CRC, but not adherent with screening at study entry Intervention Patients were randomized to usual care or to receipt of Gene Environmental Risk Assessment (GERA), which assessed Methylene Tetrahydrofolate Reductase (MTHFR) polymorphisms and serum folate level. Based on pre-specified polymorphism/folate level combinations, GERA participants were told they were at either “elevated” or at “average” risk for CRC. Measurements The primary outcome was receipt of CRC screening within 6 months of study entry. Results CRC screening rates were not statistically significantly different between usual care (35.7%) and GERA (33.1%) arms overall. After adjustment for baseline participant factors, the odds ratio (OR) for screening completion for GERA vs usual care was 0.88 (95% CI 0.64 - 1.22). Within the GERA arm, there was no significant difference in screening rates between GERA average risk (38.1%) and GERA elevated risk (26.9%) groups. Odds ratios for elevated vs. average risk remained non-significant after adjustment for covariates (OR=0.75, 95% CI 0.39 - 1.42). Limitations Only one personalized, gene-environment interaction and only one health behavior, colorectal cancer screening, were assessed. Conclusion In average risk persons, there was no positive association between CRC screening uptake and feedback of a single personalized gene-environment risk assessment (GERA). Additional

  4. Passive fluorescence measurements during SIFLEX

    NASA Astrophysics Data System (ADS)

    Moya, I.; Ounis, A.; Louis, J.; Evain, S.; Ducruet, J.-M.

    The goal of the participation of the LURE team to the SIFLEX campaign was %to provide clear evidence of quantitative absolute measurements of natural fluorescence andfluorescence flux evaluation by passive methods in the Fraunhofer lines. More specifically, to quantify the fluorescence flux in A and B absorption bands of atmospheric oxygen. The measurements have been focus on: Testing specific passive fluorescence instrumentation recently developed at LURE for assessing the sun induced fluorescence radiance from vegetation. Investigating diurnal and seasonal change of fluorescence and its behaviour with respect to plant condition, pigment content, global radiation amount and its correlation against accumulated biomass during growing period, Cross-correlate the fluorescence signal with hyperspectral reflectance and thermal IR radiance. A special attention has been paid to diurnal cycle and seasonal variations. Comparing fluorescence fluxes with CO2 fluxes measured by the already existing gas exchange equipment of the site. Instrumentation PMFD (Passive Multiwavelength Fluorescence Detector) was the main instrument used to asses fluorescence fluxes. The instrument was based on the Fraunhofer line principle, applied in the atmospheric oxygen A and B bands (760nm and 687nm, respectively). The output parameters were two stationary fluorescence flux at 687nm and 760nm and the NDVI (NDVI = (R760-R687) / (R760+R687)) index. Two additional channels of the instrument are devoted to measure reflectance variations at 531nm and 570 nm in order to calculate the PRI (PRI = (R531-R570) / (R531+R570)) index. This instrument was installed on the main tower, 10 m above the crown of the trees and maintained in the same viewing direction during the campaign (towards the north direction). The zenith angle was set to about 50-65 degrees. The footprint of the instrument contained the crowns of several trees. BD was a second passive detector operating solely in the atmospheric oxygen A

  5. Satiety and the Self-Regulation of Food Take in Children: a Potential Role for Gene-Environment Interplay.

    PubMed

    Hughes, Sheryl O; Frazier-Wood, Alexis C

    2016-03-01

    Child eating self-regulation refers to behaviors that enable children to start and stop eating in a manner consistent with maintaining energy balance. Perturbations in these behaviors, manifesting as poorer child eating self-regulation, are associated with higher child weight status. Initial research into child eating self-regulation focused on the role of parent feeding styles and behaviors. However, we argue that child eating self-regulation is better understood as arising from a complex interplay between the child and their feeding environment, and highlight newer research into the heritable child characteristics, such as cognitive ability, that play an important role in this dynamic. Therefore, child eating self-regulation arises from gene-environment interactions. Identifying the genes and environmental influences contributing to these will help us tailor our parental feeding advice to the unique nature of the child. In this way, we will devise more effective advice for preventing childhood obesity. PMID:26847550

  6. The emergence of biobanks: practical design considerations for large population-based studies of gene-environment interactions.

    PubMed

    Davis, Robert L; Khoury, Muin J

    2007-01-01

    The completion of the human genome project has spurred new thinking about launching large-scale cohort studies; as proposed, these studies will differ from past large-scale cohort studies and will focus primarily on how genetic variation interacts with environmental exposures to affect the risk for common human diseases. There is no single 'best design' for large-scale studies of gene-environment interactions. Some studies are best performed in cohort studies where unbiased information can be collected on individuals years before disease onset. Other studies may be most efficiently done with a case-control design using currently available automated data. Population-based biobanks with nested case-control or case-cohort studies offer distinct advantages to some of the resource-intensive large-scale cohort studies under consideration, and may be more acceptable to many of the countries around the world currently considering such projects. PMID:17575463

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

    PubMed

    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< 0.05) increase in frequency of GSTM1^{-}/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 (p< 0.05) high in UBC cases as compared to controls. Multiple regression analysis revealed a significant interaction between β-HCH and GSTM1^{-} genotype (p< 0.05) as well as in β-HCH and GSTT1^{-} genotype (p< 0.05) respectively. These findings indicate that "gene-environment 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. PMID:24240585

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

    PubMed

    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. PMID:26545598

  9. Effects of passive smoking on theophylline clearance.

    PubMed

    Matsunga, S K; Plezia, P M; Karol, M D; Katz, M D; Camilli, A E; Benowitz, N L

    1989-10-01

    Theophylline disposition was examined in seven passive smokers, defined as nonsmokers with long-term exposure to cigarette smoke, and seven age-matched nonsmokers with minimal smoke exposure. Subjects were given an intravenous infusion of aminophylline (6 mg/kg) and blood samples were drawn before and during the 48-hour postinfusion period. Clearance for passive smokers was 6.01 x 10(-2) L/hr.kg and for nonsmokers, clearance was 4.09 x 10(-2) L/hr.kg (p less than 0.025). Terminal elimination half-life for passive smokers was 6.93 hours versus 8.69 hours for nonsmokers (p less than 0.05). The mean residence time for passive smokers was 9.89 hours. For nonsmokers, the mean residence time was 13.11 hours (p less than 0.05). These measurements were statistically different, whereas there was no difference in volume of distribution between the groups, suggesting that passive smokers metabolize theophylline more rapidly than nonsmokers. Plasma and urine cotinine and nicotine concentrations were measured in all subjects. There was a significant difference between the subject groups in plasma (p less than 0.004) and urine (p less than 0.002) cotinine concentrations. Theophylline clearance correlated with both plasma (r = 0.73, p less than 0.01) and urine (r = 0.79, p less than 0.01) cotinine concentrations. Additional studies should be conducted to further define the pharmacokinetic characteristics of passive smokers and to assess the effects of passive smoking on drugs metabolized by the mixed function oxidase system. PMID:2791443

  10. Wireless passive radiation sensor

    SciTech Connect

    Pfeifer, Kent B; Rumpf, Arthur N; Yelton, William G; Limmer, Steven J

    2013-12-03

    A novel measurement technique is employed using surface acoustic wave (SAW) devices, passive RF, and radiation-sensitive films to provide a wireless passive radiation sensor that requires no batteries, outside wiring, or regular maintenance. The sensor is small (<1 cm.sup.2), physically robust, and will operate unattended for decades. In addition, the sensor can be insensitive to measurement position and read distance due to a novel self-referencing technique eliminating the need to measure absolute responses that are dependent on RF transmitter location and power.

