An Empirical Bayes Approach for Multiple Tissue eQTL Analysis

Expression quantitative trait loci (eQTL) analyses, which identify genetic markers associated with the expression of a gene, are an important tool in the understanding of diseases in human and other populations. While most eQTL studies to date consider the connection between genetic variation and expression in a single tissue, complex, multi-tissue data sets are now being generated by the GTEx initiative. These data sets have the potential to improve the findings of single tissue analyses by borrowing strength across tissues, and the potential to elucidate the genotypic basis of differences between tissues. In this paper we introduce and study a multivariate hierarchical Bayesian model (MT-eQTL) for multi-tissue eQTL analysis. MT-eQTL directly models the vector of correlations between expression and genotype across tissues. It explicitly captures patterns of variation in the presence or absence of eQTLs, as well as the heterogeneity of effect sizes across tissues. Moreover, the model is applicable to complex designs in which the set of donors can (i) vary from tissue to tissue, and (ii) exhibit incomplete overlap between tissues. The MT-eQTL model is marginally consistent, in the sense that the model for a subset of tissues can be obtained from the full model via marginalization. Fitting of the MT-eQTL model is carried out via empirical Bayes, using an approximate EM algorithm. Inferences concerning eQTL detection and the configuration of eQTLs across tissues are derived from adaptive thresholding of local false discovery rates, and maximum a-posteriori estimation, respectively. We investigate the MT-eQTL model through a simulation study, and rigorously establish the FDR control of the local FDR testing procedure under mild assumptions appropriate for dependent data.Comment: accepted by Biostatistic

Аналіз досвіду транскордонного співробітництва на прикладі євро регіону «Буг». (THE ANALYSIS OF THE EXPERIENCE OF TRANSBOUNDARY COOPERATION BASED ON THE EXAMPLE OF BUG EUROREGION.)

У статті подана загальна характеристика транскордонного співробітництва. Зосереджено увагу на явищі єврорегіонів, а саме Єврорегіону “Буг”. Проаналізовано діяльність даного єврорегіону. (In this work provided a general characteristics of CBC. The emphasis is on the phenomenon of European regions, namely Euroregion “Bug”. The activity of the Euroregion.

In vitro models for liver toxicity testing

Over the years, various liver-derived in vitro model systems have been developed to enable investigation of the potential adverse effects of chemicals and drugs. Liver tissue slices, isolated microsomes, perfused liver, immortalized cell lines, and primary hepatocytes have been used extensively. Immortalized cell lines and primary isolated liver cells are currently the most widely used in vitro models for liver toxicity testing. Limited throughput, loss of viability, and decreases in liver-specific functionality and gene expression are common shortcomings of these models. Recent developments in the field of in vitro hepatotoxicity include three-dimensional tissue constructs and bioartificial livers, co-cultures of various cell types with hepatocytes, and differentiation of stem cells into hepatic lineage-like cells. In an attempt to provide a more physiological environment for cultured liver cells, some of the novel cell culture systems incorporate fluid flow, micro-circulation, and other forms of organotypic microenvironments. Co-cultures aim to preserve liver-specific morphology and functionality beyond those provided by cultures of pure parenchymal cells. Stem cells, both embryonic- and adult tissue-derived, may provide a limitless supply of hepatocytes from multiple individuals to improve reproducibility and enable testing of the individual-specific toxicity. This review describes various traditional and novel in vitro liver models and provides a perspective on the challenges and opportunities afforded by each individual test system.National Institutes of Health (U.S.) (P42 ES005948)National Institutes of Health (U.S.) (R01 ES01524

Co-regulation of primary mouse hepatocyte viability and function by oxygen and matrix

