Ordonnancement parallèle de DAGs sous contraintes mémoire

Scientific workflows are frequently modeled as Directed Acyclic Graphs (DAG) oftasks, which represent computational modules and their dependencies, in the form of dataproduced by a task and used by another one. This formulation allows the use of runtime sys-tems which dynamically allocate tasks onto the resources of increasingly complex and hetero-geneous computing platforms. However, for some workflows, such a dynamic schedule mayrun out of memory by exposing too much parallelism. This paper focuses on the problem oftransforming such a DAG to prevent memory shortage, and concentrates on shared memoryplatforms. We first propose a simple model of DAG which is expressive enough to emulate com-plex memory behaviors. We then exhibit a polynomial-time algorithm that computes the max-imum peak memory of a DAG, that is, the maximum memory needed by any parallel schedule.We consider the problem of reducing this maximum peak memory to make it smaller than agiven bound by adding new fictitious edges, while trying to minimize the critical path of thegraph. After proving this problem NP-complete, we provide an ILP solution as well as severalheuristic strategies that are thoroughly compared by simulation on synthetic DAGs modelingactual computational workflows. We show that on most instances, we are able to decrease themaximum peak memory at the cost of a small increase in the critical path, thus with little im-pact on quality of the final parallel schedule.Les applications de calcul scientifique sont souvent modélisées pardes graphes de tâches orientés acycliques (DAG), qui représentent les tâchesde calcul et leurs dépendances, sous la forme de données produites par unetâche et utilisées par une autre. Cette formulation permet l’utilisation d’APIqui allouent dynamiquement les tâches sur les ressources de plateformes decalcul hétérogènes de plus en plus complexes. Cependant, pour certaines ap-plications, un tel ordonnancement dynamique peut manquer de mémoire enexploitant trop de parallélisme. Cet article porte sur le problème consistant àtransformer un tel DAG pour empêcher toute pénurie de mémoire, en se con-centrant sur les plateformes à mémoire partagée. On propose tout d’abord unmodèle simple de graphe qui est assez expressif pour émuler des comporte-ments mémoires complexes. On expose ensuite un algorithme polynomial quicalcule le pic mémoire maximum d’un DAG, qui représente la mémoire maxi-male requise par tout ordonnancement parallèle. On considère ensuite le prob-lème consistant à réduire ce pic mémoire maximal pour qu’il devienne plus pe-tit qu’une borne donnée en rajoutant des arêtes fictives, tout en essayant deminimiser le chemin critique du graphe. Après avoir prouvé ce problème NP-complet, on fournit un programme linéaire en nombres entiers le résolvant,ainsi que plusieurs stratégies heuristiques qui sont minitieusement comparées-sur des graphes synthétiques modélisant des applications de calcul réelles. Onmontre que sur la plupart des instances, on arrive à diminuer le pic mémoiremaximal, au prix d’une légère augmentation du chemin critique, et donc avecpeu d’impact sur la qualité de l’ordonnancement parallèle final

Spinal Inhibition of GABAB Receptors by the Extracellular Matrix Protein Fibulin-2 in Neuropathic Rats

In the central nervous system, the inhibitory GABAB receptor is the archetype of heterodimeric G protein-coupled receptors (GPCRs). Receptor interaction with partner proteins has emerged as a novel mechanism to alter GPCR signaling in pathophysiological conditions. We propose here that GABAB activity is inhibited through the specific binding of fibulin-2, an extracellular matrix protein, to the B1a subunit in a rat model of neuropathic pain. We demonstrate that fibulin-2 hampers GABAB activation, presumably through decreasing agonist-induced conformational changes. Fibulin-2 regulates the GABAB-mediated presynaptic inhibition of neurotransmitter release and weakens the GABAB-mediated inhibitory effect in neuronal cell culture. In the dorsal spinal cord of neuropathic rats, fibulin-2 is overexpressed and colocalized with B1a. Fibulin-2 may thus interact with presynaptic GABAB receptors, including those on nociceptive afferents. By applying anti-fibulin-2 siRNAin vivo, we enhanced the antinociceptive effect of intrathecal baclofen in neuropathic rats, thus demonstrating that fibulin-2 limits the action of GABAB agonistsin vivo. Taken together, our data provide an example of an endogenous regulation of GABAB receptor by extracellular matrix proteins and demonstrate its functional impact on pathophysiological processes of pain sensitization.This work was funded by the ANR ImNet (ANR-07-NEURO015-01). Imaging was performed on the Bordeaux Imaging Center, member of the FranceBioImaging national infrastructure (ANR-10-INBS-04)

