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Sample records for genetic covariances alter

  1. How much do genetic covariances alter the rate of adaptation?

    Agrawal, Aneil F; Stinchcombe, John R

    2009-03-22

    Genetically correlated traits do not evolve independently, and the covariances between traits affect the rate at which a population adapts to a specified selection regime. To measure the impact of genetic covariances on the rate of adaptation, we compare the rate fitness increases given the observed G matrix to the expected rate if all the covariances in the G matrix are set to zero. Using data from the literature, we estimate the effect of genetic covariances in real populations. We find no net tendency for covariances to constrain the rate of adaptation, though the quality and heterogeneity of the data limit the certainty of this result. There are some examples in which covariances strongly constrain the rate of adaptation but these are balanced by counter examples in which covariances facilitate the rate of adaptation; in many cases, covariances have little or no effect. We also discuss how our metric can be used to identify traits or suites of traits whose genetic covariances to other traits have a particularly large impact on the rate of adaptation.

  2. Alterations in Anatomical Covariance in the Prematurely Born.

    Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Vohr, Betty R; Schneider, Karen C; Papademetris, Xenophon; Constable, R Todd; Ment, Laura R

    2017-01-01

    Preterm (PT) birth results in long-term alterations in functional and structural connectivity, but the related changes in anatomical covariance are just beginning to be explored. To test the hypothesis that PT birth alters patterns of anatomical covariance, we investigated brain volumes of 25 PTs and 22 terms at young adulthood using magnetic resonance imaging. Using regional volumetrics, seed-based analyses, and whole brain graphs, we show that PT birth is associated with reduced volume in bilateral temporal and inferior frontal lobes, left caudate, left fusiform, and posterior cingulate for prematurely born subjects at young adulthood. Seed-based analyses demonstrate altered patterns of anatomical covariance for PTs compared with terms. PTs exhibit reduced covariance with R Brodmann area (BA) 47, Broca's area, and L BA 21, Wernicke's area, and white matter volume in the left prefrontal lobe, but increased covariance with R BA 47 and left cerebellum. Graph theory analyses demonstrate that measures of network complexity are significantly less robust in PTs compared with term controls. Volumes in regions showing group differences are significantly correlated with phonological awareness, the fundamental basis for reading acquisition, for the PTs. These data suggest both long-lasting and clinically significant alterations in the covariance in the PTs at young adulthood. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Altered structural covariance of the striatum in functional dyspepsia patients.

    Liu, P; Zeng, F; Yang, F; Wang, J; Liu, X; Wang, Q; Zhou, G; Zhang, D; Zhu, M; Zhao, R; Wang, A; Gong, Q; Liang, F

    2014-08-01

    Functional dyspepsia (FD) is thought to be involved in dysregulation within the brain-gut axis. Recently, altered striatum activation has been reported in patients with FD. However, the gray matter (GM) volumes in the striatum and structural covariance patterns of this area are rarely explored. The purpose of this study was to examine the GM volumes and structural covariance patterns of the striatum between FD patients and healthy controls (HCs). T1-weighted magnetic resonance images were obtained from 44 FD patients and 39 HCs. Voxel-based morphometry (VBM) analysis was adopted to examine the GM volumes in the two groups. The caudate- or putamen-related regions identified from VBM analysis were then used as seeds to map the whole brain voxel-wise structural covariance patterns. Finally, a correlation analysis was used to investigate the effects of FD symptoms on the striatum. The results showed increased GM volumes in the bilateral putamen and right caudate. Compared with the structural covariance patterns of the HCs, the FD-related differences were mainly located in the amygdala, hippocampus/parahippocampus (HIPP/paraHIPP), thalamus, lingual gyrus, and cerebellum. And significant positive correlations were found between the volumes in the striatum and the FD duration in the patients. These findings provided preliminary evidence for GM changes in the striatum and different structural covariance patterns in patients with FD. The current results might expand our understanding of the pathophysiology of FD. © 2014 John Wiley & Sons Ltd.

  4. Altered Cerebral Blood Flow Covariance Network in Schizophrenia.

    Liu, Feng; Zhuo, Chuanjun; Yu, Chunshui

    2016-01-01

    Many studies have shown abnormal cerebral blood flow (CBF) in schizophrenia; however, it remains unclear how topological properties of CBF network are altered in this disorder. Here, arterial spin labeling (ASL) MRI was employed to measure resting-state CBF in 96 schizophrenia patients and 91 healthy controls. CBF covariance network of each group was constructed by calculating across-subject CBF covariance between 90 brain regions. Graph theory was used to compare intergroup differences in global and nodal topological measures of the network. Both schizophrenia patients and healthy controls had small-world topology in CBF covariance networks, implying an optimal balance between functional segregation and integration. Compared with healthy controls, schizophrenia patients showed reduced small-worldness, normalized clustering coefficient and local efficiency of the network, suggesting a shift toward randomized network topology in schizophrenia. Furthermore, schizophrenia patients exhibited altered nodal centrality in the perceptual-, affective-, language-, and spatial-related regions, indicating functional disturbance of these systems in schizophrenia. This study demonstrated for the first time that schizophrenia patients have disrupted topological properties in CBF covariance network, which provides a new perspective (efficiency of blood flow distribution between brain regions) for understanding neural mechanisms of schizophrenia.

  5. Genetic Alterations in Glioma

    Bralten, Linda B. C.; French, Pim J.

    2011-01-01

    Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes

  6. An alternative covariance estimator to investigate genetic heterogeneity in populations.

    Heslot, Nicolas; Jannink, Jean-Luc

    2015-11-26

    For genomic prediction and genome-wide association studies (GWAS) using mixed models, covariance between individuals is estimated using molecular markers. Based on the properties of mixed models, using available molecular data for prediction is optimal if this covariance is known. Under this assumption, adding individuals to the analysis should never be detrimental. However, some empirical studies showed that increasing training population size decreased prediction accuracy. Recently, results from theoretical models indicated that even if marker density is high and the genetic architecture of traits is controlled by many loci with small additive effects, the covariance between individuals, which depends on relationships at causal loci, is not always well estimated by the whole-genome kinship. We propose an alternative covariance estimator named K-kernel, to account for potential genetic heterogeneity between populations that is characterized by a lack of genetic correlation, and to limit the information flow between a priori unknown populations in a trait-specific manner. This is similar to a multi-trait model and parameters are estimated by REML and, in extreme cases, it can allow for an independent genetic architecture between populations. As such, K-kernel is useful to study the problem of the design of training populations. K-kernel was compared to other covariance estimators or kernels to examine its fit to the data, cross-validated accuracy and suitability for GWAS on several datasets. It provides a significantly better fit to the data than the genomic best linear unbiased prediction model and, in some cases it performs better than other kernels such as the Gaussian kernel, as shown by an empirical null distribution. In GWAS simulations, alternative kernels control type I errors as well as or better than the classical whole-genome kinship and increase statistical power. No or small gains were observed in cross-validated prediction accuracy. This alternative

  7. The causes of variation in the presence of genetic covariance between sexual traits and preferences.

    Fowler-Finn, Kasey D; Rodríguez, Rafael L

    2016-05-01

    Mating traits and mate preferences often show patterns of tight correspondence across populations and species. These patterns of apparent coevolution may result from a genetic association between traits and preferences (i.e. trait-preference genetic covariance). We review the literature on trait-preference covariance to determine its prevalence and potential biological relevance. Of the 43 studies we identified, a surprising 63% detected covariance. We test multiple hypotheses for factors that may influence the likelihood of detecting this covariance. The main predictor was the presence of genetic variation in mate preferences, which is one of the three main conditions required for the establishment of covariance. In fact, 89% of the nine studies where heritability of preference was high detected covariance. Variables pertaining to the experimental methods and type of traits involved in different studies did not greatly influence the detection of trait-preference covariance. Trait-preference genetic covariance appears to be widespread and therefore represents an important and currently underappreciated factor in the coevolution of traits and preferences. © 2015 Cambridge Philosophical Society.

  8. The effects of stress and sex on selection, genetic covariance, and the evolutionary response.

    Holman, L; Jacomb, F

    2017-10-01

    The capacity of a population to adapt to selection (evolvability) depends on whether the structure of genetic variation permits the evolution of fitter trait combinations. Selection, genetic variance and genetic covariance can change under environmental stress, and males and females are not genetically independent, yet the combined effects of stress and dioecy on evolvability are not well understood. Here, we estimate selection, genetic (co)variance and evolvability in both sexes of Tribolium castaneum flour beetles under stressful and benign conditions, using a half-sib breeding design. Although stress uncovered substantial latent heritability, stress also affected genetic covariance, such that evolvability remained low under stress. Sexual selection on males and natural selection on females favoured a similar phenotype, and there was positive intersex genetic covariance. Consequently, sexual selection on males augmented adaptation in females, and intralocus sexual conflict was weak or absent. This study highlights that increased heritability does not necessarily increase evolvability, suggests that selection can deplete genetic variance for multivariate trait combinations with strong effects on fitness, and tests the recent hypothesis that sexual conflict is weaker in stressful or novel environments. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  9. A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics.

    Lu, Qiongshi; Li, Boyang; Ou, Derek; Erlendsdottir, Margret; Powles, Ryan L; Jiang, Tony; Hu, Yiming; Chang, David; Jin, Chentian; Dai, Wei; He, Qidu; Liu, Zefeng; Mukherjee, Shubhabrata; Crane, Paul K; Zhao, Hongyu

    2017-12-07

    Despite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits' genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance between traits using GWAS summary statistics. Through theoretical and numerical analyses, we demonstrate that our method provides accurate covariance estimates, thereby enabling researchers to dissect both the shared and distinct genetic architecture across traits to better understand their etiologies. Among 50 complex traits with publicly accessible GWAS summary statistics (N total ≈ 4.5 million), we identified more than 170 pairs with statistically significant genetic covariance. In particular, we found strong genetic covariance between late-onset Alzheimer disease (LOAD) and amyotrophic lateral sclerosis (ALS), two major neurodegenerative diseases, in single-nucleotide polymorphisms (SNPs) with high minor allele frequencies and in SNPs located in the predicted functional genome. Joint analysis of LOAD, ALS, and other traits highlights LOAD's correlation with cognitive traits and hints at an autoimmune component for ALS. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. The genetic covariance between life cycle stages separated by metamorphosis.

    Aguirre, J David; Blows, Mark W; Marshall, Dustin J

    2014-08-07

    Metamorphosis is common in animals, yet the genetic associations between life cycle stages are poorly understood. Given the radical changes that occur at metamorphosis, selection may differ before and after metamorphosis, and the extent that genetic associations between pre- and post-metamorphic traits constrain evolutionary change is a subject of considerable interest. In some instances, metamorphosis may allow the genetic decoupling of life cycle stages, whereas in others, metamorphosis could allow complementary responses to selection across the life cycle. Using a diallel breeding design, we measured viability at four ontogenetic stages (embryo, larval, juvenile and adult viability), in the ascidian Ciona intestinalis and examined the orientation of additive genetic variation with respect to the metamorphic boundary. We found support for one eigenvector of G: (gobsmax ), which contrasted larval viability against embryo viability and juvenile viability. Target matrix rotation confirmed that while gobsmax shows genetic associations can extend beyond metamorphosis, there is still considerable scope for decoupled phenotypic evolution. Therefore, although genetic associations across metamorphosis could limit that range of phenotypes that are attainable, traits on either side of the metamorphic boundary are capable of some independent evolutionary change in response to the divergent conditions encountered during each life cycle stage. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  11. Immunity traits in pigs: substantial genetic variation and limited covariation.

    Laurence Flori

    Full Text Available BACKGROUND: Increasing robustness via improvement of resistance to pathogens is a major selection objective in livestock breeding. As resistance traits are difficult or impossible to measure directly, potential indirect criteria are measures of immune traits (ITs. Our underlying hypothesis is that levels of ITs with no focus on specific pathogens define an individual's immunocompetence and thus predict response to pathogens in general. Since variation in ITs depends on genetic, environmental and probably epigenetic factors, our aim was to estimate the relative importance of genetics. In this report, we present a large genetic survey of innate and adaptive ITs in pig families bred in the same environment. METHODOLOGY/PRINCIPAL FINDINGS: Fifty four ITs were studied on 443 Large White pigs vaccinated against Mycoplasma hyopneumoniae and analyzed by combining a principal component analysis (PCA and genetic parameter estimation. ITs include specific and non specific antibodies, seric inflammatory proteins, cell subsets by hemogram and flow cytometry, ex vivo production of cytokines (IFNα, TNFα, IL6, IL8, IL12, IFNγ, IL2, IL4, IL10, phagocytosis and lymphocyte proliferation. While six ITs had heritabilities that were weak or not significantly different from zero, 18 and 30 ITs had moderate (0.10.4 heritability values, respectively. Phenotypic and genetic correlations between ITs were weak except for a few traits that mostly include cell subsets. PCA revealed no cluster of innate or adaptive ITs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that variation in many innate and adaptive ITs is genetically controlled in swine, as already reported for a smaller number of traits by other laboratories. A limited redundancy of the traits was also observed confirming the high degree of complementarity between innate and adaptive ITs. Our data provide a genetic framework for choosing ITs to be included as selection criteria in multitrait selection

  12. Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes.

    Hosseini, S M Hadi; Mazaika, Paul; Mauras, Nelly; Buckingham, Bruce; Weinzimer, Stuart A; Tsalikian, Eva; White, Neil H; Reiss, Allan L

    2016-11-01

    Type 1 diabetes mellitus (T1D), one of the most frequent chronic diseases in children, is associated with glucose dysregulation that contributes to an increased risk for neurocognitive deficits. While there is a bulk of evidence regarding neurocognitive deficits in adults with T1D, little is known about how early-onset T1D affects neural networks in young children. Recent data demonstrated widespread alterations in regional gray matter and white matter associated with T1D in young children. These widespread neuroanatomical changes might impact the organization of large-scale brain networks. In the present study, we applied graph-theoretical analysis to test whether the organization of structural covariance networks in the brain for a cohort of young children with T1D (N = 141) is altered compared to healthy controls (HC; N = 69). While the networks in both groups followed a small world organization-an architecture that is simultaneously highly segregated and integrated-the T1D network showed significantly longer path length compared with HC, suggesting reduced global integration of brain networks in young children with T1D. In addition, network robustness analysis revealed that the T1D network model showed more vulnerability to neural insult compared with HC. These results suggest that early-onset T1D negatively impacts the global organization of structural covariance networks and influences the trajectory of brain development in childhood. This is the first study to examine structural covariance networks in young children with T1D. Improving glycemic control for young children with T1D might help prevent alterations in brain networks in this population. Hum Brain Mapp 37:4034-4046, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Genetic covariance structure of reading, intelligence and memory in children

    van Leeuwen, Marieke; van den Berg, Stéphanie Martine; Peper, Jiska S.; Hulshoff Pol, Hilleke E.; Boomsma, Dorret I.

    2009-01-01

    This study investigates the genetic relationship among reading performance, IQ, verbal and visuospatial working memory (WM) and short-term memory (STM) in a sample of 112, 9-year-old twin pairs and their older siblings. The relationship between reading performance and the other traits was explained

  14. Genetic Covariance Structure of Reading, Intelligence and Memory in Children

    van Leeuwen, M.; van den Berg, S.M.; Peper, J.S.; Hulshoff Pol, H.E.; Boomsma, D.I.

    2009-01-01

    This study investigates the genetic relationship among reading performance, IQ, verbal and visuospatial working memory (WM) and short-term memory (STM) in a sample of 112, 9-year-old twin pairs and their older siblings. The relationship between reading performance and the other traits was explained

  15. Genetic Covariance Structure of Reading, Intelligence and Memory in Children

    van Leeuwen, Marieke; van den Berg, Stephanie M.; Peper, Jiska S.; Pol, Hilleke E. Hulshoff; Boomsma, Dorret I.

    This study investigates the genetic relationship among reading performance, IQ, verbal and visuospatial working memory (WM) and short-term memory (STM) in a sample of 112, 9-year-old twin pairs and their older siblings. The relationship between reading performance and the other traits was explained

  16. Rare endocrine cancers have novel genetic alterations

    A molecular characterization of adrenocortical carcinoma, a rare cancer of the adrenal cortex, analyzed 91 cases for alterations in the tumor genomes and identified several novel genetic mutations as likely mechanisms driving the disease as well as whole genome doubling as a probable driver of the disease.

  17. Perils of parsimony: properties of reduced-rank estimates of genetic covariance matrices.

    Meyer, Karin; Kirkpatrick, Mark

    2008-10-01

    Eigenvalues and eigenvectors of covariance matrices are important statistics for multivariate problems in many applications, including quantitative genetics. Estimates of these quantities are subject to different types of bias. This article reviews and extends the existing theory on these biases, considering a balanced one-way classification and restricted maximum-likelihood estimation. Biases are due to the spread of sample roots and arise from ignoring selected principal components when imposing constraints on the parameter space, to ensure positive semidefinite estimates or to estimate covariance matrices of chosen, reduced rank. In addition, it is shown that reduced-rank estimators that consider only the leading eigenvalues and -vectors of the "between-group" covariance matrix may be biased due to selecting the wrong subset of principal components. In a genetic context, with groups representing families, this bias is inverse proportional to the degree of genetic relationship among family members, but is independent of sample size. Theoretical results are supplemented by a simulation study, demonstrating close agreement between predicted and observed bias for large samples. It is emphasized that the rank of the genetic covariance matrix should be chosen sufficiently large to accommodate all important genetic principal components, even though, paradoxically, this may require including a number of components with negligible eigenvalues. A strategy for rank selection in practical analyses is outlined.

  18. Alternative life histories in the Atlantic salmon: genetic covariances within the sneaker sexual tactic in males.

    Páez, David James; Bernatchez, Louis; Dodson, Julian J

    2011-07-22

    Alternative reproductive tactics are ubiquitous in many species. Tactic expression often depends on whether an individual's condition surpasses thresholds that are responsible for activating particular developmental pathways. Two central goals in understanding the evolution of reproductive tactics are quantifying the extent to which thresholds are explained by additive genetic effects, and describing their covariation with condition-related traits. We monitored the development of early sexual maturation that leads to the sneaker reproductive tactic in Atlantic salmon (Salmo salar L.). We found evidence for additive genetic variance in the timing of sexual maturity (which is a measure of the surpassing of threshold values) and body-size traits. This suggests that selection can affect the patterns of sexual development by changing the timing of this event and/or body size. Significant levels of covariation between these traits also occurred, implying a potential for correlated responses to selection. Closer examination of genetic covariances suggests that the detected genetic variation is distributed along at least five directions of phenotypic variation. Our results show that the potential for evolution of the life-history traits constituting this reproductive phenotype is greatly influenced by their patterns of genetic covariance.

  19. Genetic and Environmental Contributions to Covariation Between DHEA and Testosterone in Adolescent Twins.

    Van Hulle, Carol A; Moore, Mollie N; Shirtcliff, Elizabeth A; Lemery-Chalfant, Kathryn; Goldsmith, H Hill

    2015-05-01

    Although several studies have shown that pubertal tempo and timing are shaped by genetic and environmental factors, few studies consider to what extent endocrine triggers of puberty are shaped by genetic and environmental factors. Doing so moves the field from examining correlated developmentally-sensitive biomarkers toward understanding what drives those associations. Two puberty related hormones, dehydroepiandrosterone and testosterone, were assayed from salivary samples in 118 MZ (62 % female), 111 same sex DZ (46 % female) and 103 opposite-sex DZ twin pairs, aged 12-16 years (M = 13.1, SD = 1.3). Pubertal status was assessed with a composite of mother- and self-reports. We used biometric models to estimate the genetic and environmental influences on the variance and covariance in testosterone and DHEA, with and without controlling for their association with puberty, and to test for sex differences. In males, the variance in testosterone and pubertal status was due to shared and non-shared environmental factors; variation in DHEA was due to genetic and non-shared environmental factors. In females, variance in testosterone was due to genetic and non-shared environmental factors; genetic, shared, and non-shared environmental factors contributed equally to variation in DHEA. In males, the testosterone-DHEA covariance was primarily due to shared environmental factors that overlapped with puberty as well as shared and non-shared environmental covariation specific to testosterone and DHEA. In females, the testosterone-DHEA covariance was due to genetic factors overlapping with pubertal status, and shared and non-shared environmental covariation specific to testosterone and DHEA.

  20. Genetic diversity and species diversity of stream fishes covary across a land-use gradient

    Blum, M.J.; Bagley, M.J.; Walters, D.M.; Jackson, S.A.; Daniel, F.B.; Chaloud, D.J.; Cade, B.S.

    2012-01-01

    Genetic diversity and species diversity are expected to covary according to area and isolation, but may not always covary with environmental heterogeneity. In this study, we examined how patterns of genetic and species diversity in stream fishes correspond to local and regional environmental conditions. To do so, we compared population size, genetic diversity and divergence in central stonerollers (Campostoma anomalum) to measures of species diversity and turnover in stream fish assemblages among similarly sized watersheds across an agriculture-forest land-use gradient in the Little Miami River basin (Ohio, USA). Significant correlations were found in many, but not all, pair-wise comparisons. Allelic richness and species richness were strongly correlated, for example, but diversity measures based on allele frequencies and assemblage structure were not. In-stream conditions related to agricultural land use were identified as significant predictors of genetic diversity and species diversity. Comparisons to population size indicate, however, that genetic diversity and species diversity are not necessarily independent and that variation also corresponds to watershed location and glaciation history in the drainage basin. Our findings demonstrate that genetic diversity and species diversity can covary in stream fish assemblages, and illustrate the potential importance of scaling observations to capture responses to hierarchical environmental variation. More comparisons according to life history variation could further improve understanding of conditions that give rise to parallel variation in genetic diversity and species diversity, which in turn could improve diagnosis of anthropogenic influences on aquatic ecosystems. ?? 2011 Springer-Verlag.

  1. Genetic alterations in hepatocellular carcinoma: An update

    Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Wen-Hong

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC. PMID:27895396

  2. Genetic covariance components within and among linear type traits differ among contrasting beef cattle breeds.

    Doyle, Jennifer L; Berry, Donagh P; Walsh, Siobhan W; Veerkamp, Roel F; Evans, Ross D; Carthy, Tara R

    2018-05-04

    Linear type traits describing the skeletal, muscular, and functional characteristics of an animal are routinely scored on live animals in both the dairy and beef cattle industries. Previous studies have demonstrated that genetic parameters for certain performance traits may differ between breeds; no study, however, has attempted to determine if differences exist in genetic parameters of linear type traits among breeds or sexes. Therefore, the objective of the present study was to determine if genetic covariance components for linear type traits differed among five contrasting cattle breeds, and to also investigate if these components differed by sex. A total of 18 linear type traits scored on 3,356 Angus (AA), 31,049 Charolais (CH), 3,004 Hereford (HE), 35,159 Limousin (LM), and 8,632 Simmental (SI) were used in the analysis. Data were analyzed using animal linear mixed models which included the fixed effects of sex of the animal (except in the investigation into the presence of sexual dimorphism), age at scoring, parity of the dam, and contemporary group of herd-date of scoring. Differences (P covariance parameters estimated from the CH breed with a linear function of breeding values computed conditional on covariance parameters estimated from the other breeds was estimated. Replacing the genetic covariance components estimated in the CH breed with those of the LM had least effect but the impact was considerable when the genetic covariance components of the AA were used. Genetic correlations between the same linear type traits in the two sexes were all close to unity (≥0.90) suggesting little advantage in considering these as separate traits for males and females. Results for the present study indicate the potential increase in accuracy of estimated breeding value prediction from considering, at least, the British breed traits separate to continental breed traits.

  3. The Genetic and Environmental Covariation among Psychopathic Personality Traits, and Reactive and Proactive Aggression in Childhood

    Bezdjian, Serena; Tuvblad, Catherine; Raine, Adrian; Baker, Laura A.

    2011-01-01

    The present study investigated the genetic and environmental covariance between psychopathic personality traits with reactive and proactive aggression in 9- to 10-year-old twins (N = 1,219). Psychopathic personality traits were assessed with the Child Psychopathy Scale (D. R. Lynam, 1997), while aggressive behaviors were assessed using the…

  4. Performance of penalized maximum likelihood in estimation of genetic covariances matrices

    Meyer Karin

    2011-11-01

    Full Text Available Abstract Background Estimation of genetic covariance matrices for multivariate problems comprising more than a few traits is inherently problematic, since sampling variation increases dramatically with the number of traits. This paper investigates the efficacy of regularized estimation of covariance components in a maximum likelihood framework, imposing a penalty on the likelihood designed to reduce sampling variation. In particular, penalties that "borrow strength" from the phenotypic covariance matrix are considered. Methods An extensive simulation study was carried out to investigate the reduction in average 'loss', i.e. the deviation in estimated matrices from the population values, and the accompanying bias for a range of parameter values and sample sizes. A number of penalties are examined, penalizing either the canonical eigenvalues or the genetic covariance or correlation matrices. In addition, several strategies to determine the amount of penalization to be applied, i.e. to estimate the appropriate tuning factor, are explored. Results It is shown that substantial reductions in loss for estimates of genetic covariance can be achieved for small to moderate sample sizes. While no penalty performed best overall, penalizing the variance among the estimated canonical eigenvalues on the logarithmic scale or shrinking the genetic towards the phenotypic correlation matrix appeared most advantageous. Estimating the tuning factor using cross-validation resulted in a loss reduction 10 to 15% less than that obtained if population values were known. Applying a mild penalty, chosen so that the deviation in likelihood from the maximum was non-significant, performed as well if not better than cross-validation and can be recommended as a pragmatic strategy. Conclusions Penalized maximum likelihood estimation provides the means to 'make the most' of limited and precious data and facilitates more stable estimation for multi-dimensional analyses. It should

  5. [Colorectal cancer (CCR): genetic and molecular alterations].

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  6. Identification of alterations in the Jacobian of biochemical reaction networks from steady state covariance data at two conditions.

    Kügler, Philipp; Yang, Wei

    2014-06-01

    Model building of biochemical reaction networks typically involves experiments in which changes in the behavior due to natural or experimental perturbations are observed. Computational models of reaction networks are also used in a systems biology approach to study how transitions from a healthy to a diseased state result from changes in genetic or environmental conditions. In this paper we consider the nonlinear inverse problem of inferring information about the Jacobian of a Langevin type network model from covariance data of steady state concentrations associated to two different experimental conditions. Under idealized assumptions on the Langevin fluctuation matrices we prove that relative alterations in the network Jacobian can be uniquely identified when comparing the two data sets. Based on this result and the premise that alteration is locally confined to separable parts due to network modularity we suggest a computational approach using hybrid stochastic-deterministic optimization for the detection of perturbations in the network Jacobian using the sparsity promoting effect of [Formula: see text]-penalization. Our approach is illustrated by means of published metabolomic and signaling reaction networks.

  7. Genetic alterations during radiation-induced carcinogenesis

    Kodama, Seiji

    1995-01-01

    This paper reviews radiation-induced genetic alterations and its carcinogenesis, focusing on the previous in vitro assay outcome. A colony formation assay using Syrian hamster fetal cells and focus formation assay using mouse C3H10T1/2 cells are currently available to find malignant transformation of cells. Such in vitro assays has proposed the hypothesis that radiation-induced carcinogenesis arises from at least two-stage processes; i.e., that an early step induced by irradiation plays an important role in promoting the potential to cause the subsequent mutation. A type of genetic instability induced by radiation results in a persistently elevated frequency of spontaneous mutations, so-called the phenomenon of delayed reproductive death. One possible mechanism by which genetic instability arises has been shown to be due to the development of abnormality in the gene group involved in the maintenance mechanism of genome stability. Another possibility has also been shown to stem from the loss of telomere (the extremities of a chromosome). The importance of search for radiation-induced genetic instability is emphasized in view of the elucidation of carcinogenesis. (N.K.)

  8. Evolution of the additive genetic variance–covariance matrix under continuous directional selection on a complex behavioural phenotype

    Careau, Vincent; Wolak, Matthew E.; Carter, Patrick A.; Garland, Theodore

    2015-01-01

    Given the pace at which human-induced environmental changes occur, a pressing challenge is to determine the speed with which selection can drive evolutionary change. A key determinant of adaptive response to multivariate phenotypic selection is the additive genetic variance–covariance matrix (G). Yet knowledge of G in a population experiencing new or altered selection is not sufficient to predict selection response because G itself evolves in ways that are poorly understood. We experimentally evaluated changes in G when closely related behavioural traits experience continuous directional selection. We applied the genetic covariance tensor approach to a large dataset (n = 17 328 individuals) from a replicated, 31-generation artificial selection experiment that bred mice for voluntary wheel running on days 5 and 6 of a 6-day test. Selection on this subset of G induced proportional changes across the matrix for all 6 days of running behaviour within the first four generations. The changes in G induced by selection resulted in a fourfold slower-than-predicted rate of response to selection. Thus, selection exacerbated constraints within G and limited future adaptive response, a phenomenon that could have profound consequences for populations facing rapid environmental change. PMID:26582016

  9. Evolution of the additive genetic variance-covariance matrix under continuous directional selection on a complex behavioural phenotype.

    Careau, Vincent; Wolak, Matthew E; Carter, Patrick A; Garland, Theodore

    2015-11-22

    Given the pace at which human-induced environmental changes occur, a pressing challenge is to determine the speed with which selection can drive evolutionary change. A key determinant of adaptive response to multivariate phenotypic selection is the additive genetic variance-covariance matrix ( G: ). Yet knowledge of G: in a population experiencing new or altered selection is not sufficient to predict selection response because G: itself evolves in ways that are poorly understood. We experimentally evaluated changes in G: when closely related behavioural traits experience continuous directional selection. We applied the genetic covariance tensor approach to a large dataset (n = 17 328 individuals) from a replicated, 31-generation artificial selection experiment that bred mice for voluntary wheel running on days 5 and 6 of a 6-day test. Selection on this subset of G: induced proportional changes across the matrix for all 6 days of running behaviour within the first four generations. The changes in G: induced by selection resulted in a fourfold slower-than-predicted rate of response to selection. Thus, selection exacerbated constraints within G: and limited future adaptive response, a phenomenon that could have profound consequences for populations facing rapid environmental change. © 2015 The Author(s).

  10. Analysis of stock investment selection based on CAPM using covariance and genetic algorithm approach

    Sukono; Susanti, D.; Najmia, M.; Lesmana, E.; Napitupulu, H.; Supian, S.; Putra, A. S.

    2018-03-01

    Investment is one of the economic growth factors of countries, especially in Indonesia. Stocks is a form of investment, which is liquid. In determining the stock investment decisions which need to be considered by investors is to choose stocks that can generate maximum returns with a minimum risk level. Therefore, we need to know how to allocate the capital which may give the optimal benefit. This study discusses the issue of stock investment based on CAPM which is estimated using covariance and Genetic Algorithm approach. It is assumed that the stocks analyzed follow the CAPM model. To do the estimation of beta parameter on CAPM equation is done by two approach, first is to be represented by covariance approach, and second with genetic algorithm optimization. As a numerical illustration, in this paper analyzed ten stocks traded on the capital market in Indonesia. The results of the analysis show that estimation of beta parameters using covariance and genetic algorithm approach, give the same decision, that is, six underpriced stocks with buying decision, and four overpriced stocks with a sales decision. Based on the analysis, it can be concluded that the results can be used as a consideration for investors buying six under-priced stocks, and selling four overpriced stocks.

  11. Parental Virtue and Prenatal Genetic Alteration Research.

    Tonkens, Ryan

    2015-12-01

    Although the philosophical literature on the ethics of human prenatal genetic alteration (PGA) purports to inform us about how to act, it rarely explicitly recognizes the perspective of those who will be making the PGA decision in practice. Here I approach the ethics of PGA from a distinctly virtue-based perspective, taking seriously what it means to be a good parent making this decision for one's child. From this perspective, I generate a sound verdict on the moral standing of human PGA (research): given the current state of the art, good parents have compelling reason not to consent to PGA (research) for their child, especially as part of the first wave(s) of PGA research participants and especially for non-medically oriented purposes. This is because doing otherwise is inconsistent with a plausible and defensible understanding of virtuous parenting and parental virtues, founded on a genuine concern for promoting the overall flourishing of the eventual child. In essence, given the current and foreseeable state of the art, parents who allow prenatal genetic alteration of their children are less-than-virtuous parents to those children, even in cases where they have a right to do so and even if PGA turns out to be beneficial to the eventual child.

  12. lme4qtl: linear mixed models with flexible covariance structure for genetic studies of related individuals.

    Ziyatdinov, Andrey; Vázquez-Santiago, Miquel; Brunel, Helena; Martinez-Perez, Angel; Aschard, Hugues; Soria, Jose Manuel

    2018-02-27

    Quantitative trait locus (QTL) mapping in genetic data often involves analysis of correlated observations, which need to be accounted for to avoid false association signals. This is commonly performed by modeling such correlations as random effects in linear mixed models (LMMs). The R package lme4 is a well-established tool that implements major LMM features using sparse matrix methods; however, it is not fully adapted for QTL mapping association and linkage studies. In particular, two LMM features are lacking in the base version of lme4: the definition of random effects by custom covariance matrices; and parameter constraints, which are essential in advanced QTL models. Apart from applications in linkage studies of related individuals, such functionalities are of high interest for association studies in situations where multiple covariance matrices need to be modeled, a scenario not covered by many genome-wide association study (GWAS) software. To address the aforementioned limitations, we developed a new R package lme4qtl as an extension of lme4. First, lme4qtl contributes new models for genetic studies within a single tool integrated with lme4 and its companion packages. Second, lme4qtl offers a flexible framework for scenarios with multiple levels of relatedness and becomes efficient when covariance matrices are sparse. We showed the value of our package using real family-based data in the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT2) project. Our software lme4qtl enables QTL mapping models with a versatile structure of random effects and efficient computation for sparse covariances. lme4qtl is available at https://github.com/variani/lme4qtl .

  13. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes.

    Rohde, Palle Duun; Demontis, Ditte; Cuyabano, Beatriz Castro Dias; Børglum, Anders D; Sørensen, Peter

    2016-08-01

    Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case-control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism and immunological responses, which previously have been implicated with schizophrenia based on experimental and observational studies. Copyright © 2016 by the Genetics Society of America.

  14. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes

    Rohde, Palle Duun; Demontis, Ditte; Castro Dias Cuyabano, Beatriz

    2016-01-01

    was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case–control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism......Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited...... genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT...

  15. Genetic alterations and epigenetic changes in hepatocarcinogenesis

    Luz Stella Hoyos Giraldo

    2007-02-01

    Full Text Available

    Hepatocarcinogenesis as hepatocellular carcinoma (HCC is associated with background of chronic liver disease usually in association with cirrhosis, marked hepatic fibrosis, hepatitis B virus (HBV and/or hepatitis virus (HCV infection, chronic inflammation, Aflatoxin B1(AFB1 exposure, chronic alcoholism, metabolic disorder of the liver and necroinflamatory liver disease. Hepatocarcinogenesis involve two mechanisms, genetic alterations (with changes in the cell's DNA sequence and epigenetic changes (without changes in the cell's DNA sequence, but changes in the pattern of gene expression that can persist through one or more generations (somatic sense. Hepatocarcinogenesis is associated with activation of oncogenes and decreased expression of tumor suppressor genes (TSG; include those involved in cell cycle control, apoptosis, DNA repair, immortalization and angiogenesis. AFB1 is metabolized in the liver into a potent carcinogen, aflatoxin 8, 9-epoxide, which is detoxified by epoxide hydrolase (EPHX and glutathione S-transferase M1 (GSTM1.

    A failure of detoxification processes can allow to mutagenic metabolite to bind to DNA and inducing P53 mutation. Genetic polymorphism of EPHX and GSTM1 can make individuals more susceptible to AFB1. Epigenetic inactivation of GSTP1 by promoter hypermethylation plays a role in the development of HCC because, it leads that electrophilic metabolite increase DNA damage and mutations. HBV DNA integration into the host chromosomal DNA of hepatocytes has been detected in HBV-related HCC.

    DNA tumor viruses cause cancer mainly by interfering with cell cycle controls, and activating the cell's replication machinery by blocking the action of key TSG. HBx protein is a

  16. Estimation of genetic connectedness diagnostics based on prediction errors without the prediction error variance-covariance matrix.

    Holmes, John B; Dodds, Ken G; Lee, Michael A

    2017-03-02

    An important issue in genetic evaluation is the comparability of random effects (breeding values), particularly between pairs of animals in different contemporary groups. This is usually referred to as genetic connectedness. While various measures of connectedness have been proposed in the literature, there is general agreement that the most appropriate measure is some function of the prediction error variance-covariance matrix. However, obtaining the prediction error variance-covariance matrix is computationally demanding for large-scale genetic evaluations. Many alternative statistics have been proposed that avoid the computational cost of obtaining the prediction error variance-covariance matrix, such as counts of genetic links between contemporary groups, gene flow matrices, and functions of the variance-covariance matrix of estimated contemporary group fixed effects. In this paper, we show that a correction to the variance-covariance matrix of estimated contemporary group fixed effects will produce the exact prediction error variance-covariance matrix averaged by contemporary group for univariate models in the presence of single or multiple fixed effects and one random effect. We demonstrate the correction for a series of models and show that approximations to the prediction error matrix based solely on the variance-covariance matrix of estimated contemporary group fixed effects are inappropriate in certain circumstances. Our method allows for the calculation of a connectedness measure based on the prediction error variance-covariance matrix by calculating only the variance-covariance matrix of estimated fixed effects. Since the number of fixed effects in genetic evaluation is usually orders of magnitudes smaller than the number of random effect levels, the computational requirements for our method should be reduced.

  17. Statistical power to detect genetic (covariance of complex traits using SNP data in unrelated samples.

    Peter M Visscher

    2014-04-01

    Full Text Available We have recently developed analysis methods (GREML to estimate the genetic variance of a complex trait/disease and the genetic correlation between two complex traits/diseases using genome-wide single nucleotide polymorphism (SNP data in unrelated individuals. Here we use analytical derivations and simulations to quantify the sampling variance of the estimate of the proportion of phenotypic variance captured by all SNPs for quantitative traits and case-control studies. We also derive the approximate sampling variance of the estimate of a genetic correlation in a bivariate analysis, when two complex traits are either measured on the same or different individuals. We show that the sampling variance is inversely proportional to the number of pairwise contrasts in the analysis and to the variance in SNP-derived genetic relationships. For bivariate analysis, the sampling variance of the genetic correlation additionally depends on the harmonic mean of the proportion of variance explained by the SNPs for the two traits and the genetic correlation between the traits, and depends on the phenotypic correlation when the traits are measured on the same individuals. We provide an online tool for calculating the power of detecting genetic (covariation using genome-wide SNP data. The new theory and online tool will be helpful to plan experimental designs to estimate the missing heritability that has not yet been fully revealed through genome-wide association studies, and to estimate the genetic overlap between complex traits (diseases in particular when the traits (diseases are not measured on the same samples.

  18. Dissecting high-dimensional phenotypes with bayesian sparse factor analysis of genetic covariance matrices.

    Runcie, Daniel E; Mukherjee, Sayan

    2013-07-01

    Quantitative genetic studies that model complex, multivariate phenotypes are important for both evolutionary prediction and artificial selection. For example, changes in gene expression can provide insight into developmental and physiological mechanisms that link genotype and phenotype. However, classical analytical techniques are poorly suited to quantitative genetic studies of gene expression where the number of traits assayed per individual can reach many thousand. Here, we derive a Bayesian genetic sparse factor model for estimating the genetic covariance matrix (G-matrix) of high-dimensional traits, such as gene expression, in a mixed-effects model. The key idea of our model is that we need consider only G-matrices that are biologically plausible. An organism's entire phenotype is the result of processes that are modular and have limited complexity. This implies that the G-matrix will be highly structured. In particular, we assume that a limited number of intermediate traits (or factors, e.g., variations in development or physiology) control the variation in the high-dimensional phenotype, and that each of these intermediate traits is sparse - affecting only a few observed traits. The advantages of this approach are twofold. First, sparse factors are interpretable and provide biological insight into mechanisms underlying the genetic architecture. Second, enforcing sparsity helps prevent sampling errors from swamping out the true signal in high-dimensional data. We demonstrate the advantages of our model on simulated data and in an analysis of a published Drosophila melanogaster gene expression data set.

  19. Cortical Thinning and Altered Cortico-Cortical Structural Covariance of the Default Mode Network in Patients with Persistent Insomnia Symptoms.

    Suh, Sooyeon; Kim, Hosung; Dang-Vu, Thien Thanh; Joo, Eunyeon; Shin, Chol

    2016-01-01

    Recent studies have suggested that structural abnormalities in insomnia may be linked with alterations in the default-mode network (DMN). This study compared cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia (PI) and good sleepers (GS). The current study used a clinical subsample from the longitudinal community-based Korean Genome and Epidemiology Study (KoGES). Cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia symptoms (PIS; n = 57) were compared to good sleepers (GS; n = 40). All participants underwent MRI acquisition. Based on literature review, we selected cortical regions corresponding to the DMN. A seed-based structural covariance analysis measured cortical thickness correlation between each seed region of the DMN and other cortical areas. Association of cortical thickness and covariance with sleep quality and neuropsychological assessments were further assessed. Compared to GS, cortical thinning was found in PIS in the anterior cingulate cortex, precentral cortex, and lateral prefrontal cortex. Decreased structural connectivity between anterior and posterior regions of the DMN was observed in the PIS group. Decreased structural covariance within the DMN was associated with higher PSQI scores. Cortical thinning in the lateral frontal lobe was related to poor performance in executive function in PIS. Disrupted structural covariance network in PIS might reflect malfunctioning of antero-posterior disconnection of the DMN during the wake to sleep transition that is commonly found during normal sleep. The observed structural network alteration may further implicate commonly observed sustained sleep difficulties and cognitive impairment in insomnia. © 2016 Associated Professional Sleep Societies, LLC.

  20. Estimating genetic covariance functions assuming a parametric correlation structure for environmental effects

    Meyer Karin

    2001-11-01

    Full Text Available Abstract A random regression model for the analysis of "repeated" records in animal breeding is described which combines a random regression approach for additive genetic and other random effects with the assumption of a parametric correlation structure for within animal covariances. Both stationary and non-stationary correlation models involving a small number of parameters are considered. Heterogeneity in within animal variances is modelled through polynomial variance functions. Estimation of parameters describing the dispersion structure of such model by restricted maximum likelihood via an "average information" algorithm is outlined. An application to mature weight records of beef cow is given, and results are contrasted to those from analyses fitting sets of random regression coefficients for permanent environmental effects.

  1. Genetic Alterations in Pesticide Exposed Bolivian Farmers

    Jørs, Erik; González, Ana Rosa; Ascarrunz, Maria Eugenia

    2007-01-01

    : Questionnaires were applied and blood tests taken from 81 volunteers from La Paz County, of whom 48 were pesticide exposed farmers and 33 non-exposed controls. Sixty males and 21 females participated with a mean age of 37.3 years (range 17-76). Data of exposure and possible genetic damage were collected...... and evaluated by well known statistical methods, controlling for relevant confounders. To measure genetic damage chromosomal aberrations and the comet assay analysis were performed. Results: Pesticide exposed farmers had a higher degree of genetic damage compared to the control group. The number of chromosomal......, probably related to exposure to pesticides. Due to the potentially negative long term health effects of genetic damage on reproduction and the development of cancer, preventive measures are recommended. Effective control with imports and sales, banning of the most toxic pesticides, education...

  2. Genetic and phenotypic variance and covariance components for methane emission and postweaning traits in Angus cattle.

    Donoghue, K A; Bird-Gardiner, T; Arthur, P F; Herd, R M; Hegarty, R F

    2016-04-01

    Ruminants contribute 80% of the global livestock greenhouse gas (GHG) emissions mainly through the production of methane, a byproduct of enteric microbial fermentation primarily in the rumen. Hence, reducing enteric methane production is essential in any GHG emissions reduction strategy in livestock. Data on 1,046 young bulls and heifers from 2 performance-recording research herds of Angus cattle were analyzed to provide genetic and phenotypic variance and covariance estimates for methane emissions and production traits and to examine the interrelationships among these traits. The cattle were fed a roughage diet at 1.2 times their estimated maintenance energy requirements and measured for methane production rate (MPR) in open circuit respiration chambers for 48 h. Traits studied included DMI during the methane measurement period, MPR, and methane yield (MY; MPR/DMI), with means of 6.1 kg/d (SD 1.3), 132 g/d (SD 25), and 22.0 g/kg (SD 2.3) DMI, respectively. Four forms of residual methane production (RMP), which is a measure of actual minus predicted MPR, were evaluated. For the first 3 forms, predicted MPR was calculated using published equations. For the fourth (RMP), predicted MPR was obtained by regression of MPR on DMI. Growth and body composition traits evaluated were birth weight (BWT), weaning weight (WWT), yearling weight (YWT), final weight (FWT), and ultrasound measures of eye muscle area, rump fat depth, rib fat depth, and intramuscular fat. Heritability estimates were moderate for MPR (0.27 [SE 0.07]), MY (0.22 [SE 0.06]), and the RMP traits (0.19 [SE 0.06] for each), indicating that genetic improvement to reduce methane emissions is possible. The RMP traits and MY were strongly genetically correlated with each other (0.99 ± 0.01). The genetic correlation of MPR with MY as well as with the RMP traits was moderate (0.32 to 0.63). The genetic correlation between MPR and the growth traits (except BWT) was strong (0.79 to 0.86). These results indicate that

  3. Genetic alterations in syndromes with oral manifestations

    Krishnamurthy Anuthama

    2013-01-01

    Full Text Available Ever since Gregor Johan Mendel proposed the law of inheritance, genetics has transcended the field of health and has entered all walks of life in its application. Thus, the gene is the pivoting factor for all happenings revolving around it. Knowledge of gene mapping in various diseases would be a valuable tool in prenatally diagnosing the condition and averting the future disability and stigma for the posterity. This article includes an array of genetically determined conditions in patients seen at our college out-patient department with complete manifestation, partial manifestation and array of manifestations not fitting into a particular syndrome.

  4. The genetic variance but not the genetic covariance of life-history traits changes towards the north in a time-constrained insect.

    Sniegula, Szymon; Golab, Maria J; Drobniak, Szymon M; Johansson, Frank

    2018-03-22

    Seasonal time constraints are usually stronger at higher than lower latitudes and can exert strong selection on life-history traits and the correlations among these traits. To predict the response of life-history traits to environmental change along a latitudinal gradient, information must be obtained about genetic variance in traits and also genetic correlation between traits, that is the genetic variance-covariance matrix, G. Here, we estimated G for key life-history traits in an obligate univoltine damselfly that faces seasonal time constraints. We exposed populations to simulated native temperatures and photoperiods and common garden environmental conditions in a laboratory set-up. Despite differences in genetic variance in these traits between populations (lower variance at northern latitudes), there was no evidence for latitude-specific covariance of the life-history traits. At simulated native conditions, all populations showed strong genetic and phenotypic correlations between traits that shaped growth and development. The variance-covariance matrix changed considerably when populations were exposed to common garden conditions compared with the simulated natural conditions, showing the importance of environmentally induced changes in multivariate genetic structure. Our results highlight the importance of estimating variance-covariance matrixes in environments that mimic selection pressures and not only trait variances or mean trait values in common garden conditions for understanding the trait evolution across populations and environments. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

  5. Segmenting by Risk Perceptions: Predicting Young Adults’ Genetic-Belief Profiles with Health and Opinion-Leader Covariates

    Smith, Rachel A.; Greenberg, Marisa; Parrott, Roxanne L.

    2014-01-01

    With a growing interest in using genetic information to motivate young adults’ health behaviors, audience segmentation is needed for effective campaign design. Using latent class analysis, this study identifies segments based on young adults’ (N = 327) beliefs about genetic threats to their health and personal efficacy over genetic influences on their health. A four-class model was identified. The model indicators fit the risk perception attitude framework (Rimal & Real, 2003), but the covariates (e.g., current health behaviors) did not. In addition, opinion leader qualities covaried with one profile: those in this profile engaged in fewer preventative behaviors and more dangerous treatment options, and also liked to persuade others, making them a particularly salient group for campaign efforts. The implications for adult-onset disorders, like alpha-1 antitrypsin deficiency are discussed. PMID:24111749

  6. The covariance between genetic and environmental influences across ecological gradients: reassessing the evolutionary significance of countergradient and cogradient variation.

    Conover, David O; Duffy, Tara A; Hice, Lyndie A

    2009-06-01

    Patterns of phenotypic change across environmental gradients (e.g., latitude, altitude) have long captivated the interest of evolutionary ecologists. The pattern and magnitude of phenotypic change is determined by the covariance between genetic and environmental influences across a gradient. Cogradient variation (CoGV) occurs when covariance is positive: that is, genetic and environmental influences on phenotypic expression are aligned and their joint influence accentuates the change in mean trait value across the gradient. Conversely, countergradient variation (CnGV) occurs when covariance is negative: that is, genetic and environmental influences on phenotypes oppose one another, thereby diminishing the change in mean trait expression across the gradient. CnGV has so far been found in at least 60 species, with most examples coming from fishes, amphibians, and insects across latitudinal or altitudinal gradients. Traits that display CnGV most often involve metabolic compensation, that is, the elevation of various physiological rates processes (development, growth, feeding, metabolism, activity) to counteract the dampening effect of reduced temperature, growing season length, or food supply. Far fewer examples of CoGV have been identified (11 species), and these most often involve morphological characters. Increased knowledge of spatial covariance patterns has furthered our understanding of Bergmann size clines, phenotypic plasticity, species range limits, tradeoffs in juvenile growth rate, and the design of conservation strategies for wild species. Moreover, temporal CnGV explains some cases of an apparent lack of phenotypic response to directional selection and provides a framework for predicting evolutionary responses to climate change.

  7. Distinct genetic alterations in colorectal cancer.

    Hassan Ashktorab

    Full Text Available BACKGROUND: Colon cancer (CRC development often includes chromosomal instability (CIN leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities. METHODOLOGY/PRINCIPAL FINDINGS: We applied genome-wide array comparative genome hybridization (aCGH using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes. There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations. CONCLUSIONS/SIGNIFICANCE: Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs.

  8. Genetic Alterations in Intervertebral Disc Disease

    Nikolay L. Martirosyan

    2016-11-01

    Full Text Available Background: Intervertebral disc degeneration (IVDD is considered a multifactorial disease. The last two decades of research strongly demonstrate that genetic factors contribute about 75% of the IVDD etiology. Recent total genome sequencing studies have shed light on the various single nucleotide polymorphisms (SNPs that are associated with IVDD.Aim: This review explores and presents updated information about the diversity of genetic factors in the inflammatory, degradative, homeostatic, and structural systems involved in the IVDD.Results: SNPs in the genes coding for structural proteins linked with IVDD or disc bulging include the Sp1 polymorphism of COL1A1, Trp3 polymorphism of COL9A3, several polymorphisms of COL11A1 and COL11A2, and a variable number tandem repeat polymorphism of ACAN. The rs4148941 SNP of CHST3 coding for an aggrecan sulfation enzyme is also associated with IVDD. The FokI, TaqI, and ApaI SNPs of the vitamin D receptor gene that is involved in chondrocyte functioning are also associated with IVDD. SNPs relevant to cytokine imbalance in IVDD include 889C/T of IL1a and 15T/A, as well as other SNPs (rs1800795, rs1800796, and rs1800797, of IL6, with effects limited to certain genders and populations. SNPs in collagenase genes include -1605G/D (guanine insertion/deletion of MMP1, -1306C/T of MMP2, -1562C/T and a 5-adenosine (5A variant (in the promotor region of MMP3, -1562C/T of MMP9, and -378T/C of MMP-14. SNPs in aggrecanase genes include 1877T/U of ADAMTS-4 and rs162509 of ADAMTS-5. Among the apoptosis-mediating genes, 1595T/C of the caspase 9 gene, 1525A/G and 1595T/C of the TRAIL gene, and 626C/G of the death receptor 4 gene (DR4 are SNPs associated with IVDD. Among the growth factors involved in disc homeostasis, the rs4871857 SNP of GDF5 was associated with IVDD. VEGF SNPs -2578C/A and -634G/C could foster neovascularization observed in IVDD.Conclusion: Improved understanding of the numerous genetic variants behind various

  9. Simultaneous genetic analysis of longitudinal means and covariance structure in the simplex model using twin data

    Dolan, C.V.; Molenaar, P.C.M.; Boomsma, D.I.

    1991-01-01

    D. Soerbom's (1974, 1976) simplex model approach to simultaneous analysis of means and covariance structure was applied to analysis of means observed in a single group. The present approach to the simultaneous biometric analysis of covariance and mean structure is based on the testable assumption

  10. The genetic alteration of p53 in esophageal cancer

    Cho, Jae Il; Baik, Hee Jong; Kim, Chang Min; Kim, Mi Hee [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1996-01-01

    Genetic alterations in the p53 gene have been detected in various human malignancies, and its alterations inactive the function of p53 as a tumor suppressor. Point mutation and gene deletion are the main mechanisms of p53 inactivation. To determine the incidence of genetic alteration of p53 and their clinical implications in Korean patients of esophageal cancer, we investigated p53 alterations in 26 esophageal cancer tissues paired with its normal tissue by Southern blot analysis, PCR-SSCP, and direct sequencing. Allelic loss of chromosome 17p occurred in 12 out of 21 informative cases(57%) by Southern blot analysis, and 16 cases showed mobility shift in PCR-SSCP, so overall incidence of p53 gene alterations was 77%(20/26). The mutations detected was randomly dispersed over exon4-8 and was frequently G-T transversion and C:T transitions. Three identical mutations were clustered at codon 213 suggested the same etiologic agents in this cases. The p53 gene alterations play a significant role in the development of esophageal cancers, however, no relationship between p53 mutation and clinical data was detected so far. 9 refs. (Author).

  11. A Common Genetic Factor Explains the Covariation among ADHD ODD and CD Symptoms in 9-10 Year Old Boys and Girls

    Tuvblad, Catherine; Zheng, Mo; Raine, Adrian; Baker, Laura A.

    2009-01-01

    Previous studies examining the covariation among Attention Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) have yielded inconsistent results. Some studies have concluded that the covariation among these symptoms is due to common genetic influences, whereas others have found a common…

  12. Genetic alterations in head and neck squamous cell carcinomas

    Nagai M.A.

    1999-01-01

    Full Text Available The genetic alterations observed in head and neck cancer are mainly due to oncogene activation (gain of function mutations and tumor suppressor gene inactivation (loss of function mutations, leading to deregulation of cell proliferation and death. These genetic alterations include gene amplification and overexpression of oncogenes such as myc, erbB-2, EGFR and cyclinD1 and mutations, deletions and hypermethylation leading to p16 and TP53 tumor suppressor gene inactivation. In addition, loss of heterozygosity in several chromosomal regions is frequently observed, suggesting that other tumor suppressor genes not yet identified could be involved in the tumorigenic process of head and neck cancers. The exact temporal sequence of the genetic alterations during head and neck squamous cell carcinoma (HNSCC development and progression has not yet been defined and their diagnostic or prognostic significance is controversial. Advances in the understanding of the molecular basis of head and neck cancer should help in the identification of new markers that could be used for the diagnosis, prognosis and treatment of the disease.

  13. The genetic alteration of retinoblastoma gene in esophageal cancer

    Cho, Jae Il; Shim, Yung Mok; Kim, Chang Min

    1994-12-01

    Retinoblastoma(RB) gene is the prototype of tumor suppressor gene and it's alteration have been frequently observed in a large number of human tumors. To investigate the role of RB in esophageal cancer, we studied 36 esophageal cancer tissues with Southern blot analysis to detect gross LOH and PCR-SSCP method to find minute LOH and mutation, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. Allelic loss of chromosome 13q14 occurred in 20 out of 32 informative cases (62.5%) by Southern analysis. Furthermore, PCR-LOH added three positive cases. Mobility shift by PCR-SSCP was observed in one case at exon 22, which showed 1 bp deletion in codon 771 of RB gene resulting in frame shift mutation. Besides, nine PCR-band alteration in tumor tissue compared with normal tissue were observed in exon 14 and 22, but mutation was not found on sequencing analysis suggesting the epigenetic alteration in tumor tissue. Analysis of the clinical data did not show any difference depending upon RB alteration. However, the total incidence of RB gene may play an important role in the development of esophageal cancer. The main genetic alteration of RB gene was deletion detected by Southern blot and one bp deletion leading to frame shift was also observed. 8 figs, 5 tabs. (Author)

  14. The genetic alteration of retinoblastoma gene in esophageal cancer

    Cho, Jae Il; Shim, Yung Mok; Kim, Chang Min [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1994-12-01

    Retinoblastoma(RB) gene is the prototype of tumor suppressor gene and it`s alteration have been frequently observed in a large number of human tumors. To investigate the role of RB in esophageal cancer, we studied 36 esophageal cancer tissues with Southern blot analysis to detect gross LOH and PCR-SSCP method to find minute LOH and mutation, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. Allelic loss of chromosome 13q14 occurred in 20 out of 32 informative cases (62.5%) by Southern analysis. Furthermore, PCR-LOH added three positive cases. Mobility shift by PCR-SSCP was observed in one case at exon 22, which showed 1 bp deletion in codon 771 of RB gene resulting in frame shift mutation. Besides, nine PCR-band alteration in tumor tissue compared with normal tissue were observed in exon 14 and 22, but mutation was not found on sequencing analysis suggesting the epigenetic alteration in tumor tissue. Analysis of the clinical data did not show any difference depending upon RB alteration. However, the total incidence of RB gene may play an important role in the development of esophageal cancer. The main genetic alteration of RB gene was deletion detected by Southern blot and one bp deletion leading to frame shift was also observed. 8 figs, 5 tabs. (Author).

  15. Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer.

    Tobiás, Bálint; Halászlaki, Csaba; Balla, Bernadett; Kósa, János P; Árvai, Kristóf; Horváth, Péter; Takács, István; Nagy, Zsolt; Horváth, Evelin; Horányi, János; Járay, Balázs; Székely, Eszter; Székely, Tamás; Győri, Gabriella; Putz, Zsuzsanna; Dank, Magdolna; Valkusz, Zsuzsanna; Vasas, Béla; Iványi, Béla; Lakatos, Péter

    2016-01-01

    The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2%), 5 NRAS (3.1%), 2 HRAS (1.0%) and 1 KRAS (0.5%) mutations were found, as well as 9 RET/PTC1 (4.6%) and 1 RET/PTC3 (0.5%) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature.

  16. Genetic covariance functioners for live weight, condition score, and dry-matter intake measured at different lactations stages of Holstein-Friesian heifers

    Koenen, E.P.C.; Veerkamp, R.F.

    1998-01-01

    Genetic parameters for live weight, body condition score and dry-matter intake of dairy heifers were estimated using covariance function methodology. Data were from 469 heifers of the Langhill Dairy Cattle Research Centre and included observations during the first 25 weeks in lactation. Genetic

  17. Bayesian analysis of multi-state data with individual covariates for estimating genetic effects on demography

    Converse, Sarah J.; Royle, J. Andrew; Urbanek, Richard P.

    2012-01-01

    Inbreeding depression is frequently a concern of managers interested in restoring endangered species. Decisions to reduce the potential for inbreeding depression by balancing genotypic contributions to reintroduced populations may exact a cost on long-term demographic performance of the population if those decisions result in reduced numbers of animals released and/or restriction of particularly successful genotypes (i.e., heritable traits of particular family lines). As part of an effort to restore a migratory flock of Whooping Cranes (Grus americana) to eastern North America using the offspring of captive breeders, we obtained a unique dataset which includes post-release mark-recapture data, as well as the pedigree of each released individual. We developed a Bayesian formulation of a multi-state model to analyze radio-telemetry, band-resight, and dead recovery data on reintroduced individuals, in order to track survival and breeding state transitions. We used studbook-based individual covariates to examine the comparative evidence for and degree of effects of inbreeding, genotype, and genotype quality on post-release survival of reintroduced individuals. We demonstrate implementation of the Bayesian multi-state model, which allows for the integration of imperfect detection, multiple data types, random effects, and individual- and time-dependent covariates. Our results provide only weak evidence for an effect of the quality of an individual's genotype in captivity on post-release survival as well as for an effect of inbreeding on post-release survival. We plan to integrate our results into a decision-analytic modeling framework that can explicitly examine tradeoffs between the effects of inbreeding and the effects of genotype and demographic stochasticity on population establishment.

