Nous présentons deux contributions dans le domaine de la programmation parallèle. La première est théorique : nous introduisons l’analyse SIPS, une approche nouvelle pour dénombrer le nombre d’opérations de synchronisation durant l’exécution d’un algorithme parallèle ordonnancé par vol de travail. Basée sur le concept d’horloges logiques, elle nous permet : d’une part de donner de nouvelles majorations de coût en moyenne; d’autre part de concevoir des programmes parallèles plus efficaces par adaptation dynamique de la granularité. La seconde contribution est pragmatique : nous présentons une parallélisation générique d’algorithmes pour la génération déterministe de nombres pseudo-aléatoires, indépendamment du nombre de processus concurrents lors de l’exécution. Alternative à l’utilisation d’un générateur pseudo-aléatoire séquentiel par processus, nous introduisons une API générique, appelée Par-R qui est conçue et analysée grâce à SIPS. Sa caractéristique principale est d’exploiter un générateur séquentiel qui peut “sauter” directement d’un nombre à un autre situé à une distance arbitraire dans la séquence pseudo-aléatoire. Grâce à l’analyse SIPS, nous montrons qu’en moyenne, lors d’une exécution par vol de travail d’un programme très parallèle (dont la profondeur ou chemin critique est très petite devant le travail ou nombre d’opérations), ces opérations de saut sont rares. Par-R est comparé au générateur pseudo-aléatoire DotMix écrit pour Cilk Plus, une extension de C/C++ pour la programmation parallèle par vol de travail. Le surcout théorique de Par-R se compare favorablement au surcoput de DotMix, ce qui apparait aussi expériemntalement. De plus, étant générique, Par-R est indépendant du générateur séquentiel sous-jacent. / Nós apresentamos duas contribuições para a área de programação paralela. A primeira contribuição é teórica: nós introduzimos a análise SIPS, uma nova abordagem para a estimar o número de sincronizações realizadas durante a execução de um algoritmo paralelo. SIPS generaliza o conceito de relógios lógicos para contar o número de sincronizações realizadas por um algoritmo paralelo e é capaz de calcular limites do pior caso mesmo na presença de execuções paralelas não-determinísticas, as quais não são geralmente cobertas por análises no estado-da-arte. Nossa análise nos permite estimar novos limites de pior caso para computações escalonadas pelo popular algoritmo de roubo de tarefas e também projetar programas paralelos e adaptáveis que são mais eficientes. A segunda contribuição é pragmática: nós apresentamos uma estratégia de paralelização eficiente para a geração de números pseudoaleatórios. Como uma alternativa para implementações fixas de componentes de geração aleatória nós introduzimos uma API chamada Par-R, projetada e analisada utilizando-se SIPS. Sua principal idea é o uso da capacidade de um gerador sequencial R de realizar um “pulo” eficiente dentro do fluxo de números gerados; nós os associamos a operações realizadas pelo escalonador por roubo de tarefas, o qual nossa análise baseada em SIPS demonstra ocorrer raramente em média. Par-R é comparado com o gerador paralelo de números pseudoaleatórios DotMix, escrito para a plataforma de multithreading dinâmico Cilk Plus. A latência de Par-R tem comparação favorável à latência do DotMix, o que é confirmado experimentalmente, mas não requer o uso subjacente fixado de um dado gerador aleatório. / We present two contributions to the field of parallel programming. The first contribution is theoretical: we introduce SIPS analysis, a novel approach to estimate the number of synchronizations performed during the execution of a parallel algorithm. Based on the concept of logical clocks, it allows us: on one hand, to deliver new bounds for the number of synchronizations, in expectation; on the other hand, to design more efficient parallel programs by dynamic adaptation of the granularity. The second contribution is pragmatic: we present an efficient parallelization strategy for pseudorandom number generation, independent of the number of concurrent processes participating in a computation. As an alternative to the use of one sequential generator per process, we introduce a generic API called Par-R, which is designed and analyzed using SIPS. Its main characteristic is the use of a sequential generator that can perform a “jump-ahead” directly from one number to another on an arbitrary distance within the pseudorandom sequence. Thanks to SIPS, we show that, in expectation, within an execution scheduled by work stealing of a “very parallel” program (whose depth or critical path is subtle when compared to the work or number of operations), these operations are rare. Par-R is compared with the parallel pseudorandom number generator DotMix, written for the Cilk Plus dynamic multithreading platform. The theoretical overhead of Par-R compares favorably to DotMix’s overhead, what is confirmed experimentally, while not requiring a fixed generator underneath.