Although oxygen and extracellular matrix cues both influence differentiation state and metabolic function of primary rat and human hepatocytes, relatively little is known about how these factors together regulate behaviors of primary mouse hepatocytes in culture. To determine the effects of pericellular oxygen tension on hepatocellular function, we employed two methods of altering oxygen concentration in the local cellular microenvironment of cells cultured in the presence or absence of an extracellular matrix (Matrigel) supplement. By systematically altering medium depth and gas phase oxygen tension, we created multiple oxygen regimes (hypoxic, normoxic, and hyperoxic) and measured the local oxygen concentrations in the pericellular environment using custom-designed oxygen microprobes. From these measurements of oxygen concentrations, we derived values of oxygen consumption rates under a spectrum of environmental contexts, thus providing the first reported estimates of these values for primary mouse hepatocytes. Oxygen tension and matrix microenvironment were found to synergistically regulate hepatocellular survival and function as assessed using quantitative image analysis for cells stained with vital dyes, and assessment of secretion of albumin. Hepatocellular viability was affected only at strongly hypoxic conditions. Surprisingly, albumin secretion rates were greatest at a moderately supra-physiological oxygen concentration, and this effect was mitigated at still greater supra-physiological concentrations. Matrigel enhanced the effects of oxygen on retention of function. This study underscores the importance of carefully controlling cell density, medium depth, and gas phase oxygen, as the effects of these parameters on local pericellular oxygen tension and subsequent hepatocellular function are profound.National Institutes of Health (U.S.) (Grant P50-GM068762-08)National Institutes of Health (U.S.) (Grant R01-EB010246-04)National Institutes of Health (U.S.) (Grant R01-ES015241)National Institutes of Health (U.S.) (Grant P30-ES002109

Addressing human variability in next-generation human health risk assessments of environmental chemicals

International audienceCharacterizing variability in the extent and nature of responses to environmental exposures is a critical aspect of human health risk assessment. Our goal was to explore how next-generation human health risk assessments may better characterize variability in the context of the conceptual framework for the source-to-outcome continuum. This review was informed by a National Research Council workshop titled 'Biological Factors that Underlie Individual Susceptibility to Environmental Stressors and Their Implications for Decision-Making.' We considered current experimental and in silico approaches, and emerging data streams (such as genetically defined human cells lines, genetically diverse rodent models, human omic profiling, and genome-wide association studies) that are providing new types of information and models relevant for assessing interindividual variability for application to human health risk assessments of environmental chemicals. One challenge for characterizing variability is the wide range of sources of inherent biological variability (e.g., genetic and epigenetic variants) among individuals. A second challenge is that each particular pair of health outcomes and chemical exposures involves combinations of these sources, which may be further compounded by extrinsic factors (e.g., diet, psychosocial stressors, other exogenous chemical exposures). A third challenge is that different decision contexts present distinct needs regarding the identification-and extent of characterization-of interindividual variability in the human population. Despite these inherent challenges, opportunities exist to incorporate evidence from emerging data streams for addressing interindividual variability in a range of decision-making contexts

Представництво Юридичних Осіб В Цивільному Процесі

Entities representation questions in court are considered in the given article as a variety of judicial representation. We mean a type of judicial representation under the statutory representation . It arises up on the basis of the regulations or a legal entity’s other constitutional documents. In this case a member of collective organ of management or other public person represents interests of an organization in court. We should distinguish legal representation from an entity’s activity of the governing body.В даній статті розглядаються питання щодо представництва юридичних осіб в суді як окремого різновиду судового представництва за особливостями підстав його виникнення. Під статутним представництвом слід розуміти вид судового представництва, яке в обов'язковому порядку виникає на підставі ста­туту чи інших установчих документів юридичної особи і передбачає ведення її справ в суді членом колегіального органу управління чи іншою посадовою особою

Вимоги Щодо Особи Судового Представника В Цивільному Процесуальному Законодавстві

