La culture cellulaire traditionnelle en deux dimensions (2D) ne peut pas reproduire les propriétés des tissus observées dans des organes en trois dimensions (3D). Ces tissus, en particulier les tissus de soutien comme l'os, sont soumis à des contraintes mécaniques, facteurs majeurs de régulation des interactions cellulaires et cellules/matrices. Il y a donc un intérêt croissant pour les modèles 3D, afin de mieux comprendre les différents aspects du fonctionnement cellulaire et du remodelage osseux, dans des systèmes de moindre complexité que les modèles in vivo. Nous nous sommes intéressés ici aux cellules ostéoblastiques et à une de leur protéine matricielle, la sialoprotéine osseuse (BSP). La BSP appartient à la famille des "small integrin-binding ligand N-linked glycoproteins" (SIBLING), impliquées dans le développement, le remodelage et la minéralisation de l’os, et répondant rapidement à la contrainte mécanique. Notre objectif était d’analyser l’impact de cette protéine sur la différenciation ostéoblastique et l’ostéogénèse in vitro à partir de cellules de calvaria de souris présentant une extinction génique de la BSP (BSP-/-) cultivées en 2D et en 3D. Nous avons montré que les cellules BSP-/- présentaient un défaut de formation osseuse et de minéralisation qui est dépendant de la densité cellulaire. Puis nous avons développé et validé un bioréacteur perfusé et stimulable mécaniquement via le système ZetOsTM. Les premiers résultats obtenus avec cet outil contrôlé montrent que l’environnement 3D améliore la différenciation des cellules BSP-/-. Ces travaux restent à développer, notamment pour analyser l’effet des contraintes mécaniques sur ces cellules / Traditional (2D) cell culture cannot reproduce the tissue properties observed in 3 dimensional organs (3D). Weight-bearing organs such as bone are subjected to mechanical stresses, which are major regulating factors for cell and cell/matrix interactions. There is thus a growing interest in 3D culture models, in order to better understand the different aspects of cell function and bone remodeling in systems less complex than in vivo models. We are interested here in the osteoblastic cells and in one of their matrix proteins, the bone sialoprotein (BSP). BSP belongs to the family of the "small integrin -binding ligand N -linked glycoproteins" (SIBLING), involved in the development, remodeling and mineralization of bone, and responding quickly to mechanical stress. Our goal in this work was to analyze the impact of the absence of this protein on osteoblast differentiation and bone formation in vitro from mouse calvarial cells (MCC) with a gene knockout of BSP (BSP-/-), grown in 2D and 3D. We have shown that BSP-/- cells have a defect in bone formation and mineralization which is cell density dependent. We have developed and validated a perfused bioreactor able to apply mechanical stress to culture scaffolds via the ZetOsTM system. Our first results with this powerful tool show that a 3D environment improves BSP-/- cells differentiation. This work remains to be developed, in particular to analyze the effects of mechanical stress on these cells

Exprimer le parallélisme dans la programmation de manière simple et performante est un défi auquel l'informatique fait face, en raison de l'évolution actuelle des architectures matérielles. BSML est un langage permettant une programmation parallèle de haut niveau, structurée, qui participe à cette recherche. En s'appuyant sur le coeur du langage existant, cette thèse propose d'une part des extensions qui en font un langage plus général et plus simple (traits impératifs tels que références et exceptions, syntaxe spécifique...) tout en conservant et étendant sa sûreté (sémantiques formelles, système de types...) et d'autre part une méthodologie de développement d'applications parallèles certifiées / Finding a good paradigm to represent parallel programming in a simple and efficient way is a challenge currently faced by computer science research, mainly due to the evolution of machine architectures towards multi-core processors. BSML is a high level, structured parallel programming language that takes part in the research in an original way. By building upon existing work, this thesis extends the language and makes it more general, simple and usable with added imperative features such as references and exceptions, a specific syntax, etc. The existing formal and safety characteristics of the language (semantics, type system...) are preserved and extended. A major application is given in the form of a methodology for the development of fully proved parallel programs