O surgimento e a evolução da vida na terra foram possíveis graças ao desenvolvimento de mecanismos temporais precisos capazes de ajustar os processos fisiológicos que ocorriam no interior do organismo com os ciclos ambientais, promovendo assim, ganhos na capacidade adaptativa e reprodutiva dos indivíduos. Neste contexto, luz e temperatura são as duas pistas temporais mais relevantes para resetar o relógio endógeno e, aparentemente, esses dois zeitgebers trabalham juntos para manter os ritmos circadianos. Uma ampla gama de fotorreceptores e fotopigmentos evoluiu no sentido de perceber com alta sensibilidade a informação fótica fornecida pelo ambiente e, recentemente, foi demonstrado que a detecção de temperatura também pode ser exercida pelos fotopigmentos rodopsina e melanopsina, sendo mediada por canais TRP (Shen et al., 2011). Consideramos as células B16-F10 Per1::Luc como um modelo promissor para o estudo de luz e temperatura em relógios periféricos, uma vez que essa linhagem expressa os dois fotopigmentos apontados com função de termorreceptores em Drosophila. Nossos estudos nos permitiram verificar que a luz não atua como um agente sincronizador nessas células, que se mantiveram em livre curso mesmo após um pulso de 10 min de luz azul (650 lux). Por outro lado, um pulso de temperatura de 2,5º C acima da temperatura de manutenção por 1h atuou ajustando a expressão do gene Per1, imprimindo um ritmo circadiano, diferentemente do observado no controle. Com base nessas informações, hipotetizamos que a informação de luz, percebida via melanopsina na retina de mamíferos, levaria a regulação da temperatura circadiana pelo NSQ, e a temperatura corporal, por sua vez, poderia atuar como uma pista interna para a sincronização dos tecidos periféricos, tendo os canais TRP como mediadores. Para responder esta questão, utilizamos camundongos WT e TrpV1 KO submetidos a diferentes protocolos de luz e avaliamos a expressão de genes do relógio Per1, Per2, Clock e Bmal1 e dos canais TrpV1 e TrpA1 em tecidos periféricos. Identificamos que a glândula suprarrenal, fígado e tecido adiposo marrom possuem uma maquinaria do relógio tipicamente ativa e acreditamos que a oscilação dos genes de relógio observada nesses tecidos é expressiva. Interessantemente, vimos também que o TrpV1, além de ser expresso nos tecidos analisados em animais WT, apresenta uma transcrição rítmica no fígado e tecido adiposo marrom de animais em LD, corroborando nossa hipótese de que canais TRP atuam como mediadores da informação de luz aos tecidos periféricos. Dadas as diferenças encontradas entre os animais WT e TrpV1 KO, sugerimos que a presença do canal TRPV1 pode ser essencial, embora seu grau de envolvimento varie de acordo com o tecido. No que diz respeito ao canal TRPA1, encontramos dois resultados que merecem ser destacados. Primeiramente, identificamos no fígado de camundongos TrpV1 KO mantidos em LD uma provável compensação da expressão de TrpA1 na ausência de TrpV1 e, curiosamente, que o tecido adiposo marrom não expressa o canal TrpA1. Considerando os resultados deste trabalho sobre o envolvimento dos canais TRP em resposta à luz e temperatura, acreditamos ter fortalecido nossa hipótese inicial, principalmente após demonstrarmos o papel do canal TRPV1 e que tecidos periféricos são sincronizados por alterações de temperatura. / The life emergence and evolution on Earth were made possible by the development of precise temporal mechanisms able to adjust the physiological processes within an organism with environmental cycles, thus promoting gains in the adaptive and reproductive capacity of the individuals. In this context, light and temperature are the two most relevant time cues to reset the endogenous clock; apparently these two zeitgebers work together to keep the circadian rhythms. A wide variety of photoreceptors and photopigments evolved in order to precisely perceive the photic information provided by the environment, and recently it has been shown that the temperature detection can also be exerted by the photopigments rhodopsin and melanopsin, being mediated by TRP channels (Shen et al., 2011). We have identified B16-F10 Per1::Luc cells as a promising model for the study of light and temperature effects on peripheral clocks, since this cell line expresses both photopigments pointed as thermoreceptors in Drosophila. Our studies allowed us to demonstrate that light does not act as a synchronizing agent on those cells, which remained in free running after a 10 min pulse of blue light (650 lux). On the other hand, a