Production of Superoxide Anions by Keratinocytes Initiates P. acnes-Induced Inflammation of the Skin

Acne vulgaris is a chronic inflammatory disorder of the sebaceous follicles. Propionibacterium acnes (P. acnes), a gram-positive anareobic bacterium, plays a critical role in the development of these inflammatory lesions. This study aimed at determining whether reactive oxygen species (ROS) are produced by keratinocytes upon P. acnes infection, dissecting the mechanism of this production, and investigating how this phenomenon integrates in the general inflammatory response induced by P. acnes. In our hands, ROS, and especially superoxide anions (O2•−), were rapidly produced by keratinocytes upon stimulation by P. acnes surface proteins. In P. acnes-stimulated keratinocytes, O2•− was produced by NAD(P)H oxidase through activation of the scavenger receptor CD36. O2•− was dismuted by superoxide dismutase to form hydrogen peroxide which was further detoxified into water by the GSH/GPx system. In addition, P. acnes-induced O2•− abrogated P. acnes growth and was involved in keratinocyte lysis through the combination of O2•− with nitric oxide to form peroxynitrites. Finally, retinoic acid derivates, the most efficient anti-acneic drugs, prevent O2•− production, IL-8 release and keratinocyte apoptosis, suggesting the relevance of this pathway in humans

Influence of sex, age, pubertal maturation and body mass index on circulating white blood cell counts in healthy European adolescents—the HELENA study

Percentiles 10th, 25th, 50th, 75th and 90th are presented for circulating white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils and basophils in healthy European adolescents (12.5–17.5 years, n = 405, 48.9 % boys), considering age, sex, puberty and body mass index (BMI). CD3+ (mature T cells), CD4+ (T helper), CD8+ (T cytotoxic), CD16+56+ (natural killer), CD19+ (B cells), CD3+CD45RA+, CD4+CD45RA+, CD8+CD45RA+ (naïve), CD3+CD45RO+, CD4+CD45RO+ and CD8+CD45RO+ (memory) lymphocytes were also analysed by immunophenotyping. Girls presented higher WBC, neutrophil, CD3+CD45RO+ and CD4+CD45RO+ cell counts and CD3+/CD19+ ratio, and lower CD3+CD45RA+ and CD4+CD45RA+ counts than boys. Age was associated with higher neutrophil counts and CD3+/CD19+, and lower CD19+ counts; in boys, with lower CD3+CD45RA+, CD4+CD45RA+ and CD8+CD45RA+ counts as well; in girls, with higher WBC, CD3+CD45RO+ and CD4+CD45RO+ counts. Pubertal maturation in boys was associated with lower WBC and lymphocyte counts; in girls, with higher basophil, CD3+CD45RO+ and CD4+CD45RO+ values. BMI was associated with higher WBC counts; in boys, also with higher lymphocyte counts; in girls, with higher neutrophil, CD4+, CD3+CD45RO+ and CD4+CD45RO+ counts. Conclusion: Our study provides normative values for circulating immune cells in adolescents, highlighting the importance of considering sex, age, pubertal maturation and BMI when establishing reference ranges for WBC in paediatric populations