  18. Genetic and environmental sources of covariation between early drinking and adult functioning.

    Waldron, Jordan Sparks; Malone, Stephen M; McGue, Matt; Iacono, William G

    2017-08-01

    The vast majority of individuals initiate alcohol consumption for the first time in adolescence. Given the widespread nature of its use and evidence that adolescents may be especially vulnerable to its effects, there is concern about the long-term detrimental impact of adolescent drinking on adult functioning. While some researchers have suggested that genetic processes may confound the relationship, the mechanisms linking drinking and later adjustment remain unclear. The current study utilized a genetically informed sample and biometric modeling to examine the nature of the familial influences on this association and identify the potential for genetic confounding. The sample was drawn from the Minnesota Twin Family Study (MTFS), a longitudinal study consisting of 2,764 twins assessed in 2 cohorts at regular follow-ups from age 17 to age 29 (older cohort) or age 11 to age 29 (younger cohort). A broad range of adult measures was included assessing substance use, antisocial behavior, personality, socioeconomic status, and social functioning. A bivariate Cholesky decomposition was used to examine the common genetic and environmental influences on adolescent drinking and each of the measures of adult adjustment. The results revealed that genetic factors and nonshared environmental influences were generally most important in explaining the relationship between adolescent drinking and later functioning. While the presence of nonshared environmental influences on the association are not inconsistent with a causal impact of adolescent drinking, the findings suggest that many of the adjustment issues associated with adolescent alcohol consumption are best understood as genetically influenced vulnerabilities. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. The genetic architecture of shoot-root covariation during seedling emergence of a desert tree, Populus euphratica.

    Zhang, Miaomiao; Bo, Wenhao; Xu, Fang; Li, Huan; Ye, Meixia; Jiang, Libo; Shi, Chaozhong; Fu, Yaru; Zhao, Guomiao; Huang, Yuejiao; Gosik, Kirk; Liang, Dan; Wu, Rongling

    2017-06-01

    The coordination of shoots and roots is critical for plants to adapt to changing environments by fine-tuning energy production in leaves and the availability of water and nutrients from roots. To understand the genetic architecture of how these two organs covary during developmental ontogeny, we conducted a mapping experiment using Euphrates poplar (Populus euphratica), a so-called hero tree able to grow in the desert. We geminated intraspecific F 1 seeds of Euphrates Poplar individually in a tube to obtain a total of 370 seedlings, whose shoot and taproot lengths were measured repeatedly during the early stage of growth. By fitting a growth equation, we estimated asymptotic growth, relative growth rate, the timing of inflection point and duration of linear growth for both shoot and taproot growth. Treating these heterochronic parameters as phenotypes, a univariate mapping model detected 19 heterochronic quantitative trait loci (hQTLs), of which 15 mediate the forms of shoot growth and four mediate taproot growth. A bivariate mapping model identified 11 pleiotropic hQTLs that determine the covariation of shoot and taproot growth. Most QTLs detected reside within the region of candidate genes with various functions, thus confirming their roles in the biochemical processes underlying plant growth. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  20. Genetic alterations in B-cell non-Hodgkin's lymphoma

    Magić Zvonko

    2005-01-01

    Full Text Available Background. Although the patients with diagnosed B-NHL are classified into the same disease stage on the basis of clinical, histopathological, and immunological parameters, they respond significantly different to the applied treatment. This points out the possibility that within the same group of lymphoma there are different diseases at molecular level. For that reason many studies deal with the detection of gene alterations in lymphomas to provide a better framework for diagnosis and treatment of these hematological malignancies. Aim. To define genetic alterations in the B-NHL with highest possibilities for diagnostic purposes and molecular detection of MRD. Methods. Formalin fixed and paraffin embedded lymph node tissues from 45 patients were examined by different PCR techniques for the presence of IgH and TCR γ gene rearrangement; K-ras and H-ras mutations; c-myc amplification and bcl-2 translocation. There were 34 cases of B-cell non-Hodgkin’s lymphoma (B-NHL, 5 cases of T-cell non-Hodgkin’s lymphoma (T-NHL and 6 cases of chronic lymphadenitis (CL. The mononuclear cell fraction of the peripheral blood of 12 patients with B-NHL was analyzed for the presence of monoclonality at the time of diagnosis and in 3 to 6 months time intervals after an autologous bone marrow transplantation (BMT. Results. The monoclonality of B-lymphocytes, as evidenced by DNA fragment length homogeneity, was detected in 88 % (30/34 of B-NHL, but never in CL, T-NHL, or in normal PBL. Bcl-2 translocation was detected in 7/31 (22.6% B-NHL specimens, c-myc amplification 9/31 (29%, all were more than doubled, K-ras mutations in 1/31 (3.23% and H-ras mutations in 2/31 (6.45% of the examined B-NHL samples. In the case of LC and normal PBL, however, these gene alterations were not detected. All the patients (12 with B-NHL had dominant clone of B-lymphocyte in the peripheral blood at the time of diagnosis while only in 2 of 12 patients MRD was detected 3 or 6 months after

  1. Mating animals by minimising the covariance between ancestral contributions generates less inbreeding without compromising genetic gain in breeding schemes with truncation selection

    Henryon, M; Berg, P; Sørensen, A C

    2009-01-01

    We reasoned that mating animals by minimising the covariance between ancestral contributions (MCAC mating) will generate less inbreeding and at least as much genetic gain as minimum-coancestry mating in breeding schemes where the animals are truncation-selected. We tested this hypothesis by stoch...

  2. Genetic and environmental variance and covariance parameters for some reproductive traits of Holstein and Jersey cattle in Antioquia (Colombia

    Juan Carlos Zambrano

    2014-03-01

    Full Text Available The objective of this study was to estimate the genetic, phenotypic and environmental parameters for calving interval (CI, days open (DO, number of services per conception (NSC and conception rate (CR in Holstein and Jersey cattle in Antioquia (Colombia. Variance and covariance component estimates were obtained by an animal model that was solved using the derivative-free restricted maximum likelihood method. The means and standard deviations for CI, DO, NSC and CR were: 430.32±77.93 days, 127.15±76.96 days, 1.58±1.03 services per conception and 79.88±28.66% in Holstein cattle, and 409.33±86.48 days, 125.62±86.09 days, 1.48±0.98 services per conception and 84.08±27.23% in Jersey cattle, respectively. The heritability estimates (standard errors were: 0.088(0.037, 0.082(0.037, 0.040(0.025 and 0.030(0.026 in Holstein cattle and 0.072(0.098, 0.090(0.104, 0.093(0.097 and 0.147(0.117 in Jersey cattle, respectively. The results show that the genetic, phenotypic and permanent environmental correlations in the two evaluated breeds were favorable for CI × DO, CI × NSC and DO × NSC, but not for CI × CR, DO × CR and NSC × CR. Genetic and permanent environmental correlations were high in most cases in Holstein cattle, whereas in Jersey cattle they were moderate. In contrast, phenotypic correlations were very low in both breeds, except for CI × DO and NSC × CR, which were high. Overall, the genetic component found was very low (<8% in both evaluated breeds and this implies that their selection would take long time and that a good practical management of the herd will be essential in order to improve the reproductive performance.

  3. Assessing fluctuating evolutionary pressure in yeast and mammal evolutionary rate covariation using bioinformatics of meiotic protein genetic sequences

    Dehipawala, Sunil; Nguyen, A.; Tremberger, G.; Cheung, E.; Holden, T.; Lieberman, D.; Cheung, T.

    2013-09-01

    The evolutionary rate co-variation in meiotic proteins has been reported for yeast and mammal using phylogenic branch lengths which assess retention, duplication and mutation. The bioinformatics of the corresponding DNA sequences could be classified as a diagram of fractal dimension and Shannon entropy. Results from biomedical gene research provide examples on the diagram methodology. The identification of adaptive selection using entropy marker and functional-structural diversity using fractal dimension would support a regression analysis where the coefficient of determination would serve as evolutionary pathway marker for DNA sequences and be an important component in the astrobiology community. Comparisons between biomedical genes such as EEF2 (elongation factor 2 human, mouse, etc), WDR85 in epigenetics, HAR1 in human specificity, clinical trial targeted cancer gene CD47, SIRT6 in spermatogenesis, and HLA-C in mosquito bite immunology demonstrate the diagram classification methodology. Comparisons to the SEPT4-XIAP pair in stem cell apoptosis, testesexpressed taste genes TAS1R3-GNAT3 pair, and amyloid beta APLP1-APLP2 pair with the yeast-mammal DNA sequences for meiotic proteins RAD50-MRE11 pair and NCAPD2-ICK pair have accounted for the observed fluctuating evolutionary pressure systematically. Regression with high R-sq values or a triangular-like cluster pattern for concordant pairs in co-variation among the studied species could serve as evidences for the possible location of common ancestors in the entropy-fractal dimension diagram, consistent with an example of the human-chimp common ancestor study using the FOXP2 regulated genes reported in human fetal brain study. The Deinococcus radiodurans R1 Rad-A could be viewed as an outlier in the RAD50 diagram and also in the free energy versus fractal dimension regression Cook's distance, consistent with a non-Earth source for this radiation resistant bacterium. Convergent and divergent fluctuating evolutionary

  4. DNA Fingerprinting Techniques for the Analysis of Genetic and Epigenetic Alterations in Colorectal Cancer

    Samuelsson, Johanna K.; Alonso, Sergio; Yamamoto, Fumiichiro; Perucho, Manuel

    2010-01-01

    Genetic somatic alterations are fundamental hallmarks of cancer. In addition to point and other small mutations targeting cancer genes, solid tumors often exhibit aneuploidy as well as multiple chromosomal rearrangements of large fragments of the genome. Whether somatic chromosomal alterations and aneuploidy are a driving force or a mere consequence of tumorigenesis remains controversial. Recently it became apparent that not only genetic but also epigenetic alterations play a major role in ca...

  5. An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

    Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

    2016-12-01

    Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

  6. A genetic code alteration is a phenotype diversity generator in the human pathogen Candida albicans.

    Isabel Miranda

    Full Text Available BACKGROUND: The discovery of genetic code alterations and expansions in both prokaryotes and eukaryotes abolished the hypothesis of a frozen and universal genetic code and exposed unanticipated flexibility in codon and amino acid assignments. It is now clear that codon identity alterations involve sense and non-sense codons and can occur in organisms with complex genomes and proteomes. However, the biological functions, the molecular mechanisms of evolution and the diversity of genetic code alterations remain largely unknown. In various species of the genus Candida, the leucine CUG codon is decoded as serine by a unique serine tRNA that contains a leucine 5'-CAG-3'anticodon (tRNA(CAG(Ser. We are using this codon identity redefinition as a model system to elucidate the evolution of genetic code alterations. METHODOLOGY/PRINCIPAL FINDINGS: We have reconstructed the early stages of the Candida genetic code alteration by engineering tRNAs that partially reverted the identity of serine CUG codons back to their standard leucine meaning. Such genetic code manipulation had profound cellular consequences as it exposed important morphological variation, altered gene expression, re-arranged the karyotype, increased cell-cell adhesion and secretion of hydrolytic enzymes. CONCLUSION/SIGNIFICANCE: Our study provides the first experimental evidence for an important role of genetic code alterations as generators of phenotypic diversity of high selective potential and supports the hypothesis that they speed up evolution of new phenotypes.

  7. Covariant Transform

    Kisil, Vladimir V.

    2010-01-01

    The paper develops theory of covariant transform, which is inspired by the wavelet construction. It was observed that many interesting types of wavelets (or coherent states) arise from group representations which are not square integrable or vacuum vectors which are not admissible. Covariant transform extends an applicability of the popular wavelets construction to classic examples like the Hardy space H_2, Banach spaces, covariant functional calculus and many others. Keywords: Wavelets, cohe...

  8. Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer.

    Lee, Min-Young; Ku, Bo Mi; Kim, Hae Su; Lee, Ji Yun; Lim, Sung Hee; Sun, Jong-Mu; Lee, Se-Hoon; Park, Keunchil; Oh, Young Lyun; Hong, Mineui; Jeong, Han-Sin; Son, Young-Ik; Baek, Chung-Hwan; Ahn, Myung-Ju

    2017-10-01

    Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group. Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString's nCounter technology and mutational analysis was performed by direct DNA sequencing. Data describing the clinicopathological characteristics and clinical courses were retrospectively collected. Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations. In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.

  9. [Algorithm of toxigenic genetically altered Vibrio cholerae El Tor biovar strain identification].

    Smirnova, N I; Agafonov, D A; Zadnova, S P; Cherkasov, A V; Kutyrev, V V

    2014-01-01

    Development of an algorithm of genetically altered Vibrio cholerae biovar El Tor strai identification that ensures determination of serogroup, serovar and biovar of the studied isolate based on pheno- and genotypic properties, detection of genetically altered cholera El Tor causative agents, their differentiation by epidemic potential as well as evaluation of variability of key pathogenicity genes. Complex analysis of 28 natural V. cholerae strains was carried out by using traditional microbiological methods, PCR and fragmentary sequencing. An algorithm of toxigenic genetically altered V. cholerae biovar El Tor strain identification was developed that includes 4 stages: determination of serogroup, serovar and biovar based on phenotypic properties, confirmation of serogroup and biovar based on molecular-genetic properties determination of strains as genetically altered, differentiation of genetically altered strains by their epidemic potential and detection of ctxB and tcpA key pathogenicity gene polymorphism. The algorithm is based on the use of traditional microbiological methods, PCR and sequencing of gene fragments. The use of the developed algorithm will increase the effectiveness of detection of genetically altered variants of the cholera El Tor causative agent, their differentiation by epidemic potential and will ensure establishment of polymorphism of genes that code key pathogenicity factors for determination of origins of the strains and possible routes of introduction of the infection.

  10. Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease.

    Chang, Yu-Tzu; Hsu, Shih-Wei; Tsai, Shih-Jen; Chang, Ya-Ting; Huang, Chi-Wei; Liu, Mu-En; Chen, Nai-Ching; Chang, Wen-Neng; Hsu, Jung-Lung; Lee, Chen-Chang; Chang, Chiung-Chih

    2017-06-01

    The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.

  11. Low Genetic Quality Alters Key Dimensions of the Mutational Spectrum.

    Nathaniel P Sharp

    2016-03-01

    Full Text Available Mutations affect individual health, population persistence, adaptation, diversification, and genome evolution. There is evidence that the mutation rate varies among genotypes, but the causes of this variation are poorly understood. Here, we link differences in genetic quality with variation in spontaneous mutation in a Drosophila mutation accumulation experiment. We find that chromosomes maintained in low-quality genetic backgrounds experience a higher rate of indel mutation and a lower rate of gene conversion in a manner consistent with condition-based differences in the mechanisms used to repair DNA double strand breaks. These aspects of the mutational spectrum were also associated with body mass, suggesting that the effect of genetic quality on DNA repair was mediated by overall condition, and providing a mechanistic explanation for the differences in mutational fitness decline among these genotypes. The rate and spectrum of substitutions was unaffected by genetic quality, but we find variation in the probability of substitutions and indels with respect to several aspects of local sequence context, particularly GC content, with implications for models of molecular evolution and genome scans for signs of selection. Our finding that the chances of mutation depend on genetic context and overall condition has important implications for how sequences evolve, the risk of extinction, and human health.

  12. Somatic retrotransposition alters the genetic landscape of the human brain

    Baillie, J.K.; Barnett, M.W.; Upton, K.R.; Gerhardt, D.J.; Richmond, T.A.; De Sapio, F.; Brennan, P.; Rizzu, P.; Smith, S.; Fell, M.; Talbot, R.T.; Gustincich, S.; Freeman, T.C.; Mattick, J.S.; Hume, D.A.; Heutink, P.; Carninci, P.; Jeddeloh, J.A.; Faulkner, G.J.

    2011-01-01

    Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes1. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and

  13. Critical roles for a genetic code alteration in the evolution of the genus Candida.

    Silva, Raquel M; Paredes, João A; Moura, Gabriela R; Manadas, Bruno; Lima-Costa, Tatiana; Rocha, Rita; Miranda, Isabel; Gomes, Ana C; Koerkamp, Marian J G; Perrot, Michel; Holstege, Frank C P; Boucherie, Hélian; Santos, Manuel A S

    2007-10-31

    During the last 30 years, several alterations to the standard genetic code have been discovered in various bacterial and eukaryotic species. Sense and nonsense codons have been reassigned or reprogrammed to expand the genetic code to selenocysteine and pyrrolysine. These discoveries highlight unexpected flexibility in the genetic code, but do not elucidate how the organisms survived the proteome chaos generated by codon identity redefinition. In order to shed new light on this question, we have reconstructed a Candida genetic code alteration in Saccharomyces cerevisiae and used a combination of DNA microarrays, proteomics and genetics approaches to evaluate its impact on gene expression, adaptation and sexual reproduction. This genetic manipulation blocked mating, locked yeast in a diploid state, remodelled gene expression and created stress cross-protection that generated adaptive advantages under environmental challenging conditions. This study highlights unanticipated roles for codon identity redefinition during the evolution of the genus Candida, and strongly suggests that genetic code alterations create genetic barriers that speed up speciation.

  14. Genetic alterations affecting cholesterol metabolism and human fertility.

    DeAngelis, Anthony M; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

    2014-11-01

    Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. © 2014 by the Society for the Study of Reproduction, Inc.

  15. Genetic Alterations in Gastric Cancer Associated with Helicobacter pylori Infection

    Gonzalo Castillo-Rojas

    2017-05-01

    Full Text Available Gastric cancer is a world health problem and depicts the fourth leading mortality cause from malignancy in Mexico. Causation of gastric cancer is not only due to the combined effects of environmental factors and genetic variants. Recent molecular studies have transgressed a number of genes involved in gastric carcinogenesis. The aim of this review is to understand the recent basics of gene expression in the development of the process of gastric carcinogenesis. Genetic variants, polymorphisms, desoxyribonucleic acid methylation, and genes involved in mediating inflammation have been associated with the development of gastric carcinogenesis. Recently, these genes (interleukin 10, Il-17, mucin 1, β-catenin, CDX1, SMAD4, SERPINE1, hypoxia-inducible factor 1 subunit alpha, GSK3β, CDH17, matrix metalloproteinase 7, RUNX3, RASSF1A, TFF1, HAI-2, and COX-2 have been studied in association with oncogenic activation or inactivation of tumor suppressor genes. All these mechanisms have been investigated to elucidate the process of gastric carcinogenesis, as well as their potential use as biomarkers and/or molecular targets to treatment of disease.

  16. Analysis of Genetic Diversity of Two Mangrove Species with Morphological Alterations in a Natural Environment

    Catarina Fonseca Lira-Medeiros

    2015-04-01

    Full Text Available Mangrove is an ecosystem subjected to tide, salinity and nutrient variations. These conditions are stressful to most plants, except to mangrove plants that are well-adapted. However, many mangrove areas have extremely stressful conditions, such as salt marshes, and the plants nearby usually present morphological alterations. In Sepetiba Bay, two species of mangrove plants, Avicennia schaueriana and Laguncularia racemosa, have poor development near a salt marsh (SM compared to plants at the riverside (RS, which is considered a favorable habitat in mangroves. The level of genetic diversity and its possible correlation with the morphological divergence of SM and RS plants of both species were assessed by AFLP molecular markers. We found moderate genetic differentiation between A. schaueriana plants from SM and RS areas and depleted genetic diversity on SM plants. On the other hand, Laguncularia racemosa plants had no genetic differentiation between areas. It is possible that a limited gene flow among the studied areas might be acting more intensely on A. schaueriana plants, resulting in the observed genetic differentiation. The populations of Laguncularia racemosa appear to be well connected, as genetic differentiation was not significant between the SM and RS populations. Gene flow and genetic drift are acting on neutral genetic diversity of these two mangrove species in the studied areas, and the observed genetic differentiation of A. schaueriana plants might be correlated with its morphological variation. For L. racemosa, morphological alterations could be related to epigenetic phenomena or adaptive loci polymorphism that should be further investigated.

  17. A Molecular Genetic Basis Explaining Altered Bacterial Behavior in Space.

    Luis Zea

    Full Text Available Bacteria behave differently in space, as indicated by reports of reduced lag phase, higher final cell counts, enhanced biofilm formation, increased virulence, and reduced susceptibility to antibiotics. These phenomena are theorized, at least in part, to result from reduced mass transport in the local extracellular environment, where movement of molecules consumed and excreted by the cell is limited to diffusion in the absence of gravity-dependent convection. However, to date neither empirical nor computational approaches have been able to provide sufficient evidence to confirm this explanation. Molecular genetic analysis findings, conducted as part of a recent spaceflight investigation, support the proposed model. This investigation indicated an overexpression of genes associated with starvation, the search for alternative energy sources, increased metabolism, enhanced acetate production, and other systematic responses to acidity-all of which can be associated with reduced extracellular mass transport.

  18. A Molecular Genetic Basis Explaining Altered Bacterial Behavior in Space

    Prasad, Nripesh; Levy, Shawn E.; Stodieck, Louis; Jones, Angela; Shrestha, Shristi; Klaus, David

    2016-01-01

    Bacteria behave differently in space, as indicated by reports of reduced lag phase, higher final cell counts, enhanced biofilm formation, increased virulence, and reduced susceptibility to antibiotics. These phenomena are theorized, at least in part, to result from reduced mass transport in the local extracellular environment, where movement of molecules consumed and excreted by the cell is limited to diffusion in the absence of gravity-dependent convection. However, to date neither empirical nor computational approaches have been able to provide sufficient evidence to confirm this explanation. Molecular genetic analysis findings, conducted as part of a recent spaceflight investigation, support the proposed model. This investigation indicated an overexpression of genes associated with starvation, the search for alternative energy sources, increased metabolism, enhanced acetate production, and other systematic responses to acidity—all of which can be associated with reduced extracellular mass transport. PMID:27806055

  19. Predicting evolutionary responses when genetic variance and selection covary with the environment: a large-scale Open Access Data approach

    Ramakers, J.J.C.; Culina, A.; Visser, M.E.; Gienapp, P.

    2017-01-01

    Additive genetic variance and selection are the key ingredients for evolution. In wild populations, however, predicting evolutionary trajectories is difficult, potentially by an unrecognised underlying environment dependency of both (additive) genetic variance and selection (i.e. G×E and S×E).

  20. Human diseases with genetically altered DNA repair processes

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (uv) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either x-ray-like (i.e., they cause damage that XP cells can repair) or uv-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed. (U.S.)

  1. Human diseases with genetically altered DNA repair processes

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (UV) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either X-ray-like (i.e., they cause damage that XP cells can repair) or UV-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed

  2. Radiation as agents of somatic and genetic alterations

    de Eston, V.R.

    1975-01-01

    According to the report on ''The Effects on Population of Exposure to Low Levels of Ionizing Radiation,'' whether we regard a risk as acceptable or not depends on how avoidable it is, and, if not avoidable, how it compares with the risks of alternative options and those usually accepted by society. Regarding the use of ionizing radiation: No exposure should be permitted without the expectation of a commensurable benefit. The public must be protected from radiation, but not to the extent that the degree of protection provided results in the substitution of a worse hazard than that of the radiation avoided. Medical radiation exposure can and should be reduced considerably by limiting its use to clinically indicated procedures, utilizing efficient exposure techniques and optimal operation of radiation equipment. Consideration should be given to the following: (a) Restriction of the use of radiation for public health purposes, unless there is reasonable probability of significant detection of disease. (b) Inspection and licensing of radiation and ancillary equipment. (c) Appropriate training and certification of involved personnel. (d) Gonad shielding, especially shielding of the testis, is strongly recommended as a simple and highly efficient way to reduce the genetic significant dose. In a poignant phrase, Morgan has stated ''Radiation doesn't have to be feared, but should be respected.''

  3. Genetic and epigenetic alterations induced by different levels of rye genome integration in wheat recipient.

    Zheng, X L; Zhou, J P; Zang, L L; Tang, A T; Liu, D Q; Deng, K J; Zhang, Y

    2016-06-17

    The narrow genetic variation present in common wheat (Triticum aestivum) varieties has greatly restricted the improvement of crop yield in modern breeding systems. Alien addition lines have proven to be an effective means to broaden the genetic diversity of common wheat. Wheat-rye addition lines, which are the direct bridge materials for wheat improvement, have been wildly used to produce new wheat cultivars carrying alien rye germplasm. In this study, we investigated the genetic and epigenetic alterations in two sets of wheat-rye disomic addition lines (1R-7R) and the corresponding triticales. We used expressed sequence tag-simple sequence repeat, amplified fragment length polymorphism, and methylation-sensitive amplification polymorphism analyses to analyze the effects of the introduction of alien chromosomes (either the entire genome or sub-genome) to wheat genetic background. We found obvious and diversiform variations in the genomic primary structure, as well as alterations in the extent and pattern of the genomic DNA methylation of the recipient. Meanwhile, these results also showed that introduction of different rye chromosomes could induce different genetic and epigenetic alterations in its recipient, and the genetic background of the parents is an important factor for genomic and epigenetic variation induced by alien chromosome addition.

  4. Genetic alterations during the progression of squamous cell carcinomas of the uterine cervix

    Kersemaekers, A. M.; van de Vijver, M. J.; Kenter, G. G.; Fleuren, G. J.

    1999-01-01

    Most cervical carcinomas appear to arise from cervical intraepithelial neoplasia (CIN) lesions. In addition to infection with high-risk human papilloma viruses, which is indicative of an increased risk of progression, alterations of oncogenes and tumor suppressor genes play a role. Genetic studies

  5. The wild life at Chernobyl. Analysis of a prosperous but genetically altered fauna

    Chesser, R.; Baker, R.

    1996-01-01

    The ecological study of zones contaminated by Chernobyl accident reveals that the wild life abounds, because of inhabitants absence, evacuated. On the other hand, significant genetical alterations are observed, whom functional consequences, low visible, stay, at term, unknown. This kind of studies illustrates the development of a new discipline, the evolving toxicology

  6. DNA fingerprinting techniques for the analysis of genetic and epigenetic alterations in colorectal cancer.

    Samuelsson, Johanna K; Alonso, Sergio; Yamamoto, Fumiichiro; Perucho, Manuel

    2010-11-10

    Genetic somatic alterations are fundamental hallmarks of cancer. In addition to point and other small mutations targeting cancer genes, solid tumors often exhibit aneuploidy as well as multiple chromosomal rearrangements of large fragments of the genome. Whether somatic chromosomal alterations and aneuploidy are a driving force or a mere consequence of tumorigenesis remains controversial. Recently it became apparent that not only genetic but also epigenetic alterations play a major role in carcinogenesis. Epigenetic regulation mechanisms underlie the maintenance of cell identity crucial for development and differentiation. These epigenetic regulatory mechanisms have been found substantially altered during cancer development and progression. In this review, we discuss approaches designed to analyze genetic and epigenetic alterations in colorectal cancer, especially DNA fingerprinting approaches to detect changes in DNA copy number and methylation. DNA fingerprinting techniques, despite their modest throughput, played a pivotal role in significant discoveries in the molecular basis of colorectal cancer. The aim of this review is to revisit the fingerprinting technologies employed and the oncogenic processes that they unveiled. 2010 Elsevier B.V. All rights reserved.

  7. A Behavior-Genetic Study of Parenting Quality, Infant Attachment Security, and Their Covariation in a Nationally Representative Sample

    Roisman, Glenn I.; Fraley, R. Chris

    2008-01-01

    A number of relatively small-sample, genetically sensitive studies of infant attachment security have been published in the past several years that challenge the view that all psychological phenotypes are heritable and that environmental influences on child development--to the extent that they can be detected--serve to make siblings dissimilar.…

  8. Pedigree-based estimation of covariance between dominance deviations and additive genetic effects in closed rabbit lines considering inbreeding and using a computationally simpler equivalent model.

    Fernández, E N; Legarra, A; Martínez, R; Sánchez, J P; Baselga, M

    2017-06-01

    Inbreeding generates covariances between additive and dominance effects (breeding values and dominance deviations). In this work, we developed and applied models for estimation of dominance and additive genetic variances and their covariance, a model that we call "full dominance," from pedigree and phenotypic data. Estimates with this model such as presented here are very scarce both in livestock and in wild genetics. First, we estimated pedigree-based condensed probabilities of identity using recursion. Second, we developed an equivalent linear model in which variance components can be estimated using closed-form algorithms such as REML or Gibbs sampling and existing software. Third, we present a new method to refer the estimated variance components to meaningful parameters in a particular population, i.e., final partially inbred generations as opposed to outbred base populations. We applied these developments to three closed rabbit lines (A, V and H) selected for number of weaned at the Polytechnic University of Valencia. Pedigree and phenotypes are complete and span 43, 39 and 14 generations, respectively. Estimates of broad-sense heritability are 0.07, 0.07 and 0.05 at the base versus 0.07, 0.07 and 0.09 in the final generations. Narrow-sense heritability estimates are 0.06, 0.06 and 0.02 at the base versus 0.04, 0.04 and 0.01 at the final generations. There is also a reduction in the genotypic variance due to the negative additive-dominance correlation. Thus, the contribution of dominance variation is fairly large and increases with inbreeding and (over)compensates for the loss in additive variation. In addition, estimates of the additive-dominance correlation are -0.37, -0.31 and 0.00, in agreement with the few published estimates and theoretical considerations. © 2017 Blackwell Verlag GmbH.

  9. Structural equation modeling in the genetically informative study of the covariation of intelligence, working memory and planning

    Voronin I.

    2016-01-01

    Full Text Available Structural equation modelling (SEM has become an important tool in behaviour genetic research. The application of SEM for multivariate twin analysis allows revealing the structure of genetic and environmental factors underlying individual differences in human traits. We outline the framework of twin method and SEM, describe SEM implementation of a multivariate twin model and provide an example of a multivariate twin study. The study included 901 adolescent twin pairs from Russia. We measured general cognitive ability and characteristics of working memory and planning. The individual differences in working memory and planning were explained mostly by person-specific environment. The variability of intelligence is related to genes, family environment, and person specific environment. Moderate and weak associations between intelligence, working memory, and planning were entirely explained by shared environmental effects.

  10. Effects of temperature and dietary nitrogen on genetic variation and covariation in gypsy moth larval performance traits

    Janković-Tomanić Milena

    2012-01-01

    Full Text Available To assess the plastic and genetic components of variation in responses of gypsy moth (Lymantria dispar 4th instar larvae to temperature and food quality, we applied a split-family four-environment experimental design where full-sibs were reared on two constant temperatures (23°C and 28°C and two concentrations of dietary nitrogen (1.5 and 3.7% dry weight. A temperature of 28°C and low dietary nitrogen decreased larval weight and prolonged larval developmental time, while viability was not affected. Only a marginally significant interaction between the two environmental factors was found for larval weight. The broad-sense heritability for larval developmental time did not change across environments, and across-environment genetic correlations were close to one. Heritability for larval weight depended on environmental and across-environmental genetic correlations that were not significant. There was no evidence of a trade-off between developmental time and larval weight. The implications of the obtained results for the evolution of phenotypic plasticity in complex environments are discussed. [Acknowledgments. This work was supported by Ministry of Education and Science of Serbia, grant No. 173027.

  11. Genetic Variant in Flavin-Containing Monooxygenase 3 Alters Lipid Metabolism in Laying Hens in a Diet-Specific Manner

    Wang, Jing; Long, Cheng; Zhang, Haijun; Zhang, Yanan; Wang, Hao; Yue, Hongyuan; Wang, Xiaocui; Wu, Shugeng; Qi, Guanghai

    2016-01-01

    Genetic variant T329S in flavin-containing monooxygenase 3 (FMO3) impairs trimethylamine (TMA) metabolism in birds. The TMA metabolism that under complex genetic and dietary regulation, closely linked to cardiovascular disease risk. We determined whether the genetic defects in TMA metabolism may change other metabolic traits in birds, determined whether the genetic effects depend on diets, and to identify genes or gene pathways that underlie the metabolic alteration induced by genetic and die...

  12. Genetic variation and co-variation for fitness between intra-population and inter-population backgrounds in the red flour beetle, Tribolium castaneum

    Drury, Douglas W.; Wade, Michael J.

    2010-01-01

    Hybrids from crosses between populations of the flour beetle, Tribolium castaneum, express varying degrees of inviability and morphological abnormalities. The proportion of allopatric population hybrids exhibiting these negative hybrid phenotypes varies widely, from 3% to 100%, depending upon the pair of populations crossed. We crossed three populations and measured two fitness components, fertility and adult offspring numbers from successful crosses, to determine how genes segregating within populations interact in inter-population hybrids to cause the negative phenotypes. With data from crosses of 40 sires from each of three populations to groups of 5 dams from their own and two divergent populations, we estimated the genetic variance and covariance for breeding value of fitness between the intra- and inter-population backgrounds and the sire × dam-population interaction variance. The latter component of the variance in breeding values estimates the change in genic effects between backgrounds owing to epistasis. Interacting genes with a positive effect, prior to fixation, in the sympatric background but a negative effect in the hybrid background cause reproductive incompatibility in the Dobzhansky-Muller speciation model. Thus, the sire × dam-population interaction provides a way to measure the progress toward speciation of genetically differentiating populations on a trait by trait basis using inter-population hybrids. PMID:21044199

  13. Generation of Infectious Poliovirus with Altered Genetic Information from Cloned cDNA.

    Bujaki, Erika

    2016-01-01

    The effect of specific genetic alterations on virus biology and phenotype can be studied by a great number of available assays. The following method describes the basic protocol to generate infectious poliovirus with altered genetic information from cloned cDNA in cultured cells.The example explained here involves generation of a recombinant poliovirus genome by simply replacing a portion of the 5' noncoding region with a synthetic gene by restriction cloning. The vector containing the full length poliovirus genome and the insert DNA with the known mutation(s) are cleaved for directional cloning, then ligated and transformed into competent bacteria. The recombinant plasmid DNA is then propagated in bacteria and transcribed to RNA in vitro before RNA transfection of cultured cells is performed. Finally, viral particles are recovered from the cell culture.

  14. Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression

    Ren, Shancheng; Wei, Gong-Hong; Liu, Dongbing

    2018-01-01

    BACKGROUND: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men. OBJECTIVE: To systematically explore the genomic complexity and define disease-driven genetic......-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment....... alterations in PCa. DESIGN, SETTING, AND PARTICIPANTS: The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors. OUTCOME...

  15. Structure and stability of genetic variance-covariance matrices: A Bayesian sparse factor analysis of transcriptional variation in the three-spined stickleback.

    Siren, J; Ovaskainen, O; Merilä, J

    2017-10-01

    The genetic variance-covariance matrix (G) is a quantity of central importance in evolutionary biology due to its influence on the rate and direction of multivariate evolution. However, the predictive power of empirically estimated G-matrices is limited for two reasons. First, phenotypes are high-dimensional, whereas traditional statistical methods are tuned to estimate and analyse low-dimensional matrices. Second, the stability of G to environmental effects and over time remains poorly understood. Using Bayesian sparse factor analysis (BSFG) designed to estimate high-dimensional G-matrices, we analysed levels variation and covariation in 10,527 expressed genes in a large (n = 563) half-sib breeding design of three-spined sticklebacks subject to two temperature treatments. We found significant differences in the structure of G between the treatments: heritabilities and evolvabilities were higher in the warm than in the low-temperature treatment, suggesting more and faster opportunity to evolve in warm (stressful) conditions. Furthermore, comparison of G and its phenotypic equivalent P revealed the latter is a poor substitute of the former. Most strikingly, the results suggest that the expected impact of G on evolvability-as well as the similarity among G-matrices-may depend strongly on the number of traits included into analyses. In our results, the inclusion of only few traits in the analyses leads to underestimation in the differences between the G-matrices and their predicted impacts on evolution. While the results highlight the challenges involved in estimating G, they also illustrate that by enabling the estimation of large G-matrices, the BSFG method can improve predicted evolutionary responses to selection. © 2017 John Wiley & Sons Ltd.

  16. Tissue culture-induced genetic and epigenetic alterations in rice pure-lines, F1 hybrids and polyploids.

    Wang, Xiaoran; Wu, Rui; Lin, Xiuyun; Bai, Yan; Song, Congdi; Yu, Xiaoming; Xu, Chunming; Zhao, Na; Dong, Yuzhu; Liu, Bao

    2013-05-05

    Genetic and epigenetic alterations can be invoked by plant tissue culture, which may result in heritable changes in phenotypes, a phenomenon collectively termed somaclonal variation. Although extensive studies have been conducted on the molecular nature and spectrum of tissue culture-induced genomic alterations, the issue of whether and to what extent distinct plant genotypes, e.g., pure-lines, hybrids and polyploids, may respond differentially to the tissue culture condition remains poorly understood. We investigated tissue culture-induced genetic and epigenetic alterations in a set of rice genotypes including two pure-lines (different subspecies), a pair of reciprocal F1 hybrids parented by the two pure-lines, and a pair of reciprocal tetraploids resulted from the hybrids. Using two molecular markers, amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP), both genetic and DNA methylation alterations were detected in calli and regenerants from all six genotypes, but genetic alteration is more prominent than epigenetic alteration. While significant genotypic difference was observed in frequencies of both types of alterations, only genetic alteration showed distinctive features among the three types of genomes, with one hybrid (N/9) being exceptionally labile. Surprisingly, difference in genetic alteration frequencies between the pair of reciprocal F1 hybrids is much greater than that between the two pure-line subspecies. Difference also exists in the pair of reciprocal tetraploids, but is to a less extent than that between the hybrids. The steady-state transcript abundance of genes involved in DNA repair and DNA methylation was significantly altered in both calli and regenerants, and some of which were correlated with the genetic and/or epigenetic alterations. Our results, based on molecular marker analysis of ca. 1,000 genomic loci, document that genetic alteration is the major cause of somaclonal variation in rice

  17. Phytoplasmal infection derails genetically preprogrammed meristem fate and alters plant architecture

    Wei, Wei; Davis, Robert Edward; Nuss, Donald L.; Zhao, Yan

    2013-01-01

    In higher plants, the destiny of apical meristems (stem cells) is specific organogenesis, which determines the pattern of plant growth, and therefore morphotype and fertility. We found that bacterial infection can derail the meristems from their genetically preprogrammed destiny, altering plant morphogenesis. We identified four abnormal growth patterns, symptoms, in tomato infected with a cell wall-less bacterium, and found that each symptom corresponds to a distinct phase in meristem fate de...

  18. Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis

    Plo, Isabelle; Bellanné-Chantelot, Christine; Mosca, Matthieu; Mazzi, Stefania; Marty, Caroline; Vainchenker, William

    2017-01-01

    Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) act...

  19. Genetic variance and covariance and breed differences for feed intake and average daily gain to improve feed efficiency in growing cattle.

    Retallick, K J; Bormann, J M; Weaber, R L; MacNeil, M D; Bradford, H L; Freetly, H C; Hales, K E; Moser, D W; Snelling, W M; Thallman, R M; Kuehn, L A

    2017-04-01

    Feed costs are a major economic expense in finishing and developing cattle; however, collection of feed intake data is costly. Examining relationships among measures of growth and intake, including breed differences, could facilitate selection for efficient cattle. Objectives of this study were to estimate genetic parameters for growth and intake traits and compare indices for feed efficiency to accelerate selection response. On-test ADFI and on-test ADG (TESTADG) and postweaning ADG (PWADG) records for 5,606 finishing steers and growing heifers were collected at the U.S. Meat Animal Research Center in Clay Center, NE. On-test ADFI and ADG data were recorded over testing periods that ranged from 62 to 148 d. Individual quadratic regressions were fitted for BW on time, and TESTADG was predicted from the resulting equations. We included PWADG in the model to improve estimates of growth and intake parameters; PWADG was derived by dividing gain from weaning weight to yearling weight by the number of days between the weights. Genetic parameters were estimated using multiple-trait REML animal models with TESTADG, ADFI, and PWADG for both sexes as dependent variables. Fixed contemporary groups were cohorts of calves simultaneously tested, and covariates included age on test, age of dam, direct and maternal heterosis, and breed composition. Genetic correlations (SE) between steer TESTADG and ADFI, PWADG and ADFI, and TESTADG and PWADG were 0.33 (0.10), 0.59 (0.06), and 0.50 (0.09), respectively, and corresponding estimates for heifers were 0.66 (0.073), 0.77 (0.05), and 0.88 (0.05), respectively. Indices combining EBV for ADFI with EBV for ADG were developed and evaluated. Greater improvement in feed efficiency can be expected using an unrestricted index versus a restricted index. Heterosis significantly affected each trait contributing to greater ADFI and TESTADG. Breed additive effects were estimated for ADFI, TESTADG, and the efficiency indices.

  20. Image-based computational quantification and visualization of genetic alterations and tumour heterogeneity.

    Zhong, Qing; Rüschoff, Jan H; Guo, Tiannan; Gabrani, Maria; Schüffler, Peter J; Rechsteiner, Markus; Liu, Yansheng; Fuchs, Thomas J; Rupp, Niels J; Fankhauser, Christian; Buhmann, Joachim M; Perner, Sven; Poyet, Cédric; Blattner, Miriam; Soldini, Davide; Moch, Holger; Rubin, Mark A; Noske, Aurelia; Rüschoff, Josef; Haffner, Michael C; Jochum, Wolfram; Wild, Peter J

    2016-04-07

    Recent large-scale genome analyses of human tissue samples have uncovered a high degree of genetic alterations and tumour heterogeneity in most tumour entities, independent of morphological phenotypes and histopathological characteristics. Assessment of genetic copy-number variation (CNV) and tumour heterogeneity by fluorescence in situ hybridization (ISH) provides additional tissue morphology at single-cell resolution, but it is labour intensive with limited throughput and high inter-observer variability. We present an integrative method combining bright-field dual-colour chromogenic and silver ISH assays with an image-based computational workflow (ISHProfiler), for accurate detection of molecular signals, high-throughput evaluation of CNV, expressive visualization of multi-level heterogeneity (cellular, inter- and intra-tumour heterogeneity), and objective quantification of heterogeneous genetic deletions (PTEN) and amplifications (19q12, HER2) in diverse human tumours (prostate, endometrial, ovarian and gastric), using various tissue sizes and different scanners, with unprecedented throughput and reproducibility.

  1. Population genetic dynamics of three-spined sticklebacks (Gasterosteus aculeatus) in anthropogenic altered habitats.

    Scharsack, Joern P; Schweyen, Hannah; Schmidt, Alexander M; Dittmar, Janine; Reusch, Thorsten Bh; Kurtz, Joachim

    2012-06-01

    In industrialized and/or agriculturally used landscapes, inhabiting species are exposed to a variety of anthropogenic changes in their environments. Genetic diversity may be reduced if populations encounter founder events, bottlenecks, or isolation. Conversely, genetic diversity may increase if populations adapt to changes in selective regimes in newly created habitats. With the present study, genetic variability of 918 sticklebacks from 43 samplings (21.3 ± 3.8 per sample) at 36 locations from cultivated landscapes in Northwest Germany was analyzed at nine neutral microsatellite loci. To test if differentiation is influenced by habitat alterations, sticklebacks were collected from ancient running waters and adjacent artificial stagnant waters, from brooks with salt water inflow of anthropogenic and natural origin and adjacent freshwater sites. Overall population structure was dominated by isolation by distance (IBD), which was significant across all populations, and analysis of molecular variance (AMOVA) revealed that 10.6% of the variation was explained by river catchment area. Populations in anthropogenic modified habitats deviated from the general IBD structure and in the AMOVA, grouping by habitat type running/stagnant water explained 4.9% of variation and 1.4% of the variation was explained by salt-/freshwater habitat. Sticklebacks in salt-polluted water systems seem to exhibit elevated migratory activity between fresh- and saltwater habitats, reducing IBD. In other situations, populations showed distinct signs of genetic isolation, which in some locations was attributed to mechanical migration barriers, but in others to potential anthropogenic induced bottleneck or founder effects. The present study shows that anthropogenic habitat alterations may have diverse effects on the population genetic structure of inhabiting species. Depending on the type of habitat change, increased genetic differentiation, diversification, or isolation are possible consequences.

  2. Introgression from cultivated rice alters genetic structures of wild relative populations: implications for in situ conservation

    Jin, Xin; Chen, Yu; Liu, Ping; Li, Chen; Cai, Xingxing; Rong, Jun

    2018-01-01

    Abstract Maintaining genetic integrity is essential for in situ and ex situ conservation of crop wild relative (CWR) species. However, introgression of crop alleles into CWR species/populations may change their genetic structure and diversity, resulting in more invasive weeds or, in contrast, the extinction of endangered populations. To determine crop-wild introgression and its consequences, we examined the genetic structure and diversity of six wild rice (Oryza rufipogon) populations under in situ conservation in China. Thirty-four simple sequence repeat (SSR) and 34 insertion/deletion markers were used to genotype the wild rice populations and two sets of rice cultivars (O. sativa), corresponding to the two types of molecular markers. Shared alleles and STRUCTURE analyses suggested a variable level of crop-wild introgression and admixture. Principal coordinates and cluster analyses indicated differentiation of wild rice populations, which was associated with the spatial distances to cultivated rice fields. The level of overall genetic diversity was comparable between wild rice populations and rice cultivars, but a great number of wild-specific alleles was detected in the wild populations. We conclude based on the results that crop-wild introgression can considerably alter the pattern of genetic structure and relationships of CWR populations. Appropriate measures should be taken for effective in situ conservation of CWR species under the scenario of crop-wild introgression. PMID:29308123

  3. Genetic Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the Cancer Genome Atlas Dataset.

    Choi, Woonyoung; Ochoa, Andrea; McConkey, David J; Aine, Mattias; Höglund, Mattias; Kim, William Y; Real, Francisco X; Kiltie, Anne E; Milsom, Ian; Dyrskjøt, Lars; Lerner, Seth P

    2017-09-01

    Recent whole genome mRNA expression profiling studies revealed that bladder cancers can be grouped into molecular subtypes, some of which share clinical properties and gene expression patterns with the intrinsic subtypes of breast cancer and the molecular subtypes found in other solid tumors. The molecular subtypes in other solid tumors are enriched with specific mutations and copy number aberrations that are thought to underlie their distinct progression patterns, and biological and clinical properties. The availability of comprehensive genomic data from The Cancer Genome Atlas (TCGA) and other large projects made it possible to correlate the presence of DNA alterations with tumor molecular subtype membership. Our overall goal was to determine whether specific DNA mutations and/or copy number variations are enriched in specific molecular subtypes. We used the complete TCGA RNA-seq dataset and three different published classifiers developed by our groups to assign TCGA's bladder cancers to molecular subtypes, and examined the prevalence of the most common DNA alterations within them. We interpreted the results against the background of what was known from the published literature about the prevalence of these alterations in nonmuscle-invasive and muscle-invasive bladder cancers. The results confirmed that alterations involving RB1 and NFE2L2 were enriched in basal cancers, whereas alterations involving FGFR3 and KDM6A were enriched in luminal tumors. The results further reinforce the conclusion that the molecular subtypes of bladder cancer are distinct disease entities with specific genetic alterations. Our observation showed that some of subtype-enriched mutations and copy number aberrations are clinically actionable, which has direct implications for the clinical management of patients with bladder cancer. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  4. Genetic variants alter T-bet binding and gene expression in mucosal inflammatory disease.

    Katrina Soderquest

    2017-02-01

    Full Text Available The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection, but aberrant T cell polarization can cause autoimmunity. The transcription factor T-bet (TBX21 specifies the Th1 lineage and represses alternative T cell fates. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs that may be causative for autoimmune diseases. The majority of these polymorphisms are located within non-coding distal regulatory elements. It is considered that these genetic variants contribute to disease by altering the binding of regulatory proteins and thus gene expression, but whether these variants alter the binding of lineage-specifying transcription factors has not been determined. Here, we show that SNPs associated with the mucosal inflammatory diseases Crohn's disease, ulcerative colitis (UC and celiac disease, but not rheumatoid arthritis or psoriasis, are enriched at T-bet binding sites. Furthermore, we identify disease-associated variants that alter T-bet binding in vitro and in vivo. ChIP-seq for T-bet in individuals heterozygous for the celiac disease-associated SNPs rs1465321 and rs2058622 and the IBD-associated SNPs rs1551398 and rs1551399, reveals decreased binding to the minor disease-associated alleles. Furthermore, we show that rs1465321 is an expression quantitative trait locus (eQTL for the neighboring gene IL18RAP, with decreased T-bet binding associated with decreased expression of this gene. These results suggest that genetic polymorphisms may predispose individuals to mucosal autoimmune disease through alterations in T-bet binding. Other disease-associated variants may similarly act by modulating the binding of lineage-specifying transcription factors in a tissue-selective and disease-specific manner.

  5. Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma

    Kastrup, I.B.; Worm, J.; Ralfkiaer, E.

    2008-01-01

    The reduced folate carrier (RFC) is a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs, including methotrexate (MTX). Acquired alterations of the RFC gene have been associated with resistance to MTX in cancer cell lines and primary osteosarcomas. Here, w...... with adverse outcome. In DLBCL, genetic and epigenetic alterations of RFC were detected at diagnosis in the absence of a selective MTX pressure, suggesting that these alterations may possibly contribute to the development of lymphoma Udgivelsesdato: 2008/1...

  6. Production of extracellular nucleic acids by genetically altered bacteria in aquatic-environment microcosms

    Paul, J.H.; David, A.W.

    1989-01-01

    The factors which affect the production of extracellular DNA by genetically altered strains of Escherichia coli, Pseudomonas aeruginosa, Pseudomonas cepacia, and Bradyrhizobium japonicum in aquatic environments were investigated. Cellular nucleic acids were labeled in vivo by incubation with [ 3 H]thymidine or [ 3 H]adenine, and production of extracellular DNA in marine waters, artificial seawater, or minimal salts media was determined by detecting radiolabeled macromolecules in incubation filtrates. The presence or absence of the ambient microbial community had little effect on the production of extracellular DNA. Three of four organisms produced the greatest amounts of extracellular nucleic acids when incubated in low-salinity media (2% artificial seawater) rather than high-salinity media (10 to 50% artificial seawater). The greatest production of extracellular nucleic acids by P. cepacia occurred at pH 7 and 37 degree C, suggesting that extracellular-DNA production may be a normal physiologic function of the cell. Incubation of labeled P. cepacia cells in water from Bimini Harbor, Bahamas, resulted in labeling of macromolecules of the ambient microbial population. Collectively these results indicate that (i) extracellular-DNA production by genetically altered bacteria released into aquatic environments is more strongly influenced by physicochemical factors than biotic factors, (ii) extracellular-DNA production rates are usually greater for organisms released in freshwater than marine environments, and (iii) ambient microbial populations can readily utilize materials released by these organisms

  7. The Landscape of Somatic Genetic Alterations in Breast Cancers From ATM Germline Mutation Carriers.

    Weigelt, Britta; Bi, Rui; Kumar, Rahul; Blecua, Pedro; Mandelker, Diana L; Geyer, Felipe C; Pareja, Fresia; James, Paul A; Couch, Fergus J; Eccles, Diana M; Blows, Fiona; Pharoah, Paul; Li, Anqi; Selenica, Pier; Lim, Raymond S; Jayakumaran, Gowtham; Waddell, Nic; Shen, Ronglai; Norton, Larry; Wen, Hannah Y; Powell, Simon N; Riaz, Nadeem; Robson, Mark E; Reis-Filho, Jorge S; Chenevix-Trench, Georgia

    2018-02-28

    Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic.

  8. The evolution of phenotypic integration: How directional selection reshapes covariation in mice.

    Penna, Anna; Melo, Diogo; Bernardi, Sandra; Oyarzabal, Maria Inés; Marroig, Gabriel

    2017-10-01

    Variation is the basis for evolution, and understanding how variation can evolve is a central question in biology. In complex phenotypes, covariation plays an even more important role, as genetic associations between traits can bias and alter evolutionary change. Covariation can be shaped by complex interactions between loci, and this genetic architecture can also change during evolution. In this article, we analyzed mouse lines experimentally selected for changes in size to address the question of how multivariate covariation changes under directional selection, as well as to identify the consequences of these changes to evolution. Selected lines showed a clear restructuring of covariation in their cranium and, instead of depleting their size variation, these lines increased their magnitude of integration and the proportion of variation associated with the direction of selection. This result is compatible with recent theoretical works on the evolution of covariation that take the complexities of genetic architecture into account. This result also contradicts the traditional view of the effects of selection on available covariation and suggests a much more complex view of how populations respond to selection. © 2017 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

  9. Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease

    Kamdar, Karishma; Khakpour, Samira; Chen, Jingyu; Leone, Vanessa; Brulc, Jennifer; Mangatu, Thomas; Antonopoulos, Dionysios A.; Chang, Eugene B; Kahn, Stacy A.; Kirschner, Barbara S; Young, Glenn; DePaolo, R. William

    2016-01-13

    Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, and chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.

  10. Behavior of genetic (covariance components in populations simulated from non-additive genetic models of dominance and overdominance Comportamento dos componentes de (covariância genética em populações simuladas a partir de modelos genéticos não-aditivos de dominância e sobredominância

    Elizângela Emídio Cunha

    2010-09-01

    Full Text Available The aim of this work was to investigate the short-term behavior of the genetic variability of quantitative traits simulated from models with additive and non-additive gene action in control and phenotypic selection populations. Both traits, one with low (h² = 0.10 and the other with high (h² = 0.60 heritability, were controlled by 600 biallelic loci. From a standard genome, it was obtained six genetic models which included the following: only the additive gene effects; complete and positive dominance for 25, 50, 75 and 100% of the loci; and positive overdominance for 50% of the loci. In the models with dominance deviation, the additive allelic effects were also included for 100% of the loci. Genetic variability was quantified from generation to generation using the genetic variance components. In the absence of selection, genotypic and additive genetic variances were higher. In the models with non-additive gene action, a small magnitude covariance component raised between the additive and dominance genetic effects whose correlation tended to be positive on the control population and negative under selection. Dominance variance increased as the number of loci with dominance deviation or the value of the deviation increased, implying on the increase in genotypic and additive genetic variances among the successive models.Objetivou-se estudar a variabilidade genética a curto prazo de características quantitativas simuladas a partir de modelos com ação gênica aditiva e não-aditiva em populações controle e de seleção fenotípica. As duas características, uma de baixa (h² = 0,10 e outra de alta (h² = 0,60 herdabilidade, foram controladas por 600 locos bialélicos. A partir de um genoma-padrão, foram obtidos seis modelos genéticos que incluíram: apenas efeitos aditivos dos genes; dominância completa e positiva para 25, 50, 75 e 100% dos locos; e sobredominância positiva para 50% dos locos. Nos modelos com desvio da dominância tamb

  11. A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes.

    Mühlhausen, Stefanie; Findeisen, Peggy; Plessmann, Uwe; Urlaub, Henning; Kollmar, Martin

    2016-07-01

    The genetic code is the cellular translation table for the conversion of nucleotide sequences into amino acid sequences. Changes to the meaning of sense codons would introduce errors into almost every translated message and are expected to be highly detrimental. However, reassignment of single or multiple codons in mitochondria and nuclear genomes, although extremely rare, demonstrates that the code can evolve. Several models for the mechanism of alteration of nuclear genetic codes have been proposed (including "codon capture," "genome streamlining," and "ambiguous intermediate" theories), but with little resolution. Here, we report a novel sense codon reassignment in Pachysolen tannophilus, a yeast related to the Pichiaceae. By generating proteomics data and using tRNA sequence comparisons, we show that Pachysolen translates CUG codons as alanine and not as the more usual leucine. The Pachysolen tRNACAG is an anticodon-mutated tRNA(Ala) containing all major alanine tRNA recognition sites. The polyphyly of the CUG-decoding tRNAs in yeasts is best explained by a tRNA loss driven codon reassignment mechanism. Loss of the CUG-tRNA in the ancient yeast is followed by gradual decrease of respective codons and subsequent codon capture by tRNAs whose anticodon is not part of the aminoacyl-tRNA synthetase recognition region. Our hypothesis applies to all nuclear genetic code alterations and provides several testable predictions. We anticipate more codon reassignments to be uncovered in existing and upcoming genome projects. © 2016 Mühlhausen et al.; Published by Cold Spring Harbor Laboratory Press.

  12. Microbial community responses to 17 years of altered precipitation are seasonally dependent and coupled to co-varying effects of water content on vegetation and soil C

    Sorensen, Patrick O.; Germino, Matthew J.; Feris, Kevin P.

    2013-01-01

    Precipitation amount and seasonal timing determine the duration and distribution of water available for plant and microbial activity in the cold desert sagebrush steppe. In this study, we sought to determine if a sustained shift in the amount and timing of precipitation would affect soil microbial diversity, community composition, and soil carbon (C) storage. Field plots were irrigated (+200 mm) during the dormant or growing-season for 17 years. Microbial community responses were assessed over the course of a year at two depths (15–20 cm, 95–100 cm) by terminal restriction fragment length polymorphism (T-RFLP), along with co-occurring changes in plant cover and edaphic properties. Bacterial richness, Shannon Weaver diversity, and composition in shallow soils (15–20 cm) as well as evenness in deep soils (95–100 cm) differed across irrigation treatments during July. Irrigation timing affected fungal community diversity and community composition during the dormant season and most strongly in deep soils (95–100 cm). Dormant-season irrigation increased the ratio of shrubs to forbs and reduced soil C in shallow soils by 16% relative to ambient conditions. It is unclear whether or not soil C will continue to decline with continued treatment application or if microbial adaptation could mitigate sustained soil C losses. Future changes in precipitation timing will affect soil microbes in a seasonally dependent manner and be coupled to co-varying effects of water content on vegetation and soil C.

  13. Parkinson's disease and pesticides: A meta-analysis of disease connection and genetic alterations.

    Ahmed, Hussien; Abushouk, Abdelrahman Ibrahim; Gabr, Mohamed; Negida, Ahmed; Abdel-Daim, Mohamed M

    2017-06-01

    Parkinson's disease (PD) is a globally prevalent, multifactorial disorder that occurs due to interactions between genetic and environmental factors. Observational studies have shown a link between exposure to pesticides and the risk of PD. We performed this study to systemically review published case-control studies and estimate quantitatively the association between pesticide exposure and PD. We searched Medline (through PubMed) for eligible case-control studies. The association between pesticide exposure and PD risk or occurrence of certain genetic alterations, related to the pathogenesis of PD was presented as odds ratios (OR) and pooled under the random effects model, using the statistical add-in (MetaXL, version 5.0). The pooled result showed that exposure to pesticides is linked to PD (OR 1.46, 95% CI [1.21, 1.77]), but there was a significant heterogeneity among included studies. Exposure to pesticides increased the risk of alterations in different PD pathogenesis-related genes, such as GST (OR 1.97, 95% CI [1.41, 2.76]), PON-1 (OR 1.32, 95% CI [1.09, 1.6]), MDR1 (OR 2.06, 95% CI [1.58, 2.68]), and SNCA genes (OR 1.28, 95% CI [1.02, 1.37]). There was no statistically significant association between exposure to pesticides and alteration of CYP2D6 (OR 1.19, 95% CI [0.91, 1.54]), SLC6A3 (OR 0.74, 95% CI [0.55, 1]), MnSOD (OR 1.45, 95% CI [0.97, 2.16]), NQO1 (OR 1.35, 95% CI [0.91, 2.01]), and PON-2 genes (OR 0.88, 95% CI [0.53, 1.45]). In conclusion, this meta-analysis provides evidence that pesticide exposure is significantly associated with the risk of PD and alterations in genes involved in PD pathogenesis. However, the underlying mechanism of this association and the effect of the duration of exposure or the type of pesticides should be addressed by future research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Transforming growth factor-β and breast cancer: Lessons learned from genetically altered mouse models

    Wakefield, Lalage M; Yang, Yu-an; Dukhanina, Oksana

    2000-01-01

    Transforming growth factor (TGF)-βs are plausible candidate tumor suppressors in the breast. They also have oncogenic activities under certain circumstances, however. Genetically altered mouse models provide powerful tools to analyze the complexities of TGF-βaction in the context of the whole animal. Overexpression of TGF-β can suppress tumorigenesis in the mammary gland, raising the possibility that use of pharmacologic agents to enhance TGF-β function locally might be an effective method for the chemoprevention of breast cancer. Conversely, loss of TGF-β response increases spontaneous and induced tumorigenesis in the mammary gland. This confirms that endogenous TGF-βs have tumor suppressor activity in the mammary gland, and suggests that the loss of TGF-β receptors seen in some human breast hyperplasias may play a causal role in tumor development

  15. Drug-induced and genetic alterations in stress-responsive systems: Implications for specific addictive diseases.

    Zhou, Yan; Proudnikov, Dmitri; Yuferov, Vadim; Kreek, Mary Jeanne

    2010-02-16

    From the earliest work in our laboratory, we hypothesized, and with studies conducted in both clinical research and animal models, we have shown that drugs of abuse, administered or self-administered, on a chronic basis, profoundly alter stress-responsive systems. Alterations of expression of specific genes involved in stress responsivity, with increases or decreases in mRNA levels, receptor, and neuropeptide levels, and resultant changes in hormone levels, have been documented to occur after chronic intermittent exposure to heroin, morphine, other opiates, cocaine, other stimulants, and alcohol in animal models and in human molecular genetics. The best studied of the stress-responsive systems in humans and mammalian species in general is undoubtedly the HPA axis. In addition, there are stress-responsive systems in other parts in the brain itself, and some of these include components of the HPA axis, such as CRF and CRF receptors, along with POMC gene and gene products. Several other stress-responsive systems are known to influence the HPA axis, such as the vasopressin-vasopressin receptor system. Orexin-hypocretin, acting at its receptors, may effect changes which suggest that it should be properly categorized as a stress-responsive system. However, less is known about the interactions and connectivity of some of these different neuropeptide and receptor systems, and in particular, about the possible connectivity of fast-acting (e.g., glutamate and GABA) and slow-acting (including dopamine, serotonin, and norepinephrine) neurotransmitters with each of these stress-responsive components and the resultant impact, especially in the setting of chronic exposure to drugs of abuse. Several of these stress-responsive systems and components, primarily based on our laboratory-based and human molecular genetics research of addictive diseases, will be briefly discussed in this review. Copyright 2009 Elsevier B.V. All rights reserved.