temperature pulse of 2.5º C above the maintenance temperature, for 1h, adjusted Per1 gene expression, imprinting a circadian rhythm, which was not observed in the control. Based on this information, we hypothesized that the light perceived via melanopsin by the mammalian retina would lead to the regulation of the circadian temperature by the SCN, and the body temperature, in turn, could act as an inner cue for the synchronization of the peripheral tissues, having the TRP channels as mediators. To answer this question, we have used WT and TrpV1 KO mice under different light protocols and evaluated the expression of clock genes Per1, Per2, Clock and Bmal1 and TrpV1 and TrpA1 channels in peripheral tissues. We found that the adrenal gland, liver and brown adipose tissue have a typically active clock machinery, and the oscillation of clock genes observed in these tissues is significant. Interestingly, we observed that TrpV1 is expressed in those tissues, and presents a rhythmic transcription in the liver and brown adipose tissue of LD maintained animals, confirming our hypothesis that TRP channels act as mediators of light information to peripheral tissues. In face of the differences between WT and trpV1 KO animals, we suggest that the presence of the TRPV1 channel may be essential, although its degree of involvement may vary according to the tissue. In terms of TRPA1 channel, we found two results that deserve to be highlighted. Firstly, we identified in the liver of TrpV1 KO mice maintained in LD a presumable compensation of TrpA1 expression in the absence of TrpV1 and, interestingly, the brown adipose tissue does not express TrpA1 channel. Considering the findings of this study on the participation of TRP channels in responses to light and temperature, we believe we have strengthened our initial hypothesis, especially after we have demonstrated the role of TRPV1 channel, and that peripheral tissues may be synchronized by temperature changes.

Orientadores: Flavio Caldas Da Cruz, Luiz Eduardo Evangelista de Araujo / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-28T03:18:42Z (GMT). No. of bitstreams: 1 LamillaRubio_ErickAbraham_M.pdf: 5773132 bytes, checksum: 33effe596fdd1deb74be96f588fc6150 (MD5) Previous issue date: 2015 / Resumo: Neste trabalho foi feito um estudo experimental da transmissão de padrões de frequência atómicos através de uma rede de fibra optica. Até onde sabemos este tipo de transmissão foi realizada pela primeira vez no Brasil. Utilizamos uma conexão de fibra óptica entre o Instituto de Física Gleb Wataghin (IFGW) e a Faculdade de Engenharia Elétrica e Computação (FEEC) da UNICAMP, correspondendo a uma distância de aproximadamente 2 km, e um comprimento total de fibra de 18 km. Frequências de RF derivadas de padrões de frequência de Rubídio e de um receptor GPS foram transmitidas e caracterizadas através de medidas de frequência, particularmente por gráficos de variância de Allan, e medidas da fase / Abstract: In this experimental work, transmission of an atomic frequency standard through an optical fiber network has been implemented for first time in Brazil, to the best of our knowledge. We have used a fiber link between the Institute of Physics (IFGW) and the Department of Electrical Engineering inside the campus of the University of Campinas (UNICAMP) corresponding to 18 km fiber link (2km between buildings). Radio frequencies derived from a Rubidium standard and a GPS (Global Position system) receiver has been transmitted and characterized via phase and frequency measurements, particularly trough Allan deviation plots and phase measurements / Mestrado / Física / Mestre em Física / 2013/15492-2 / FAPESP

Les rythmes circadiens contrôlent de nombreux aspects de la physiologie chez les mammifères. Parmi ces processus physiologiques, les horloges circadiennes contrôlent entre autres la réponse immunitaire innée et adaptative. Depuis des décennies, de nombreuses études ont commencé à couvrir ce sujet. Cependant, le contrôle circadien de la réponse adaptative reste peu étudié. Dans le cadre de ce projet de recherche de doctorat, nous avons exploré le rôle des rythmes circadiens dans la réponse des lymphocytes T CD8 à la présentation antigénique par des cellules dendritiques. Des travaux du laboratoire publiés par Erin E. Fortier et al. ont mis en évidence une différence jour/nuit dans l’expansion des lymphocytes T CD8 dont le récepteur T (TCR) est spécifique au complexe KbOVA exprimé par les cellules dendritiques ainsi que dans le nombre de lymphocytes T CD8 CD44hi