  11. Method of passivating semiconductor surfaces

    DOEpatents

    Wanlass, M.W.

    1990-06-19

    A method is described for passivating Group III-V or II-VI semiconductor compound surfaces. The method includes selecting a passivating material having a lattice constant substantially mismatched to the lattice constant of the semiconductor compound. The passivating material is then grown as an ultrathin layer of passivating material on the surface of the Group III-V or II-VI semiconductor compound. The passivating material is grown to a thickness sufficient to maintain a coherent interface between the ultrathin passivating material and the semiconductor compound. In addition, a device formed from such method is also disclosed.

  12. Method of passivating semiconductor surfaces

    DOEpatents

    Wanlass, Mark W.

    1990-01-01

    A method of passivating Group III-V or II-VI semiconductor compound surfaces. The method includes selecting a passivating material having a lattice constant substantially mismatched to the lattice constant of the semiconductor compound. The passivating material is then grown as an ultrathin layer of passivating material on the surface of the Group III-V or II-VI semiconductor compound. The passivating material is grown to a thickness sufficient to maintain a coherent interface between the ultrathin passivating material and the semiconductor compound. In addition, a device formed from such method is also disclosed.

  13. Passive adaptive imaging through turbulence

    NASA Astrophysics Data System (ADS)

    Tofsted, David

    2016-05-01

    Standard methods for improved imaging system performance under degrading optical turbulence conditions typically involve active adaptive techniques or post-capture image processing. Here, passive adaptive methods are considered where active sources are disallowed, a priori. Theoretical analyses of short-exposure turbulence impacts indicate that varying aperture sizes experience different degrees of turbulence impacts. Smaller apertures often outperform larger aperture systems as turbulence strength increases. This suggests a controllable aperture system is advantageous. In addition, sub-aperture sampling of a set of training images permits the system to sense tilts in different sub-aperture regions through image acquisition and image cross-correlation calculations. A four sub-aperture pattern supports corrections involving five realizable operating modes (beyond tip and tilt) for removing aberrations over an annular pattern. Progress to date will be discussed regarding development and field trials of a prototype system.

  14. Passive Magnetic Bearing

    NASA Technical Reports Server (NTRS)

    Studer, P. A.

    1983-01-01

    Magnetic bearing for limited rotation devices requires no feedback control system to sense and correct shaft position. Passive Magnetic Torsion Bearing requires no power supply and has no rubbing parts. Torsion wire restrains against axial instability. Magnetic flux geometry chosen to assure lateral stability with radial restoring force that maintains alignment.

  15. Hood River Passive House

    SciTech Connect

    Hales, D.

    2014-01-01

    The Hood River Passive Project was developed by Root Design Build of Hood River Oregon using the Passive House Planning Package (PHPP) to meet all of the requirements for certification under the European Passive House standards. The Passive House design approach has been gaining momentum among residential designers for custom homes and BEopt modeling indicates that these designs may actually exceed the goal of the U.S. Department of Energy's (DOE) Building America program to reduce home energy use by 30%-50% (compared to 2009 energy codes for new homes). This report documents the short term test results of the Shift House and compares the results of PHPP and BEopt modeling of the project. The design includes high R-Value assemblies, extremely tight construction, high performance doors and windows, solar thermal DHW, heat recovery ventilation, moveable external shutters and a high performance ductless mini-split heat pump. Cost analysis indicates that many of the measures implemented in this project did not meet the BA standard for cost neutrality. The ductless mini-split heat pump, lighting and advanced air leakage control were the most cost effective measures. The future challenge will be to value engineer the performance levels indicated here in modeling using production based practices at a significantly lower cost.

  16. Hood River Passive House

    SciTech Connect

    Hales, David

    2014-01-01

    The Hood River Passive Project was developed by Root Design Build of Hood River Oregon using the Passive House Planning Package (PHPP) to meet all of the requirements for certification under the European Passive House standards. The Passive House design approach has been gaining momentum among residential designers for custom homes and BEopt modeling indicates that these designs may actually exceed the goal of the U.S. Department of Energy's (DOE) Building America program to "reduce home energy use by 30%-50% (compared to 2009 energy codes for new homes). This report documents the short term test results of the Shift House and compares the results of PHPP and BEopt modeling of the project. The design includes high R-Value assemblies, extremely tight construction, high performance doors and windows, solar thermal DHW, heat recovery ventilation, moveable external shutters and a high performance ductless mini-split heat pump. Cost analysis indicates that many of the measures implemented in this project did not meet the BA standard for cost neutrality. The ductless mini-split heat pump, lighting and advanced air leakage control were the most cost effective measures. The future challenge will be to value engineer the performance levels indicated here in modeling using production based practices at a significantly lower cost.

  17. Validation of PhenX measures in the personalized medicine research project for use in gene/environment studies

    PubMed Central

    2014-01-01

    symptoms associated with a major depressive episode. Conclusions The approach employed resulted in a high response rate and valuable data for future gene/environment analyses. These results and high response rate highlight the utility of the PhenX Toolkit to collect valid phenotypic data that can be shared across groups to facilitate gene/environment studies. PMID:24423110

  18. BAYESIAN METHODS FOR GENETIC ASSOCIATION ANALYSIS WITH HETEROGENEOUS SUBGROUPS: FROM META-ANALYSES TO GENE-ENVIRONMENT INTERACTIONS

