Synthèse d'endopéroxydes analogues des facteurs G et évaluation de leurs propriétés antipaludiques

Les peroxydes cycliques tels que les facteurs G présentent des activités antipaludiques contre le Plasmodium falciparum, l'espèce responsable de la majorité des cas de décès dus au paludisme. Dans l'optique de développer de nouveaux antipaludiques dérivés des facteurs G, de nouveaux peroxydes cycliques analogues cyclopropyles du facteur G3, de nouveaux peroxydes tricycliques pontés et des molécules hybrides endoperoxyde-7-chloro-4-aminoquinoléine, ont été synthétisés. Les peroxydes cycliques ont été synthétisés par autoxydation. Cette réaction s'effectue via une addition d'oxygène triplet sur un précurseur diénol. Ces précurseurs sont obtenus par une procédure modifiée de type Knoevenagel en deux étapes à partir des di- et tri-cétones correspondantes. Les analogues cyclopropyles du G3 et les peroxydes tricycliques pontés ont présenté des activités in vitro faibles contre la souche 3D7 sensible à la chloroquine et la souche W2 résistante à la chloroquine de Plasmodium falciparum. Dans le but d'identifier les mécanismes qui ont lieu après le transfert électronique du pont peroxyde O-O et sa rupture homolytique, la réduction par le Fe(II) de l'endoperoxyde méthylé analogue cyclopropyle du facteur G3Me a été étudiée. La recombinaison intramoléculaire et la polymérisation sont les principaux mécanismes observés et peuvent expliquer la faible activité antipaludique de l'analogue cyclopropyle du facteur G3Me. Les molécules hybrides endoperoxyde-7-chloro-4-aminoquinoléine ont été obtenues selon deux voies de synthèse : par autoxydation des précurseurs contenant le motif quinoléine ou par couplage du peroxyde cyclique avec un dérivé 7-chloro-4-aminoquinoléine. Les molécules hybrides ont présenté des activités antipaludiques intéressantes, inférieures au micromolaire. La molécule hybride la plus active, obtenue par couplage, possède des activités antipaludiques de l'ordre de 10 nM.G-factors are cyclic peroxyketals, exhibiting antimalarial activity against Plasmodium falciparum, the species responsible of the majority of deaths due to malaria. In order to develop new antimalarial G-factor derivatives, new cyclic peroxyketals containing cyclopropyl moieties, new bridged tricyclic peroxyketals and endoperoxide-7-chloro-4-aminoquinoline hybrid compounds were synthesized. Cyclic peroxides were prepared by autoxidation. This reaction proceeds via addition of triplet dioxygen on dienol precursor. The precursors were obtained through a modified Knoevenagel type two-step procedure from corresponding cyclic di- and tri-ketones and bicyclic diketones. Endoperoxides with cyclopropyl moieties and bridged endoperoxides showed low in vitro activities against the chloroquine sensitive strain 3D7 and the chloroquine resistant strain W2 of Plasmodium falciparum. In order to understand the mode of action of the methylated endoperoxyde with the cyclopropyl moieties, Fe(II) induced reduction was carried on and mechanisms implicated after the electron transfer in the O-O bond and its homolytic breaking were studied. Self-quenching and polymerization were suggested as being the major mechanisms explaining the low antimalarial activities. Endoperoxide-7-chloro-4-aminoquinoline hybrid compounds were obtained following two methodologies: by autoxidation of precursors containing the aminoquinoline moities or by coupling of the endoperoxide compound with the 7-chloro-4-aminoquinoline compound. The synthesized hybrid compounds exhibited interesting antimalarial activities, lower than the micromolar range. Especially, the most active hybrid compound, obtained by coupling, showed antimalarial activities in the 10 nM range

Two limit cases of Born-Infeld equations

International audienceWe study two limit cases \l \rightarrow \infty and \l \rightarrow 0 in Born-Infeld equations. Here the parameter \l >0 is interpreted as the maximal electric field in the electromagnetic theory and the case \l = 0 corresponds to the string theory. Formal limits are governed by the classical Maxwell equations and pressureless magnetohydrodynamics system, respectively. For studying the limit \l \rightarrow \infty, a new scaling is introduced. We give the relations between these limits and Brenier high and low field limits. Finally, using compensated compactness arguments, the limits are rigorously justified for global entropy solutions in $L^\infty$ in one space dimension, based on derived uniform estimates and techniques for linear Lagrangian systems

Multi-agent deep reinforcement learning based Predictive Maintenance on parallel machines

In the context of Industry 4.0, companies understand the advantages of performing Predictive Maintenance (PdM). However, when moving towards PdM, several considerations must be carefully examined. First, they need to have a sufficient number of production machines and relative fault data to generate maintenance predictions. Second, they need to adopt the right maintenance approach, which, ideally, should self-adapt to the machinery, priorities of the organization, technician skills, but also to be able to deal with uncertainty. Reinforcement learning (RL) is envisioned as a key technique in this regard due to its inherent ability to learn by interacting through trials and errors, but very few RL-based maintenance frameworks have been proposed so far in the literature, or are limited in several respects. This paper proposes a new multi-agent approach that learns a maintenance policy performed by technicians, under the uncertainty of multiple machine failures. This approach comprises RL agents that partially observe the state of each machine to coordinate the decision-making in maintenance scheduling, resulting in the dynamic assignment of maintenance tasks to technicians (with different skills) over a set of machines. Experimental evaluation shows that our RL-based maintenance policy outperforms traditional maintenance policies (incl., corrective and preventive ones) in terms of failure prevention and downtime, improving by ≈75% the overall performance