  16. Targeted molecular profiling of rare genetic alterations in colorectal cancer using next-generation sequencing.

    Jauhri, Mayank; Bhatnagar, Akanksha; Gupta, Satish; Shokeen, Yogender; Minhas, Sachin; Aggarwal, Shyam

    2016-10-01

    Mutation frequencies of common genetic alterations in colorectal cancer have been in the spotlight for many years. This study highlights few rare somatic mutations, which possess the attributes of a potential CRC biomarker yet are often neglected. Next-generation sequencing was performed over 112 tumor samples to detect genetic alterations in 31 rare genes in colorectal cancer. Mutations were detected in 26/31 (83.9 %) uncommon genes, which together contributed toward 149 gene mutations in 67/112 (59.8 %) colorectal cancer patients. The most frequent mutations include KDR (19.6 %), PTEN (17 %), FBXW7 (10.7 %), SMAD4 (10.7 %), VHL (8 %), KIT (8 %), MET (7.1 %), ATM (6.3 %), CTNNB1 (4.5 %) and CDKN2A (4.5 %). RB1, ERBB4 and ERBB2 mutations were persistent in 3.6 % patients. GNAS, FGFR2 and FGFR3 mutations were persistent in 1.8 % patients. Ten genes (EGFR, NOTCH1, SMARCB1, ABL1, STK11, SMO, RET, GNAQ, CSF1R and FLT3) were found mutated in 0.9 % patients. Lastly, no mutations were observed in AKT, HRAS, MAP2K1, PDGFR and JAK2. Significant associations were observed between VHL with tumor site, ERBB4 and SMARCB1 with tumor invasion, CTNNB1 with lack of lymph node involvement and CTNNB1, FGFR2 and FGFR3 with TNM stage. Significantly coinciding mutation pairs include PTEN and SMAD4, PTEN and KDR, EGFR and RET, EGFR and RB1, FBXW7 and CTNNB1, KDR and FGFR2, FLT3 and CTNNB1, RET and RB1, ATM and SMAD4, ATM and CDKN2A, ERBB4 and SMARCB1. This study elucidates few potential colorectal cancer biomarkers, specifically KDR, PTEN, FBXW7 and SMAD4, which are found mutated in more than 10 % patients.

  17. Distinct genetic alteration profiles of acute myeloid leukemia between Caucasian and Eastern Asian population.

    Wei, Hui; Wang, Ying; Zhou, Chunlin; Lin, Dong; Liu, Bingcheng; Liu, Kaiqi; Qiu, Shaowei; Gong, Benfa; Li, Yan; Zhang, Guangji; Wei, Shuning; Gong, Xiaoyuan; Liu, Yuntao; Zhao, Xingli; Gu, Runxia; Mi, Yingchang; Wang, Jianxiang

    2018-02-10

    Racial and ethnic disparities in malignancies attract extensive attention. To investigate whether there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population, data from several prospective AML trials were retrospectively analyzed in this study. We found that there were more patients with core binding factor (CBF) leukemia in Eastern Asian cohorts and there were different CBF leukemia constitutions between them. The ratios of CBF leukemia are 27.7, 22.1, 21.1, and 23.4%, respectively, in our (ChiCTR-TRC-10001202), another Chinese, Korean, and Japanese Eastern Asian cohorts, which are significantly higher than those in ECOG1900, MRC AML15, UK NCRI AML17, HOVON/SAKK AML-42, and German AML2003 (15.5, 12.5, 9.3, 10.2, and 12%, respectively). And CBFbeta-MYH11 occurred more prevalently in HOVON/SAKK AML- 42 and ECOG1900 trials (50.0 and 54.3% of CBF leukemia, respectively) than in Chinese and Japanese trials (20.1 and 20.8%, respectively). The proportion of FLT3-ITD mutation is 11.2% in our cohort, which is lower than that in MRC AML15 and UK NCRI AML17 (24.6 and 17.9%, respectively). Even after excluding the age bias, there are still different incidence rates of mutation between Caucasian and Eastern Asian population. These data suggest that there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population.

  18. Genetic alterations of hepatocellular carcinoma by random amplified polymorphic DNA analysis and cloning sequencing of tumor differential DNA fragment

    Xian, Zhi-Hong; Cong, Wen-Ming; Zhang, Shu-Hui; Wu, Meng-Chao

    2005-01-01

    AIM: To study the genetic alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC), and to find the tumor related DNA fragments. METHODS: DNA isolated from tumors and corresponding noncancerous liver tissues of 56 HCC patients was amplified by random amplified polymorphic DNA (RAPD) with 10 random 10-mer arbitrary primers. The RAPD bands showing obvious differences in tumor tissue DNA corresponding to that of normal tissue were separated, purified, cloned and sequenced. DNA sequences were analyzed and compared with GenBank data. RESULTS: A total of 56 cases of HCC were demonstrated to have genetic alterations, which were detected by at least one primer. The detestability of genetic alterations ranged from 20% to 70% in each case, and 17.9% to 50% in each primer. Serum HBV infection, tumor size, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with genetic alterations on certain primers. A band with a higher intensity of 480 bp or so amplified fragments in tumor DNA relative to normal DNA could be seen in 27 of 56 tumor samples using primer 4. Sequence analysis of these fragments showed 91% homology with Homo sapiens double homeobox protein DUX10 gene. CONCLUSION: Genetic alterations are a frequent event in HCC, and tumor related DNA fragments have been found in this study, which may be associated with hepatocarcin-ogenesis. RAPD is an effective method for the identification and analysis of genetic alterations in HCC, and may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis. PMID:15996039

  19. Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis.

    Plo, Isabelle; Bellanné-Chantelot, Christine; Mosca, Matthieu; Mazzi, Stefania; Marty, Caroline; Vainchenker, William

    2017-01-01

    Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) activity ( MPL, JAK2, CALR ) and loss-of-function (LOF) activity of negative regulators ( CBL, LNK ) or the extrinsic MPL signaling by THPO GOF mutations leading to increased TPO synthesis. Alternatively, thrombocytosis may paradoxically result from mutations of MPL leading to an abnormal MPL trafficking, inducing increased TPO levels by alteration of its clearance. In contrast, thrombocytopenia can also result from LOF THPO or MPL mutations, which cause a complete defect in MPL trafficking to the cell membrane, impaired MPL signaling or stability, defects in the TPO/MPL interaction, or an absence of TPO production.

  20. A Note on the Power Provided by Sibships of Sizes 2, 3, and 4 in Genetic Covariance Modeling of a Codominant QTL.

    Dolan, C.V.; Boomsma, D.I.; Neale, M.C.

    1999-01-01

    The contribution of size 3 and size 4 sibships to power in covariance structure modeling of a codominant QTL is investigated. Power calculations are based on the noncentral chi-square distribution. Sixteen sets of parameter values are considered. Results indicate that size 3 and size 4 sibships

  1. Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer's disease.

    Huang, Chi-Wei; Hsu, Shih-Wei; Tsai, Shih-Jen; Chen, Nai-Ching; Liu, Mu-En; Lee, Chen-Chang; Huang, Shu-Hua; Chang, Weng-Neng; Chang, Ya-Ting; Tsai, Wan-Chen; Chang, Chiung-Chih

    2017-01-18

    Inflammatory processes play a pivotal role in the degenerative process of Alzheimer's disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer's disease. We enrolled a total of 135 patients with Alzheimer's disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations. There were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores. Interleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white

  2. Covariance evaluation system

    Kawano, Toshihiko; Shibata, Keiichi.

    1997-09-01

    A covariance evaluation system for the evaluated nuclear data library was established. The parameter estimation method and the least squares method with a spline function are used to generate the covariance data. Uncertainties of nuclear reaction model parameters are estimated from experimental data uncertainties, then the covariance of the evaluated cross sections is calculated by means of error propagation. Computer programs ELIESE-3, EGNASH4, ECIS, and CASTHY are used. Covariances of 238 U reaction cross sections were calculated with this system. (author)

  3. Genetic alterations in lung cancer: Assessing limitations in routine clinical use

    Joana Espiga Macedo

    2007-01-01

    Full Text Available Lung cancer is the most frequent cause of cancer mortality worldwide, responsible for approximately 1.1 million deaths per year. Median survival is short, both as most tumours are diagnosed at an advanced stage and because of the limited efficacy of available treatments. The development of tumour molecular genetics carries the promise of altering this state of affairs, as it should lead to a more precise classification of tumours, identify specific molecular targets for therapy and, above all, allow the development of new methods for early diagnosis. Despite numerous studies demonstrating the usefulness of molecular genetic techniques in the study of lung cancer, its routine clinical use in Portugal has, however, been limited.In this study, we used a p53 mutation screen in multiple clinical samples from a series of lung cancer patients to attempt to identify the main practical limitations to the integration of molecular genetics in routine clinical practice. Our results suggest that the main limiting factor is the availability of samples with good quality DNA; a problem that could be overcome by alterations in common sample collection and storage procedures. Resumo: O cancro do pulmão é a causa mais frequente de mortalidade por cancro no mundo, sendo responsável por cerca de 1,1 milhões de mortes por ano. A sobrevivência média dos doentes é geralmente curta, por a doença se encontrar em estádios avançados na altura do diagnóstico, mas também devido à falta de eficácia dos tratamentos disponíveis. O advento da genética molecular dos tumores trouxe consigo a possibilidade de modificar esta situação, quer através do refinamento do diagnóstico, quer da identificação de alvos terapêuticos específicos, quer sobretudo por – pelo menos em teoria – permitir o diagnóstico precoce da doença. No entanto, e apesar de numerosos trabalhos terem já demonstrado a utilidade

  4. Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma.

    Stine H Kresse

    Full Text Available BACKGROUND: Osteosarcomas are the most common non-haematological primary malignant tumours of bone, and all conventional osteosarcomas are high-grade tumours showing complex genomic aberrations. We have integrated genome-wide genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma cell lines based on microarray technologies. PRINCIPAL FINDINGS: The cell lines showed complex patterns of DNA copy number changes, where genomic copy number gains were significantly associated with gene-rich regions and losses with gene-poor regions. By integrating the datasets, 350 genes were identified as having two types of aberrations (gain/over-expression, hypo-methylation/over-expression, loss/under-expression or hyper-methylation/under-expression using a recurrence threshold of 6/19 (>30% cell lines. The genes showed in general alterations in either DNA copy number or DNA methylation, both within individual samples and across the sample panel. These 350 genes are involved in embryonic skeletal system development and morphogenesis, as well as remodelling of extracellular matrix. The aberrations of three selected genes, CXCL5, DLX5 and RUNX2, were validated in five cell lines and five tumour samples using PCR techniques. Several genes were hyper-methylated and under-expressed compared to normal osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2'-deoxycytidine treatment for four genes tested; AKAP12, CXCL5, EFEMP1 and IL11RA. Globally, there was as expected a significant positive association between gain and over-expression, loss and under-expression as well as hyper-methylation and under-expression, but gain was also associated with hyper-methylation and under-expression, suggesting that hyper-methylation may oppose the effects of increased copy number for detrimental genes. CONCLUSIONS: Integrative analysis of genome-wide genetic and epigenetic alterations identified dependencies and relationships between

  5. Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation.

    Hasumi, Hisashi; Yao, Masahiro

    2018-03-01

    Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, USA and the first kidney cancer-associated gene, VHL, was identified through kindred analysis of von Hippel-Lindau (VHL) syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia-inducible factor (HIF), which provided the basis for the development of tyrosine kinase inhibitors targeting the HIF-VEGF/PDGF pathway. Recent whole-exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at the germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of the causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms of how an alteration of each kidney cancer-associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  6. Short communication: Alteration of priors for random effects in Gaussian linear mixed model

    Vandenplas, Jérémie; Christensen, Ole Fredslund; Gengler, Nicholas

    2014-01-01

    such alterations. Therefore, the aim of this study was to propose a method to alter both the mean and (co)variance of the prior multivariate normal distributions of random effects of linear mixed models while using currently available software packages. The proposed method was tested on simulated examples with 3......, multiple-trait predictions of lactation yields, and Bayesian approaches integrating external information into genetic evaluations) need to alter both the mean and (co)variance of the prior distributions and, to our knowledge, most software packages available in the animal breeding community do not permit...... different software packages available in animal breeding. The examples showed the possibility of the proposed method to alter both the mean and (co)variance of the prior distributions with currently available software packages through the use of an extended data file and a user-supplied (co)variance matrix....

  7. Genetics

    Hubitschek, H.E.

    1975-01-01

    Progress is reported on the following research projects: genetic effects of high LET radiations; genetic regulation, alteration, and repair; chromosome replication and the division cycle of Escherichia coli; effects of radioisotope decay in the DNA of microorganisms; initiation and termination of DNA replication in Bacillus subtilis; mutagenesis in mouse myeloma cells; lethal and mutagenic effects of near-uv radiation; effect of 8-methoxypsoralen on photodynamic lethality and mutagenicity in Escherichia coli; DNA repair of the lethal effects of far-uv; and near uv irradiation of bacterial cells

  8. Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches.

    Ruben Perez-Carrasco

    2016-10-01

    Full Text Available During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules-morphogens-guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can

  9. Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches

    Page, Karen M.

    2016-01-01

    During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules—morphogens—guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can qualitatively

  10. Genetic deletion of Mst1 alters T cell function and protects against autoimmunity.

    Konstantin V Salojin

    Full Text Available Mammalian sterile 20-like kinase 1 (Mst1 is a MAPK kinase kinase kinase which is involved in a wide range of cellular responses, including apoptosis, lymphocyte adhesion and trafficking. The contribution of Mst1 to Ag-specific immune responses and autoimmunity has not been well defined. In this study, we provide evidence for the essential role of Mst1 in T cell differentiation and autoimmunity, using both genetic and pharmacologic approaches. Absence of Mst1 in mice reduced T cell proliferation and IL-2 production in vitro, blocked cell cycle progression, and elevated activation-induced cell death in Th1 cells. Mst1 deficiency led to a CD4+ T cell development path that was biased toward Th2 and immunoregulatory cytokine production with suppressed Th1 responses. In addition, Mst1-/- B cells showed decreased stimulation to B cell mitogens in vitro and deficient Ag-specific Ig production in vivo. Consistent with altered lymphocyte function, deletion of Mst1 reduced the severity of experimental autoimmune encephalomyelitis (EAE and protected against collagen-induced arthritis development. Mst1-/- CD4+ T cells displayed an intrinsic defect in their ability to respond to encephalitogenic antigens and deletion of Mst1 in the CD4+ T cell compartment was sufficient to alleviate CNS inflammation during EAE. These findings have prompted the discovery of novel compounds that are potent inhibitors of Mst1 and exhibit desirable pharmacokinetic properties. In conclusion, this report implicates Mst1 as a critical regulator of adaptive immune responses, Th1/Th2-dependent cytokine production, and as a potential therapeutic target for immune disorders.

  11. Brownian distance covariance

    Székely, Gábor J.; Rizzo, Maria L.

    2010-01-01

    Distance correlation is a new class of multivariate dependence coefficients applicable to random vectors of arbitrary and not necessarily equal dimension. Distance covariance and distance correlation are analogous to product-moment covariance and correlation, but generalize and extend these classical bivariate measures of dependence. Distance correlation characterizes independence: it is zero if and only if the random vectors are independent. The notion of covariance with...

  12. Genetic and epigenetic alteration among three homoeologous genes of a class E MADS box gene in hexaploid wheat.

    Shitsukawa, Naoki; Tahira, Chikako; Kassai, Ken-Ichiro; Hirabayashi, Chizuru; Shimizu, Tomoaki; Takumi, Shigeo; Mochida, Keiichi; Kawaura, Kanako; Ogihara, Yasunari; Murai, Koji

    2007-06-01

    Bread wheat (Triticum aestivum) is a hexaploid species with A, B, and D ancestral genomes. Most bread wheat genes are present in the genome as triplicated homoeologous genes (homoeologs) derived from the ancestral species. Here, we report that both genetic and epigenetic alterations have occurred in the homoeologs of a wheat class E MADS box gene. Two class E genes are identified in wheat, wheat SEPALLATA (WSEP) and wheat LEAFY HULL STERILE1 (WLHS1), which are homologs of Os MADS45 and Os MADS1 in rice (Oryza sativa), respectively. The three wheat homoeologs of WSEP showed similar genomic structures and expression profiles. By contrast, the three homoeologs of WLHS1 showed genetic and epigenetic alterations. The A genome WLHS1 homoeolog (WLHS1-A) had a structural alteration that contained a large novel sequence in place of the K domain sequence. A yeast two-hybrid analysis and a transgenic experiment indicated that the WLHS1-A protein had no apparent function. The B and D genome homoeologs, WLHS1-B and WLHS1-D, respectively, had an intact MADS box gene structure, but WLHS1-B was predominantly silenced by cytosine methylation. Consequently, of the three WLHS1 homoeologs, only WLHS1-D functions in hexaploid wheat. This is a situation where three homoeologs are differentially regulated by genetic and epigenetic mechanisms.

  13. Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model.

    Mottron, Laurent; Belleville, Sylvie; Rouleau, Guy A; Collignon, Olivier

    2014-11-01

    The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Covariant w∞ gravity

    Bergshoeff, E.; Pope, C.N.; Stelle, K.S.

    1990-01-01

    We discuss the notion of higher-spin covariance in w∞ gravity. We show how a recently proposed covariant w∞ gravity action can be obtained from non-chiral w∞ gravity by making field redefinitions that introduce new gauge-field components with corresponding new gauge transformations.

  15. Implications of Genetic and Epigenetic Alterations of CDKN2A (p16INK4a in Cancer

    Ran Zhao

    2016-06-01

    Full Text Available Aberrant gene silencing is highly associated with altered cell cycle regulation during carcinogenesis. In particular, silencing of the CDKN2A tumor suppressor gene, which encodes the p16INK4a protein, has a causal link with several different types of cancers. The p16INK4a protein plays an executional role in cell cycle and senescence through the regulation of the cyclin-dependent kinase (CDK 4/6 and cyclin D complexes. Several genetic and epigenetic aberrations of CDKN2A lead to enhanced tumorigenesis and metastasis with recurrence of cancer and poor prognosis. In these cases, the restoration of genetic and epigenetic reactivation of CDKN2A is a practical approach for the prevention and therapy of cancer. This review highlights the genetic status of CDKN2A as a prognostic and predictive biomarker in various cancers.

  16. Genetic KCa3.1-deficiency produces locomotor hyperactivity and alterations in cerebral monoamine levels.

    Kate Lykke Lambertsen

    Full Text Available The calmodulin/calcium-activated K(+ channel KCa3.1 is expressed in red and white blood cells, epithelia and endothelia, and possibly central and peripheral neurons. However, our knowledge about its contribution to neurological functions and behavior is incomplete. Here, we investigated whether genetic deficiency or pharmacological activation of KCa3.1 change behavior and cerebral monoamine levels in mice.In the open field test, KCa3.1-deficiency increased horizontal activity, as KCa3.1(-/- mice travelled longer distances (≈145% of KCa3.1(+/+ and at higher speed (≈1.5-fold of KCa3.1(+/+. Working memory in the Y-maze was reduced by KCa3.1-deficiency. Motor coordination on the rotarod and neuromuscular functions were unchanged. In KCa3.1(-/- mice, HPLC analysis revealed that turn-over rates of serotonin were reduced in frontal cortex, striatum and brain stem, while noradrenalin turn-over rates were increased in the frontal cortex. Dopamine turn-over rates were unaltered. Plasma catecholamine and corticosterone levels were unaltered. Intraperitoneal injections of 10 mg/kg of the KCa3.1/KCa2-activator SKA-31 reduced rearing and turning behavior in KCa3.1(+/+ but not in KCa3.1(-/- mice, while 30 mg/kg SKA-31 caused strong sedation in 50% of the animals of either genotypes. KCa3.1(-/- mice were hyperactive (≈+60% in their home cage and SKA-31-administration reduced nocturnal physical activity in KCa3.1(+/+ but not in KCa3.1(-/- mice.KCa3.1-deficiency causes locomotor hyperactivity and altered monoamine levels in selected brain regions, suggesting a so far unknown functional link of KCa3.1 channels to behavior and monoaminergic neurotransmission in mice. The tranquilizing effects of low-dose SKA-31 raise the possibility to use KCa3.1/KCa2 channels as novel pharmacological targets for the treatment of neuropsychiatric hyperactivity disorders.

  17. Macro-environment of breast carcinoma: frequent genetic alterations in the normal appearing skins of patients with breast cancer.

    Moinfar, Farid; Beham, Alfred; Friedrich, Gerhard; Deutsch, Alexander; Hrzenjak, Andelko; Luschin, Gero; Tavassoli, Fattaneh A

    2008-05-01

    Genetic abnormalities in microenvironmental tissues with subsequent alterations of reciprocal interactions between epithelial and mesenchymal cells play a key role in the breast carcinogenesis. Although a few reports have demonstrated abnormal fibroblastic functions in normal-appearing fibroblasts taken from the skins of breast cancer patients, the genetic basis of this phenomenon and its implication for carcinogenesis are unexplored. We analyzed 12 mastectomy specimens showing invasive ductal carcinomas. In each case, morphologically normal epidermis and dermis, carcinoma, normal stroma close to carcinoma, and stroma at a distant from carcinoma were microdissected. Metastatic-free lymphatic tissues from lymph nodes served as a control. Using PCR, DNA extracts were examined with 11 microsatellite markers known for a high frequency of allelic imbalances in breast cancer. Losses of heterozygosity and/or microsatellite instability were detected in 83% of the skin samples occurring either concurrently with or independently from the cancerous tissues. In 80% of these cases at least one microsatellite marker displayed loss of heterozygosity or microsatellite instability in the skin, which was absent in carcinoma. A total of 41% of samples showed alterations of certain loci observed exclusively in the carcinoma but not in the skin compartments. Our study suggests that breast cancer is not just a localized genetic disorder, but rather part of a larger field of genetic alterations/instabilities affecting multiple cell populations in the organ with various cellular elements, ultimately contributing to the manifestation of the more 'localized' carcinoma. These data indicate that more global assessment of tumor micro- and macro-environment is crucial for our understanding of breast carcinogenesis.

  18. Covariant representations of nuclear *-algebras

    Moore, S.M.

    1978-01-01

    Extensions of the Csup(*)-algebra theory for covariant representations to nuclear *-algebra are considered. Irreducible covariant representations are essentially unique, an invariant state produces a covariant representation with stable vacuum, and the usual relation between ergodic states and covariant representations holds. There exist construction and decomposition theorems and a possible relation between derivations and covariant representations

  19. Efeito da inclusão da covariância genética aditiva direta-materna no modelo de análise sobre a magnitude das estimativas de parâmetros e valores genéticos preditos para ganho de peso na raça Brangus Effect of genetic direct-maternal covariance inclusion in the model of analizys on the estimate of parameters and predicted genetic values for weight gain in Brangus breed

    Luiz Felipe Waihrich Guterres

    2007-06-01

    this research was to study the effect of accouting for the covariance between the additive genetic direct and the maternal effects (covd-m on the estimates of genetic parameters and on predictions of genetic values (VG, for average daily gain from birth to weaning (GMDND and from weaning to 550 days of age (GMDDS. They were analyzed 28,949 records for GMDND and 11,884 for GMDDS of a Brangus breed population (58 Angus x 3/8 Nellore, collected from 1986 to 2002. The (covariance components were obtained by REML. In the animal model for GMDND, the additive genetic direct and maternal and residual effects were considered as random, and the effects of contemporaneous group at weaning (Gc²05, the interaction of the Nellore-Angus breed genetic percentage of the bull and cow (FGNA and the covariables, age of the cow at birth (IV and age at weaning (ID as fixed effects. For GMDDS, the model was the same, except that Gc²05 was substituted by contemporaneous group at 550 days of age (CG550 and ID by age at 550 days. In both models, permanent environmental effect of the cow was considered as a random effect. The heritabilities estimated for direct genetic effects ranged from 0.14 ± 0.03 to 0.21 ± 0.03 and for maternal effects from 0.00 ± 0.01 to 0.15 ± 0.02, the estimates had smaller values when covd-m was included in the model for GMDND. The correlations between genetic direct and maternal effects were negative -0.25 ± 0.12 (GMDND and -0.77 ± 0.19 (GMDDS. The likelihood ratio test showed that there is no significant diference, at 5% significance level, between the adopted models for boths characteristics. The rank correlation between the VG predicted by the two models, were 0.89 for GMDND and 0.98 for GMDND, suggesting that a slight change in the rank of the animals can happen, for GMDND.

  20. Covariant Noncommutative Field Theory

    Estrada-Jimenez, S [Licenciaturas en Fisica y en Matematicas, Facultad de Ingenieria, Universidad Autonoma de Chiapas Calle 4a Ote. Nte. 1428, Tuxtla Gutierrez, Chiapas (Mexico); Garcia-Compean, H [Departamento de Fisica, Centro de Investigacion y de Estudios Avanzados del IPN P.O. Box 14-740, 07000 Mexico D.F., Mexico and Centro de Investigacion y de Estudios Avanzados del IPN, Unidad Monterrey Via del Conocimiento 201, Parque de Investigacion e Innovacion Tecnologica (PIIT) Autopista nueva al Aeropuerto km 9.5, Lote 1, Manzana 29, cp. 66600 Apodaca Nuevo Leon (Mexico); Obregon, O [Instituto de Fisica de la Universidad de Guanajuato P.O. Box E-143, 37150 Leon Gto. (Mexico); Ramirez, C [Facultad de Ciencias Fisico Matematicas, Universidad Autonoma de Puebla, P.O. Box 1364, 72000 Puebla (Mexico)

    2008-07-02

    The covariant approach to noncommutative field and gauge theories is revisited. In the process the formalism is applied to field theories invariant under diffeomorphisms. Local differentiable forms are defined in this context. The lagrangian and hamiltonian formalism is consistently introduced.

  1. Covariant Noncommutative Field Theory

    Estrada-Jimenez, S.; Garcia-Compean, H.; Obregon, O.; Ramirez, C.

    2008-01-01

    The covariant approach to noncommutative field and gauge theories is revisited. In the process the formalism is applied to field theories invariant under diffeomorphisms. Local differentiable forms are defined in this context. The lagrangian and hamiltonian formalism is consistently introduced

  2. Decomposing variation in male reproductive success: age-specific variances and covariances through extra-pair and within-pair reproduction.

    Lebigre, Christophe; Arcese, Peter; Reid, Jane M

    2013-07-01

    Age-specific variances and covariances in reproductive success shape the total variance in lifetime reproductive success (LRS), age-specific opportunities for selection, and population demographic variance and effective size. Age-specific (co)variances in reproductive success achieved through different reproductive routes must therefore be quantified to predict population, phenotypic and evolutionary dynamics in age-structured populations. While numerous studies have quantified age-specific variation in mean reproductive success, age-specific variances and covariances in reproductive success, and the contributions of different reproductive routes to these (co)variances, have not been comprehensively quantified in natural populations. We applied 'additive' and 'independent' methods of variance decomposition to complete data describing apparent (social) and realised (genetic) age-specific reproductive success across 11 cohorts of socially monogamous but genetically polygynandrous song sparrows (Melospiza melodia). We thereby quantified age-specific (co)variances in male within-pair and extra-pair reproductive success (WPRS and EPRS) and the contributions of these (co)variances to the total variances in age-specific reproductive success and LRS. 'Additive' decomposition showed that within-age and among-age (co)variances in WPRS across males aged 2-4 years contributed most to the total variance in LRS. Age-specific (co)variances in EPRS contributed relatively little. However, extra-pair reproduction altered age-specific variances in reproductive success relative to the social mating system, and hence altered the relative contributions of age-specific reproductive success to the total variance in LRS. 'Independent' decomposition showed that the (co)variances in age-specific WPRS, EPRS and total reproductive success, and the resulting opportunities for selection, varied substantially across males that survived to each age. Furthermore, extra-pair reproduction increased

  3. Covariance data processing code. ERRORJ

    Kosako, Kazuaki

    2001-01-01

    The covariance data processing code, ERRORJ, was developed to process the covariance data of JENDL-3.2. ERRORJ has the processing functions of covariance data for cross sections including resonance parameters, angular distribution and energy distribution. (author)

  4. The genetic alteration of MTS1/CDKN2 gene in esophageal cancer

    Zo, Jae Ill; Paik, Hee Jong; Park, Jong Ho; Kim, Mi Hee

    1996-12-01

    MTS1/CDKN2 gene plays a key role in cell cycle regulation, and there have been many studies about the significance of this gene in tumorigenesis. To investigate the frequency of MTS1/CDKN2 gene alteration in Korean esophageal cancer, we studied 36 esophageal cancer tissues with paired PCR analysis to detect homozygous deletion and PCR-SSCP methods to find minute mutations, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. And in cases without RB gene a alterations, direct sequence analysis was also done. There was no homozygous deletions. Mobility shift by PCR-SSCP was observed in four cases at exon 2, which showed 1 bp deletion in codon 97 of mutation in codon 100 which changed TAT (Tyr) from GAT (Asp). But there were not MTS1/CDKN2 gene alterations in cases without Rb gene alterations. Analysis of clinical data did not show any differences depending upon MTS1/CDKN2 gene alterations. Therefore the MTS1/CDKN2 gene mutations were infrequent events and do not play a major role in the group of patients examined. More study for contribution of methylation in MTS1/CDKN2 gene for inactivation of p16 should be done before evaluation and application of MTS1/CDKN2 gene in tumorigenesis and as an candidate of gene therapy. (author). 15 refs

  5. The genetic alteration of MTS1/CDKN2 gene in esophageal cancer

    Zo, Jae Ill; Paik, Hee Jong; Park, Jong Ho; Kim, Mi Hee [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1996-12-01

    MTS1/CDKN2 gene plays a key role in cell cycle regulation, and there have been many studies about the significance of this gene in tumorigenesis. To investigate the frequency of MTS1/CDKN2 gene alteration in Korean esophageal cancer, we studied 36 esophageal cancer tissues with paired PCR analysis to detect homozygous deletion and PCR-SSCP methods to find minute mutations, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. And in cases without RB gene a alterations, direct sequence analysis was also done. There was no homozygous deletions. Mobility shift by PCR-SSCP was observed in four cases at exon 2, which showed 1 bp deletion in codon 97 of mutation in codon 100 which changed TAT (Tyr) from GAT (Asp). But there were not MTS1/CDKN2 gene alterations in cases without Rb gene alterations. Analysis of clinical data did not show any differences depending upon MTS1/CDKN2 gene alterations. Therefore the MTS1/CDKN2 gene mutations were infrequent events and do not play a major role in the group of patients examined. More study for contribution of methylation in MTS1/CDKN2 gene for inactivation of p16 should be done before evaluation and application of MTS1/CDKN2 gene in tumorigenesis and as an candidate of gene therapy. (author). 15 refs.

  6. Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations

    Ariel B. Ganz

    2017-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75 consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9 for 10–12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.

  7. Beyond mean allelic effects: A locus at the major color gene MC1R associates also with differing levels of phenotypic and genetic (co)variance for coloration in barn owls.

    San-Jose, Luis M; Ducret, Valérie; Ducrest, Anne-Lyse; Simon, Céline; Roulin, Alexandre

    2017-10-01

    The mean phenotypic effects of a discovered variant help to predict major aspects of the evolution and inheritance of a phenotype. However, differences in the phenotypic variance associated to distinct genotypes are often overlooked despite being suggestive of processes that largely influence phenotypic evolution, such as interactions between the genotypes with the environment or the genetic background. We present empirical evidence for a mutation at the melanocortin-1-receptor gene, a major vertebrate coloration gene, affecting phenotypic variance in the barn owl, Tyto alba. The white MC1R allele, which associates with whiter plumage coloration, also associates with a pronounced phenotypic and additive genetic variance for distinct color traits. Contrarily, the rufous allele, associated with a rufous coloration, relates to a lower phenotypic and additive genetic variance, suggesting that this allele may be epistatic over other color loci. Variance differences between genotypes entailed differences in the strength of phenotypic and genetic associations between color traits, suggesting that differences in variance also alter the level of integration between traits. This study highlights that addressing variance differences of genotypes in wild populations provides interesting new insights into the evolutionary mechanisms and the genetic architecture underlying the phenotype. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  8. Y chromosome microdeletions and alterations of spermatogenesis, patient approach and genetic counseling.

    Rives, Nathalie

    2014-05-01

    Infertility affects 15% of couples at reproductive age and human male infertility appears frequently idiopathic. The main genetic causes of spermatogenesis defect responsible for non-obstructive azoospermia and severe oligozoospermia are constitutional chromosomal abnormalities and microdeletions in the azoospermia factor region of the Y chromosome. The improvement of the Yq microdeletion screening method gave new insights in the mechanism responsible for the genesis of Yq microdeletions and for the consequences of the management of male infertility and genetic counselling in case of assisted reproductive technology. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Temporal organization of feeding in Syrian hamsters with a genetically altered circadian period

    Oklejewicz, M; Overkamp, GJF; Stirland, JA; Daan, S

    2001-01-01

    The variation in spontaneous meal patterning was studied in three genotypes (tau +/+, tau +/- and tau -/-) of the Syrian hamster with an altered circadian period. Feeding activity was monitored continuously in 13 individuals from each genotype in constant dim light conditions. All three genotypes

  10. Genetic KCa3.1-deficiency produces locomotor hyperactivity and alterations in cerebral monoamine levels

    Lambertsen, Kate Lykke; Gramsbergen, Jan Bert; Sivasaravanaparan, Mithula

    2012-01-01

    The calmodulin/calcium-activated K(+) channel KCa3.1 is expressed in red and white blood cells, epithelia and endothelia, and possibly central and peripheral neurons. However, our knowledge about its contribution to neurological functions and behavior is incomplete. Here, we investigated whether...... genetic deficiency or pharmacological activation of KCa3.1 change behavior and cerebral monoamine levels in mice....

  11. Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome

    Chen, T-C; Hou, H-A; Chou, W-C; Tang, J-L; Kuo, Y-Y; Chen, C-Y; Tseng, M-H; Huang, C-F; Lai, Y-J; Chiang, Y-C; Lee, F-Y; Liu, M-C; Liu, C-W; Liu, C-Y; Yao, M; Huang, S-Y; Ko, B-S; Hsu, S-C; Wu, S-J; Tsay, W; Chen, Y-C; Tien, H-F

    2014-01-01

    Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression

  12. Altering BDNF expression by genetics and/or environment: impact for emotional and depression-like behaviour in laboratory mice.

    Chourbaji, Sabine; Brandwein, Christiane; Gass, Peter

    2011-01-01

    According to the "neurotrophin hypothesis", brain-derived neurotrophic factor (BDNF) is an important candidate gene in depression. Moreover, environmental stress is known to represent a risk factor in the pathophysiology and treatment of this disease. To elucidate, whether changes of BDNF availability signify cause or consequence of depressive-like alterations, it is essential to look for endophenotypes under distinct genetic conditions (e.g. altered BDNF expression). Furthermore it is crucial to examine environment-driven BDNF regulation and its effect on depressive-linked features. Consequently, gene × environment studies investigating prospective genetic mouse models of depression in different environmental contexts become increasingly important. The present review summarizes recent findings in BDNF-mutant mice, which have been controversially discussed as models of depression and anxiety. It furthermore illustrates the potential of environment to serve as naturalistic stressor with the potential to modulate the phenotype in wildtype and mutant mice. Moreover, environment may exert protective effects by regulating BDNF levels as attributed to "environmental enrichment". The effect of this beneficial condition will also be discussed with regard to probable "curative/therapeutic" approaches. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Covariance Bell inequalities

    Pozsgay, Victor; Hirsch, Flavien; Branciard, Cyril; Brunner, Nicolas

    2017-12-01

    We introduce Bell inequalities based on covariance, one of the most common measures of correlation. Explicit examples are discussed, and violations in quantum theory are demonstrated. A crucial feature of these covariance Bell inequalities is their nonlinearity; this has nontrivial consequences for the derivation of their local bound, which is not reached by deterministic local correlations. For our simplest inequality, we derive analytically tight bounds for both local and quantum correlations. An interesting application of covariance Bell inequalities is that they can act as "shared randomness witnesses": specifically, the value of the Bell expression gives device-independent lower bounds on both the dimension and the entropy of the shared random variable in a local model.

  14. Validity of covariance models for the analysis of geographical variation

    Guillot, Gilles; Schilling, Rene L.; Porcu, Emilio

    2014-01-01

    1. Due to the availability of large molecular data-sets, covariance models are increasingly used to describe the structure of genetic variation as an alternative to more heavily parametrised biological models. 2. We focus here on a class of parametric covariance models that received sustained att...

  15. The covariant chiral ring

    Bourget, Antoine; Troost, Jan [Laboratoire de Physique Théorique, École Normale Supérieure, 24 rue Lhomond, 75005 Paris (France)

    2016-03-23

    We construct a covariant generating function for the spectrum of chiral primaries of symmetric orbifold conformal field theories with N=(4,4) supersymmetry in two dimensions. For seed target spaces K3 and T{sup 4}, the generating functions capture the SO(21) and SO(5) representation theoretic content of the chiral ring respectively. Via string dualities, we relate the transformation properties of the chiral ring under these isometries of the moduli space to the Lorentz covariance of perturbative string partition functions in flat space.

  16. Dimension from covariance matrices.

    Carroll, T L; Byers, J M

    2017-02-01

    We describe a method to estimate embedding dimension from a time series. This method includes an estimate of the probability that the dimension estimate is valid. Such validity estimates are not common in algorithms for calculating the properties of dynamical systems. The algorithm described here compares the eigenvalues of covariance matrices created from an embedded signal to the eigenvalues for a covariance matrix of a Gaussian random process with the same dimension and number of points. A statistical test gives the probability that the eigenvalues for the embedded signal did not come from the Gaussian random process.

  17. Genetic Alterations within the DENND1A Gene in Patients with Polycystic Ovary Syndrome (PCOS)

    Eriksen, Mette B; Nielsen, Michael F B; Brusgaard, Klaus

    2013-01-01

    sequencing. SNP genotyping was tested by allelic discrimination in real-time PCR in the additional patients and controls. Sequencing of the DENND1A gene identified eight SNPs; seven were not known to be associated with any diseases. One missense SNP was detected (rs189947178, A/C), potentially altering......Polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women, is caused by both genes and environment. We and others previously reported association between single nucleotide polymorphisms (SNPs) in the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene...... and FG-score or PCOS diagnosis, this could be a false positive finding. In conclusion, sequence analysis of the DENND1A gene of patients with PCOS did not identify alterations that alone could be responsible for the PCOS pathogenesis, but a missense SNP (rs189947178) was identified in one patient...

  18. Flight initiation and maintenance deficits in flies with genetically altered biogenic amine levels

    Brembs, Björn; Christiansen, F.; Pflüger, J.; Duch, C.

    2007-01-01

    Insect flight is one of the fastest, most intense and most energy-demanding motor behaviors. It is modulated on multiple levels by the biogenic amine octopamine. Within the CNS, octopamine acts directly on the flight central pattern generator, and it affects motivational states. In the periphery, octopamine sensitizes sensory receptors, alters muscle contraction kinetics, and enhances flight muscle glycolysis. This study addresses the roles for octopamine and its precursor tyramine in flight ...

  19. Altered expression of MGMT in high-grade gliomas results from the combined effect of epigenetic and genetic aberrations.

    João Ramalho-Carvalho

    Full Text Available MGMT downregulation in high-grade gliomas (HGG has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA. By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation and genetic (monosomy, locus deletion changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy.

  20. Quantitative Chemical-Genetic Interaction Map Connects Gene Alterations to Drug Responses | Office of Cancer Genomics

    In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation.

  1. [Environmental and genetic variables related with alterations in language acquisition in early childhood].

    Moriano-Gutierrez, A; Colomer-Revuelta, J; Sanjuan, J; Carot-Sierra, J M

    2017-01-01

    A great deal of research has addressed problems in the correct acquisition of language, but with few overall conclusions. The reasons for this lie in the individual variability, the existence of different measures for assessing language and the fact that a complex network of genetic and environmental factors are involved in its development. To review the environmental and genetic variables that have been studied to date, in order to gain a better under-standing of the causes of specific language impairment and create new evidence that can help in the development of screening systems for the early detection of these disorders. The environmental variables related with poorer early child language development include male gender, low level of education of the mother, familial history of problems with language or psychiatric problems, perinatal problems and health problems in early childhood. Bilingualism seems to be a protective factor. Temperament and language are related. Within the genetic factors there are several specific genes associated with language, two of which have a greater influence on its physiological acquisition: FOXP2 and CNTNAP2. The other genes that are most related with specific language disorders are ATP2C2, CMIP, ROBO2, ZNF277 and NOP9. The key to comprehending the development of specific language disorders lies in reaching an understanding of the true role played by genes in the ontogenesis, in the regulation of the different developmental processes, and how this role is modulated by the environment.

  2. Partial genetic deletion of neuregulin 1 and adolescent stress interact to alter NMDA receptor binding in the medial prefrontal cortex

    Tariq Waseem Chohan

    2014-09-01

    Full Text Available Schizophrenia is thought to arise due to a complex interaction between genetic and environmental factors during early neurodevelopment. We have recently shown that partial genetic deletion of the schizophrenia susceptibility gene neuregulin 1 (Nrg1 and adolescent stress interact to disturb sensorimotor gating, neuroendocrine activity and dendritic morphology in mice. Both stress and Nrg1 may have converging effects upon N-methyl-D-aspartate receptors (NMDARs which are implicated in the pathogenesis of schizophrenia, sensorimotor gating and dendritic spine plasticity. Using an identical repeated restraint stress paradigm to our previous study, here we determined NMDAR binding across various brain regions in adolescent Nrg1 heterozygous (HET and wild-type (WT mice using [3H] MK-801 autoradiography. Repeated restraint stress increased NMDAR binding in the ventral part of the lateral septum (LSV and the dentate gyrus (DG of the hippocampus irrespective of genotype. Partial genetic deletion of Nrg1 interacted with adolescent stress to promote an altered pattern of NMDAR binding in the infralimbic (IL subregion of the medial prefrontal cortex. In the IL, whilst stress tended to increase NMDAR binding in WT mice, it decreased binding in Nrg1 HET mice. However in the DG, stress selectively increased the expression of NMDAR binding in Nrg1 HET mice but not WT mice. These results demonstrate a Nrg1-stress interaction during adolescence on NMDAR binding in the medial prefrontal cortex.

  3. Generalized Linear Covariance Analysis

    Carpenter, James R.; Markley, F. Landis

    2014-01-01

    This talk presents a comprehensive approach to filter modeling for generalized covariance analysis of both batch least-squares and sequential estimators. We review and extend in two directions the results of prior work that allowed for partitioning of the state space into solve-for'' and consider'' parameters, accounted for differences between the formal values and the true values of the measurement noise, process noise, and textita priori solve-for and consider covariances, and explicitly partitioned the errors into subspaces containing only the influence of the measurement noise, process noise, and solve-for and consider covariances. In this work, we explicitly add sensitivity analysis to this prior work, and relax an implicit assumption that the batch estimator's epoch time occurs prior to the definitive span. We also apply the method to an integrated orbit and attitude problem, in which gyro and accelerometer errors, though not estimated, influence the orbit determination performance. We illustrate our results using two graphical presentations, which we call the variance sandpile'' and the sensitivity mosaic,'' and we compare the linear covariance results to confidence intervals associated with ensemble statistics from a Monte Carlo analysis.

  4. Genetic alterations within the DENND1A gene in patients with polycystic ovary syndrome (PCOS.

    Mette B Eriksen

    Full Text Available Polycystic ovary syndrome (PCOS, the most common endocrine disease among premenopausal women, is caused by both genes and environment. We and others previously reported association between single nucleotide polymorphisms (SNPs in the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene in white patients with PCOS to identify possible alterations that may be implicated in the PCOS pathogenesis. Patients were referred with PCOS and/or hirsutism between 1998 and 2011 (n = 261. PCOS was diagnosed according to the Rotterdam criteria (n = 165. Sequence analysis was performed in 10 patients with PCOS. Additional patients (n = 251 and healthy female controls (n = 248 were included for SNP genotyping. Patients underwent clinical examination including Ferriman-Gallwey score (FG-score, biochemical analyses and transvaginal ultrasound. Mutation analysis was carried out by bidirectional sequencing. SNP genotyping was tested by allelic discrimination in real-time PCR in the additional patients and controls. Sequencing of the DENND1A gene identified eight SNPs; seven were not known to be associated with any diseases. One missense SNP was detected (rs189947178, A/C, potentially altering the structural conformation of the DENND1A protein. SNP genotyping of rs189947178 showed significantly more carriers among patients with PCOS and moderate hirsutism compared to controls. However, due to small sample size and lack of multiple regression analysis supporting an association between rs189947178 and FG-score or PCOS diagnosis, this could be a false positive finding. In conclusion, sequence analysis of the DENND1A gene of patients with PCOS did not identify alterations that alone could be responsible for the PCOS pathogenesis, but a missense SNP (rs189947178 was identified in one patient and significantly more carriers of rs189947178 were found among patients with PCOS and moderate hirsutism vs. controls. Additional studies with independent cohort are needed

  5. Assessing glycolytic flux alterations resulting from genetic perturbations in E. coli using a biosensor

    Lehning, Christina Eva; Siedler, Solvej; Ellabaan, Mostafa M Hashim

    2017-01-01

    validated the glycolytic flux dependency of the biosensor in a range of different carbon sources in six different E. coli strains and during mevalonate production. Furthermore, we studied the flux-altering effects of genome-wide single gene knock-outs in E. coli in a multiplex FlowSeq experiment. From...... a library consisting of 2126 knock-out mutants, we identified 3 mutants with high-flux and 95 mutants with low-flux phenotypes that did not have severe growth defects. This approach can improve our understanding of glycolytic flux regulation improving metabolic models and engineering efforts....

  6. Componentes de (covariância e parâmetros genéticos para caracteres produtivos à desmama de bezerros Angus criados no Estado do Rio Grande do Sul (Covariance components and genetic parameters for weaning production traits of Angus calves raised in the State of Rio Grande do Sul

    Fernando Flores Cardoso

    2001-02-01

    Full Text Available Foram estimados componentes de (covariância e parâmetros genéticos para peso ao nascer (PN, ganho do nascimento à desmama (G205 e escores de conformação (CD, precocidade de terminação (GD, musculatura (MD e tamanho (TD à desmama, utilizando-se registros de desmama de 40.915 bezerros Angus, criados no Estado do Rio Grande do Sul, sul do Brasil. Desses, 12.706 tinham pesagem ao nascer e 11.863, avaliação completa para escores visuais (EV. Os dados foram analisados por meio de um modelo animal, em análises uni e multivariadas, e os componentes de variância estimados pela máxima verossimilhança restrita. As herdabilidades aditivas diretas estimadas foram 0,29; 0,25; 0,18; 0,19; 0,19; e 0,21, respectivamente, para PN, G205, CD, GD, MD e TD. A herdabilidade materna para G205 foi 0,16 e a correlação entre efeito genético direto e materno, -0,51. Essa correlação negativa indica antagonismo entre esses efeitos e provocou decréscimo na herdabilidade total para G205, que foi 0,18. A contribuição do ambiente permanente da vaca para a variância fenotípica esteve entre um mínimo de 0,05 para PN e máximo de 0,12 para G205. A correlação genética entre PN e G205 foi --0,06, mostrando que estes caracteres são independentes geneticamente. As correlações genéticas encontradas entre G205 e EV foram entre 0,71 e 0,86 e de EV entre si, 0,58 a 0,91. Essas associações positivas entre os escores visuais e destes com o crescimento na fase pré-desmama favorecem a seleção conjunta destes caracteres, por meio de índices de seleção.(Co variance components and genetic parameters for birth weight (BW, adjusted weaning gain (AWG and for conformation (WC, precocity (WP, muscling (WM and size (WS scores at weaning were estimated, from records of 40,915 Angus calves, raised in the state of Rio Grande do Sul, southern Brazil. From that data, 12,706 had birth weight records and 11,863 had complete records for visual scores (VS. The data were

  7. Alteration of Box-Jenkins methodology by implementing genetic algorithm method

    Ismail, Zuhaimy; Maarof, Mohd Zulariffin Md; Fadzli, Mohammad

    2015-02-01

    A time series is a set of values sequentially observed through time. The Box-Jenkins methodology is a systematic method of identifying, fitting, checking and using integrated autoregressive moving average time series model for forecasting. Box-Jenkins method is an appropriate for a medium to a long length (at least 50) time series data observation. When modeling a medium to a long length (at least 50), the difficulty arose in choosing the accurate order of model identification level and to discover the right parameter estimation. This presents the development of Genetic Algorithm heuristic method in solving the identification and estimation models problems in Box-Jenkins. Data on International Tourist arrivals to Malaysia were used to illustrate the effectiveness of this proposed method. The forecast results that generated from this proposed model outperformed single traditional Box-Jenkins model.

  8. Genetic and Epigenetic Alterations of Brassica nigra Introgression Lines from Somatic Hybridization: A Resource for Cauliflower Improvement.

    Wang, Gui-Xiang; Lv, Jing; Zhang, Jie; Han, Shuo; Zong, Mei; Guo, Ning; Zeng, Xing-Ying; Zhang, Yue-Yun; Wang, You-Ping; Liu, Fan

    2016-01-01

    Broad phenotypic variations were obtained previously in derivatives from the asymmetric somatic hybridization of cauliflower "Korso" (Brassica oleracea var. botrytis, 2n = 18, CC genome) and black mustard "G1/1" (Brassica nigra, 2n = 16, BB genome). However, the mechanisms underlying these variations were unknown. In this study, 28 putative introgression lines (ILs) were pre-selected according to a series of morphological (leaf shape and color, plant height and branching, curd features, and flower traits) and physiological (black rot/club root resistance) characters. Multi-color fluorescence in situ hybridization revealed that these plants contained 18 chromosomes derived from "Korso." Molecular marker (65 simple sequence repeats and 77 amplified fragment length polymorphisms) analysis identified the presence of "G1/1" DNA segments (average 7.5%). Additionally, DNA profiling revealed many genetic and epigenetic differences among the ILs, including sequence alterations, deletions, and variation in patterns of cytosine methylation. The frequency of fragments lost (5.1%) was higher than presence of novel bands (1.4%), and the presence of fragments specific to Brassica carinata (BBCC 2n = 34) were common (average 15.5%). Methylation-sensitive amplified polymorphism analysis indicated that methylation changes were common and that hypermethylation (12.4%) was more frequent than hypomethylation (4.8%). Our results suggested that asymmetric somatic hybridization and alien DNA introgression induced genetic and epigenetic alterations. Thus, these ILs represent an important, novel germplasm resource for cauliflower improvement that can be mined for diverse traits of interest to breeders and researchers.

  9. Genetic and epigenetic alterations of Brassica nigra introgression lines from somatic hybridization: a resource for cauliflower improvement

    Guixiang Wang

    2016-08-01

    Full Text Available Broad phenotypic variations were obtained previously in derivatives from the asymmetric somatic hybridization of cauliflower ‘Korso’ (Brassica oleracea var. botrytis, 2n = 18, CC genome and black mustard ‘G1/1’ (Brassica nigra, 2n = 16, BB genome. However, the mechanisms underlying these variations were unknown. In this study, 28 putative introgression lines (ILs were pre-selected according to a series of morphological (leaf shape and color, plant height and branching, curd features, and flower traits and physiological (black rot/club root resistance characters. Multi-color fluorescence in situ hybridization revealed that these plants contained 18 chromosomes derived from ‘Korso’. Molecular marker (65 simple sequence repeats and 77 amplified fragment length polymorphisms analysis identified the presence of ‘G1/1’ DNA segments (average 7.5%. Additionally, DNA profiling revealed many genetic and epigenetic differences among the ILs, including sequence alterations, deletions, and variation in patterns of cytosine methylation. The frequency of fragments lost (5.1% was significantly higher than presence of novel bands (1.4%, and the presence of fragments specific to B. carinata (BBCC 2n = 34 were common (average 15.5%. Methylation-sensitive amplified polymorphism analysis indicated that methylation changes were common and that hypermethylation (12.4% was more frequent than hypomethylation (4.8%. Our results suggested that asymmetric somatic hybridization and alien DNA introgression induced genetic and epigenetic alterations. Thus, these ILs represent an important, novel germplasm resource for cauliflower improvement that can be mined for diverse traits of interest to breeders and researchers.

  10. Multiple feature fusion via covariance matrix for visual tracking

    Jin, Zefenfen; Hou, Zhiqiang; Yu, Wangsheng; Wang, Xin; Sun, Hui

    2018-04-01

    Aiming at the problem of complicated dynamic scenes in visual target tracking, a multi-feature fusion tracking algorithm based on covariance matrix is proposed to improve the robustness of the tracking algorithm. In the frame-work of quantum genetic algorithm, this paper uses the region covariance descriptor to fuse the color, edge and texture features. It also uses a fast covariance intersection algorithm to update the model. The low dimension of region covariance descriptor, the fast convergence speed and strong global optimization ability of quantum genetic algorithm, and the fast computation of fast covariance intersection algorithm are used to improve the computational efficiency of fusion, matching, and updating process, so that the algorithm achieves a fast and effective multi-feature fusion tracking. The experiments prove that the proposed algorithm can not only achieve fast and robust tracking but also effectively handle interference of occlusion, rotation, deformation, motion blur and so on.

  11. Covariant field equations in supergravity

    Vanhecke, Bram [KU Leuven, Institute for Theoretical Physics, Leuven (Belgium); Ghent University, Faculty of Physics, Gent (Belgium); Proeyen, Antoine van [KU Leuven, Institute for Theoretical Physics, Leuven (Belgium)

    2017-12-15

    Covariance is a useful property for handling supergravity theories. In this paper, we prove a covariance property of supergravity field equations: under reasonable conditions, field equations of supergravity are covariant modulo other field equations. We prove that for any supergravity there exist such covariant equations of motion, other than the regular equations of motion, that are equivalent to the latter. The relations that we find between field equations and their covariant form can be used to obtain multiplets of field equations. In practice, the covariant field equations are easily found by simply covariantizing the ordinary field equations. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  12. Covariant field equations in supergravity

    Vanhecke, Bram; Proeyen, Antoine van

    2017-01-01

    Covariance is a useful property for handling supergravity theories. In this paper, we prove a covariance property of supergravity field equations: under reasonable conditions, field equations of supergravity are covariant modulo other field equations. We prove that for any supergravity there exist such covariant equations of motion, other than the regular equations of motion, that are equivalent to the latter. The relations that we find between field equations and their covariant form can be used to obtain multiplets of field equations. In practice, the covariant field equations are easily found by simply covariantizing the ordinary field equations. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  13. Generally covariant gauge theories

    Capovilla, R.

    1992-01-01

    A new class of generally covariant gauge theories in four space-time dimensions is investigated. The field variables are taken to be a Lie algebra valued connection 1-form and a scalar density. Modulo an important degeneracy, complex [euclidean] vacuum general relativity corresponds to a special case in this class. A canonical analysis of the generally covariant gauge theories with the same gauge group as general relativity shows that they describe two degrees of freedom per space point, qualifying therefore as a new set of neighbors of general relativity. The modification of the algebra of the constraints with respect to the general relativity case is computed; this is used in addressing the question of how general relativity stands out from its neighbors. (orig.)

  14. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers.

    Nath, Aritro; Chan, Christina

    2016-01-04

    Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers.

  15. Genetic transformation of rare Verbascum eriophorum Godr. plants and metabolic alterations revealed by NMR-based metabolomics.

    Marchev, Andrey; Yordanova, Zhenya; Alipieva, Kalina; Zahmanov, Georgi; Rusinova-Videva, Snezhana; Kapchina-Toteva, Veneta; Simova, Svetlana; Popova, Milena; Georgiev, Milen I

    2016-09-01

    To develop a protocol to transform Verbascum eriophorum and to study the metabolic differences between mother plants and hairy root culture by applying NMR and processing the datasets with chemometric tools. Verbascum eriophorum is a rare species with restricted distribution, which is poorly studied. Agrobacterium rhizogenes-mediated genetic transformation of V. eriophorum and hairy root culture induction are reported for the first time. To determine metabolic alterations, V. eriophorum mother plants and relevant hairy root culture were subjected to comprehensive metabolomic analyses, using NMR (1D and 2D). Metabolomics data, processed using chemometric tools (and principal component analysis in particular) allowed exploration of V. eriophorum metabolome and have enabled identification of verbascoside (by means of 2D-TOCSY NMR) as the most abundant compound in hairy root culture. Metabolomics data contribute to the elucidation of metabolic alterations after T-DNA transfer to the host V. eriophorum genome and the development of hairy root culture for sustainable bioproduction of high value verbascoside.

  16. The Bayesian Covariance Lasso.

    Khondker, Zakaria S; Zhu, Hongtu; Chu, Haitao; Lin, Weili; Ibrahim, Joseph G

    2013-04-01

    Estimation of sparse covariance matrices and their inverse subject to positive definiteness constraints has drawn a lot of attention in recent years. The abundance of high-dimensional data, where the sample size ( n ) is less than the dimension ( d ), requires shrinkage estimation methods since the maximum likelihood estimator is not positive definite in this case. Furthermore, when n is larger than d but not sufficiently larger, shrinkage estimation is more stable than maximum likelihood as it reduces the condition number of the precision matrix. Frequentist methods have utilized penalized likelihood methods, whereas Bayesian approaches rely on matrix decompositions or Wishart priors for shrinkage. In this paper we propose a new method, called the Bayesian Covariance Lasso (BCLASSO), for the shrinkage estimation of a precision (covariance) matrix. We consider a class of priors for the precision matrix that leads to the popular frequentist penalties as special cases, develop a Bayes estimator for the precision matrix, and propose an efficient sampling scheme that does not precalculate boundaries for positive definiteness. The proposed method is permutation invariant and performs shrinkage and estimation simultaneously for non-full rank data. Simulations show that the proposed BCLASSO performs similarly as frequentist methods for non-full rank data.