    PubMed Central

    Wen, Xiaoquan; Stephens, Matthew

    2015-01-01

    Genetic association analyses often involve data from multiple potentially-heterogeneous subgroups. The expected amount of heterogeneity can vary from modest (e.g. a typical meta-analysis), to large (e.g. a strong gene-environment interaction). However, existing statistical tools are limited in their ability to address such heterogeneity. Indeed, most genetic association meta-analyses use a “fixed effects” analysis, which assumes no heterogeneity. Here we develop and apply Bayesian association methods to address this problem. These methods are easy to apply (in the simplest case, requiring only a point estimate for the genetic effect, and its standard error, from each subgroup), and effectively include standard frequentist meta-analysis methods, including the usual “fixed effects” analysis, as special cases. We apply these tools to two large genetic association studies: one a meta-analysis of genome-wide association studies from the Global Lipids consortium, and the second a cross-population analysis for expression quantitative trait loci (eQTLs). In the Global Lipids data we find, perhaps surprisingly, that effects are generally quite homogeneous across studies. In the eQTL study we find that eQTLs are generally shared among different continental groups, and discuss consequences of this for study design. PMID:26413181

  19. Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines

    PubMed Central

    Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif

    2015-01-01

    Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. 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, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM. PMID:25987962

  20. Refining the Candidate Environment: Interpersonal Stress, the Serotonin Transporter Polymorphism, and Gene-Environment Interactions in Major Depression

    PubMed Central

    Vrshek-Schallhorn, Suzanne; Mineka, Susan; Zinbarg, Richard E.; Craske, Michelle G.; Griffith, James W.; Sutton, Jonathan; Redei, Eva E.; Wolitzky-Taylor, Kate; Hammen, Constance; Adam, Emma K.

    2014-01-01

    Meta-analytic evidence supports a gene-environment (G×E) interaction between life stress and the serotonin transporter polymorphism (5-HTTLPR) on depression, but few studies have examined factors that influence detection of this effect, despite years of inconsistent results. We propose that the “candidate environment” (akin to a candidate gene) is key. Theory and evidence implicate major stressful life events (SLEs)—particularly major interpersonal SLEs—as well as chronic family stress. Participants (N = 400) from the Youth Emotion Project (which began with 627 high school juniors oversampled for high neuroticism) completed up to five annual diagnostic and life stress interviews and provided DNA samples. A significant G×E effect for major SLEs and S-carrier genotype was accounted for significantly by major interpersonal SLEs but not significantly by major non-interpersonal SLEs. S-carrier genotype and chronic family stress also significantly interacted. Identifying such candidate environments may facilitate future G×E research in depression and psychopathology more broadly.

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

    PubMed

    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. PMID:19175757

  2. Gene-environment interactions in determining differences in genetic susceptibility to cancer in subsites of the head and neck.

    PubMed

    Maurya, Shailendra S; Katiyar, Tridiv; Dhawan, Ankur; Singh, Sudhir; Jain, Swatantra K; Pant, Mohan C; Parmar, Devendra

    2015-04-01

    Genetic differences in susceptibility to cancer in subsites of the head and neck were investigated in a case-control study involving 750 cases of cancers of the oral cavity, larynx, or pharynx, and an equal number of healthy controls. The prevalence of variant genotypes of cytochrome P450 (CYP) 1A1, 1B1, 2E1, or glutathione-S-transferase M1 (null) in cases suggests that polymorphisms in drug metabolizing enzymes (DMEs) modify cancer risk within subsites of the head and neck. Tobacco or alcohol use was found to increase the risk in cases of laryngeal, pharyngeal, or oral cavity cancers. Interaction between genetic variation in DMEs and tobacco smoke (or smoking) exposures conferred significant risk for laryngeal cancer. Likewise, strong associations of the polymorphic genotypes of DMEs with cases of pharyngeal and oral cavity cancer who were tobacco chewers or alcohol users demonstrate that gene-environment interactions may explain differences in genetic susceptibility for cancers of the oral cavity, larynx, and pharynx. PMID:25399842

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

    PubMed

    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. PMID:26538244

  4. Molecular pathways: gene-environment interactions regulating dietary fiber induction of proliferation and apoptosis via butyrate for cancer prevention.

    PubMed

    Bultman, Scott J

    2014-02-15

    Gene-environment interactions are so numerous and biologically complicated that it can be challenging to understand their role in cancer. However, dietary fiber and colorectal cancer prevention may represent a tractable model system. Fiber is fermented by colonic bacteria into short-chain fatty acids such as butyrate. One molecular pathway that has emerged involves butyrate having differential effects depending on its concentration and the metabolic state of the cell. Low-moderate concentrations, which are present near the base of colonic crypts, are readily metabolized in the mitochondria to stimulate cell proliferation via energetics. Higher concentrations, which are present near the lumen, exceed the metabolic capacity of the colonocyte. Unmetabolized butyrate enters the nucleus and functions as a histone deacetylase (HDAC) inhibitor that epigenetically regulates gene expression to inhibit cell proliferation and induce apoptosis as the colonocytes exfoliate into the lumen. Butyrate may therefore play a role in normal homeostasis by promoting turnover of the colonic epithelium. Because cancerous colonocytes undergo the Warburg effect, their preferred energy source is glucose instead of butyrate. Consequently, even moderate concentrations of butyrate accumulate in cancerous colonocytes and function as HDAC inhibitors to inhibit cell proliferation and induce apoptosis. These findings implicate a bacterial metabolite with metaboloepigenetic properties in tumor suppression. PMID:24270685

  5. Gene-Environment Interaction Effects on the Development of Immune Responses in the 1st Year of Life

    PubMed Central

    Hoffjan, Sabine; Nicolae, Dan; Ostrovnaya, Irina; Roberg, Kathy; Evans, Michael; Mirel, Daniel B.; Steiner, Lori; Walker, Karen; Shult, Peter; Gangnon, Ronald E.; Gern, James E.; Martinez, Fernando D.; Lemanske, Robert F.; Ober, Carole

    2005-01-01

    Asthma is a common disease that results from both genetic and environmental risk factors. Children attending day care in the 1st year of life have lower risks for developing asthma, although the mechanism for this “day care” effect is largely unknown. We investigated the interactions between day care exposure in the 1st 6 mo of life and genotypes for 72 polymorphisms at 45 candidate loci and their effects on cytokine response profiles and on the development of atopic phenotypes in the 1st year of life in the Childhood Onset of Asthma (COAST) cohort of children. Six interactions (at four polymorphisms in three loci) with “day care” that had an effect on early-life immune phenotypes were significant at P<.001. The estimated false-discovery rate was 33%, indicating that an estimated four P values correspond to true associations. Moreover, the “day care” effect at some loci was accounted for by the increased number of viral infections among COAST children attending day care, whereas interactions at other loci were independent of the number of viral infections, indicating the presence of additional risk factors associated with day care environment. This study identified significant gene-environment interactions influencing the early patterning of the immune system and the subsequent development of asthma and highlights the importance of considering environmental risk factors in genetic analyses. PMID:15726497

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

    PubMed

    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. PMID:25977357

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

    PubMed

    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. PMID:26024343

  8. Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines.