IFN+ spécifiques pour l’antigène de l’ovalbumine (OVA)1. En effet, la réponse des lymphocytes T CD8 est plus importante après une vaccination faite en milieu de jour (zeitgeber time (ZT) 6) par rapport à une vaccination faite en milieu de nuit (ZT18). Cependant, ces travaux de recherche n’ont pas démontré le rôle des horloges circadiennes dans le rythme de réponse des lymphocytes T CD8 à la présentation antigénique. Mes travaux de recherche de doctorat ont dans un premier temps confirmé l’implication des horloges circadiennes dans le rythme de réponse des lymphocytes T CD8 à la présentation antigénique. Nous avons ensuite démontré la contribution des horloges circadiennes des cellules dendritiques ainsi que le rôle essentiel des horloges circadiennes des lymphocytes T CD8 dans ce rythme de réponse. De plus, nous avons montré que ce rythme avait un impact sur la capacité des lymphocytes T CD8 à contrôler une infection bactérienne (Listeria monocytogenes). En effet, les variations jour/nuit de la charge bactérienne dans la rate et le foie des souris de type sauvage étaient abolies dans les souris déficientes pour le gène des horloges circadiennes Bmal1 dans les lymphocytes T CD8. Dans un second temps, nous avons mis en évidence suite à l’analyse du transcriptome des lymphocytes T CD8 de souris naïves collectés toutes les 4 heures sur 48 heures que ces cellules sont plus enclines à être activées le jour et à l’opposé plus enclines à être inhibées la nuit. Ces résultats corrèlent avec le rythme de réponse des lymphocytes T CD8 à la vaccination. Dans un dernier temps, nous avons confirmé que le rythme de réponse des lymphocytes T CD8 à la présentation antigénique agissait de manière précoce dans l’activation de ces cellules. Pour cela nous avons irradié des souris de type sauvage et nous les avons ensuite reconstituées avec une moelle osseuse contenant 1% de précurseurs de cellules OT-I (lymphocytes T CD8 spécifiques au complexe KbOVA, exprimant la chaîne du TCR V5. Après vaccination de ces souris en milieu de jour subjectif (circadian time (CT) 6) ou en milieu de nuit subjective (CT18), nous avons observé un rythme de la réponse des lymphocytes CD8 pour différents marqueurs impliqués dans la réponse précoce des lymphocytes T CD8, telles que CD69, CD5, IRF4, et la phosphorylation de S6 (marqueur de l’activité de mTOR) et de AKT. L’ensemble des recherches de mon doctorat ont permis de mettre en évidence un tout nouveau mécanisme impliquant les horloges circadiennes dans la réponse des lymphocytes T CD8 en réponse à une vaccination. Une meilleure compréhension du fonctionnement des horloges circadiennes dans la réponse immunitaire permettra de mettre en place des nouveaux traitements personnalisés en fonction du type d’infection et du type de maladie, délivré à un certain moment de la journée dans le but d’améliorer l’efficacité tout en réduisant les effets secondaires. / Circadian rhythms control various aspects of the physiology in mammals. Among these processes, circadian clocks control the innate and the adaptive immune responses. Since few decades, numerous studies started to uncover the role of the circadian system in the immune response. However, the circadian control of the adaptive immune response remains poorly studied. My PhD work focused on the circadian control of the CD8 T cell response to vaccination by dendritic cells. Erin E. Fortier et al. published in The Journal of Immunology that wild type mice vaccinated with antigen presenting cells loaded with the OVA peptide present a day/night variation of the CD8 T cell response after a vaccination done during the middle of the day (zeitgeber time (ZT) 6) compared to a vaccination done during the middle of the night (ZT18)1. Indeed, the proportion of CD8 KbOVA+ cells and the proportion of CD8 CD44hi IFN+ T cells were higher during the middle of the day than the middle of the night. However, this work showed a diurnal but not a circadian rhythm, that remained to be confirmed. The first part of my PhD research confirmed a role of the circadian system in the rhythm of the CD8 T cell response to vaccination. We showed a contribution of the dendritic cell clock as well as an essential role of the CD8 T cell clock. Moreover, this rhythm impacts the ability to control an infectious challenge as shown by a circadian variation in bacterial load (Listeria monocytogenes) in wild type but not in mice lacking clock in mature CD8 T cells. The second part of my research focused on the analysis of the transcriptome of CD8 T cells from naive mice