Distributed systems are everywhere. From large datacenters to mobile devices, an ever richer assortment of applications and services relies on distributed systems, infrastructure, and protocols. Despite their ubiquity, testing and debugging distributed systems remains notoriously hard. Moreover, aside from inherent design challenges posed by partial failure, concurrency, or asynchrony, there remain significant challenges in the implementation of distributed systems. These programming challenges stem from the increasing complexity of the concurrent activities and reactive behaviors in a distributed system on the one hand, and the need to effectively leverage the parallelism offered by modern multi-core hardware, on the other hand. This thesis contributes Kompics, a programming model designed to alleviate some of these challenges. Kompics is a component model and programming framework for building distributed systems by composing message-passing concurrent components. Systems built with Kompics leverage multi-core machines out of the box, and they can be dynamically reconfigured to support hot software upgrades. A simulation framework enables deterministic execution replay for debugging, testing, and reproducible behavior evaluation for largescale Kompics distributed systems. The same system code is used for both simulation and production deployment, greatly simplifying the system development, testing, and debugging cycle. We highlight the architectural patterns and abstractions facilitated by Kompics through a case study of a non-trivial distributed key-value storage system. CATS is a scalable, fault-tolerant, elastic, and self-managing key-value store which trades off service availability for guarantees of atomic data consistency and tolerance to network partitions. We present the composition architecture for the numerous protocols employed by the CATS system, as well as our methodology for testing the correctness of key CATS algorithms using the Kompics simulation framework. Results from a comprehensive performance evaluation attest that CATS achieves its claimed properties and delivers a level of performance competitive with similar systems which provide only weaker consistency guarantees. More importantly, this testifies that Kompics admits efficient system implementations. Its use as a teaching framework as well as its use for rapid prototyping, development, and evaluation of a myriad of scalable distributed systems, both within and outside our research group, confirm the practicality of Kompics. / <p>QC 20130520</p>

La organización productiva descentralizada y flexible que, bajo el impulso de las nuevas tecnologías y la globalización, viene sustituyendo a partir del último cuarto del siglo XX al fordismo de inspiración keynesiana, está deteriorando los mercados laborales, lo que supone una precarización de las condiciones de empleo, un notable repliegue de los «Estados del bienestar» y la desactivación del factor trabajo. Superado el tradicional principio de «unicidad» empresarial, un empresario «complejo» y múltiple –el grupo de empresas-, caracterizado por su dificultad identificatoria, absorbe un protagonismo creciente, en un contexto normativo-laboral casi desregulado, en el que al margen del fraude, la dirección unitaria de las empresas agrupadas no implica deducir de su funcionamiento una responsabilidad (solidaria). En esa «cierta unidad económica» que constituye el grupo, se detecta un punto de conflicto o desconexión, entre las facultades empresariales decisorias -unidad de decisión- y las organizativas –dependencia y ajenidad de frutos-. / The decentralized and flexible productive organization, boosted by globalization, new information and knowledge technologies, has been replacing the Fordist Keynesian inspiration since the last quarter of the 20th century; besides it has been worsening the labour markets, which involves a precariousness of employment conditions and an outstanding backing down of “welfare states” and job factor neutralization. Once the traditional principle of business uniqueness has been overwhelmed, a complex and multiple –the corporate group- employer arises; this employer is characterized by the difficulty of being identified and acquires an increasingly featuring role, inside a regulatory working context almost deregulated, where, on the fringe fraud, the unitarian corporate group management doesn’t imply deducing a solidarity liability from its activity. Inside that “particular economical unity” made up by the group, a deal-breaker or a gap is detected between the decision-making management faculties –decision unity- and the organizational ones –dependence and another person’s benefits-.

Generating functions express a sequence as coefficients arising from a power series in variables. They have many applications in combinatorics and probability. In this paper, we will investigate the important properties of four kinds of generating functions in one variables: ordinary generating unction, exponential generating function, probability generating function and moment generating function. Many examples with applications in combinatorics and probability, will be discussed. Finally, some well-known contest problems related to generating functions will be addressed.

