A manufatura celular tem um importante destaque entre os sistemas de produção, sendo empregada em parte significativa das empresas de manufatura classe mundial e alvo de constantes pesquisas. Um dos aspectos fundamentais para a aplicação desse sistema de produção é a solução de problemas de formação de células. Ao longo das últimas três décadas muitos algoritmos foram propostos para auxiliar esta decisão, porém, eles não têm sido intensamente aplicados na rotina das empresas, que na maioria dos casos, definem as células com base no bom senso e experiência. Alguns dos fatores que contribuem para isso são: a não disponibilidade de dados necessários para a solução do problema, e o fato de que cada algoritmo retrata situações particulares, necessitando de um especialista que seja capaz de escolhê-los ou desenvolvê-los e aplicá-los conforme as características específicas do problema enfrentado. Neste trabalho propõe-se que uma arquitetura que busca integrar os diversos algoritmos de formação de célula, permitindo que estes sejam aplicados a um mesmo conjunto de dados. O objetivo é disponibilizar aos profissionais de empresa o maior número possível de algoritmos de maneira simples e sem a necessidade de dispendiosos levantamentos de dados, seguindo um procedimento em que possam analisar diferentes soluções de um problema. A arquitetura é composta de um procedimento, um modelo orientado a objeto e um sistema de apoio à decisão para formação de células. Os resultados obtidos da aplicação mostram que a arquitetura proposta é viável com grandes possibilidades para continuar a ser desenvolvida em pesquisas futuras. / The celular manufacturing has an important prominence among the production systems, being used in significant part of the world class manufacturing companies and it is objective of constant researches. One of the fundamental aspects for the application of this production system is the solution to the problem of cells formation. Along the last three decades many algorithms were proposed to aid this decision, even so, they have not been applied intensively in the normal routine of the companies that in most of the cases, they cells design with base on the good sense and experience. Some of the factors that contribute to that are: there are not available necessary data to the solution of the problem, and the fact that each algorithm presents private situations, needing a specialist that is capable to choose them or to develop them and to apply them according to the specific characteristics of the problem. In this work we propose a framework that looks for to integrate the several algorithms of cell formation, al/owing that these are applied to a same group of data. The purpose is become available to professional of a company, the largest possible number of algorithms in a simple way and without the necessity of expensive survey of data, following a procedure in that it can analyze different solutions of a problem. The framework is composed of a procedure, an object-oriented model and a decision support system for cells formation. The obtained results of the application show that the proposal framework is acceptable with great possibilities to continue to be developed in future researches.

Atherosclerosis, characterized by the build-up of cholesterol, immune cells and cellular debris within arterial walls, is accelerated following myocardial infarction by poorly understood mechanisms. Ubiquitin, a small, well-studied intracellular protein involved in protein turnover via the proteasome pathway, has recently been shown to exert extracellular effects on cardiac myocytes, in vitro, and in mice undergoing myocardial remodeling. This study investigates the potential role of extracellular ubiquitin in atherosclerosis by determining its effects on two critical atherosclerotic processes: the migration of vascular smooth muscles cells and the uptake of modified LDL by monocyte/macrophages in foam cell formation. In the presence of ubiquitin, smooth muscle cell migration was accelerated and foam cell formation was enhanced, suggesting that ubiquitin has an active role in atherosclerosis.

