Paul Sabatier University

About: Paul Sabatier University is a education organization based out in Toulouse, France. It is known for research contribution in the topics: Population & Catalysis. The organization has 15431 authors who have published 23386 publications receiving 858364 citations.

Non-empirical pseudopotentials for molecular calculations

Abstract: Improved three-parameter atomic pseudopotentials are theoretically determined from lithium to krypton. In view of further molecular calculations, accurate expressions are given for the pseudopotent...

Increased Tolerance to Artemisinin in Plasmodium falciparum Is Mediated by a Quiescence Mechanism

Abstract: Artemisinin (ART)-based combination therapies (ACTs) are the first-line drugs-and often the last treatments-that can effectively cure Plasmodium falciparum infections. Unfortunately, the decreased clinical efficacy of artesunate, one of the major ART derivatives, was recently reported along the Thailand-Cambodia border. Through long-term artemisinin pressure in vitro, we have obtained an ART-tolerant strain that can survive extremely high doses of ART. We showed that drug pressure could induce a subpopulation of ring stages into developmental arrest, which can explain the ART tolerance in P. falciparum. We also observed interesting transcriptomic modifications possibly associated with the acquisition of ART tolerance. These modifications include the overexpression of heat shock and erythrocyte surface proteins and the downexpression of a cell cycle regulator and a DNA biosynthesis protein. This study highlights a new phenomenon in the Plasmodium response to ART that may explain the delayed clearance of parasites after artesunate treatment observed on the Thailand-Cambodia border and that provides important information for achieving a better understanding of the mechanisms of antimalarial resistance.

Singular Kähler-Einstein metrics

Abstract: We study degenerate complex Monge-Ampere equations of the form $(\omega+dd^c\f)^n = e^{t \f}\mu$ where $\omega$ is a big semi-Kahler form on a compact Kahler manifold $X$ of dimension $n$, $t \in \R^+$, and $\mu=f\omega^n$ is a positive measure with density $f\in L^p(X,\omega^n)$, $p>1$. We prove the existence and unicity of continuous $\o$-plurisubharmonic solutions. In case $X$ is projective and $\omega=\psi^*\omega'$, where $\psi:X\to V$ is a proper birational morphism to a normal projective variety, $[\omega']\in NS_{\R} (V)$ is an ample class and $\mu$ has only algebraic singularities, we prove that the solution is smooth in the regular locus of the equation. We use these results to construct singular Kahler-Einstein metrics of non-positive curvature on projective klt pairs, in particular on canonical models of algebraic varieties of general type.

Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase II regimen-finding study.

Abstract: Background: Interleukin-17A has major proinflammatory activity in psoriatic lesional skin. Objectives: Assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-interleukin-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study. Methods: 404 patients were randomised to subcutaneous placebo (67 patients) or one of three secukinumab 150 mg induction regimens: Single (week 0; 66 patients), Early (weeks 0, 1, 2, 4; 133 patients), and Monthly (weeks 0, 4, 8; 138 patients). The primary outcome was ≥75% improvement from baseline Psoriasis Area and Severity Index (PASI) score at week 12. PASI 75 responders from active treatment arms at week 12 were re-randomised to either a fixed-interval (secukinumab 150 mg at weeks 12 and 24; 65 patients) or a treatment-at-start-of-relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; 67 patients). Results: At week 12, Early and Monthly induction regimens resulted in higher PASI 75 response rates versus placebo (54·5% and 42·0% vs. 1·5%; P<0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed-interval regimen (84·6% [n = 55] and 58·5% [n = 38], respectively) versus the start-of-relapse regimen (67·2% [n = 45], P = 0·020 and 20·9% [n = 14], respectively). Fifteen weeks after last study drug administration, <10% of patients in the fixed-interval and start-of-relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection site reactions were reported. Reported cases of neutropaenia were mild-to-moderate (≤grade 2); none were associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long-term safety. Conclusions: Secukinumab shows efficacy for induction and maintenance treatment of moderate-to-severe plaque psoriasis.