科学研究費補助金 研究種目:一般研究(C) 課題番号:03650275 研究代表者:森 正和 研究期間:1991-1992年度

La recherche porte sur les patrons de distribution longitudinale (amont-aval) et transversale (rive nord - rive sud) des communautés de crustacés planctoniques qui ont été analysés le long du fleuve Saint-Laurent entre le lac Saint-François et la zone de transition estuarienne, à deux hydropériodes en mai (crue) et en août (étiage). Les données zooplanctoniques et environnementales ont été récoltées à 52 stations réparties sur 16 transects transversaux en 2006. Au chapitre 1, nous présentons les principaux modèles écosystémiques en rivière, une synthèse des facteurs influençant le zooplancton en rivières et les objectifs et hypothèses de recherche. Au chapitre 2, nous décrivons la structure des communautés de zooplancton dans trois zones biogéographiques du fleuve et 6 habitats longitudinaux, ainsi que les relations entre la structure du zooplancton et la distribution spatiale des masses d’eau et les variables environnementales. Au chapitre 3, nous réalisons une partition de la variation des variables spatiales AEM (basées sur la distribution des masses d’eau) et des variables environnementales pour évaluer quelle part de la variation du zooplancton est expliquée par les processus hydrologiques (variables AEM) et les conditions locales (facteurs environnementaux). Le gradient salinité-conductivité relié à la discontinuité fleuve-estuaire a déterminé la distribution à grande échelle du zooplancton. Dans les zones fluviales, la distribution du zooplancton est davantage influencée par la distribution des masses d’eau que par les facteurs environnementaux locaux. La distribution des masses d’eau explique une plus grande partie de la variation dans la distribution du zooplancton en août qu’en mai. / The research aims to determine the distribution patterns of crustacean plankton along the longitudinal (west-east) and transversal (north shore - south shore) axes of the St. Lawrence River between Lake Saint-François and the estuarine transition zone, during two hydroperiods in May (high discharge) and August (low discharge). The zooplankton samples and the environmental data were collected at 52 stations distributed along 16 transversal transects in 2006. In chapter 1, we present the theoretical concepts of river ecosystem models, and a synthesis on the generative processes driving zooplankton spatial patterns in rivers. We also present our research objectives and hypotheses. In chapter 2, we describe spatial patterns of the zooplankton community structure in three biogeographic zones of the St. Lawrence and 6 longitudinal habitats, together with the relationships between zooplankton spatial structure and water masses spatial distribution and environmental characteristics. In chapter 3, we perform a variation partitioning procedure on spatial variables AEM (based on water masses spatial distribution) and environmental variables in order to assess how much of the zooplankton variation is explained by hydrological processes (AEM variables) and local conditions (environmental factors). The salinity-conductivity gradient related to the fluvial-estuary discontinuity determines the large-scale spatial patterns of the crustacean zooplankton. In the fluvial zones, the zooplankton distribution patterns are more influenced by the water masses spatial structure than by local environmental factors. The spatial distribution of the water masses explained more of the spatial structure of zooplankton communities in August than in May.