  17. An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients

    Parlanti, Eleonora; Pietraforte, Donatella; Iorio, Egidio; Visentin, Sergio; De Nuccio, Chiara; Zijno, Andrea; D’Errico, Mariarosaria; Simonelli, Valeria; Sanchez, Massimo; Fattibene, Paola; Falchi, Mario; Dogliotti, Eugenia

    2015-01-01

    Highlights: • Increased levels and different types of intracellular radical species as well as an altered glutathione redox state characterize XP-A human cells when compared to normal. • A more glycolytic metabolism and higher ATP levels are associated with alteration of mitochondrial morphology and response to mitochondrial toxicants when XPA is defective. • XP-A human cells show increased spontaneous micronuclei frequency, a hallmark of cancer risk. - Abstract: Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O_2_−· and H_2O_2 being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance ("1H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a hallmark of cancer

  18. An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients

    Parlanti, Eleonora [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Pietraforte, Donatella; Iorio, Egidio; Visentin, Sergio; De Nuccio, Chiara [Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Zijno, Andrea; D’Errico, Mariarosaria; Simonelli, Valeria [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Sanchez, Massimo [Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Fattibene, Paola [Department of Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Falchi, Mario [National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Dogliotti, Eugenia, E-mail: dogliotti@iss.it [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy)

    2015-12-15

    Highlights: • Increased levels and different types of intracellular radical species as well as an altered glutathione redox state characterize XP-A human cells when compared to normal. • A more glycolytic metabolism and higher ATP levels are associated with alteration of mitochondrial morphology and response to mitochondrial toxicants when XPA is defective. • XP-A human cells show increased spontaneous micronuclei frequency, a hallmark of cancer risk. - Abstract: Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O{sub 2−}· and H{sub 2}O{sub 2} being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance ({sup 1}H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a

  19. The genetic basis for altered blood vessel function in disease: large artery stiffening

    Alex Agrotis

    2005-12-01

    Full Text Available Alex AgrotisThe Cell Biology Laboratory, Baker Heart Research Institute, Melbourne, Victoria, AustraliaAbstract: The progressive stiffening of the large arteries in humans that occurs during aging constitutes a potential risk factor for increased cardiovascular morbidity and mortality, and is accompanied by an elevation in systolic blood pressure and pulse pressure. While the underlying basis for these changes remains to be fully elucidated, factors that are able to influence the structure and composition of the extracellular matrix and the way it interacts with arterial smooth muscle cells could profoundly affect the properties of the large arteries. Thus, while age and sex represent important factors contributing to large artery stiffening, the variation in growth-stimulating factors and those that modulate extracellular production and homeostasis are also being increasingly recognized to play a key role in the process. Therefore, elucidating the contribution that genetic variation makes to large artery stiffening could ultimately provide the basis for clinical strategies designed to regulate the process for therapeutic benefit.Keywords: arterial stiffness, genes, polymorphism, extracellular matrix proteins

  20. Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins

    Khanichi N. Charles

    2017-10-01

    Full Text Available Summary: Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp-deficient mice exhibit extended metabolic healthspan, with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice. : Deterioration of metabolic health is a hallmark of aging and generally thought to be detrimental to longevity. Charles et al. utilize FABP-deficient mice as a model to demonstrate that the preservation of metabolic health in this model persists throughout life, even under metabolic stress, but does not increase longevity. Keywords: fatty acid binding protein, aging, calorie restriction, metabolic health, inflammation, metaflammation, diabetes, obesity, de novo lipogenesis

  1. Combined M-FISH and CGH analysis allows comprehensive description of genetic alterations in neuroblastoma cell lines.

    Van Roy, N; Van Limbergen, H; Vandesompele, J; Van Gele, M; Poppe, B; Salwen, H; Laureys, G; Manoel, N; De Paepe, A; Speleman, F

    2001-10-01

    Cancer cell lines are essential gene discovery tools and have often served as models in genetic and functional studies of particular tumor types. One of the future challenges is comparison and interpretation of gene expression data with the available knowledge on the genomic abnormalities in these cell lines. In this context, accurate description of these genomic abnormalities is required. Here, we show that a combination of M-FISH with banding analysis, standard FISH, and CGH allowed a detailed description of the genetic alterations in 16 neuroblastoma cell lines. In total, 14 cryptic chromosome rearrangements were detected, including a balanced t(2;4)(p24.3;q34.3) translocation in cell line NBL-S, with the 2p24 breakpoint located at about 40 kb from MYCN. The chromosomal origin of 22 marker chromosomes and 41 cytogenetically undefined translocated segments was determined. Chromosome arm 2 short arm translocations were observed in six cell lines (38%) with and five (31%) without MYCN amplification, leading to partial chromosome arm 2p gain in all but one cell line and loss of material in the various partner chromosomes, including 1p and 11q. These 2p gains were often masked in the GGH profiles due to MYCN amplification. The commonly overrepresented region was chromosome segment 2pter-2p22, which contains the MYCN gene, and five out of eleven 2p breakpoints clustered to the interface of chromosome bands 2p16 and 2p21. In neuroblastoma cell line SJNB-12, with double minutes (dmins) but no MYCN amplification, the dmins were shown to be derived from 16q22-q23 sequences. The ATBF1 gene, an AT-binding transcription factor involved in normal neurogenesis and located at 16q22.2, was shown to be present in the amplicon. This is the first report describing the possible implication of ATBF1 in neuroblastoma cells. We conclude that a combined approach of M-FISH, cytogenetics, and CGH allowed a more complete and accurate description of the genetic alterations occurring in the

  2. Lorentz Covariance of Langevin Equation

    Koide, T.; Denicol, G.S.; Kodama, T.

    2008-01-01

    Relativistic covariance of a Langevin type equation is discussed. The requirement of Lorentz invariance generates an entanglement between the force and noise terms so that the noise itself should not be a covariant quantity. (author)

  3. PIK3CA Mutation in Colorectal Cancer: Relationship with Genetic and Epigenetic Alterations

    Katsuhiko Nosho

    2008-06-01

    Full Text Available Somatic PIK3CA mutations are often present in colorectal cancer. Mutant PIK3CA activates AKT signaling, which up-regulates fatty acid synthase (FASN. Microsatellite instability (MSI and CpG island methylator phenotype (CIMP are important molecular classifiers in colorectal cancer. However, the relationship between PIK3CA mutation, MSI and CIMP remains uncertain. Using Pyrosequencing technology, we detected PIK3CA mutations in 91 (15% of 590 population-based colorectal cancers. To determine CIMP status, we quantified DNA methylation in eight CIMP-specific promoters [CACNA1G, CDKN2A (p16, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1] by real-time polymerase chain reaction (MethyLight. PIK3CA mutation was significantly associated with mucinous tumors [P = .0002; odds ratio (OR = 2.44], KRAS mutation (P < .0001; OR = 2.68, CIMP-high (P = .03; OR = 2.08, phospho–ribosomal protein S6 expression (P = .002; OR = 2.19, and FASN expression (P = .02; OR = 1.85 and inversely with p53 expression (P = .01; OR = 0.54 and β-catenin (CTNNB1 alteration (P = .004; OR = 0.43. In addition, PIK3CA G-to-A mutations were associated with MGMT loss (P = .001; OR = 3.24 but not with MGMT promoter methylation. In conclusion, PIK3CA mutation is significantly associated with other key molecular events in colorectal cancer, and MGMT loss likely contributes to the development of PIK3CA G>A mutation. In addition, Pyrosequencing is useful in detecting PIK3CA mutation in archival paraffin tumor tissue. PIK3CA mutational data further emphasize heterogeneity of colorectal cancer at the molecular level.

  4. Ontogeny of mouse vestibulo-ocular reflex following genetic or environmental alteration of gravity sensing.

    Mathieu Beraneck

    Full Text Available The vestibular organs consist of complementary sensors: the semicircular canals detect rotations while the otoliths detect linear accelerations, including the constant pull of gravity. Several fundamental questions remain on how the vestibular system would develop and/or adapt to prolonged changes in gravity such as during long-term space journey. How do vestibular reflexes develop if the appropriate assembly of otoliths and semi-circular canals is perturbed? The aim of present work was to evaluate the role of gravity sensing during ontogeny of the vestibular system. In otoconia-deficient mice (ied, gravity cannot be sensed and therefore maculo-ocular reflexes (MOR were absent. While canals-related reflexes were present, the ied deficit also led to the abnormal spatial tuning of the horizontal angular canal-related VOR. To identify putative otolith-related critical periods, normal C57Bl/6J mice were subjected to 2G hypergravity by chronic centrifugation during different periods of development or adulthood (Adult-HG and compared to non-centrifuged (control C57Bl/6J mice. Mice exposed to hypergravity during development had completely normal vestibulo-ocular reflexes 6 months after end of centrifugation. Adult-HG mice all displayed major abnormalities in maculo-ocular reflexe one month after return to normal gravity. During the next 5 months, adaptation to normal gravity occurred in half of the individuals. In summary, genetic suppression of gravity sensing indicated that otolith-related signals might be necessary to ensure proper functioning of canal-related vestibular reflexes. On the other hand, exposure to hypergravity during development was not sufficient to modify durably motor behaviour. Hence, 2G centrifugation during development revealed no otolith-specific critical period.

  5. Distance covariance for stochastic processes

    Matsui, Muneya; Mikosch, Thomas Valentin; Samorodnitsky, Gennady

    2017-01-01

    The distance covariance of two random vectors is a measure of their dependence. The empirical distance covariance and correlation can be used as statistical tools for testing whether two random vectors are independent. We propose an analog of the distance covariance for two stochastic processes...

  6. Earth Observing System Covariance Realism

    Zaidi, Waqar H.; Hejduk, Matthew D.

    2016-01-01

    The purpose of covariance realism is to properly size a primary object's covariance in order to add validity to the calculation of the probability of collision. The covariance realism technique in this paper consists of three parts: collection/calculation of definitive state estimates through orbit determination, calculation of covariance realism test statistics at each covariance propagation point, and proper assessment of those test statistics. An empirical cumulative distribution function (ECDF) Goodness-of-Fit (GOF) method is employed to determine if a covariance is properly sized by comparing the empirical distribution of Mahalanobis distance calculations to the hypothesized parent 3-DoF chi-squared distribution. To realistically size a covariance for collision probability calculations, this study uses a state noise compensation algorithm that adds process noise to the definitive epoch covariance to account for uncertainty in the force model. Process noise is added until the GOF tests pass a group significance level threshold. The results of this study indicate that when outliers attributed to persistently high or extreme levels of solar activity are removed, the aforementioned covariance realism compensation method produces a tuned covariance with up to 80 to 90% of the covariance propagation timespan passing (against a 60% minimum passing threshold) the GOF tests-a quite satisfactory and useful result.

  7. Semi-automatic classification of skeletal morphology in genetically altered mice using flat-panel volume computed tomography.

    Christian Dullin

    2007-07-01

    Full Text Available Rapid progress in exploring the human and mouse genome has resulted in the generation of a multitude of mouse models to study gene functions in their biological context. However, effective screening methods that allow rapid noninvasive phenotyping of transgenic and knockout mice are still lacking. To identify murine models with bone alterations in vivo, we used flat-panel volume computed tomography (fpVCT for high-resolution 3-D imaging and developed an algorithm with a computational intelligence system. First, we tested the accuracy and reliability of this approach by imaging discoidin domain receptor 2- (DDR2- deficient mice, which display distinct skull abnormalities as shown by comparative landmark-based analysis. High-contrast fpVCT data of the skull with 200 microm isotropic resolution and 8-s scan time allowed segmentation and computation of significant shape features as well as visualization of morphological differences. The application of a trained artificial neuronal network to these datasets permitted a semi-automatic and highly accurate phenotype classification of DDR2-deficient compared to C57BL/6 wild-type mice. Even heterozygous DDR2 mice with only subtle phenotypic alterations were correctly determined by fpVCT imaging and identified as a new class. In addition, we successfully applied the algorithm to classify knockout mice lacking the DDR1 gene with no apparent skull deformities. Thus, this new method seems to be a potential tool to identify novel mouse phenotypes with skull changes from transgenic and knockout mice on the basis of random mutagenesis as well as from genetic models. However for this purpose, new neuronal networks have to be created and trained. In summary, the combination of fpVCT images with artificial neuronal networks provides a reliable, novel method for rapid, cost-effective, and noninvasive primary screening tool to detect skeletal phenotypes in mice.

  8. Evaluation of genetic alteration induced by radon gas using the micronucleus test (Tradescantia sp. clone KU-20)

    Bruschi, Armando L.; Azevedo, Heliana de; Macacini, Jose F.; Roque, Claudio V.

    2011-01-01

    The first observations over the existence of radon gas (Rn), initially known as 'thorium emanation', were carried out between the end of 19 th and beginning of 20 th centuries. A result of uranium-238 (U 238 ) radioactive decay, radon is a tasteless, odorless and colorless gas under room temperature, with a 3.825-day half life and particle α emission in its decay, and as final product of its disintegration, the stable lead-206 isotope (Pb 206 ). Being it is the gas with the highest density known, closed and poor ventilated environments are favorable to its accumulation, with its inhalation being the highest health risk. The use of vegetal bioindicators has shown to be excellent on the monitoring of air quality and on mutagenic potential of various pollutants contained in the atmosphere. Within this context, the objective of this study was to evaluate the micronucleus test application potential utilizing the Tradescantia sp. clone KU-20, in order to evaluate genetic alterations induced by radon gas. Stems of Tradescantia sp. clone KU-20, previously immerse in Hoagland solution, were introduced in a radon detection equipment's calibration chamber (Alphaguard), containing radium salt. Afterwards, the accommodated stems were exposed to radon gas (the average radon concentration was 7.639 KBq/m3) for 24 hours. The results demonstrated an increase on micronucleus formation (39.23 + 2.143 MCN/100 tetrads) in stems exposed in relation to the negative control (18.00 + 1.396 MCN/100 tetrads). The difference between the values indicated a significant increase on micronucleus frequency in the inflorescences subjected to radon gas. The presented results demonstrated the micronucleus test application potential using Tradescantia clone KU-20 to evaluate genetic effects induced by radon gas. (author)

  9. Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature

    Jackline P. Ayres-Silva

    2018-02-01

    Full Text Available The genetic events associated with transformation of myeloproliferative neoplasms (MPNs to secondary acute myeloid leukemia (sAML, particularly in the subgroup of essential thrombocythemia (ET patients, remain incompletely understood. Deep studies using high-throughput methods might lead to a better understanding of genetic landscape of ET patients who transformed to sAML. We performed array-based comparative genomic hybridization (aCGH and whole exome sequencing (WES to analyze paired samples from ET and sAML phases. We investigated five patients with previous history of MPN, which four had initial diagnosis of ET (one case harboring JAK2 p.Val617Phe and the remaining three CALR type II p.Lys385fs*47, and one was diagnosed with MPN/myelodysplastic syndrome with thrombocytosis (SF3B1 p.Lys700Glu. All were homogeneously treated with hydroxyurea, but subsequently transformed to sAML (mean time of 6 years/median of 4 years to transformation. Two of them have chromosomal abnormalities, and both acquire 2p gain and 5q deletion at sAML stage. The molecular mechanisms associated with leukemic progression in MPN patients are not clear. Our WES data showed TP53 alterations recurrently observed as mutations (missense and frameshift and monoallelic loss. On the other hand, aCGH showed novel chromosome abnormalities (+2p and del5q potentially associated with disease progression. The results reported here add valuable information to the still fragmented molecular basis of ET to sAML evolution. Further studies are necessary to identify minimal deleted/amplified region and genes relevant to sAML transformation.

  10. Advanced Covariance-Based Stochastic Inversion and Neuro-Genetic Optimization for Rosetta CONSERT Radar Data to Improve Spatial Resolution of Multi-Fractal Depth Profiles for Cometary Nucleus

    Edenhofer, Peter; Ulamec, Stephan

    2015-04-01

    The paper is devoted to results of doctoral research work at University of Bochum as applied to the radar transmission experiment CONSERT of the ESA cometary mission Rosetta. This research aims at achieving the limits of optimum spatial (and temporal) resolution for radar remote sensing by implementation of covariance informations concerned with error-balanced control as well as coherence of wave propagation effects through random composite media involved (based on Joel Franklin's approach of extended stochastic inversion). As a consequence the well-known inherent numerical instabilities of remote sensing are significantly reduced in a robust way by increasing the weight of main diagonal elements of the resulting composite matrix to be inverted with respect to off-diagonal elements following synergy relations as to the principle of correlation receiver in wireless telecommunications. It is shown that the enhancement of resolution for remote sensing holds for an integral and differential equation approach of inversion as well. In addition to that the paper presents a discussion on how the efficiency of inversion for radar data gets achieved by an overall optimization of inversion due to a novel neuro-genetic approach. Such kind of approach is in synergy with the priority research program "Organic Computing" of DFG / German Research Organization. This Neuro-Genetic Optimization (NGO) turns out, firstly, to take into account more detailed physical informations supporting further improved resolution such as the process of accretion for cometary nucleus, wave propagation effects from rough surfaces, ground clutter, nonlinear focusing, etc. as well as, secondly, to accelerate the computing process of inversion in a really significantly enhanced and fast way, e.g., enabling online-control of autonomous processes such as detection of unknown objects, navigation, etc. The paper describes in some detail how this neuro-genetic approach of optimization is incorporated into the

  11. Genetically altering the expression of neutral trehalase gene affects conidiospore thermotolerance of the entomopathogenic fungus Metarhizium acridum

    Peng Guoxiong

    2011-02-01

    Full Text Available Abstract Background The entomopathogenic fungus Metarhizium acridum has been used as an important biocontrol agent instead of insecticides for controlling crop pests throughout the world. However, its virulence varies with environmental factors, especially temperature. Neutral trehalase (Ntl hydrolyzes trehalose, which plays a role in environmental stress response in many organisms, including M. acridum. Demonstration of a relationship between Ntl and thermotolerance or virulence may offer a new strategy for enhancing conidiospore thermotolerance of entomopathogenic fungi through genetic engineering. Results We selected four Ntl over-expression and four Ntl RNA interference (RNAi transformations in which Ntl expression is different. Compared to the wild-type, Ntl mRNA expression was reduced to 35-66% in the RNAi mutants and increased by 2.5-3.5-fold in the over-expression mutants. The RNAi conidiospores exhibited less trehalase activity, accumulated more trehalose, and were much more tolerant of heat stress than the wild-type. The opposite effects were found in conidiospores of over-expression mutants compared to RNAi mutants. Furthermore, virulence was not altered in the two types of mutants compared to the wild type. Conclusions Ntl controlled trehalose accumulation in M. acridum by degrading trehalose, and thus affected conidiospore thermotolerance. These results offer a new strategy for enhancing conidiospore thermotolerance of entomopathogenic fungi without affecting virulence.

  12. Advancement of Phenotype Transformation of Cancer-associated Fibroblasts: 
from Genetic Alterations to Epigenetic Modification

    Dali CHEN

    2015-02-01

    Full Text Available In the field of human cancer research, even though the vast majority attentions were paid to tumor cells as “the seeds”, the roles of tumor microenvironments as “the soil” are gradually explored in recent years. As a dominant compartment of tumor microenvironments, cancer-associated fibroblasts (CAFs were discovered to correlated with tumorigenesis, tumor progression and prognosis. And the exploration of the mechanisms of CAF phenotype transformation would conducive to the further understand of the CAFs function in human cancers. As we known that CAFs have four main origins, including epithelial cells, endothelial cells, mesenchymal stem cells (MSCs and local mesenchymal cells. However, researchers found that all these origins finally conduct similiar phenotypes from intrinsic to extrinsic ones. Thus, what and how a mechanism can conduct the phenotype transformation of CAFs with different origins? Two viewpoints are proposed to try to answer the quetsion, involving genetic alterations and epigenetic modifications. This review will systematically summarize the advancement of mechanisms of CAF phenotype transformations in the aspect of genentic and epigenetic modifications.

  13. Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism

    Wanchun Yang

    2014-01-01

    Full Text Available Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR, a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1 activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1 as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals.

  14. Contributions to Large Covariance and Inverse Covariance Matrices Estimation

    Kang, Xiaoning

    2016-01-01

    Estimation of covariance matrix and its inverse is of great importance in multivariate statistics with broad applications such as dimension reduction, portfolio optimization, linear discriminant analysis and gene expression analysis. However, accurate estimation of covariance or inverse covariance matrices is challenging due to the positive definiteness constraint and large number of parameters, especially in the high-dimensional cases. In this thesis, I develop several approaches for estimat...

  15. Covariant Lyapunov vectors

    Ginelli, Francesco; Politi, Antonio; Chaté, Hugues; Livi, Roberto

    2013-01-01

    Recent years have witnessed a growing interest in covariant Lyapunov vectors (CLVs) which span local intrinsic directions in the phase space of chaotic systems. Here, we review the basic results of ergodic theory, with a specific reference to the implications of Oseledets’ theorem for the properties of the CLVs. We then present a detailed description of a ‘dynamical’ algorithm to compute the CLVs and show that it generically converges exponentially in time. We also discuss its numerical performance and compare it with other algorithms presented in the literature. We finally illustrate how CLVs can be used to quantify deviations from hyperbolicity with reference to a dissipative system (a chain of Hénon maps) and a Hamiltonian model (a Fermi–Pasta–Ulam chain). This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Lyapunov analysis: from dynamical systems theory to applications’. (paper)

  16. Deriving covariant holographic entanglement

    Dong, Xi [School of Natural Sciences, Institute for Advanced Study, Princeton, NJ 08540 (United States); Lewkowycz, Aitor [Jadwin Hall, Princeton University, Princeton, NJ 08544 (United States); Rangamani, Mukund [Center for Quantum Mathematics and Physics (QMAP), Department of Physics, University of California, Davis, CA 95616 (United States)

    2016-11-07

    We provide a gravitational argument in favour of the covariant holographic entanglement entropy proposal. In general time-dependent states, the proposal asserts that the entanglement entropy of a region in the boundary field theory is given by a quarter of the area of a bulk extremal surface in Planck units. The main element of our discussion is an implementation of an appropriate Schwinger-Keldysh contour to obtain the reduced density matrix (and its powers) of a given region, as is relevant for the replica construction. We map this contour into the bulk gravitational theory, and argue that the saddle point solutions of these replica geometries lead to a consistent prescription for computing the field theory Rényi entropies. In the limiting case where the replica index is taken to unity, a local analysis suffices to show that these saddles lead to the extremal surfaces of interest. We also comment on various properties of holographic entanglement that follow from this construction.

  17. Networks of myelin covariance.

    Melie-Garcia, Lester; Slater, David; Ruef, Anne; Sanabria-Diaz, Gretel; Preisig, Martin; Kherif, Ferath; Draganski, Bogdan; Lutti, Antoine

    2018-04-01

    Networks of anatomical covariance have been widely used to study connectivity patterns in both normal and pathological brains based on the concurrent changes of morphometric measures (i.e., cortical thickness) between brain structures across subjects (Evans, ). However, the existence of networks of microstructural changes within brain tissue has been largely unexplored so far. In this article, we studied in vivo the concurrent myelination processes among brain anatomical structures that gathered together emerge to form nonrandom networks. We name these "networks of myelin covariance" (Myelin-Nets). The Myelin-Nets were built from quantitative Magnetization Transfer data-an in-vivo magnetic resonance imaging (MRI) marker of myelin content. The synchronicity of the variations in myelin content between anatomical regions was measured by computing the Pearson's correlation coefficient. We were especially interested in elucidating the effect of age on the topological organization of the Myelin-Nets. We therefore selected two age groups: Young-Age (20-31 years old) and Old-Age (60-71 years old) and a pool of participants from 48 to 87 years old for a Myelin-Nets aging trajectory study. We found that the topological organization of the Myelin-Nets is strongly shaped by aging processes. The global myelin correlation strength, between homologous regions and locally in different brain lobes, showed a significant dependence on age. Interestingly, we also showed that the aging process modulates the resilience of the Myelin-Nets to damage of principal network structures. In summary, this work sheds light on the organizational principles driving myelination and myelin degeneration in brain gray matter and how such patterns are modulated by aging. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  18. General Galilei Covariant Gaussian Maps

    Gasbarri, Giulio; Toroš, Marko; Bassi, Angelo

    2017-09-01

    We characterize general non-Markovian Gaussian maps which are covariant under Galilean transformations. In particular, we consider translational and Galilean covariant maps and show that they reduce to the known Holevo result in the Markovian limit. We apply the results to discuss measures of macroscopicity based on classicalization maps, specifically addressing dissipation, Galilean covariance and non-Markovianity. We further suggest a possible generalization of the macroscopicity measure defined by Nimmrichter and Hornberger [Phys. Rev. Lett. 110, 16 (2013)].

  19. Fast Computing for Distance Covariance

    Huo, Xiaoming; Szekely, Gabor J.

    2014-01-01

    Distance covariance and distance correlation have been widely adopted in measuring dependence of a pair of random variables or random vectors. If the computation of distance covariance and distance correlation is implemented directly accordingly to its definition then its computational complexity is O($n^2$) which is a disadvantage compared to other faster methods. In this paper we show that the computation of distance covariance and distance correlation of real valued random variables can be...

  20. Targeted capture massively parallel sequencing analysis of LCIS and invasive lobular cancer: Repertoire of somatic genetic alterations and clonal relationships.

    Sakr, Rita A; Schizas, Michail; Carniello, Jose V Scarpa; Ng, Charlotte K Y; Piscuoglio, Salvatore; Giri, Dilip; Andrade, Victor P; De Brot, Marina; Lim, Raymond S; Towers, Russell; Weigelt, Britta; Reis-Filho, Jorge S; King, Tari A

    2016-02-01

    Lobular carcinoma in situ (LCIS) has been proposed as a non-obligate precursor of invasive lobular carcinoma (ILC). Here we sought to define the repertoire of somatic genetic alterations in pure LCIS and in synchronous LCIS and ILC using targeted massively parallel sequencing. DNA samples extracted from microdissected LCIS, ILC and matched normal breast tissue or peripheral blood from 30 patients were subjected to massively parallel sequencing targeting all exons of 273 genes, including the genes most frequently mutated in breast cancer and DNA repair-related genes. Single nucleotide variants and insertions and deletions were identified using state-of-the-art bioinformatics approaches. The constellation of somatic mutations found in LCIS (n = 34) and ILC (n = 21) were similar, with the most frequently mutated genes being CDH1 (56% and 66%, respectively), PIK3CA (41% and 52%, respectively) and CBFB (12% and 19%, respectively). Among 19 LCIS and ILC synchronous pairs, 14 (74%) had at least one identical mutation in common, including identical PIK3CA and CDH1 mutations. Paired analysis of independent foci of LCIS from 3 breasts revealed at least one common mutation in each of the 3 pairs (CDH1, PIK3CA, CBFB and PKHD1L1). LCIS and ILC have a similar repertoire of somatic mutations, with PIK3CA and CDH1 being the most frequently mutated genes. The presence of identical mutations between LCIS-LCIS and LCIS-ILC pairs demonstrates that LCIS is a clonal neoplastic lesion, and provides additional evidence that at least some LCIS are non-obligate precursors of ILC. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  1. An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients.

    Parlanti, Eleonora; Pietraforte, Donatella; Iorio, Egidio; Visentin, Sergio; De Nuccio, Chiara; Zijno, Andrea; D'Errico, Mariarosaria; Simonelli, Valeria; Sanchez, Massimo; Fattibene, Paola; Falchi, Mario; Dogliotti, Eugenia

    2015-12-01

    Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O₂₋• and H₂O₂ being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance (¹H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a hallmark of cancer risk. The increased MN frequency was not affected by inhibition of ROS to normal levels by N-acetyl-L-cysteine. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Covariant electromagnetic field lines

    Hadad, Y.; Cohen, E.; Kaminer, I.; Elitzur, A. C.

    2017-08-01

    Faraday introduced electric field lines as a powerful tool for understanding the electric force, and these field lines are still used today in classrooms and textbooks teaching the basics of electromagnetism within the electrostatic limit. However, despite attempts at generalizing this concept beyond the electrostatic limit, such a fully relativistic field line theory still appears to be missing. In this work, we propose such a theory and define covariant electromagnetic field lines that naturally extend electric field lines to relativistic systems and general electromagnetic fields. We derive a closed-form formula for the field lines curvature in the vicinity of a charge, and show that it is related to the world line of the charge. This demonstrates how the kinematics of a charge can be derived from the geometry of the electromagnetic field lines. Such a theory may also provide new tools in modeling and analyzing electromagnetic phenomena, and may entail new insights regarding long-standing problems such as radiation-reaction and self-force. In particular, the electromagnetic field lines curvature has the attractive property of being non-singular everywhere, thus eliminating all self-field singularities without using renormalization techniques.

  3. Covariation in Natural Causal Induction.

    Cheng, Patricia W.; Novick, Laura R.

    1991-01-01

    Biases and models usually offered by cognitive and social psychology and by philosophy to explain causal induction are evaluated with respect to focal sets (contextually determined sets of events over which covariation is computed). A probabilistic contrast model is proposed as underlying covariation computation in natural causal induction. (SLD)

  4. Networks of myelin covariance

    Slater, David; Ruef, Anne; Sanabria‐Diaz, Gretel; Preisig, Martin; Kherif, Ferath; Draganski, Bogdan; Lutti, Antoine

    2017-01-01

    Abstract Networks of anatomical covariance have been widely used to study connectivity patterns in both normal and pathological brains based on the concurrent changes of morphometric measures (i.e., cortical thickness) between brain structures across subjects (Evans, 2013). However, the existence of networks of microstructural changes within brain tissue has been largely unexplored so far. In this article, we studied in vivo the concurrent myelination processes among brain anatomical structures that gathered together emerge to form nonrandom networks. We name these “networks of myelin covariance” (Myelin‐Nets). The Myelin‐Nets were built from quantitative Magnetization Transfer data—an in‐vivo magnetic resonance imaging (MRI) marker of myelin content. The synchronicity of the variations in myelin content between anatomical regions was measured by computing the Pearson's correlation coefficient. We were especially interested in elucidating the effect of age on the topological organization of the Myelin‐Nets. We therefore selected two age groups: Young‐Age (20–31 years old) and Old‐Age (60–71 years old) and a pool of participants from 48 to 87 years old for a Myelin‐Nets aging trajectory study. We found that the topological organization of the Myelin‐Nets is strongly shaped by aging processes. The global myelin correlation strength, between homologous regions and locally in different brain lobes, showed a significant dependence on age. Interestingly, we also showed that the aging process modulates the resilience of the Myelin‐Nets to damage of principal network structures. In summary, this work sheds light on the organizational principles driving myelination and myelin degeneration in brain gray matter and how such patterns are modulated by aging. PMID:29271053

  5. Covariance Manipulation for Conjunction Assessment

    Hejduk, M. D.

    2016-01-01

    The manipulation of space object covariances to try to provide additional or improved information to conjunction risk assessment is not an uncommon practice. Types of manipulation include fabricating a covariance when it is missing or unreliable to force the probability of collision (Pc) to a maximum value ('PcMax'), scaling a covariance to try to improve its realism or see the effect of covariance volatility on the calculated Pc, and constructing the equivalent of an epoch covariance at a convenient future point in the event ('covariance forecasting'). In bringing these methods to bear for Conjunction Assessment (CA) operations, however, some do not remain fully consistent with best practices for conducting risk management, some seem to be of relatively low utility, and some require additional information before they can contribute fully to risk analysis. This study describes some basic principles of modern risk management (following the Kaplan construct) and then examines the PcMax and covariance forecasting paradigms for alignment with these principles; it then further examines the expected utility of these methods in the modern CA framework. Both paradigms are found to be not without utility, but only in situations that are somewhat carefully circumscribed.

  6. Defining population structure and genetic signatures of decline in the giant garter snake (Thamnophis gigas): implications for conserving threatened species within highly altered landscapes

    Wood, Dustin A.; Halstead, Brian J.; Casazza, Michael L.; Hansen, Eric C.; Wylie, Glenn D.; Vandergast, Amy

    2015-01-01

    Anthropogenic habitat fragmentation can disrupt the ability of species to disperse across landscapes, which can alter the levels and distribution of genetic diversity within populations and negatively impact long-term viability. The giant gartersnake (Thamnophis gigas) is a state and federally threatened species that historically occurred in the wetland habitats of California’s Great Central Valley. Despite the loss of 93 % of historic wetlands throughout the Central Valley, giant gartersnakes continue to persist in relatively small, isolated patches of highly modified agricultural wetlands. Gathering information regarding genetic diversity and effective population size represents an essential component for conservation management programs aimed at this species. Previous mitochondrial sequence studies have revealed historical patterns of differentiation, yet little is known about contemporary population structure and diversity. On the basis of 15 microsatellite loci, we estimate population structure and compare indices of genetic diversity among populations spanning seven drainage basins within the Central Valley. We sought to understand how habitat loss may have affected genetic differentiation, genetic diversity and effective population size, and what these patterns suggest in terms of management and restoration actions. We recovered five genetic clusters that were consistent with regional drainage basins, although three northern basins within the Sacramento Valley formed a single genetic cluster. Our results show that northern drainage basin populations have higher connectivity than among central and southern basins populations, and that greater differentiation exists among the more geographically isolated populations in the central and southern portion of the species’ range. Genetic diversity measures among basins were significantly different, and were generally lower in southern basin populations. Levels of inbreeding and evidence of population

  7. Covariance matrices of experimental data

    Perey, F.G.

    1978-01-01

    A complete statement of the uncertainties in data is given by its covariance matrix. It is shown how the covariance matrix of data can be generated using the information available to obtain their standard deviations. Determination of resonance energies by the time-of-flight method is used as an example. The procedure for combining data when the covariance matrix is non-diagonal is given. The method is illustrated by means of examples taken from the recent literature to obtain an estimate of the energy of the first resonance in carbon and for five resonances of 238 U

  8. Evaluation and processing of covariance data

    Wagner, M.

    1993-01-01

    These proceedings of a specialists'meeting on evaluation and processing of covariance data is divided into 4 parts bearing on: part 1- Needs for evaluated covariance data (2 Papers), part 2- generation of covariance data (15 Papers), part 3- Processing of covariance files (2 Papers), part 4-Experience in the use of evaluated covariance data (2 Papers)

  9. Alterations of social interaction through genetic and environmental manipulation of the 22q11.2 gene Sept5 in the mouse brain.

    Harper, Kathryn M; Hiramoto, Takeshi; Tanigaki, Kenji; Kang, Gina; Suzuki, Go; Trimble, William; Hiroi, Noboru

    2012-08-01

    Social behavior dysfunction is a symptomatic element of schizophrenia and autism spectrum disorder (ASD). Although altered activities in numerous brain regions are associated with defective social cognition and perception, the causative relationship between these altered activities and social cognition and perception-and their genetic underpinnings-are not known in humans. To address these issues, we took advantage of the link between hemizygous deletion of human chromosome 22q11.2 and high rates of social behavior dysfunction, schizophrenia and ASD. We genetically manipulated Sept5, a 22q11.2 gene, and evaluated its role in social interaction in mice. Sept5 deficiency, against a high degree of homogeneity in a congenic genetic background, selectively impaired active affiliative social interaction in mice. Conversely, virally guided overexpression of Sept5 in the hippocampus or, to a lesser extent, the amygdala elevated levels of active affiliative social interaction in C57BL/6J mice. Congenic knockout mice and mice overexpressing Sept5 in the hippocampus or amygdala were indistinguishable from control mice in novelty and olfactory responses, anxiety or motor activity. Moreover, post-weaning individual housing, an environmental condition designed to reduce stress in male mice, selectively raised levels of Sept5 protein in the amygdala and increased active affiliative social interaction in C57BL/6J mice. These findings identify this 22q11.2 gene in the hippocampus and amygdala as a determinant of social interaction and suggest that defective social interaction seen in 22q11.2-associated schizophrenia and ASD can be genetically and environmentally modified by altering this 22q11.2 gene.

  10. MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

    Valera, Alexandra; López-Guillermo, Armando; Cardesa-Salzmann, Teresa; Climent, Fina; González-Barca, Eva; Mercadal, Santiago; Espinosa, Iñigo; Novelli, Silvana; Briones, Javier; Mate, José L; Salamero, Olga; Sancho, Juan M; Arenillas, Leonor; Serrano, Sergi; Erill, Nadina; Martínez, Daniel; Castillo, Paola; Rovira, Jordina; Martínez, Antonio; Campo, Elias; Colomo, Luis

    2013-10-01

    MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rearrangements (MYC double/triple-hit) in 4%, MYC amplifications in 2% and MYC gains in 19%. MYC single-hit, MYC double/triple-hit and MYC amplifications, but not MYC gains or other gene rearrangements, were associated with unfavorable progression-free survival and overall survival. MYC protein expression, evaluated using computerized image analysis, captured the unfavorable prognosis of MYC translocations/amplifications and identified an additional subset of patients without gene alterations but with similar poor prognosis. Patients with tumors expressing both MYC/BCL2 had the worst prognosis, whereas those with double-negative tumors had the best outcome. High MYC expression was associated with shorter overall survival irrespectively of the International Prognostic Index and BCL2 expression. In conclusion, MYC protein expression identifies a subset of diffuse large B-cell lymphoma with very poor prognosis independently of gene alterations and other prognostic parameters.

  11. On Galilean covariant quantum mechanics

    Horzela, A.; Kapuscik, E.; Kempczynski, J.; Joint Inst. for Nuclear Research, Dubna

    1991-08-01

    Formalism exhibiting the Galilean covariance of wave mechanics is proposed. A new notion of quantum mechanical forces is introduced. The formalism is illustrated on the example of the harmonic oscillator. (author)

  12. Genetic variations altering FSH action affect circulating hormone levels as well as follicle growth in healthy peripubertal girls.

    Busch, Alexander S; Hagen, Casper P; Almstrup, Kristian; Main, Katharina M; Juul, Anders

    2016-04-01

    Do variants of the genes encoding follicle stimulating hormone (FSH) beta subunit (B) and FSH receptor (R) impact circulating reproductive hormone levels and ovarian follicle maturation in healthy peripubertal girls? FSHB and FSHR genetic variants exert, alone or their combination, distinct effects on reproductive hormone levels as well as ovarian follicle maturation in healthy peripubertal girls. FSHB and FSHR genetic variants impact reproductive hormone levels as well as associated pathologies in women. While FSHR c. 2039A>G is known to alter gonadotrophin levels in women, FSHR c.-29G>A has not yet been shown to exert effect and there are conflicting results concerning FSHB c.-211G>T. This population-based study included 633 girls recruited as part of two cohorts, the COPENHAGEN Puberty Study (2006-2014, a cross-sectional and ongoing longitudinal study) and the Copenhagen Mother-Child Cohort (1997-2002, including transabdominal ultrasound (TAUS) of the ovaries in a subset of 91 peripubertal girls). Clinical examinations, including pubertal breast stage (Tanner's classification B1-B5) were performed. Circulating levels of FSH, luteinizing hormone (LH), estradiol, anti-Mullerian hormone (AMH) and inhibin-B were assessed by immunoassays. In a subset of the girls (n = 91), ovarian volume and the number/size of antral follicles were assessed by TAUS. Genotypes were determined by competitive PCR. FSHR c.2039A>G minor alleles were positively associated with serum FSH (β = 0.08, P = 0.004), LH (β = 0.06, P = 0.012) and estradiol (β = 0.06, P = 0.017) (adjusted for Tanner stages). In a combined model, FSHR c.-29G>A and FSHR c.2039A>G alleles were positively associated with FSH levels in early-pubertal girls (B2 + B3, n = 327, r = 0.1, P = 0.02) and in young adolescents (B4 + B5, n = 149, r = 0.2, P = 0.01). Serum AMH and inhibin B levels were not significantly influenced by the single nucleotide polymorphisms (SNPs). Single SNPs were not associated with follicles

  13. Recent and projected increases in atmospheric CO2 concentration can enhance gene flow between wild and genetically altered rice (Oryza sativa).

    Ziska, Lewis H; Gealy, David R; Tomecek, Martha B; Jackson, Aaron K; Black, Howard L

    2012-01-01

    Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO(2) between genetically modified crops and wild, weedy relatives increase the spread of novel genes, potentially altering evolutionary fitness? Here we show that increasing CO(2) from an early 20(th) century concentration (300 µmol mol(-1)) to current (400 µmol mol(-1)) and projected, mid-21(st) century (600 µmol mol(-1)) values, enhanced the flow of genes from wild, weedy rice to the genetically altered, herbicide resistant, cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300 to 600 µmol mol(-1). The increase in outcrossing and gene transfer was associated with differential increases in plant height, as well as greater tiller and panicle production in the wild, relative to the cultivated population. In addition, increasing CO(2) also resulted in a greater synchronicity in flowering times between the two populations. The observed changes reported here resulted in a subsequent increase in rice dedomestication and a greater number of weedy, herbicide-resistant hybrid progeny. Overall, these data suggest that differential phenological responses to rising atmospheric CO(2) could result in enhanced flow of novel genes and greater success of feral plant species in agroecosystems.

  14. Recent and projected increases in atmospheric CO2 concentration can enhance gene flow between wild and genetically altered rice (Oryza sativa.

    Lewis H Ziska

    Full Text Available Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO(2 between genetically modified crops and wild, weedy relatives increase the spread of novel genes, potentially altering evolutionary fitness? Here we show that increasing CO(2 from an early 20(th century concentration (300 µmol mol(-1 to current (400 µmol mol(-1 and projected, mid-21(st century (600 µmol mol(-1 values, enhanced the flow of genes from wild, weedy rice to the genetically altered, herbicide resistant, cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300 to 600 µmol mol(-1. The increase in outcrossing and gene transfer was associated with differential increases in plant height, as well as greater tiller and panicle production in the wild, relative to the cultivated population. In addition, increasing CO(2 also resulted in a greater synchronicity in flowering times between the two populations. The observed changes reported here resulted in a subsequent increase in rice dedomestication and a greater number of weedy, herbicide-resistant hybrid progeny. Overall, these data suggest that differential phenological responses to rising atmospheric CO(2 could result in enhanced flow of novel genes and greater success of feral plant species in agroecosystems.

  15. VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.

    Nyhan, Michelle J

    2012-01-31

    BACKGROUND: von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-alpha (HIF-alpha), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP) A2\\/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited. We evaluated the impact of VHL genetic alterations on the expression of several pVHL protein targets in paired normal and tumor tissue. METHODS: The VHL gene was sequenced in 23 CCRCC patients and VHL transcript levels were evaluated by real-time RT-PCR. Expression of pVHL\\'s protein targets were determined by Western blotting in 17 paired patient samples. RESULTS: VHL genetic alterations were identified in 43.5% (10\\/23) of CCRCCs. HIF-1alpha, HIF-2alpha and CAIX were up-regulated in 88.2% (15\\/17), 100% (17\\/17) and 88.2% (15\\/17) of tumors respectively and their expression is independent of VHL status. hnRNP A2\\/B1 and osteopontin expression was variable in CCRCCs and had no association with VHL genetic status. CONCLUSION: As expression of these proposed pVHL targets can be achieved independently of VHL mutation (and possibly by hypoxia alone), these data suggests that other pVHL targets may be more crucial in renal carcinogenesis.

  16. Rapid Genetic and Epigenetic Alterations under Intergeneric Genomic Shock in Newly Synthesized Chrysanthemum morifolium × Leucanthemum paludosum Hybrids (Asteraceae)

    Wang, Haibin; Jiang, Jiafu; Chen, Sumei; Qi, Xiangyu; Fang, Weimin; Guan, Zhiyong; Teng, Nianjun; Liao, Yuan; Chen, Fadi

    2014-01-01

    The Asteraceae family is at the forefront of the evolution due to frequent hybridization. Hybridization is associated with the induction of widespread genetic and epigenetic changes and has played an important role in the evolution of many plant taxa. We attempted the intergeneric cross Chrysanthemum morifolium × Leucanthemum paludosum. To obtain the success in cross, we have to turn to ovule rescue. DNA profiling of the amphihaploid and amphidiploid was investigated using amplified fragment length polymorphism, sequence-related amplified polymorphism, start codon targeted polymorphism, and methylation-sensitive amplification polymorphism (MSAP). Hybridization induced rapid changes at the genetic and the epigenetic levels. The genetic changes mainly involved loss of parental fragments and gaining of novel fragments, and some eliminated sequences possibly from the noncoding region of L. paludosum. The MSAP analysis indicated that the level of DNA methylation was lower in the amphiploid (∼45%) than in the parental lines (51.5–50.6%), whereas it increased after amphidiploid formation. Events associated with intergeneric genomic shock were a feature of C. morifolium × L. paludosum hybrid, given that the genetic relationship between the parental species is relatively distant. Our results provide genetic and epigenetic evidence for understanding genomic shock in wide crosses between species in Asteraceae and suggest a need to expand our current evolutionary framework to encompass a genetic/epigenetic dimension when seeking to understand wide crosses. PMID:24407856

  17. Rapid genetic and epigenetic alterations under intergeneric genomic shock in newly synthesized Chrysanthemum morifolium x Leucanthemum paludosum hybrids (Asteraceae).

    Wang, Haibin; Jiang, Jiafu; Chen, Sumei; Qi, Xiangyu; Fang, Weimin; Guan, Zhiyong; Teng, Nianjun; Liao, Yuan; Chen, Fadi

    2014-01-01

    The Asteraceae family is at the forefront of the evolution due to frequent hybridization. Hybridization is associated with the induction of widespread genetic and epigenetic changes and has played an important role in the evolution of many plant taxa. We attempted the intergeneric cross Chrysanthemum morifolium × Leucanthemum paludosum. To obtain the success in cross, we have to turn to ovule rescue. DNA profiling of the amphihaploid and amphidiploid was investigated using amplified fragment length polymorphism, sequence-related amplified polymorphism, start codon targeted polymorphism, and methylation-sensitive amplification polymorphism (MSAP). Hybridization induced rapid changes at the genetic and the epigenetic levels. The genetic changes mainly involved loss of parental fragments and gaining of novel fragments, and some eliminated sequences possibly from the noncoding region of L. paludosum. The MSAP analysis indicated that the level of DNA methylation was lower in the amphiploid (∼45%) than in the parental lines (51.5-50.6%), whereas it increased after amphidiploid formation. Events associated with intergeneric genomic shock were a feature of C. morifolium × L. paludosum hybrid, given that the genetic relationship between the parental species is relatively distant. Our results provide genetic and epigenetic evidence for understanding genomic shock in wide crosses between species in Asteraceae and suggest a need to expand our current evolutionary framework to encompass a genetic/epigenetic dimension when seeking to understand wide crosses.

  18. Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression

    Neha S. Raghavan

    2018-01-01

    Full Text Available Major depressive disorder (MDD is a debilitating illness that affects twice as many women than men postpuberty. This female bias is thought to be caused by greater heritability of MDD in women and increased vulnerability induced by female sex hormones. We tested this hypothesis by removing the ovaries from prepubertal Wistar Kyoto (WKY more immobile (WMI females, a genetic animal model of depression, and its genetically close control, the WKY less immobile (WLI. In adulthood, prepubertally ovariectomized (PrePubOVX animals and their Sham-operated controls were tested for depression- and anxiety-like behaviors, using the routinely employed forced swim and open field tests, respectively, and RNA-sequencing was performed on their hippocampal RNA. Our results confirmed that the behavioral and hippocampal expression changes that occur after prepubertal ovariectomy are the consequences of an interaction between genetic predisposition to depressive behavior and ovarian hormone-regulated processes. Lack of ovarian hormones during and after puberty in the WLIs led to increased depression-like behavior. In WMIs, both depression- and anxiety-like behaviors worsened by prepubertal ovariectomy. The unbiased exploration of the hippocampal transcriptome identified sets of differentially expressed genes (DEGs between the strains and treatment groups. The relatively small number of hippocampal DEGs resulting from the genetic differences between the strains confirmed the genetic relatedness of these strains. Nevertheless, the differences in DEGs between the strains in response to prepubertal ovariectomy identified different molecular processes, including the importance of glucocorticoid receptor-mediated mechanisms, that may be causative of the increased depression-like behavior in the presence or absence of genetic predisposition. This study contributes to the understanding of hormonal maturation-induced changes in affective behaviors and the hippocampal

  19. Anthropogenic fragmentation may not alter pre-existing patterns of genetic diversity and differentiation in perennial shrubs.

    Llorens, Tanya M; Ayre, David J; Whelan, Robert J

    2018-04-01

    Many plant species have pollination and seed dispersal systems and evolutionary histories that have produced strong genetic structuring. These genetic patterns may be consistent with expectations following recent anthropogenic fragmentation, making it difficult to detect fragmentation effects if no prefragmentation genetic data are available. We used microsatellite markers to investigate whether severe habitat fragmentation may have affected the structure and diversity of populations of the endangered Australian bird-pollinated shrub Grevillea caleyi R.Br., by comparing current patterns of genetic structure and diversity with those of the closely related G. longifolia R.Br. that has a similar life history but has not experienced anthropogenic fragmentation. Grevillea caleyi and G. longifolia showed similar and substantial population subdivision at all spatial levels (global F' ST  = 0.615 and 0.454; S p  = 0.039 and 0.066), marked isolation by distance and large heterozygous deficiencies. These characteristics suggest long-term effects of inbreeding in self-compatible species that have poor seed dispersal, limited connectivity via pollen flow and undergo population bottlenecks because of periodic fires. Highly structured allele size distributions, most notably in G. caleyi, imply historical processes of drift and mutation were important in isolated subpopulations. Genetic diversity did not vary with population size but was lower in more isolated populations for both species. Through this comparison, we reject the hypothesis that anthropogenic fragmentation has impacted substantially on the genetic composition or structure of G. caleyi populations. Our results suggest that highly self-compatible species with limited dispersal may be relatively resilient to the genetic changes predicted to follow habitat fragmentation. © 2018 John Wiley & Sons Ltd.

  20. The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds

    Arati A. Inamdar

    2012-01-01

    Full Text Available Epidemiological studies link the herbicide paraquat to increased incidence of Parkinson's disease (PD. We previously reported that Drosophila exposed to paraquat recapitulate PD symptoms, including region-specific degeneration of dopaminergic neurons. Minocycline, a tetracycline derivative, exerts ameliorative effects in neurodegenerative disease models, including Drosophila. We investigated whether our environmental toxin-based PD model could contribute to an understanding of cellular and genetic mechanisms of minocycline action and whether we could assess potential interference with these drug effects in altered genetic backgrounds. Cofeeding of minocycline with paraquat prolonged survival, rescued mobility defects, blocked generation of reactive oxygen species, and extended dopaminergic neuron survival, as has been reported previously for a genetic model of PD in Drosophila. We then extended this study to identify potential interactions of minocycline with genes regulating dopamine homeostasis that might modify protection against paraquat and found that deficits in GTP cyclohydrolase adversely affect minocycline rescue. We further performed genetic studies to identify signaling pathways that are necessary for minocycline protection against paraquat toxicity and found that mutations in the Drosophila genes that encode c-Jun N-terminal kinase (JNK and Akt/Protein kinase B block minocycline rescue.

  1. FADS2 Genetic Variance in Combination with Fatty Acid Intake Might Alter Composition of the Fatty Acids in Brain.

    Thais S Rizzi

    Full Text Available Multiple lines of evidence suggest that fatty acids (FA play an important role in cognitive function. However, little is known about the functional genetic pathways involved in cognition. The main goals of this study were to replicate previously reported interaction effects between breast feeding (BF and FA desaturase (FADS genetic variation on IQ and to investigate the possible mechanisms by which these variants might moderate BF effect, focusing on brain expression. Using a sample of 534 twins, we observed a trend in the moderation of BF effects on IQ by FADS2 variation. In addition, we made use of publicly available gene expression databases from both humans (193 and mice (93 and showed that FADS2 variants also correlate with FADS1 brain expression (P-value<1.1E-03. Our results provide novel clues for the understanding of the genetic mechanisms regulating FA brain expression and improve the current knowledge of the FADS moderation effect on cognition.

  2. Multivariate covariance generalized linear models

    Bonat, W. H.; Jørgensen, Bent

    2016-01-01

    are fitted by using an efficient Newton scoring algorithm based on quasi-likelihood and Pearson estimating functions, using only second-moment assumptions. This provides a unified approach to a wide variety of types of response variables and covariance structures, including multivariate extensions......We propose a general framework for non-normal multivariate data analysis called multivariate covariance generalized linear models, designed to handle multivariate response variables, along with a wide range of temporal and spatial correlation structures defined in terms of a covariance link...... function combined with a matrix linear predictor involving known matrices. The method is motivated by three data examples that are not easily handled by existing methods. The first example concerns multivariate count data, the second involves response variables of mixed types, combined with repeated...

  3. GLq(N)-covariant quantum algebras and covariant differential calculus

    Isaev, A.P.; Pyatov, P.N.

    1992-01-01

    GL q (N)-covariant quantum algebras with generators satisfying quadratic polynomial relations are considered. It is that, up to some innessential arbitrariness, there are only two kinds of such quantum algebras, namely, the algebras with q-deformed commutation and q-deformed anticommutation relations. 25 refs

  4. GLq(N)-covariant quantum algebras and covariant differential calculus

    Isaev, A.P.; Pyatov, P.N.

    1993-01-01

    We consider GL q (N)-covariant quantum algebras with generators satisfying quadratic polynomial relations. We show that, up to some inessential arbitrariness, there are only two kinds of such quantum algebras, namely, the algebras with q-deformed commutation and q-deformed anticommutation relations. The connection with the bicovariant differential calculus on the linear quantum groups is discussed. (orig.)

  5. A class of covariate-dependent spatiotemporal covariance functions

    Reich, Brian J; Eidsvik, Jo; Guindani, Michele; Nail, Amy J; Schmidt, Alexandra M.

    2014-01-01

    In geostatistics, it is common to model spatially distributed phenomena through an underlying stationary and isotropic spatial process. However, these assumptions are often untenable in practice because of the influence of local effects in the correlation structure. Therefore, it has been of prolonged interest in the literature to provide flexible and effective ways to model non-stationarity in the spatial effects. Arguably, due to the local nature of the problem, we might envision that the correlation structure would be highly dependent on local characteristics of the domain of study, namely the latitude, longitude and altitude of the observation sites, as well as other locally defined covariate information. In this work, we provide a flexible and computationally feasible way for allowing the correlation structure of the underlying processes to depend on local covariate information. We discuss the properties of the induced covariance functions and discuss methods to assess its dependence on local covariate information by means of a simulation study and the analysis of data observed at ozone-monitoring stations in the Southeast United States. PMID:24772199

  6. Covariance functions across herd production levels for test day records on milk, fat, and protein yields

    Veerkamp, R.F.; Goddard, M.E.

    1998-01-01

    Multiple-trait BLUP evaluations of test day records require a large number of genetic parameters. This study estimated covariances with a reduced model that included covariance functions in two dimensions (stage of lactation and herd production level) and all three yield traits. Records came from

  7. Cosmic censorship conjecture revisited: covariantly

    Hamid, Aymen I M; Goswami, Rituparno; Maharaj, Sunil D

    2014-01-01

    In this paper we study the dynamics of the trapped region using a frame independent semi-tetrad covariant formalism for general locally rotationally symmetric (LRS) class II spacetimes. We covariantly prove some important geometrical results for the apparent horizon, and state the necessary and sufficient conditions for a singularity to be locally naked. These conditions bring out, for the first time in a quantitative and transparent manner, the importance of the Weyl curvature in deforming and delaying the trapped region during continual gravitational collapse, making the central singularity locally visible. (paper)

  8. Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma

    Kastrup, Ingelise Bjerring; Worm, Jesper; Ralfkiaer, Elisabeth

    2007-01-01

    The reduced folate carrier (RFC) is a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs, including methotrexate (MTX). Acquired alterations of the RFC gene have been associated with resistance to MTX in cancer cell lines and primary osteosarcomas. Here, we...

  9. Genetics

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  10. Alteration of sexual reproduction and genetic diversity in the kelp species Laminaria digitata at the southern limit of its range.

    Luz Valeria Oppliger

    Full Text Available Adaptation to marginal habitats at species range-limits has often been associated with parthenogenetic reproduction in terrestrial animals and plants. Laboratory observations have shown that brown algae exhibit a high propensity for parthenogenesis by various mechanisms. The kelp Laminaria digitata is an important component of the ecosystem in Northern European rocky intertidal habitats. We studied four L. digitata populations for the effects of marginality on genetic diversity and sexual reproduction. Two populations were marginal: One (Locquirec, in Northern Brittany was well within the geographic range, but was genetically isolated from other populations by large stretches of sandy beaches. Another population was at the range limits of the species (Quiberon, in Southern Brittany and was exposed to much higher seasonal temperature changes. Microsatellite analyses confirmed that these populations showed decreased genetic and allelic diversity, consistent with marginality and genetic isolation. Sporophytes from both marginal populations showed greatly diminished spore-production compared to central populations, but only the southern-limit population (Quiberon showed a high propensity for producing unreduced (2N spores. Unreduced 2N spores formed phenotypically normal gametophytes with nuclear area consistent with ≥2N DNA contents, and microsatellite studies suggested these were produced at least in part by automixis. However, despite this being the dominant path of spore production in Quiberon sporophyte individuals, the genetic evidence indicated the population was maintained mostly by sexual reproduction. Thus, although spore production and development showed the expected tendency of geographical parthenogenesis in marginal populations, this appeared to be a consequence of maladaptation, rather than an adaptation to, life in a marginal habitat.

  11. Alterations in the α2 δ ligand, thrombospondin-1, in a rat model of spontaneous absence epilepsy and in patients with idiopathic/genetic generalized epilepsies.

    Santolini, Ines; Celli, Roberta; Cannella, Milena; Imbriglio, Tiziana; Guiducci, Michela; Parisi, Pasquale; Schubert, Julian; Iacomino, Michele; Zara, Federico; Lerche, Holger; Moyanova, Slavianka; Ngomba, Richard Teke; van Luijtelaar, Gilles; Battaglia, Giuseppe; Bruno, Valeria; Striano, Pasquale; Nicoletti, Ferdinando

    2017-11-01

    Thrombospondins, which are known to interact with the α 2 δ subunit of voltage-sensitive calcium channels to stimulate the formation of excitatory synapses, have recently been implicated in the process of epileptogenesis. No studies have been so far performed on thrombospondins in models of absence epilepsy. We examined whether expression of the gene encoding for thrombospondin-1 was altered in the brain of WAG/Rij rats, which model absence epilepsy in humans. In addition, we examined the frequency of genetic variants of THBS1 in a large cohort of children affected by idiopathic/genetic generalized epilepsies (IGE/GGEs). We measured the transcripts of thrombospondin-1 and α 2 δ subunit, and protein levels of α 2 δ, Rab3A, and the vesicular glutamate transporter, VGLUT1, in the somatosensory cortex and ventrobasal thalamus of presymptomatic and symptomatic WAG/Rij rats and in two control strains by real-time polymerase chain reaction (PCR) and immunoblotting. We examined the genetic variants of THBS1 and CACNA2D1 in two independent cohorts of patients affected by IGE/GGE recruited through the Genetic Commission of the Italian League Against Epilepsy (LICE) and the EuroEPINOMICS-CoGIE Consortium. Thrombospondin-1 messenger RNA (mRNA) levels were largely reduced in the ventrobasal thalamus of both presymptomatic and symptomatic WAG/Rij rats, whereas levels in the somatosensory cortex were unchanged. VGLUT1 protein levels were also reduced in the ventrobasal thalamus of WAG/Rij rats. Genetic variants of THBS1 were significantly more frequent in patients affected by IGE/GGE than in nonepileptic controls, whereas the frequency of CACNA2D1 was unchanged. These findings suggest that thrombospondin-1 may have a role in the pathogenesis of IGE/GGEs. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  12. Hierarchical multivariate covariance analysis of metabolic connectivity.

    Carbonell, Felix; Charil, Arnaud; Zijdenbos, Alex P; Evans, Alan C; Bedell, Barry J

    2014-12-01

    Conventional brain connectivity analysis is typically based on the assessment of interregional correlations. Given that correlation coefficients are derived from both covariance and variance, group differences in covariance may be obscured by differences in the variance terms. To facilitate a comprehensive assessment of connectivity, we propose a unified statistical framework that interrogates the individual terms of the correlation coefficient. We have evaluated the utility of this method for metabolic connectivity analysis using [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. As an illustrative example of the utility of this approach, we examined metabolic connectivity in angular gyrus and precuneus seed regions of mild cognitive impairment (MCI) subjects with low and high β-amyloid burdens. This new multivariate method allowed us to identify alterations in the metabolic connectome, which would not have been detected using classic seed-based correlation analysis. Ultimately, this novel approach should be extensible to brain network analysis and broadly applicable to other imaging modalities, such as functional magnetic resonance imaging (MRI).

  13. Covariance matrix estimation for stationary time series

    Xiao, Han; Wu, Wei Biao

    2011-01-01

    We obtain a sharp convergence rate for banded covariance matrix estimates of stationary processes. A precise order of magnitude is derived for spectral radius of sample covariance matrices. We also consider a thresholded covariance matrix estimator that can better characterize sparsity if the true covariance matrix is sparse. As our main tool, we implement Toeplitz [Math. Ann. 70 (1911) 351–376] idea and relate eigenvalues of covariance matrices to the spectral densities or Fourier transforms...