    PubMed

    Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif

    2015-05-15

    Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. 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, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM. PMID:25987962

  9. Enacting the molecular imperative: How gene-environment interaction research links bodies and environments in the post-genomic age.

    PubMed

    Darling, Katherine Weatherford; Ackerman, Sara L; Hiatt, Robert H; Lee, Sandra Soo-Jin; Shim, Janet K

    2016-04-01

    Despite a proclaimed shift from 'nature versus nurture' to 'genes and environment' paradigms within biomedical and genomic science, capturing the environment and identifying gene-environment interactions (GEIs) has remained a challenge. What does 'the environment' mean in the post-genomic age? In this paper, we present qualitative data from a study of 33 principal investigators funded by the U.S. National Institutes of Health to conduct etiological research on three complex diseases (cancer, cardiovascular disease and diabetes). We examine their research practices and perspectives on the environment through the concept of molecularization: the social processes and transformations through which phenomena (diseases, identities, pollution, food, racial/ethnic classifications) are re-defined in terms of their molecular components and described in the language of molecular biology. We show how GEI researchers' expansive conceptualizations of the environment ultimately yield to the imperative to molecularize and personalize the environment. They seek to 'go into the body' and re-work the boundaries between bodies and environments. In the process, they create epistemic hinges to facilitate a turn from efforts to understand social and environmental exposures outside the body, to quantifying their effects inside the body. GEI researchers respond to these emergent imperatives with a mixture of excitement, ambivalence and frustration. We reflect on how GEI researchers struggle to make meaning of molecules in their work, and how they grapple with molecularization as a methodological and rhetorical imperative as well as a process transforming biomedical research practices. PMID:26994357

  10. Interpretations of education about gene-environment influences on health in rural Ethiopia: the context of a neglected tropical disease

    PubMed Central

    Tora, Abebayehu; Ayode, Desta; Tadele, Getnet; Farrell, David; Davey, Gail; McBride, Colleen M.

    2016-01-01

    Background Misunderstandings of the role of genetics in disease development are associated with stigmatizing behaviors and fatalistic attitudes about prevention. This report describes an evaluation of community understanding of an educational module about genetic and environmental influences on the development of podoconiosis, a neglected tropical disease endemic in highland Ethiopia. Methods A qualitative process assessment was conducted as part of a large prospective intervention trial in August 2013, in Wolaita Zone, southern Ethiopia. Sixty five participants were purposively selected from 600 households randomized to receive the inherited susceptibility module. The educational module used pictorial representations and oral explanations of the interaction of inherited sensitivity and soil exposure and was delivered by lay health educators in participants' homes. Data were collected using semi-structured individual interviews (IDIs) or focus group discussions (FGDs). Results Qualitative analyses showed that most participants improved their understanding of inherited soil sensitivity and susceptibility to podoconiosis. Participants linked their new understanding to decreased stigma-related attitudes. The module also corrected misconceptions that the condition was contagious, again diminishing stigmatizing attitudes. Lastly, these improvements in understanding increased the perceived value of foot protection. Conclusions Taken together, these improvements support the acceptability, feasibility and potential benefits of implementing gene-environment education in low and middle income countries. PMID:27114426

  11. Identifying novel interventional strategies for psychiatric disorders: integrating genomics, 'enviromics' and gene-environment interactions in valid preclinical models.

    PubMed

    McOmish, Caitlin E; Burrows, Emma L; Hannan, Anthony J

    2014-10-01

    Psychiatric disorders affect a substantial proportion of the population worldwide. This high prevalence, combined with the chronicity of the disorders and the major social and economic impacts, creates a significant burden. As a result, an important priority is the development of novel and effective interventional strategies for reducing incidence rates and improving outcomes. This review explores the progress that has been made to date in establishing valid animal models of psychiatric disorders, while beginning to unravel the complex factors that may be contributing to the limitations of current methodological approaches. We propose some approaches for optimizing the validity of animal models and developing effective interventions. We use schizophrenia and autism spectrum disorders as examples of disorders for which development of valid preclinical models, and fully effective therapeutics, have proven particularly challenging. However, the conclusions have relevance to various other psychiatric conditions, including depression, anxiety and bipolar disorders. We address the key aspects of construct, face and predictive validity in animal models, incorporating genetic and environmental factors. Our understanding of psychiatric disorders is accelerating exponentially, revealing extraordinary levels of genetic complexity, heterogeneity and pleiotropy. The environmental factors contributing to individual, and multiple, disorders also exhibit breathtaking complexity, requiring systematic analysis to experimentally explore the environmental mediators and modulators which constitute the 'envirome' of each psychiatric disorder. Ultimately, genetic and environmental factors need to be integrated via animal models incorporating the spatiotemporal complexity of gene-environment interactions and experience-dependent plasticity, thus better recapitulating the dynamic nature of brain development, function and dysfunction. PMID:24846457

  12. Muscle Quality and Myosteatosis: Novel Associations With Mortality Risk: The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.

    PubMed

    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. PMID:26643983

  13. The Influence of Major Life Events on Economic Attitudes in a World of Gene-Environment Interplay.

    PubMed

    Hatemi, Peter K

    2013-10-01

    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

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

    PubMed

    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. PMID:22829212

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

    PubMed

    Hollman, Antoinesha L; Tchounwou, Paul B; Huang, Hung-Chung

    2016-04-01

    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. PMID:27043589

  16. The Influence of Major Life Events on Economic Attitudes in a World of Gene-Environment Interplay

    PubMed Central

    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

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

    PubMed Central

    Hollman, Antoinesha L.; Tchounwou, Paul B.; Huang, Hung-Chung

    2016-01-01

    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. PMID:27043589

  18. Electret-based passive dust sampler: sampling of organic dusts.

    PubMed

    Brown, R C; Hemingway, M A; Wake, D; Thorpe, A

    1996-09-01

    Passive samplers are light, convenient and cheap. However, the sample size tends to be small and a correlation exercise between the results of a passive sampler and a conventional sampler must be carried out. The design principles and mode of action of an electret-based passive dust sampler are described. The device captures dust particles at a rate independent of the velocity of air except when this is very low but dependent on the electrical properties of the dust being sampled. Experimental results are presented of measurements made in bakeries, pig farms, a dairy farm, an arable farm and a rubber-manufacturing plant. Correlation between measurements made with the passive sampler and measurements of inhalable dust performed by other means are reasonable. The results are interpreted in terms of the physical properties of the dust being sampled. PMID:8831282

  19. Passivated niobium cavities

    DOEpatents

    Myneni, Ganapati Rao; Hjorvarsson, Bjorgvin; Ciovati, Gianluigi

    2006-12-19

    A niobium cavity exhibiting high quality factors at high gradients is provided by treating a niobium cavity through a process comprising: 1) removing surface oxides by plasma etching or a similar process; 2) removing hydrogen or other gases absorbed in the bulk niobium by high temperature treatment of the cavity under ultra high vacuum to achieve hydrogen outgassing; and 3) assuring the long term chemical stability of the niobium cavity by applying a passivating layer of a superconducting material having a superconducting transition temperature higher than niobium thereby reducing losses from electron (cooper pair) scattering in the near surface region of the interior of the niobium cavity. According to a preferred embodiment, the passivating layer comprises niobium nitride (NbN) applied by reactive sputtering.