collected every 4 hours over 48 hours. We showed that CD8 T cells are more prone to be activated during the day and at the opposite are more prone to be inhibited during the night. These results are correlated with the rhythm of the CD8 T cell response to vaccination. Finally, during the third part of my PhD, we confirmed that the rhythm of the CD8 T cell response to antigen presentation was acting at the early stage of the CD8 T cell activation. We used wild type mice reconstituted with bone marrow cells containing 1% of OT-I precursor cells (CD8 T cells restricted for the KbOVA complex, expressing the receptor chain of the TCR for the OVA peptide, V5) and vaccinate these mice during the middle of the subjective day (CT6) or during the middle of the subjective night (CT18). At the early stage of the CD8 T cell response to vaccination, we showed a higher expression of several activation markers after a vaccination done during the middle of the day than during the middle of the night, such as CD5, CD69, IRF4 and the phosphorylation of S6 (marker of the mTOR activity) and AKT. Altogether, my PhD work highlights a new mechanism involving the circadian system in the control of the immune response. A better understanding of how circadian clocks act on the immune response will allow implementing new treatment strategies in order to increase their efficacy as well as to decrease side effects.

Ce travail de thèse porte sur la conception, la réalisation et l'étude de sources laser à semi-conducteur de haute cohérence, émettant à 894 nm, pour application aux horloges atomiques Césium compactes pompées optiquement, dans un contexte de développement industriel. Nous nous intéressons plus particulièrement aux lasers à émission par la tranche, dits "Distributed-Feedback" (DFB), pompés électriquement. L'objectif est d'obtenir un laser monomode en fréquence, à faible seuil, à rendement optique élevé et de largeur de raie inférieure à 1 MHz. Nous traitons d'abord de la conception et de la caractérisation au 1er ordre des diodes DFB, jusqu'à leur mise en modules pour horloge, puis nous effectuons une étude approfondie des propriétés physiques de l'émission laser en terme de cohérence temporelle, en introduisant une nouvelle méthode universelle de caractérisation du bruit de fréquence optique. Enfin, nous nous intéressons aux propriétés spectrales de l'émission en configuration d'asservissement sur une raie de fluorescence du Césium ("Dither-Locking"). Nous montrons que les propriétés intrinsèques du composant satisfont aux exigences du système industriel tel qu'il a été défini lors de l'étude. / This PhD work deals with the design, the fabrication and the study of high-coherence semiconductor laser sources emitting at 894 nm, for application to compact, optically-pumped cesium atomic clocks in an industrial context. We are particularly interested in the electrically pumped "Distributed-Feedback" in-plane laser diodes (DFB). The aim is to obtain a low-threshold, single-mode laser with high optical efficiency and a linewidth of less than 1 MHz. We first deal with the design and first-order characterization of the DFB diodes until they are put into modules for the clock. We then carry out an in-depth study of the physical properties of the laser emission in terms of coherence time. For that purpose, a new universal method for characterizing the optical frequency noise is introduced. Finally, we look further into the spectral properties of the emission in a servo configuration on a fluorescence line of the cesium ("Dither-Locking"). We show that the intrinsic properties of the component satisfy the requirements of the industrial system as defined in the study.

Data processing on a continuously growing amount of information and the increasing power restrictions have become an ubiquitous challenge in our world today. Besides parallel computing, a promising approach to improve the energy efficiency of current systems is to integrate specialized hardware. This paper presents a Tensilica RISC processor extended with an instruction set to accelerate basic database operators frequently used in modern database systems. The core was taped out in a 28 nm SLP CMOS technology and allows energy-efficient query processing as well as query optimization by applying selectivity estimation techniques. Our chip measurements show an 1000x energy improvement on selected database operators compared to state-of-the-art systems.

Thesis (M.S.)-- Air Force Institute of Technology. / The original document contains color images.