Les techniques de groupement technologique sont aujourd’hui utilisées dans de nombreux ateliers de fabrication; elles consistent à décomposer les systèmes industriels en sous-systèmes ou cellules constitués de pièces et de machines. Trouver le groupement technologique le plus efficace est formulé en recherche opérationnelle comme un problème de formation de cellules. La résolution de ce problème permet de tirer plusieurs avantages tels que la réduction des stocks et la simplification de la programmation. Plusieurs critères peuvent être définis au niveau des contraintes du problème tel que le flot intercellulaire,l’équilibrage de charges intracellulaires, les coûts de sous-traitance, les coûts de duplication des machines, etc. Le problème de formation de cellules est un problème d'optimisation NP-difficile. Par conséquent les méthodes exactes ne peuvent être utilisées pour résoudre des problèmes de grande dimension dans un délai raisonnable. Par contre des méthodes heuristiques peuvent générer des solutions de qualité inférieure, mais dans un temps d’exécution raisonnable. Dans ce mémoire, nous considérons ce problème dans un contexte bi-objectif spécifié en termes d’un facteur d’autonomie et de l’équilibre de charge entre les cellules. Nous présentons trois types de méthodes métaheuristiques pour sa résolution et nous comparons numériquement ces métaheuristiques. De plus, pour des problèmes de petite dimension qui peuvent être résolus de façon exacte avec CPLEX, nous vérifions que ces métaheuristiques génèrent des solutions optimales. / Group technology techniques are now widely used in many manufacturing systems. Those techniques aim to decompose industrial systems into subsystems or cells of parts and machines. The problem of finding the most effectivegroup technology is formulated in operations research as the Cell Formation Problem. Several criteria can be used to specify the optimal solution such as flood intercellular, intracellular load balancing, etc. Solving this problem leads to several advantages such as reducing inventory and simplifying programming. The Cell Formation Problem is an NP-hard problem; therefore, exact methods cannot be used to solve large problems within a reasonabletime, whereas heuristics can generate solutions of lower quality, but in a reasonable execution time. We suggest in this work, three different metaheuristics to solve the cell formation problem having two objectives functions: cell autonomy and load balancing between the cells.We compare numerically these metaheuristics. Furthermore, for problems of smaller dimension that can be solved exactly with CPLEX, we verify that the metaheuristics can reach the optimal value.

The objective of the cellular manufacturing is to simplify the management of the<p>manufacturing industries. In regrouping the production of different parts into clusters,<p>the management of the manufacturing is reduced to manage different small<p>entities. One of the most important problems in the cellular manufacturing is the<p>design of these entities called cells. These cells represent a cluster of machines that<p>can be dedicated to the production of one or several parts. The ideal design of a<p>cellular manufacturing is to make these cells totally independent from one another,<p>i.e. that each part is dedicated to only one cell (i.e. if it can be achieved completely<p>inside this cell). The reality is a little more complex. Once the cells are created,<p>there exists still some traffic between them. This traffic corresponds to a transfer of<p>a part between two machines belonging to different cells. The final objective is to<p>reduce this traffic between the cells (called inter-cellular traffic).<p>Different methods exist to produce these cells and dedicated them to parts. To<p>create independent cells, the choice can be done between different ways to produce<p>each part. Two interdependent problems must be solved:<p>• the allocation of each operation on a machine: each part is defined by one or<p>several sequences of operations and each of them can be achieved by a set of<p>machines. A final sequence of machines must be chosen to produce each part.<p>• the grouping of each machine in cells producing traffic inside and outside the<p>cells.<p>In function of the solution to the first problem, different clusters will be created to<p>minimise the inter-cellular traffic.<p>In this thesis, an original method based on the grouping genetic algorithm (Gga)<p>is proposed to solve simultaneously these two interdependent problems. The efficiency<p>of the method is highlighted compared to the methods based on two integrated algorithms<p>or heuristics. Indeed, to form these cells of machines with the allocation<p>of operations on the machines, the used methods permitting to solve large scale<p>problems are generally composed by two nested algorithms. The main one calls the<p>secondary one to complete the first part of the solution. The application domain goes<p>beyond the manufacturing industry and can for example be applied to the design of<p>the electronic systems as explained in the future research.<p> / Doctorat en Sciences de l'ingénieur / info:eu-repo/semantics/nonPublished