  20. Passive broadband acoustic thermometry

    NASA Astrophysics Data System (ADS)

    Anosov, A. A.; Belyaev, R. V.; Klin'shov, V. V.; Mansfel'd, A. D.; Subochev, P. V.

    2016-04-01

    The 1D internal (core) temperature profiles for the model object (plasticine) and the human hand are reconstructed using the passive acoustothermometric broadband probing data. Thermal acoustic radiation is detected by a broadband (0.8-3.5 MHz) acoustic radiometer. The temperature distribution is reconstructed using a priori information corresponding to the experimental conditions. The temperature distribution for the heated model object is assumed to be monotonic. For the hand, we assume that the temperature distribution satisfies the heat-conduction equation taking into account the blood flow. The average error of reconstruction determined for plasticine from the results of independent temperature measurements is 0.6 K for a measuring time of 25 s. The reconstructed value of the core temperature of the hand (36°C) generally corresponds to physiological data. The obtained results make it possible to use passive broadband acoustic probing for measuring the core temperatures in medical procedures associated with heating of human organism tissues.

  1. Passive-solar design manual for the United States Navy

    SciTech Connect

    Wray, W.O.; Biehl, F.A.; Kosiewicz, C.R.; Miles, C.R. Durlak, E.R.

    1982-01-01

    A passive solar design manual for single-family detached residences and dormitory-type buildings is being developed. The design procedure employed in the manual is a simplification of the original monthly solar load ratio (SLR) method. The new SLR correlations involve a single constant for each system. The correlation constant appears as a scale factor permitting the use of a universal performance curve for all passive systems. Furthermore, by providing location-dependent correlations between the annual solar heating fraction (SHF)* and the minimum monthly SHF, we have eliminated the need to perform an SLR calculation for each month of the heating season.

  2. Passive fetal monitoring sensor

    NASA Technical Reports Server (NTRS)

    Zuckerwar, Allan J. (Inventor); Hall, Earl T. (Inventor); Baker, Donald A. (Inventor); Bryant, Timothy D. (Inventor)

    1992-01-01

    An ambulatory, passive sensor for use in a fetal monitoring system is discussed. The invention is comprised of a piezoelectric polymer film, combined with a metallic mounting plate fastened to a belt, and electrically connected to a signal processing unit by means of a shielded cable. The purpose of the sensor is to receive pressure pulses emitted by a fetus inside an expectant mother. Additionally, the monitor will filter out pressure pulses arising from other sources, such as the maternal heart.

  3. Passively actuated valve

    SciTech Connect

    Modro, S. Michael; Ougouag, Abderrafi M.

    2005-09-20

    A passively actuated valve for isolating a high pressure zone from a low pressure zone and discontinuing the isolation when the pressure in the high pressure zone drops below a preset threshold. If the pressure in the high pressure zone drops below the preset threshold, the valve opens and allows flow from the high pressure zone to the low pressure zone. The valve remains open allowing pressure equalization and back-flow should a pressure inversion between the two pressure zone occur.

  4. Passive fetal monitoring sensor

    NASA Astrophysics Data System (ADS)

    Zuckerwar, Allan J.; Hall, Earl T.; Baker, Donald A.; Bryant, Timothy D.

    1992-08-01

    An ambulatory, passive sensor for use in a fetal monitoring system is discussed. The invention is comprised of a piezoelectric polymer film, combined with a metallic mounting plate fastened to a belt, and electrically connected to a signal processing unit by means of a shielded cable. The purpose of the sensor is to receive pressure pulses emitted by a fetus inside an expectant mother. Additionally, the monitor will filter out pressure pulses arising from other sources, such as the maternal heart.

  5. Passive in vivo elastography from skeletal muscle noise

    SciTech Connect

    Sabra, Karim G.; Conti, Stephane; Roux, Philippe; Kuperman, W. A.

    2007-05-07

    Measuring the in vivo elastic properties of muscles (e.g., stiffness) provides a means for diagnosing and monitoring muscular activity. The authors demonstrated a passive in vivo elastography technique without an active external radiation source. This technique instead uses cross correlations of contracting skeletal muscle noise recorded with skin-mounted sensors. Each passive sensor becomes a virtual in vivo shear wave source. The results point to a low-cost, noninvasive technique for monitoring biomechanical in vivo muscle properties. The efficacy of the passive elastography technique originates from the high density of cross paths between all sensor pairs, potentially achieving the same sensitivity obtained from active elastography methods.

  6. Gene-environment interactions between JAZF1 and occupational and household lead exposure in prostate cancer among African American men

    PubMed Central

    Neslund-Dudas, Christine; Levin, Albert M.; Beebe-Dimmer, Jennifer L.; Bock, Cathryn H.; Nock, Nora L.; Rundle, Andrew; Jankowski, Michelle; Krajenta, Richard; Dou, Q. Ping; Mitra, Bharati; Tang, Deliang; Rebbeck, Timothy R.; Rybicki, Benjamin A.

    2014-01-01

    Purpose A single nucleotide polymorphism, rs10486567, in JAZF1 has consistently been associated with increased risk of prostate cancer. The physical interaction of zinc finger proteins, such as JAZF1, with heavy metals may play a role in carcinogenesis. This study assessed potential gene-environment statistical interactions (GxE) between rs10486567 and heavy metals in prostate cancer. Methods In a case-only study of 228 African American prostate cancer cases, GxE between rs10486567 and sources of cadmium (Cd) and lead (Pb) were assessed. Unconditional logistic regression was used to estimate interaction odds ratios and GEE was used for models containing nested data. Case-control validation of IORs was performed, using 82 controls frequency matched to cases on age-race. Results Among cases, a potential GxE interaction was observed between rs10486567 CC genotype and living in a Census tract with a high proportion of housing built before 1950, a proxy for household Pb exposure, when compared to CT or TT carriers (OR 1.81; 95% CI 1.04-3.16; p=0.036). A stronger GxE interaction was observed when both housing and occupational Pb exposure were taken into account (OR 2.62; 95% CI 1.03-6.68; p=0.04). Case-control stratified analyses showed the odds of being a CC carrier was higher in cases compared to controls among men living in areas with older housing (OR 2.03; CI 0.99-4.19; p=0.05) or having high occupational Pb exposure (OR 2.50; CI 1.01-6.18; p=0.05). Conclusions In African American men, the association between JAZF1 rs10486567 and prostate cancer may be modified by exposure to heavy metals such as Pb. PMID:24801046

