Study of the desorption of ethylene oxide fixed on various materials during sterilization by a new procedure

A continuous sterilization process using ethylene oxide was studied in comparison with a classical method in order to evaluate gas retention as a function of time and temperature on polyethylene, PVC, and rubber materials

Description of the Grover algorithm based on geometric considerations

This paper concerns the Grover algorithm that permits to make amplification of quantum states previously tagged by an Oracle. Grover's algorithm allows searches in an unstructure database of n entries finding a marked element with a quadratic speedup. The algorithm requires a predefined number of runs to succeed with probability close to one.This article provides a description of the amplitude amplification quantum algorithm mechanism in a very short computational way, based on tensor products and provides a geometric presentation of the successive system states. All the basis changes are fully described to provide an alternative to the wide spread Grover description based only on matrices and complex tensor computation. Our experiments encompass numerical evaluations of circuit using the Qiskit library of IBM that meet the theoretical consideration

CLIC: An Agent-Based Interactive and Autonomous Piece of Art

International audienceThis work consists of integrating programming paradigms such as multi-agent systems and rule-based reasoning into a multimedia creation and display platform for interactive artistic creation. It has been developed in order to allow artists to build dynamic and interactive exhibitions based on pictures and sounds and featuring self-evolving and autonomous configurations

A GRASPxELS with Depth First Search Split Procedure for the HVRP

Split procedures have been proved to be efficient within global framework optimization for routing problems by splitting giant tour into trips. This is done by generating optimal shortest path within an auxiliary graph built from the giant tour. An efficient application has been introduced for the first time by Lacomme et al. (2001) within a metaheuristic approach to solve the Capacitated Arc Routing Problem (CARP) and second for the Vehicle Routing Problem (VRP) by Prins (2004). In a further step, the Split procedure embedded in metaheuristics has been extended to address more complex routing problems thanks to a heuristic splitting of the giant tour using the generation of labels on the nodes of the auxiliary graph linked to resource management. Lately, Duhamel et al. (2010) defined a new Split family based on a depth first search approach during labels generation in graph. The efficiency of the new split method has been first evaluated in location routing problem with a GRASP metaheuristic. Duhamel et al. (2010) provided full numerical experiments on this topic

Identification of new early markers of the hypersensitive response in Arabidopsis thaliana11The Genbank accession numbers for the sequences reported in this paper are AJ131391 (Athsr2), AJ131392 (Athsr3),AJ243377 (Athsr4), AJ243378 (Athsr5), AJ243379 (Athsr6) and AJ243380 (Athsr7).

AbstractNew molecular markers of the hypersensitive response (HR) of Arabidopsis thaliana to the bacterial pathogen Xanthomonas campestris pv. campestris (X.c.c..) have been identified by differential screening of a cDNA library constructed from suspension cells inoculated by an HR-inducing strain in the presence of cycloheximide. Seven families of genes (called Athsr) have been isolated, show similarities to voltage-dependent anion channels (VDAC) and alternative oxidases, or are novel proteins. Athsr genes have shown to be specifically or preferentially expressed during the HR. These data suggest that Athsr genes might be involved in early events conditioning the establishment of the HR

Mathematical formulations for scheduling jobs on identical parallel machines with family setup times and total weighted completion time minimization

This paper addresses the parallel machine scheduling problem with family dependent setup times and total weighted completion time minimization. In this problem, when two jobs j and k are scheduled consecutively on the same machine, a setup time is performed between the finishing time of j and the starting time of k if and only if j and k belong to different families. The problem is strongly NP-hard and is commonly addressed in the literature by heuristic approaches and by branch-and-bound algorithms. Achieving proven optimal solution is a challenging task even for small size instances. Our contribution is to introduce five novel mixed integer linear programs based on concepts derived from one-commodity, arc-flow and set covering formulations. Numerical experiments on more than 13000 benchmark instances show that one of the arc-flow models and the set covering model are quite efficient, as they provide on average better solutions than state-of-the-art approaches, with shorter computation times, and solve to proven optimality a large number of open instances from the literature