Les systèmes multiprocesseurs sur puce électronique (On-Chip Multiprocessor [OCM]) sont considérés comme les meilleures structures pour occuper l'espace disponible sur les circuits intégrés actuels. Dans nos travaux, nous nous intéressons à un modèle architectural, appelé architecture isométrique de systèmes multiprocesseurs sur puce, qui permet d'évaluer, de prédire et d'optimiser les systèmes OCM en misant sur une organisation efficace des nœuds (processeurs et mémoires), et à des méthodologies qui permettent d'utiliser efficacement ces architectures. Dans la première partie de la thèse, nous nous intéressons à la topologie du modèle et nous proposons une architecture qui permet d'utiliser efficacement et massivement les mémoires sur la puce. Les processeurs et les mémoires sont organisés selon une approche isométrique qui consiste à rapprocher les données des processus plutôt que d'optimiser les transferts entre les processeurs et les mémoires disposés de manière conventionnelle. L'architecture est un modèle maillé en trois dimensions. La disposition des unités sur ce modèle est inspirée de la structure cristalline du chlorure de sodium (NaCl), où chaque processeur peut accéder à six mémoires à la fois et où chaque mémoire peut communiquer avec autant de processeurs à la fois. Dans la deuxième partie de notre travail, nous nous intéressons à une méthodologie de décomposition où le nombre de nœuds du modèle est idéal et peut être déterminé à partir d'une spécification matricielle de l'application qui est traitée par le modèle proposé. Sachant que la performance d'un modèle dépend de la quantité de flot de données échangées entre ses unités, en l'occurrence leur nombre, et notre but étant de garantir une bonne performance de calcul en fonction de l'application traitée, nous proposons de trouver le nombre idéal de processeurs et de mémoires du système à construire. Aussi, considérons-nous la décomposition de la spécification du modèle à construire ou de l'application à traiter en fonction de l'équilibre de charge des unités. Nous proposons ainsi une approche de décomposition sur trois points : la transformation de la spécification ou de l'application en une matrice d'incidence dont les éléments sont les flots de données entre les processus et les données, une nouvelle méthodologie basée sur le problème de la formation des cellules (Cell Formation Problem [CFP]), et un équilibre de charge de processus dans les processeurs et de données dans les mémoires. Dans la troisième partie, toujours dans le souci de concevoir un système efficace et performant, nous nous intéressons à l'affectation des processeurs et des mémoires par une méthodologie en deux étapes. Dans un premier temps, nous affectons des unités aux nœuds du système, considéré ici comme un graphe non orienté, et dans un deuxième temps, nous affectons des valeurs aux arcs de ce graphe. Pour l'affectation, nous proposons une modélisation des applications décomposées en utilisant une approche matricielle et l'utilisation du problème d'affectation quadratique (Quadratic Assignment Problem [QAP]). Pour l'affectation de valeurs aux arcs, nous proposons une approche de perturbation graduelle, afin de chercher la meilleure combinaison du coût de l'affectation, ceci en respectant certains paramètres comme la température, la dissipation de chaleur, la consommation d'énergie et la surface occupée par la puce. Le but ultime de ce travail est de proposer aux architectes de systèmes multiprocesseurs sur puce une méthodologie non traditionnelle et un outil systématique et efficace d'aide à la conception dès la phase de la spécification fonctionnelle du système. / On-Chip Multiprocessor (OCM) systems are considered to be the best structures to occupy the abundant space available on today integrated circuits (IC). In our thesis, we are interested on an architectural model, called Isometric on-Chip Multiprocessor Architecture (ICMA), that optimizes the OCM systems by focusing on an effective organization of cores (processors and memories) and on methodologies that optimize the use of these architectures. In the first part of this work, we study the topology of ICMA and propose an architecture that enables efficient and massive use of on-chip memories. ICMA organizes processors and memories in an isometric structure with the objective to get processed data close to the processors that use them rather than to optimize transfers between processors and memories, arranged in a conventional manner. ICMA is a mesh model in three dimensions. The organization of our architecture is inspired by the crystal structure of sodium chloride (NaCl), where each processor can access six different memories and where each memory can communicate with six processors at once. In the second part of our work, we focus on a methodology of decomposition. This methodology is used to find the optimal number of nodes for a given application or specification. The approach we use is to transform an application or a specification into an incidence matrix, where the entries of this matrix are the interactions between processors and memories as entries. In other words, knowing that the performance of a model depends on the intensity of the data flow exchanged between its units, namely their number, we aim to guarantee a good computing performance by finding the optimal number of processors and memories that are suitable for the application computation. We also consider the load balancing of the units of ICMA during the specification phase of the design. Our proposed decomposition is on three points: the transformation of the specification or application into an incidence matrix, a new methodology based on the Cell Formation Problem (CFP), and load balancing processes in the processors and data in memories. In the third part, we focus on the allocation of processor and memory by a two-step methodology. Initially, we allocate units to the nodes of the system structure, considered here as an undirected graph, and subsequently we assign values to the arcs of this graph. For the assignment, we propose modeling of the decomposed application using a matrix approach and the Quadratic Assignment Problem (QAP). For the assignment of the values to the arcs, we propose an approach of gradual changes of these values in order to seek the best combination of cost allocation, this under certain metric constraints such as temperature, heat dissipation, power consumption and surface occupied by the chip. The ultimate goal of this work is to propose a methodology for non-traditional, systematic and effective decision support design tools for multiprocessor system architects, from the phase of functional specification.