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

    PubMed Central

    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

    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 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. PMID:24967710

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

    PubMed Central

    Fan, Ruzong; Manga, Prashiela

    2015-01-01

    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. PMID:26191336

  9. I Just Ran a Thousand Analyses: Benefits of Multiple Testing in Understanding Equivocal Evidence on Gene-Environment Interactions

    PubMed Central

    Heininga, Vera E.; Oldehinkel, Albertine J.; Veenstra, René; Nederhof, Esther

    2015-01-01

    Background 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. Method 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. Results 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. Conclusion 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

  10. Fundamental studies of passivity and passivity breakdown. Final report

    SciTech Connect

    Macdonald, D.D.; Urquidi-Macdonald, M.; Song, H.; Biaggio-Rocha, S.; Searson, P.

    1991-11-01

    This report summarizes the findings of our fundamental research program on passivity and passivity breakdown. During the past three and one half years in this program (including the three year incrementally-funded grant prior to the present grant), we developed and experimentally tested various physical models for the growth and breakdown of passive films on metal surfaces. These models belong to a general class termed ``point defects models`` (PDMs), in which the growth and breakdown of passive films are described in terms of the movement of anion and cation vacancies.

  11. Folding in and out: passive morphing in flapping wings.

    PubMed

    Stowers, Amanda K; Lentink, David

    2015-04-01

    We present a new mechanism for passive wing morphing of flapping wings inspired by bat and bird wing morphology. The mechanism consists of an unactuated hand wing connected to the arm wing with a wrist joint. Flapping motion generates centrifugal accelerations in the hand wing, forcing it to unfold passively. Using a robotic model in hover, we made kinematic measurements of unfolding kinematics as functions of the non-dimensional wingspan fold ratio (2-2.5) and flapping frequency (5-17 Hz) using stereo high-speed cameras. We find that the wings unfold passively within one to two flaps and remain unfolded with only small amplitude oscillations. To better understand the passive dynamics, we constructed a computer model of the unfolding process based on rigid body dynamics, contact models, and aerodynamic correlations. This model predicts the measured passive unfolding within about one flap and shows that unfolding is driven by centrifugal acceleration induced by flapping. The simulations also predict that relative unfolding time only weakly depends on flapping frequency and can be reduced to less than half a wingbeat by increasing flapping amplitude. Subsequent dimensional analysis shows that the time required to unfold passively is of the same order of magnitude as the flapping period. This suggests that centrifugal acceleration can drive passive unfolding within approximately one wingbeat in small and large wings. Finally, we show experimentally that passive unfolding wings can withstand impact with a branch, by first folding and then unfolding passively. This mechanism enables flapping robots to squeeze through clutter without sophisticated control. Passive unfolding also provides a new avenue in morphing wing design that makes future flapping morphing wings possibly more energy efficient and light-weight. Simultaneously these results point to possible inertia driven, and therefore metabolically efficient, control strategies in bats and birds to morph or recover

  12. Passive Immunization Against Poliomyelitis

    PubMed Central

    Rinaldo, Charles R.

    2005-01-01

    Poliomyelitis has gone from being one of the worst scourges of the 20th century to nearing eradication in the 21st. This success is well known to be attributable to the Salk inactivated and Sabin attenuated poliovirus vaccines. However, before introduction of these vaccines, William McDowall Hammon of the University of Pittsburgh Graduate School of Public Health led the first major breakthrough in prevention of the disease by using passive immunization in one of the earliest double-blind, placebo-controlled clinical trials. This study provided the first evidence that antibodies to poliovirus could prevent the disease in humans. PMID:15855454

  13. Passive propellant system

    NASA Technical Reports Server (NTRS)

    Hess, D. A.; Regnier, W. W.; Jacobs, V. L. (Inventor)

    1979-01-01

    A passive propellant acquisition and feed system is disclosed which acquires and feeds gas-free propellant in low or zero-g environments during orbital maneuvers and retains this propellant under high axially directed acceleration such as may be experienced during launch of a space vehicle and orbit-to-orbit transfer is described. The propellant system includes a dual compartment propellant tank with independent surface tension acquisition channels in each compartment to provide gas-free flow of pressurized liquid propellant from one compartment to the other in one direction only.

  14. Passive bistatic radar analysis

    NASA Astrophysics Data System (ADS)

    O'Hagan, Daniel W.; Kuschel, H.; Schiller, Joachim

    2009-06-01

    Passive Bistatic Radar (PBR) research is at its zenith with several notable PBR systems currently operational, or available for deployment. Such PBRs include the Manastash Ridge Radar (MRR) developed for and by academia; Silent Sentry developed as a commercial concern by Lockheed Martin; and Homeland Alerter (HA100) also a commercial system developed by Thales. However at present, despite the existence of numerous PBR prototypes, take up of commercial passive radar technology remains slow. This is due in part to technology immaturity, in part to politics, and particularly due to the fact that monostatic radars perform so well. If PBRs are to enjoy longevity as a viable technology then it is imperative that they address certain niche application areas, with the aforementioned MRR being one prime example of this. The focus of this paper will be an analysis of a PBR system that utilised FM radio signals of opportunity to detect aircraft targets with an RCS generally not lower than 20 m2. The paper will demonstrate the theoretical detection coverage of an FM based PBR operating in a severe interference environment.

  15. Passive field reflectance measurements

    NASA Astrophysics Data System (ADS)

    Weber, Christian; Schinca, Daniel C.; Tocho, Jorge O.; Videla, Fabian

    2008-10-01

    The results of reflectance measurements performed with a three-band passive radiometer with independent channels for solar irradiance reference are presented. Comparative operation between the traditional method that uses downward-looking field and reference white panel measurements and the new approach involving duplicated downward- and upward-looking spectral channels (each latter one with its own diffuser) is analyzed. The results indicate that the latter method performs in very good agreement with the standard method and is more suitable for passive sensors under rapidly changing atmospheric conditions (such as clouds, dust, mist, smog and other scatterers), since a more reliable synchronous recording of reference and incident light is achieved. Besides, having separate channels for the reference and the signal allows a better balancing of gains in the amplifiers for each spectral channel. We show the results obtained in the determination of the normalized difference vegetation index (NDVI) corresponding to the period 2004-2007 field experiments concerning weed detection in soybean stubbles and fertilizer level assessment in wheat. The method may be used to refine sensor-based nitrogen fertilizer rate recommendations and to determine suitable zones for herbicide applications.

