p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response.

The human DNA damage response (DDR) triggers profound changes in gene expression, whose nature and regulation remain uncertain. Although certain micro-(mi)RNA species including miR34, miR-18, miR-16 and miR-143 have been implicated in the DDR, there is as yet no comprehensive description of genome-wide changes in the expression of miRNAs triggered by DNA breakage in human cells. We have used next-generation sequencing (NGS), combined with rigorous integrative computational analyses, to describe genome-wide changes in the expression of miRNAs during the human DDR. The changes affect 150 of 1523 miRNAs known in miRBase v18 from 4-24 h after the induction of DNA breakage, in cell-type dependent patterns. The regulatory regions of the most-highly regulated miRNA species are enriched in conserved binding sites for p53. Indeed, genome-wide changes in miRNA expression during the DDR are markedly altered in TP53-/- cells compared to otherwise isogenic controls. The expression levels of certain damage-induced, p53-regulated miRNAs in cancer samples correlate with patient survival. Our work reveals genome-wide and cell type-specific alterations in miRNA expression during the human DDR, which are regulated by the tumor suppressor protein p53. These findings provide a genomic resource to identify new molecules and mechanisms involved in the DDR, and to examine their role in tumor suppression and the clinical outcome of cancer patients

RSAT: regulatory sequence analysis tools

The regulatory sequence analysis tools (RSAT, http://rsat.ulb.ac.be/rsat/) is a software suite that integrates a wide collection of modular tools for the detection of cis-regulatory elements in genome sequences. The suite includes programs for sequence retrieval, pattern discovery, phylogenetic footprint detection, pattern matching, genome scanning and feature map drawing. Random controls can be performed with random gene selections or by generating random sequences according to a variety of background models (Bernoulli, Markov). Beyond the original word-based pattern-discovery tools (oligo-analysis and dyad-analysis), we recently added a battery of tools for matrix-based detection of cis-acting elements, with some original features (adaptive background models, Markov-chain estimation of P-values) that do not exist in other matrix-based scanning tools. The web server offers an intuitive interface, where each program can be accessed either separately or connected to the other tools. In addition, the tools are now available as web services, enabling their integration in programmatic workflows. Genomes are regularly updated from various genome repositories (NCBI and EnsEMBL) and 682 organisms are currently supported. Since 1998, the tools have been used by several hundreds of researchers from all over the world. Several predictions made with RSAT were validated experimentally and published

NeAT: a toolbox for the analysis of biological networks, clusters, classes and pathways

The network analysis tools (NeAT) (http://rsat.ulb.ac.be/neat/) provide a user-friendly web access to a collection of modular tools for the analysis of networks (graphs) and clusters (e.g. microarray clusters, functional classes, etc.). A first set of tools supports basic operations on graphs (comparison between two graphs, neighborhood of a set of input nodes, path finding and graph randomization). Another set of programs makes the connection between networks and clusters (graph-based clustering, cliques discovery and mapping of clusters onto a network). The toolbox also includes programs for detecting significant intersections between clusters/classes (e.g. clusters of co-expression versus functional classes of genes). NeAT are designed to cope with large datasets and provide a flexible toolbox for analyzing biological networks stored in various databases (protein interactions, regulation and metabolism) or obtained from high-throughput experiments (two-hybrid, mass-spectrometry and microarrays). The web interface interconnects the programs in predefined analysis flows, enabling to address a series of questions about networks of interest. Each tool can also be used separately by entering custom data for a specific analysis. NeAT can also be used as web services (SOAP/WSDL interface), in order to design programmatic workflows and integrate them with other available resources

NeAT: a toolbox for the analysis of biological networks, clusters, classes and pathways

The network analysis tools (NeAT) (http://rsat.ulb.ac.be/neat/) provide a user-friendly web access to a collection of modular tools for the analysis of networks (graphs) and clusters (e.g. microarray clusters, functional classes, etc.). A first set of tools supports basic operations on graphs (comparison between two graphs, neighborhood of a set of input nodes, path finding and graph randomization). Another set of programs makes the connection between networks and clusters (graph-based clustering, cliques discovery and mapping of clusters onto a network). The toolbox also includes programs for detecting significant intersections between clusters/classes (e.g. clusters of co-expression versus functional classes of genes). NeAT are designed to cope with large datasets and provide a flexible toolbox for analyzing biological networks stored in various databases (protein interactions, regulation and metabolism) or obtained from high-throughput experiments (two-hybrid, mass-spectrometry and microarrays). The web interface interconnects the programs in predefined analysis flows, enabling to address a series of questions about networks of interest. Each tool can also be used separately by entering custom data for a specific analysis. NeAT can also be used as web services (SOAP/WSDL interface), in order to design programmatic workflows and integrate them with other available resources

The modeling of a tokamak plasma discharge, from first principles to a flight simulator