  14. Condition Number Regularized Covariance Estimation.

    Won, Joong-Ho; Lim, Johan; Kim, Seung-Jean; Rajaratnam, Bala

    2013-06-01

    Estimation of high-dimensional covariance matrices is known to be a difficult problem, has many applications, and is of current interest to the larger statistics community. In many applications including so-called the "large p small n " setting, the estimate of the covariance matrix is required to be not only invertible, but also well-conditioned. Although many regularization schemes attempt to do this, none of them address the ill-conditioning problem directly. In this paper, we propose a maximum likelihood approach, with the direct goal of obtaining a well-conditioned estimator. No sparsity assumption on either the covariance matrix or its inverse are are imposed, thus making our procedure more widely applicable. We demonstrate that the proposed regularization scheme is computationally efficient, yields a type of Steinian shrinkage estimator, and has a natural Bayesian interpretation. We investigate the theoretical properties of the regularized covariance estimator comprehensively, including its regularization path, and proceed to develop an approach that adaptively determines the level of regularization that is required. Finally, we demonstrate the performance of the regularized estimator in decision-theoretic comparisons and in the financial portfolio optimization setting. The proposed approach has desirable properties, and can serve as a competitive procedure, especially when the sample size is small and when a well-conditioned estimator is required.

  15. Condition Number Regularized Covariance Estimation*

    Won, Joong-Ho; Lim, Johan; Kim, Seung-Jean; Rajaratnam, Bala

    2012-01-01

    Estimation of high-dimensional covariance matrices is known to be a difficult problem, has many applications, and is of current interest to the larger statistics community. In many applications including so-called the “large p small n” setting, the estimate of the covariance matrix is required to be not only invertible, but also well-conditioned. Although many regularization schemes attempt to do this, none of them address the ill-conditioning problem directly. In this paper, we propose a maximum likelihood approach, with the direct goal of obtaining a well-conditioned estimator. No sparsity assumption on either the covariance matrix or its inverse are are imposed, thus making our procedure more widely applicable. We demonstrate that the proposed regularization scheme is computationally efficient, yields a type of Steinian shrinkage estimator, and has a natural Bayesian interpretation. We investigate the theoretical properties of the regularized covariance estimator comprehensively, including its regularization path, and proceed to develop an approach that adaptively determines the level of regularization that is required. Finally, we demonstrate the performance of the regularized estimator in decision-theoretic comparisons and in the financial portfolio optimization setting. The proposed approach has desirable properties, and can serve as a competitive procedure, especially when the sample size is small and when a well-conditioned estimator is required. PMID:23730197

  16. Covariant Gauss law commutator anomaly

    Dunne, G.V.; Trugenberger, C.A.; Massachusetts Inst. of Tech., Cambridge

    1990-01-01

    Using a (fixed-time) hamiltonian formalism we derive a covariant form for the anomaly in the commutator algebra of Gauss law generators for chiral fermions interacting with a dynamical non-abelian gauge field in 3+1 dimensions. (orig.)

  17. Covariant gauges for constrained systems

    Gogilidze, S.A.; Khvedelidze, A.M.; Pervushin, V.N.

    1995-01-01

    The method of constructing of extended phase space for singular theories which permits the consideration of covariant gauges without the introducing of a ghost fields, is proposed. The extension of the phase space is carried out by the identification of the initial theory with an equivalent theory with higher derivatives and applying to it the Ostrogradsky method of Hamiltonian description. 7 refs

  18. Uncertainty covariances in robotics applications

    Smith, D.L.

    1984-01-01

    The application of uncertainty covariance matrices in the analysis of robot trajectory errors is explored. First, relevant statistical concepts are reviewed briefly. Then, a simple, hypothetical robot model is considered to illustrate methods for error propagation and performance test data evaluation. The importance of including error correlations is emphasized

  19. Touch imprint cytology with massively parallel sequencing (TIC-seq): a simple and rapid method to snapshot genetic alterations in tumors.

    Amemiya, Kenji; Hirotsu, Yosuke; Goto, Taichiro; Nakagomi, Hiroshi; Mochizuki, Hitoshi; Oyama, Toshio; Omata, Masao

    2016-12-01

    Identifying genetic alterations in tumors is critical for molecular targeting of therapy. In the clinical setting, formalin-fixed paraffin-embedded (FFPE) tissue is usually employed for genetic analysis. However, DNA extracted from FFPE tissue is often not suitable for analysis because of its low levels and poor quality. Additionally, FFPE sample preparation is time-consuming. To provide early treatment for cancer patients, a more rapid and robust method is required for precision medicine. We present a simple method for genetic analysis, called touch imprint cytology combined with massively paralleled sequencing (touch imprint cytology [TIC]-seq), to detect somatic mutations in tumors. We prepared FFPE tissues and TIC specimens from tumors in nine lung cancer patients and one patient with breast cancer. We found that the quality and quantity of TIC DNA was higher than that of FFPE DNA, which requires microdissection to enrich DNA from target tissues. Targeted sequencing using a next-generation sequencer obtained sufficient sequence data using TIC DNA. Most (92%) somatic mutations in lung primary tumors were found to be consistent between TIC and FFPE DNA. We also applied TIC DNA to primary and metastatic tumor tissues to analyze tumor heterogeneity in a breast cancer patient, and showed that common and distinct mutations among primary and metastatic sites could be classified into two distinct histological subtypes. TIC-seq is an alternative and feasible method to analyze genomic alterations in tumors by simply touching the cut surface of specimens to slides. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  20. Characterization of a cultured human T-cell line with genetically altered ribonucleotide reductase activity. Model for immunodeficiency.

    Waddell, D; Ullman, B

    1983-04-10

    From human CCRF-CEM T-cells growing in continuous culture, we have selected, isolated, and characterized a clonal cell line, APHID-D2, with altered ribonucleotide reductase activity. In comparative growth rate experiments, the APHID-D2 cell line is less sensitive than the parental cell line to growth inhibition by deoxyadenosine in the presence of 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of adenosine deaminase. The APHID-D2 cell line has elevated levels of all four dNTPs. The resistance of the APHID-D2 cell line to growth inhibition by deoxyadenosine and the abnormal dNTP levels can be explained by the fact that the APHID-D2 ribonucleotide reductase, unlike the parental ribonucleotide reductase, is not normally sensitive to inhibition by dATP. These results suggest that the allosteric site of ribonucleotide reductase which binds both dATP and ATP is altered in the APHID-D2 line. The isolation of a mutant clone of human T-cells which contains a ribonucleotide reductase that has lost its normal sensitivity to dATP and which is resistant to deoxyadenosine-mediated growth inhibition suggests that a primary pathogenic target of accumulated dATP in lymphocytes from patients with adenosine deaminase deficiency may be the cellular ribonucleotide reductase.

  1. Structural and Maturational Covariance in Early Childhood Brain Development.

    Geng, Xiujuan; Li, Gang; Lu, Zhaohua; Gao, Wei; Wang, Li; Shen, Dinggang; Zhu, Hongtu; Gilmore, John H

    2017-03-01

    Brain structural covariance networks (SCNs) composed of regions with correlated variation are altered in neuropsychiatric disease and change with age. Little is known about the development of SCNs in early childhood, a period of rapid cortical growth. We investigated the development of structural and maturational covariance networks, including default, dorsal attention, primary visual and sensorimotor networks in a longitudinal population of 118 children after birth to 2 years old and compared them with intrinsic functional connectivity networks. We found that structural covariance of all networks exhibit strong correlations mostly limited to their seed regions. By Age 2, default and dorsal attention structural networks are much less distributed compared with their functional maps. The maturational covariance maps, however, revealed significant couplings in rates of change between distributed regions, which partially recapitulate their functional networks. The structural and maturational covariance of the primary visual and sensorimotor networks shows similar patterns to the corresponding functional networks. Results indicate that functional networks are in place prior to structural networks, that correlated structural patterns in adult may arise in part from coordinated cortical maturation, and that regional co-activation in functional networks may guide and refine the maturation of SCNs over childhood development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Group covariance and metrical theory

    Halpern, L.

    1983-01-01

    The a priori introduction of a Lie group of transformations into a physical theory has often proved to be useful; it usually serves to describe special simplified conditions before a general theory can be worked out. Newton's assumptions of absolute space and time are examples where the Euclidian group and translation group have been introduced. These groups were extended to the Galilei group and modified in the special theory of relativity to the Poincare group to describe physics under the given conditions covariantly in the simplest way. The criticism of the a priori character leads to the formulation of the general theory of relativity. The general metric theory does not really give preference to a particular invariance group - even the principle of equivalence can be adapted to a whole family of groups. The physical laws covariantly inserted into the metric space are however adapted to the Poincare group. 8 references

  3. Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity.

    Nengyi Zhang

    2010-04-01

    Full Text Available Central carbon metabolism (CCM is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species. Association mapping utilizes a rich history of mutation and recombination to achieve high resolution mapping. Therefore, applying association mapping in maize (Zea mays ssp. mays, the most diverse model crop species, to study the genetics of CCM is a particularly attractive system.We used a maize diversity panel to test the CCM functional conservation. We found heritable variation in enzyme activity for every enzyme tested. One of these enzymes was the NAD-dependent isocitrate dehydrogenase (IDH, E.C. 1.1.1.41, in which we identified a novel amino-acid substitution in a phylogenetically conserved site. Using candidate gene association mapping, we identified that this non-synonymous polymorphism was associated with IDH activity variation. The proposed mechanism for the IDH activity variation includes additional components regulating protein level. With the comparison of sequences from maize and teosinte (Zea mays ssp. Parviglumis, the maize wild ancestor, we found that some CCM genes had also been targeted for selection during maize domestication.Our results demonstrate the efficacy of association mapping for dissecting natural variation in primary metabolic pathways. The considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites.

  4. Phenotypic covariance at species' borders.

    Caley, M Julian; Cripps, Edward; Game, Edward T

    2013-05-28

    Understanding the evolution of species limits is important in ecology, evolution, and conservation biology. Despite its likely importance in the evolution of these limits, little is known about phenotypic covariance in geographically marginal populations, and the degree to which it constrains, or facilitates, responses to selection. We investigated phenotypic covariance in morphological traits at species' borders by comparing phenotypic covariance matrices (P), including the degree of shared structure, the distribution of strengths of pair-wise correlations between traits, the degree of morphological integration of traits, and the ranks of matricies, between central and marginal populations of three species-pairs of coral reef fishes. Greater structural differences in P were observed between populations close to range margins and conspecific populations toward range centres, than between pairs of conspecific populations that were both more centrally located within their ranges. Approximately 80% of all pair-wise trait correlations within populations were greater in the north, but these differences were unrelated to the position of the sampled population with respect to the geographic range of the species. Neither the degree of morphological integration, nor ranks of P, indicated greater evolutionary constraint at range edges. Characteristics of P observed here provide no support for constraint contributing to the formation of these species' borders, but may instead reflect structural change in P caused by selection or drift, and their potential to evolve in the future.

  5. Temporal and seasonal changes of genetic polymorphisms associated with altered drug susceptibility to chloroquine, lumefantrine and quinine in Guinea-Bissau between 2003 and 2012

    Jovel, Irina Tatiana; Kofoed, Poul-Erik; Rombo, Lars

    2015-01-01

    BACKGROUND: Guinea-Bissau, West-Africa introduced artemether-lumefantrine in 2008 but quinine has also been commonly prescribed for treatment of uncomplicated Plasmodium falciparum malaria. An efficacious high-dose chloroquine treatment regimen was used previously. Temporal and seasonal changes...... of genetic polymorphisms associated with altered drug susceptibility to chloroquine, lumefantrine and quinine are described. METHODS: Pfcrt K76T, pfmdr1 gene copy numbers, N86Y, Y184F and 1034-1246 sequences were determined using PCR-based methods. Blood samples came from virtually all (n=1806) children aged.......001). CONCLUSIONS: Following the discontinuation of an effective chloroquine regimen highly artemether-lumefantrine susceptible P. falciparum (with pfcrt 76T) accumulated possibly due to suboptimal use of quinine and despite a fitness cost linked to 76T....

  6. Targeted sequencing identifies genetic alterations that confer primary resistance to EGFR tyrosine kinase inhibitor (Korean Lung Cancer Consortium).

    Lim, Sun Min; Kim, Hye Ryun; Cho, Eun Kyung; Min, Young Joo; Ahn, Jin Seok; Ahn, Myung-Ju; Park, Keunchil; Cho, Byoung Chul; Lee, Ji-Hyun; Jeong, Hye Cheol; Kim, Eun Kyung; Kim, Joo-Hang

    2016-06-14

    Non-small-cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations may exhibit primary resistance to EGFR tyrosine kinase inhibitor (TKI). We aimed to examine genomic alterations associated with de novo resistance to gefitinib in a prospective study of NSCLC patients. One-hundred and fifty two patients with activating EGFR mutations were included in this study and 136 patients' tumor sample were available for targeted sequencing of genomic alterations in 22 genes using the Colon and Lung Cancer panel (Ampliseq, Life Technologies). All 132 patients with EGFR mutation were treated with gefitinib for their treatment of advanced NSCLC. Twenty patients showed primary resistance to EGFR TKI, and were classified as non-responders. A total of 543 somatic single-nucleotide variants (498 missense, 13 nonsense) and 32 frameshift insertions/deletions, with a median of 3 mutations per sample. TP53 was most commonly mutated (47%) and mutations in SMAD4 was also common (19%), as well as DDR2 (16%), PIK3CA (15%), STK11 (14%), and BRAF (7%). Genomic mutations in the PI3K/Akt/mTOR pathway were commonly found in non-responders (45%) compared to responders (27%), and they had significantly shorter progression-free survival and overall survival compared to patients without mutations (2.1 vs. 12.8 months, P=0.04, 15.7 vs. not reached, PAkt/mTOR pathway were commonly identified in non-responders and may confer resistance to EGFR TKI. Screening lung adenocarcinoma patients with clinical cancer gene test may aid in selecting out those who show primary resistance to EGFR TKI (NCT01697163).

  7. Genetic deletion of the P2Y2 receptor offers significant resistance to development of lithium-induced polyuria accompanied by alterations in PGE2 signaling.

    Zhang, Yue; Pop, Ioana L; Carlson, Noel G; Kishore, Bellamkonda K

    2012-01-01

    Lithium (Li)-induced polyuria is due to resistance of the medullary collecting duct (mCD) to the action of arginine vasopressin (AVP), apparently mediated by increased production of PGE(2). We previously reported that the P2Y(2) receptor (P2Y(2)-R) antagonizes the action of AVP on the mCD and may play a role in Li-induced polyuria by enhancing the production of PGE(2) in mCD. Hence, we hypothesized that genetic deletion of P2Y(2)-R should ameliorate Li-induced polyuria. Wild-type (WT) or P2Y(2)-R knockout (KO) mice were fed normal or Li-added diets for 14 days and euthanized. Li-induced polyuria, and decreases in urine osmolality and AQP2 protein abundance in the renal medulla, were significantly less compared with WT mice despite the lack of differences in Li intake or terminal serum or inner medullary tissue Li levels. Li-induced increased urinary excretion of PGE(2) was not affected in KO mice. However, prostanoid EP(3) receptor (EP3-R) protein abundance in the renal medulla of KO mice was markedly lower vs. WT mice, irrespective of the dietary regimen. The protein abundances of other EP-Rs were not altered across the groups irrespective of the dietary regimen. Ex vivo stimulation of mCD with PGE(2) generated significantly more cAMP in Li-fed KO mice (130%) vs. Li-fed WT mice (100%). Taken together, these data suggest 1) genetic deletion of P2Y(2)-R offers significant resistance to the development of Li-induced polyuria; and 2) this resistance is apparently due to altered PGE(2) signaling mediated by a marked decrease in EP3-R protein abundance in the medulla, thus attenuating the EP3-mediated decrease in cAMP levels in mCD.

  8. Modeling Covariance Breakdowns in Multivariate GARCH

    Jin, Xin; Maheu, John M

    2014-01-01

    This paper proposes a flexible way of modeling dynamic heterogeneous covariance breakdowns in multivariate GARCH (MGARCH) models. During periods of normal market activity, volatility dynamics are governed by an MGARCH specification. A covariance breakdown is any significant temporary deviation of the conditional covariance matrix from its implied MGARCH dynamics. This is captured through a flexible stochastic component that allows for changes in the conditional variances, covariances and impl...

  9. Proofs of Contracted Length Non-covariance

    Strel'tsov, V.N.

    1994-01-01

    Different proofs of contracted length non covariance are discussed. The way based on the establishment of interval inconstancy (dependence on velocity) seems to be the most convincing one. It is stressed that the known non covariance of the electromagnetic field energy and momentum of a moving charge ('the problem 4/3') is a direct consequence of contracted length non covariance. 8 refs

  10. Structural Analysis of Covariance and Correlation Matrices.

    Joreskog, Karl G.

    1978-01-01

    A general approach to analysis of covariance structures is considered, in which the variances and covariances or correlations of the observed variables are directly expressed in terms of the parameters of interest. The statistical problems of identification, estimation and testing of such covariance or correlation structures are discussed.…

  11. Construction of covariance matrix for experimental data

    Liu Tingjin; Zhang Jianhua

    1992-01-01

    For evaluators and experimenters, the information is complete only in the case when the covariance matrix is given. The covariance matrix of the indirectly measured data has been constructed and discussed. As an example, the covariance matrix of 23 Na(n, 2n) cross section is constructed. A reasonable result is obtained

  12. Genetic alterations of the long terminal repeat of an ecotropic porcine endogenous retrovirus during passage in human cells

    Denner, Joachim; Specke, Volker; Thiesen, Ulla; Karlas, Alexander; Kurth, Reinhard

    2003-01-01

    Human-tropic porcine endogenous retroviruses (PERV) such as PERV-A and PERV-B can infect human cells and are therefore a potential risk to recipients of xenotransplants. A similar risk is posed by recombinant viruses containing the receptor-binding site of PERV-A and large parts of the genome of the ecotropic PERV-C including its long terminal repeat (LTR). We describe here the unique organization of the PERV-C LTR and its changes during serial passage of recombinant virus in human cells. An increase in virus titer correlated with an increase in LTR length, caused by multiplication of 37-bp repeats containing nuclear factor Y binding sites. Luciferase dual reporter assays revealed a correlation between the number of repeats and the extent of expression. No alterations have been observed in the receptor-binding site, indicating that the increased titer is due to the changes in the LTR. These data indicate that recombinant PERVs generated during infection of human cells can adapt and subsequently replicate with greater efficiency

  13. Epidermal growth factor receptor signaling pathway is frequently altered in ampullary carcinoma at protein and genetic levels.

    Mikhitarian, Kaidi; Pollen, Maressa; Zhao, Zhiguo; Shyr, Yu; Merchant, Nipun B; Parikh, Alexander; Revetta, Frank; Washington, M Kay; Vnencak-Jones, Cindy; Shi, Chanjuan

    2014-05-01

    Our objective was to explore alteration of the epidermal growth factor receptor (EGFR) signaling pathway in ampullary carcinoma. Immunohistochemical studies were employed to evaluate expression of amphiregulin as well as expression and activation of EGFR. A lab-developed assay was used to identify mutations in the EGFR pathway genes, including KRAS, BRAF, PIK3CA, PTEN, and AKT1. A total of 52 ampullary carcinomas were identified, including 25 intestinal-type and 24 pancreatobiliary-type tumors, with the intestinal type being associated with a younger age at diagnosis (P=0.03) and a better prognosis (PSMAD4 and BRAF. KRAS mutations at codons 12 and 13 did not adversely affect overall survival. In conclusion, EGFR expression and activation were different between intestinal- and pancreatobiliary-type ampullary carcinoma. KRAS mutation was common in both histologic types; however, the incidence appeared to be lower in the pancreatobiliary type compared with its pancreatic counterpart, pancreatic ductal adenocarcinoma. Mutational analysis of the EGFR pathway genes may provide important insights into personalized treatment for patients with ampullary carcinoma.

  14. Clinical characterization of a novel calcium sensing receptor genetic alteration in a Greek patient with autosomal dominant hypocalcemia type 1.

    Papadopoulou, Anna; Gole, Evangelia; Melachroinou, Katerina; Trangas, Theoni; Bountouvi, Evaggelia; Papadimitriou, Anastasios

    2017-04-01

    Autosomal dominant hypocalcemia (ADH) is a rare familial or sporadic syndrome associated with activating mutations in the calcium sensing receptor (CaSR) gene. The aim of this study was to assess the functional significance of a novel CaSR mutation and, moreover, to present the clinical characteristics and the bone mineral density (BMD) progression from early childhood to late puberty in a patient with ADH. Genetic analysis of the CaSR gene was performed in a patient who presented in the neonatal period with hypocalcemic seizures and biochemical features of ADH. The functional impact of the novel mutation identified was assessed in cultured HEK 293T cells, transfected with either the wild type (WT) or mutant CaSR, by evaluating intracellular calcium ([Ca2+]i) influx after stimulation with extracellular calcium (Ca2+). Several BMD measurements were performed during the patient's follow-up until late puberty. A novel CaSR mutation (p.L123S) was identified, which, as demonstrated by functional analysis, renders CaSR more sensitive to extracellular changes of Ca2+ compared with the WT, although the difference is not statistically significant. BMD measurements, from early childhood to late puberty, revealed high normal to elevated BMD. We present the first Greek patient, to our knowledge, with sporadic ADH due to a novel gain-of-function mutation of the CaSR gene.

  15. Evaluation of the genetic alterations in direct and indirect exposures of hexavalent chromium [Cr(VI)] in leather tanning industry workers North Arcot District, South India.

    Balachandar, Vellingiri; Arun, Meyyazhagan; Mohana Devi, Subramaniam; Velmurugan, Palanivel; Manikantan, Pappusamy; Karthick Kumar, Alagamuthu; Sasikala, Keshavarao; Venkatesan, Chinnakulandai

    2010-10-01

    The focal aim of the present study was to identify the genetic alterations occurring in the tannery workers and surrounding inhabitants chronically exposed to hexavalent chromium [Cr(VI)]. A total of 108 samples which includes 72 exposed subjects [36 directly exposed (DE) subjects and 36 indirectly exposed (IE) subjects] and 36 controls were recruited for this study. The exposed subjects and controls were selected based on the Cr level present in air and their urine. Directly exposed subjects were categorized based on their work duration in the tannery industries, whereas the indirectly exposed subjects were categorized based on their year of residence in the place adjacent to tannery industries for more than 3 decades. Controls were normal and healthy. Age was matched for the exposed subjects and controls. The exposed subjects as well as the controls were categorized based on their age (group I, 41 years). Cell cultures were established from blood samples (5 ml from each subject) collected from the subjects (exposed subjects and controls) after obtaining informed consent. G-banding (Giemsa staining) of the cultures, micronucleus (MN) assay and comet assay were used to identify the genetic alterations of individuals exposed to Cr(VI) in comparison with the controls. A higher degree of total CA [12 ± 8.49 (21-25 years)] and MN [18.69 ± 7.39 (11-15 years)] was found in DE subjects compared to other groups. In IE subjects, elevated levels of CA [5.67 ± 1.15 (51-60 years)] and MN [25 ± 9.89 (71-80 years)] were observed. As expected, controls exhibited minimal number of alterations. The overall CA frequency due to Cr exposure was significantly different from that of the controls for both chromatid and chromosome type aberrations (P < 0.05 by ANOVA). The MN/1,000 binucleated cells were significantly increased (P < 0.05) in the peripheral lymphocytes of DE and IE subjects in comparison with controls. The mean tail length of comet assay for DE, IE and controls were

  16. Lorentz covariant theory of gravitation

    Fagundes, H.V.

    1974-12-01

    An alternative method for the calculation of second order effects, like the secular shift of Mercury's perihelium is developed. This method uses the basic ideas of thirring combined with the more mathematical approach of Feyman. In the case of a static source, the treatment used is greatly simplified. Besides, Einstein-Infeld-Hoffmann's Lagrangian for a system of two particles and spin-orbit and spin-spin interactions of two particles with classical spin, ie, internal angular momentum in Moller's sense, are obtained from the Lorentz covariant theory

  17. On an extension of covariance

    Sebestyen, A.

    1975-07-01

    The principle of covariance is extended to coordinates corresponding to internal degrees of freedom. The conditions for a system to be isolated are given. It is shown how internal forces arise in such systems. Equations for internal fields are derived. By an interpretation of the generalized coordinates based on group theory it is shown how particles of the ordinary sense enter into the model and as a simple application the gravitational interaction of two pointlike particles is considered and the shift of the perihelion is deduced. (Sz.Z.)

  18. Covariant gauges at finite temperature

    Landshoff, Peter V

    1992-01-01

    A prescription is presented for real-time finite-temperature perturbation theory in covariant gauges, in which only the two physical degrees of freedom of the gauge-field propagator acquire thermal parts. The propagators for the unphysical degrees of freedom of the gauge field, and for the Faddeev-Popov ghost field, are independent of temperature. This prescription is applied to the calculation of the one-loop gluon self-energy and the two-loop interaction pressure, and is found to be simpler to use than the conventional one.

  19. Structural covariance networks in the mouse brain.

    Pagani, Marco; Bifone, Angelo; Gozzi, Alessandro

    2016-04-01

    The presence of networks of correlation between regional gray matter volume as measured across subjects in a group of individuals has been consistently described in several human studies, an approach termed structural covariance MRI (scMRI). Complementary to prevalent brain mapping modalities like functional and diffusion-weighted imaging, the approach can provide precious insights into the mutual influence of trophic and plastic processes in health and pathological states. To investigate whether analogous scMRI networks are present in lower mammal species amenable to genetic and experimental manipulation such as the laboratory mouse, we employed high resolution morphoanatomical MRI in a large cohort of genetically-homogeneous wild-type mice (C57Bl6/J) and mapped scMRI networks using a seed-based approach. We show that the mouse brain exhibits robust homotopic scMRI networks in both primary and associative cortices, a finding corroborated by independent component analyses of cortical volumes. Subcortical structures also showed highly symmetric inter-hemispheric correlations, with evidence of distributed antero-posterior networks in diencephalic regions of the thalamus and hypothalamus. Hierarchical cluster analysis revealed six identifiable clusters of cortical and sub-cortical regions corresponding to previously described neuroanatomical systems. Our work documents the presence of homotopic cortical and subcortical scMRI networks in the mouse brain, thus supporting the use of this species to investigate the elusive biological and neuroanatomical underpinnings of scMRI network development and its derangement in neuropathological states. The identification of scMRI networks in genetically homogeneous inbred mice is consistent with the emerging view of a key role of environmental factors in shaping these correlational networks. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Genetic alteration with variable intron/exon organization amongst five PI-homoeologous genes in Platanus acerifolia.

    Zhang, Jiaqi; Guo, Cong; Liu, Guofeng; Li, Zhineng; Li, Xiaomei; Bao, Manzhu

    2011-03-01

    Flower development has been extensively characterized in the model species Arabidopsis thaliana and Antirrhinum majus. However, there have been few studies in woody species. Here, we report the isolation and characterization of five PISTILLATA (PI) homoeologous genes (PaPI1-to-5) from the London Plane tree (Platanus acerifolia Willd). PaPI1 and PaPI2 show a similar genomic structure to other known PI homoeologs, but PaPI3/4/5 lack intron sequences. In addition, PaPI5 lacks the third, fourth and fifth exons which encode the K-domain. These altered gene copies may have originated as 'processed' retrogenes. PaPI2 appears micro-regulated by alternative splicing, displaying three splice forms (PaPI2a, PaPI2b and PaPI2c). RT-PCR analysis showed different expression profiles and transcript abundance for the five PaPI genes. PaPI transcripts encoding full-length polypeptides were expressed predominantly in male/female inflorescences and PaPI2a was the most abundant transcript (59%) indicating that PaPI2 may be the major functional PI-homoeolog in London Plane. Phenotypic characterization in a heterologous expression system demonstrated that the full-length PaPI product functions as a B class gene. By contrast the PaPI5 form, which lacks the K-domain, had no apparent effect on flower development. In vitro studies also demonstrated that the K-domain is required to form PaPI/PaAP3 heterodimers. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Covariance Evaluation Methodology for Neutron Cross Sections

    Herman,M.; Arcilla, R.; Mattoon, C.M.; Mughabghab, S.F.; Oblozinsky, P.; Pigni, M.; Pritychenko, b.; Songzoni, A.A.

    2008-09-01

    We present the NNDC-BNL methodology for estimating neutron cross section covariances in thermal, resolved resonance, unresolved resonance and fast neutron regions. The three key elements of the methodology are Atlas of Neutron Resonances, nuclear reaction code EMPIRE, and the Bayesian code implementing Kalman filter concept. The covariance data processing, visualization and distribution capabilities are integral components of the NNDC methodology. We illustrate its application on examples including relatively detailed evaluation of covariances for two individual nuclei and massive production of simple covariance estimates for 307 materials. Certain peculiarities regarding evaluation of covariances for resolved resonances and the consistency between resonance parameter uncertainties and thermal cross section uncertainties are also discussed.

  2. Structural Covariance Networks in Children with Autism or ADHD.

    Bethlehem, R A I; Romero-Garcia, R; Mak, E; Bullmore, E T; Baron-Cohen, S

    2017-08-01

    While autism and attention-deficit/hyperactivity disorder (ADHD) are considered distinct conditions from a diagnostic perspective, clinically they share some phenotypic features and have high comorbidity. Regardless, most studies have focused on only one condition, with considerable heterogeneity in their results. Taking a dual-condition approach might help elucidate shared and distinct neural characteristics. Graph theory was used to analyse topological properties of structural covariance networks across both conditions and relative to a neurotypical (NT; n = 87) group using data from the ABIDE (autism; n = 62) and ADHD-200 datasets (ADHD; n = 69). Regional cortical thickness was used to construct the structural covariance networks. This was analysed in a theoretical framework examining potential differences in long and short-range connectivity, with a specific focus on relation between central graph measures and cortical thickness. We found convergence between autism and ADHD, where both conditions show an overall decrease in CT covariance with increased Euclidean distance between centroids compared with a NT population. The 2 conditions also show divergence. Namely, there is less modular overlap between the 2 conditions than there is between each condition and the NT group. The ADHD group also showed reduced cortical thickness and lower degree in hub regions than the autism group. Lastly, the ADHD group also showed reduced wiring costs compared with the autism groups. Our results indicate a need for taking an integrated approach when considering highly comorbid conditions such as autism and ADHD. Furthermore, autism and ADHD both showed alterations in the relation between inter-regional covariance and centroid distance, where both groups show a steeper decline in covariance as a function of distance. The 2 groups also diverge on modular organization, cortical thickness of hub regions and wiring cost of the covariance network. Thus, on some network features the

  3. Poincare covariance and κ-Minkowski spacetime

    Dabrowski, Ludwik; Piacitelli, Gherardo

    2011-01-01

    A fully Poincare covariant model is constructed as an extension of the κ-Minkowski spacetime. Covariance is implemented by a unitary representation of the Poincare group, and thus complies with the original Wigner approach to quantum symmetries. This provides yet another example (besides the DFR model), where Poincare covariance is realised a la Wigner in the presence of two characteristic dimensionful parameters: the light speed and the Planck length. In other words, a Doubly Special Relativity (DSR) framework may well be realised without deforming the meaning of 'Poincare covariance'. -- Highlights: → We construct a 4d model of noncommuting coordinates (quantum spacetime). → The coordinates are fully covariant under the undeformed Poincare group. → Covariance a la Wigner holds in presence of two dimensionful parameters. → Hence we are not forced to deform covariance (e.g. as quantum groups). → The underlying κ-Minkowski model is unphysical; covariantisation does not cure this.

  4. Componentes de (covariância e parâmetros genéticos de caracteres pós-desmama em bovinos da raça Angus (Co variance components and genetic parameters of post-weaning traits in Angus cattle

    Fernando Flores Cardoso

    2004-04-01

    Full Text Available Foram determinados os componentes de (covariância para caracteres do período pós-desmama na raça Angus e de covariância com peso ao nascer (PN e caracteres do período pré-desmama por intermédio de um modelo animal. Utilizaram-se dados de 18.921 animais com registros de peso à desmama e ao sobreano, dos quais 4.452 tinham avaliações completas para escores visuais à desmama e ao sobreano. Registros de PN estavam disponíveis para 11.788 animais. As herdabilidades do ganho de peso pós-desmama (GP205 e dos escores de conformação (CS, precocidade (GS, musculatura (MS e tamanho (TS ao sobreano foram de 0,20, 0,19, 0,25, 0,26 e 0,24 respectivamente. As correlações genéticas entre os caracteres estudados foram todas positivas: entre GP205 e escores visuais variaram de 0,50 a 0,71; para os escores ao sobreano entre si, de 0,22 a 0,94; entre GP205 e PN foram de 0,14; entre GP205 e ganho pré-desmama, de 0,23; e para o mesmo escore visual observado à desmama e ao sobreano, de 0,90 a 0,99. Esses resultados indicam que é possível selecionar para GP205, sem aumento importante do PN, e que a seleção para GP205 deverá promover uma mudança genética correlacionada em escores visuais ao sobreano.(Covariance components were determined for post-weaning traits, and covariances with birth weight (BW and pre-weaning traits, in Angus cattle using an animal model. Records of weaning and yearling weights of 18,921 animals were used and from these 4,452 had complete evaluations of visual scores at weaning and post-weaning phases. Records of BW were available for 11,788 animals. Heritabilities of post-weaning gain (GP205 and visual scores for conformation (YC, precocity (YP, muscling (YM and size (YS were 0.20, 0.19, 0.25, 0.26 and 0.24, respectively. Genetic correlations among all traits considered were positive: between GP205 and visual scores the range was from 0.50 to 0.71; for yearling scores among themselves from 0.22 to 0.94; between GP205

  5. COVARIANCE ASSISTED SCREENING AND ESTIMATION.

    Ke, By Tracy; Jin, Jiashun; Fan, Jianqing

    2014-11-01

    Consider a linear model Y = X β + z , where X = X n,p and z ~ N (0, I n ). The vector β is unknown and it is of interest to separate its nonzero coordinates from the zero ones (i.e., variable selection). Motivated by examples in long-memory time series (Fan and Yao, 2003) and the change-point problem (Bhattacharya, 1994), we are primarily interested in the case where the Gram matrix G = X ' X is non-sparse but sparsifiable by a finite order linear filter. We focus on the regime where signals are both rare and weak so that successful variable selection is very challenging but is still possible. We approach this problem by a new procedure called the Covariance Assisted Screening and Estimation (CASE). CASE first uses a linear filtering to reduce the original setting to a new regression model where the corresponding Gram (covariance) matrix is sparse. The new covariance matrix induces a sparse graph, which guides us to conduct multivariate screening without visiting all the submodels. By interacting with the signal sparsity, the graph enables us to decompose the original problem into many separated small-size subproblems (if only we know where they are!). Linear filtering also induces a so-called problem of information leakage , which can be overcome by the newly introduced patching technique. Together, these give rise to CASE, which is a two-stage Screen and Clean (Fan and Song, 2010; Wasserman and Roeder, 2009) procedure, where we first identify candidates of these submodels by patching and screening , and then re-examine each candidate to remove false positives. For any procedure β̂ for variable selection, we measure the performance by the minimax Hamming distance between the sign vectors of β̂ and β. We show that in a broad class of situations where the Gram matrix is non-sparse but sparsifiable, CASE achieves the optimal rate of convergence. The results are successfully applied to long-memory time series and the change-point model.

  6. Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma.

    Conti, Salvatore; Gallo, Enzo; Sioletic, Stefano; Facciolo, Francesco; Palmieri, Giovannella; Lauriola, Libero; Evoli, Amelia; Martucci, Robert; Di Benedetto, Anna; Novelli, Flavia; Giannarelli, Diana; Deriu, Gloria; Granone, Pierluigi; Ottaviano, Margaret; Muti, Paola; Pescarmona, Edoardo; Marino, Mirella

    2016-03-01

    The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series. We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes. We found two prevalent CA-SSR-1 genotypes: a homozygous 16 CA repeat and a heterozygous genotype, bearing alleles with 16 and 20 CA repeats. The average combined allele length was correlated with tumor subtype: shorter sequences were significantly associated with the more aggressive WHO thymoma subtype group including B2/B3, B3 and B3/C histotypes. Four out of 29 informative cases analysed for somatic CA-SSR-1 loss of heterozygosity showed allelic imbalance (AI), 3/4 with loss of the longer allele. By egfr-FISH analysis, 9 out of 33 cases were FISH positive. Moreover, the two integrated techniques demonstrated that 3 out of 4 CA-SSR-1-AI positive cases with short allele relative prevalence showed significantly low or high chromosome 7 "polysomy"/increased gene copy number by egfr-FISH. Our molecular and genetic and follow up data indicated that CA-SSR-1-allelic imbalance with short allele relative prevalence significantly correlated with EGFR 3+ immunohistochemical score, increased egfr Gene Copy Number, advanced stage and with relapsing/metastatic behaviour in thymomas.

  7. Non-Critical Covariant Superstrings

    Grassi, P A

    2005-01-01

    We construct a covariant description of non-critical superstrings in even dimensions. We construct explicitly supersymmetric hybrid type variables in a linear dilaton background, and study an underlying N=2 twisted superconformal algebra structure. We find similarities between non-critical superstrings in 2n+2 dimensions and critical superstrings compactified on CY_(4-n) manifolds. We study the spectrum of the non-critical strings, and in particular the Ramond-Ramond massless fields. We use the supersymmetric variables to construct the non-critical superstrings sigma-model action in curved target space backgrounds with coupling to the Ramond-Ramond fields. We consider as an example non-critical type IIA strings on AdS_2 background with Ramond-Ramond 2-form flux.

  8. ISSUES IN NEUTRON CROSS SECTION COVARIANCES

    Mattoon, C.M.; Oblozinsky,P.

    2010-04-30

    We review neutron cross section covariances in both the resonance and fast neutron regions with the goal to identify existing issues in evaluation methods and their impact on covariances. We also outline ideas for suitable covariance quality assurance procedures.We show that the topic of covariance data remains controversial, the evaluation methodologies are not fully established and covariances produced by different approaches have unacceptable spread. The main controversy is in very low uncertainties generated by rigorous evaluation methods and much larger uncertainties based on simple estimates from experimental data. Since the evaluators tend to trust the former, while the users tend to trust the latter, this controversy has considerable practical implications. Dedicated effort is needed to arrive at covariance evaluation methods that would resolve this issue and produce results accepted internationally both by evaluators and users.

  9. Covariant diagrams for one-loop matching

    Zhang, Zhengkang [Michigan Center for Theoretical Physics (MCTP), University of Michigan,450 Church Street, Ann Arbor, MI 48109 (United States); Deutsches Elektronen-Synchrotron (DESY),Notkestraße 85, 22607 Hamburg (Germany)

    2017-05-30

    We present a diagrammatic formulation of recently-revived covariant functional approaches to one-loop matching from an ultraviolet (UV) theory to a low-energy effective field theory. Various terms following from a covariant derivative expansion (CDE) are represented by diagrams which, unlike conventional Feynman diagrams, involve gauge-covariant quantities and are thus dubbed “covariant diagrams.” The use of covariant diagrams helps organize and simplify one-loop matching calculations, which we illustrate with examples. Of particular interest is the derivation of UV model-independent universal results, which reduce matching calculations of specific UV models to applications of master formulas. We show how such derivation can be done in a more concise manner than the previous literature, and discuss how additional structures that are not directly captured by existing universal results, including mixed heavy-light loops, open covariant derivatives, and mixed statistics, can be easily accounted for.

  10. Covariant diagrams for one-loop matching

    Zhang, Zhengkang

    2017-01-01

    We present a diagrammatic formulation of recently-revived covariant functional approaches to one-loop matching from an ultraviolet (UV) theory to a low-energy effective field theory. Various terms following from a covariant derivative expansion (CDE) are represented by diagrams which, unlike conventional Feynman diagrams, involve gauge-covariant quantities and are thus dubbed “covariant diagrams.” The use of covariant diagrams helps organize and simplify one-loop matching calculations, which we illustrate with examples. Of particular interest is the derivation of UV model-independent universal results, which reduce matching calculations of specific UV models to applications of master formulas. We show how such derivation can be done in a more concise manner than the previous literature, and discuss how additional structures that are not directly captured by existing universal results, including mixed heavy-light loops, open covariant derivatives, and mixed statistics, can be easily accounted for.

  11. Improvement of covariance data for fast reactors

    Shibata, Keiichi; Hasegawa, Akira

    2000-02-01

    We estimated covariances of the JENDL-3.2 data on the nuclides and reactions needed to analyze fast-reactor cores for the past three years, and produced covariance files. The present work was undertaken to re-examine the covariance files and to make some improvements. The covariances improved are the ones for the inelastic scattering cross section of 16 O, the total cross section of 23 Na, the fission cross section of 235 U, the capture cross section of 238 U, and the resolved resonance parameters for 238 U. Moreover, the covariances of 233 U data were newly estimated by the present work. The covariances obtained were compiled in the ENDF-6 format. (author)

  12. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

    Whitcomb, David C.; LaRusch, Jessica; Krasinskas, Alyssa M.; Klei, Lambertus; Smith, Jill P.; Brand, Randall E.; Neoptolemos, John P.; Lerch, Markus M.; Tector, Matt; Sandhu, Bimaljit S.; Guda, Nalini M.; Orlichenko, Lidiya; Alkaade, Samer; Amann, Stephen T.; Anderson, Michelle A.; Baillie, John; Banks, Peter A.; Conwell, Darwin; Coté, Gregory A.; Cotton, Peter B.; DiSario, James; Farrer, Lindsay A.; Forsmark, Chris E.; Johnstone, Marianne; Gardner, Timothy B.; Gelrud, Andres; Greenhalf, William; Haines, Jonathan L.; Hartman, Douglas J.; Hawes, Robert A.; Lawrence, Christopher; Lewis, Michele; Mayerle, Julia; Mayeux, Richard; Melhem, Nadine M.; Money, Mary E.; Muniraj, Thiruvengadam; Papachristou, Georgios I.; Pericak-Vance, Margaret A.; Romagnuolo, Joseph; Schellenberg, Gerard D.; Sherman, Stuart; Simon, Peter; Singh, Vijay K.; Slivka, Adam; Stolz, Donna; Sutton, Robert; Weiss, Frank Ulrich; Wilcox, C. Mel; Zarnescu, Narcis Octavian; Wisniewski, Stephen R.; O'Connell, Michael R.; Kienholz, Michelle L.; Roeder, Kathryn; Barmada, M. Michael; Yadav, Dhiraj; Devlin, Bernie; Albert, Marilyn S.; Albin, Roger L.; Apostolova, Liana G.; Arnold, Steven E.; Baldwin, Clinton T.; Barber, Robert; Barnes, Lisa L.; Beach, Thomas G.; Beecham, Gary W.; Beekly, Duane; Bennett, David A.; Bigio, Eileen H.; Bird, Thomas D.; Blacker, Deborah; Boxer, Adam; Burke, James R.; Buxbaum, Joseph D.; Cairns, Nigel J.; Cantwell, Laura B.; Cao, Chuanhai; Carney, Regina M.; Carroll, Steven L.; Chui, Helena C.; Clark, David G.; Cribbs, David H.; Crocco, Elizabeth A.; Cruchaga, Carlos; DeCarli, Charles; Demirci, F. Yesim; Dick, Malcolm; Dickson, Dennis W.; Duara, Ranjan; Ertekin-Taner, Nilufer; Faber, Kelley M.; Fallon, Kenneth B.; Farlow, Martin R.; Ferris, Steven; Foroud, Tatiana M.; Frosch, Matthew P.; Galasko, Douglas R.; Ganguli, Mary; Gearing, Marla; Geschwind, Daniel H.; Ghetti, Bernardino; Gilbert, John R.; Gilman, Sid; Glass, Jonathan D.; Goate, Alison M.; Graff-Radford, Neill R.; Green, Robert C.; Growdon, John H.; Hakonarson, Hakon; Hamilton-Nelson, Kara L.; Hamilton, Ronald L.; Harrell, Lindy E.; Head, Elizabeth; Honig, Lawrence S.; Hulette, Christine M.; Hyman, Bradley T.; Jicha, Gregory A.; Jin, Lee-Way; Jun, Gyungah; Kamboh, M. Ilyas; Karydas, Anna; Kaye, Jeffrey A.; Kim, Ronald; Koo, Edward H.; Kowall, Neil W.; Kramer, Joel H.; Kramer, Patricia; Kukull, Walter A.; LaFerla, Frank M.; Lah, James J.; Leverenz, James B.; Levey, Allan I.; Li, Ge; Lin, Chiao-Feng; Lieberman, Andrew P.; Lopez, Oscar L.; Lunetta, Kathryn L.; Lyketsos, Constantine G.; Mack, Wendy J.; Marson, Daniel C.; Martin, Eden R.; Martiniuk, Frank; Mash, Deborah C.; Masliah, Eliezer; McKee, Ann C.; Mesulam, Marsel; Miller, Bruce L.; Miller, Carol A.; Miller, Joshua W.; Montine, Thomas J.; Morris, John C.; Murrell, Jill R.; Naj, Adam C.; Olichney, John M.; Parisi, Joseph E.; Peskind, Elaine; Petersen, Ronald C.; Pierce, Aimee; Poon, Wayne W.; Potter, Huntington; Quinn, Joseph F.; Raj, Ashok; Raskind, Murray; Reiman, Eric M.; Reisberg, Barry; Reitz, Christiane; Ringman, John M.; Roberson, Erik D.; Rosen, Howard J.; Rosenberg, Roger N.; Sano, Mary; Saykin, Andrew J.; Schneider, Julie A.; Schneider, Lon S.; Seeley, William W.; Smith, Amanda G.; Sonnen, Joshua A.; Spina, Salvatore; Stern, Robert A.; Tanzi, Rudolph E.; Trojanowski, John Q.; Troncoso, Juan C.; Tsuang, Debby W.; Valladares, Otto; Van Deerlin, Vivianna M.; Van Eldik, Linda J.; Vardarajan, Badri N.; Vinters, Harry V.; Vonsattel, Jean Paul; Wang, Li-San; Weintraub, Sandra; Welsh-Bohmer, Kathleen A.; Williamson, Jennifer; Woltjer, Randall L.; Wright, Clinton B.; Younkin, Steven G.; Yu, Chang-En; Yu, Lei

    2012-01-01

    Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07. PMID:23143602

  13. The application of sparse estimation of covariance matrix to quadratic discriminant analysis

    Sun, Jiehuan; Zhao, Hongyu

    2015-01-01

    Background Although Linear Discriminant Analysis (LDA) is commonly used for classification, it may not be directly applied in genomics studies due to the large p, small n problem in these studies. Different versions of sparse LDA have been proposed to address this significant challenge. One implicit assumption of various LDA-based methods is that the covariance matrices are the same across different classes. However, rewiring of genetic networks (therefore different covariance matrices) acros...

  14. ANL Critical Assembly Covariance Matrix Generation - Addendum

    McKnight, Richard D. [Argonne National Lab. (ANL), Argonne, IL (United States); Grimm, Karl N. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2014-01-13

    In March 2012, a report was issued on covariance matrices for Argonne National Laboratory (ANL) critical experiments. That report detailed the theory behind the calculation of covariance matrices and the methodology used to determine the matrices for a set of 33 ANL experimental set-ups. Since that time, three new experiments have been evaluated and approved. This report essentially updates the previous report by adding in these new experiments to the preceding covariance matrix structure.

  15. Neutron spectrum adjustment. The role of covariances

    Remec, I.

    1992-01-01

    Neutron spectrum adjustment method is shortly reviewed. Practical example dealing with power reactor pressure vessel exposure rates determination is analysed. Adjusted exposure rates are found only slightly affected by the covariances of measured reaction rates and activation cross sections, while the multigroup spectra covariances were found important. Approximate spectra covariance matrices, as suggested in Astm E944-89, were found useful but care is advised if they are applied in adjustments of spectra at locations without dosimetry. (author) [sl

  16. Modifications of Sp(2) covariant superfield quantization

    Gitman, D.M.; Moshin, P.Yu

    2003-12-04

    We propose a modification of the Sp(2) covariant superfield quantization to realize a superalgebra of generating operators isomorphic to the massless limit of the corresponding superalgebra of the osp(1,2) covariant formalism. The modified scheme ensures the compatibility of the superalgebra of generating operators with extended BRST symmetry without imposing restrictions eliminating superfield components from the quantum action. The formalism coincides with the Sp(2) covariant superfield scheme and with the massless limit of the osp(1,2) covariant quantization in particular cases of gauge-fixing and solutions of the quantum master equations.

  17. Competing risks and time-dependent covariates

    Cortese, Giuliana; Andersen, Per K

    2010-01-01

    Time-dependent covariates are frequently encountered in regression analysis for event history data and competing risks. They are often essential predictors, which cannot be substituted by time-fixed covariates. This study briefly recalls the different types of time-dependent covariates......, as classified by Kalbfleisch and Prentice [The Statistical Analysis of Failure Time Data, Wiley, New York, 2002] with the intent of clarifying their role and emphasizing the limitations in standard survival models and in the competing risks setting. If random (internal) time-dependent covariates...

  18. Activities of covariance utilization working group

    Tsujimoto, Kazufumi

    2013-01-01

    During the past decade, there has been a interest in the calculational uncertainties induced by nuclear data uncertainties in the neutronics design of advanced nuclear system. The covariance nuclear data is absolutely essential for the uncertainty analysis. In the latest version of JENDL, JENDL-4.0, the covariance data for many nuclides, especially actinide nuclides, was substantialy enhanced. The growing interest in the uncertainty analysis and the covariance data has led to the organisation of the working group for covariance utilization under the JENDL committee. (author)

  19. General covariance and quantum theory

    Mashhoon, B.

    1986-01-01

    The extension of the principle of relativity to general coordinate systems is based on the hypothesis that an accelerated observer is locally equivalent to a hypothetical inertial observer with the same velocity as the noninertial observer. This hypothesis of locality is expected to be valid for classical particle phenomena as well as for classical wave phenomena but only in the short-wavelength approximation. The generally covariant theory is therefore expected to be in conflict with the quantum theory which is based on wave-particle duality. This is explicitly demonstrated for the frequency of electromagnetic radiation measured by a uniformly rotating observer. The standard Doppler formula is shown to be valid only in the geometric optics approximation. A new definition for the frequency is proposed, and the resulting formula for the frequency measured by the rotating observer is shown to be consistent with expectations based on the classical theory of electrons. A tentative quantum theory is developed on the basis of the generalization of the Bohr frequency condition to include accelerated observers. The description of the causal sequence of events is assumed to be independent of the motion of the observer. Furthermore, the quantum hypothesis is supposed to be valid for all observers. The implications of this theory are critically examined. The new formula for frequency, which is still based on the hypothesis of locality, leads to the observation of negative energy quanta by the rotating observer and is therefore in conflict with the quantum theory

  20. variance components and genetic parameters for live weight

    admin

    Against this background the present study estimated the (co)variance .... Starting values for the (co)variance components of two-trait models were ..... Estimates of genetic parameters for weaning weight of beef accounting for direct-maternal.

  1. Parameters of the covariance function of galaxies

    Fesenko, B.I.; Onuchina, E.V.

    1988-01-01

    The two-point angular covariance functions for two samples of galaxies are considered using quick methods of analysis. It is concluded that in the previous investigations the amplitude of the covariance function in the Lick counts was overestimated and the rate of decrease of the function underestimated

  2. Covariance Function for Nearshore Wave Assimilation Systems

    2018-01-30

    which is applicable for any spectral wave model. The four dimensional variational (4DVar) assimilation methods are based on the mathematical ...covariance can be modeled by a parameterized Gaussian function, for nearshore wave assimilation applications , the covariance function depends primarily on...SPECTRAL ACTION DENSITY, RESPECTIVELY. ............................ 5 FIGURE 2. TOP ROW: STATISTICAL ANALYSIS OF THE WAVE-FIELD PROPERTIES AT THE

  3. Treatment Effects with Many Covariates and Heteroskedasticity

    Cattaneo, Matias D.; Jansson, Michael; Newey, Whitney K.

    The linear regression model is widely used in empirical work in Economics. Researchers often include many covariates in their linear model specification in an attempt to control for confounders. We give inference methods that allow for many covariates and heteroskedasticity. Our results...

  4. Covariance and sensitivity data generation at ORNL

    Leal, L. C.; Derrien, H.; Larson, N. M.; Alpan, A.

    2005-01-01

    Covariance data are required to assess uncertainties in design parameters in several nuclear applications. The error estimation of calculated quantities relies on the nuclear data uncertainty information available in the basic nuclear data libraries, such as the US Evaluated Nuclear Data Library, ENDF/B. The uncertainty files in the ENDF/B library are obtained from the analysis of experimental data and are stored as variance and covariance data. In this paper we address the generation of covariance data in the resonance region done with the computer code SAMMY. SAMMY is used in the evaluation of the experimental data in the resolved and unresolved resonance energy regions. The data fitting of cross sections is based on the generalised least-squares formalism (Bayesian theory) together with the resonance formalism described by R-matrix theory. Two approaches are used in SAMMY for the generation of resonance parameter covariance data. In the evaluation process SAMMY generates a set of resonance parameters that fit the data, and, it provides the resonance parameter covariances. For resonance parameter evaluations where there are no resonance parameter covariance data available, the alternative is to use an approach called the 'retroactive' resonance parameter covariance generation. In this paper, we describe the application of the retroactive covariance generation approach for the gadolinium isotopes. (authors)

  5. Position Error Covariance Matrix Validation and Correction

    Frisbee, Joe, Jr.

    2016-01-01

    In order to calculate operationally accurate collision probabilities, the position error covariance matrices predicted at times of closest approach must be sufficiently accurate representations of the position uncertainties. This presentation will discuss why the Gaussian distribution is a reasonable expectation for the position uncertainty and how this assumed distribution type is used in the validation and correction of position error covariance matrices.

  6. Quality Quantification of Evaluated Cross Section Covariances

    Varet, S.; Dossantos-Uzarralde, P.; Vayatis, N.

    2015-01-01

    Presently, several methods are used to estimate the covariance matrix of evaluated nuclear cross sections. Because the resulting covariance matrices can be different according to the method used and according to the assumptions of the method, we propose a general and objective approach to quantify the quality of the covariance estimation for evaluated cross sections. The first step consists in defining an objective criterion. The second step is computation of the criterion. In this paper the Kullback-Leibler distance is proposed for the quality quantification of a covariance matrix estimation and its inverse. It is based on the distance to the true covariance matrix. A method based on the bootstrap is presented for the estimation of this criterion, which can be applied with most methods for covariance matrix estimation and without the knowledge of the true covariance matrix. The full approach is illustrated on the 85 Rb nucleus evaluations and the results are then used for a discussion on scoring and Monte Carlo approaches for covariance matrix estimation of the cross section evaluations

  7. On the algebraic structure of covariant anomalies and covariant Schwinger terms

    Kelnhofer, G.

    1992-01-01

    A cohomological characterization of covariant anomalies and covariant Schwinger terms in an anomalous Yang-Mills theory is formulated and w ill be geometrically interpreted. The BRS and anti-BRS transformations are defined as purely differential geometric objects. Finally the covariant descent equations are formulated within this context. (author)

  8. Covariant diagrams for one-loop matching

    Zhang, Zhengkang

    2016-10-01

    We present a diagrammatic formulation of recently-revived covariant functional approaches to one-loop matching from an ultraviolet (UV) theory to a low-energy effective field theory. Various terms following from a covariant derivative expansion (CDE) are represented by diagrams which, unlike conventional Feynman diagrams, involve gaugecovariant quantities and are thus dubbed ''covariant diagrams.'' The use of covariant diagrams helps organize and simplify one-loop matching calculations, which we illustrate with examples. Of particular interest is the derivation of UV model-independent universal results, which reduce matching calculations of specific UV models to applications of master formulas. We show how such derivation can be done in a more concise manner than the previous literature, and discuss how additional structures that are not directly captured by existing universal results, including mixed heavy-light loops, open covariant derivatives, and mixed statistics, can be easily accounted for.

  9. Covariant diagrams for one-loop matching

    Zhang, Zhengkang [Michigan Univ., Ann Arbor, MI (United States). Michigan Center for Theoretical Physics; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2016-10-15

    We present a diagrammatic formulation of recently-revived covariant functional approaches to one-loop matching from an ultraviolet (UV) theory to a low-energy effective field theory. Various terms following from a covariant derivative expansion (CDE) are represented by diagrams which, unlike conventional Feynman diagrams, involve gaugecovariant quantities and are thus dubbed ''covariant diagrams.'' The use of covariant diagrams helps organize and simplify one-loop matching calculations, which we illustrate with examples. Of particular interest is the derivation of UV model-independent universal results, which reduce matching calculations of specific UV models to applications of master formulas. We show how such derivation can be done in a more concise manner than the previous literature, and discuss how additional structures that are not directly captured by existing universal results, including mixed heavy-light loops, open covariant derivatives, and mixed statistics, can be easily accounted for.

  10. On estimating cosmology-dependent covariance matrices

    Morrison, Christopher B.; Schneider, Michael D.

    2013-01-01

    We describe a statistical model to estimate the covariance matrix of matter tracer two-point correlation functions with cosmological simulations. Assuming a fixed number of cosmological simulation runs, we describe how to build a 'statistical emulator' of the two-point function covariance over a specified range of input cosmological parameters. Because the simulation runs with different cosmological models help to constrain the form of the covariance, we predict that the cosmology-dependent covariance may be estimated with a comparable number of simulations as would be needed to estimate the covariance for fixed cosmology. Our framework is a necessary first step in planning a simulations campaign for analyzing the next generation of cosmological surveys

  11. Covariance descriptor fusion for target detection

    Cukur, Huseyin; Binol, Hamidullah; Bal, Abdullah; Yavuz, Fatih

    2016-05-01

    Target detection is one of the most important topics for military or civilian applications. In order to address such detection tasks, hyperspectral imaging sensors provide useful images data containing both spatial and spectral information. Target detection has various challenging scenarios for hyperspectral images. To overcome these challenges, covariance descriptor presents many advantages. Detection capability of the conventional covariance descriptor technique can be improved by fusion methods. In this paper, hyperspectral bands are clustered according to inter-bands correlation. Target detection is then realized by fusion of covariance descriptor results based on the band clusters. The proposed combination technique is denoted Covariance Descriptor Fusion (CDF). The efficiency of the CDF is evaluated by applying to hyperspectral imagery to detect man-made objects. The obtained results show that the CDF presents better performance than the conventional covariance descriptor.

  12. A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities.

    Geng, Yanyan; Ferreira, Juan J; Dzikunu, Victor; Butler, Alice; Lybaert, Pascale; Yuan, Peng; Magleby, Karl L; Salkoff, Lawrence; Santi, Celia M

    2017-05-26

    To fertilize an oocyte, sperm must first undergo capacitation in which the sperm plasma membrane becomes hyperpolarized via activation of potassium (K + ) channels and resultant K + efflux. Sperm-specific SLO3 K + channels are responsible for these membrane potential changes critical for fertilization in mouse sperm, and they are only sensitive to pH i However, in human sperm, the major K + conductance is both Ca 2+ - and pH i -sensitive. It has been debated whether Ca 2+ -sensitive SLO1 channels substitute for human SLO3 (hSLO3) in human sperm or whether human SLO3 channels have acquired Ca 2+ sensitivity. Here we show that hSLO3 is rapidly evolving and reveal a natural structural variant with enhanced apparent Ca 2+ and pH sensitivities. This variant allele (C382R) alters an amino acid side chain at a principal interface between the intramembrane-gated pore and the cytoplasmic gating ring of the channel. Because the gating ring contains sensors to intracellular factors such as pH and Ca 2+ , the effectiveness of transduction between the gating ring and the pore domain appears to be enhanced. Our results suggest that sperm-specific genes can evolve rapidly and that natural genetic variation may have led to a SLO3 variant that differs from wild type in both pH and intracellular Ca 2+ sensitivities. Whether this physiological variation confers differences in fertility among males remains to be established. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Structural covariance of neostriatal and limbic regions in patients with obsessive-compulsive disorder.