This thesis is concerned with the modeling and the analysis of distributedreal-time systems. In distributed systems, components evolve partlyindependently: concurrent actions may be performed in any order, withoutinfluencing each other and the state reached after these actions does notdepends on the order of execution. The time constraints in distributed real-timesystems create complex dependencies between the components and the events thatoccur. So far, distributed real-time systems have not been deeply studied, andin particular the distributed aspect of these systems is often left aside. Thisthesis explores distributed real-time systems. Our work on distributed real-timesystems is based on two formalisms: time Petri nets and networks of timedautomata, and is divided into two parts.In the first part, we highlight the differences between centralized anddistributed timed systems. We compare the main formalisms and their extensions,with a novel approach that focuses on the preservation of concurrency. Inparticular, we show how to translate a time Petri net into a network of timedautomata with the same distributed behavior. We then study a concurrency relatedproblem: shared clocks in networks of timed automata can be problematic when oneconsiders the implementation of a model on a multi-core architecture. We showhow to avoid shared clocks while preserving the distributed behavior, when thisis possible.In the second part, we focus on formalizing the dependencies between events inpartial order representations of the executions of Petri nets and time Petrinets. Occurrence nets is one of these partial order representations, and theirstructure directly provides the causality, conflict and concurrency relationsbetween events. However, we show that, even in the untimed case, some logicaldependencies between event occurrences are not directly described by thesestructural relations. After having formalized these logical dependencies, wesolve the following synthesis problem: from a formula that describes a set ofruns, we build an associated occurrence net. Then we study the logicalrelations in a simplified timed setting and show that time creates complexdependencies between event occurrences. These dependencies can be used to definea canonical unfolding, for this particular timed setting.

Ectopic calcification can cause pain and limit mobility. Studies suggest that circadian genes may play a role in the calcification process. Core circadian genes Clock, Npas2, and Bmal1 are transcription factors that form CLOCK:BMAL1 or NPAS2:BMAL1 transactivator complexes that drive the rhythmic expression of circadian oscillator genes and output genes. Circadian oscillator genes Period1-3 and Cryptochrome1-2 encode proteins that form transcription repressor complexes that feedback to inhibit CLOCK/NPAS2:BMAL1 activity, thus completing the feedback loop that is the basis of the molecular circadian clockwork. Arrhythmic Bmal1-/- mice exhibit site-specific, age-dependent arthropathy. While studying the circadian phenotype of Clock-/-;Npas2m/m double mutant mice, we discovered that these double mutant mice develop site-specific arthropathy similar to the arthropathy described in Bmal1-/- mice. Based on the circadian clockwork mechanism, we hypothesized that CLOCK/NPAS2:BMAL1 transactivator complexes drive the expression of a gene (or genes) that prevents age-dependent arthropathy. To investigate Clock-/-;Npas2m/m double mutant mouse arthropathy, we evaluated mutant mice using X-ray, micro-computed tomography, and histology, and found that Clock-/-;Npas2m/m double mutant mice exhibit age-dependent, site-specific arthropathy that phenocopies that of Bmal1-/- mice. The costosternal junction and calcaneal tendon are most prominently affected, in that calcification of those tissues is detectable as early as 4-5 weeks and 11-12 weeks, respectively. The arthropathic lesions in these tissues consist of calcium phosphate vii deposits, and in Bmal1-/- costosternal junction calcifications, the deposits contain calcium pyrophosphate dihydrate crystals. Mechanical stress, disregulation of centrally-regulated circadian rhythms, and systemic serum mineral imbalances likely do not contribute to this pathology. In vitro micromass cultures generated from Clock-/-;Npas2m/m double mutant mouse embryonic fibroblasts do not exhibit irregular chondrocyte differentiation compared to wild-type cultures, suggesting that chondrocyte cell-autonomous mechanisms are insufficient to induce this arthropathy. Analysis of Clock-/-;Npas2m/m double mutant intersternebral tissue RNA did not reveal significant changes in chondrocyte or calcification-related gene expression. Histological stains showed an absence of osteoblasts and osteoclasts around costosternal junction calcifications, suggesting that these cell types are not contributing to this pathology. Instead, chondrocytes are localized to the costosternal junction but there were no significant changes in the distribution of chondrocyte markers in this tissue, as evaluated by immunohistochemistry. These findings suggest that Clock or Npas2, and Bmal1, regulate ectopic calcification through a combination of systemic and local factors, and that the cells affected by Clock and Npas2, or Bmal1, disruption are a subset of the cells distributed in specific tissues that develop age-dependent arthropathy. The significance of these findings is that “circadian genes” play a role in the regulation of ectopic calcification in a non-oscillator capacity. Understanding this new mechanism by which ectopic calcification is controlled could lead to novel approaches for the treatment of some human calcification diseases.

