Modernization’s Doppelgänger

This is the author accepted manuscript. The final version is available from Cambridge University Press via http://dx.doi.org/10.1017/S147924431500041

Simulation of Real-Time Scheduling with Various Execution Time Models

Presented during the Work-in-Progress session (WiP session)International audienceIn this paper, we present SimSo, a simulator that aims at facilitating the design of experimental evaluations for real-time scheduling algorithms. Currently, more than twenty-five algorithms were implemented. Special attention is paid to the execution time model of tasks. We show that the worst-case execution time for experimental simulation can introduce a bias in evaluation and we discuss as a work in progress how cache effects could be taken into consideration in the simulation

3D advanced integration technology for heterogeneous systems

International audience3D integration technology is nowadays mature enough, offering today further system integration using heterogeneous technologies, with already many different industrial successes (Imagers, 2.5D Interposers, 3D Memory Cube, etc.). CEA-LETI has been developing for a decade 3D integration, and have pursued research in both directions: developing advanced 3D technology bricks (TSVs, µ-bumps, Hybrid Bonding, etc), and designing advanced 3D circuits as pioneer prototypes. In this paper, a short overview of some recent advanced 3D technology results is presented, including some latest 3D circuit's description

Localization of striatal excitatory amino acid binding site subtypes to striatonigral projection neurons

Quantitative autoradiography was used to examine the cellular localization of excitatory amino acid binding sites in the striatum following selective lesion of striatonigral projection neurons. Degeneration of striatonigral neurons was induced unilaterally by injection of the suicide transport toxin, volkensin, into the left substantia nigra. Twelve days following nigral volkensin injection there was a reduction of all excitatory amino acid binding site subtypes in the striatum ipsilateral to the injected nigra. The reduction in (NMDA) binding sites was significantly greater than the loss of -[alpha]-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA), kainate and metabotropic binding. These results indicate that there are NMDA, AMPA, metabotropic and kainate binding sites on striatonigral projection neurons and suggest that the NMDA subtype may be selectively enriched on striatonigral neurons.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29784/1/0000123.pd

Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes

A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD65. Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD65 autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD65, but not with control antigens, compared with placebo subjects. GAD65-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD65 enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD65-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD65 immunity

Characteristics of GADA in Type 1 Diabetes following Immunomodulation with GAD65

Type 1 diabetes (T1D) is a serious autoimmune disease which increases worldwide and affects children at a young age, but there still is no cure available. Clinical intervention trials in recent onset T1D patients are therefore very important, since even a modest preservation of β-cell function has proven to reduce end-organ complications. Glutamic acid decarboxylase 65 (GAD65) is one of the major antigens in T1D, to which autoantibodies (GADA) are formed. Immunomodulation with aluminum-formulated GAD65 (GAD-alum) has been considered both in the prevention and intervention of T1D. In a phase II trial using GADalum we showed clinical benefits in C-peptide preservation, but unfortunately a following larger European phase III trial failed to reach primary end-point. The general aim of this thesis was to study the characteristics and phenotypes of GADA following immunomodulation with GAD-alum in T1D patients during a phase II and III trial. In the phase II trial, a transient increase of the GADA IgG3 and IgG4 subclasses, and a decrease in IgG1 was detected as part of the treatment-induced GADA levels after 2 GADalum doses, a result interpreted to be T helper (Th) 2-associated. This Th2-associated immune response was also observed, in parallel to increased GADA levels, during the following phase III trial including a larger group of patients. However, enhanced Th2-like IgG subclass distribution, reflected as increased IgG4 frequency, was in contrast only observed in the group treated with 4 doses of GAD-alum. In addition, the GADA fold-change was associated with in vitro GAD65-stimulated cytokine secretion, but only in patients receiving 2 GAD-alum doses. Furthermore, a 4-year follow-up of the phase II trial showed that the effect of GAD-alum treatment was long-lasting as GADA titers remained elevated. Even though the phase III trial did not reach primary end-point, and was closed after 15 months, preservation of β-cell function was observed in the small sub-group of Swedish patients receiving 2 GAD-alum doses that completed the 30 months trial-period. During the trials, concerns were raised whether the elevated GADA titers might induce Stiff person syndrome (SPS), a disease affecting the nervous system, but in vitro analysis of GADA phenotypes showed that the GAD65-enzyme activity and GADA epitope distribution differed from that detected in SPS patients. Continued research to clarify how immunomodulation with autoantigens affects immune responses and also to identify which patients are suitable for treatment, is crucial for optimizing future T1D intervention- and prevention trials

Étude et évaluation des politiques d'ordonnancement temps réel multiprocesseur

Numerous algorithms have been proposed to address the scheduling of real-time tasks for multiprocessor architectures. Yet, new scheduling algorithms have been defined very recently. Therefore, and without any guarantee of completeness, we have identified more than fifty of them. This large diversity makes the comparison of their behavior and performance difficult. This research aims at allowing the study and the evaluation of key scheduling algorithms. The first contribution is SimSo, a new simulation tool dedicated to the evaluation of scheduling algorithms. Using this tool, we were able to compare the performance of twenty algorithms. The second contribution is the consideration, in the simulation, of temporal overheads related to the execution of the scheduler and the impact of memory caches on the computation time of the jobs. This is done by the introduction of statistical models evaluating the cache miss ratios.De multiples algorithmes ont été proposés pour traiter de l’ordonnancement de tâches temps réel dans un contexte multiprocesseur. Encore très récemment de nouvelles politiques ont été définies. Ainsi, sans garantie d’exhaustivité, nous en avons recensé plus d’une cinquantaine. Cette grande diversité rend difficile une analyse comparée de leurs comportements et performances. L’objectif de ce travail de thèse est de permettre l’étude et l’évaluation des principales politiques d’ordonnancement existantes. La première contribution est SimSo, un nouvel outil de simulation dédié à l’évaluation des politiques. Grâce à cet outil, nous avons pu comparer les performances d’une vingtaine d’algorithmes. La seconde contribution est la prise en compte, dans la simulation, des surcoûts temporels liés à l’exécution du code de l’ordonnanceur et à l’influence des mémoires caches sur la durée d’exécution des travaux par l’introduction de modèles statistiques évaluant les échecs d’accès à ces mémoires