    Subirà, Marta; Cano, Marta; de Wit, Stella J; Alonso, Pino; Cardoner, Narcís; Hoexter, Marcelo Q; Kwon, Jun Soo; Nakamae, Takashi; Lochner, Christine; Sato, João R; Jung, Wi Hoon; Narumoto, Jin; Stein, Dan J; Pujol, Jesus; Mataix-Cols, David; Veltman, Dick J; Menchón, José M; van den Heuvel, Odile A; Soriano-Mas, Carles

    2016-03-01

    Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive-compulsive disorder (OCD) have been typically described in functional neuroimaging studies. However, structural covariance, or volumetric correlations across distant brain regions, also provides network-level information. Altered structural covariance has been described in patients with different psychiatric disorders, including OCD, but to our knowledge, alterations within frontostriatal and frontoamygdalar circuits have not been explored. We performed a mega-analysis pooling structural MRI scans from the Obsessive-compulsive Brain Imaging Consortium and assessed whole-brain voxel-wise structural covariance of 4 striatal regions (dorsal and ventral caudate nucleus, and dorsal-caudal and ventral-rostral putamen) and 2 amygdalar nuclei (basolateral and centromedial-superficial). Images were preprocessed with the standard pipeline of voxel-based morphometry studies using Statistical Parametric Mapping software. Our analyses involved 329 patients with OCD and 316 healthy controls. Patients showed increased structural covariance between the left ventral-rostral putamen and the left inferior frontal gyrus/frontal operculum region. This finding had a significant interaction with age; the association held only in the subgroup of older participants. Patients with OCD also showed increased structural covariance between the right centromedial-superficial amygdala and the ventromedial prefrontal cortex. This was a cross-sectional study. Because this is a multisite data set analysis, participant recruitment and image acquisition were performed in different centres. Most patients were taking medication, and treatment protocols differed across centres. Our results provide evidence for structural network-level alterations in patients with OCD involving 2 frontosubcortical circuits of relevance for the disorder and indicate that structural covariance contributes to fully characterizing brain

  14. Covariant quantizations in plane and curved spaces

    Assirati, J.L.M.; Gitman, D.M.

    2017-01-01

    We present covariant quantization rules for nonsingular finite-dimensional classical theories with flat and curved configuration spaces. In the beginning, we construct a family of covariant quantizations in flat spaces and Cartesian coordinates. This family is parametrized by a function ω(θ), θ element of (1,0), which describes an ambiguity of the quantization. We generalize this construction presenting covariant quantizations of theories with flat configuration spaces but already with arbitrary curvilinear coordinates. Then we construct a so-called minimal family of covariant quantizations for theories with curved configuration spaces. This family of quantizations is parametrized by the same function ω(θ). Finally, we describe a more wide family of covariant quantizations in curved spaces. This family is already parametrized by two functions, the previous one ω(θ) and by an additional function Θ(x,ξ). The above mentioned minimal family is a part at Θ = 1 of the wide family of quantizations. We study constructed quantizations in detail, proving their consistency and covariance. As a physical application, we consider a quantization of a non-relativistic particle moving in a curved space, discussing the problem of a quantum potential. Applying the covariant quantizations in flat spaces to an old problem of constructing quantum Hamiltonian in polar coordinates, we directly obtain a correct result. (orig.)

  15. Covariant quantizations in plane and curved spaces

    Assirati, J.L.M. [University of Sao Paulo, Institute of Physics, Sao Paulo (Brazil); Gitman, D.M. [Tomsk State University, Department of Physics, Tomsk (Russian Federation); P.N. Lebedev Physical Institute, Moscow (Russian Federation); University of Sao Paulo, Institute of Physics, Sao Paulo (Brazil)

    2017-07-15

    We present covariant quantization rules for nonsingular finite-dimensional classical theories with flat and curved configuration spaces. In the beginning, we construct a family of covariant quantizations in flat spaces and Cartesian coordinates. This family is parametrized by a function ω(θ), θ element of (1,0), which describes an ambiguity of the quantization. We generalize this construction presenting covariant quantizations of theories with flat configuration spaces but already with arbitrary curvilinear coordinates. Then we construct a so-called minimal family of covariant quantizations for theories with curved configuration spaces. This family of quantizations is parametrized by the same function ω(θ). Finally, we describe a more wide family of covariant quantizations in curved spaces. This family is already parametrized by two functions, the previous one ω(θ) and by an additional function Θ(x,ξ). The above mentioned minimal family is a part at Θ = 1 of the wide family of quantizations. We study constructed quantizations in detail, proving their consistency and covariance. As a physical application, we consider a quantization of a non-relativistic particle moving in a curved space, discussing the problem of a quantum potential. Applying the covariant quantizations in flat spaces to an old problem of constructing quantum Hamiltonian in polar coordinates, we directly obtain a correct result. (orig.)

  16. Examination of the causes of covariation between conduct disorder symptoms and vulnerability to drug dependence.

    Button, Tanya M M; Hewitt, John K; Rhee, Soo Hyun; Young, Susan E; Corley, Robin P; Stallings, Michael C

    2006-02-01

    Conduct disorder (CD) symptoms and substance dependence commonly co-occur. Both phenotypes are highly heritable and a common genetic influence on the covariation has been suggested. The aim of this study was to determine the extent to which genes and environment contribute to the covariance between CD and drug dependence using twins from the Colorado Longitudinal Twin Sample and the Colorado Twin Registry. A total of 880 twin pairs (237 monozygotic [MZ] female, 195 MZ male, 116 dizygotic [DZ] female, 118 DZ male and 214 DZ opposite-sex) aged 13 to 18 (mean = 15.65) were included in the analysis. CD was assessed by lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) symptom count and a polysubstance dependence vulnerability index was developed from responses to the Composite International Diagnostic Interview--Substance Abuse Module. A bivariate Cholesky Decomposition model was used to partition the cause of variation and covariation of the two phenotypes. No sex-limitation was observed in our data, and male and female parameter estimates were constrained to be equal. Both CD symptoms and dependence vulnerability were significantly heritable, and genes, shared environment and nonshared environment all contributed to the covariation between them. Genes contributed 35% of the phenotypic covariance, shared environment contributed 46%, and nonshared environmental influences contributed the remaining 19% to the phenotypic covariance. Therefore, there appears to be pleiotropic genetic influence on CD symptoms and dependence vulnerability.

  17. Structural whole-brain covariance of the anterior and posterior hippocampus: Associations with age and memory.

    Nordin, Kristin; Persson, Jonas; Stening, Eva; Herlitz, Agneta; Larsson, Elna-Marie; Söderlund, Hedvig

    2018-02-01

    The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole-brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole-brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole-brain covariance of the HC in addition to regional volume, in young, middle-aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior-specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single-item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole-brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age-related alterations. © 2017 Wiley Periodicals, Inc.

  18. Heritability, covariation and natural selection on 24 traits of common evening primrose (Oenothera biennis) from a field experiment.

    Johnson, M T J; Agrawal, A A; Maron, J L; Salminen, J-P

    2009-06-01

    This study explored genetic variation and co-variation in multiple functional plant traits. Our goal was to characterize selection, heritabilities and genetic correlations among different types of traits to gain insight into the evolutionary ecology of plant populations and their interactions with insect herbivores. In a field experiment, we detected significant heritable variation for each of 24 traits of Oenothera biennis and extensive genetic covariance among traits. Traits with diverse functions formed several distinct groups that exhibited positive genetic covariation with each other. Genetic variation in life-history traits and secondary chemistry together explained a large proportion of variation in herbivory (r(2) = 0.73). At the same time, selection acted on lifetime biomass, life-history traits and two secondary compounds of O. biennis, explaining over 95% of the variation in relative fitness among genotypes. The combination of genetic covariances and directional selection acting on multiple traits suggests that adaptive evolution of particular traits is constrained, and that correlated evolution of groups of traits will occur, which is expected to drive the evolution of increased herbivore susceptibility. As a whole, our study indicates that an examination of genetic variation and covariation among many different types of traits can provide greater insight into the evolutionary ecology of plant populations and plant-herbivore interactions.

  19. Genetic polymorphism of human cytochrome P-450 (S)-mephenytoin 4-hydroxylase. Studies with human autoantibodies suggest a functionally altered cytochrome P-450 isozyme as cause of the genetic deficiency

    Meier, U.T.; Meyer, U.A.

    1987-01-01

    The metabolism of the anticonvulsant mephenytoin is subject to a genetic polymorphism. In 2-5% of Caucasians and 18-23% of Japanese subjects a specific cytochrome P-450 isozyme, P-450 meph, is functionally deficient or missing. The authors have accumulated evidence that autoimmune antibodies observed in sera of patients with tienilic acid induced hepatitis (anti-liver kidney microsome 2 or anti-LKM2 antibodies) specifically recognize the cytochrome P-450 involved in the mephrenytoin hydroxylation polymorphism. This is demonstrated by immunoinhibition and immunoprecipitation of microsomal (S)-mephenytoin 4-hydroxylation activity and by the recognition by anti-LKM2 antibodies of a single [ 125 I]-protein band on immunoblots of human liver microsomes after sodium dodecyl sulfate-polyacrylamide gel electrophoresis or isoelectric focusing. The cytochrome P-450 recognized by anti-LKM2 antibodies was immunopurified from microsomes derived from livers of extensive (EM) or poor metabolizers (PM) of (S)-mephenytoin. Comparison of the EM-type cytochrome P-450 to that isolated from PM livers revealed no difference in regard to immuno-cross-reactivity, molecular weight, isoelectric point, relative content in microsomes, two-dimensional tryptic peptide maps, one-dimensional peptide maps with three proteases, amino acid composition, and amino-terminal protein sequence. Finally, the same protein was precipitated from microsomes prepared from the liver biopsy of a subject phenotyped in vivo as a poor metabolizer of mephenytoin. These data strongly suggest that the mephenytoin hydroxylation deficiency is caused by a minor structural change leading to a functionally altered cytochrome P-450 isozyme

  20. Treating Sample Covariances for Use in Strongly Coupled Atmosphere-Ocean Data Assimilation

    Smith, Polly J.; Lawless, Amos S.; Nichols, Nancy K.

    2018-01-01

    Strongly coupled data assimilation requires cross-domain forecast error covariances; information from ensembles can be used, but limited sampling means that ensemble derived error covariances are routinely rank deficient and/or ill-conditioned and marred by noise. Thus, they require modification before they can be incorporated into a standard assimilation framework. Here we compare methods for improving the rank and conditioning of multivariate sample error covariance matrices for coupled atmosphere-ocean data assimilation. The first method, reconditioning, alters the matrix eigenvalues directly; this preserves the correlation structures but does not remove sampling noise. We show that it is better to recondition the correlation matrix rather than the covariance matrix as this prevents small but dynamically important modes from being lost. The second method, model state-space localization via the Schur product, effectively removes sample noise but can dampen small cross-correlation signals. A combination that exploits the merits of each is found to offer an effective alternative.

  1. Genes e epilepsia I: epilepsia e alterações genéticas Genes and epilepsy I: epilepsy and genetic alterations

    Daniel L. G. Gitaí

    2008-06-01

    hypersynchronous electrical activity, preferentially in cortical areas, caused by panoply of structural and neurochemical dysfunctions. Recent advances in the field have focused on the molecular mechanisms involved in the epileptogenic process. OBJECTIVES: In the present review, we describe the main genetic alterations associated to the process of epileptogenesis and discuss the new findings that are shedding light on the molecular substrates of monogenic idiopathic epilepsies (MIE and on genetically complex epilepsies (GCE. RESULTS AND CONCLUSION: Linkage and association studies have shown that mutations in ion channel genes are the main causes of MIE and of predisposition for GCE. Moreover, mutations in genes involved in neuronal migration, glycogen metabolism and respiratory chain are associated to other syndromes involving seizures. Therefore, different gene classes contribute to the epileptic trait. The identification of epilepsy-related gene families can help us understand the molecular mechanisms of neuronal hyperexcitability and recognize markers of early diagnosis as well as new treatments for these epilepsies.

  2. Students’ Covariational Reasoning in Solving Integrals’ Problems

    Harini, N. V.; Fuad, Y.; Ekawati, R.

    2018-01-01

    Covariational reasoning plays an important role to indicate quantities vary in learning calculus. This study investigates students’ covariational reasoning during their studies concerning two covarying quantities in integral problem. Six undergraduate students were chosen to solve problems that involved interpreting and representing how quantities change in tandem. Interviews were conducted to reveal the students’ reasoning while solving covariational problems. The result emphasizes that undergraduate students were able to construct the relation of dependent variables that changes in tandem with the independent variable. However, students faced difficulty in forming images of continuously changing rates and could not accurately apply the concept of integrals. These findings suggest that learning calculus should be increased emphasis on coordinating images of two quantities changing in tandem about instantaneously rate of change and to promote conceptual knowledge in integral techniques.

  3. Covariant Quantization with Extended BRST Symmetry

    Geyer, B.; Gitman, D. M.; Lavrov, P. M.

    1999-01-01

    A short rewiev of covariant quantization methods based on BRST-antiBRST symmetry is given. In particular problems of correct definition of Sp(2) symmetric quantization scheme known as triplectic quantization are considered.

  4. Covariant extensions and the nonsymmetric unified field

    Borchsenius, K.

    1976-01-01

    The problem of generally covariant extension of Lorentz invariant field equations, by means of covariant derivatives extracted from the nonsymmetric unified field, is considered. It is shown that the contracted curvature tensor can be expressed in terms of a covariant gauge derivative which contains the gauge derivative corresponding to minimal coupling, if the universal constant p, characterizing the nonsymmetric theory, is fixed in terms of Planck's constant and the elementary quantum of charge. By this choice the spinor representation of the linear connection becomes closely related to the spinor affinity used by Infeld and Van Der Waerden (Sitzungsber. Preuss. Akad. Wiss. Phys. Math. Kl.; 9:380 (1933)) in their generally covariant formulation of Dirac's equation. (author)

  5. Covariance Spectroscopy for Fissile Material Detection

    Trainham, Rusty; Tinsley, Jim; Hurley, Paul; Keegan, Ray

    2009-01-01

    Nuclear fission produces multiple prompt neutrons and gammas at each fission event. The resulting daughter nuclei continue to emit delayed radiation as neutrons boil off, beta decay occurs, etc. All of the radiations are causally connected, and therefore correlated. The correlations are generally positive, but when different decay channels compete, so that some radiations tend to exclude others, negative correlations could also be observed. A similar problem of reduced complexity is that of cascades radiation, whereby a simple radioactive decay produces two or more correlated gamma rays at each decay. Covariance is the usual means for measuring correlation, and techniques of covariance mapping may be useful to produce distinct signatures of special nuclear materials (SNM). A covariance measurement can also be used to filter data streams because uncorrelated signals are largely rejected. The technique is generally more effective than a coincidence measurement. In this poster, we concentrate on cascades and the covariance filtering problem

  6. Covariant amplitudes in Polyakov string theory

    Aoyama, H.; Dhar, A.; Namazie, M.A.

    1986-01-01

    A manifestly Lorentz-covariant and reparametrization-invariant procedure for computing string amplitudes using Polyakov's formulation is described. Both bosonic and superstring theories are dealt with. The computation of string amplitudes is greatly facilitated by this formalism. (orig.)

  7. Covariance upperbound controllers for networked control systems

    Ko, Sang Ho

    2012-01-01

    This paper deals with designing covariance upperbound controllers for a linear system that can be used in a networked control environment in which control laws are calculated in a remote controller and transmitted through a shared communication link to the plant. In order to compensate for possible packet losses during the transmission, two different techniques are often employed: the zero-input and the hold-input strategy. These use zero input and the latest control input, respectively, when a packet is lost. For each strategy, we synthesize a class of output covariance upperbound controllers for a given covariance upperbound and a packet loss probability. Existence conditions of the covariance upperbound controller are also provided for each strategy. Through numerical examples, performance of the two strategies is compared in terms of feasibility of implementing the controllers

  8. Forecasting Covariance Matrices: A Mixed Frequency Approach

    Halbleib, Roxana; Voev, Valeri

    This paper proposes a new method for forecasting covariance matrices of financial returns. The model mixes volatility forecasts from a dynamic model of daily realized volatilities estimated with high-frequency data with correlation forecasts based on daily data. This new approach allows for flexi......This paper proposes a new method for forecasting covariance matrices of financial returns. The model mixes volatility forecasts from a dynamic model of daily realized volatilities estimated with high-frequency data with correlation forecasts based on daily data. This new approach allows...... for flexible dependence patterns for volatilities and correlations, and can be applied to covariance matrices of large dimensions. The separate modeling of volatility and correlation forecasts considerably reduces the estimation and measurement error implied by the joint estimation and modeling of covariance...

  9. Covariance data evaluation for experimental data

    Liu Tingjin

    1993-01-01

    Some methods and codes have been developed and utilized for covariance data evaluation of experimental data, including parameter analysis, physical analysis, Spline fitting etc.. These methods and codes can be used in many different cases

  10. Earth Observing System Covariance Realism Updates

    Ojeda Romero, Juan A.; Miguel, Fred

    2017-01-01

    This presentation will be given at the International Earth Science Constellation Mission Operations Working Group meetings June 13-15, 2017 to discuss the Earth Observing System Covariance Realism updates.

  11. Laser Covariance Vibrometry for Unsymmetrical Mode Detection

    Kobold, Michael C

    2006-01-01

    Simulated cross - spectral covariance (CSC) from optical return from simulated surface vibration indicates CW phase modulation may be an appropriate phenomenology for adequate classification of vehicles by structural mode...

  12. Error Covariance Estimation of Mesoscale Data Assimilation

    Xu, Qin

    2005-01-01

    The goal of this project is to explore and develop new methods of error covariance estimation that will provide necessary statistical descriptions of prediction and observation errors for mesoscale data assimilation...

  13. Genetic polymorphisms in 19q13.3 genes associated with alteration of repair capacity to BPDE-DNA adducts in primary cultured lymphocytes.

    Xiao, Mingyang; Xiao, Sha; Straaten, Tahar van der; Xue, Ping; Zhang, Guopei; Zheng, Xiao; Zhang, Qianye; Cai, Yuan; Jin, Cuihong; Yang, Jinghua; Wu, Shengwen; Zhu, Guolian; Lu, Xiaobo

    2016-12-01

    Benzo[a]pyrene(B[a]P), and its ultimate metabolite Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), are classic DNA damaging carcinogens. DNA damage in cells caused by BPDE is normally repaired by Nucleotide Excision Repair (NER) and Base Excision Repair (BER). Genetic variations in NER and BER can change individual DNA repair capacity to DNA damage induced by BPDE. In the present study we determined the number of in vitro induced BPDE-DNA adducts in lymphocytes, to reflect individual susceptibility to Polycyclic aromatic hydrocarbons (PAHs)-induced carcinogenesis. The BPDE-DNA adduct level in lymphocytes were assessed by high performance liquid chromatography (HPLC) in 281 randomly selected participants. We genotyped for 9 single nucleotide polymorphisms (SNPs) in genes involved in NER (XPB rs4150441, XPC rs2228001, rs2279017 and XPF rs4781560), BER (XRCC1 rs25487, rs25489 and rs1799782) and genes located on chromosome 19q13.2-3 (PPP1R13L rs1005165 and CAST rs967591). We found that 3 polymorphisms in chromosome 19q13.2-3 were associated with lower levels of BPDE-DNA adducts (MinorT allele in XRCC1 rs1799782, minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571). In addition, a modified comet assay was performed to further confirm the above conclusions. We found both minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571 were associated with the lower levels of BPDE-adducts. Our data suggested that the variant genotypes of genes in chromosome 19q13.2-3 are associated with the alteration of repair efficiency to DNA damage caused by Benzo[a]pyrene, and may contribute to enhance predictive value for individual's DNA repair capacity in response to environmental carcinogens. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Heteroscedasticity resistant robust covariance matrix estimator

    Víšek, Jan Ámos

    2010-01-01

    Roč. 17, č. 27 (2010), s. 33-49 ISSN 1212-074X Grant - others:GA UK(CZ) GA402/09/0557 Institutional research plan: CEZ:AV0Z10750506 Keywords : Regression * Covariance matrix * Heteroscedasticity * Resistant Subject RIV: BB - Applied Statistics, Operational Research http://library.utia.cas.cz/separaty/2011/SI/visek-heteroscedasticity resistant robust covariance matrix estimator.pdf

  15. Phase-covariant quantum cloning of qudits

    Fan Heng; Imai, Hiroshi; Matsumoto, Keiji; Wang, Xiang-Bin

    2003-01-01

    We study the phase-covariant quantum cloning machine for qudits, i.e., the input states in a d-level quantum system have complex coefficients with arbitrary phase but constant module. A cloning unitary transformation is proposed. After optimizing the fidelity between input state and single qudit reduced density operator of output state, we obtain the optimal fidelity for 1 to 2 phase-covariant quantum cloning of qudits and the corresponding cloning transformation

  16. Noncommutative Gauge Theory with Covariant Star Product

    Zet, G.

    2010-01-01

    We present a noncommutative gauge theory with covariant star product on a space-time with torsion. In order to obtain the covariant star product one imposes some restrictions on the connection of the space-time. Then, a noncommutative gauge theory is developed applying this product to the case of differential forms. Some comments on the advantages of using a space-time with torsion to describe the gravitational field are also given.

  17. Covariant phase difference observables in quantum mechanics

    Heinonen, Teiko; Lahti, Pekka; Pellonpaeae, Juha-Pekka

    2003-01-01

    Covariant phase difference observables are determined in two different ways, by a direct computation and by a group theoretical method. A characterization of phase difference observables which can be expressed as the difference of two phase observables is given. The classical limits of such phase difference observables are determined and the Pegg-Barnett phase difference distribution is obtained from the phase difference representation. The relation of Ban's theory to the covariant phase theories is exhibited

  18. Hierarchical matrix approximation of large covariance matrices

    Litvinenko, Alexander

    2015-01-07

    We approximate large non-structured covariance matrices in the H-matrix format with a log-linear computational cost and storage O(n log n). We compute inverse, Cholesky decomposition and determinant in H-format. As an example we consider the class of Matern covariance functions, which are very popular in spatial statistics, geostatistics, machine learning and image analysis. Applications are: kriging and optimal design

  19. Hierarchical matrix approximation of large covariance matrices

    Litvinenko, Alexander

    2015-01-05

    We approximate large non-structured covariance matrices in the H-matrix format with a log-linear computational cost and storage O(nlogn). We compute inverse, Cholesky decomposition and determinant in H-format. As an example we consider the class of Matern covariance functions, which are very popular in spatial statistics, geostatistics, machine learning and image analysis. Applications are: kriging and op- timal design.

  20. Covariate analysis of bivariate survival data

    Bennett, L.E.

    1992-01-01

    The methods developed are used to analyze the effects of covariates on bivariate survival data when censoring and ties are present. The proposed method provides models for bivariate survival data that include differential covariate effects and censored observations. The proposed models are based on an extension of the univariate Buckley-James estimators which replace censored data points by their expected values, conditional on the censoring time and the covariates. For the bivariate situation, it is necessary to determine the expectation of the failure times for one component conditional on the failure or censoring time of the other component. Two different methods have been developed to estimate these expectations. In the semiparametric approach these expectations are determined from a modification of Burke's estimate of the bivariate empirical survival function. In the parametric approach censored data points are also replaced by their conditional expected values where the expected values are determined from a specified parametric distribution. The model estimation will be based on the revised data set, comprised of uncensored components and expected values for the censored components. The variance-covariance matrix for the estimated covariate parameters has also been derived for both the semiparametric and parametric methods. Data from the Demographic and Health Survey was analyzed by these methods. The two outcome variables are post-partum amenorrhea and breastfeeding; education and parity were used as the covariates. Both the covariate parameter estimates and the variance-covariance estimates for the semiparametric and parametric models will be compared. In addition, a multivariate test statistic was used in the semiparametric model to examine contrasts. The significance of the statistic was determined from a bootstrap distribution of the test statistic.

  1. Hierarchical matrix approximation of large covariance matrices

    Litvinenko, Alexander; Genton, Marc G.; Sun, Ying; Tempone, Raul

    2015-01-01

    We approximate large non-structured covariance matrices in the H-matrix format with a log-linear computational cost and storage O(n log n). We compute inverse, Cholesky decomposition and determinant in H-format. As an example we consider the class of Matern covariance functions, which are very popular in spatial statistics, geostatistics, machine learning and image analysis. Applications are: kriging and optimal design

  2. Hierarchical matrix approximation of large covariance matrices

    Litvinenko, Alexander; Genton, Marc G.; Sun, Ying; Tempone, Raul

    2015-01-01

    We approximate large non-structured covariance matrices in the H-matrix format with a log-linear computational cost and storage O(nlogn). We compute inverse, Cholesky decomposition and determinant in H-format. As an example we consider the class of Matern covariance functions, which are very popular in spatial statistics, geostatistics, machine learning and image analysis. Applications are: kriging and op- timal design.

  3. Covariant perturbations of Schwarzschild black holes

    Clarkson, Chris A; Barrett, Richard K

    2003-01-01

    We present a new covariant and gauge-invariant perturbation formalism for dealing with spacetimes having spherical symmetry (or some preferred spatial direction) in the background, and apply it to the case of gravitational wave propagation in a Schwarzschild black-hole spacetime. The 1 + 3 covariant approach is extended to a '1 + 1 + 2 covariant sheet' formalism by introducing a radial unit vector in addition to the timelike congruence, and decomposing all covariant quantities with respect to this. The background Schwarzschild solution is discussed and a covariant characterization is given. We give the full first-order system of linearized 1 + 1 + 2 covariant equations, and we show how, by introducing (time and spherical) harmonic functions, these may be reduced to a system of first-order ordinary differential equations and algebraic constraints for the 1 + 1 + 2 variables which may be solved straightforwardly. We show how both odd- and even-parity perturbations may be unified by the discovery of a covariant, frame- and gauge-invariant, transverse-traceless tensor describing gravitational waves, which satisfies a covariant wave equation equivalent to the Regge-Wheeler equation for both even- and odd-parity perturbations. We show how the Zerilli equation may be derived from this tensor, and derive a similar transverse-traceless tensor equation equivalent to this equation. The so-called special quasinormal modes with purely imaginary frequency emerge naturally. The significance of the degrees of freedom in the choice of the two frame vectors is discussed, and we demonstrate that, for a certain frame choice, the underlying dynamics is governed purely by the Regge-Wheeler tensor. The two transverse-traceless Weyl tensors which carry the curvature of gravitational waves are discussed, and we give the closed system of four first-order ordinary differential equations describing their propagation. Finally, we consider the extension of this work to the study of

  4. Radiation protection philosophy alters

    Firmin, G.

    1977-01-01

    Two significant events that have taken place this year in the field of radiation protection are reported. New SI units have been proposed (and effectively adopted), and the ICRP has revised its recommendations. Changes of emphasis in the latest recommendations (ICRP Publication 26) imply an altered radiation protection philosophy, in particular the relation of dose limits to estimates of average risk, an altered view of the critical organ approach and a new attitude to genetic dose to the population. (author)

  5. Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity.

    Yee, Yohan; Fernandes, Darren J; French, Leon; Ellegood, Jacob; Cahill, Lindsay S; Vousden, Dulcie A; Spencer Noakes, Leigh; Scholz, Jan; van Eede, Matthijs C; Nieman, Brian J; Sled, John G; Lerch, Jason P

    2018-05-18

    An organizational pattern seen in the brain, termed structural covariance, is the statistical association of pairs of brain regions in their anatomical properties. These associations, measured across a population as covariances or correlations usually in cortical thickness or volume, are thought to reflect genetic and environmental underpinnings. Here, we examine the biological basis of structural volume covariance in the mouse brain. We first examined large scale associations between brain region volumes using an atlas-based approach that parcellated the entire mouse brain into 318 regions over which correlations in volume were assessed, for volumes obtained from 153 mouse brain images via high-resolution MRI. We then used a seed-based approach and determined, for 108 different seed regions across the brain and using mouse gene expression and connectivity data from the Allen Institute for Brain Science, the variation in structural covariance data that could be explained by distance to seed, transcriptomic similarity to seed, and connectivity to seed. We found that overall, correlations in structure volumes hierarchically clustered into distinct anatomical systems, similar to findings from other studies and similar to other types of networks in the brain, including structural connectivity and transcriptomic similarity networks. Across seeds, this structural covariance was significantly explained by distance (17% of the variation, up to a maximum of 49% for structural covariance to the visceral area of the cortex), transcriptomic similarity (13% of the variation, up to maximum of 28% for structural covariance to the primary visual area) and connectivity (15% of the variation, up to a maximum of 36% for structural covariance to the intermediate reticular nucleus in the medulla) of covarying structures. Together, distance, connectivity, and transcriptomic similarity explained 37% of structural covariance, up to a maximum of 63% for structural covariance to the

  6. Econometric analysis of realised covariation: high frequency covariance, regression and correlation in financial economics

    Ole E. Barndorff-Nielsen; Neil Shephard

    2002-01-01

    This paper analyses multivariate high frequency financial data using realised covariation. We provide a new asymptotic distribution theory for standard methods such as regression, correlation analysis and covariance. It will be based on a fixed interval of time (e.g. a day or week), allowing the number of high frequency returns during this period to go to infinity. Our analysis allows us to study how high frequency correlations, regressions and covariances change through time. In particular w...

  7. Deriving Genomic Breeding Values for Residual Feed Intake from Covariance Functions of Random Regression Models

    Strathe, Anders B; Mark, Thomas; Nielsen, Bjarne

    2014-01-01

    Random regression models were used to estimate covariance functions between cumulated feed intake (CFI) and body weight (BW) in 8424 Danish Duroc pigs. Random regressions on second order Legendre polynomials of age were used to describe genetic and permanent environmental curves in BW and CFI...

  8. Variance and covariance components for liability of piglet survival during different periods

    Su, G; Sorensen, D; Lund, M S

    2008-01-01

    Variance and covariance components for piglet survival in different periods were estimated from individual records of 133 004 Danish Landrace piglets and 89 928 Danish Yorkshire piglets, using a liability threshold model including both direct and maternal additive genetic effects. At the individu...

  9. A special covariance structure for random coefficient models with both between and within covariates

    Riedel, K.S.

    1990-07-01

    We review random coefficient (RC) models in linear regression and propose a bias correction to the maximum likelihood (ML) estimator. Asymmptotic expansion of the ML equations are given when the between individual variance is much larger or smaller than the variance from within individual fluctuations. The standard model assumes all but one covariate varies within each individual, (we denote the within covariates by vector χ 1 ). We consider random coefficient models where some of the covariates do not vary in any single individual (we denote the between covariates by vector χ 0 ). The regression coefficients, vector β k , can only be estimated in the subspace X k of X. Thus the number of individuals necessary to estimate vector β and the covariance matrix Δ of vector β increases significantly in the presence of more than one between covariate. When the number of individuals is sufficient to estimate vector β but not the entire matrix Δ , additional assumptions must be imposed on the structure of Δ. A simple reduced model is that the between component of vector β is fixed and only the within component varies randomly. This model fails because it is not invariant under linear coordinate transformations and it can significantly overestimate the variance of new observations. We propose a covariance structure for Δ without these difficulties by first projecting the within covariates onto the space perpendicular to be between covariates. (orig.)

  10. Are your covariates under control? How normalization can re-introduce covariate effects.

    Pain, Oliver; Dudbridge, Frank; Ronald, Angelica

    2018-04-30

    Many statistical tests rely on the assumption that the residuals of a model are normally distributed. Rank-based inverse normal transformation (INT) of the dependent variable is one of the most popular approaches to satisfy the normality assumption. When covariates are included in the analysis, a common approach is to first adjust for the covariates and then normalize the residuals. This study investigated the effect of regressing covariates against the dependent variable and then applying rank-based INT to the residuals. The correlation between the dependent variable and covariates at each stage of processing was assessed. An alternative approach was tested in which rank-based INT was applied to the dependent variable before regressing covariates. Analyses based on both simulated and real data examples demonstrated that applying rank-based INT to the dependent variable residuals after regressing out covariates re-introduces a linear correlation between the dependent variable and covariates, increasing type-I errors and reducing power. On the other hand, when rank-based INT was applied prior to controlling for covariate effects, residuals were normally distributed and linearly uncorrelated with covariates. This latter approach is therefore recommended in situations were normality of the dependent variable is required.

  11. Nuclear data covariances in the Indian context

    Ganesan, S.

    2014-01-01

    The topic of covariances is recognized as an important part of several ongoing nuclear data science activities, since 2007, in the Nuclear Data Physics Centre of India (NDPCI). A Phase-1 project in collaboration with the Statistics department in Manipal University, Karnataka (Prof. K.M. Prasad and Prof. S. Nair) on nuclear data covariances was executed successfully during 2007-2011 period. In Phase-I, the NDPCI has conducted three national Theme meetings sponsored by the DAE-BRNS in 2008, 2010 and 2013 on nuclear data covariances. In Phase-1, the emphasis was on a thorough basic understanding of the concept of covariances including assigning uncertainties to experimental data in terms of partial errors and micro correlations, through a study and a detailed discussion of open literature. Towards the end of Phase-1, measurements and a first time covariance analysis of cross-sections for 58 Ni (n, p) 58 Co reaction measured in Mumbai Pelletron accelerator using 7 Li (p,n) reactions as neutron source in the MeV energy region were performed under a PhD programme on nuclear data covariances in which enrolled are two students, Shri B.S. Shivashankar and Ms. Shanti Sheela. India is also successfully evolving a team of young researchers to code nuclear data of uncertainties, with the perspectives on covariances, in the IAEA-EXFOR format. A Phase-II DAE-BRNS-NDPCI proposal of project at Manipal has been submitted and the proposal is undergoing a peer-review at this time. In Phase-2, modern nuclear data evaluation techniques that including covariances will be further studied as a research and development effort, as a first time effort. These efforts include the use of techniques such as that of the Kalman filter. Presently, a 48 hours lecture series on treatment of errors and their propagation is being formulated under auspices of the Homi Bhabha National Institute. The talk describes the progress achieved thus far in the learning curve of the above-mentioned and exciting

  12. Cross-covariance functions for multivariate geostatistics

    Genton, Marc G.

    2015-05-01

    Continuously indexed datasets with multiple variables have become ubiquitous in the geophysical, ecological, environmental and climate sciences, and pose substantial analysis challenges to scientists and statisticians. For many years, scientists developed models that aimed at capturing the spatial behavior for an individual process; only within the last few decades has it become commonplace to model multiple processes jointly. The key difficulty is in specifying the cross-covariance function, that is, the function responsible for the relationship between distinct variables. Indeed, these cross-covariance functions must be chosen to be consistent with marginal covariance functions in such a way that the second-order structure always yields a nonnegative definite covariance matrix. We review the main approaches to building cross-covariance models, including the linear model of coregionalization, convolution methods, the multivariate Matérn and nonstationary and space-time extensions of these among others. We additionally cover specialized constructions, including those designed for asymmetry, compact support and spherical domains, with a review of physics-constrained models. We illustrate select models on a bivariate regional climate model output example for temperature and pressure, along with a bivariate minimum and maximum temperature observational dataset; we compare models by likelihood value as well as via cross-validation co-kriging studies. The article closes with a discussion of unsolved problems. © Institute of Mathematical Statistics, 2015.

  13. Schroedinger covariance states in anisotropic waveguides

    Angelow, A.; Trifonov, D.

    1995-03-01

    In this paper Squeezed and Covariance States based on Schroedinger inequality and their connection with other nonclassical states are considered for particular case of anisotropic waveguide in LiNiO 3 . Here, the problem of photon creation and generation of squeezed and Schroedinger covariance states in optical waveguides is solved in two steps: 1. Quantization of electromagnetic field is provided in the presence of dielectric waveguide using normal-mode expansion. The photon creation and annihilation operators are introduced, expanding the solution A-vector(r-vector,t) in a series in terms of the Sturm - Liouville mode-functions. 2. In terms of these operators the Hamiltonian of the field in a nonlinear waveguide is derived. For such Hamiltonian we construct the covariance states as stable (with nonzero covariance), which minimize the Schroedinger uncertainty relation. The evolutions of the three second momenta of q-circumflex j and p-circumflex j are calculated. For this Hamiltonian all three momenta are expressed in terms of one real parameters s only. It is found out how covariance, via this parameter s, depends on the waveguide profile n(x,y), on the mode-distributions u-vector j (x,y), and on the waveguide phase mismatching Δβ. (author). 37 refs

  14. Form of the manifestly covariant Lagrangian

    Johns, Oliver Davis

    1985-10-01

    The preferred form for the manifestly covariant Lagrangian function of a single, charged particle in a given electromagnetic field is the subject of some disagreement in the textbooks. Some authors use a ``homogeneous'' Lagrangian and others use a ``modified'' form in which the covariant Hamiltonian function is made to be nonzero. We argue in favor of the ``homogeneous'' form. We show that the covariant Lagrangian theories can be understood only if one is careful to distinguish quantities evaluated on the varied (in the sense of the calculus of variations) world lines from quantities evaluated on the unvaried world lines. By making this distinction, we are able to derive the Hamilton-Jacobi and Klein-Gordon equations from the ``homogeneous'' Lagrangian, even though the covariant Hamiltonian function is identically zero on all world lines. The derivation of the Klein-Gordon equation in particular gives Lagrangian theoretical support to the derivations found in standard quantum texts, and is also shown to be consistent with the Feynman path-integral method. We conclude that the ``homogeneous'' Lagrangian is a completely adequate basis for covariant Lagrangian theory both in classical and quantum mechanics. The article also explores the analogy with the Fermat theorem of optics, and illustrates a simple invariant notation for the Lagrangian and other four-vector equations.

  15. Cross-covariance functions for multivariate geostatistics

    Genton, Marc G.; Kleiber, William

    2015-01-01

    Continuously indexed datasets with multiple variables have become ubiquitous in the geophysical, ecological, environmental and climate sciences, and pose substantial analysis challenges to scientists and statisticians. For many years, scientists developed models that aimed at capturing the spatial behavior for an individual process; only within the last few decades has it become commonplace to model multiple processes jointly. The key difficulty is in specifying the cross-covariance function, that is, the function responsible for the relationship between distinct variables. Indeed, these cross-covariance functions must be chosen to be consistent with marginal covariance functions in such a way that the second-order structure always yields a nonnegative definite covariance matrix. We review the main approaches to building cross-covariance models, including the linear model of coregionalization, convolution methods, the multivariate Matérn and nonstationary and space-time extensions of these among others. We additionally cover specialized constructions, including those designed for asymmetry, compact support and spherical domains, with a review of physics-constrained models. We illustrate select models on a bivariate regional climate model output example for temperature and pressure, along with a bivariate minimum and maximum temperature observational dataset; we compare models by likelihood value as well as via cross-validation co-kriging studies. The article closes with a discussion of unsolved problems. © Institute of Mathematical Statistics, 2015.

  16. Convex Banding of the Covariance Matrix.

    Bien, Jacob; Bunea, Florentina; Xiao, Luo

    2016-01-01

    We introduce a new sparse estimator of the covariance matrix for high-dimensional models in which the variables have a known ordering. Our estimator, which is the solution to a convex optimization problem, is equivalently expressed as an estimator which tapers the sample covariance matrix by a Toeplitz, sparsely-banded, data-adaptive matrix. As a result of this adaptivity, the convex banding estimator enjoys theoretical optimality properties not attained by previous banding or tapered estimators. In particular, our convex banding estimator is minimax rate adaptive in Frobenius and operator norms, up to log factors, over commonly-studied classes of covariance matrices, and over more general classes. Furthermore, it correctly recovers the bandwidth when the true covariance is exactly banded. Our convex formulation admits a simple and efficient algorithm. Empirical studies demonstrate its practical effectiveness and illustrate that our exactly-banded estimator works well even when the true covariance matrix is only close to a banded matrix, confirming our theoretical results. Our method compares favorably with all existing methods, in terms of accuracy and speed. We illustrate the practical merits of the convex banding estimator by showing that it can be used to improve the performance of discriminant analysis for classifying sound recordings.

  17. Gas seepage from Tokamachi mud volcanoes, onshore Niigata Basin (Japan): Origin, post-genetic alterations and CH{sub 4}-CO{sub 2} fluxes

    Etiope, G., E-mail: etiope@ingv.it [Istituto Nazionale di Geofisica e Vulcanologia, via V. Murata 605, 00143 Roma (Italy); Nakada, R. [Dept. of Earth and Planetary Systems Science, Graduate School of Science, Hiroshima University (Japan); Tanaka, K. [Graduate School of Science and Engineering, Yamaguchi University (Japan); Yoshida, N. [Dept. of Environmental Chemistry and Engineering, Tokyo Institute of Technology (Japan)

    2011-03-15

    Research highlights: {yields} Tokamachi gas shows signals of subsurface hydrocarbon biodegradation. {yields} Hydrocarbon molecular fractionation depends on gas flux. {yields} Substantial gas emission from mud volcanoes is from invisible diffuse seepage. {yields} Global mud volcano methane emission is likely higher than 10 Mt a{sup -1}. - Abstract: Methane and CO{sub 2} emissions from the two most active mud volcanoes in central Japan, Murono and Kamou (Tokamachi City, Niigata Basin), were measured in from both craters or vents (macro-seepage) and invisible exhalation from the soil (mini- and microseepage). Molecular and isotopic compositions of the released gases were also determined. Gas is thermogenic ({delta}{sup 13}C{sub CH4} from -32.9 per mille to -36.2 per mille), likely associated with oil, and enrichments of {sup 13}C in CO{sub 2} ({delta}{sup 13}C{sub CO2} up to +28.3 per mille) and propane ({delta}{sup 13}C{sub C3H8} up to -8.6 per mille) suggest subsurface petroleum biodegradation. Gas source and post-genetic alteration processes did not change from 2004 to 2010. Methane flux ranged within the orders of magnitude of 10{sup 1}-10{sup 4} g m{sup -2} d{sup -1} in macro-seeps, and up to 446 g m{sup -2} d{sup -1} from diffuse seepage. Positive CH{sub 4} fluxes from dry soil were widespread throughout the investigated areas. Total CH{sub 4} emission from Murono and Kamou were estimated to be at least 20 and 3.7 ton a{sup -1}, respectively, of which more than half was from invisible seepage surrounding the mud volcano vents. At the macro-seeps, CO{sub 2} fluxes were directly proportional to CH{sub 4} fluxes, and the volumetric ratios between CH{sub 4} flux and CO{sub 2} flux were similar to the compositional CH{sub 4}/CO{sub 2} volume ratio. Macro-seep flux data, in addition to those of other 13 mud volcanoes, supported the hypothesis that molecular fractionation (increase of the 'Bernard ratio' C{sub 1}/(C{sub 2} + C{sub 3})) is inversely

  18. Directional selection effects on patterns of phenotypic (co)variation in wild populations.

    Assis, A P A; Patton, J L; Hubbe, A; Marroig, G

    2016-11-30

    Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient. © 2016 The Author(s).

  19. Progress on Nuclear Data Covariances: AFCI-1.2 Covariance Library

    Oblozinsky, P.; Oblozinsky, P.; Mattoon, C.M.; Herman, M.; Mughabghab, S.F.; Pigni, M.T.; Talou, P.; Hale, G.M.; Kahler, A.C.; Kawano, T.; Little, R.C.; Young, P.G

    2009-01-01

    Improved neutron cross section covariances were produced for 110 materials including 12 light nuclei (coolants and moderators), 78 structural materials and fission products, and 20 actinides. Improved covariances were organized into AFCI-1.2 covariance library in 33-energy groups, from 10 -5 eV to 19.6 MeV. BNL contributed improved covariance data for the following materials: 23 Na and 55 Mn where more detailed evaluation was done; improvements in major structural materials 52 Cr, 56 Fe and 58 Ni; improved estimates for remaining structural materials and fission products; improved covariances for 14 minor actinides, and estimates of mubar covariances for 23 Na and 56 Fe. LANL contributed improved covariance data for 235 U and 239 Pu including prompt neutron fission spectra and completely new evaluation for 240 Pu. New R-matrix evaluation for 16 O including mubar covariances is under completion. BNL assembled the library and performed basic testing using improved procedures including inspection of uncertainty and correlation plots for each material. The AFCI-1.2 library was released to ANL and INL in August 2009.

  20. The Effect of Unequal Samples, Heterogeneity of Covariance Matrices, and Number of Variables on Discriminant Analysis Classification Tables and Related Statistics.

    Spearing, Debra; Woehlke, Paula

    To assess the effect on discriminant analysis in terms of correct classification into two groups, the following parameters were systematically altered using Monte Carlo techniques: sample sizes; proportions of one group to the other; number of independent variables; and covariance matrices. The pairing of the off diagonals (or covariances) with…

  1. ACORNS, Covariance and Correlation Matrix Diagonalization

    Szondi, E.J.

    1990-01-01

    1 - Description of program or function: The program allows the user to verify the different types of covariance/correlation matrices used in the activation neutron spectrometry. 2 - Method of solution: The program performs the diagonalization of the input covariance/relative covariance/correlation matrices. The Eigen values are then analyzed to determine the rank of the matrices. If the Eigen vectors of the pertinent correlation matrix have also been calculated, the program can perform a complete factor analysis (generation of the factor matrix and its rotation in Kaiser's 'varimax' sense to select the origin of the correlations). 3 - Restrictions on the complexity of the problem: Matrix size is limited to 60 on PDP and to 100 on IBM PC/AT

  2. Group covariant protocols for quantum string commitment

    Tsurumaru, Toyohiro

    2006-01-01

    We study the security of quantum string commitment (QSC) protocols with group covariant encoding scheme. First we consider a class of QSC protocol, which is general enough to incorporate all the QSC protocols given in the preceding literatures. Then among those protocols, we consider group covariant protocols and show that the exact upperbound on the binding condition can be calculated. Next using this result, we prove that for every irreducible representation of a finite group, there always exists a corresponding nontrivial QSC protocol which reaches a level of security impossible to achieve classically

  3. The covariant entropy bound in gravitational collapse

    Gao, Sijie; Lemos, Jose P. S.

    2004-01-01

    We study the covariant entropy bound in the context of gravitational collapse. First, we discuss critically the heuristic arguments advanced by Bousso. Then we solve the problem through an exact model: a Tolman-Bondi dust shell collapsing into a Schwarzschild black hole. After the collapse, a new black hole with a larger mass is formed. The horizon, L, of the old black hole then terminates at the singularity. We show that the entropy crossing L does not exceed a quarter of the area of the old horizon. Therefore, the covariant entropy bound is satisfied in this process. (author)

  4. Modular invariance and covariant loop calculus

    Petersen, J.L.; Roland, K.O.; Sidenius, J.R.

    1988-01-01

    The covariant loop calculus provides and efficient technique for computing explicit expressions for the density on moduli space corresponding to arbitrary (bosonic string) loop diagrams. Since modular invariance is not manifest, however, we carry out a detailed comparison with known explicit 2- and 3- loop results derived using analytic geometry (1 loop is known to be ok). We establish identity to 'high' order in some moduli and exactly in others. Agreement is found as a result of various non-trivial cancellations, in part related to number theory. We feel our results provide very strong support for the correctness of the covariant loop calculus approach. (orig.)

  5. Remarks on Bousso's covariant entropy bound

    Mayo, A E

    2002-01-01

    Bousso's covariant entropy bound is put to the test in the context of a non-singular cosmological solution of general relativity found by Bekenstein. Although the model complies with every assumption made in Bousso's original conjecture, the entropy bound is violated due to the occurrence of negative energy density associated with the interaction of some the matter components in the model. We demonstrate how this property allows for the test model to 'elude' a proof of Bousso's conjecture which was given recently by Flanagan, Marolf and Wald. This corroborates the view that the covariant entropy bound should be applied only to stable systems for which every matter component carries positive energy density.

  6. Modular invariance and covariant loop calculus

    Petersen, J.L.; Roland, K.O.; Sidenius, J.R.

    1988-01-01

    The covariant loop calculus provides an efficient technique for computing explicit expressions for the density on moduli space corresponding to arbitrary (bosonic string) loop diagrams. Since modular invariance is not manifest, however, we carry out a detailed comparison with known explicit two- and three-loop results derived using analytic geometry (one loop is known to be okay). We establish identity to 'high' order in some moduli and exactly in others. Agreement is found as a result of various nontrivial cancellations, in part related to number theory. We feel our results provide very strong support for the correctness of the covariant loop calculus approach. (orig.)

  7. Covariant n2-plet mass formulas

    Davidson, A.

    1979-01-01

    Using a generalized internal symmetry group analogous to the Lorentz group, we have constructed a covariant n 2 -plet mass operator. This operator is built as a scalar matrix in the (n;n*) representation, and its SU(n) breaking parameters are identified as intrinsic boost ones. Its basic properties are: covariance, Hermiticity, positivity, charge conjugation, quark contents, and a self-consistent n 2 -1, 1 mixing. The GMO and the Okubo formulas are obtained by considering two different limits of the same generalized mass formula

  8. Parametric number covariance in quantum chaotic spectra.

    Vinayak; Kumar, Sandeep; Pandey, Akhilesh

    2016-03-01

    We study spectral parametric correlations in quantum chaotic systems and introduce the number covariance as a measure of such correlations. We derive analytic results for the classical random matrix ensembles using the binary correlation method and obtain compact expressions for the covariance. We illustrate the universality of this measure by presenting the spectral analysis of the quantum kicked rotors for the time-reversal invariant and time-reversal noninvariant cases. A local version of the parametric number variance introduced earlier is also investigated.

  9. Language Ability Predicts Cortical Structure and Covariance in Boys with Autism Spectrum Disorder.

    Sharda, Megha; Foster, Nicholas E V; Tryfon, Ana; Doyle-Thomas, Krissy A R; Ouimet, Tia; Anagnostou, Evdokia; Evans, Alan C; Zwaigenbaum, Lonnie; Lerch, Jason P; Lewis, John D; Hyde, Krista L

    2017-03-01

    There is significant clinical heterogeneity in language and communication abilities of individuals with Autism Spectrum Disorders (ASD). However, no consistent pathology regarding the relationship of these abilities to brain structure has emerged. Recent developments in anatomical correlation-based approaches to map structural covariance networks (SCNs), combined with detailed behavioral characterization, offer an alternative for studying these relationships. In this study, such an approach was used to study the integrity of SCNs of cortical thickness and surface area associated with language and communication, in 46 high-functioning, school-age children with ASD compared with 50 matched, typically developing controls (all males) with IQ > 75. Findings showed that there was alteration of cortical structure and disruption of fronto-temporal cortical covariance in ASD compared with controls. Furthermore, in an analysis of a subset of ASD participants, alterations in both cortical structure and covariance were modulated by structural language ability of the participants, but not communicative function. These findings indicate that structural language abilities are related to altered fronto-temporal cortical covariance in ASD, much more than symptom severity or cognitive ability. They also support the importance of better characterizing ASD samples while studying brain structure and for better understanding individual differences in language and communication abilities in ASD. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Activities on covariance estimation in Japanese Nuclear Data Committee

    Shibata, Keiichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-03-01

    Described are activities on covariance estimation in the Japanese Nuclear Data Committee. Covariances are obtained from measurements by using the least-squares methods. A simultaneous evaluation was performed to deduce covariances of fission cross sections of U and Pu isotopes. A code system, KALMAN, is used to estimate covariances of nuclear model calculations from uncertainties in model parameters. (author)

  11. Covariant canonical quantization of fields and Bohmian mechanics

    Nikolic, H.

    2005-01-01

    We propose a manifestly covariant canonical method of field quantization based on the classical De Donder-Weyl covariant canonical formulation of field theory. Owing to covariance, the space and time arguments of fields are treated on an equal footing. To achieve both covariance and consistency with standard non-covariant canonical quantization of fields in Minkowski spacetime, it is necessary to adopt a covariant Bohmian formulation of quantum field theory. A preferred foliation of spacetime emerges dynamically owing to a purely quantum effect. The application to a simple time-reparametrization invariant system and quantum gravity is discussed and compared with the conventional non-covariant Wheeler-DeWitt approach. (orig.)

  12. Abnormalities in Structural Covariance of Cortical Gyrification in Parkinson's Disease.

    Xu, Jinping; Zhang, Jiuquan; Zhang, Jinlei; Wang, Yue; Zhang, Yanling; Wang, Jian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

    2017-01-01

    Although abnormal cortical morphology and connectivity between brain regions (structural covariance) have been reported in Parkinson's disease (PD), the topological organizations of large-scale structural brain networks are still poorly understood. In this study, we investigated large-scale structural brain networks in a sample of 37 PD patients and 34 healthy controls (HC) by assessing the structural covariance of cortical gyrification with local gyrification index (lGI). We demonstrated prominent small-world properties of the structural brain networks for both groups. Compared with the HC group, PD patients showed significantly increased integrated characteristic path length and integrated clustering coefficient, as well as decreased integrated global efficiency in structural brain networks. Distinct distributions of hub regions were identified between the two groups, showing more hub regions in the frontal cortex in PD patients. Moreover, the modular analyses revealed significantly decreased integrated regional efficiency in lateral Fronto-Insula-Temporal module, and increased integrated regional efficiency in Parieto-Temporal module in the PD group as compared to the HC group. In summary, our study demonstrated altered topological properties of structural networks at a global, regional and modular level in PD patients. These findings suggests that the structural networks of PD patients have a suboptimal topological organization, resulting in less effective integration of information between brain regions.

  13. Evaluation of genetically altered medflies for use in sterile insect technique programmes. Proceedings of the final research co-ordination meeting

    1997-01-01

    Although the medfly is a key pest in many areas of the world, there are important fruit growing areas where other fruit flies are key pests. It was concluded that it would be of value for any future CRP on genetic sexing to include these species. For the development of genetic sexing systems in these species much can be gained from the experiences with the medfly. However, at present, a similar procedure will have to be followed which will entail the construction of genetic maps, the development of cytological techniques and the induction of male linked translocation. In future, the availability of molecular methods could enable sexing systems to be transferred between species. The proceedings contain 11 papers, which range from an initial molecular analysis of the genome of the fly to a field experiment to assess the impact of an all-male release

  14. Hierarchical matrix approximation of large covariance matrices

    Litvinenko, Alexander; Genton, Marc G.; Sun, Ying

    2015-01-01

    We approximate large non-structured Matérn covariance matrices of size n×n in the H-matrix format with a log-linear computational cost and storage O(kn log n), where rank k ≪ n is a small integer. Applications are: spatial statistics, machine learning and image analysis, kriging and optimal design.

  15. Zero curvature conditions and conformal covariance

    Akemann, G.; Grimm, R.

    1992-05-01

    Two-dimensional zero curvature conditions were investigated in detail, with special emphasis on conformal properties, and the appearance of covariant higher order differential operators constructed in terms of a projective connection was elucidated. The analysis is based on the Kostant decomposition of simple Lie algebras in terms of representations with respect to their 'principal' SL(2) subalgebra. (author) 27 refs

  16. On superfield covariant quantization in general coordinates

    Gitman, D.M.; Moshin, P. Yu.; Tomazelli, J.L.

    2005-01-01

    We propose a natural extension of the BRST-antiBRST superfield covariant scheme in general coordinates. Thus, the coordinate dependence of the basic tensor fields and scalar density of the formalism is extended from the base supermanifold to the complete set of superfield variables. (orig.)

  17. On superfield covariant quantization in general coordinates

    Gitman, D.M. [Universidade de Sao Paulo, Instituto de Fisica, Sao Paulo, S.P (Brazil); Moshin, P. Yu. [Universidade de Sao Paulo, Instituto de Fisica, Sao Paulo, S.P (Brazil); Tomsk State Pedagogical University, Tomsk (Russian Federation); Tomazelli, J.L. [UNESP, Departamento de Fisica e Quimica, Campus de Guaratingueta (Brazil)

    2005-12-01

    We propose a natural extension of the BRST-antiBRST superfield covariant scheme in general coordinates. Thus, the coordinate dependence of the basic tensor fields and scalar density of the formalism is extended from the base supermanifold to the complete set of superfield variables. (orig.)

  18. Covariant field theory of closed superstrings

    Siopsis, G.

    1989-01-01

    The authors construct covariant field theories of both type-II and heterotic strings. Toroidal compactification is also considered. The interaction vertices are based on Witten's vertex representing three strings interacting at the mid-point. For closed strings, the authors thus obtain a bilocal interaction

  19. Conformally covariant composite operators in quantum chromodynamics

    Craigie, N.S.; Dobrev, V.K.; Todorov, I.T.

    1983-03-01

    Conformal covariance is shown to determine renormalization properties of composite operators in QCD and in the C 6 3 -model at the one-loop level. Its relevance to higher order (renormalization group improved) perturbative calculations in the short distance limit is also discussed. Light cone operator product expansions and spectral representations for wave functions in QCD are derived. (author)

  20. Soft covariant gauges on the lattice

    Henty, D.S.; Oliveira, O.; Parrinello, C.; Ryan, S. [Department of Physics and Astronomy, University of Edinburgh, Edinburgh EH9 3JZ, Scotland (UKQCD Collaboration)

    1996-12-01

    We present an exploratory study of a one-parameter family of covariant, nonperturbative lattice gauge-fixing conditions that can be implemented through a simple Monte Carlo algorithm. We demonstrate that at the numerical level the procedure is feasible, and as a first application we examine the gauge dependence of the gluon propagator. {copyright} {ital 1996 The American Physical Society.}

  1. Covariant differential calculus on the quantum hyperplane

    Wess, J.

    1991-01-01

    We develop a differential calculus on the quantum hyperplane covariant with respect to the action of the quantum group GL q (n). This is a concrete example of noncommutative differential geometry. We describe the general constraints for a noncommutative differential calculus and verify that the example given here satisfies all these constraints. We also discuss briefly the integration over the quantum plane. (orig.)

  2. Covariant single-hole optical potential

    Kam, J. de

    1982-01-01

    In this investigation a covariant optical potential model is constructed for scattering processes of mesons from nuclei in which the meson interacts repeatedly with one of the target nucleons. The nuclear binding interactions in the intermediate scattering state are consistently taken into account. In particular for pions and K - projectiles this is important in view of the strong energy dependence of the elementary projectile-nucleon amplitude. Furthermore, this optical potential satisfies unitarity and relativistic covariance. The starting point in our discussion is the three-body model for the optical potential. To obtain a practical covariant theory I formulate the three-body model as a relativistic quasi two-body problem. Expressions for the transition interactions and propagators in the quasi two-body equations are found by imposing the correct s-channel unitarity relations and by using dispersion integrals. This is done in such a way that the correct non-relativistic limit is obtained, avoiding clustering problems. Corrections to the quasi two-body treatment from the Pauli principle and the required ground-state exclusion are taken into account. The covariant equations that we arrive at are amenable to practical calculations. (orig.)

  3. Nonlinear realization of general covariance group

    Hamamoto, Shinji

    1979-01-01

    The structure of the theory resulting from the nonlinear realization of general covariance group is analysed. We discuss the general form of free Lagrangian for Goldstone fields, and propose as a special choice one reasonable form which is shown to describe a gravitational theory with massless tensor graviton and massive vector tordion. (author)

  4. Covariant quantum mechanics on a null plane

    Leutwyler, H.; Stern, J.

    1977-03-01

    Lorentz invariance implies that the null plane wave functions factorize into a kinematical part describing the motion of the system as a whole and an inner wave function that involves the specific dynamical properties of the system - in complete correspondence with the non-relativistic situation. Covariance is equivalent to an angular condition which admits non-trivial solutions

  5. Hierarchical matrix approximation of large covariance matrices

    Litvinenko, Alexander

    2015-11-30

    We approximate large non-structured Matérn covariance matrices of size n×n in the H-matrix format with a log-linear computational cost and storage O(kn log n), where rank k ≪ n is a small integer. Applications are: spatial statistics, machine learning and image analysis, kriging and optimal design.

  6. Approximate methods for derivation of covariance data

    Tagesen, S.

    1992-01-01

    Several approaches for the derivation of covariance information for evaluated nuclear data files (EFF2 and ENDF/B-VI) have been developed and used at IRK and ORNL respectively. Considerations, governing the choice of a distinct method depending on the quantity and quality of available data are presented, advantages/disadvantages are discussed and examples of results are given

  7. Optimal covariate designs theory and applications

    Das, Premadhis; Mandal, Nripes Kumar; Sinha, Bikas Kumar

    2015-01-01

    This book primarily addresses the optimality aspects of covariate designs. A covariate model is a combination of ANOVA and regression models. Optimal estimation of the parameters of the model using a suitable choice of designs is of great importance; as such choices allow experimenters to extract maximum information for the unknown model parameters. The main emphasis of this monograph is to start with an assumed covariate model in combination with some standard ANOVA set-ups such as CRD, RBD, BIBD, GDD, BTIBD, BPEBD, cross-over, multi-factor, split-plot and strip-plot designs, treatment control designs, etc. and discuss the nature and availability of optimal covariate designs. In some situations, optimal estimations of both ANOVA and the regression parameters are provided. Global optimality and D-optimality criteria are mainly used in selecting the design. The standard optimality results of both discrete and continuous set-ups have been adapted, and several novel combinatorial techniques have been applied for...