A GRASPxELS with Depth First Search Split Procedure for the HVRP

Split procedures have been proved to be efficient within global framework optimization for routing problems by splitting giant tour into trips. This is done by generating optimal shortest path within an auxiliary graph built from the giant tour. An efficient application has been introduced for the first time by Lacomme et al. (2001) within a metaheuristic approach to solve the Capacitated Arc Routing Problem (CARP) and second for the Vehicle Routing Problem (VRP) by Prins (2004). In a further step, the Split procedure embedded in metaheuristics has been extended to address more complex routing problems thanks to a heuristic splitting of the giant tour using the generation of labels on the nodes of the auxiliary graph linked to resource management. Lately, Duhamel et al. (2010) defined a new Split family based on a depth first search approach during labels generation in graph. The efficiency of the new split method has been first evaluated in location routing problem with a GRASP metaheuristic. Duhamel et al. (2010) provided full numerical experiments on this topic

A bi-objective stochastic approach for stochastic CARP

The Capacitated Arc Routing Problem (CARP) occurs in applications like urban waste collection or winter gritting. It is usually defined in literature on an undirected graph G = (V, E) , with a set V of n nodes and a set E of m edges. A fleet of identical vehicles of capacity Q is based at a depot node. Each edge i has a cost (length) ci and a demand qi (e.g. an amount of waste), and it may be traversed any number of times. The edges with non-zero demands or tasks require service by a vehicle. The goal is to determine a set of vehicle trips (routes) of minimum total cost, such that each trip starts and ends at the depot, each task is serviced by one single trip, and the total demand handled by any vehicle does not exceed Q . To the best of our knowledge the best published method is a memetic algorithm first introduced in 2001. This article provides a new extension of the NSGA II (Non-dominated Sorting Genetic Algorithm) template to comply with the stochastic sight of the CARP. The main contribution is: - to introduce mathematical expression to evaluate both cost and duration of the longest trip and also standard deviation of these two criteria. - to use a NGA-II template to optimize simultaneously the cost and the duration of the longest trip including standard deviation. The numerical experiments managed on the thee well-known benchmark sets of DeArmon, Belenguer and Benavent and Eglese, prove it is possible to obtain robust solutions in four simultaneous criteria in rather short computation times

Contribution du récepteur GPR55 dans la formation des contacts synaptiques

La synaptogenèse est un processus biologique aboutissant à la mise en place d’un réseau de connexions neuronales, par la genèse de synapses. La mise en place de ce réseau de connexions est essentielle au développement du système nerveux central (SNC) et de ses fonctions. Tout comme les autres étapes du développement du SNC, la synaptogenèse est régulée par une multitude de signaux cellulaires, et le système endocannabinoïde en fait partie. Les dérivés du cannabis tel que le Δ-9-tétrahydrocannabinol (THC) et le cannabidiol (CBD) sont capables de traverser la barrière placentaire et de se retrouver dans le lait maternel. Par leur interaction avec le SNC, entre autres, ces phytocannabinoïdes sont capables d’influencer son développement. Le récepteur couplé à une protéine G 55 (GPR55) est catégorisé comme récepteur atypique du système endocannabinoïde, et il est capable d’être antagonisé par le CBD. Il a été prouvé par de précédentes études qu’il est lui aussi impliqué dans le développement du SNC, notamment dans le guidage et la croissance des axones durant les périodes fœtale et périnatale. Dans la littérature, il est souvent rapporté que les signaux impliqués dans le guidage axonal le sont aussi dans la synaptogenèse. C’est pourquoi le présent mémoire vise à examiner le rôle du récepteur GPR55 et l’effet de sa modulation par le CBD dans la formation de contacts synaptiques. Le modèle utilisé pour cette