Grades computacionais oportunistas utilizam recursos ociosos de máquinas compartilhadas para executar aplicações que necessitam de um alto poder computacional e/ou trabalham com grandes quantidades de dados. Mas a execução de aplicações paralelas computacionalmente intensivas em ambientes dinâmicos e heterogêneos, como grades computacionais oportunistas, é uma tarefa difícil. Máquinas podem falhar, ficar inacessíveis ou passar de ociosas para ocupadas inesperadamente, comprometendo a execução de aplicações. Um mecanismo de tolerância a falhas que dê suporte a arquiteturas heterogêneas é um importante requisito para estes sistemas. Neste trabalho, analisamos, implementamos e avaliamos um mecanismo de tolerância a falhas baseado em checkpointing para aplicações paralelas em grades computacionais oportunistas. Este mecanismo permite o monitoramento de execuções e a migração de aplicações entre nós heterogêneos da grade. Mas além da execução, é preciso gerenciar e armazenar os dados gerados e utilizados por estas aplicações. Desejamos uma infra-estrutura de armazenamento de dados de baixo custo e que utilize o espaço livre em disco de máquinas compartilhadas da grade. Devemos utilizar somente os ciclos ociosos destas máquinas para armazenar e recuperar dados, de modo que um sistema de armazenamento distribuído que as utilize deve ser redundante e tolerante a falhas. Para resolver o problema do armazenamento de dados em grades oportunistas, projetamos, implementamos e avaliamos o middleware OppStore. Este middleware provê armazenamento distribuído e confiável de dados, que podem ser acessados de qualquer máquina da grade. As máquinas são organizadas em aglomerados, que são conectados por uma rede peer-to-peer auto-organizável e tolerante a falhas. Dados são codificados em fragmentos redundantes antes de serem armazenados, de modo que arquivos podem ser reconstruídos utilizando apenas um subconjunto destes fragmentos. Finalmente, para lidar com a heterogeneidade dos recursos, desenvolvemos uma extensão ao protocolo de roteamento em redes peer-to-peer Pastry. Esta extensão adiciona balanceamento de carga e suporte à heterogeneidade de máquinas ao protocolo Pastry. / Opportunistic computational grids use idle resources from shared machines to execute applications that need large amounts of computational power and/or deal with large amounts of data. But executing computationally intensive parallel applications in dynamic and heterogeneous environments, such as opportunistic grids, is a daunting task. Machines may fail, become inaccessible, or change from idle to occupied unexpectedly, compromising the application execution. A fault tolerance mechanism that supports heterogeneous architectures is an important requisite for such systems. In this work, we analyze, implement and evaluate a checkpointing-based fault tolerance mechanism for parallel applications running on opportunistic grids. The mechanism monitors application execution and allows the migration of applications between heterogeneous nodes of the grid. But besides application execution, it is necessary to manage data generated and used by those applications. We want a low cost data storage infrastructure that utilizes the unused disk space of grid shared machines. The system should use the machines to store and recover data only during their idle periods, requiring the system to be redundant and fault-tolerant. To solve the data storage problem in opportunistic grids, we designed, implemented and evaluated the OppStore middleware. This middleware provides reliable distributed storage for application data, which can be accessed from any machine in the grid. The machines are organized in clusters, connected by a self-organizing and fault-tolerant peer-to-peer network. During storage, data is codified into redundant fragments, allowing the reconstruction of the original file using only a subset of those fragments. Finally, to deal with resource heterogeneity, we developed an extension to the Pastry peer-to-peer routing substrate, enabling heterogeneity-aware load-balancing message routing.