Doctor of Philosophy / Department of Human Nutrition / Denis M. Medeiros / Laman Mamedova / The internalization of aggregated low-­density lipoprotein (agLDL) may involve the actin cytoskeleton in ways that differ from the endocytosis of soluble LDL. Based on previous findings the P2Y[subscript]2 receptor (P2Y[subscript]2R) mediates these effects through interaction with filamin‐A (FLN‐A), an actin binding protein. Our findings also showed that uridine 5’‐ triphosphate (UTP), a preferential agonist of the P2Y[subscript]2R, stimulates the uptake of agLDL, and increases expression of low‐density lipoprotein receptor related protein 1 (LRP 1) in cultured mouse vascular smooth muscle cells (SMCs). The strategy of this research was to define novel mechanisms of LDL uptake through the modulation of the actin cytoskeleton in order to identify molecular targets involved in foam cell formation in vascular SMCs. For this project, we isolated aortic SMCs from wild type (WT) and P2Y[subscript]2R‐/‐ mice to investigate whether UTP and the P2Y[subscript]2R modulate expression of LRP 1 and low‐density lipoprotein receptor (LDLR). We also investigated the effects of UTP on uptake of DiI‐labeled agLDL in WT and P2Y[subscript]2R‐/‐ vascular SMCs. For LRP1 expression, cells were stimulated in the presence or absence of 10 [mu]M UTP. To determine LDLR mRNA expression, and for agLDL uptake, cells were transiently transfected for 24 h with cDNA encoding hemagglutinin-­tagged (HA-­tagged) WT P2Y[subscript]2R or a mutant P2Y[subscript]2R that does not bind FLN‐A, and afterwards treated with 10 [mu]M UTP. Total RNA was isolated, reversed transcribed to cDNA, and mRNA relative abundance determined by RT-­PCR using the delta-­delta Ct method with GAPDH as control gene. Results show SMCs expressing the mutant P2Y[subscript]2R that lacks the FLN‐A binding domain exhibit 3‐fold lower LDLR expression than SMCs expressing the WT P2Y[subscript]2R. There was also decrease in LRP1 mRNA expression in response to UTP in P2Y[subscript]2R‐/‐ SMCs compared to WT. Actinomycin‐D (20 [mu]g/ml) significantly reduced UTP-­induced LRP1 mRNA expression in P2Y[subscript]2R‐/‐ SMCs (P < 0.05). Compared to cells transfected with mutant P2Y[subscript]2R, cells transfected with WT P2Y[subscript]2R showed greater agLDL uptake in both WT VSMC and P2Y[subscript]2R-­/-­ cells. Together these results show that both LRP 1 and LDLR expressions are dependent on an intact P2Y[subscript]2R, and P2Y[subscript]2R/ FLN‐ A interaction is necessary for agLDL uptake.