A newly developed tool to simulate a tokamak full discharge is presented. The tokamak \u27flight simulator\u27 Fenix couples the tokamak control system with a fast and reduced plasma model, which is realistic enough to take into account several of the plasma non-linearities. A distinguishing feature of this modeling tool is that it only requires the pulse schedule (PS) as input to the simulator. The output is a virtual realization of the full discharge, whose time traces can then be used to judge if the PS satisfies control/physics goals or needs to be revised. This tool is envisioned for routine use in the control room before each pulse is performed, but can also be used off-line to correct PS in advance, or to develop and validate reduced models, control schemes for future machines like a commercial reactor, simulating realistic actuators and sensors behavior

Impact of plasma-wall interaction and exhaust on the EU-DEMO design

In the present work, the role of plasma facing components protection in driving the EU-DEMO design will be reviewed, focusing on steady-state and, especially, on transients. This work encompasses both the first wall (FW) as well as the divertor. In fact, while the ITER divertor heat removal technology has been adopted, the ITER FW concept has been shown in the past years to be inadequate for EU-DEMO. This is due to the higher foreseen irradiation damage level, which requires structural materials (like Eurofer) able to withstand more than 5 dpa of neutron damage. This solution, however, limits the tolerable steady-state heat flux to ~1 MW/m2, i.e. a factor 3–4 below the ITER specifications. For this reason, poloidally and toroidally discontinuous protection limiters are implemented in EU-DEMO. Their role consists in reducing the heat load on the FW due to charged particles, during steady state and, more importantly, during planned and off-normal plasma transients. Concerning the divertor configuration, EU-DEMO currently assumes an ITER-like, lower single null (LSN) divertor, with seeded impurities for the dissipation of the power. However, this concept has been shown by numerous simulations in the past years to be marginal during steady-state (where a detached divertor is necessary to maintain the heat flux below the technological limit and to avoid excessive erosion) and unable to withstand some relevant transients, such as large ELMs and accidental loss of detachment. Various concepts, deviating from the ITER design, are currently under investigation to mitigate such risks, for example in-vessel coils for strike point sweeping in case of reattachment, as well as alternative divertor configurations. Finally, a broader discussion on the impact of divertor protection on the overall machine design is presented

Development of a concept and basis for the DEMO diagnostic and control system

An initial concept for the plasma diagnostic and control (D&C) system has been developed as part of European studies towards the development of a demonstration tokamak fusion reactor (DEMO). The main objective is to develop a feasible, integrated concept design of the DEMO D&C system that can provide reliable plasma control and high performance (electricity output) over extended periods of operation. While the fusion power is maximized when operating near to the operational limits of the tokamak, the reliability of operation typically improves when choosing parameters significantly distant from these limits. In addition to these conflicting requirements, the D&C development has to cope with strong adverse effects acting on all in vessel components on DEMO (harsh neutron environment, particle fluxes, temperatures, electromagnetic forces, etc.). Moreover, space allocation and plasma access are constrained by the needs for first wall integrity and optimization of tritium breeding. Taking into account these boundary conditions, the main DEMO plasma control issues have been formulated, and a list of diagnostic systems and channels needed for plasma control has been developed, which were selected for their robustness and the required coverage of control issues. For a validation and refinement of this concept, simulation tools are being refined and applied for equilibrium, kinetic and mode control studies

Consistency of ℓ1\ell_1-Regularized Maximum-Likelihood for Compressive Poisson Regression

We consider Poisson regression with the canonical link function. This regression model is widely used in regression analysis involving count data; one important application in electrical engineering is transmission tomography. In this paper, we establish the variable selection consistency and estimation consistency of the $\ell_1$-regularized maximum-likelihood estimator in this regression model, and characterize the asymptotic sample complexity that ensures consistency even under the compressive sensing setting (or the $n \ll p$ setting in high-dimensional statistics)

Parallel assessment of male reproductive function in workers and wild rats exposed to pesticides in banana plantations in Guadeloupe

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that reproductive abnormalities are increasing in frequency in both human population and among wild fauna. This increase is probably related to exposure to toxic contaminants in the environment. The use of sentinel species to raise alarms relating to human reproductive health has been strongly recommended. However, no simultaneous studies at the same site have been carried out in recent decades to evaluate the utility of wild animals for monitoring human reproductive disorders. We carried out a joint study in Guadeloupe assessing the reproductive function of workers exposed to pesticides in banana plantations and of male wild rats living in these plantations.</p> <p>Methods</p> <p>A cross-sectional study was performed to assess semen quality and reproductive hormones in banana workers and in men working in non-agricultural sectors. These reproductive parameters were also assessed in wild rats captured in the plantations and were compared with those in rats from areas not directly polluted by humans.</p> <p>Results</p> <p>No significant difference in sperm characteristics and/or hormones was found between workers exposed and not exposed to pesticide. By contrast, rats captured in the banana plantations had lower testosterone levels and gonadosomatic indices than control rats.</p> <p>Conclusion</p> <p>Wild rats seem to be more sensitive than humans to the effects of pesticide exposure on reproductive health. We conclude that the concept of sentinel species must be carefully validated as the actual nature of exposure may varies between human and wild species as well as the vulnerable time period of exposure and various ecological factors.</p