Genome-wide co-expression analysis in multiple tissues

Expression quantitative trait loci (eQTLs) represent genetic control points of gene expression, and can be categorized as cis- and trans-acting, reflecting local and distant regulation of gene expression respectively. Although there is evidence of co-regulation within clusters of trans-eQTLs, the extent of co-expression patterns and their relationship with the genotypes at eQTLs are not fully understood. We have mapped thousands of cis- and trans-eQTLs in four tissues (fat, kidney, adrenal and left ventricle) in a large panel of rat recombinant inbred (RI) strains. Here we investigate the genome-wide correlation structure in expression levels of eQTL transcripts and underlying genotypes to elucidate the nature of co-regulation within cis- and trans-eQTL datasets. Across the four tissues, we consistently found statistically significant correlations of cis-regulated gene expression to be rare (<0.9% of all pairs tested). Most (>80%) of the observed significant correlations of cis-regulated gene expression are explained by correlation of the underlying genotypes. In comparison, co-expression of trans-regulated gene expression is more common, with significant correlation ranging from 2.9%-14.9% of all pairs of trans-eQTL transcripts. We observed a total of 81 trans-eQTL clusters (hot-spots), defined as consisting of > or =10 eQTLs linked to a common region, with very high levels of correlation between trans-regulated transcripts (77.2-90.2%). Moreover, functional analysis of large trans-eQTL clusters (> or =30 eQTLs) revealed significant functional enrichment among genes comprising 80% of the large clusters. The results of this genome-wide co-expression study show the effects of the eQTL genotypes on the observed patterns of correlation, and suggest that functional relatedness between genes underlying trans-eQTLs is reflected in the degree of co-expression observed in trans-eQTL clusters. Our results demonstrate the power of an integrative, systematic approach to the analysis of a large gene expression dataset to uncover underlying structure, and inform future eQTL studies

Fatigue analysis-based numerical design of stamping tools made of cast iron

This work concerns stress and fatigue analysis of stamping tools made of cast iron with an essentially pearlitic matrix and containing foundry defects. Our approach consists at first, in coupling the stamping numerical processing simulations and structure analysis in order to improve the tool stiffness geometry for minimizing the stress state and optimizing their fatigue lifetime. The method consists in simulating the stamping process by considering the tool as a perfect rigid body. The estimated contact pressure is then used as boundary condition for FEM structure loading analysis of the tool. The result of this analysis is compared with the critical stress limit depending on the automotive model. The acceptance of this test allows calculating the fatigue lifetime of the critical zone by using the S–N curve of corresponding load ratio. If the prescribed tool life requirements are not satisfied, then the critical region of the tool is redesigned and the whole simulation procedures are reactivated. This method is applied for a cast iron EN-GJS-600-3. The stress-failure (S–N) curves for this material is determined at room temperature under push pull loading with different load ratios R0σmin/σmax0−2, R0−1 and R00.1. The effects of the foundry defects are determined by SEM observations of crack initiation sites. Their presence in tested specimens is associated with a reduction of fatigue lifetime by a factor of 2. However, the effect of the load ratio is more important

Kneadings, Symbolic Dynamics and Painting Lorenz Chaos. A Tutorial

A new computational technique based on the symbolic description utilizing kneading invariants is proposed and verified for explorations of dynamical and parametric chaos in a few exemplary systems with the Lorenz attractor. The technique allows for uncovering the stunning complexity and universality of bi-parametric structures and detect their organizing centers - codimension-two T-points and separating saddles in the kneading-based scans of the iconic Lorenz equation from hydrodynamics, a normal model from mathematics, and a laser model from nonlinear optics.Comment: Journal of Bifurcations and Chaos, 201

Cauchy boundaries in linearized gravitational theory

We investigate the numerical stability of Cauchy evolution of linearized gravitational theory in a 3-dimensional bounded domain. Criteria of robust stability are proposed, developed into a testbed and used to study various evolution-boundary algorithms. We construct a standard explicit finite difference code which solves the unconstrained linearized Einstein equations in the 3+1 formulation and measure its stability properties under Dirichlet, Neumann and Sommerfeld boundary conditions. We demonstrate the robust stability of a specific evolution-boundary algorithm under random constraint violating initial data and random boundary data.Comment: 23 pages including 3 figures and 2 tables, revte

'Return to equilibrium' for weakly coupled quantum systems: a simple polymer expansion

Recently, several authors studied small quantum systems weakly coupled to free boson or fermion fields at positive temperature. All the approaches we are aware of employ complex deformations of Liouvillians or Mourre theory (the infinitesimal version of the former). We present an approach based on polymer expansions of statistical mechanics. Despite the fact that our approach is elementary, our results are slightly sharper than those contained in the literature up to now. We show that, whenever the small quantum system is known to admit a Markov approximation (Pauli master equation \emph{aka} Lindblad equation) in the weak coupling limit, and the Markov approximation is exponentially mixing, then the weakly coupled system approaches a unique invariant state that is perturbatively close to its Markov approximation.Comment: 23 pages, v2-->v3: Revised version: The explanatory section 1.7 has changed and Section 3.2 has been made more explici

Norm reasoning services

Norms are used in open Multi-Agent Systems as a formal specification of deontic statements aimed at regulating the actions of agents and the interactions among them. In this paper, we propose a set of services facilitating the development of both non-normative and normative agents for norm-governed MAS. Specifically, we propose to provide agents with norm reasoning services. These services will help agent designers/developers to programme agents that consider norm reasoning without having to implement the needed mechanisms to reason about norms by themselves. This article shows how these services perform as well as the results of the experiments that we conducted to evaluate their performance