École normale supérieure de Cachan

About: École normale supérieure de Cachan is a education organization based out in Cachan, Île-de-France, France. It is known for research contribution in the topics: Decidability & Nonlinear system. The organization has 2717 authors who have published 5585 publications receiving 175925 citations.

Styrylquinolines, Integrase Inhibitors Acting Prior to Integration: a New Mechanism of Action for Anti-Integrase Agents

Abstract: We have previously shown that styrylquinolines (SQLs) are integrase inhibitors in vitro. They compete with the long terminal repeat substrate for integrase. Here, we describe the cellular mode of action of these molecules. We show that SQLs do not interfere with virus entry. In fact, concentrations of up to 20 times the 50% inhibitory concentration did not inhibit cell-to-cell fusion or affect the interaction between GP120 and CD4 in vitro. Moreover, the pseudotype of the retrovirus envelope did not affect drug activity. Quantitative reverse transcription PCR experiments showed that SQLs do not inhibit the entry of the genomic RNA. In contrast, the treatment of human immunodeficiency virus type 1-infected cells with SQLs reduced the amount of the late cDNA, suggesting for the first time that integrase targeting molecules may affect the accumulation of DNA during reverse transcription. The cellular target of SQLs was confirmed by the appearance of mutations in the integrase gene when viruses were grown in the presence of increasing concentrations of SQLs. Finally, these mutations led to SQL-resistant viruses when introduced into the wild-type sequence. In contrast, SQLs were fully active against reverse transcriptase inhibitor- and diketo acid-resistant viruses, positioning SQLs as a second group of anti-integrase compounds.

Inhibition of human immunodeficiency virus type 1 reverse transcriptase, RNase H, and integrase activities by hydroxytropolones.

Abstract: Human immunodeficiency virus type I reverse transcriptase (RT) possesses distinct DNA polymerase and RNase H sites, whereas integrase (IN) uses the same active site to perform 3'-end processing and strand transfer of the proviral DNA. These four enzymatic activities are essential for viral replication and require metal ions. Two Mg2+ ions are present in the RT polymerase site, and one or two Mg2+ ions are required for the catalytic activities of RNase H and IN. We tested the possibility of inhibition of the RT polymerase and RNase H as well as the IN 3'-end processing and transfer activities of purified enzymes by a series of 3,7-dihydroxytropolones designed to target two Mg2+ ions separated by approximately 3.7 angstroms. The RT polymerase and IN 3' processing and strand transfer activities were inhibited at submicromolar concentrations, while the RNase H activity was inhibited in the low micromolar range. In all cases, the lack of inhibition by tropolones and O-methylated 3,7-dihydroxytropolones was consistent with the active molecules binding the metal ions in the active site. In addition, inhibition of the DNA polymerase activity was shown to depend on the Mg2+ concentration. Furthermore, selective inhibitors were identified for several of the activities tested, leaving some potential for design of improved inhibitors. However, all tested compounds exhibited cellular toxicity that presently limits their applications.

Thermoelectric generator placed on the human body: system modeling and energy conversion improvements

Abstract: This paper focuses on the production of electricity using a thermoelectric generator placed on the human body connected to a dc-dc converter. The small difference in temperature between the hot heat source (e.g. the human body, T b = 37 °C) and the cold heat source (e.g. ambient air, T a = 22 °C), associated with a poor quality thermal coupling (mainly with the cold source), leads to a very low temperature gradient at the thermoelectric generator terminals and hence low productivity. Under these use conditions, the present article proposes an analysis of various ways to improve productivity given a surface capture system. Furthermore, we demonstrated, in this particular context, that maximizing the recovered electric power proves to be a different problem from that of maximizing efficiency, e.g. the figure of merit Z . We therefore define a new factor Z E , depending on the physical characteristics of thermoelectric materials, that maximizes electric power in the particular case where the thermal coupling is poor. Finally, this study highlights the benefit of sub-optimization of the power extracted from the thermoelectric generator to further improve efficiency of the overall system. We show that, given the conversion efficiency of the dc-dc converter, the maximum power point of the overall system is no more reached when the output voltage of the thermoelectric generator is equal to half of its electromotive force.

Flatness Is Not a Weakness

Abstract: We propose an extension, called Lp+, of the temporal logic LTL, which enables talking about finitely many register values: the models are infinite words over tuples of integers (resp. real numbers). The formulas of Lp+ are flat: on the left of an until, only atomic formulas or LTL formulas are allowed. We prove, in the spirit of the correspondence between automata and temporal logics, that the models of a Lp+ formula are recognized by a piecewise flat counter machine; for each state q, at most one loop of the machine on q may modify the register values. Emptiness of (piecewise) flat counter machines is decidable (this follows from a result in [9]). It follows that satisfiability and model-checking the negation of a formula are decidable for Lp+. On the other hand, we show that inclusion is undecidable for such languages. This shows that validity and model-checking positive formulas are undecidable.