Relentless CMOS scaling coupled with lower design tolerances is making ICs increasingly susceptible to transient faults, wear-out related permanent faults and process variations. Decreasing CMOS reliability implies that high-availability systems which were previously restricted to the domain of mainframe computers or specially designed fault-tolerant systems may be come important for the commodity market as well. In this thesis we tackle the problem of enabling efficient, low cost and configurable fault-tolerance using Chip Multiprocessors (CMPs). Our work studies architectural fault detection methods based on redundant execution, specifically focusing on “leader-follower” architectures. In such architectures redundant execution is performed on two cores/threads of a CMP. One thread acts as the leading thread while the other acts as the trailing thread. The leading thread assists the execution of the trailing thread by forwarding the results of its execution. These forwarded results are used as predictions in the trailing thread and help improve its performance. In this thesis, we introduce a new form of execution assistance called critical value forwarding. Critical value forwarding uses heuristics to identify instructions on the critical path of execution and forwards the results of these instructions to the trailing core. The advantage of critical value forwarding is that it provides much of the speed up obtained by forwarding all values at a fraction of the bandwidth cost. We propose two architectures to exploit the idea of critical value forwarding. The first of these operates the trailing core at lower voltage/frequency levels in order to provide energy-efficient redundant execution. In this context, we also introduce algorithms to dynamically adapt the voltage/frequency level of the trailing core based on program behavior. Our experimental evaluation shows that this proposal consumes only 1.26 times the energy of a non-fault-tolerant baseline and has a mean performance overhead of about 1%. We compare our proposal to two previous energy-efficient fault-tolerant CMP proposals and find that our proposal delivers higher energy-efficiency and lower performance degradation than both while providing a similar level of fault coverage. Our second proposal uses the idea of critical value forwarding to improve fault-tolerant CMP throughput. This is done by using coarse-grained multithreading to mul-tiplex trailing threads on a single core. Our evaluation shows that this architecture delivers 9–13% higher throughput than previous proposals, including one configuration that uses simultaneous multithreading(SMT) to multiplex trailing threads. Since this proposal increases fault-tolerant CMP throughput by executing multiple threads on a single core, it comes at a modest cost in single-threaded performance, a mean slowdown between11–14%.

Les effets des agents anti-ostéoporotiques sur le tissu osseux sont évalués au niveau de la crête iliaque (CI) mais les réponses aux traitements peuvent varier selon le site osseux. Le but de cette étude était de comprarer les effets de l’acide zolérodronique (ZOL) et du tériparatide (TPTD) au niveau de la crête iliaque et de la vertèbre lombaire L1 (VL1) chez la brebis âgée. Le ZOL a induit une forte diminution du remodelage osseux et une augmentation des microendommagements au niveau des deux sites et une modification des crosslinks du collagène surtout au niveau de l’os cortical de la CI. Trois mois de TPTD ont augmenté le remodelage osseux uniquement au niveau de la VL1. En conclusion, les délais et les amplitudes de réponses au ZOL ou au TPTD diffèrent entre la CI et la VL1 chez la brebis. Ces résultats montrent l’importance de prendre en compte le site osseux pour évaluer les effets des agents anti-ostéoporotiques / The effects of anti-osteoporotic agents on bone tissue are evaluated on iliac crest (IC) but the answers to treatments may vary according to the skeletal site. The purpose of this study was to compare the effect of zoledronic acid (ZOL) and teriparatide (TPTD) on IC and lumbar vertebrae (LV1) in ewes. ZOL has induced a high decrease of bone remodeling, an increase in microdamages in both sites and a modification of collagen crosslinks mainly in cortical bone of IC. Three months of TPTD has increased the bone remodeling only in LV1. In conclusion, the delays and the magnitudes of responses to ZOL or to TPTD differ between IC and LV1 in ewes. These results show that the distinction of bone sites to study the early effects of antiosteoporotic therapies appears meaningful

No description available.