Les modèles pharmacocinétiques à base physiologique (PBPK) permettent de simuler la dose interne de substances chimiques sur la base de paramètres spécifiques à l’espèce et à la substance. Les modèles de relation quantitative structure-propriété (QSPR) existants permettent d’estimer les paramètres spécifiques au produit (coefficients de partage (PC) et constantes de métabolisme) mais leur domaine d’application est limité par leur manque de considération de la variabilité de leurs paramètres d’entrée ainsi que par leur domaine d’application restreint (c. à d., substances contenant CH3, CH2, CH, C, C=C, H, Cl, F, Br, cycle benzénique et H sur le cycle benzénique). L’objectif de cette étude est de développer de nouvelles connaissances et des outils afin d’élargir le domaine d’application des modèles QSPR-PBPK pour prédire la toxicocinétique de substances organiques inhalées chez l’humain. D’abord, un algorithme mécaniste unifié a été développé à partir de modèles existants pour prédire les PC de 142 médicaments et polluants environnementaux aux niveaux macro (tissu et sang) et micro (cellule et fluides biologiques) à partir de la composition du tissu et du sang et de propriétés physicochimiques. L’algorithme résultant a été appliqué pour prédire les PC tissu:sang, tissu:plasma et tissu:air du muscle (n = 174), du foie (n = 139) et du tissu adipeux (n = 141) du rat pour des médicaments acides, basiques et neutres ainsi que pour des cétones, esters d’acétate, éthers, alcools, hydrocarbures aliphatiques et aromatiques. Un modèle de relation quantitative propriété-propriété (QPPR) a été développé pour la clairance intrinsèque (CLint) in vivo (calculée comme le ratio du Vmax (μmol/h/kg poids de rat) sur le Km (μM)), de substrats du CYP2E1 (n = 26) en fonction du PC n octanol:eau, du PC sang:eau et du potentiel d’ionisation). Les prédictions du QPPR, représentées par les limites inférieures et supérieures de l’intervalle de confiance à 95% à la moyenne, furent ensuite intégrées dans un modèle PBPK humain. Subséquemment, l’algorithme de PC et le QPPR pour la CLint furent intégrés avec des modèles QSPR pour les PC hémoglobine:eau et huile:air pour simuler la pharmacocinétique et la dosimétrie cellulaire d’inhalation de composés organiques volatiles (COV) (benzène, 1,2-dichloroéthane, dichlorométhane, m-xylène, toluène, styrène, 1,1,1 trichloroéthane et 1,2,4 trimethylbenzène) avec un modèle PBPK chez le rat. Finalement, la variabilité de paramètres de composition des tissus et du sang de l’algorithme pour les PC tissu:air chez le rat et sang:air chez l’humain a été caractérisée par des simulations Monte Carlo par chaîne de Markov (MCMC). Les distributions résultantes ont été utilisées pour conduire des simulations Monte Carlo pour prédire des PC tissu:sang et sang:air. Les distributions de PC, avec celles des paramètres physiologiques et du contenu en cytochrome P450 CYP2E1, ont été incorporées dans un modèle PBPK pour caractériser la variabilité de la toxicocinétique sanguine de quatre COV (benzène, chloroforme, styrène et trichloroéthylène) par simulation Monte Carlo. Globalement, les approches quantitatives mises en œuvre pour les PC et la CLint dans cette étude ont permis l’utilisation de descripteurs moléculaires génériques plutôt que de fragments moléculaires spécifiques pour prédire la pharmacocinétique de substances organiques chez l’humain. La présente étude a, pour la première fois, caractérisé la variabilité des paramètres biologiques des algorithmes de PC pour étendre l’aptitude des modèles PBPK à prédire les distributions, pour la population, de doses internes de substances organiques avant de faire des tests chez l’animal ou l’humain. / Physiologically-based pharmacokinetic (PBPK) models simulate the internal dose metrics of chemicals based on species-specific and chemical-specific parameters. The existing quantitative structure-property relationships (QSPRs) allow to estimate the chemical-specific parameters (partition coefficients (PCs) and metabolic constants) but their applicability is limited by their lack of consideration of variability in input parameters and their restricted application domain (i.e., substances containing CH3, CH2, CH, C, C=C, H, Cl, F, Br, benzene ring and H in benzene ring). The objective of this study was to develop new knowledge and tools to increase the applicability domain of QSPR-PBPK models