étude est la culture de neurones corticaux issus d’embryons de souris de génotypes gpr55+/+ et gpr55-/-. Pour comprendre le rôle physiologique de GPR55 dans la synaptogenèse nous avons étudié l’effet de la délétion du récepteur GPR55 à deux temps, Day In Vitro (DIV) 9-10 au début de la synaptogenèse, et à DIV14-15 un temps plus avancé. Ensuite pour comprendre comment le CBD est capable d’influencer la formation de contacts synaptiques de manière dépendante ou non de GPR55, les cultures de neurones corticaux de chaque génotype ont été exposées à DIV9 pour 24h à différentes concentrations du CBD (0,3uM ou 0,6uM ou 1uM). Les effets sur la formation de contacts synaptiques ont été étudiés en immunocytochimie, en immunobuvardage et en électrophysiologie de type patch clamp. Les résultats montrent que la délétion de GPR55 entraine à DIV14-15 une augmentation de la densité des contacts synaptiques, mais une réduction de leur aire et de l’expression de la synaptophysine, en affectant l’activité synaptique. L’exposition au CBD 0,6uM et 1uM entrainent de manière dépendante ou partiellement dépendante à GPR55, une augmentation de la densité des contacts synaptiques sans affecter leur aire, l’expression de protéines synaptiques ainsi que l’activité synaptique. La fréquence de décharge des neurones est diminuée de manière dépendante de GPR55 après l’exposition au CBD 1uM. Ces résultats suggèrent que GPR55 pourrait être un signal important pour l’arrêt de la formation de nouvelles synapses et un signal d’induction pour la maturation des synapses existantes.Synaptogenesis is a biological process that leads to the establishment of a network of neuronal connections through the genesis of synapses. The formation of this network of connections is essential for the development of the central nervous system (CNS) and its functions. Like other stages of CNS development, synaptogenesis is regulated by multiple cellular signals, and the endocannabinoid system is part of it. Cannabis derivatives such as Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) can cross the placental barrier and be present in breast milk. Through their interaction with the endocannabinoid system, among others, these phytocannabinoids can influence CNS development. The G protein-coupled receptor 55 (GPR55) is categorized as an atypical receptor of the endocannabinoid system, and it can be antagonized by CBD. Previous studies have shown that GPR55 is also involved in CNS development, particularly in the guidance and growth of axons during fetal and perinatal periods. It is often reported in the literature that the signals involved in axonal guidance are also involved in synaptogenesis. Therefore, this study investigates the role of the GPR55 receptor and the effect of its modulation by CBD in the formation of synaptic contacts. The model used for this study consists of cortical neuron cultures from mouse embryos gpr55+/+ and gpr55-/- . To understand the physiological role of GPR55 in synaptogenesis, we studied the effect of gpr55 deletion at two-time points: Day In Vitro (DIV) 9- 10 at the beginning of synaptogenesis, and DIV14-15 at a later time point. Then, to understand how CBD can influence the formation of synaptic contacts, whether dependent or independent of GPR55, cortical neuron cultures of each genotype were exposed to different concentrations of CBD (0.3µM or 0.6µM or 1µM) at DIV9 for 24 hours. The effects on the formation of synaptic contacts were studied through immunocytochemistry, western blot, and patch clamp electrophysiology. The results show that gpr55 deletion leads to an increase in synaptic contact density at DIV14-15 but a reduction in their area and synaptophysin expression, by affecting synaptic activity. Exposure to 0.6µM and 1µM CBD results in a GPR55-dependent or partially dependent increase in synaptic contact density without affecting their area, expression of synaptic proteins, and synaptic activity. The firing frequency of neurons is decreased in a GPR55- dependent manner after exposure to 1µM CBD. These results suggest that GPR55 could be an important signal for stopping the formation of new synapses and an induction signal for the maturation of existing synapses