Dans les systèmes répartis asynchrones, l'horloge logique et le vecteur d'horloges sont deux outils fondamentaux pour gérer la communication et le partage de données entre les entités constitutives de ces systèmes. L'objectif de cette thèse est d'exploiter ces outils avec une perspective d'implantation. Dans une première partie, nous nous concentrons sur la communication de données et contribuons au domaine de la diffusion uniforme à ordre total. Nous proposons le protocole des trains : des jetons (appelés trains) circulent en parallèle entre les processus participants répartis sur un anneau virtuel. Chaque train est équipé d'une horloge logique utilisée pour retrouver les train(s) perdu(s) en cas de défaillance de processus. Nous prouvons que le protocole des trains est un protocole de diffusion uniforme à ordre total. Puis, nous créons une nouvelle métrique : le rendement en termes de débit. Cette métrique nous permet de montrer que le protocole des trains a un rendement supérieur au meilleur, en termes de débit, des protocoles présentés dans la littérature. Par ailleurs, cette métrique fournit une limite théorique du débit maximum atteignable en implantant un protocole de diffusion donné. Il est ainsi possible d'évaluer la qualité d'une implantation de protocole. Les performances en termes de débit du protocole des trains, notamment pour les messages de petites tailles, en font un candidat remarquable pour le partage de données entre coeurs d'un même processeur. De plus, sa sobriété en termes de surcoût réseau en font un candidat privilégié pour la réplication de données entre serveurs dans le cloud. Une partie de ces travaux a été implantée dans un système de contrôle-commande et de supervision déployé sur plusieurs dizaines de sites industriels. Dans une seconde partie, nous nous concentrons sur le partage de données et contribuons au domaine de la RFID. Nous proposons une mémoire répartie partagée basée sur des étiquettes RFID. Cette mémoire permet de s'affranchir d'un réseau informatique global. Pour ce faire, elle s'appuie sur des vecteurs d'horloges et exploite le réseau formé par les utilisateurs mobiles de l'application répartie. Ainsi, ces derniers peuvent lire le contenu d'étiquettes RFID distantes. Notre mémoire répartie partagée à base de RFID apporte une alternative aux trois architectures à base de RFID disponibles dans la littérature. Notre mémoire répartie partagée a été implantée dans un jeu pervasif qui a été expérimenté par un millier de personnes. / In asynchronous distributed systems, logical clock and vector clocks are two core tools to manage data communication and data sharing between entities of these systems. The goal of this PhD thesis is to exploit these tools with a coding viewpoint. In the first part of this thesis, we focus on data communication and contribute to the total order broadcast domain. We propose trains protocol: Tokens (called trains) rotate in parallel between participating processes distributed on a virtual ring. Each train contains a logical clock to recover lost train(s) in case of process(es) failure. We prove that trains protocol is a uniform and totally ordered broadcast protocol. Afterwards, we create a new metric: the throughput efficiency. With this metric, we are able to prove that, from a throughput point of view, trains protocol performs better than protocols presented in literature. Moreover, this metric gives the maximal theoretical throughput which can be reached when coding a given protocol. Thus, it is possible to evaluate the quality of the coding of a protocol. Thanks to its throughput performances, in particular for small messages, trains protocol is a remarkable candidate for data sharing between the cores of a processor. Moreover, thanks to its temperance concerning network usage, it can be worthwhile for data replication between servers in the cloud. Part of this work was implemented inside a control-command and supervision system deployed among several dozens of industrial sites. In the second part of this thesis, we focus on data sharing and contribute to RFID domain. We propose a distributed shared memory based on RFID tags. Thanks to this memory, we can avoid installing a computerized global network. This is possible because this memory uses vector clocks and relies on the network made by the mobile users of the distributed application. Thus, the users are able to read the contents of remote RFID tags. Our RFID-based distributed shared memory is an alternative to the three RFID-based architectures available in the literature. This distributed shared memory was implemented in a pervasive game tested by one thousand users.