for predicting the inhalation toxicokinetics of organic compounds in humans. First, a unified mechanistic algorithm was developed from existing models to predict macro (tissue and blood) and micro (cell and biological fluid) level PCs of 142 drugs and environmental pollutants on the basis of tissue and blood composition along with physicochemical properties. The resulting algorithm was applied to compute the tissue:blood, tissue:plasma and tissue:air PCs in rat muscle (n = 174), liver (n = 139) and adipose tissue (n = 141) for acidic, neutral, zwitterionic and basic drugs as well as ketones, acetate esters, alcohols, ethers, aliphatic and aromatic hydrocarbons. Then, a quantitative property-property relationship (QPPR) model was developed for the in vivo rat intrinsic clearance (CLint) (calculated as the ratio of the in vivo Vmax (μmol/h/kg bw rat) to the Km (μM)) of CYP2E1 substrates (n = 26) as a function of n-octanol:water PC, blood:water PC, and ionization potential). The predictions of the QPPR as lower and upper bounds of the 95% mean confidence intervals were then integrated within a human PBPK model. Subsequently, the PC algorithm and QPPR for CLint were integrated along with a QSPR model for the hemoglobin:water and oil:air PCs to simulate the inhalation pharmacokinetics and cellular dosimetry of volatile organic compounds (VOCs) (benzene, 1,2-dichloroethane, dichloromethane, m-xylene, toluene, styrene, 1,1,1-trichloroethane and 1,2,4 trimethylbenzene) using a PBPK model for rats. Finally, the variability in the tissue and blood composition parameters of the PC algorithm for rat tissue:air and human blood:air PCs was characterized by performing Markov chain Monte Carlo (MCMC) simulations. The resulting distributions were used for conducting Monte Carlo simulations to predict tissue:blood and blood:air PCs for VOCs. The distributions of PCs, along with distributions of physiological parameters and CYP2E1 content, were then incorporated within a PBPK model, to characterize the human variability of the blood toxicokinetics of four VOCs (benzene, chloroform, styrene and trichloroethylene) using Monte Carlo simulations. Overall, the quantitative approaches for PCs and CLint implemented in this study allow the use of generic molecular descriptors rather than specific molecular fragments to predict the pharmacokinetics of organic substances in humans. In this process, the current study has, for the first time, characterized the variability of the biological input parameters of the PC algorithms to expand the ability of PBPK models to predict the population distributions of the internal dose metrics of organic substances prior to testing in animals or humans.

Ce travail de thèse a été réalisé dans le cadre d'une collaboration internationale entre l'Université de Lorraine (France) et l'Université d'Oujda (Maroc). Les travaux réalisés concernent la modélisation de l'usinage par enlèvement de matière. Deux aspects importants de l'usinage ont été abordés : le processus de la formation de copeaux et les échanges thermiques à l'interface outil-copeau. Dans la première partie de la thèse, une modélisation par élément finis (EF) du processus de la coupe a été mise en place. La segmentation des copeaux a été particulièrement analysée grâce à l'introduction d'un nouveau paramètre, le Rapport d'Intensité de Segmentation, permettant de quantifier ce phénomène. Une corrélation entre la réduction de l'effort de coupe et l'intensité de segmentation a été établie. La deuxième partie de la thèse a été consacrée à l'étude des échanges thermiques à l'interface outil-copeau, qui contribuent entre autres à l'usure de l'outil de coupe. Un des points importants de l'étude est la mise en place d'une procédure d'identification hybride (analytique/numérique) permettant d'estimer le flux thermique transmis dans l'outil de coupe et de remonter au coefficient de partage de la chaleur à l'interface outil-copeau pour chaque vitesse de coupe. Avec les valeurs identifiées du coefficient de partage de la chaleur pour chaque vitesse de coupe, une loi d'échange thermique multi-branches a été proposée et ses paramètres identifiés. Cette loi donnant l'évolution du coefficient de partage de la chaleur en fonction de la vitesse de coupe a également été définie en fonction de la vitesse relative de glissement à l'interface outil-copeau dans le but de l'implanter