European fitness landscape for children and adolescents: updated reference values, fitness maps and country rankings based on nearly 8 million test results from 34 countries gathered by the FitBack network

Objectives (1) To develop reference values for health-related fitness in European children and adolescents aged 6–18 years that are the foundation for the web-based, open-access and multilanguage fitness platform (FitBack); (2) to provide comparisons across European countries. Methods This study builds on a previous large fitness reference study in European youth by (1) widening the age demographic, (2) identifying the most recent and representative country-level data and (3) including national data from existing fitness surveillance and monitoring systems. We used the Assessing Levels of PHysical Activity and fitness at population level (ALPHA) test battery as it comprises tests with the highest test–retest reliability, criterion/construct validity and health-related predictive validity: the 20 m shuttle run (cardiorespiratory fitness); handgrip strength and standing long jump (muscular strength); and body height, body mass, body mass index and waist circumference (anthropometry). Percentile values were obtained using the generalised additive models for location, scale and shape method. Results A total of 7 966 693 test results from 34 countries (106 datasets) were used to develop sex-specific and age-specific percentile values. In addition, country-level rankings based on mean percentiles are provided for each fitness test, as well as an overall fitness ranking. Finally, an interactive fitness platform, including individual and group reporting and European fitness maps, is provided and freely available online (www.fitbackeurope.eu). Conclusion This study discusses the major implications of fitness assessment in youth from health, educational and sport perspectives, and how the FitBack reference values and interactive web-based platform contribute to it. Fitness testing can be conducted in school and/or sport settings, and the interpreted results be integrated in the healthcare systems across Europe

European fitness landscape for children and adolescents: updated reference values, fitness maps and country rankings based on nearly 8 million test results from 34 countries gathered by the FitBack network

Objectives (1) To develop reference values for health-related fitness in European children and adolescents aged 6–18 years that are the foundation for the web-based, open-access and multilanguage fitness platform (FitBack); (2) to provide comparisons across European countries. Methods This study builds on a previous large fitness reference study in European youth by (1) widening the age demographic, (2) identifying the most recent and representative country-level data and (3) including national data from existing fitness surveillance and monitoring systems. We used the Assessing Levels of Physical Activity and fitness at population level (ALPHA) test battery as it comprises tests with the highest test–retest reliability, criterion/construct validity and health-related predictive validity: the 20 m shuttle run (cardiorespiratory fitness); handgrip strength and standing long jump (muscular strength); and body height, body mass, body mass index and waist circumference (anthropometry). Percentile values were obtained using the generalised additive models for location, scale and shape method. Results A total of 7 966 693 test results from 34 countries (106 datasets) were used to develop sex-specific and age-specific percentile values. In addition, country-level rankings based on mean percentiles are provided for each fitness test, as well as an overall fitness ranking. Finally, an interactive fitness platform, including individual and group reporting and European fitness maps, is provided and freely available online (www.fitbackeurope.eu)

Synthèse d'endopéroxydes analogues des facteurs G et évaluation de leurs propriétés antipaludiques

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Analyse mathématique des équations de Born-Infeld

Cette thèse est consacrée à l'étude du système de Born-Infeld (BI). Nous étudions deux limites dans ce système. Les limites sont les équations de Maxwell linéaires et le système magnétohydrodynamique sans pression. En utilisant des arguments de compacité par compensation, les limites sont justifiées pour des solutions entropiques globales en une dimension. Nous considérons le système BI sans contraintes différentielles. Ce système est linéairement dégénéré mais non-strictement hyperbolique. Nous prouvons que dans les régions non-strictement hyperboliques, le problème de Riemann admet une solution unique pour des données initiales larges. Le système de BI appartenant à la classe des systèmes riches, non-strictement hyperboliques. Nous nous intéressons au problème de Cauchy pour un système hyperbolique, linéairement dégénéré, de type riche. Nous construisons les formules explicites des solutions régulières et entropiques et nous prouvons l'existence globale de solutions entropiquesCLERMONT FD-BCIU Sci.et Tech. (630142101) / SudocSudocFranceF

Differential temperature sensor with high sensitivity, wide dynamic range and digital offset calibration

The goal of this paper is twofold: first to add together all different causes that can alter the offset of a differential temperature sensor and, second, to present a new differential temperature sensor architecture that can digitally compensate for this behavior and therefore extends the sensor dynamic range. Measurements performed on a 65 nm CMOS differential temperature sensor are presented to illustrate the discussion. As evolution of the state of the art, an automatic calibration procedure and the new sensor topology is presented. With this new topology, not only the thermal offset can be digitally calibrated, but the application field of differential temperature sensors is widened, being now suitable for use in measurements where both wide input range and high differential sensitivity are required.Peer ReviewedPostprint (author's final draft

Entropy solutions for linearly degenerate hyperbolic systems of rich type

International audienc