  16. Volcanic passive margins

    NASA Astrophysics Data System (ADS)

    Geoffroy, Laurent

    2005-12-01

    Compared to non-volcanic ones, volcanic passive margins mark continental break-up over a hotter mantle, probably subject to small-scale convection. They present distinctive genetic and structural features. High-rate extension of the lithosphere is associated with catastrophic mantle melting responsible for the accretion of a thick igneous crust. Distinctive structural features of volcanic margins are syn-magmatic and continentward-dipping crustal faults accommodating the seaward flexure of the igneous crust. Volcanic margins present along-axis a magmatic and tectonic segmentation with wavelength similar to adjacent slow-spreading ridges. Their 3D organisation suggests a connection between loci of mantle melting at depths and zones of strain concentration within the lithosphere. Break-up would start and propagate from localized thermally-softened lithospheric zones. These 'soft points' could be localized over small-scale convection cells found at the bottom of the lithosphere, where adiabatic mantle melting would specifically occur. The particular structure of the brittle crust at volcanic passive margins could be interpreted by active and sudden oceanward flow of both the unstable hot mantle and the ductile part of the lithosphere during the break-up stage. To cite this article: L. Geoffroy, C. R. Geoscience 337 (2005).

  17. Fly ash carbon passivation

    DOEpatents

    La Count, Robert B; Baltrus, John P; Kern, Douglas G

    2013-05-14

    A thermal method to passivate the carbon and/or other components in fly ash significantly decreases adsorption. The passivated carbon remains in the fly ash. Heating the fly ash to about 500 and 800 degrees C. under inert gas conditions sharply decreases the amount of surfactant adsorbed by the fly ash recovered after thermal treatment despite the fact that the carbon content remains in the fly ash. Using oxygen and inert gas mixtures, the present invention shows that a thermal treatment to about 500 degrees C. also sharply decreases the surfactant adsorption of the recovered fly ash even though most of the carbon remains intact. Also, thermal treatment to about 800 degrees C. under these same oxidative conditions shows a sharp decrease in surfactant adsorption of the recovered fly ash due to the fact that the carbon has been removed. This experiment simulates the various "carbon burnout" methods and is not a claim in this method. The present invention provides a thermal method of deactivating high carbon fly ash toward adsorption of AEAs while retaining the fly ash carbon. The fly ash can be used, for example, as a partial Portland cement replacement in air-entrained concrete, in conductive and other concretes, and for other applications.

  18. Mechanical passive logic module

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, Tanay; Caulfield, H. John

    2015-02-01

    Nothing from nothing gives simple simile, but something from nothing is an interesting and challenging task. Adolf Lohmann once proposed 'do nothing machine' in optics, which only copies input to output. Passive logic module (PALM) is a special type of 'do nothing machine' which can converts inputs into one of 16 possible binary outputs. This logic module is not like the conventional irreversible one. It is a simple type of reversible Turing machine. In this manuscript we discussed and demonstrated PALM using mechanical movement of plane mirrors. Also we discussed the theoretical model of micro electro mechanical system (MEMS) based PALM in this manuscript. It may have several valuable properties such as passive operation (no need for nonlinear elements as other logic device require) and modular logic (one device implementing any Boolean logic function with simple internal changes). The result is obtained from the demonstration by only looking up the output. No calculation is required to get the result. Not only that, PALM is a simple type of the famous 'billiard ball machine', which also discussed in this manuscript.

  19. Passive-solar construction handbook

    SciTech Connect

    Levy, E.; Evans, D.; Gardstein, C.

    1981-02-01

    Many of the basic elements of passive solar design are reviewed. Passive solar construction is covered according to system type, each system type discussion including a general discussion of the important design and construction issues which apply to the particular system and case studies illustrating designed and built examples of the system type. The three basic types of passive solar systems discussed are direct gain, thermal storage wall, and attached sunspace. Thermal performance and construction information is presented for typical materials used in passive solar collector components, storage components, and control components. Appended are an overview of analysis methods and a technique for estimating performance. (LEW)

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

    PubMed

    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. PMID:27270123

  1. Commentary on "Capturing the Evasive Passive"

    ERIC Educational Resources Information Center

    Lillo-Martin, Diane; Snyder, William

    2009-01-01

    Passives has been the focus of much research in language acquisition since the 1970s. It has been clear from this research that young children seldom produce passives spontaneously, particularly "long" or "full" passives with a by-phrase; and they usually perform poorly on experimental tests of the comprehension of passives, especially passives of…

  2. Next-generation analysis of cataracts: determining knowledge driven gene-gene interactions using biofilter, and gene-environment interactions using the Phenx Toolkit*.

    PubMed

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

    2015-01-01

    Investigating the association between biobank derived genomic data and the information of linked electronic health records (EHRs) is an emerging area of research for dissecting the architecture of complex human traits, where cases and controls for study are defined through the use of electronic phenotyping algorithms deployed in large EHR systems. For our study, cataract cases and controls were identified within the Marshfield Personalized Medicine Research Project (PMRP) biobank and linked EHR, which is a member of the NHGRI-funded electronic Medical Records and Genomics (eMERGE) Network. Our goal was to explore potential gene-gene and gene-environment interactions within these data for 527,953 and 527,936 single nucleotide polymorphisms (SNPs) for gene-gene and gene-environment analyses, respectively, with minor allele frequency > 1%, in order to explore higher level associations with cataract risk beyond investigations of single SNP-phenotype associations. To build our SNP-SNP interaction models we utilized a prior-knowledge driven filtering method called Biofilter to minimize the multiple testing burden of exploring the vast array of interaction models possible from our extensive number of SNPs. Using Biofilter, we developed 57,376 prior-knowledge directed SNP-SNP models to test for association with cataract status. We selected models that required 6 sources of external domain knowledge. We identified 13 statistically significant SNP-SNP models with an interaction with p-value < 1 × 10(-4), as well as an overall model with p-value < 0.01 associated with cataract status. We also conducted gene-environment interaction analyses for all GWAS SNPs and a set of environmental factors from the PhenX Toolkit: smoking, UV exposure, and alcohol use;these environmental factors have been previously associated with the formation of cataracts. We found a total of 782 gene-environment models that exhibit an interaction with a p-value < 1 × 10(-4) associatedwith cataract

  3. Passive Ball Capture Joint

    NASA Technical Reports Server (NTRS)

    Cloyd, Richard A. (Inventor); Bryan, Thomas C. (Inventor)

    2003-01-01

    A passive ball capture joint has a sleeve with a plurality of bores distributed about a circumference thereof and formed therethrough at an acute angle relative to the sleeve's longitudinal axis. A spring-loaded retainer is slidingly fitted in each bore and is biased such that, if allowed, will extend at least partially into the sleeve to retain a ball therein. A ring, rotatably mounted about the bores, has an interior wall defining a plurality of shaped races that bear against the spring-loaded retainers. A mechanized rotational force producer is coupled to the ring. The ring can be rotated from a first position (that presses the retainers into the sleeve to lock the ball in place) to a second position (that allows the retainers to springback out of the sleeve to release the ball).