  8. Asymptotics for the minimum covariance determinant estimator

    Butler, R.W.; Davies, P.L.; Jhun, M.

    1993-01-01

    Consistency is shown for the minimum covariance determinant (MCD) estimators of multivariate location and scale and asymptotic normality is shown for the former. The proofs are made possible by showing a separating ellipsoid property for the MCD subset of observations. An analogous property is shown

  9. EQUIVALENT MODELS IN COVARIANCE STRUCTURE-ANALYSIS

    LUIJBEN, TCW

    1991-01-01

    Defining equivalent models as those that reproduce the same set of covariance matrices, necessary and sufficient conditions are stated for the local equivalence of two expanded identified models M1 and M2 when fitting the more restricted model M0. Assuming several regularity conditions, the rank

  10. Partial covariance based functional connectivity computation using Ledoit-Wolf covariance regularization.

    Brier, Matthew R; Mitra, Anish; McCarthy, John E; Ances, Beau M; Snyder, Abraham Z

    2015-11-01

    Functional connectivity refers to shared signals among brain regions and is typically assessed in a task free state. Functional connectivity commonly is quantified between signal pairs using Pearson correlation. However, resting-state fMRI is a multivariate process exhibiting a complicated covariance structure. Partial covariance assesses the unique variance shared between two brain regions excluding any widely shared variance, hence is appropriate for the analysis of multivariate fMRI datasets. However, calculation of partial covariance requires inversion of the covariance matrix, which, in most functional connectivity studies, is not invertible owing to rank deficiency. Here we apply Ledoit-Wolf shrinkage (L2 regularization) to invert the high dimensional BOLD covariance matrix. We investigate the network organization and brain-state dependence of partial covariance-based functional connectivity. Although RSNs are conventionally defined in terms of shared variance, removal of widely shared variance, surprisingly, improved the separation of RSNs in a spring embedded graphical model. This result suggests that pair-wise unique shared variance plays a heretofore unrecognized role in RSN covariance organization. In addition, application of partial correlation to fMRI data acquired in the eyes open vs. eyes closed states revealed focal changes in uniquely shared variance between the thalamus and visual cortices. This result suggests that partial correlation of resting state BOLD time series reflect functional processes in addition to structural connectivity. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. ENDF-6 File 30: Data covariances obtained from parameter covariances and sensitivities

    Muir, D.W.

    1989-01-01

    File 30 is provided as a means of describing the covariances of tabulated cross sections, multiplicities, and energy-angle distributions that result from propagating the covariances of a set of underlying parameters (for example, the input parameters of a nuclear-model code), using an evaluator-supplied set of parameter covariances and sensitivities. Whenever nuclear data are evaluated primarily through the application of nuclear models, the covariances of the resulting data can be described very adequately, and compactly, by specifying the covariance matrix for the underlying nuclear parameters, along with a set of sensitivity coefficients giving the rate of change of each nuclear datum of interest with respect to each of the model parameters. Although motivated primarily by these applications of nuclear theory, use of File 30 is not restricted to any one particular evaluation methodology. It can be used to describe data covariances of any origin, so long as they can be formally separated into a set of parameters with specified covariances and a set of data sensitivities

  12. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease

    Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J

    2015-01-01

    Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset....

  13. Econometric analysis of realized covariation: high frequency based covariance, regression, and correlation in financial economics

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2004-01-01

    This paper analyses multivariate high frequency financial data using realized covariation. We provide a new asymptotic distribution theory for standard methods such as regression, correlation analysis, and covariance. It will be based on a fixed interval of time (e.g., a day or week), allowing...... the number of high frequency returns during this period to go to infinity. Our analysis allows us to study how high frequency correlations, regressions, and covariances change through time. In particular we provide confidence intervals for each of these quantities....

  14. Depressive-like behavioral alterations and c-fos expression in the dopaminergic brain regions in wag/rij rats with genetic absence epilepsy

    Sarkisova, K.Y.; Midzyanovskaya, I.S.; Kulikov, M.A.; Luijtelaar, E.L.J.M. van; Luijtelaar, E.L.J.M. van; Kuznetsova, G.D.; Coenen, A.M.L.; Chepurnov, S.A.

    2004-01-01

    A Wistar derived inbred line, the WAG/Rij rats, genetically absence epilepsy prone, and their normal counterparts, outbred Wistar rats, were compared in respect to differences in behavior, in acute and chronic antidepressant imipramine treatment and in the immediate early gene c-fos expression in

  15. Co-inheritance of the rare β hemoglobin variants Hb Yaounde, Hb Görwihl and Hb City of Hope with other alterations in globin genes: impact in genetic counseling.

    Vinciguerra, Margherita; Passarello, Cristina; Leto, Filippo; Cassarà, Filippo; Cannata, Monica; Maggio, Aurelio; Giambona, Antonino

    2015-04-01

    Nearly 1183 different molecular defects of the globin genes leading to hemoglobin variants have been identified (http://globin.bx.psu.edu) over the past decades. The purpose of this study was to report three cases, never described in the literature, of co-inheritance of three β hemoglobin variants with other alterations in globin genes and to evaluate the clinical significance to conduct an appropriate genetic counseling. We report the molecular study performed in three probands and their families, sampling during the screening program conducted at the Laboratory for Molecular Prenatal Diagnosis of Hemoglobinopathies at Villa Sofia-Cervello Hospital in Palermo, Italy. This work allowed us to describe the co-inheritance of three rare β hemoglobin variants with other alterations in globin genes: the β hemoglobin variant Hb Yaounde [β134(H12)Val>Ala], found for the first time in combination with ααα(anti3.7) arrangement, and the β hemoglobin variants Hb Görwihl [β5(A2)Pro>Ala] and Hb City of Hope [β69(E13)Gly>Ser], found both in association with β(0) -thalassemia. The present work emphasizes the importance of a careful evaluation of the hematological data, especially in cases of atypical hematological parameters, to carry out an adequate and complete molecular study and to formulate an appropriate genetic counseling for couples at risk. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia

    Francesca Managò

    2016-08-01

    Full Text Available Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc complex is a convergence signal for several genes implicated in schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses. Furthermore, genetic disruption of Arc leads to concomitant hypoactive mesocortical and hyperactive mesostriatal dopamine pathways. Application of a D1 agonist to the prefrontal cortex or a D2 antagonist in the ventral striatum rescues Arc-dependent cognitive or psychomotor abnormalities, respectively. Our findings demonstrate a role for Arc in the regulation of dopaminergic neurotransmission and related behaviors. The results also provide initial biological support implicating Arc in dopaminergic and behavioral abnormalities related to schizophrenia.

  17. Genetic Modification of Lignin in Hybrid Poplar (Populus alba × Populus tremula) Does Not Substantially Alter Plant Defense or Arthropod Communities.

    Buhl, Christine; Meilan, Richard; Lindroth, Richard L

    2017-05-01

    Lignin impedes access to cellulose during biofuel production and pulping but trees can be genetically modified to improve processing efficiency. Modification of lignin may have nontarget effects on mechanical and chemical resistance and subsequent arthropod community responses with respect to pest susceptibility and arthropod biodiversity. We quantified foliar mechanical and chemical resistance traits in lignin-modified and wild-type (WT) poplar (Populus alba × Populus tremula) grown in a plantation and censused arthropods present on these trees to determine total abundance, as well as species richness, diversity and community composition. Our results indicate that mechanical resistance was not affected by lignin modification and only one genetic construct resulted in a (modest) change in chemical resistance. Arthropod abundance and community composition were consistent across modified and WT trees, but transgenics produced using one construct exhibited higher species richness and diversity relative to the WT. Our findings indicate that modification of lignin in poplar does not negatively affect herbivore resistance traits or arthropod community response, and may even result in a source of increased genetic diversity in trees and arthropod communities. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America.

  18. Disruption of structural covariance networks for language in autism is modulated by verbal ability.

    Sharda, Megha; Khundrakpam, Budhachandra S; Evans, Alan C; Singh, Nandini C

    2016-03-01

    The presence of widespread speech and language deficits is a core feature of autism spectrum disorders (ASD). These impairments have often been attributed to altered connections between brain regions. Recent developments in anatomical correlation-based approaches to map structural covariance offer an effective way of studying such connections in vivo. In this study, we employed such a structural covariance network (SCN)-based approach to investigate the integrity of anatomical networks in fronto-temporal brain regions of twenty children with ASD compared to an age and gender-matched control group of twenty-two children. Our findings reflected large-scale disruption of inter and intrahemispheric covariance in left frontal SCNs in the ASD group compared to controls, but no differences in right fronto-temporal SCNs. Interhemispheric covariance in left-seeded networks was further found to be modulated by verbal ability of the participants irrespective of autism diagnosis, suggesting that language function might be related to the strength of interhemispheric structural covariance between frontal regions. Additionally, regional cortical thickening was observed in right frontal and left posterior regions, which was predicted by decreasing symptom severity and increasing verbal ability in ASD. These findings unify reports of regional differences in cortical morphology in ASD. They also suggest that reduced left hemisphere asymmetry and increased frontal growth may not only reflect neurodevelopmental aberrations but also compensatory mechanisms.

  19. Determination of covariant Schwinger terms in anomalous gauge theories

    Kelnhofer, G.

    1991-01-01

    A functional integral method is used to determine equal time commutators between the covariant currents and the covariant Gauss-law operators in theories which are affected by an anomaly. By using a differential geometrical setup we show how the derivation of consistent- and covariant Schwinger terms can be understood on an equal footing. We find a modified consistency condition for the covariant anomaly. As a by-product the Bardeen-Zumino functional, which relates consistent and covariant anomalies, can be interpreted as connection on a certain line bundle over all gauge potentials. Finally the covariant commutator anomalies are calculated for the two- and four dimensional case. (orig.)

  20. Paragrassmann analysis and covariant quantum algebras

    Filippov, A.T.; Isaev, A.P.; Kurdikov, A.B.; Pyatov, P.N.

    1993-01-01

    This report is devoted to the consideration from the algebraic point of view the paragrassmann algebras with one and many paragrassmann generators Θ i , Θ p+1 i = 0. We construct the paragrassmann versions of the Heisenberg algebra. For the special case, this algebra is nothing but the algebra for coordinates and derivatives considered in the context of covariant differential calculus on quantum hyperplane. The parameter of deformation q in our case is (p+1)-root of unity. Our construction is nondegenerate only for even p. Taking bilinear combinations of paragrassmann derivatives and coordinates we realize generators for the covariant quantum algebras as tensor products of (p+1) x (p+1) matrices. (orig./HSI)

  1. Covariant holography of a tachyonic accelerating universe

    Rozas-Fernandez, Alberto [Consejo Superior de Investigaciones Cientificas, Instituto de Fisica Fundamental, Madrid (Spain); University of Portsmouth, Institute of Cosmology and Gravitation, Portsmouth (United Kingdom)

    2014-08-15

    We apply the holographic principle to a flat dark energy dominated Friedmann-Robertson-Walker spacetime filled with a tachyon scalar field with constant equation of state w = p/ρ, both for w > -1 and w < -1. By using a geometrical covariant procedure, which allows the construction of holographic hypersurfaces, we have obtained for each case the position of the preferred screen and have then compared these with those obtained by using the holographic dark energy model with the future event horizon as the infrared cutoff. In the phantom scenario, one of the two obtained holographic screens is placed on the big rip hypersurface, both for the covariant holographic formalism and the holographic phantom model. It is also analyzed whether the existence of these preferred screens allows a mathematically consistent formulation of fundamental theories based on the existence of an S-matrix at infinite distances. (orig.)

  2. On covariance structure in noisy, big data

    Paffenroth, Randy C.; Nong, Ryan; Du Toit, Philip C.

    2013-09-01

    Herein we describe theory and algorithms for detecting covariance structures in large, noisy data sets. Our work uses ideas from matrix completion and robust principal component analysis to detect the presence of low-rank covariance matrices, even when the data is noisy, distorted by large corruptions, and only partially observed. In fact, the ability to handle partial observations combined with ideas from randomized algorithms for matrix decomposition enables us to produce asymptotically fast algorithms. Herein we will provide numerical demonstrations of the methods and their convergence properties. While such methods have applicability to many problems, including mathematical finance, crime analysis, and other large-scale sensor fusion problems, our inspiration arises from applying these methods in the context of cyber network intrusion detection.

  3. Structural covariance in the hallucinating brain: a voxel-based morphometry study

    Modinos, Gemma; Vercammen, Ans; Mechelli, Andrea; Knegtering, Henderikus; McGuire, Philip K.; Aleman, André

    2009-01-01

    Background Neuroimaging studies have indicated that a number of cortical regions express altered patterns of structural covariance in schizophrenia. The relation between these alterations and specific psychotic symptoms is yet to be investigated. We used voxel-based morphometry to examine regional grey matter volumes and structural covariance associated with severity of auditory verbal hallucinations. Methods We applied optimized voxel-based morphometry to volumetric magnetic resonance imaging data from 26 patients with medication-resistant auditory verbal hallucinations (AVHs); statistical inferences were made at p < 0.05 after correction for multiple comparisons. Results Grey matter volume in the left inferior frontal gyrus was positively correlated with severity of AVHs. Hallucination severity influenced the pattern of structural covariance between this region and the left superior/middle temporal gyri, the right inferior frontal gyrus and hippocampus, and the insula bilaterally. Limitations The results are based on self-reported severity of auditory hallucinations. Complementing with a clinician-based instrument could have made the findings more compelling. Future studies would benefit from including a measure to control for other symptoms that may covary with AVHs and for the effects of antipsychotic medication. Conclusion The results revealed that overall severity of AVHs modulated cortical intercorrelations between frontotemporal regions involved in language production and verbal monitoring, supporting the critical role of this network in the pathophysiology of hallucinations. PMID:19949723

  4. Developmental constraints revealed by co-variation within and among molar rows in two murine rodents.

    Renaud, Sabrina; Pantalacci, Sophie; Quéré, Jean-Pierre; Laudet, Vincent; Auffray, Jean-Christophe

    2009-01-01

    Morphological integration corresponds to interdependency between characters that can arise from several causes. Proximal causes of integration include that different phenotypic features may share common genetic sets and/or interact during their development. Ultimate causes may be the prolonged effect of selection favoring integration of functionally interacting characters, achieved by the molding of these proximal causes. Strong and direct interactions among successive teeth of a molar row are predicted by genetic and developmental evidences. Functional constraints related to occlusion, however, should have selected more strongly for a morphological integration of occluding teeth and a corresponding evolution of the underlying developmental and genetic pathways. To investigate how these predictions match the patterns of phenotypic integration, we studied the co-variation among the six molars of the murine molar row, focusing on two populations of house mice (Mus musculus domesticus) and wood mice (Apodemus sylvaticus). The size and shape of the three upper and lower molars were quantified and compared. Our results evidenced similar patterns in both species, size being more integrated than shape among all the teeth, and both size and shape co-varying strongly between adjacent teeth, but also between occluding teeth. Strong co-variation within each molar row is in agreement with developmental models showing a cascade influence of the first molar on the subsequent molars. In contrast, the strong co-variation between molars of the occluding tooth rows confirms that functional constraints molded patterns of integration and probably the underlying developmental pathways despite the low level of direct developmental interactions occurring among molar rows. These patterns of co-variation are furthermore conserved between the house mouse and the wood mouse that diverged >10 Ma, suggesting that they may constitute long-running constraints to the diversification of the murine

  5. Twisted covariant noncommutative self-dual gravity

    Estrada-Jimenez, S.; Garcia-Compean, H.; Obregon, O.; Ramirez, C.

    2008-01-01

    A twisted covariant formulation of noncommutative self-dual gravity is presented. The formulation for constructing twisted noncommutative Yang-Mills theories is used. It is shown that the noncommutative torsion is solved at any order of the θ expansion in terms of the tetrad and some extra fields of the theory. In the process the first order expansion in θ for the Plebanski action is explicitly obtained.

  6. Superfield quantization in Sp(2) covariant formalism

    Lavrov, P M

    2001-01-01

    The rules of the superfield Sp(2) covariant quantization of the arbitrary gauge theories for the case of the introduction of the gauging with the derivative equations for the gauge functional are generalized. The possibilities of realization of the expanded anti-brackets are considered and it is shown, that only one of the realizations is compatible with the transformations of the expanded BRST-symmetry in the form of super translations along the Grassmann superspace coordinates

  7. Torsion and geometrostasis in covariant superstrings

    Zachos, C.

    1985-01-01

    The covariant action for freely propagating heterotic superstrings consists of a metric and a torsion term with a special relative strength. It is shown that the strength for which torsion flattens the underlying 10-dimensional superspace geometry is precisely that which yields free oscillators on the light cone. This is in complete analogy with the geometrostasis of two-dimensional sigma-models with Wess-Zumino interactions. 13 refs

  8. Covariant derivatives of the Berezin transform

    Engliš, Miroslav; Otáhalová, R.

    2011-01-01

    Roč. 363, č. 10 (2011), s. 5111-5129 ISSN 0002-9947 R&D Projects: GA AV ČR IAA100190802 Keywords : Berezin transform * Berezin symbol * covariant derivative Subject RIV: BA - General Mathematics Impact factor: 1.093, year: 2011 http://www.ams.org/journals/tran/2011-363-10/S0002-9947-2011-05111-1/home.html

  9. Torsion and geometrostasis in covariant superstrings

    Zachos, C.

    1985-01-01

    The covariant action for freely propagating heterotic superstrings consists of a metric and a torsion term with a special relative strength. It is shown that the strength for which torsion flattens the underlying 10-dimensional superspace geometry is precisely that which yields free oscillators on the light cone. This is in complete analogy with the geometrostasis of two-dimensional sigma-models with Wess-Zumino interactions. 13 refs.

  10. Covariance expressions for eigenvalue and eigenvector problems

    Liounis, Andrew J.

    There are a number of important scientific and engineering problems whose solutions take the form of an eigenvalue--eigenvector problem. Some notable examples include solutions to linear systems of ordinary differential equations, controllability of linear systems, finite element analysis, chemical kinetics, fitting ellipses to noisy data, and optimal estimation of attitude from unit vectors. In many of these problems, having knowledge of the eigenvalue and eigenvector Jacobians is either necessary or is nearly as important as having the solution itself. For instance, Jacobians are necessary to find the uncertainty in a computed eigenvalue or eigenvector estimate. This uncertainty, which is usually represented as a covariance matrix, has been well studied for problems similar to the eigenvalue and eigenvector problem, such as singular value decomposition. There has been substantially less research on the covariance of an optimal estimate originating from an eigenvalue-eigenvector problem. In this thesis we develop two general expressions for the Jacobians of eigenvalues and eigenvectors with respect to the elements of their parent matrix. The expressions developed make use of only the parent matrix and the eigenvalue and eigenvector pair under consideration. In addition, they are applicable to any general matrix (including complex valued matrices, eigenvalues, and eigenvectors) as long as the eigenvalues are simple. Alongside this, we develop expressions that determine the uncertainty in a vector estimate obtained from an eigenvalue-eigenvector problem given the uncertainty of the terms of the matrix. The Jacobian expressions developed are numerically validated with forward finite, differencing and the covariance expressions are validated using Monte Carlo analysis. Finally, the results from this work are used to determine covariance expressions for a variety of estimation problem examples and are also applied to the design of a dynamical system.

  11. Linear Covariance Analysis for a Lunar Lander

    Jang, Jiann-Woei; Bhatt, Sagar; Fritz, Matthew; Woffinden, David; May, Darryl; Braden, Ellen; Hannan, Michael

    2017-01-01

    A next-generation lunar lander Guidance, Navigation, and Control (GNC) system, which includes a state-of-the-art optical sensor suite, is proposed in a concept design cycle. The design goal is to allow the lander to softly land within the prescribed landing precision. The achievement of this precision landing requirement depends on proper selection of the sensor suite. In this paper, a robust sensor selection procedure is demonstrated using a Linear Covariance (LinCov) analysis tool developed by Draper.

  12. The covariant formulation of f ( T ) gravity

    Krššák, Martin; Saridakis, Emmanuel N

    2016-01-01

    We show that the well-known problem of frame dependence and violation of local Lorentz invariance in the usual formulation of f ( T ) gravity is a consequence of neglecting the role of spin connection. We re-formulate f ( T ) gravity starting from, instead of the ‘pure tetrad’ teleparallel gravity, the covariant teleparallel gravity, using both the tetrad and the spin connection as dynamical variables, resulting in a fully covariant, consistent, and frame-independent version of f ( T ) gravity, which does not suffer from the notorious problems of the usual, pure tetrad, f ( T ) theory. We present the method to extract solutions for the most physically important cases, such as the Minkowski, the Friedmann–Robertson–Walker (FRW) and the spherically symmetric ones. We show that in covariant f ( T ) gravity we are allowed to use an arbitrary tetrad in an arbitrary coordinate system along with the corresponding spin connection, resulting always in the same physically relevant field equations. (paper)

  13. Development of covariance capabilities in EMPIRE code

    Herman,M.; Pigni, M.T.; Oblozinsky, P.; Mughabghab, S.F.; Mattoon, C.M.; Capote, R.; Cho, Young-Sik; Trkov, A.

    2008-06-24

    The nuclear reaction code EMPIRE has been extended to provide evaluation capabilities for neutron cross section covariances in the thermal, resolved resonance, unresolved resonance and fast neutron regions. The Atlas of Neutron Resonances by Mughabghab is used as a primary source of information on uncertainties at low energies. Care is taken to ensure consistency among the resonance parameter uncertainties and those for thermal cross sections. The resulting resonance parameter covariances are formatted in the ENDF-6 File 32. In the fast neutron range our methodology is based on model calculations with the code EMPIRE combined with experimental data through several available approaches. The model-based covariances can be obtained using deterministic (Kalman) or stochastic (Monte Carlo) propagation of model parameter uncertainties. We show that these two procedures yield comparable results. The Kalman filter and/or the generalized least square fitting procedures are employed to incorporate experimental information. We compare the two approaches analyzing results for the major reaction channels on {sup 89}Y. We also discuss a long-standing issue of unreasonably low uncertainties and link it to the rigidity of the model.

  14. Covariant electrodynamics in linear media: Optical metric

    Thompson, Robert T.

    2018-03-01

    While the postulate of covariance of Maxwell's equations for all inertial observers led Einstein to special relativity, it was the further demand of general covariance—form invariance under general coordinate transformations, including between accelerating frames—that led to general relativity. Several lines of inquiry over the past two decades, notably the development of metamaterial-based transformation optics, has spurred a greater interest in the role of geometry and space-time covariance for electrodynamics in ponderable media. I develop a generally covariant, coordinate-free framework for electrodynamics in general dielectric media residing in curved background space-times. In particular, I derive a relation for the spatial medium parameters measured by an arbitrary timelike observer. In terms of those medium parameters I derive an explicit expression for the pseudo-Finslerian optical metric of birefringent media and show how it reduces to a pseudo-Riemannian optical metric for nonbirefringent media. This formulation provides a basis for a unified approach to ray and congruence tracing through media in curved space-times that may smoothly vary among positively refracting, negatively refracting, and vacuum.

  15. SG39 Deliverables. Comments on Covariance Data

    Yokoyama, Kenji

    2015-01-01

    The covariance matrix of a scattered data set, x_i (i=1,n), must be symmetric and positive-definite. As one of WPEC/SG39 contributions to the SG40/CIELO project, several comments or recommendations on the covariance data are described here from the viewpoint of nuclear-data users. To make the comments concrete and useful for nuclear-data evaluators, the covariance data of the latest evaluated nuclear data library, JENDL-4.0 and ENDF/B-VII.1 are treated here as the representative materials. The surveyed nuclides are five isotopes that are most important for fast reactor application. The nuclides, reactions and energy regions dealt with are followings: Pu-239: fission (2.5∼10 keV) and capture (2.5∼10 keV), U-235: fission (500 eV∼10 keV) and capture (500 eV∼30 keV), U-238: fission (1∼10 MeV), capture (below 20 keV, 20∼150 keV), inelastic (above 100 keV) and elastic (above 20 keV), Fe-56: elastic (below 850 keV) and average scattering cosine (above 10 keV), and, Na-23: capture (600 eV∼600 keV), inelastic (above 1 MeV) and elastic (around 2 keV)

  16. Makeup of the genetic correlation between milk production traits using genome-wide single nucleotide polymorphism information

    Binsbergen, van R.; Veerkamp, R.F.; Calus, M.P.L.

    2012-01-01

    The correlated responses between traits may differ depending on the makeup of genetic covariances, and may differ from the predictions of polygenic covariances Therefore, the objective of the present study was to investigate the makeup of the genetic covariances between the well-studied traits: milk

  17. Journal of Genetics | Indian Academy of Sciences

    Knowledge of genetic correlations is essential to understand the joint evolution of traits through correlated responses to selection, a difficult and seldom, very precise task even with easy-to-breed species. Here, a simulation-based method to estimate genetic correlations and genetic covariances that relies only on ...

  18. Genetic deletion of P-glycoprotein alters stress responsivity and increases depression-like behavior, social withdrawal and microglial activation in the hippocampus of female mice.

    Brzozowska, Natalia I; Smith, Kristie L; Zhou, Cilla; Waters, Peter M; Cavalcante, Ligia Menezes; Abelev, Sarah V; Kuligowski, Michael; Clarke, David J; Todd, Stephanie M; Arnold, Jonathon C

    2017-10-01

    P-glycoprotein (P-gp) is an ABC transporter expressed at the blood brain barrier and regulates the brain uptake of various xenobiotics and endogenous mediators including glucocorticoid hormones which are critically important to the stress response. Moreover, P-gp is expressed on microglia, the brain's immune cells, which are activated by stressors and have an emerging role in psychiatric disorders. We therefore hypothesised that germline P-gp deletion in mice might alter the behavioral and microglial response to stressors. Female P-gp knockout mice displayed an unusual, frantic anxiety response to intraperitoneal injection stress in the light-dark test. They also tended to display reduced conditioned fear responses compared to wild-type (WT) mice in a paradigm where a single electric foot-shock stressor was paired to a context. Foot-shock stress reduced social interaction and decreased microglia cell density in the amygdala which was not varied by P-gp genotype. Independently of stressor exposure, female P-gp deficient mice displayed increased depression-like behavior, idiosyncratic darting behavior, age-related social withdrawal and hyperactivity, facilitated sensorimotor gating and altered startle reactivity. In addition, P-gp deletion increased microglia cell density in the CA3 region of the hippocampus, and the microglial cells exhibited a reactive, hypo-ramified morphology. Further, female P-gp KO mice displayed increased glucocorticoid receptor (GR) expression in the hippocampus. In conclusion, this research shows that germline P-gp deletion affected various behaviors of relevance to psychiatric conditions, and that altered microglial cell activity and enhanced GR expression in the hippocampus may play a role in mediating these behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. | Office of Cancer Genomics

    A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant-protein product (for example, EGFR-inhibitor treatment in EGFR-mutant lung cancers). However, genetically driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1,122 EGFR-mutant lung cancer cell-free DNA samples and whole-exome analysis of seven longitudinally collected tumor samples from a patient with EGFR-mutant lung cancer, we identified critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers.

  20. Flexible Bayesian Dynamic Modeling of Covariance and Correlation Matrices

    Lan, Shiwei; Holbrook, Andrew; Fortin, Norbert J.; Ombao, Hernando; Shahbaba, Babak

    2017-01-01

    Modeling covariance (and correlation) matrices is a challenging problem due to the large dimensionality and positive-definiteness constraint. In this paper, we propose a novel Bayesian framework based on decomposing the covariance matrix

  1. ERRORJ. Covariance processing code. Version 2.2

    Chiba, Go

    2004-07-01

    ERRORJ is the covariance processing code that can produce covariance data of multi-group cross sections, which are essential for uncertainty analyses of nuclear parameters, such as neutron multiplication factor. The ERRORJ code can process the covariance data of cross sections including resonance parameters, angular and energy distributions of secondary neutrons. Those covariance data cannot be processed by the other covariance processing codes. ERRORJ has been modified and the version 2.2 has been developed. This document describes the modifications and how to use. The main topics of the modifications are as follows. Non-diagonal elements of covariance matrices are calculated in the resonance energy region. Option for high-speed calculation is implemented. Perturbation amount is optimized in a sensitivity calculation. Effect of the resonance self-shielding on covariance of multi-group cross section can be considered. It is possible to read a compact covariance format proposed by N.M. Larson. (author)

  2. New perspective in covariance evaluation for nuclear data

    Kanda, Y.

    1992-01-01

    Methods of nuclear data evaluation have been highly developed during the past decade, especially after introducing the concept of covariance. This makes it utmost important how to evaluate covariance matrices for nuclear data. It can be said that covariance evaluation is just the nuclear data evaluation, because the covariance matrix has quantitatively decisive function in current evaluation methods. The covariance primarily represents experimental uncertainties. However, correlation of individual uncertainties between different data must be taken into account and it can not be conducted without detailed physical considerations on experimental conditions. This procedure depends on the evaluator and the estimated covariance does also. The mathematical properties of the covariance have been intensively discussed. Their physical properties should be studied to apply it to the nuclear data evaluation, and then, in this report, are reviewed to give the base for further development of the covariance application. (orig.)

  3. In vitro short-term exposure to air pollution PM{sub 2.5-0.3} induced cell cycle alterations and genetic instability in a human lung cell coculture model

    Abbas, Imane [Université de Lille, Lille (France); EA4492-UCEIV, Université du Littoral-Côte d’Opale, Dunkerque (France); Lebanese Atomic Energy Commission – CNRS, Beirut (Lebanon); Verdin, Anthony [Université de Lille, Lille (France); EA4492-UCEIV, Université du Littoral-Côte d’Opale, Dunkerque (France); Escande, Fabienne [Centre de Biologie Pathologie, Centre Hospitalier Régional et Universitaire, Lille (France); Saint-Georges, Françoise [Université de Lille, Lille (France); Groupement Hospitalier de l’Institut Catholique de Lille, Lille (France); Cazier, Fabrice [Université de Lille, Lille (France); Centre Commun de Mesures, Université du Littoral-Côte d’Opale, Dunkerque (France); Mulliez, Philippe [Université de Lille, Lille (France); Groupement Hospitalier de l’Institut Catholique de Lille, Lille (France); Courcot, Dominique; Shirali, Pirouz [Université de Lille, Lille (France); EA4492-UCEIV, Université du Littoral-Côte d’Opale, Dunkerque (France); Gosset, Pierre [Université de Lille, Lille (France); Groupement Hospitalier de l’Institut Catholique de Lille, Lille (France); and others

    2016-05-15

    Although its adverse health effects of air pollution particulate matter (PM2.5) are well-documented and often related to oxidative stress and pro-inflammatory response, recent evidence support the role of the remodeling of the airway epithelium involving the regulation of cell death processes. Hence, the overarching goals of the present study were to use an in vitro coculture model, based on human AM and L132 cells to study the possible alteration of TP53-RB gene signaling pathways (i.e. cell cycle phases, gene expression of TP53, BCL2, BAX, P21, CCND1, and RB, and protein concentrations of their active forms), and genetic instability (i.e. LOH and/or MSI) in the PM{sub 2.5-0.3}-exposed coculture model. PM{sub 2.5-0.3} exposure of human AM from the coculture model induced marked cell cycle alterations after 24 h, as shown by increased numbers of L132 cells in subG1 and S+G2 cell cycle phases, indicating apoptosis and proliferation. Accordingly, activation of the TP53-RB gene signaling pathways after the coculture model exposure to PM{sub 2.5-0.3} was reported in the L132 cells. Exposure of human AM from the coculture model to PM{sub 2.5-0.3} resulted in MS alterations in 3p chromosome multiple critical regions in L132 cell population. Hence, in vitro short-term exposure of the coculture model to PM{sub 2.5-0.3} induced cell cycle alterations relying on the sequential occurrence of molecular abnormalities from TP53-RB gene signaling pathway activation and genetic instability. - Highlights: • Better knowledge on health adverse effects of air pollution PM{sub 2.5}. • Human alveolar macrophage and normal human epithelial lung cell coculture. • Molecular abnormalities from TP53-RB gene signaling pathway. • Loss of heterozygosity and microsatellite instability. • Pathologic changes in morphology and number of cells in relation to airway remodeling.

  4. High-dimensional covariance estimation with high-dimensional data

    Pourahmadi, Mohsen

    2013-01-01

    Methods for estimating sparse and large covariance matrices Covariance and correlation matrices play fundamental roles in every aspect of the analysis of multivariate data collected from a variety of fields including business and economics, health care, engineering, and environmental and physical sciences. High-Dimensional Covariance Estimation provides accessible and comprehensive coverage of the classical and modern approaches for estimating covariance matrices as well as their applications to the rapidly developing areas lying at the intersection of statistics and mac

  5. A Phylogenetic Analysis of Shape Covariance Structure in the Anthropoid Skull

    De Oliveira, Felipe; Marroig, Gabriel; Garcia, Guilherme

    2016-01-01

    Phenotypic traits evolve in a coordinated manner due to developmental and functional interactions, mediated by the dynamics of natural selection; the dependence between traits arising from these three factors is captured by genetic ( G ) and phenotypic ( P ) covariance matrices. Mammalian skull development produces an intricate pattern of tissue organization and mutual signaling that integrates this structure, although the set of functions it performs is quite disparate. Therefore, the interp...

  6. Comparative Analyses of Phenotypic Trait Covariation within and among Populations.

    Peiman, Kathryn S; Robinson, Beren W

    2017-10-01

    Many morphological, behavioral, physiological, and life-history traits covary across the biological scales of individuals, populations, and species. However, the processes that cause traits to covary also change over these scales, challenging our ability to use patterns of trait covariance to infer process. Trait relationships are also widely assumed to have generic functional relationships with similar evolutionary potentials, and even though many different trait relationships are now identified, there is little appreciation that these may influence trait covariation and evolution in unique ways. We use a trait-performance-fitness framework to classify and organize trait relationships into three general classes, address which ones more likely generate trait covariation among individuals in a population, and review how selection shapes phenotypic covariation. We generate predictions about how trait covariance changes within and among populations as a result of trait relationships and in response to selection and consider how these can be tested with comparative data. Careful comparisons of covariation patterns can narrow the set of hypothesized processes that cause trait covariation when the form of the trait relationship and how it responds to selection yield clear predictions about patterns of trait covariation. We discuss the opportunities and limitations of comparative approaches to evaluate hypotheses about the evolutionary causes and consequences of trait covariation and highlight the importance of evaluating patterns within populations replicated in the same and in different selective environments. Explicit hypotheses about trait relationships are key to generating effective predictions about phenotype and its evolution using covariance data.

  7. Covariant differential calculus on quantum spheres of odd dimension

    Welk, M.

    1998-01-01

    Covariant differential calculus on the quantum spheres S q 2N-1 is studied. Two classification results for covariant first order differential calculi are proved. As an important step towards a description of the noncommutative geometry of the quantum spheres, a framework of covariant differential calculus is established, including first and higher order calculi and a symmetry concept. (author)

  8. On the covariance matrices in the evaluated nuclear data

    Corcuera, R.P.

    1983-05-01

    The implications of the uncertainties of nuclear data on reactor calculations are shown. The concept of variance, covariance and correlation are expressed first by intuitive definitions and then through statistical theory. The format of the covariance data for ENDF/B is explained and the formulas to obtain the multigroup covariances are given. (Author) [pt

  9. Evaluation of covariance in theoretical calculation of nuclear data

    Kikuchi, Yasuyuki

    1981-01-01

    Covariances of the cross sections are discussed on the statistical model calculations. Two categories of covariance are discussed: One is caused by the model approximation and the other by the errors in the model parameters. As an example, the covariances are calculated for 100 Ru. (author)

  10. Covariate Imbalance and Precision in Measuring Treatment Effects

    Liu, Xiaofeng Steven

    2011-01-01

    Covariate adjustment can increase the precision of estimates by removing unexplained variance from the error in randomized experiments, although chance covariate imbalance tends to counteract the improvement in precision. The author develops an easy measure to examine chance covariate imbalance in randomization by standardizing the average…

  11. Earth Observation System Flight Dynamics System Covariance Realism

    Zaidi, Waqar H.; Tracewell, David

    2016-01-01

    This presentation applies a covariance realism technique to the National Aeronautics and Space Administration (NASA) Earth Observation System (EOS) Aqua and Aura spacecraft based on inferential statistics. The technique consists of three parts: collection calculation of definitive state estimates through orbit determination, calculation of covariance realism test statistics at each covariance propagation point, and proper assessment of those test statistics.

  12. Evaluation of covariance for 238U cross sections

    Kawano, Toshihiko; Nakamura, Masahiro; Matsuda, Nobuyuki; Kanda, Yukinori

    1995-01-01

    Covariances of 238 U are generated using analytic functions for representation of the cross sections. The covariances of the (n,2n) and (n,3n) reactions are derived with a spline function, while the covariances of the total and the inelastic scattering cross section are estimated with a linearized nuclear model calculation. (author)

  13. Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers.

    Mlynarsky, Liat; Bejarano-Achache, Idit; Muszkat, Mordechai; Caraco, Yoseph

    2012-05-01

    Warfarin responsiveness is characterized by marked interindividual variability. A major portion of this variability is attributed to CYP2C9 and VKORC1 polymorphisms, but almost 50% is still unaccounted for. This paper reports the first prospective study on the association between factor VII R353Q polymorphism and warfarin responsiveness during induction. Genotyping for factor VII R353Q and 323D/I polymorphisms was performed in a cohort consisting of 374 patients (198 CYP2C9*1/*1) treated with warfarin who were prospectively followed from warfarin initiation. Compared with *1/*1-R/R and *1/*1-R/Q genotype carriers, *1/*1-Q/Q homozygotes achieved higher International Normalized Ratio (INR) values while consuming lower warfarin doses. The greater sensitivity was illustrated by 82.1% higher Warfarin Sensitivity Index During Induction (WSIDI) (0.14 ± 0.11 vs. 0.08 ± 0.50 mg⁻¹ Mann-Whitney, P = 0.043). Multiple regression analysis consisting of both genetic and nongenetic factors explained 26% of WSIDI variability, with R353Q genetic polymorphism having a modest yet significant effect and accounting for 1.7% of the overall variability. Moreover, the incidence of overanticoagulation (i.e., INR > 4) was 6.94-fold higher among *1/*1-Q/Q vs. *1/*1-R/R&R/Q carriers during warfarin induction (Pearson chi-square, P = 0.005). These findings were not accounted for by a chance difference in the distribution of VKORC1 genotypes. Analysis of these parameters among the entire cohort, including CYP2C9*2 and CYP2C9*3 variant allele carriers, did not reach statistical significance. Warfarin responsiveness during induction was unrelated to factor VII 323D/I genetic polymorphism. The response to warfarin during induction is influenced by factor VII R353Q polymorphism. The prospective use of this polymorphism, along with CYP2C9 and VKORC1, may enhance the accuracy of warfarin loading. However, the impact of R353Q polymorphism on overall warfarin response is subtle, and it is therefore

  14. Altered Tuber Yield in Genetically Modified High-Amylose and Oil Potato Lines Is Associated With Changed Whole-Plant Nitrogen Economy

    Fereshteh Pourazari

    2018-03-01

    Full Text Available Breeding for improved crop quality traits can affect non-target traits related to growth and resource use, and these effects may vary in different cultivation conditions (e. g., greenhouse vs. field. The objectives of this study are to investigate the growth and whole-plant nitrogen (N economy of two genetically modified (GM potato lines compared to their non-GM parental varieties and when grown in different cultivation conditions. A high-amylose GM potato line and its parent were grown under field and greenhouse conditions for one growing season in Sweden; and a GM oil potato line and its parent were grown in greenhouse conditions only. Tuber yield, above ground biomass, N uptake efficiency and other plant N economy traits were assessed. In both cultivation conditions, the GM lines produced between 1.5 and two times more tubers as compared with their parents. In the greenhouse, fresh tuber yield and N uptake efficiency were unaffected by the genetic modifications, but the GM-lines produced less tuber biomass per plant-internal N compared to their parents. In the field, the fresh tuber yield was 40% greater in the high-amylose line as compared with its parent; the greater fresh tuber yield in the high-amylose GM line was accomplished by higher water allocation to the harvested tubers, and associated with increased N recovery from soil (+20%, N uptake efficiency (+53%, tuber N content (+20%, and N accumulation (+120% compared with the non-GM parent. The cultivation conditions influenced the yield and N economy. For example, the final fresh above-ground plant biomass and N pool were considerably higher in the greenhouse conditions, whilst the tuber yield was higher in the field conditions. In conclusion, the genetic modification inducing high accumulation of amylose in potato tubers affected several non-target traits related to plant N economy, and increased the plant N uptake and accumulation efficiency of the field-grown plants. Due to strongly

  15. Altered Tuber Yield in Genetically Modified High-Amylose and Oil Potato Lines Is Associated With Changed Whole-Plant Nitrogen Economy.

    Pourazari, Fereshteh; Andersson, Mariette; Weih, Martin

    2018-01-01

    Breeding for improved crop quality traits can affect non-target traits related to growth and resource use, and these effects may vary in different cultivation conditions (e. g., greenhouse vs. field). The objectives of this study are to investigate the growth and whole-plant nitrogen (N) economy of two genetically modified (GM) potato lines compared to their non-GM parental varieties and when grown in different cultivation conditions. A high-amylose GM potato line and its parent were grown under field and greenhouse conditions for one growing season in Sweden; and a GM oil potato line and its parent were grown in greenhouse conditions only. Tuber yield, above ground biomass, N uptake efficiency and other plant N economy traits were assessed. In both cultivation conditions, the GM lines produced between 1.5 and two times more tubers as compared with their parents. In the greenhouse, fresh tuber yield and N uptake efficiency were unaffected by the genetic modifications, but the GM-lines produced less tuber biomass per plant-internal N compared to their parents. In the field, the fresh tuber yield was 40% greater in the high-amylose line as compared with its parent; the greater fresh tuber yield in the high-amylose GM line was accomplished by higher water allocation to the harvested tubers, and associated with increased N recovery from soil (+20%), N uptake efficiency (+53%), tuber N content (+20%), and N accumulation (+120%) compared with the non-GM parent. The cultivation conditions influenced the yield and N economy. For example, the final fresh above-ground plant biomass and N pool were considerably higher in the greenhouse conditions, whilst the tuber yield was higher in the field conditions. In conclusion, the genetic modification inducing high accumulation of amylose in potato tubers affected several non-target traits related to plant N economy, and increased the plant N uptake and accumulation efficiency of the field-grown plants. Due to strongly increased

  16. The application of sparse estimation of covariance matrix to quadratic discriminant analysis.

    Sun, Jiehuan; Zhao, Hongyu

    2015-02-18

    Although Linear Discriminant Analysis (LDA) is commonly used for classification, it may not be directly applied in genomics studies due to the large p, small n problem in these studies. Different versions of sparse LDA have been proposed to address this significant challenge. One implicit assumption of various LDA-based methods is that the covariance matrices are the same across different classes. However, rewiring of genetic networks (therefore different covariance matrices) across different diseases has been observed in many genomics studies, which suggests that LDA and its variations may be suboptimal for disease classifications. However, it is not clear whether considering differing genetic networks across diseases can improve classification in genomics studies. We propose a sparse version of Quadratic Discriminant Analysis (SQDA) to explicitly consider the differences of the genetic networks across diseases. Both simulation and real data analysis are performed to compare the performance of SQDA with six commonly used classification methods. SQDA provides more accurate classification results than other methods for both simulated and real data. Our method should prove useful for classification in genomics studies and other research settings, where covariances differ among classes.

  17. Two genetic determinants acquired late in Mus evolution regulate the inclusion of exon 5, which alters mouse APOBEC3 translation efficiency.

    Jun Li

    2012-01-01

    Full Text Available Mouse apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3 (mA3, an intracellular antiviral factor, has 2 allelic variations that are linked with different susceptibilities to beta- and gammaretrovirus infections among various mouse strains. In virus-resistant C57BL/6 (B6 mice, mA3 transcripts are more abundant than those in susceptible BALB/c mice both in the spleen and bone marrow. These strains of mice also express mA3 transcripts with different splicing patterns: B6 mice preferentially express exon 5-deficient (Δ5 mA3 mRNA, while BALB/c mice produce exon 5-containing full-length mA3 mRNA as the major transcript. Although the protein product of the Δ5 mRNA exerts stronger antiretroviral activities than the full-length protein, how exon 5 affects mA3 antiviral activity, as well as the genetic mechanisms regulating exon 5 inclusion into the mA3 transcripts, remains largely uncharacterized. Here we show that mA3 exon 5 is indeed a functional element that influences protein synthesis at a post-transcriptional level. We further employed in vitro splicing assays using genomic DNA clones to identify two critical polymorphisms affecting the inclusion of exon 5 into mA3 transcripts: the number of TCCT repeats upstream of exon 5 and the single nucleotide polymorphism within exon 5 located 12 bases upstream of the exon 5/intron 5 boundary. Distribution of the above polymorphisms among different Mus species indicates that the inclusion of exon 5 into mA3 mRNA is a relatively recent event in the evolution of mice. The widespread geographic distribution of this exon 5-including genetic variant suggests that in some Mus populations the cost of maintaining an effective but mutagenic enzyme may outweigh its antiviral function.

  18. Multisample adjusted U-statistics that account for confounding covariates.

    Satten, Glen A; Kong, Maiying; Datta, Somnath

    2018-06-19

    Multisample U-statistics encompass a wide class of test statistics that allow the comparison of 2 or more distributions. U-statistics are especially powerful because they can be applied to both numeric and nonnumeric data, eg, ordinal and categorical data where a pairwise similarity or distance-like measure between categories is available. However, when comparing the distribution of a variable across 2 or more groups, observed differences may be due to confounding covariates. For example, in a case-control study, the distribution of exposure in cases may differ from that in controls entirely because of variables that are related to both exposure and case status and are distributed differently among case and control participants. We propose to use individually reweighted data (ie, using the stratification score for retrospective data or the propensity score for prospective data) to construct adjusted U-statistics that can test the equality of distributions across 2 (or more) groups in the presence of confounding covariates. Asymptotic normality of our adjusted U-statistics is established and a closed form expression of their asymptotic variance is presented. The utility of our approach is demonstrated through simulation studies, as well as in an analysis of data from a case-control study conducted among African-Americans, comparing whether the similarity in haplotypes (ie, sets of adjacent genetic loci inherited from the same parent) occurring in a case and a control participant differs from the similarity in haplotypes occurring in 2 control participants. Copyright © 2018 John Wiley & Sons, Ltd.

  19. MATXTST, Basic Operations for Covariance Matrices

    Geraldo, Luiz P.; Smith, Donald

    1989-01-01

    1 - Description of program or function: MATXTST and MATXTST1 perform the following operations for a covariance matrix: - test for singularity; - test for positive definiteness; - compute the inverse if the matrix is non-singular; - compute the determinant; - determine the number of positive, negative, and zero eigenvalues; - examine all possible 3 X 3 cross correlations within a sub-matrix corresponding to a leading principal minor which is non-positive definite. While the two programs utilize the same input, the calculational procedures employed are somewhat different and their functions are complementary. The available input options include: i) the full covariance matrix, ii) the basic variables plus the relative covariance matrix, or iii) uncertainties in the basic variables plus the correlation matrix. 2 - Method of solution: MATXTST employs LINPACK subroutines SPOFA and SPODI to test for positive definiteness and to perform further optional calculations. Subroutine SPOFA factors a symmetric matrix M using the Cholesky algorithm to determine the elements of a matrix R which satisfies the relation M=R'R, where R' is the transposed matrix of R. Each leading principal minor of M is tested until the first one is found which is not positive definite. MATXTST1 uses LINPACK subroutines SSICO, SSIFA, and SSIDI to estimate whether the matrix is near to singularity or not (SSICO), and to perform the matrix diagonalization process (SSIFA). The algorithm used in SSIFA is generalization of the Method of Lagrange Reduction. SSIDI is used to compute the determinant and inertia of the matrix. 3 - Restrictions on the complexity of the problem: Matrices of sizes up to 50 X 50 elements can be treated by present versions of the programs

  20. Non-evaluation applications for covariance matrices

    Smith, D.L.

    1982-05-01

    The possibility for application of covariance matrix techniques to a variety of common research problems other than formal data evaluation are demonstrated by means of several examples. These examples deal with such matters as fitting spectral data, deriving uncertainty estimates for results calculated from experimental data, obtaining the best values for plurally-measured quantities, and methods for analysis of cross section errors based on properties of the experiment. The examples deal with realistic situations encountered in the laboratory, and they are treated in sufficient detail to enable a careful reader to extrapolate the methods to related problems.

  1. Covariant, chirally symmetric, confining model of mesons

    Gross, F.; Milana, J.

    1991-01-01

    We introduce a new model of mesons as quark-antiquark bound states. The model is covariant, confining, and chirally symmetric. Our equations give an analytic solution for a zero-mass pseudoscalar bound state in the case of exact chiral symmetry, and also reduce to the familiar, highly successful nonrelativistic linear potential models in the limit of heavy-quark mass and lightly bound systems. In this fashion we are constructing a unified description of all the mesons from the π through the Υ. Numerical solutions for other cases are also presented

  2. Cosmology of a covariant Galilean field.

    De Felice, Antonio; Tsujikawa, Shinji

    2010-09-10

    We study the cosmology of a covariant scalar field respecting a Galilean symmetry in flat space-time. We show the existence of a tracker solution that finally approaches a de Sitter fixed point responsible for cosmic acceleration today. The viable region of model parameters is clarified by deriving conditions under which ghosts and Laplacian instabilities of scalar and tensor perturbations are absent. The field equation of state exhibits a peculiar phantomlike behavior along the tracker, which allows a possibility to observationally distinguish the Galileon gravity from the cold dark matter model with a cosmological constant.

  3. Covariant differential complexes of quantum linear groups

    Isaev, A.P.; Pyatov, P.N.

    1993-01-01

    We consider the possible covariant external algebra structures for Cartan's 1-forms (Ω) on G L q (N) and S L q (N). Our starting point is that Ω s realize an adjoint representation of quantum group and all monomials of Ω s possess the unique ordering. For the obtained external algebras we define the differential mapping d possessing the usual nilpotence condition, and the generally deformed version of Leibnitz rules. The status of the known examples of G L q (N)-differential calculi in the proposed classification scheme and the problems of S L q (N)-reduction are discussed. (author.). 26 refs

  4. Minimal covariant observables identifying all pure states

    Carmeli, Claudio, E-mail: claudio.carmeli@gmail.com [D.I.M.E., Università di Genova, Via Cadorna 2, I-17100 Savona (Italy); I.N.F.N., Sezione di Genova, Via Dodecaneso 33, I-16146 Genova (Italy); Heinosaari, Teiko, E-mail: teiko.heinosaari@utu.fi [Turku Centre for Quantum Physics, Department of Physics and Astronomy, University of Turku (Finland); Toigo, Alessandro, E-mail: alessandro.toigo@polimi.it [Dipartimento di Matematica, Politecnico di Milano, Piazza Leonardo da Vinci 32, I-20133 Milano (Italy); I.N.F.N., Sezione di Milano, Via Celoria 16, I-20133 Milano (Italy)

    2013-09-02

    It has been recently shown by Heinosaari, Mazzarella and Wolf (2013) [1] that an observable that identifies all pure states of a d-dimensional quantum system has minimally 4d−4 outcomes or slightly less (the exact number depending on d). However, no simple construction of this type of minimal observable is known. We investigate covariant observables that identify all pure states and have minimal number of outcomes. It is shown that the existence of this kind of observables depends on the dimension of the Hilbert space.

  5. Linear Covariance Analysis and Epoch State Estimators

    Markley, F. Landis; Carpenter, J. Russell

    2014-01-01

    This paper extends in two directions the results of prior work on generalized linear covariance analysis of both batch least-squares and sequential estimators. The first is an improved treatment of process noise in the batch, or epoch state, estimator with an epoch time that may be later than some or all of the measurements in the batch. The second is to account for process noise in specifying the gains in the epoch state estimator. We establish the conditions under which the latter estimator is equivalent to the Kalman filter.

  6. Agnostic Estimation of Mean and Covariance

    Lai, Kevin A.; Rao, Anup B.; Vempala, Santosh

    2016-01-01

    We consider the problem of estimating the mean and covariance of a distribution from iid samples in $\\mathbb{R}^n$, in the presence of an $\\eta$ fraction of malicious noise; this is in contrast to much recent work where the noise itself is assumed to be from a distribution of known type. The agnostic problem includes many interesting special cases, e.g., learning the parameters of a single Gaussian (or finding the best-fit Gaussian) when $\\eta$ fraction of data is adversarially corrupted, agn...

  7. On the Galilean covariance of classical mechanics

    Horzela, A.; Kapuscik, E.; Kempczynski, J.; Joint Inst. for Nuclear Research, Dubna

    1991-08-01

    A Galilean covariant approach to classical mechanics of a single interacting particle is described. In this scheme constitutive relations defining forces are rejected and acting forces are determined by some fundamental differential equations. It is shown that total energy of the interacting particle transforms under Galilean transformations differently from the kinetic energy. The statement is illustrated on the exactly solvable examples of the harmonic oscillator and the case of constant forces and also, in the suitable version of the perturbation theory, for the anharmonic oscillator. (author)

  8. Additive genetic variation in the craniofacial skeleton of baboons (genus Papio) and its relationship to body and cranial size.

    Joganic, Jessica L; Willmore, Katherine E; Richtsmeier, Joan T; Weiss, Kenneth M; Mahaney, Michael C; Rogers, Jeffrey; Cheverud, James M

    2018-02-01

    Determining the genetic architecture of quantitative traits and genetic correlations among them is important for understanding morphological evolution patterns. We address two questions regarding papionin evolution: (1) what effect do body and cranial size, age, and sex have on phenotypic (V P ) and additive genetic (V A ) variation in baboon crania, and (2) how might additive genetic correlations between craniofacial traits and body mass affect morphological evolution? We use a large captive pedigreed baboon sample to estimate quantitative genetic parameters for craniofacial dimensions (EIDs). Our models include nested combinations of the covariates listed above. We also simulate the correlated response of a given EID due to selection on body mass alone. Covariates account for 1.2-91% of craniofacial V P . EID V A decreases across models as more covariates are included. The median genetic correlation estimate between each EID and body mass is 0.33. Analysis of the multivariate response to selection reveals that observed patterns of craniofacial variation in extant baboons cannot be attributed solely to correlated response to selection on body mass, particularly in males. Because a relatively large proportion of EID V A is shared with body mass variation, different methods of correcting for allometry by statistically controlling for size can alter residual V P patterns. This may conflate direct selection effects on craniofacial variation with those resulting from a correlated response to body mass selection. This shared genetic variation may partially explain how selection for increased body mass in two different papionin lineages produced remarkably similar craniofacial phenotypes. © 2017 Wiley Periodicals, Inc.

  9. Determination of covariant Schwinger terms in anomalous gauge theories

    Kelnhofer, G.

    1991-01-01

    A functional integral method is used to determine equal time commutators between the covariant currents and the covariant Gauss-law operators in theories which are affected by an anomaly. By using a differential geometrical setup we show how the derivation of consistent- and covariant Schwinger terms can be understood on an equal footing. We find a modified consistency condition for the covariant anomaly. As a by-product the Bardeen-Zumino functional, which relates consistent and covariant anomalies, can be interpreted as connection on a certain line bundle over all gauge potentials. Finally the commutator anomalies are calculated for the two- and four dimensional case. (Author) 13 refs

  10. ERRORJ. Covariance processing code system for JENDL. Version 2

    Chiba, Gou

    2003-09-01

    ERRORJ is the covariance processing code system for Japanese Evaluated Nuclear Data Library (JENDL) that can produce group-averaged covariance data to apply it to the uncertainty analysis of nuclear characteristics. ERRORJ can treat the covariance data for cross sections including resonance parameters as well as angular distributions and energy distributions of secondary neutrons which could not be dealt with by former covariance processing codes. In addition, ERRORJ can treat various forms of multi-group cross section and produce multi-group covariance file with various formats. This document describes an outline of ERRORJ and how to use it. (author)

  11. Structural Covariance of Sensory Networks, the Cerebellum, and Amygdala in Autism Spectrum Disorder

    Garrett J. Cardon

    2017-11-01

    Full Text Available Sensory dysfunction is a core symptom of autism spectrum disorder (ASD, and abnormalities with sensory responsivity and processing can be extremely debilitating to ASD patients and their families. However, relatively little is known about the underlying neuroanatomical and neurophysiological factors that lead to sensory abnormalities in ASD. Investigation into these aspects of ASD could lead to significant advancements in our general knowledge about ASD, as well as provide targets for treatment and inform diagnostic procedures. Thus, the current study aimed to measure the covariation of volumes of brain structures (i.e., structural magnetic resonance imaging that may be involved in abnormal sensory processing, in order to infer connectivity of these brain regions. Specifically, we quantified the structural covariation of sensory-related cerebral cortical structures, in addition to the cerebellum and amygdala by computing partial correlations between the structural volumes of these structures. These analyses were performed in participants with ASD (n = 36, as well as typically developing peers (n = 32. Results showed decreased structural covariation between sensory-related cortical structures, especially between the left and right cerebral hemispheres, in participants with ASD. In contrast, these same participants presented with increased structural covariation of structures in the right cerebral hemisphere. Additionally, sensory-related cerebral structures exhibited decreased structural covariation with functionally identified cerebellar networks. Also, the left amygdala showed significantly increased structural covariation with cerebral structures related to visual processing. Taken together, these results may suggest several patterns of altered connectivity both within and between cerebral cortices and other brain structures that may be related to sensory processing.

  12. Covariance Between Genotypic Effects and its Use for Genomic Inference in Half-Sib Families

    Wittenburg, Dörte; Teuscher, Friedrich; Klosa, Jan; Reinsch, Norbert

    2016-01-01

    In livestock, current statistical approaches utilize extensive molecular data, e.g., single nucleotide polymorphisms (SNPs), to improve the genetic evaluation of individuals. The number of model parameters increases with the number of SNPs, so the multicollinearity between covariates can affect the results obtained using whole genome regression methods. In this study, dependencies between SNPs due to linkage and linkage disequilibrium among the chromosome segments were explicitly considered in methods used to estimate the effects of SNPs. The population structure affects the extent of such dependencies, so the covariance among SNP genotypes was derived for half-sib families, which are typical in livestock populations. Conditional on the SNP haplotypes of the common parent (sire), the theoretical covariance was determined using the haplotype frequencies of the population from which the individual parent (dam) was derived. The resulting covariance matrix was included in a statistical model for a trait of interest, and this covariance matrix was then used to specify prior assumptions for SNP effects in a Bayesian framework. The approach was applied to one family in simulated scenarios (few and many quantitative trait loci) and using semireal data obtained from dairy cattle to identify genome segments that affect performance traits, as well as to investigate the impact on predictive ability. Compared with a method that does not explicitly consider any of the relationship among predictor variables, the accuracy of genetic value prediction was improved by 10–22%. The results show that the inclusion of dependence is particularly important for genomic inference based on small sample sizes. PMID:27402363

  13. Clinical diagnostic exome evaluation for an infant with a lethal disorder: genetic diagnosis of TARP syndrome and expansion of the phenotype in a patient with a newly reported RBM10 alteration.

    Powis, Zöe; Hart, Alexa; Cherny, Sara; Petrik, Igor; Palmaer, Erika; Tang, Sha; Jones, Carolyn

    2017-06-02

    Diagnostic Exome Sequencing (DES) has been shown to be an effective tool for diagnosis individuals with suspected genetic conditions. We report a male infant born with multiple anomalies including bilateral dysplastic kidneys, cleft palate, bilateral talipes, and bilateral absence of thumbs and first toes. Prenatal testing including chromosome analysis and microarray did not identify a cause for the multiple congenital anomalies. Postnatal diagnostic exome studies (DES) were utilized to find a molecular diagnosis for the patient. Exome sequencing of the proband, mother, and father showed a previously unreported maternally inherited RNA binding motif protein 10 (RBM10) c.1352_1353delAG (p.E451Vfs*66) alteration. Mutations in RBM10 are associated with TARP syndrome, an X-linked recessive disorder originally described with cardinal features of talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava. DES established a molecular genetic diagnosis of TARP syndrome for a neonatal patient with a poor prognosis in whom traditional testing methods were uninformative and allowed for efficient diagnosis and future reproductive options for the parents. Other reported cases of TARP syndrome demonstrate significant variability in clinical phenotype. The reported features in this infant including multiple hemivertebrae, imperforate anus, aplasia of thumbs and first toes have not been reported in previous patients, thus expanding the clinical phenotype for this rare disorder.

