TANGO: Transparent heterogeneous hardware Architecture deployment for eNergy Gain in Operation

The paper is concerned with the issue of how software systems actually use Heterogeneous Parallel Architectures (HPAs), with the goal of optimizing power consumption on these resources. It argues the need for novel methods and tools to support software developers aiming to optimise power consumption resulting from designing, developing, deploying and running software on HPAs, while maintaining other quality aspects of software to adequate and agreed levels. To do so, a reference architecture to support energy efficiency at application construction, deployment, and operation is discussed, as well as its implementation and evaluation plans.Comment: Part of the Program Transformation for Programmability in Heterogeneous Architectures (PROHA) workshop, Barcelona, Spain, 12th March 2016, 7 pages, LaTeX, 3 PNG figure

Molecular Responses to Photogenotoxic Stress Induced by the Antibiotic Lomefloxacin in Human Skin Cells: From DNA Damage to Apoptosis

Photo-unstable chemicals sometimes behave as phototoxins in skin, inducing untoward clinical side-effects when exposed to sunlight. Some drugs, such as psoralens or fluoroquinolones, can damage genomic DNA, thus increasing the risk of photocarcinogenesis. Here, lomefloxacin, an antibiotic from the fluoroquinolone family known to be involved in skin tumor development in photoexposed mice, was studied using normal human skin cells in culture: fibroblasts, keratinocytes, and Caucasian melanocytes. When treated cells were exposed to simulated solar ultraviolet A (320–400 nm), lomefloxacin induced damage such as strand breaks and pyrimidine dimers in genomic DNA. Lomefloxacin also triggered various stress responses: heme-oxygenase-1 expression in fibroblasts, changes in p53 status as shown by the accumulation of p53 and p21 proteins or the induction of MDM2 and GADD45 genes, and stimulation of melanogenesis by increasing the tyrosinase activity in melanocytes. Lomefloxacin could also lead to apoptosis in keratinocytes exposed to ultraviolet A: caspase-3 was activated and FAS-L gene was induced. Moreover, keratinocytes were shown to be the most sensitive cell type to lomefloxacin phototoxic effects, in spite of the well-established effectiveness of their antioxidant equipment. These data show that the phototoxicity of a given drug can be driven by different mechanisms and that its biologic impact varies according to cell type

Identification of Genes Regulating Gene Targeting by a High-Throughput Screening Approach

Homologous gene targeting (HGT) is a precise but inefficient process for genome engineering. Several methods for increasing its efficiency have been developed, including the use of rare cutting endonucleases. However, there is still room for improvement, as even nuclease-induced HGT may vary in efficiency as a function of the nuclease, target site, and cell type considered. We have developed a high-throughput screening assay for the identification of factors stimulating meganuclease-induced HGT. We used this assay to explore a collection of siRNAs targeting 19,121 human genes. At the end of secondary screening, we had identified 64 genes for which knockdown affected nuclease-induced HGT. Two of the strongest candidates were characterized further. We showed that siRNAs directed against the ATF7IP gene, encoding a protein involved in chromatin remodeling, stimulated HGT by a factor of three to eight, at various loci and in different cell types. This method thus led to the identification of a number of genes, the manipulation of which might increase rates of targeted recombination

Combiner connaissances expertes, hors-ligne, transientes et en ligne pour l'exploration Monte-Carlo

National audienceNous combinons pour de l'exploration Monte-Carlo d'arbres de l'apprentissage arti- RÉSUMÉ. ficiel à 4 échelles de temps : – regret en ligne, via l'utilisation d'algorithmes de bandit et d'estimateurs Monte-Carlo ; – de l'apprentissage transient, via l'utilisation d'estimateur rapide de Q-fonction (RAVE, pour Rapid Action Value Estimate) qui sont appris en ligne et utilisés pour accélérer l'explora- tion mais sont ensuite peu à peu laissés de côté à mesure que des informations plus fines sont disponibles ; – apprentissage hors-ligne, par fouille de données de jeux ; – utilisation de connaissances expertes comme information a priori. L'algorithme obtenu est plus fort que chaque élément séparément. Nous mettons en évidence par ailleurs un dilemne exploration-exploitation dans l'exploration Monte-Carlo d'arbres et obtenons une très forte amélioration par calage des paramètres correspondant. We combine for Monte-Carlo exploration machine learning at four different time ABSTRACT. scales: – online regret, through the use of bandit algorithms and Monte-Carlo estimates; – transient learning, through the use of rapid action value estimates (RAVE) which are learnt online and used for accelerating the exploration and are thereafter neglected; – offline learning, by data mining of datasets of games; – use of expert knowledge coming from the old ages as prior information

Characterization of single chain antibody targets through yeast two hybrid

<p>Abstract</p> <p>Background</p> <p>Due to their unique ability to bind their targets with high fidelity, antibodies are used widely not only in biomedical research, but also in many clinical applications. Recombinant antibodies, including single chain variable fragments (scFv), are gaining momentum because they allow powerful <it>in vitro </it>selection and manipulation without loss of function. Regardless of the ultimate application or type of antibody used, precise understanding of the interaction between the antibody's binding site and its specific target epitope(s) is of great importance. However, such data is frequently difficult to obtain.</p> <p>Results</p> <p>We describe an approach that allows detailed characterization of a given antibody's target(s) using the yeast two-hybrid system. Several recombinant scFv were used as bait and screened against highly complex cDNA libraries. Systematic sequencing of all retained clones and statistical analysis allowed efficient ranking of the prey fragments. Multiple alignment of the obtained cDNA fragments provided a selected interacting domain (SID), efficiently narrowing the epitope-containing region.</p> <p>Interactions between antibodies and their respective targets were characterized for several scFv. For AA2 and ROF7, two conformation-specific sensors that exclusively bind the activated forms of the small GTPases Rab6 and Rab1 respectively, only fragments expressing the entire target protein's core region were retained. This strongly suggested interaction with a non-linear epitope. For two other scFv, TA10 and SF9, which recognize the large proteins giantin and non-muscle myosin IIA, respectively, precise antibody-binding regions within the target were defined. Finally, for some antibodies, secondary targets within and across species could be revealed.</p> <p>Conclusions</p> <p>Our method, utilizing the yeast two-hybrid technology and scFv as bait, is a simple yet powerful approach for the detailed characterization of antibody targets. It allows precise domain mapping for linear epitopes, confirmation of non-linear epitopes for conformational sensors, and detection of secondary binding partners. This approach may thus prove to be an elegant and rapid method for the target characterization of newly obtained scFv antibodies. It may be considered prior to any research application and particularly before any use of such recombinant antibodies in clinical medicine.</p