Les ostéocytes sont les plus nombreuses cellules du tissu osseux, enterrées dans la matrice osseuse. Elles sont interconnectées par des dendrites, situées dans des canaux appelés canalicules. Les lacunes ostéocytaires, les cavités dans lesquelles les cellules sont logées, avec les canalicules forment un réseau de communication à travers la matrice osseuse, permettant le transport des nutriments et des signaux. Ces cellules, considérées d’abord passives, ont révélé dernièrement leur rôle en tant que cellules mécanosensitives et orchestratrices du remodelage osseux. Malgré les progrès récents des techniques d'imagerie, aucune méthode disponible ne fournit une évaluation 3D adéquate du réseau lacuno-canaliculaire (LCN). Les objectifs de cette thèse ont porté sur l’imagerie 3D du LCN par tomographie synchrotron à rayons X (SR-CT), et le développement d’outils de détection et segmentation 3D de ce réseau cellulaire, afin de le quantifier et analyser. Nous démontrons la faisabilité de la SR-CT en géométrie parallèle pour imager le LCN dans le tissu osseux (voxel~300nm). Cette technique fournit des données 3D sur la morphologie du réseau cellulaire et aussi sur la composition de la matrice osseuse. Comparée aux méthodes d'imagerie 3D existantes, la SR-CT permet l'imagerie d’un volume de tissu beaucoup plus important, d'une manière plus simple et rapide. Cela rend possible l'étude de séries de spécimens afin d'obtenir des conclusions biomédicales. Nous proposons aussi l'utilisation de l’holotomographie divergente synchrotron, pour imager l'ultrastructure du tissu osseux (voxel~60nm). La reconstruction d'image fournit des cartes de phase, obtenues après application d'un algorithme d’inversion de phase adéquat. Cette technique a permis l'évaluation du réseau cellulaire avec une précision plus élevée et de visualiser, pour la première fois en 3D, l'organisation des fibres de collagène. Afin d'obtenir des résultats quantitatifs sur la géométrie du réseau cellulaire, celui doit être segmenté. À cause des limitations de la résolution spatiale, les canalicules apparaissent comme de structures tubulaires très fines (diamètre 1-3 voxels). Ceci, combiné avec le bruit, le faible contraste et la grande taille des images (8Go), rendent la segmentation difficile. Nous proposons une méthode de filtrage non-linéaire 3D, basée sur le rehaussement des structures linéaires, combiné avec un filtrage bilatéral. Cela permet une amélioration de la détection des canalicules, la réduction du bruit de fond et de la préservation des lacunes cellulaires. Pour la segmentation d'images, nous avons développé une méthode basée sur la croissance de région variationnelle. Nous proposons deux expressions de fonctionnelles d'énergie à minimiser, afin de détecter la structure souhaitée. Des résultats quantitatifs préliminaires sont obtenus à partir d’une analyse en composantes connexes sur des échantillons humaines et des observations relatives au réseau ostéocytaire sont présentés. / The osteocytes are the most abundant and longest living bone cells, embedded in the bone matrix. They are interconnected with each other through dendrites, located in slender canals called canaliculi. The osteocyte lacunae, cavities in which the cells are located, together with the canaliculi form a communication network throughout the bone matrix, permitting transport of nutrients, waste and signals. These cells were firstly considered passive, but lately it has become increasingly clear their role as mechanosensory cells and orchestrators of bone remodeling. Despite recent advances in imaging techniques, none of the available methods can provide an adequate 3D assessment of the lacuno-canalicular network (LCN). The aims of this thesis were to achieve 3D imaging of the LCN with synchrotron radiation X-ray computed tomography (SR-CT) and to develop tools for 3D detection and segmentation of this cell network, leading towards automatic quantification of this structure. We demonstrate the feasibility of parallel beam SR-CT to image in 3D the LCN (voxel~300 nm). This technique can provide data on both the morphology of the cell network and the composition of the bone matrix. Compared to the other 3D imaging methods, this enables imaging of tissue covering a number of cell lacunae three orders of magnitude greater, in a simpler and faster way. This makes possible the study of sets of specimens in order to reach biomedical conclusions. Furthermore, we propose the use of divergent holotomography, to image the ultrastructure of bone tissue (voxel~60 nm). The image reconstruction provides phase maps, obtained after the application of a suitable phase retrieval algorithm. This technique permits assessment of the cell network with higher accuracy and it enables the 3D organization of collagen fibres organization in the bone matrix, to be visualized for the first time. In order to obtain quantitative parameters on the geometry of the cell network, this has to be segmented. Due to the limitations in spatial resolution, canaliculi appear as 3D tube-like structures measuring only 1-3 voxels in diameter. This, combined with the noise, the low contrast and the large size of each image (8 GB), makes the segmentation a difficult task. We propose an image enhancement method, based on a 3D line filter combined with bilateral filtering. This enables improvement in canaliculi detection, reduction of the background noise and cell lacunae preservation. For the image segmentation we developed a method based on variational region growing. We propose two expressions for energy functionals to minimize in order to detect the desired structure, based on the 3D line filter map and the original image. Preliminary quantitative results on human femoral samples are obtained based on connected components analysis and a few observations related to the bone cell network and its relation with the bone matrix are presented.