dans un code de calcul EF. L'interface utilisateur VUINTER du code Abaqus/Explicit a été exploitée pour implanter la loi proposée, afin d'appréhender complètement le contact d'un point de vue mécanique et thermique. Il est désormais possible d'implanter via cette interface-utilisateur n'importe quelle autre loi de contact thermomécanique (frottement, coefficient de partage de la chaleur, etc.). L'implantation via la subroutine VUINTER a été validée sur des cas tests d'abord, et puis ensuite en usinage. Les résultats obtenus pour les flux thermiques avec cette nouvelle procédure sont en très bon accord avec les mesures expérimentales pour le couple outil-matière considéré : AA2024-T351/WC-Co / This PhD. thesis is realised in the framework of an international cooperation between the University of Lorraine (France) and the University of Oujda (Morocco). The work done concerns the modelling of machining process by material removal. Two important aspects of machining have been investigated: the chip formation process and the heat exchange at the tool-chip interface. In the first part of the thesis, a FE modelling of the cutting process has been established. Chips segmentation have been particularly analysed using à new parameter (Segmentation Intensity Ratio) allowing the quantification of the phenomenon. A correlation has been established between the cutting force reduction and the chip segmentation intensity. The second part of the thesis has been devoted to the study of heat exchange at the tool-chip interface, among other phenomena that contribute to the tool wear. One important point of the study is the establishment of a hybrid identification procedure (analytical/numerical) to estimate the heat flux transmitted into the cutting tool, and identification of the heat partition coefficient at the contact interface for each cutting speed. With identified values of the heat partition coefficient obtained by varying the cutting speed, a heat exchange multi-branch law has been proposed and parameters of this law have been identified. This law corresponds firstly to the evolution of the heat partition coefficient as a function of the cutting speed. Thereafter, it was defined in term of the relative sliding velocity at the tool-chip contact interface, in order to implement it in a FE code. The user interface VUINTER of Abaqus/Explicit has been used to implement the proposed law, to fully control the mechanical and thermal contact. It is henceforth possible to implement with this user interface any thermomechanical contact (friction, heat partition coefficient, etc.). The implementation via the user subroutine VUINTER was validated first on adequate tests, then on machining. The obtained results for heat fluxes with this new procedure are in good agreement with experimental measurements for the tool-workmaterial couple considered: AA2024-T351/WC-Co

Petróleo Brasileiro S.A. / O presente trabalho aborda o comportamento da planta de processamento primário com alimentação por fluxo em padrão de golfadas. O fluxo no sistema de tubulações é descrito por um modelo de parâmetros concentrados, fornecendo as características principais necessárias para o controle da planta, e a resposta dinâmica desta pode então ser analisada. Usando a estratégia de controle tradicional verifica-se que as oscilações de fluxo são transmitidas para as vazões de saída de líquido e gás, para obter uma vazão de saída mais estável é permitida a flutuação de carga no separador dentro de uma tolerância, isto é possível reduzindo a atuação do controlador e estabelecendo um controle adicional diretamente na válvula de entrada. / The present work addresses the behavior of a primary processing plant subjected to slug flow pattern at its entrance. The flow in a pipeline system is described by a simplified concentrated parameter model, which preserves the main physical features that are important to control the plant. The dynamic response of the plant is then analyzed. Using a standard control strategy for the gas liquid separator, it is seen that the flow oscillations are transmitted to the liquid and gas outlets. In order to obtain a more stable outlet flow, the liquid level in the separator is then allowed to fluctuate within a given range, by reducing the effect of the controller constants, and establishing an additional control directly on the inlet entrance valve.