Das Ziel der vorliegenden Arbeit ist es, den Einsatz der konfokalen Laser-Scanning-Mikroskopie (LSM) für die Beurteilung von humanen Osteoblasten auf experimentellen Implantatoberflächen zu prüfen. Die acht Probekörper besaßen anodische Konversionsoberflächen, die aus den Elektrolyten Zirkoniumsulfat, Phosphorsäure und Kaliumfluorid sowie deren Kombinationen hergestellt waren. Als Positivstandard dienten TICER® und Cercon®, als Negativstandard commercial pure Titan (CPT/Reintitan). Diese Probekörper wurden in Chamber Slides mit einer humanen Osteoblastenkultur inkubiert. Am 3., 5., 7. und 10. Versuchstag erfolgte die immunhistochemische Darstellung von Bone-Sialoprotein (BSP). Anschließend wurden im LSM fluoreszenzmikroskopisch 3D-Bildstapel aufgenommen und mit dem 2D-mikroskopischen Verfahren verglichen. Es zeigte sich, dass das Bone-Sialoprotein einen Hinweis auf aktive Osteoblasten darstellt. Die BSP-exprimierenden Strukturen, die sich zu Volumina zusammenfügen, variieren an den verschiedenen Versuchstagen und bei den unterschiedlichen Oberflächenstrukturen. Eine deutlich erhöhte BSP-Expressionsrate wurde bei den elektrolytisch beschichteten Probekörpern aus Zirkoniumsulfat, Kaliumfluorid und Phosphorsäure erfasst. Ein eindeutiger Unterschied zwischen der 2D-Mikroskopie und der LSM ergab sich jedoch nicht. Die LSM erlaubt aber zusätzlich Aussagen über absorbierte Proteine an den Probekörperoberflächen durch eine um 90°-gedrehte Projektion der 3D-Bildstapel.

This thesis takes part in the formal verification of parallel programs. The aim of formal verification is to ensure that a program will run as it should, without making mistakes, blocking, or terminating abnormally. This is even more important in the parallel computation field, where the cost of calculations can be very high. The BSP model (Bulk Synchronous Parallelism) is a model of parallelism well suited for the use of formal methods. It guarantees a structure in the parallel program, by organising it into super-steps, each of them consisting of a phase of computations, then communications between the processes. In this thesis, we chose to extend an existing tool to adapt it for the proof of BSP programs. We based ourselves on Why, a VCG (verification condition generator) that has the advantage of being able to interface with several automatic provers and proof assistants to discharge the proof obligations. There are multiple contributions in this thesis. In a first part, we present a comparison of the existing BSP libraries, in order to show the most used BSP primitives, which are the most interesting to formalise. We then present BSP-Why, our tool for the proof of BSP programs. This tools uses a generation of a sequential program to simulate the parallel program in input, thus allowing the use of Why and the numerous associated provers to prove the proof obligations. We then show how BSP-Why can be used to prove the correctness of some basic BSP algorithms, and also on a more complex example, the generation of the state-space (model-checking) of systems, especially for security protocols. Finally, in order to ensure the greatest confidence in the BSP-Why tool, we give a formalisation of the language semantics, in the Coq proof assistant. We also prove the correctness of the transformation used to go from a parallel program to a sequential program

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mammalian fertilization is a sequence of unique and fascinating events, during which seminal proteins are of crucial role. In case of bull (Bos taurus), proteins of seminal plasma (BSP), especially its major component PDC-109, are known to be in aggregated forms, but little is known about mechanism of forming aggregates and their biological function. In present thesis we discovered some interesting properties of PDC-109 and BSP proteins. We found that concentration of these proteins influences their aggregation state significantly, which can be of great biological importance. Separation of seminal proteins by size exclusion chromatography revealed three main fractions denoted I, II and III, with apparent molecular weights of Mr > 150 000, Mr = 30 000 and Mr = 13 000, respectively. In case of PDC-109, molecular weights of theese fractions were retained even after purification procedure, which implies very stable interactions in forming of aggregates. In addition, there was a difference in distribution of PDC-109 glycoforms among fractions, which can be related to the fact, that theese fractions have different sperm membrane binding patterns as we determined by fluorescence microscopy. However, further experiments are needed for better understanding this issue.

För att kunna minska arbetsbelastningen på grafiker och speldesigners används Procedural Content Generation (PCG) för att kunna skapa varierat spelinnehåll med lite ansträngning. Denna studie undersöker algoritmerna Binary Space Partitioning (BSP) och Shortest Path (SP) för generering av grottsystem. Syftet med undersökningen är att ta reda på hur tidseffektivt algoritmerna kan generera ett grottsystem samt hur komplext ett grottsystem genererat av respektive algoritm är. Efter undersökning kan slutsatsen dras att BSP är den mest effektiva algoritmen på att generera grottsystem medan SP bidrar med mest skillnad i komplexitet mellan genereringar.