This article concerns the question of the requirements to the persons, who can carry out the judicial representative actions. The judicial legislation does not contain a list of persons, who can carry out the judicial representative actions. General requirements to them are: presence of judicial capability; presence of plenary powers; absence of limitations for realization of representative power; absence of conflict of interests; the special requirements is presence of definite status. According to author's opinion current legislation should be added with the legal norms about right for the minor parents to carry out the legal representation of their children, and also about prohibition to carry out the judicial representative power at presence of conflict of interests.В даній статті розглянуті питання про вимоги до осіб, які можуть здійснюва­ти судове представництво. Діюче процесуальне законодавство не містить закрі­пленого переліку осіб, які можуть здійснювати представницькі повноваження. Загальними вимогами щодо процесуальної правосуб'єктності представника є: наявність цивільної процесуальної дієздатності; наявність належно посвідчених повноважень; відсутність встановлених законодавством обмежень щодо здійс­нення судового представництва; відсутність конфлікту інтересів. Спеціальними вимогами щодо процесуальної правосуб'єктності представника, що обов'язкові для здійснення певних видів судового представництва, є наявність в особи пев­ного статусу (адвоката, батьків та ін.). Чинне процесуальне законодавство слід доповнити положеннями щодо права неповнолітніх батьків здійснювати закон­не представництво їхніх дітей, а також заборони бути судовими представниками тим особам, інтереси яких суперечать інтересам, які необхідно представляти

Моделювання та дослідження хаотичної системи Реслера з допомогою програмних середовищ LabView і MultiSim

Introduction. In this paper is presented a theoretical basis of chaotic Rossler system. Modelling of Chaotic Rossler System in LabView. Submitted programming interface that has been developed in LabView software environment. It allows generating and researching chaotic Rossler system. Submitted by time distribution of three chaotic coordinates and spectral analysis. Also submitted values of variables in which generated different period (controlled) attractors of the chaotic Rossler system. The software interface demonstrates masking and decrypt information carrier of the chaotic Rossler system. Modelling of Chaotic Rossler System in MultiSim. Using MultiSim software environment conducted scheme technical analysis circuit of a generator that implements a chaotic Rossler system. Conclusions. Modelled circuit of generator confirming correspondence scheme-technical solution to mathematical apparatus that describing chaotic Rossler system. Keywords: chaos; control; system; Rossler; LabView; MultiSimВ работе представлен программный интерфейс, разработанный в программной среде LabView. Он позволяет генерировать и исследовать хаотическую систему Рёслера. Представлено временное распределение трех хаотических координат и спектральный анализ. Также приведены значения переменных, при которых генерируются разнопериодические (управляемые) хаотические аттракторы системы Рёлера. Созданный программный интерфейс демонстрирует маскировку и расшифровку информационного носителя хаотической системой Рёслера. С помощью программной среды MultiSim проведен схемотехнический анализ генератора, что реализует хаотическую систему Рёслера. Смоделированная схема генератора подтверждает соответствие схемотехнического решения математическому аппарату, что описывает хаотическую систему Рёслера.У роботі представлений програмний інтерфейс, що був розроблений в програмному середовищі LabView. Він дає змогу генерувати та досліджувати хаотичну систему Реслера. Представлено часовий розподіл трьох хаотичних координат та спектральний аналіз. Також приведено значення змінних, при яких генеруються різноперіодні (керовані) хаотичні атрактори системи Реслера. Створений програмний інтерфейс демонструє маскування та розшифрування інформаційного носія хаотичною системою Реслера. За допомогою програмного середовища MultiSim проведено схемотехнічний аналіз генератора, що реалізує хаотичну систему Реслера. Змодельована схема генератора підтверджує відповідність схемотехнічного рішення математичному апарату, що описує хаотичну систему Реслера

Dynamical Analysis and Circuit Design for Malasoma System

In this paper, the Malasoma system based cubic function is presented. This system contains operational amplifiers, resistors, capacitors, multipliers, and voltage sources. The first stage, we analyze the Malasoma model and execute its stability. The phase portraits and bifurcation diagram are used to analyze the dynamic behaviors of the Malasoma model. The proposed circuit was modelled by utilizing NI’s MultiSim software environment. The electronic circuit is realized by using off-the-shelf components. MATLAB and MultiSim simulation results show a good agreement