Réseaux géniques initiés par NEUROG2 dans la moelle épinière en développement : analyse globale et étude de la régulation de PAX6

Le système nerveux central est un réseau de circuits élaborés formé par des neurones par lesquels circule l'influx nerveux et des cellules de soutien, les cellules gliales. Initialement, la moelle épinière embryonnaire est constituée de cellules souches en prolifération capables de produire tous les types neuraux. Au cours de la neurogenèse une combinaison de signaux va restreindre les potentialités de ces cellules. La différenciation d'une cellule souche en neurone repose sur une séquence stéréotypée d'évènements d'arrêt de prolifération, de spécification et de différenciation des cellules neurales progénitrices. La caractérisation des mécanismes qui régissent ces différents évènements et les coordonnent est cruciale pour comprendre comment à partir d'une cellule souche, l'embryon peut générer la diversité des cellules qui composent le système nerveux central. Les gènes proneuraux sont des acteurs majeurs de la neurogenèse. Ils confèrent aux cellules qui les expriment un destin neuronal et contrôlent la sortie du cycle cellulaire, la spécification et la différenciation en neurone de ces cellules. Un des enjeux majeurs à l'heure actuelle est d'identifier les acteurs moléculaires mis en jeu en aval des proneuraux pour réaliser ces différentes fonctions. Mon travail de thèse a consisté à étudier les événements moléculaires mis en jeu en aval du proneural NEUROG2 dans la moelle épinière en développement. Malgré le rôle prépondérant de NEUROG2 dans la formation des neurones moteurs de la moelle épinière, peu de ses gènes cibles étaient identifiés dans ce tissus. J'ai donc développé une approche à grande échelle pour identifier l'ensemble des gènes de réponse précoce à NEUROG2 dans la moelle épinière. Cette approche m'a permis de caractériser les réseaux géniques mis en jeu pour initier la cascade d'événements moléculaires nécessaires à sa fonction. J'ai notamment montré que NEUROG2 contrôle la sortie du cycle cellulaire des progéniteurs neuraux en régulant négativement l'expression des cyclines spécifiques des phases G1 et S du cycle cellulaire, ce contrôle se faisant en amont de l'activation du CKI p27KIP1. Un deuxième objectif de ma thèse a été d'étudier en détail les mécanismes moléculaires par lesquels NEUROG2 réprime l'expression du facteur de spécification PAX6. Pax6 est un facteur de transcription qui contrôle à la fois la spécification des neurones ventraux et le moment où les neurones se différencient. Le maintien de ce gène dans les précurseurs de neurones empêche leur différenciation car il contrecarre dans ces précurseurs l'activité proneurale de NEUROG2 (Bel-Vialar 2007). Il était établi que Pax6 contrôle positivement l'expression de NEUROG2 dans la partie ventrale du tube neural et que de forts niveaux de NEUROG2 éteignent en retour l'expression de PAX6 dans les précurseurs de neurones. J'ai montré que NEUROG2 agit à la fois sur le transcrit et la protéine PAX6 et que la répression du transcrit Pax6 se fait via l'activation d'un gène intermédiaire X. Pour identifier cet intermédiaire, j'ai testé plusieurs candidats potentiels et à l'heure actuelle le gène PROX1 se présente comme le meilleur candidat. L'ensemble de mes travaux, au-delà de la mise en évidence d'un contrôle de NEUROG2 sur les cyclines des phases G1 et S du cycle cellulaire et de la caractérisation des mécanismes de répression de PAX6, a permis d'identifier un grand nombre de nouveaux gènes, activés en aval de NEUROG2, dont la fonction dans les différentes étapes de neurogenèse reste à élucider.The central nervous system is a complex network formed of neurons that processes and transmits the nerve impulse and of glial cells that maintain homeostasis, form myelin, and provide support and protection for neurons. Initially, the embryonic spinal cord consists of proliferating stem cells capable of producing all the neural cells types and during neurogenesis a combination of signals will progressively restrict the potential of these cells. Neurogenesis involves a stereotyped sequence of events that trigger proliferation arrest, specification and differentiation of neural progenitor cells. The characterization of the mechanisms governing and coordinating these events is crucial to understand how from a pluripotent stem cell, the embryo can generate the diversity of cells that make up the central nervous system. Proneural genes are major players of neurogenesis. They confer cells a neuronal fate and trigger cell cycle arrest, specification and differentiation of neuronal progenitors. A major challenge is now to identify the molecular players involved downstream of proneurals to perform and coordinate these different events. In this context, the aim of my PhD was to identify the gene networks initiated downstream the proneural NEUROG2 in the developing spinal cord. Indeed, despite its important role in motor neurons production, only a handful of NEUROG2 targets genes have been identified in the spinal cord. To fill this gap, I developed a large scale approach to identify the entirety of genes modulated shortly after NEUROG2 activation. This approach allowed me to characterize gene networks that trigger the different aspects of NEUROG2 function. In particular, I showed that NEUROG2 controls cell cycle exit of neuronal precursors by extinguishing the expression of a subset of cyclins that are specific of the G1 and S phases of the cell cycle and that this event takes place upstream of the activation of the CKI p27kip1. A second objective of my thesis was to study in detail the molecular mechanisms by which NEUROG2 represses the expression of the PAX6 gene. PAX6 is a transcription factor that controls both the specification of ventral neurons and the time when neurons differentiate. Maintaining this gene in neural precursors prevents their differentiation because it counteracts NEUROG2 proneural activity in these precursors (Bel Vialar 2007). It was established that PAX6 positively controls the expression of NEUROG2 in the ventral neural tube and that inn turn high levels of NEUROG2 extinguish the expression of PAX6 in neural precursors, hence triggering neuronal differentiation. I showed that NEUROG2 reduce both the transcript and PAX6 protein levels and that the repression of PAX6 transcripts is achieved via the activation of an intermediary gene. To identify this intermediary gene, I tested several potential candidates and at the moment the best candidate left is the PROX1 transcription factor. Altogether my work, beyond the demonstration of a control of NEUROG2 on G1 and S phases cyclins of the cell cycle and the characterization of the mechanisms of PAX6 repression, allowed identifying a large number of new genes, activated downstream of NEUROG2, whose elucidation of function in different stages of neurogenesis will provide important information in the aim of better understanding the neurogenesis process and elaborating new treatments of neuropathologies