  4. Passive magnetic bearing system

    DOEpatents

    Post, Richard F.

    2014-09-02

    An axial stabilizer for the rotor of a magnetic bearing provides external control of stiffness through switching in external inductances. External control also allows the stabilizer to become a part of a passive/active magnetic bearing system that requires no external source of power and no position sensor. Stabilizers for displacements transverse to the axis of rotation are provided that require only a single cylindrical Halbach array in its operation, and thus are especially suited for use in high rotation speed applications, such as flywheel energy storage systems. The elimination of the need of an inner cylindrical array solves the difficult mechanical problem of supplying support against centrifugal forces for the magnets of that array. Compensation is provided for the temperature variation of the strength of the magnetic fields of the permanent magnets in the levitating magnet arrays.

  5. Passive containment cooling system

    DOEpatents

    Billig, P.F.; Cooke, F.E.; Fitch, J.R.

    1994-01-25

    A passive containment cooling system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel and is vented to the drywell. An isolation pool is disposed above the GDCS pool and includes an isolation condenser therein. The condenser has an inlet line disposed in flow communication with the drywell for receiving the non-condensable gas along with any steam released therein following a loss-of-coolant accident (LOCA). The condenser also has an outlet line disposed in flow communication with the drywell for returning to the drywell both liquid condensate produced upon cooling of the steam and the non-condensable gas for reducing pressure within the containment vessel following the LOCA. 1 figure.

  6. Passive containment cooling system

    DOEpatents

    Billig, Paul F.; Cooke, Franklin E.; Fitch, James R.

    1994-01-01

    A passive containment cooling system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel and is vented to the drywell. An isolation pool is disposed above the GDCS pool and includes an isolation condenser therein. The condenser has an inlet line disposed in flow communication with the drywell for receiving the non-condensable gas along with any steam released therein following a loss-of-coolant accident (LOCA). The condenser also has an outlet line disposed in flow communication with the drywell for returning to the drywell both liquid condensate produced upon cooling of the steam and the non-condensable gas for reducing pressure within the containment vessel following the LOCA.

  7. Temperature initiated passive cooling system

    DOEpatents

    Forsberg, C.W.

    1994-11-01

    A passive cooling system for cooling an enclosure only when the enclosure temperature exceeds a maximum standby temperature comprises a passive heat transfer loop containing heat transfer fluid having a particular thermodynamic critical point temperature just above the maximum standby temperature. An upper portion of the heat transfer loop is insulated to prevent two phase operation below the maximum standby temperature. 1 fig.

  8. Temperature initiated passive cooling system

    DOEpatents

    Forsberg, Charles W.

    1994-01-01

    A passive cooling system for cooling an enclosure only when the enclosure temperature exceeds a maximum standby temperature comprises a passive heat transfer loop containing heat transfer fluid having a particular thermodynamic critical point temperature just above the maximum standby temperature. An upper portion of the heat transfer loop is insulated to prevent two phase operation below the maximum standby temperature.

  9. MSL DAN Passive Data and Interpretations

    NASA Astrophysics Data System (ADS)

    Tate, C. G.; Moersch, J.; Jun, I.; Ming, D. W.; Mitrofanov, I. G.; Litvak, M. L.; Behar, A.; Boynton, W. V.; Drake, D.; Lisov, D.; Mischna, M. A.; Hardgrove, C. J.; Milliken, R.; Sanin, A. B.; Starr, R. D.; Martín-Torres, J.; Zorzano, M. P.; Fedosov, F.; Golovin, D.; Harshman, K.; Kozyrev, A.; Malakhov, A. V.; Mokrousov, M.; Nikiforov, S.; Varenikov, A.

    2014-12-01

    In its passive mode of operation, The Mars Science Laboratory Dynamic Albedo of Neutrons experiment (DAN) detects low energy neutrons that are produced by two different sources on Mars. Neutrons are produced by the rover's Multi-Mission Radioisotope Thermoelectric Generator (MMRTG) and by interactions of high energy galactic cosmic rays (GCR) within the atmosphere and regolith. As these neutrons propagate through the subsurface, their energies can be moderated by interactions with hydrogen nuclei. More hydrogen leads to greater moderation (thermalization) of the neutron population energies. The presence of high thermal neutron absorbing elements within the regolith also complicates the spectrum of the returning neutron population, as shown by Hardgrove et al. DAN measures the thermal and epithermal neutron populations leaking from the surface to infer the amount of water equivalent hydrogen (WEH) in the shallow regolith. Extensive modeling is performed using a Monte Carlo approach (MCNPX) to analyze DAN passive measurements at fixed locations and along rover traverse segments. DAN passive WEH estimates along Curiosity's traverse will be presented along with an analysis of trends in the data and a description of correlations between these results and the geologic characteristics of the surfaces traversed.

  10. Power Analysis for Population-Based Longitudinal Studies Investigating Gene-Environment Interactions in Chronic Diseases: A Simulation Study

    PubMed Central

    Ma, Jinhui; Thabane, Lehana; Beyene, Joseph; Raina, Parminder

    2016-01-01

    very low (≥0.1) and the disease of interest was not rare (such as diabetes and dementia). The CLSA had enough power to detect a large effect of the gene-environment interaction only when both risk exposures had relatively high prevalence (0.2) and the disease of interest was very common (such as diabetes). The minimum detectable hazard ratios (MDHR) of the CLSA for the environmental and genetic risk exposures obtained from this simulation study were larger than those calculated according to the conventional sample size calculation method. For example, the MDHR for the environmental risk exposure was 1.15 according to the conventional method if the prevalence of the risk exposure was 0.1 and the disease of interest was dementia. In contrast, the MDHR was 1.61 if the same exposure was measured every 3 years with a misclassification rate of 0.1 according to this simulation study. With a given sample size, higher statistical power could be achieved by increasing the measuring frequency in participants with high risk of declining health status or changing risk exposures, and by increasing measurement accuracy of diseases and risk exposures. A properly designed simulation-based sample size calculation is superior to conventional methods when rigorous sample size calculation is necessary. PMID:26901422