Petróleo Brasileiro S.A. / O presente trabalho aborda o comportamento da planta de processamento primário com alimentação por fluxo em padrão de golfadas. O fluxo no sistema de tubulações é descrito por um modelo de parâmetros concentrados, fornecendo as características principais necessárias para o controle da planta, e a resposta dinâmica desta pode então ser analisada. Usando a estratégia de controle tradicional verifica-se que as oscilações de fluxo são transmitidas para as vazões de saída de líquido e gás, para obter uma vazão de saída mais estável é permitida a flutuação de carga no separador dentro de uma tolerância, isto é possível reduzindo a atuação do controlador e estabelecendo um controle adicional diretamente na válvula de entrada. / The present work addresses the behavior of a primary processing plant subjected to slug flow pattern at its entrance. The flow in a pipeline system is described by a simplified concentrated parameter model, which preserves the main physical features that are important to control the plant. The dynamic response of the plant is then analyzed. Using a standard control strategy for the gas liquid separator, it is seen that the flow oscillations are transmitted to the liquid and gas outlets. In order to obtain a more stable outlet flow, the liquid level in the separator is then allowed to fluctuate within a given range, by reducing the effect of the controller constants, and establishing an additional control directly on the inlet entrance valve.

Para um composto químico exercer seu efeito bioativo é necessário que ele atravesse várias barreiras biológicas até alcançar seu sitio de ação. Propriedades farmacocinéticas insatisfatórias (como absorção, distribuição, metabolismo e excreção) são reconhecidamente as principais causas na descontinuidade de pesquisas na busca por novos fármacos. Neste trabalho, modelos biofísicos foram utilizados para o estudo de absorção de uma série de flavonóides naturais com atividade tripanossomicida. O coeficiente cromatográfico de partição, kw, foi determinado através da cromatografia líquida de alta eficiência em fase reversa, RP-HPLC, utilizando-se de colunas cromatográficas empacotadas com constituintes básicos da membrana biológica (fosfatidilcolina e colesterol). Os resultados obtidos demonstraram que nas colunas compostas por fosfatidilcolina a retenção de flavonóides hidroxilados é determinada por interações secundárias, além da partição, e no caso da coluna de colesterol, a partição é o principal mecanismo que rege a retenção. Uma série de descritores físico-químicos foi gerada pelos campos moleculares de interações (MIFs) entre os flavonóides naturais e algumas sondas químicas virtuais, utilizando o programa GRID. Os descritores físico-químicos gerados foram correlacionados com os log kw por análise dos mínimos múltiplos parciais (PLS), utilizando o programa VolSurf, com a finalidade de gerar um modelo quantitativo entre estrutura e propriedade (QSPR) para esta classe de compostos. O modelo produzido por este estudo, ao utilizar os dados de partição em colesterol, log kwCol, apresentou elevada consistência interna, com bom poder de correlação (R2 = 0, 97) e predição (Q2 = 0,86) para a partição destas moléculas / In order to a chemical compound exert its bioactive effect it is necessary that it crosses some biological barriers until reaching its site of action. Unfavorable pharmacokinetics properties (absorption, distribution, metabolism and excretion) are admittedly one of the main causes in the discontinuity of research in the search for new drugs. In this work, biophysics models were used for the study of absorption of a series of natural flavonoids with trypanocide activity. The chromatographic retention indices (log kw) were determined on immobilized artificial membranes columns (IAM.PC.DD, IAM.PC.DD2, Cholesteryl 10-Undecetonoato) obtained by the extrapolation method. The results demonstrated that in the composed columns for fosfatidilcolina the retention of hydroxil flavonoids is determined by secondary interactions, beyond the partition. In the case of the retention for the cholesterol column, the partition is the main mechanism that drives the retention. A series of physico-chemical descriptors were generated by the molecular interaction fields (MIF) between the flavonoids and some virtual chemical probes, using the program GRID. The descriptors were correlated with log kw by the partial least squares regression (PLS), using the VolSurf program, with the purpose to generate a quantitative model between the structure and the retention (QSRR) for this compounds class. The model produced for this study, when using the data of partition in cholesterol, log kwCol, presented high internal consistency, with good correlation power (R2 = 0, 97) and prediction (Q2 = 0,86) for the partition of these molecules