Spread of Avian Influenza Viruses by Common Teal (Anas crecca) in Europe

Since the recent spread of highly pathogenic (HP) H5N1 subtypes, avian influenza virus (AIV) dispersal has become an increasing focus of research. As for any other bird-borne pathogen, dispersal of these viruses is related to local and migratory movements of their hosts. In this study, we investigated potential AIV spread by Common Teal (Anas crecca) from the Camargue area, in the South of France, across Europe. Based on bird-ring recoveries, local duck population sizes and prevalence of infection with these viruses, we built an individual-based spatially explicit model describing bird movements, both locally (between wintering areas) and at the flyway scale. We investigated the effects of viral excretion duration and inactivation rate in water by simulating AIV spread with varying values for these two parameters. The results indicate that an efficient AIV dispersal in space is possible only for excretion durations longer than 7 days. Virus inactivation rate in the environment appears as a key parameter in the model because it allows local persistence of AIV over several months, the interval between two migratory periods. Virus persistence in water thus represents an important component of contamination risk as ducks migrate along their flyway. Based on the present modelling exercise, we also argue that HP H5N1 AIV is unlikely to be efficiently spread by Common Teal dispersal only

Strategy for the management of diabetic macular edema: the European Vitreo-Retinal Society macular edema study

Objective. To compare the efficacy of different therapies in the treatment of diabetic macular edema (DME). Design. Nonrandomized, multicenter clinical study. Participants. 86 retina specialists from 29 countries provided clinical information on 2,603 patients with macular edema including 870 patients with DME. Methods. Reported data included the type and number of treatment(s) performed, the pre-and posttreatment visual acuities, and other clinical findings.The results were analyzed by the French INSEE (National Institute of Statistics and Economic Studies). Main Outcome Measures. Mean change of visual acuity and mean number of treatments performed. Results.The change in visual acuity over time in response to each treatment was plotted in second order polynomial regression trend lines. Intravitreal triamcinolone monotherapy resulted in some improvement in vision. Treatmentwith threshold or subthreshold grid laser also resulted in minimal vision gain. Anti-VEGF therapy resulted in more significant visual improvement. Treatment with pars plana vitrectomy and internal limiting membrane (ILM) peeling alone resulted in an improvement in vision greater than that observed with anti-VEGF injection alone. In our DME study, treatment with vitrectomy and ILM peeling alone resulted in the better visual improvement compared to other therapies

Récepteurs GABA

Les récepteurs au GABA de type GABAB appartiennent à la famille des récepteurs métabotropiques de classe C. Ce sont des récepteurs inhibiteurs formant des hétérodimères obligatoires. Leur rôle analgésique dans les cornes dorsales de la moelle épinière est connu depuis plus de 25 ans. Toutefois, le Baclofen, agoniste de référence du GABAB, s'avère peu efficace en clinique chez des patients neuropathiques. Il apparaît donc nécessaire de préciser les fonctions du GABAB dans la circuiterie nociceptive, et leur régulation en conditions de douleurs chroniques. Dans cette revue, nous préciserons d'abord la distribution des deux sous-types du récepteur GABAB. Puis, nous envisagerons leurs fonctions pré- et post-synaptiques dans les cornes dorsales de la moelle de rats naïfs. Nous nous intéresserons enfin aux mécanismes qui pourraient conduire à un dysfonctionnement de ce récepteur en conditions neuropathiques

DATA DEPTH FOR MEASURABLE NOISY RANDOM FUNCTIONS

International audienceIn the literature on data depth applicable to random functions it is usually assumed that the trajectories of all the random curves are continuous, known at each point of the domain, and observed exactly. These assumptions turn out to be unrealistic in practice, as the functions are often observed only at a finite grid of time points, and in the presence of measurement errors. In this work, we provide the necessary theoretical background enabling the extension of the statistical methodology based on data depth to measurable (not necessarily continuous) random functions observed within the latter framework. It is shown that even if the random functions are discontin-uous, observed discretely, and contaminated with additive noise, many common depth functionals maintain the fine consistency properties valid in the ideal case of completely observed noiseless functions. For the integrated depth for functions, we provide uniform rates of convergence over the space of integrable functions