  14. Piecewise linear regression splines with hyperbolic covariates

    Cologne, John B.; Sposto, Richard

    1992-09-01

    Consider the problem of fitting a curve to data that exhibit a multiphase linear response with smooth transitions between phases. We propose substituting hyperbolas as covariates in piecewise linear regression splines to obtain curves that are smoothly joined. The method provides an intuitive and easy way to extend the two-phase linear hyperbolic response model of Griffiths and Miller and Watts and Bacon to accommodate more than two linear segments. The resulting regression spline with hyperbolic covariates may be fit by nonlinear regression methods to estimate the degree of curvature between adjoining linear segments. The added complexity of fitting nonlinear, as opposed to linear, regression models is not great. The extra effort is particularly worthwhile when investigators are unwilling to assume that the slope of the response changes abruptly at the join points. We can also estimate the join points (the values of the abscissas where the linear segments would intersect if extrapolated) if their number and approximate locations may be presumed known. An example using data on changing age at menarche in a cohort of Japanese women illustrates the use of the method for exploratory data analysis. (author)

  15. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease.

    Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J; Kay, Chris; Collins, Jennifer A; Arenillas, David; Lilja, Tobias; Gaudenzi, Giulia; Manoharan, Shiana; Doty, Crystal N; Beck, Jessalyn; Lahiri, Nayana; Portales-Casamar, Elodie; Warby, Simon C; Connolly, Colúm; De Souza, Rebecca A G; Tabrizi, Sarah J; Hermanson, Ola; Langbehn, Douglas R; Hayden, Michael R; Wasserman, Wyeth W; Leavitt, Blair R

    2015-06-01

    Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset. HTT promoter analysis identified a NF-κB binding site that regulates HTT promoter transcriptional activity. A non-coding SNP, rs13102260:G > A, in this binding site impaired NF-κB binding and reduced HTT transcriptional activity and HTT protein expression. The presence of the rs13102260 minor (A) variant on the HD disease allele was associated with delayed age of onset in familial cases, whereas the presence of the rs13102260 (A) variant on the wild-type HTT allele was associated with earlier age of onset in HD patients in an extreme case-based cohort. Our findings suggest a previously unknown mechanism linking allele-specific effects of rs13102260 on HTT expression to HD age of onset and have implications for HTT silencing treatments that are currently in development.

  16. Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities

    Langland, Gregory T.; Yannone, Steven M.; Langland, Rachel A.; Nakao, Aki; Guan, Yinghui; Long, Sydney B.T.; Vonguyen, Lien; Chen, David J.; Gray, Joe W; Chen, Fanqing

    2009-09-07

    The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood. Since both DNA repair capacity and p53 status can significantly alter radiation sensitivity, we evaluated these factors along with radiation sensitivity in a panel of sporadic human ovarian carcinoma cell lines. We observed a gradation of radiation sensitivity among these sixteen lines, with a five-fold difference in the LD50 between the most radiosensitive and the most radioresistant cells. The DNA-dependent protein kinase (DNA-PK) is essential for the repair of radiation induced DNA double-strand breaks in human somatic cells. Therefore, we measured gene copy number, expression levels, protein abundance, genomic copy and kinase activity for DNA-PK in all of our cell lines. While there were detectable differences in DNA-PK between the cell lines, there was no clear correlation with any of these differences and radiation sensitivity. In contrast, p53 function as determined by two independent methods, correlated well with radiation sensitivity, indicating p53 mutant ovarian cancer cells are typically radioresistant relative to p53 wild-type lines. These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNAPK in ovarian cancer.

  17. Genetic variants associated with altered plasma levels of C-reactive protein are not associated with late-life cognitive ability in four Scottish samples.

    Marioni, Riccardo E; Deary, Ian J; Murray, Gordon D; Lowe, Gordon D O; Rafnsson, Snorri B; Strachan, Mark W J; Luciano, Michelle; Houlihan, Lorna M; Gow, Alan J; Harris, Sarah E; Stewart, Marlene C; Rumley, Ann; Fowkes, F Gerry R; Price, Jackie F

    2010-01-01

    It is unknown whether the relationship between raised inflammatory biomarker levels and late-life cognitive ability is causal. We explored this issue by testing the association between genetic regulators of plasma C-reactive protein (CRP) and cognition. Data were analysed from four cohorts based in central Scotland (Total N = 4,782). Associations were tested between variants in the CRP gene and both plasma CRP levels and a battery of neuropsychological tests, including a vocabulary-based estimate of peak prior cognitive ability and a general (summary) cognitive factor score, or 'g'. CRP levels were associated with a number of variants in the CRP gene (SNPs), including rs1205, rs1130864, rs1800947, and rs1417938 (P range 4.2e-06 to 0.041). Higher CRP levels were also associated with vocabulary-adjusted cognitive ability, used here to estimate lifetime cognitive change (P range 1.7e-04 to 0.038). After correction for multiple testing and adjustment for age and sex, no statistically significant associations were found between the SNPs and cognition. CRP is unlikely to be a causal determinant of late-life cognitive ability.

  18. Suppressor T-cell factor(s) display an altered pattern of Igh (immunoglobulin heavy chain locus) genetic restriction when developed in an Igh-congeneic host

    HayGlass, K.T.; Naides, S.J.; Benacerraf, B.; Sy, M.S.

    1985-01-01

    Suppressor T cell factor(s) (TsF 1 ) inhibit the in vivo priming of azobenzenearsonate-specific cytotoxic T-cell responses. The activity of TsF 1 is restricted by genes linked to Igh-1 allotypic markers. TsF 1 obtained from B6.Igh-1/sup n/ mice was unable to suppress the immune response in B6.Igh-1/sup b/ mice and vice versa. However, TsF 1 prepared from B6.Igh-1/sup n/ T cells parked in an Igh-congeneic B6.Igh-1/sup b/ environment displays an additional restriction specificity of the host. Thus, TsF 1 prepared from these Igh-chimeric mice suppressed immune responses in both B6.Igh-1/sup n/ (donor) and B6.Igh-1/sup b/ (recipient) mice but not in mice of the unrelated strain BALB/c.Igh-1/sup a/. The results indicate that the establishment of the suppressor T-cell repertoire is dependent not only upon the genetic background of the individual T cell but also upon the influence of Igh-linked determinants present when T-cell clones are selected during the response

  19. Spatiotemporal noise covariance estimation from limited empirical magnetoencephalographic data

    Jun, Sung C; Plis, Sergey M; Ranken, Doug M; Schmidt, David M

    2006-01-01

    The performance of parametric magnetoencephalography (MEG) and electroencephalography (EEG) source localization approaches can be degraded by the use of poor background noise covariance estimates. In general, estimation of the noise covariance for spatiotemporal analysis is difficult mainly due to the limited noise information available. Furthermore, its estimation requires a large amount of storage and a one-time but very large (and sometimes intractable) calculation or its inverse. To overcome these difficulties, noise covariance models consisting of one pair or a sum of multi-pairs of Kronecker products of spatial covariance and temporal covariance have been proposed. However, these approaches cannot be applied when the noise information is very limited, i.e., the amount of noise information is less than the degrees of freedom of the noise covariance models. A common example of this is when only averaged noise data are available for a limited prestimulus region (typically at most a few hundred milliseconds duration). For such cases, a diagonal spatiotemporal noise covariance model consisting of sensor variances with no spatial or temporal correlation has been the common choice for spatiotemporal analysis. In this work, we propose a different noise covariance model which consists of diagonal spatial noise covariance and Toeplitz temporal noise covariance. It can easily be estimated from limited noise information, and no time-consuming optimization and data-processing are required. Thus, it can be used as an alternative choice when one-pair or multi-pair noise covariance models cannot be estimated due to lack of noise information. To verify its capability we used Bayesian inference dipole analysis and a number of simulated and empirical datasets. We compared this covariance model with other existing covariance models such as conventional diagonal covariance, one-pair and multi-pair noise covariance models, when noise information is sufficient to estimate them. We

  20. Unexpected Nongenetic Individual Heterogeneity and Trait Covariance in Daphnia and Its Consequences for Ecological and Evolutionary Dynamics.

    Cressler, Clayton E; Bengtson, Stefan; Nelson, William A

    2017-07-01

    Individual differences in genetics, age, or environment can cause tremendous differences in individual life-history traits. This individual heterogeneity generates demographic heterogeneity at the population level, which is predicted to have a strong impact on both ecological and evolutionary dynamics. However, we know surprisingly little about the sources of individual heterogeneity for particular taxa or how different sources scale up to impact ecological and evolutionary dynamics. Here we experimentally study the individual heterogeneity that emerges from both genetic and nongenetic sources in a species of freshwater zooplankton across a large gradient of food quality. Despite the tight control of environment, we still find that the variation from nongenetic sources is greater than that from genetic sources over a wide range of food quality and that this variation has strong positive covariance between growth and reproduction. We evaluate the general consequences of genetic and nongenetic covariance for ecological and evolutionary dynamics theoretically and find that increasing nongenetic variation slows evolution independent of the correlation in heritable life-history traits but that the impact on ecological dynamics depends on both nongenetic and genetic covariance. Our results demonstrate that variation in the relative magnitude of nongenetic versus genetic sources of variation impacts the predicted ecological and evolutionary dynamics.

  1. Covariance Partition Priors: A Bayesian Approach to Simultaneous Covariance Estimation for Longitudinal Data.

    Gaskins, J T; Daniels, M J

    2016-01-02

    The estimation of the covariance matrix is a key concern in the analysis of longitudinal data. When data consists of multiple groups, it is often assumed the covariance matrices are either equal across groups or are completely distinct. We seek methodology to allow borrowing of strength across potentially similar groups to improve estimation. To that end, we introduce a covariance partition prior which proposes a partition of the groups at each measurement time. Groups in the same set of the partition share dependence parameters for the distribution of the current measurement given the preceding ones, and the sequence of partitions is modeled as a Markov chain to encourage similar structure at nearby measurement times. This approach additionally encourages a lower-dimensional structure of the covariance matrices by shrinking the parameters of the Cholesky decomposition toward zero. We demonstrate the performance of our model through two simulation studies and the analysis of data from a depression study. This article includes Supplementary Material available online.

  2. Impact of chromosome alterations, genetic mutations and clonal hematopoiesis of indeterminate potential (CHIP) on the classification and risk stratification of MDS.

    Ganguly, Bani Bandana; Banerjee, Debasis; Agarwal, Mohan B

    2018-03-01

    The advent of technological development has undoubtedly advanced biological and molecular inputs for better understanding the heterogeneous hematopoietic pre-malignant disorder of the stem cells known as myelodysplastic syndromes (MDS). Chromosomal rearrangements, including del(3q/5q/7q/11q/12p/20q), loss of 5/7/Y, trisomy 8/19, i(17q), etc. frequently detected in MDS with variable frequencies and combinations, are the integral components of the 5-tier risk-stratification and WHO-2016 classification. Observations on mutations in genes involved in RNA-splicing, DNA methylation, chromatin modification, transcription factor, signal transduction/kinases, RAS pathway, cohesin complex, DNA repair and other pathways have given insights in independent effects and biological interaction of co-occurrence on disease-phenotype and treatment outcome. However, recent concepts of clonal hematopoiesis of indeterminate potential (CHIP) and idiopathic cytopenia of undetermined significance (ICUS) have urged a re-definition of mutational events in non-clonal cytopenia and non-MDS healthy elderly but with a higher risk of overt leukemia. Considering gene mutations, chromosomal alterations, CHIP, ICUS and their significance in classification and risk-scoring certainly presents a comprehensive picture of disease-phenotype towards better understanding of MDS-pathogenesis, its evolution to AML and its response to therapeutic agents. The present review summarizes chromosomal and gene mutations, co-existence of mutational complexity, and WHO-2016 classification and risk-stratifications of MDS to facilitate a better understanding of its pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The order of exercise during concurrent training for rehabilitation does not alter acute genetic expression, mitochondrial enzyme activity or improvements in muscle function.

    Lauren G MacNeil

    Full Text Available Concurrent exercise combines different modes of exercise (e.g., aerobic and resistance into one training protocol, providing stimuli meant to increase muscle strength, aerobic capacity and mass. As disuse is associated with decrements in strength, aerobic capacity and muscle size concurrent training is an attractive modality for rehabilitation. However, interference between the signaling pathways may result in preferential improvements for one of the exercise modes. We recruited 18 young adults (10 ♂, 8 ♀ to determine if order of exercise mode during concurrent training would differentially affect gene expression, protein content and measures of strength and aerobic capacity after 2 weeks of knee-brace induced disuse. Concurrent exercise sessions were performed 3x/week for 6 weeks at gradually increasing intensities either with endurance exercise preceding (END>RES or following (RES>END resistance exercise. Biopsies were collected from the vastus lateralis before, 3 h after the first exercise bout and 48 h after the end of training. Concurrent exercise altered the expression of genes involved in mitochondrial biogenesis (PGC-1α, PRC, PPARγ, hypertrophy (PGC-1α4, REDD2, Rheb and atrophy (MuRF-1, Runx1, increased electron transport chain complex protein content, citrate synthase and mitochondrial cytochrome c oxidase enzyme activity, muscle mass, maximum isometric strength and VO 2peak. However, the order in which exercise was completed (END>RES or RES>END only affected the protein content of mitochondrial complex II subunit. In conclusion, concurrent exercise training is an effective modality for the rehabilitation of the loss of skeletal muscle mass, maximum strength, and peak aerobic capacity resulting from disuse, regardless of the order in which the modes of exercise are performed.

  4. Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression.

    Wegener, Gregers; Finger, Beate C; Elfving, Betina; Keller, Kirsten; Liebenberg, Nico; Fischer, Christina W; Singewald, Nicolas; Slattery, David A; Neumann, Inga D; Mathé, Aleksander A

    2012-04-01

    Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats. We found that FSL showed greater immobility in the forced swim test (FST) than FRL, confirming their phenotype. However, NPS did not affect depression-related behaviour in any rat line. No significant differences in baseline anxiety levels between the FSL and FRL strains were observed, but FSL and FRL rats displayed less anxiety-like behaviour compared to SD rats. NPS decreased anxiety-like behaviour on the elevated plus-maze in all strains. The expression of the NPSR in the amygdala, periventricular hypothalamic nucleus, and hippocampus was equal in all male strains, although a trend towards reduced expression within the amygdala was observed in FSL rats compared to SD rats. In conclusion, NPS had a marked anxiolytic effect in FSL, FRL and SD rats, but did not modify the depression-related behaviour in any strain, in spite of the significant differences in innate level between the strains. These findings suggest that NPS specifically modifies anxiety behaviour but cannot overcome/reverse a genetically mediated depression phenotype.

  5. Chimeric Feline Coronaviruses That Encode Type II Spike Protein on Type I Genetic Background Display Accelerated Viral Growth and Altered Receptor Usage▿

    Tekes, Gergely; Hofmann-Lehmann, Regina; Bank-Wolf, Barbara; Maier, Reinhard; Thiel, Heinz-Jürgen; Thiel, Volker

    2010-01-01

    Persistent infection of domestic cats with feline coronaviruses (FCoVs) can lead to a highly lethal, immunopathological disease termed feline infectious peritonitis (FIP). Interestingly, there are two serotypes, type I and type II FCoVs, that can cause both persistent infection and FIP, even though their main determinant of host cell tropism, the spike (S) protein, is of different phylogeny and displays limited sequence identity. In cell culture, however, there are apparent differences. Type II FCoVs can be propagated to high titers by employing feline aminopeptidase N (fAPN) as a cellular receptor, whereas the propagation of type I FCoVs is usually difficult, and the involvement of fAPN as a receptor is controversial. In this study we have analyzed the phenotypes of recombinant FCoVs that are based on the genetic background of type I FCoV strain Black but encode the type II FCoV strain 79-1146 S protein. Our data demonstrate that recombinant FCoVs expressing a type II FCoV S protein acquire the ability to efficiently use fAPN for host cell entry and corroborate the notion that type I FCoVs use another main host cell receptor. We also observed that recombinant FCoVs display a large-plaque phenotype and, unexpectedly, accelerated growth kinetics indistinguishable from that of type II FCoV strain 79-1146. Thus, the main phenotypic differences for type I and type II FCoVs in cell culture, namely, the growth kinetics and the efficient usage of fAPN as a cellular receptor, can be attributed solely to the FCoV S protein. PMID:19906918

  6. Noisy covariance matrices and portfolio optimization II

    Pafka, Szilárd; Kondor, Imre

    2003-03-01

    Recent studies inspired by results from random matrix theory (Galluccio et al.: Physica A 259 (1998) 449; Laloux et al.: Phys. Rev. Lett. 83 (1999) 1467; Risk 12 (3) (1999) 69; Plerou et al.: Phys. Rev. Lett. 83 (1999) 1471) found that covariance matrices determined from empirical financial time series appear to contain such a high amount of noise that their structure can essentially be regarded as random. This seems, however, to be in contradiction with the fundamental role played by covariance matrices in finance, which constitute the pillars of modern investment theory and have also gained industry-wide applications in risk management. Our paper is an attempt to resolve this embarrassing paradox. The key observation is that the effect of noise strongly depends on the ratio r= n/ T, where n is the size of the portfolio and T the length of the available time series. On the basis of numerical experiments and analytic results for some toy portfolio models we show that for relatively large values of r (e.g. 0.6) noise does, indeed, have the pronounced effect suggested by Galluccio et al. (1998), Laloux et al. (1999) and Plerou et al. (1999) and illustrated later by Laloux et al. (Int. J. Theor. Appl. Finance 3 (2000) 391), Plerou et al. (Phys. Rev. E, e-print cond-mat/0108023) and Rosenow et al. (Europhys. Lett., e-print cond-mat/0111537) in a portfolio optimization context, while for smaller r (around 0.2 or below), the error due to noise drops to acceptable levels. Since the length of available time series is for obvious reasons limited in any practical application, any bound imposed on the noise-induced error translates into a bound on the size of the portfolio. In a related set of experiments we find that the effect of noise depends also on whether the problem arises in asset allocation or in a risk measurement context: if covariance matrices are used simply for measuring the risk of portfolios with a fixed composition rather than as inputs to optimization, the

  7. Epigenetic Alterations in Alzheimer's Disease

    Johannes eGräff

    2015-12-01

    Full Text Available Alzheimer’s disease (AD is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

  8. Epigenetic Alterations in Alzheimer's Disease.

    Sanchez-Mut, Jose V; Gräff, Johannes

    2015-01-01

    Alzheimer's disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

  9. Melanoma genetics

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  10. Computing more proper covariances of energy dependent nuclear data

    Vanhanen, R.

    2016-01-01

    Highlights: • We present conditions for covariances of energy dependent nuclear data to be proper. • We provide methods to detect non-positive and inconsistent covariances in ENDF-6 format. • We propose methods to find nearby more proper covariances. • The methods can be used as a part of a quality assurance program. - Abstract: We present conditions for covariances of energy dependent nuclear data to be proper in the sense that the covariances are positive, i.e., its eigenvalues are non-negative, and consistent with respect to the sum rules of nuclear data. For the ENDF-6 format covariances we present methods to detect non-positive and inconsistent covariances. These methods would be useful as a part of a quality assurance program. We also propose methods that can be used to find nearby more proper energy dependent covariances. These methods can be used to remove unphysical components, while preserving most of the physical components. We consider several different senses in which the nearness can be measured. These methods could be useful if a re-evaluation of improper covariances is not feasible. Two practical examples are processed and analyzed. These demonstrate some of the properties of the methods. We also demonstrate that the ENDF-6 format covariances of linearly dependent nuclear data should usually be encoded with the derivation rules.

  11. Impact of the 235U Covariance Data in Benchmark Calculations

    Leal, Luiz C.; Mueller, D.; Arbanas, G.; Wiarda, D.; Derrien, H.

    2008-01-01

    The error estimation for calculated quantities relies on nuclear data uncertainty information available in the basic nuclear data libraries such as the U.S. Evaluated Nuclear Data File (ENDF/B). The uncertainty files (covariance matrices) in the ENDF/B library are generally obtained from analysis of experimental data. In the resonance region, the computer code SAMMY is used for analyses of experimental data and generation of resonance parameters. In addition to resonance parameters evaluation, SAMMY also generates resonance parameter covariance matrices (RPCM). SAMMY uses the generalized least-squares formalism (Bayes method) together with the resonance formalism (R-matrix theory) for analysis of experimental data. Two approaches are available for creation of resonance-parameter covariance data. (1) During the data-evaluation process, SAMMY generates both a set of resonance parameters that fit the experimental data and the associated resonance-parameter covariance matrix. (2) For existing resonance-parameter evaluations for which no resonance-parameter covariance data are available, SAMMY can retroactively create a resonance-parameter covariance matrix. The retroactive method was used to generate covariance data for 235U. The resulting 235U covariance matrix was then used as input to the PUFF-IV code, which processed the covariance data into multigroup form, and to the TSUNAMI code, which calculated the uncertainty in the multiplication factor due to uncertainty in the experimental cross sections. The objective of this work is to demonstrate the use of the 235U covariance data in calculations of critical benchmark systems

  12. Development of covariance date for fast reactor cores. 3

    Shibata, Keiichi; Hasegawa, Akira

    1999-03-01

    Covariances have been estimated for nuclear data contained in JENDL-3.2. As for Cr and Ni, the physical quantities for which covariances are deduced are cross sections and the first order Legendre-polynomial coefficient for the angular distribution of elastically scattered neutrons. The covariances were estimated by using the same methodology that had been used in the JENDL-3.2 evaluation in order to keep a consistency between mean values and their covariances. In a case where evaluated data were based on experimental data, the covariances were estimated from the same experimental data. For cross section that had been evaluated by nuclear model calculations, the same model was applied to generate the covariances. The covariances obtained were compiled into ENDF-6 format files. The covariances, which had been prepared by the previous fiscal year, were re-examined, and some improvements were performed. Parts of Fe and 235 U covariances were updated. Covariances of nu-p and nu-d for 241 Pu and of fission neutron spectra for 233,235,238 U and 239,240 Pu were newly added to data files. (author)

  13. Anomalous current from the covariant Wigner function

    Prokhorov, George; Teryaev, Oleg

    2018-04-01

    We consider accelerated and rotating media of weakly interacting fermions in local thermodynamic equilibrium on the basis of kinetic approach. Kinetic properties of such media can be described by covariant Wigner function incorporating the relativistic distribution functions of particles with spin. We obtain the formulae for axial current by summation of the terms of all orders of thermal vorticity tensor, chemical potential, both for massive and massless particles. In the massless limit all the terms of fourth and higher orders of vorticity and third order of chemical potential and temperature equal zero. It is shown, that axial current gets a topological component along the 4-acceleration vector. The similarity between different approaches to baryon polarization is established.

  14. Covariant non-commutative space–time

    Jonathan J. Heckman

    2015-05-01

    Full Text Available We introduce a covariant non-commutative deformation of 3+1-dimensional conformal field theory. The deformation introduces a short-distance scale ℓp, and thus breaks scale invariance, but preserves all space–time isometries. The non-commutative algebra is defined on space–times with non-zero constant curvature, i.e. dS4 or AdS4. The construction makes essential use of the representation of CFT tensor operators as polynomials in an auxiliary polarization tensor. The polarization tensor takes active part in the non-commutative algebra, which for dS4 takes the form of so(5,1, while for AdS4 it assembles into so(4,2. The structure of the non-commutative correlation functions hints that the deformed theory contains gravitational interactions and a Regge-like trajectory of higher spin excitations.

  15. Covariant entropy bound and loop quantum cosmology

    Ashtekar, Abhay; Wilson-Ewing, Edward

    2008-01-01

    We examine Bousso's covariant entropy bound conjecture in the context of radiation filled, spatially flat, Friedmann-Robertson-Walker models. The bound is violated near the big bang. However, the hope has been that quantum gravity effects would intervene and protect it. Loop quantum cosmology provides a near ideal setting for investigating this issue. For, on the one hand, quantum geometry effects resolve the singularity and, on the other hand, the wave function is sharply peaked at a quantum corrected but smooth geometry, which can supply the structure needed to test the bound. We find that the bound is respected. We suggest that the bound need not be an essential ingredient for a quantum gravity theory but may emerge from it under suitable circumstances.

  16. Nonparametric Bayesian models for a spatial covariance.

    Reich, Brian J; Fuentes, Montserrat

    2012-01-01

    A crucial step in the analysis of spatial data is to estimate the spatial correlation function that determines the relationship between a spatial process at two locations. The standard approach to selecting the appropriate correlation function is to use prior knowledge or exploratory analysis, such as a variogram analysis, to select the correct parametric correlation function. Rather that selecting a particular parametric correlation function, we treat the covariance function as an unknown function to be estimated from the data. We propose a flexible prior for the correlation function to provide robustness to the choice of correlation function. We specify the prior for the correlation function using spectral methods and the Dirichlet process prior, which is a common prior for an unknown distribution function. Our model does not require Gaussian data or spatial locations on a regular grid. The approach is demonstrated using a simulation study as well as an analysis of California air pollution data.

  17. Covariant Derivatives and the Renormalization Group Equation

    Dolan, Brian P.

    The renormalization group equation for N-point correlation functions can be interpreted in a geometrical manner as an equation for Lie transport of amplitudes in the space of couplings. The vector field generating the diffeomorphism has components given by the β functions of the theory. It is argued that this simple picture requires modification whenever any one of the points at which the amplitude is evaluated becomes close to any other. This modification necessitates the introduction of a connection on the space of couplings and new terms appear in the renormalization group equation involving covariant derivatives of the β function and the curvature associated with the connection. It is shown how the connection is related to the operator product expansion coefficients, but there remains an arbitrariness in its definition.

  18. Generation of phase-covariant quantum cloning

    Karimipour, V.; Rezakhani, A.T.

    2002-01-01

    It is known that in phase-covariant quantum cloning, the equatorial states on the Bloch sphere can be cloned with a fidelity higher than the optimal bound established for universal quantum cloning. We generalize this concept to include other states on the Bloch sphere with a definite z component of spin. It is shown that once we know the z component, we can always clone a state with a fidelity higher than the universal value and that of equatorial states. We also make a detailed study of the entanglement properties of the output copies and show that the equatorial states are the only states that give rise to a separable density matrix for the outputs

  19. Covariant formulation of scalar-torsion gravity

    Hohmann, Manuel; Järv, Laur; Ualikhanova, Ulbossyn

    2018-05-01

    We consider a generalized teleparallel theory of gravitation, where the action contains an arbitrary function of the torsion scalar and a scalar field, f (T ,ϕ ) , thus encompassing the cases of f (T ) gravity and a nonminimally coupled scalar field as subclasses. The action is manifestly Lorentz invariant when besides the tetrad one allows for a flat but nontrivial spin connection. We derive the field equations and demonstrate how the antisymmetric part of the tetrad equations is automatically satisfied when the spin connection equation holds. The spin connection equation is a vital part of the covariant formulation, since it determines the spin connection associated with a given tetrad. We discuss how the spin connection equation can be solved in general and provide the cosmological and spherically symmetric examples. Finally, we generalize the theory to an arbitrary number of scalar fields.

  20. Genetic Mutations in Cancer

    Many different types of genetic mutations are found in cancer cells. This infographic outlines certain types of alterations that are present in cancer, such as missense, nonsense, frameshift, and chromosome rearrangements.

  1. Incorporation of covariates in simultaneous localization of two linked loci using affected relative pairs

    Liang Kung-Yee

    2010-07-01

    Full Text Available Abstract Background Many dichotomous traits for complex diseases are often involved more than one locus and/or associated with quantitative biomarkers or environmental factors. Incorporating these quantitative variables into linkage analysis as well as localizing two linked disease loci simultaneously could therefore improve the efficiency in mapping genes. We extended the robust multipoint Identity-by-Descent (IBD approach with incorporation of covariates developed previously to simultaneously estimate two linked loci using different types of affected relative pairs (ARPs. Results We showed that the efficiency was enhanced by incorporating a quantitative covariate parametrically or non-parametrically while localizing two disease loci using ARPs. In addition to its help in identifying factors associated with the disease and in improving the efficiency in estimating disease loci, this extension also allows investigators to account for heterogeneity in risk-ratios for different ARPs. Data released from the collaborative study on the genetics of alcoholism (COGA for Genetic Analysis Workshop 14 (GAW 14 were used to illustrate the application of this extended method. Conclusions The simulation studies and example illustrated that the efficiency in estimating disease loci was demonstratively enhanced by incorporating a quantitative covariate and by using all relative pairs while mapping two linked loci simultaneously.

  2. Introduction to covariant formulation of superstring (field) theory

    Anon.

    1987-01-01

    The author discusses covariant formulation of superstring theories based on BRS invariance. New formulation of superstring was constructed by Green and Schwarz in the light-cone gauge first and then a covariant action was discovered. The covariant action has some interesting geometrical interpretation, however, covariant quantizations are difficult to perform because of existence of local supersymmetries. Introducing extra variables into the action, a modified action has been proposed. However, it would be difficult to prescribe constraints to define a physical subspace, or to reproduce the correct physical spectrum. Hence the old formulation, i.e., the Neveu-Schwarz-Ramond (NSR) model for covariant quantization is used. The author begins by quantizing the NSR model in a covariant way using BRS charges. Then the author discusses the field theory of (free) superstring

  3. The method of covariant symbols in curved space-time

    Salcedo, L.L.

    2007-01-01

    Diagonal matrix elements of pseudodifferential operators are needed in order to compute effective Lagrangians and currents. For this purpose the method of symbols is often used, which however lacks manifest covariance. In this work the method of covariant symbols, introduced by Pletnev and Banin, is extended to curved space-time with arbitrary gauge and coordinate connections. For the Riemannian connection we compute the covariant symbols corresponding to external fields, the covariant derivative and the Laplacian, to fourth order in a covariant derivative expansion. This allows one to obtain the covariant symbol of general operators to the same order. The procedure is illustrated by computing the diagonal matrix element of a nontrivial operator to second order. Applications of the method are discussed. (orig.)

  4. Physical properties of the Schur complement of local covariance matrices

    Haruna, L F; Oliveira, M C de

    2007-01-01

    General properties of global covariance matrices representing bipartite Gaussian states can be decomposed into properties of local covariance matrices and their Schur complements. We demonstrate that given a bipartite Gaussian state ρ 12 described by a 4 x 4 covariance matrix V, the Schur complement of a local covariance submatrix V 1 of it can be interpreted as a new covariance matrix representing a Gaussian operator of party 1 conditioned to local parity measurements on party 2. The connection with a partial parity measurement over a bipartite quantum state and the determination of the reduced Wigner function is given and an operational process of parity measurement is developed. Generalization of this procedure to an n-partite Gaussian state is given, and it is demonstrated that the n - 1 system state conditioned to a partial parity projection is given by a covariance matrix such that its 2 x 2 block elements are Schur complements of special local matrices

  5. Fermionic covariant prolongation structure theory for supernonlinear evolution equation

    Cheng Jipeng; Wang Shikun; Wu Ke; Zhao Weizhong

    2010-01-01

    We investigate the superprincipal bundle and its associated superbundle. The super(nonlinear)connection on the superfiber bundle is constructed. Then by means of the connection theory, we establish the fermionic covariant prolongation structure theory of the supernonlinear evolution equation. In this geometry theory, the fermionic covariant fundamental equations determining the prolongation structure are presented. As an example, the supernonlinear Schroedinger equation is analyzed in the framework of this fermionic covariant prolongation structure theory. We obtain its Lax pairs and Baecklund transformation.

  6. Bayesian hierarchical model for large-scale covariance matrix estimation.

    Zhu, Dongxiao; Hero, Alfred O

    2007-12-01

    Many bioinformatics problems implicitly depend on estimating large-scale covariance matrix. The traditional approaches tend to give rise to high variance and low accuracy due to "overfitting." We cast the large-scale covariance matrix estimation problem into the Bayesian hierarchical model framework, and introduce dependency between covariance parameters. We demonstrate the advantages of our approaches over the traditional approaches using simulations and OMICS data analysis.

  7. Rapid changes in genetic architecture of behavioural syndromes following colonization of a novel environment.

    Karlsson Green, K; Eroukhmanoff, F; Harris, S; Pettersson, L B; Svensson, E I

    2016-01-01

    Behavioural syndromes, that is correlated behaviours, may be a result from adaptive correlational selection, but in a new environmental setting, the trait correlation might act as an evolutionary constraint. However, knowledge about the quantitative genetic basis of behavioural syndromes, and the stability and evolvability of genetic correlations under different ecological conditions, is limited. We investigated the quantitative genetic basis of correlated behaviours in the freshwater isopod Asellus aquaticus. In some Swedish lakes, A. aquaticus has recently colonized a novel habitat and diverged into two ecotypes, presumably due to habitat-specific selection from predation. Using a common garden approach and animal model analyses, we estimated quantitative genetic parameters for behavioural traits and compared the genetic architecture between the ecotypes. We report that the genetic covariance structure of the behavioural traits has been altered in the novel ecotype, demonstrating divergence in behavioural correlations. Thus, our study confirms that genetic correlations behind behaviours can change rapidly in response to novel selective environments. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  8. Widespread covariation of early environmental exposures and trait-associated polygenic variation.

    Krapohl, E; Hannigan, L J; Pingault, J-B; Patel, H; Kadeva, N; Curtis, C; Breen, G; Newhouse, S J; Eley, T C; O'Reilly, P F; Plomin, R

    2017-10-31

    Although gene-environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between trait-associated polygenic variation identified by genome-wide association studies (GWASs) and specific environmental exposures, controlling for overall genetic relatedness using a genomic relatedness matrix restricted maximum-likelihood model. In a UK-representative sample ( n = 6,710), we find widespread covariation between offspring trait-associated polygenic variation and parental behavior and characteristics relevant to children's developmental outcomes-independently of population stratification. For instance, offspring genetic risk for schizophrenia was associated with paternal age ( R 2 = 0.002; P = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding ( R 2 = 0.021; P = 7e-30), maternal smoking during pregnancy ( R 2 = 0.008; P = 5e-13), parental smacking ( R 2 = 0.01; P = 4e-15), household income ( R 2 = 0.032; P = 1e-22), watching television ( R 2 = 0.034; P = 5e-47), and maternal education ( R 2 = 0.065; P = 3e-96). Education-associated polygenic variation also captured covariation between environmental exposures and children's inattention/hyperactivity, conduct problems, and educational achievement. The finding that genetic variation identified by trait GWASs partially captures environmental risk factors or protective factors has direct implications for risk prediction models and the interpretation of GWAS findings.

  9. Some remarks on general covariance of quantum theory

    Schmutzer, E.

    1977-01-01

    If one accepts Einstein's general principle of relativity (covariance principle) also for the sphere of microphysics (quantum, mechanics, quantum field theory, theory of elemtary particles), one has to ask how far the fundamental laws of traditional quantum physics fulfil this principle. Attention is here drawn to a series of papers that have appeared during the last years, in which the author criticized the usual scheme of quantum theory (Heisenberg picture, Schroedinger picture etc.) and presented a new foundation of the basic laws of quantum physics, obeying the 'principle of fundamental covariance' (Einstein's covariance principle in space-time and covariance principle in Hilbert space of quantum operators and states). (author)

  10. Summary report of technical meeting on neutron cross section covariances

    Trkov, A.; Smith, D.L.; Capote Noy, R.

    2011-01-01

    A summary is given of the Technical Meeting on Neutron Cross Section Covariances. The meeting goal was to assess covariance data needs and recommend appropriate methodologies to address those needs. Discussions on covariance data focused on three general topics: 1) Resonance and unresolved resonance regions; 2) Fast neutron region; and 3) Users' perspective: benchmarks' uncertainty and reactor dosimetry. A number of recommendations for further work were generated and the important work that remains to be done in the field of covariances was identified. (author)

  11. Genome-Wide Scan for Adaptive Divergence and Association with Population-Specific Covariates.

    Gautier, Mathieu

    2015-12-01

    In population genomics studies, accounting for the neutral covariance structure across population allele frequencies is critical to improve the robustness of genome-wide scan approaches. Elaborating on the BayEnv model, this study investigates several modeling extensions (i) to improve the estimation accuracy of the population covariance matrix and all the related measures, (ii) to identify significantly overly differentiated SNPs based on a calibration procedure of the XtX statistics, and (iii) to consider alternative covariate models for analyses of association with population-specific covariables. In particular, the auxiliary variable model allows one to deal with multiple testing issues and, providing the relative marker positions are available, to capture some linkage disequilibrium information. A comprehensive simulation study was carried out to evaluate the performances of these different models. Also, when compared in terms of power, robustness, and computational efficiency to five other state-of-the-art genome-scan methods (BayEnv2, BayScEnv, BayScan, flk, and lfmm), the proposed approaches proved highly effective. For illustration purposes, genotyping data on 18 French cattle breeds were analyzed, leading to the identification of 13 strong signatures of selection. Among these, four (surrounding the KITLG, KIT, EDN3, and ALB genes) contained SNPs strongly associated with the piebald coloration pattern while a fifth (surrounding PLAG1) could be associated to morphological differences across the populations. Finally, analysis of Pool-Seq data from 12 populations of Littorina saxatilis living in two different ecotypes illustrates how the proposed framework might help in addressing relevant ecological issues in nonmodel species. Overall, the proposed methods define a robust Bayesian framework to characterize adaptive genetic differentiation across populations. The BayPass program implementing the different models is available at http://www1.montpellier

  12. Smooth individual level covariates adjustment in disease mapping.

    Huque, Md Hamidul; Anderson, Craig; Walton, Richard; Woolford, Samuel; Ryan, Louise

    2018-05-01

    Spatial models for disease mapping should ideally account for covariates measured both at individual and area levels. The newly available "indiCAR" model fits the popular conditional autoregresssive (CAR) model by accommodating both individual and group level covariates while adjusting for spatial correlation in the disease rates. This algorithm has been shown to be effective but assumes log-linear associations between individual level covariates and outcome. In many studies, the relationship between individual level covariates and the outcome may be non-log-linear, and methods to track such nonlinearity between individual level covariate and outcome in spatial regression modeling are not well developed. In this paper, we propose a new algorithm, smooth-indiCAR, to fit an extension to the popular conditional autoregresssive model that can accommodate both linear and nonlinear individual level covariate effects while adjusting for group level covariates and spatial correlation in the disease rates. In this formulation, the effect of a continuous individual level covariate is accommodated via penalized splines. We describe a two-step estimation procedure to obtain reliable estimates of individual and group level covariate effects where both individual and group level covariate effects are estimated separately. This distributed computing framework enhances its application in the Big Data domain with a large number of individual/group level covariates. We evaluate the performance of smooth-indiCAR through simulation. Our results indicate that the smooth-indiCAR method provides reliable estimates of all regression and random effect parameters. We illustrate our proposed methodology with an analysis of data on neutropenia admissions in New South Wales (NSW), Australia. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Central subspace dimensionality reduction using covariance operators.

    Kim, Minyoung; Pavlovic, Vladimir

    2011-04-01

    We consider the task of dimensionality reduction informed by real-valued multivariate labels. The problem is often treated as Dimensionality Reduction for Regression (DRR), whose goal is to find a low-dimensional representation, the central subspace, of the input data that preserves the statistical correlation with the targets. A class of DRR methods exploits the notion of inverse regression (IR) to discover central subspaces. Whereas most existing IR techniques rely on explicit output space slicing, we propose a novel method called the Covariance Operator Inverse Regression (COIR) that generalizes IR to nonlinear input/output spaces without explicit target slicing. COIR's unique properties make DRR applicable to problem domains with high-dimensional output data corrupted by potentially significant amounts of noise. Unlike recent kernel dimensionality reduction methods that employ iterative nonconvex optimization, COIR yields a closed-form solution. We also establish the link between COIR, other DRR techniques, and popular supervised dimensionality reduction methods, including canonical correlation analysis and linear discriminant analysis. We then extend COIR to semi-supervised settings where many of the input points lack their labels. We demonstrate the benefits of COIR on several important regression problems in both fully supervised and semi-supervised settings.

  14. The covariance of GPS coordinates and frames

    Lachieze-Rey, Marc

    2006-01-01

    We explore, in the general relativistic context, the properties of the recently introduced global positioning system (GPS) coordinates, as well as those of the associated frames and coframes that they define. We show that they are covariant and completely independent of any observer. We show that standard spectroscopic and astrometric observations allow any observer to measure (i) the values of the GPS coordinates at his position (ii) the components of his 4-velocity and (iii) the components of the metric in the GPS frame. This provides this system with a unique value both for conceptual discussion (no frame dependence) and for practical use (involved quantities are directly measurable): localization, motion monitoring, astrometry, cosmography and tests of gravitation theories. We show explicitly, in the general relativistic context, how an observer may estimate his position and motion, and reconstruct the components of the metric. This arises from two main results: the extension of the velocity fields of the probes to the whole (curved) spacetime, and the identification of the components of the observer's velocity in the GPS frame with the (inversed) observed redshifts of the probes. Specific cases (non-relativistic velocities, Minkowski and Friedmann-Lemaitre spacetimes, geodesic motions) are studied in detail

  15. Covariant path integrals on hyperbolic surfaces

    Schaefer, Joe

    1997-11-01

    DeWitt's covariant formulation of path integration [B. De Witt, "Dynamical theory in curved spaces. I. A review of the classical and quantum action principles," Rev. Mod. Phys. 29, 377-397 (1957)] has two practical advantages over the traditional methods of "lattice approximations;" there is no ordering problem, and classical symmetries are manifestly preserved at the quantum level. Applying the spectral theorem for unbounded self-adjoint operators, we provide a rigorous proof of the convergence of certain path integrals on Riemann surfaces of constant curvature -1. The Pauli-DeWitt curvature correction term arises, as in DeWitt's work. Introducing a Fuchsian group Γ of the first kind, and a continuous, bounded, Γ-automorphic potential V, we obtain a Feynman-Kac formula for the automorphic Schrödinger equation on the Riemann surface ΓH. We analyze the Wick rotation and prove the strong convergence of the so-called Feynman maps [K. D. Elworthy, Path Integration on Manifolds, Mathematical Aspects of Superspace, edited by Seifert, Clarke, and Rosenblum (Reidel, Boston, 1983), pp. 47-90] on a dense set of states. Finally, we give a new proof of some results in C. Grosche and F. Steiner, "The path integral on the Poincare upper half plane and for Liouville quantum mechanics," Phys. Lett. A 123, 319-328 (1987).

  16. Spinors, tensors and the covariant form of Dirac's equation

    Chen, W.Q.; Cook, A.H.

    1986-01-01

    The relations between tensors and spinors are used to establish the form of the covariant derivative of a spinor, making use of the fact that certain bilinear combinations of spinors are vectors. The covariant forms of Dirac's equation are thus obtained and examples in specific coordinate systems are displayed. (author)

  17. A scale invariant covariance structure on jet space

    Pedersen, Kim Steenstrup; Loog, Marco; Markussen, Bo

    2005-01-01

    This paper considers scale invariance of statistical image models. We study statistical scale invariance of the covariance structure of jet space under scale space blurring and derive the necessary structure and conditions of the jet covariance matrix in order for it to be scale invariant. As par...

  18. Transformation of covariant quark Wigner operator to noncovariant one

    Selikhov, A.V.

    1989-01-01

    The gauge in which covariant and noncovariant quark Wigner operators coincide has been found. In this gauge the representations of vector potential via field strength tensor is valid. The system of equations for the coefficients of covariant Wigner operator expansion in the basis γ-matrices algebra is obtained. 12 refs.; 3 figs

  19. Covariance as input to and output from resonance analyses

    Larson, N.M.

    1992-01-01

    Accurate data analysis requires understanding of the roles played by both data and parameter covariance matrices. In this paper the entire data reduction/analysis process is examined, for neutron-induced reactions in the resonance region. Interrelationships between data and parameter covariance matrices are examined and alternative reduction/analysis methods discussed

  20. A three domain covariance framework for EEG/MEG data

    Ros, B.P.; Bijma, F.; de Gunst, M.C.M.; de Munck, J.C.

    2015-01-01

    In this paper we introduce a covariance framework for the analysis of single subject EEG and MEG data that takes into account observed temporal stationarity on small time scales and trial-to-trial variations. We formulate a model for the covariance matrix, which is a Kronecker product of three

  1. application of covariance analysis to feed/ ration experimental data

    Prince Acheampong

    ABSTRACT. The use Analysis of Covariance (ANOCOVA) to feed/ration experimental data for birds was examined. Correlation and Regression analyses were used to adjust for the covariate – initial weight of the experimental birds. The Fisher's F statistic for the straight forward Analysis of Variance (ANOVA) showed ...

  2. Covariant Theory of Gravitation in the Spacetime with Finsler Structure

    Huang, Xin-Bing

    2007-01-01

    The theory of gravitation in the spacetime with Finsler structure is constructed. It is shown that the theory keeps general covariance. Such theory reduces to Einstein's general relativity when the Finsler structure is Riemannian. Therefore, this covariant theory of gravitation is an elegant realization of Einstein's thoughts on gravitation in the spacetime with Finsler structure.

  3. Some observations on interpolating gauges and non-covariant gauges

    We discuss the viability of using interpolating gauges to define the non-covariant gauges starting from the covariant ones. We draw attention to the need for a very careful treatment of boundary condition defining term. We show that the boundary condition needed to maintain gauge-invariance as the interpolating parameter ...

  4. Theory of Covariance Equivalent ARMAV Models of Civil Engineering Structures

    Andersen, P.; Brincker, Rune; Kirkegaard, Poul Henning

    1996-01-01

    In this paper the theoretical background for using covariance equivalent ARMAV models in modal analysis is discussed. It is shown how to obtain a covariance equivalent ARMA model for a univariate linear second order continous-time system excited by Gaussian white noise. This result is generalized...

  5. Theory of Covariance Equivalent ARMAV Models of Civil Engineering Structures

    Andersen, P.; Brincker, Rune; Kirkegaard, Poul Henning

    In this paper the theoretical background for using covariance equivalent ARMAV models in modal analysis is discussed. It is shown how to obtain a covariance equivalent ARMA model for a univariate linear second order continuous-time system excited by Gaussian white noise. This result is generalize...

  6. The K-Step Spatial Sign Covariance Matrix

    Croux, C.; Dehon, C.; Yadine, A.

    2010-01-01

    The Sign Covariance Matrix is an orthogonal equivariant estimator of mul- tivariate scale. It is often used as an easy-to-compute and highly robust estimator. In this paper we propose a k-step version of the Sign Covariance Matrix, which improves its e±ciency while keeping the maximal breakdown

  7. On the bilinear covariants associated to mass dimension one spinors

    Silva, J.M.H. da; Villalobos, C.H.C.; Rogerio, R.J.B. [DFQ, UNESP, Guaratingueta, SP (Brazil); Scatena, E. [Universidade Federal de Santa Catarina-CEE, Blumenau, SC (Brazil)

    2016-10-15

    In this paper we approach the issue of Clifford algebra basis deformation, allowing for bilinear covariants associated to Elko spinors which satisfy the Fierz-Pauli-Kofink identities. We present a complete analysis of covariance, taking into account the involved dual structure associated to Elko spinors. Moreover, the possible generalizations to the recently presented new dual structure are performed. (orig.)

  8. Multilevel maximum likelihood estimation with application to covariance matrices

    Turčičová, Marie; Mandel, J.; Eben, Kryštof

    Published online: 23 January ( 2018 ) ISSN 0361-0926 R&D Projects: GA ČR GA13-34856S Institutional support: RVO:67985807 Keywords : Fisher information * High dimension * Hierarchical maximum likelihood * Nested parameter spaces * Spectral diagonal covariance model * Sparse inverse covariance model Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.311, year: 2016

  9. Positive semidefinite integrated covariance estimation, factorizations and asynchronicity

    Boudt, Kris; Laurent, Sébastien; Lunde, Asger

    2017-01-01

    An estimator of the ex-post covariation of log-prices under asynchronicity and microstructure noise is proposed. It uses the Cholesky factorization of the covariance matrix in order to exploit the heterogeneity in trading intensities to estimate the different parameters sequentially with as many...

  10. Precomputing Process Noise Covariance for Onboard Sequential Filters

    Olson, Corwin G.; Russell, Ryan P.; Carpenter, J. Russell

    2017-01-01

    Process noise is often used in estimation filters to account for unmodeled and mismodeled accelerations in the dynamics. The process noise covariance acts to inflate the state covariance over propagation intervals, increasing the uncertainty in the state. In scenarios where the acceleration errors change significantly over time, the standard process noise covariance approach can fail to provide effective representation of the state and its uncertainty. Consider covariance analysis techniques provide a method to precompute a process noise covariance profile along a reference trajectory using known model parameter uncertainties. The process noise covariance profile allows significantly improved state estimation and uncertainty representation over the traditional formulation. As a result, estimation performance on par with the consider filter is achieved for trajectories near the reference trajectory without the additional computational cost of the consider filter. The new formulation also has the potential to significantly reduce the trial-and-error tuning currently required of navigation analysts. A linear estimation problem as described in several previous consider covariance analysis studies is used to demonstrate the effectiveness of the precomputed process noise covariance, as well as a nonlinear descent scenario at the asteroid Bennu with optical navigation.

  11. Cross-population myelination covariance of human cerebral cortex.

    Ma, Zhiwei; Zhang, Nanyin

    2017-09-01

    Cross-population covariance of brain morphometric quantities provides a measure of interareal connectivity, as it is believed to be determined by the coordinated neurodevelopment of connected brain regions. Although useful, structural covariance analysis predominantly employed bulky morphological measures with mixed compartments, whereas studies of the structural covariance of any specific subdivisions such as myelin are rare. Characterizing myelination covariance is of interest, as it will reveal connectivity patterns determined by coordinated development of myeloarchitecture between brain regions. Using myelin content MRI maps from the Human Connectome Project, here we showed that the cortical myelination covariance was highly reproducible, and exhibited a brain organization similar to that previously revealed by other connectivity measures. Additionally, the myelination covariance network shared common topological features of human brain networks such as small-worldness. Furthermore, we found that the correlation between myelination covariance and resting-state functional connectivity (RSFC) was uniform within each resting-state network (RSN), but could considerably vary across RSNs. Interestingly, this myelination covariance-RSFC correlation was appreciably stronger in sensory and motor networks than cognitive and polymodal association networks, possibly due to their different circuitry structures. This study has established a new brain connectivity measure specifically related to axons, and this measure can be valuable to investigating coordinated myeloarchitecture development. Hum Brain Mapp 38:4730-4743, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. HIGH DIMENSIONAL COVARIANCE MATRIX ESTIMATION IN APPROXIMATE FACTOR MODELS.

    Fan, Jianqing; Liao, Yuan; Mincheva, Martina

    2011-01-01

    The variance covariance matrix plays a central role in the inferential theories of high dimensional factor models in finance and economics. Popular regularization methods of directly exploiting sparsity are not directly applicable to many financial problems. Classical methods of estimating the covariance matrices are based on the strict factor models, assuming independent idiosyncratic components. This assumption, however, is restrictive in practical applications. By assuming sparse error covariance matrix, we allow the presence of the cross-sectional correlation even after taking out common factors, and it enables us to combine the merits of both methods. We estimate the sparse covariance using the adaptive thresholding technique as in Cai and Liu (2011), taking into account the fact that direct observations of the idiosyncratic components are unavailable. The impact of high dimensionality on the covariance matrix estimation based on the factor structure is then studied.

  13. Covariate-adjusted measures of discrimination for survival data

    White, Ian R; Rapsomaniki, Eleni; Frikke-Schmidt, Ruth

    2015-01-01

    by the study design (e.g. age and sex) influence discrimination and can make it difficult to compare model discrimination between studies. Although covariate adjustment is a standard procedure for quantifying disease-risk factor associations, there are no covariate adjustment methods for discrimination...... statistics in censored survival data. OBJECTIVE: To develop extensions of the C-index and D-index that describe the prognostic ability of a model adjusted for one or more covariate(s). METHOD: We define a covariate-adjusted C-index and D-index for censored survival data, propose several estimators......, and investigate their performance in simulation studies and in data from a large individual participant data meta-analysis, the Emerging Risk Factors Collaboration. RESULTS: The proposed methods perform well in simulations. In the Emerging Risk Factors Collaboration data, the age-adjusted C-index and D-index were...

  14. Parametric Covariance Model for Horizon-Based Optical Navigation

    Hikes, Jacob; Liounis, Andrew J.; Christian, John A.

    2016-01-01

    This Note presents an entirely parametric version of the covariance for horizon-based optical navigation measurements. The covariance can be written as a function of only the spacecraft position, two sensor design parameters, the illumination direction, the size of the observed planet, the size of the lit arc to be used, and the total number of observed horizon points. As a result, one may now more clearly understand the sensitivity of horizon-based optical navigation performance as a function of these key design parameters, which is insight that was obscured in previous (and nonparametric) versions of the covariance. Finally, the new parametric covariance is shown to agree with both the nonparametric analytic covariance and results from a Monte Carlo analysis.

  15. Cortical Dysconnectivity Measured by Structural Covariance Is Associated With the Presence of Psychotic Symptoms in 22q11.2 Deletion Syndrome.

    Sandini, Corrado; Scariati, Elisa; Padula, Maria Carmela; Schneider, Maude; Schaer, Marie; Van De Ville, Dimitri; Eliez, Stephan

    2018-05-01

    22q11.2 deletion syndrome (22q11DS) is the third-largest known genetic risk factor for the development of psychosis. Dysconnectivity has consistently been implicated in the physiopathology of psychosis. Structural covariance of cortical morphology is a method of exploring connectivity among brain regions that to date has not been employed in 22q11DS. In the present study we employed structural covariance of cortical thickness to explore connectivity alterations in a group of 108 patients with 22q11DS compared with 96 control subjects. We subsequently divided patients into two subgroups of 31 subjects each according to the presence of attenuated psychotic symptoms. FreeSurfer software was used to obtain the mean cortical thickness in 148 brain regions from T1-weighted 3T images. For each population we reconstructed a brain graph using Pearson correlation between the average thickness of each couple of brain regions, which we characterized in terms of mean correlation strength and in terms of network architecture using graph theory. Patients with 22q11DS presented increased mean correlation strength, but there was no difference in global architecture compared with control subjects. However, symptomatic patients presented increased mean correlation strength coupled with increased segregation and decreased integration compared with both control subjects and nonsymptomatic patients. They also presented increased centrality for a cluster of anterior cingulate and dorsomedial prefrontal regions. These results confirm the importance of cortical dysconnectivity in the physiopathology of psychosis. Moreover they support the significance of aberrant anterior cingulate connectivity. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Covariant path integrals on hyperbolic surfaces

    Schaefer, J.

    1997-01-01

    DeWitt close-quote s covariant formulation of path integration [B. De Witt, open-quotes Dynamical theory in curved spaces. I. A review of the classical and quantum action principles,close quotes Rev. Mod. Phys. 29, 377 endash 397 (1957)] has two practical advantages over the traditional methods of open-quotes lattice approximations;close quotes there is no ordering problem, and classical symmetries are manifestly preserved at the quantum level. Applying the spectral theorem for unbounded self-adjoint operators, we provide a rigorous proof of the convergence of certain path integrals on Riemann surfaces of constant curvature -1. The Pauli endash DeWitt curvature correction term arises, as in DeWitt close-quote s work. Introducing a Fuchsian group Γ of the first kind, and a continuous, bounded, Γ-automorphic potential V, we obtain a Feynman endash Kac formula for the automorphic Schroedinger equation on the Riemann surface Γ backslash H. We analyze the Wick rotation and prove the strong convergence of the so-called Feynman maps [K. D. Elworthy, Path Integration on Manifolds, Mathematical Aspects of Superspace, edited by Seifert, Clarke, and Rosenblum (Reidel, Boston, 1983), pp. 47 endash 90] on a dense set of states. Finally, we give a new proof of some results in C. Grosche and F. Steiner, open-quotes The path integral on the Poincare upper half plane and for Liouville quantum mechanics,close quotes Phys. Lett. A 123, 319 endash 328 (1987). copyright 1997 American Institute of Physics

  17. Schwinger mechanism in linear covariant gauges

    Aguilar, A. C.; Binosi, D.; Papavassiliou, J.

    2017-02-01

    In this work we explore the applicability of a special gluon mass generating mechanism in the context of the linear covariant gauges. In particular, the implementation of the Schwinger mechanism in pure Yang-Mills theories hinges crucially on the inclusion of massless bound-state excitations in the fundamental nonperturbative vertices of the theory. The dynamical formation of such excitations is controlled by a homogeneous linear Bethe-Salpeter equation, whose nontrivial solutions have been studied only in the Landau gauge. Here, the form of this integral equation is derived for general values of the gauge-fixing parameter, under a number of simplifying assumptions that reduce the degree of technical complexity. The kernel of this equation consists of fully dressed gluon propagators, for which recent lattice data are used as input, and of three-gluon vertices dressed by a single form factor, which is modeled by means of certain physically motivated Ansätze. The gauge-dependent terms contributing to this kernel impose considerable restrictions on the infrared behavior of the vertex form factor; specifically, only infrared finite Ansätze are compatible with the existence of nontrivial solutions. When such Ansätze are employed, the numerical study of the integral equation reveals a continuity in the type of solutions as one varies the gauge-fixing parameter, indicating a smooth departure from the Landau gauge. Instead, the logarithmically divergent form factor displaying the characteristic "zero crossing," while perfectly consistent in the Landau gauge, has to undergo a dramatic qualitative transformation away from it, in order to yield acceptable solutions. The possible implications of these results are briefly discussed.

  18. Smectite alteration

    Anderson, D.M.

    1984-11-01

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  19. Impact of the 235U covariance data in benchmark calculations

    Leal, Luiz; Mueller, Don; Arbanas, Goran; Wiarda, Dorothea; Derrien, Herve

    2008-01-01

    The error estimation for calculated quantities relies on nuclear data uncertainty information available in the basic nuclear data libraries such as the U.S. Evaluated Nuclear Data File (ENDF/B). The uncertainty files (covariance matrices) in the ENDF/B library are generally obtained from analysis of experimental data. In the resonance region, the computer code SAMMY is used for analyses of experimental data and generation of resonance parameters. In addition to resonance parameters evaluation, SAMMY also generates resonance parameter covariance matrices (RPCM). SAMMY uses the generalized least-squares formalism (Bayes' method) together with the resonance formalism (R-matrix theory) for analysis of experimental data. Two approaches are available for creation of resonance-parameter covariance data. (1) During the data-evaluation process, SAMMY generates both a set of resonance parameters that fit the experimental data and the associated resonance-parameter covariance matrix. (2) For existing resonance-parameter evaluations for which no resonance-parameter covariance data are available, SAMMY can retroactively create a resonance-parameter covariance matrix. The retroactive method was used to generate covariance data for 235 U. The resulting 235 U covariance matrix was then used as input to the PUFF-IV code, which processed the covariance data into multigroup form, and to the TSUNAMI code, which calculated the uncertainty in the multiplication factor due to uncertainty in the experimental cross sections. The objective of this work is to demonstrate the use of the 235 U covariance data in calculations of critical benchmark systems. (authors)

  20. A New Approach for Nuclear Data Covariance and Sensitivity Generation

    Leal, L.C.; Larson, N.M.; Derrien, H.; Kawano, T.; Chadwick, M.B.

    2005-01-01

    Covariance data are required to correctly assess uncertainties in design parameters in nuclear applications. The error estimation of calculated quantities relies on the nuclear data uncertainty information available in the basic nuclear data libraries, such as the U.S. Evaluated Nuclear Data File, ENDF/B. The uncertainty files in the ENDF/B library are obtained from the analysis of experimental data and are stored as variance and covariance data. The computer code SAMMY is used in the analysis of the experimental data in the resolved and unresolved resonance energy regions. The data fitting of cross sections is based on generalized least-squares formalism (Bayes' theory) together with the resonance formalism described by R-matrix theory. Two approaches are used in SAMMY for the generation of resonance-parameter covariance data. In the evaluation process SAMMY generates a set of resonance parameters that fit the data, and, in addition, it also provides the resonance-parameter covariances. For existing resonance-parameter evaluations where no resonance-parameter covariance data are available, the alternative is to use an approach called the 'retroactive' resonance-parameter covariance generation. In the high-energy region the methodology for generating covariance data consists of least-squares fitting and model parameter adjustment. The least-squares fitting method calculates covariances directly from experimental data. The parameter adjustment method employs a nuclear model calculation such as the optical model and the Hauser-Feshbach model, and estimates a covariance for the nuclear model parameters. In this paper we describe the application of the retroactive method and the parameter adjustment method to generate covariance data for the gadolinium isotopes