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 & Finite element method. The organization has 2717 authors who have published 5585 publications receiving 175925 citations.

Chemical modification of coumarin dimer and HIV-1 integrase inhibitory activity.

Abstract: A systematic series of chemically modified coumarin dimmers has been synthesized and tested for their inhibitory activity against HIV-1 integrase. We observed that modified coumarin dimmers containing hydrophobic moiety on the linker display potent inhibitory activities.

An intensity similarity measure in low-light conditions

Abstract: In low-light conditions, it is known that Poisson noise and quantization noise become dominant sources of noise. While intensity difference is usually measured by Euclidean distance, it often breaks down due to an unnegligible amount of uncertainty in observations caused by noise. In this paper, we develop a new noise model based upon Poisson noise and quantization noise. We then propose a new intensity similarity function built upon the proposed noise model. The similarity measure is derived by maximum likelihood estimation based on the nature of Poisson noise and quantization process in digital imaging systems, and it deals with the uncertainty embedded in observations. The proposed intensity similarity measure is useful in many computer vision applications which involve intensity differencing, e.g., block matching, optical flow, and image alignment. We verified the correctness of the proposed noise model by comparisons with real-world noise data and confirmed superior robustness of the proposed similarity measure compared with the standard Euclidean norm.

Higher-Order Averaging, Formal Series and Numerical Integration I: B-series

Abstract: We show how B-series may be used to derive in a systematic way the analytical expressions of the high-order stroboscopic averaged equations that approximate the slow dynamics of highly oscillatory systems. For first-order systems we give explicitly the form of the averaged systems with $\mathcal{O}(\epsilon^{j})$errors, j=1,2,3 (2π e denotes the period of the fast oscillations). For second-order systems with large $\mathcal{O}(\epsilon^{-1})$forces, we give the explicit form of the averaged systems with $\mathcal{O}(\epsilon^{j})$errors, j=1,2. A variant of the Fermi–Pasta–Ulam model and the inverted Kapitsa pendulum are used as illustrations. For the former it is shown that our approach establishes the adiabatic invariance of the oscillatory energy. Finally we use B-series to analyze multiscale numerical integrators that implement the method of averaging. We construct integrators that are able to approximate not only the simplest, lowest-order averaged equation but also its high-order counterparts.

New raltegravir resistance pathways induce broad cross-resistance to all currently used integrase inhibitors

Abstract: OBJECTIVES: The possibility of replacing raltegravir or elvitegravir with dolutegravir in heavily treatment-experienced patients failing on raltegravir/elvitegravir has been evaluated in VIKING trials. All studied patients failed by the most common pathways, Y143, Q148 and N155, and dolutegravir demonstrated efficacy except for Q148 viruses. The aim of this study was to explore, in the same way, the behaviour of dolutegravir in comparison with raltegravir and elvitegravir against the atypical resistance integrase profiles, G118R and F121Y, described in HIV-1 patients failing on raltegravir therapy. METHODS: The behaviour of integrases with mutations G118R and F121Y towards raltegravir, elvitegravir and dolutegravir was analysed by evaluating phenotypic susceptibility and by means of in silico techniques (investigating binding affinities and the stabilization of the inhibitors in terms of their hydrogen bond network). RESULTS: The phenotypic analysis of G118R and F121Y showed high resistance to raltegravir, elvitegravir and dolutegravir with a fold change >100 when the clinically derived integrase was used, and resistance was also seen when mutations were tested alone in an NL43 backbone, but more often with a lower fold change. In silico, results showed that G118R and F121Y enzymes were associated with reduced binding affinities to each of the inhibitors and with a decreased number of hydrogen bonds compared with the wild-type complexes. CONCLUSIONS: This study showed that G118R and F121Y mutations, rarely described in patients failing on raltegravir, induced broad cross-resistance to all currently used integrase inhibitors. These results are in accordance with our thermodynamic and geometric analysis indicating decreased stability compared with the wild-type complexes.