Indium antimonide photovoltaic cells for near-field thermophotovoltaics

International audienceIndium antimonide photovoltaic cells are specifically designed and fabricated for use in a near-field thermophotovoltaic device demonstrator. The optimum conditions for growing the p-n junction stack of the cell by means of solid-source molecular beam epitaxy are investigated. Then processing of circular micron-sized mesa structures, including passivation of the side walls, is described. The resulting photovoltaic cells, cooled down to around 77 K in order to operate optimally, exhibit excellent performances in the dark and under far-field illumination by thermal sources in the [600-1000] °C temperature range. A short-circuit current beyond 10 µA, open-circuit voltage reaching almost 85 mV, fill factor of 0.64 and electrical power at the maximum power point larger than 0.5 W are measured for the cell with the largest mesa diameter under the highest illumination. These results demonstrate that these photovoltaic cells will be suitable for measuring a near-field enhancement of the generated electrical power

Shigella Effector IpaB-Induced Cholesterol Relocation Disrupts the Golgi Complex and Recycling Network to Inhibit Host Cell Secretion

Shigella infection causes destruction of the human colonic epithelial barrier. The Golgi network and recycling endosomes are essential for maintaining epithelial barrier function. Here we show that Shigella epithelial invasion induces fragmentation of the Golgi complex with consequent inhibition of both secretion and retrograde transport in the infected host cell. Shigella induces tubulation of the Rab11-positive compartment, thereby affecting cell surface receptor recycling. The molecular process underlying the observed damage to the Golgi complex and receptor recycling is a massive redistribution of plasma membrane cholesterol to the sites of Shigella entry. IpaB, a virulence factor of Shigella that is known to bind cholesterol, is necessary and sufficient to induce Golgi fragmentation and reorganization of the recycling compartment. Shigella infection-induced Golgi disorganization was also observed in vivo, suggesting that this mechanism affecting the sorting of cell surface molecules likely contributes to host epithelial barrier disruption associated with Shigella pathogenesis

THBD sequence variants potentially related to recurrent pregnancy loss

Recurrent pregnancy loss (RPL) is a frequently occurring disease, which is classified as idiopathic in more than 50% of cases. THBD, the endothelial cell receptor for thrombin, has been associated with distinct biological processes and considered a coherent RPL-related candidate gene. In the present study, we have sequenced the complete coding region of THBD in 262 patients affected by RPL. Bioinformatics analysis and screening of controls strongly suggested that the THBD-p.Trp153Gly mutation might be related to RPL aetiology. It could be used, after its validation by functional assays, as a molecular marker for diagnostic/prognostic purposes. © 2017 The Author(s)

Sustainable process for adipic acid production from cyclohexene in microemulsion

Adipic acid appears as an intermediate compound for the synthesis of polyamides and preferentially for the production of nylon-6,6 polyamide. It can be synthesized by the oxidation of cyclohexene by hydrogen peroxide in microemulsion media which has the main advantage to lead a better contact between the two phases thus increasing the yield of the reaction. The microemulsion is generated by stearyl dimethyl benzyl ammonium chloride (C18) as a surfactant avoiding the use of harmful organic solvents and phase-transfer catalysts. The reaction is performed under mild conditions (85 °C, 8 h) with sodium tungstate, - a no heavy metal catalyst - leading to the production of adipic acid in high yield (>80%). By recycling the catalyst and the surfactant, the process becomes truly green

Combiner connaissances expertes, hors-ligne, transientes et en ligne pour l'exploration Monte-Carlo

National audienceNous combinons pour de l'exploration Monte-Carlo d'arbres de l'apprentissage arti- RÉSUMÉ. ficiel à 4 échelles de temps : – regret en ligne, via l'utilisation d'algorithmes de bandit et d'estimateurs Monte-Carlo ; – de l'apprentissage transient, via l'utilisation d'estimateur rapide de Q-fonction (RAVE, pour Rapid Action Value Estimate) qui sont appris en ligne et utilisés pour accélérer l'explora- tion mais sont ensuite peu à peu laissés de côté à mesure que des informations plus fines sont disponibles ; – apprentissage hors-ligne, par fouille de données de jeux ; – utilisation de connaissances expertes comme information a priori. L'algorithme obtenu est plus fort que chaque élément séparément. Nous mettons en évidence par ailleurs un dilemne exploration-exploitation dans l'exploration Monte-Carlo d'arbres et obtenons une très forte amélioration par calage des paramètres correspondant. We combine for Monte-Carlo exploration machine learning at four different time ABSTRACT. scales: – online regret, through the use of bandit algorithms and Monte-Carlo estimates; – transient learning, through the use of rapid action value estimates (RAVE) which are learnt online and used for accelerating the exploration and are thereafter neglected; – offline learning, by data mining of datasets of games; – use of expert knowledge coming from the old ages as prior information