Les systèmes multiprocesseurs sur puce électronique (On-Chip Multiprocessor [OCM]) sont considérés comme les meilleures structures pour occuper l'espace disponible sur les circuits intégrés actuels. Dans nos travaux, nous nous intéressons à un modèle architectural, appelé architecture isométrique de systèmes multiprocesseurs sur puce, qui permet d'évaluer, de prédire et d'optimiser les systèmes OCM en misant sur une organisation efficace des nœuds (processeurs et mémoires), et à des méthodologies qui permettent d'utiliser efficacement ces architectures. Dans la première partie de la thèse, nous nous intéressons à la topologie du modèle et nous proposons une architecture qui permet d'utiliser efficacement et massivement les mémoires sur la puce. Les processeurs et les mémoires sont organisés selon une approche isométrique qui consiste à rapprocher les données des processus plutôt que d'optimiser les transferts entre les processeurs et les mémoires disposés de manière conventionnelle. L'architecture est un modèle maillé en trois dimensions. La disposition des unités sur ce modèle est inspirée de la structure cristalline du chlorure de sodium (NaCl), où chaque processeur peut accéder à six mémoires à la fois et où chaque mémoire peut communiquer avec autant de processeurs à la fois. Dans la deuxième partie de notre travail, nous nous intéressons à une méthodologie de décomposition où le nombre de nœuds du modèle est idéal et peut être déterminé à partir d'une spécification matricielle de l'application qui est traitée par le modèle proposé. Sachant que la performance d'un modèle dépend de la quantité de flot de données échangées entre ses unités, en l'occurrence leur nombre, et notre but étant de garantir une bonne performance de calcul en fonction de l'application traitée, nous proposons de trouver le nombre idéal de processeurs et de mémoires du système à construire. Aussi, considérons-nous la décomposition de la spécification du modèle à construire ou de l'application à traiter en fonction de l'équilibre de charge des unités. Nous proposons ainsi une approche de décomposition sur trois points : la transformation de la spécification ou de l'application en une matrice d'incidence dont les éléments sont les flots de données entre les processus et les données, une nouvelle méthodologie basée sur le problème de la formation des cellules (Cell Formation Problem [CFP]), et un équilibre de charge de processus dans les processeurs et de données dans les mémoires. Dans la troisième partie, toujours dans le souci de concevoir un système efficace et performant, nous nous intéressons à l'affectation des processeurs et des mémoires par une méthodologie en deux étapes. Dans un premier temps, nous affectons des unités aux nœuds du système, considéré ici comme un graphe non orienté, et dans un deuxième temps, nous affectons des valeurs aux arcs de ce graphe. Pour l'affectation, nous proposons une modélisation des applications décomposées en utilisant une approche matricielle et l'utilisation du problème d'affectation quadratique (Quadratic Assignment Problem [QAP]). Pour l'affectation de valeurs aux arcs, nous proposons une approche de perturbation graduelle, afin de chercher la meilleure combinaison du coût de l'affectation, ceci en respectant certains paramètres comme la température, la dissipation de chaleur, la consommation d'énergie et la surface occupée par la puce. Le but ultime de ce travail est de proposer aux architectes de systèmes multiprocesseurs sur puce une méthodologie non traditionnelle et un outil systématique et efficace d'aide à la conception dès la phase de la spécification fonctionnelle du système. / On-Chip Multiprocessor (OCM) systems are considered to be the best structures to occupy the abundant space available on today integrated circuits (IC). In our thesis, we are interested on an architectural model, called Isometric on-Chip Multiprocessor Architecture (ICMA), that optimizes the OCM systems by focusing on an effective organization of cores (processors and memories) and on methodologies that optimize the use of these architectures. In the first part of this work, we study the topology of ICMA and propose an architecture that enables efficient and massive use of on-chip memories. ICMA organizes processors and memories in an isometric structure with the objective to get processed data close to the processors that use them rather than to optimize transfers between processors and memories, arranged in a conventional manner. ICMA is a mesh model in three dimensions. The organization of our architecture is inspired by the crystal structure of sodium chloride (NaCl), where each processor can access six different memories and where each memory can communicate with six processors at once. In the second part of our work, we focus on a methodology of decomposition. This methodology is used to find the optimal number of nodes for a given application or specification. The approach we use is to transform an application or a specification into an incidence matrix, where the entries of this matrix are the interactions between processors and memories as entries. In other words, knowing that the performance of a model depends on the intensity of the data flow exchanged between its units, namely their number, we aim to guarantee a good computing performance by finding the optimal number of processors and memories that are suitable for the application computation. We also consider the load balancing of the units of ICMA during the specification phase of the design. Our proposed decomposition is on three points: the transformation of the specification or application into an incidence matrix, a new methodology based on the Cell Formation Problem (CFP), and load balancing processes in the processors and data in memories. In the third part, we focus on the allocation of processor and memory by a two-step methodology. Initially, we allocate units to the nodes of the system structure, considered here as an undirected graph, and subsequently we assign values to the arcs of this graph. For the assignment, we propose modeling of the decomposed application using a matrix approach and the Quadratic Assignment Problem (QAP). For the assignment of the values to the arcs, we propose an approach of gradual changes of these values in order to seek the best combination of cost allocation, this under certain metric constraints such as temperature, heat dissipation, power consumption and surface occupied by the chip. The ultimate goal of this work is to propose a methodology for non-traditional, systematic and effective decision support design tools for multiprocessor system architects, from the phase of functional specification.