Depuis une vingtaine d’années, les historiens de l’art s’intéressent de près à la microarchitecture, c’est-à-dire la miniaturisation d’édifices dans les oeuvres d’art, en particulier dans l’orfèvrerie. Les études sur le sujet se concentrent toutefois essentiellement sur la période médiévale et s’attachent à définir dans quelle mesure ces oeuvres imitent des édifices existants. Elles sont rarement étendues à d’autres périodes. Or, la Renaissance florentine, marquée par une mutation profonde de l’art d’édifier et de concevoir l’architecture, constitue une fenêtre d’observation privilégiée, que nous mettons à profit pour explorer les liens que les édifices miniaturisés en orfèvrerie entretiennent avec leurs homologues monumentaux architecturés. Pour ce faire, nous identifions trois fonctions de la microarchitecture : celle d’objet ou de partie d’un objet (Objectum), celle d’assemblage d’éléments architecturaux (Ædiculum), celle d’image offerte au regard du spectateur (Imago). Dans Objectum, la microarchitecture est envisagée à travers la pièce d’orfèvrerie qu’elle contribue à orner, son contexte de fabrication et sa matérialité. Cet examen est aussi l’occasion de présenter les matériaux et les techniques utilisées en orfèvrerie. Ædiculum est consacré à l’étude des éléments architecturaux qui composent les petits édifices. Ces éléments mettent au jour des correspondances entre l’orfèvrerie et d’autres arts, tels que la sculpture ou la peinture. Dans Imago, nous montrons que les petites dimensions de la microarchitecture, qui la rendent propre à être embrassée du regard, en font une image qui engage un dialogue privilégié avec le spectateur grâce à un ensemble de dispositifs, qui vont de ses qualités esthétiques à sa capacité évocatrice en passant par les significations religieuses et politiques dont elle est chargée. Au total, cette étude montre que la microarchitecture ne se définit pas nécessairement dans son rapport avec la grande architecture mais consiste plutôt en un phénomène artistique indépendant et universel. / For the last twenty years art historians have developed an interest in microarchitecture: the miniaturization of architecture in works of art, especially in goldsmithery. Studies dedicated to the topic mostly focus on medieval period, trying to define which large-scale buildings these works might imitate. However, these studies are rarely extended to other periods of time. Renaissance Florence, characterized by a deep transformation of the art of architecture, is a significant period we chose in order to observe the connections between miniaturized and monumental buildings. This requires the identification of three aspects of microarchitecture: being an object or part of an object (Objectum), combining different architectural motives (Ædiculum) and presenting itself as an image to be seen by a viewer (Imago). With Objectum, we examine the microarchitecture in relation to the work it contributes to ornate as well as within its context of production. This inspection is also a relevant opportunity to present the materials and the techniques used by the goldsmiths. With Ædicula, we study the architectural motives that compose the miniaturized buildings. The motives show the similarities between goldsmithery and other arts like sculpture and painting. With Imago, we consider the dialog that microarchitecture establishes with the viewer thanks to several dispositives such as the æsthetic qualities of the pieces, their ability to evocated something familiar (a building) and, sometimes, their religious and political meanings. In total, this study argues that micorarchitecture does not necessarily define itself within its relationship to large-scale architecture but should rather be understood as an independent, universal artistic phenomenon.

SIMLOX is a discrete-event simulation software developed by Systecon AB for analysing logistic support solution scenarios. To cope with ever larger problems, SIMLOX's simulation engine was recently enhanced with a parallel execution mechanism in order to take advantage of multi-core processors. However, this extension did not result in the desired reduction in runtime for all simulation scenarios even though the parallelisation strategy applied had promised linear speedup. Therefore, an in-depth analysis of the limiting scalability bottlenecks became necessary and has been carried out in this project. Through the use of a low-overhead profiler and microarchitecture analysis, the root causes were identified: atomic operations causing a high communication overhead, poor locality leading to translation lookaside buffer thrashing, and hot spots that consume significant amounts of CPU time. Subsequently, appropriate optimisations to overcome the limiting factors were implemented: eliminating the expensive operations, more efficient handling of heap memory through the use of a scalable memory allocator, and data structures that make better use of caches. Experimental evaluation using real world test cases demonstrated a speedup of at least 6.75x on an eight-core processor. Most cases even achieve a speedup of more than 7.2x. The various optimisations implemented further helped to lower run times for sequential execution by 1.5x or more. It can be concluded that achieving nearly linear speedup on a multi-core processor is possible in practice for discrete-event simulation. / SIMLOX är en kommersiell mjukvara utvecklad av Systecon AB, vars huvudsakliga funktion är en händelsestyrd simuleringskärna för analys av underhållslösningar för komplexa tekniska system. För hantering av stora problem så används parallellexekvering för simuleringen, vilket i teorin borde ge en nästan linjär skalning med antal trådar. Prestandaförbättringen som observerats i praktiken var dock ytterst begränsad, varför en ordentlig analys av skalbarheten har gjorts i detta projekt. Genom användandet av ett profileringsverktyg med liten overhead och mikroarkitektur-analys, så kunde orsakerna hittas: atomiska operationer som skapar mycket overhead för kommunikation, dålig lokalitet ger fragmentering vid översättning till fysiska adresser och dåligt utnyttjande av TLB-cachen, och vissa flaskhalsar som kräver mycket CPU-kraft. Därefter implementerades och testade optimeringar för att undvika de identifierade problem. Testade lösningar inkluderar eliminering av dyra operationer, ökad effektivitet i minneshantering genom skalbara minneshanteringsalgoritmer och implementation av datastrukturer som ger bättre lokalitet och därmed bättre användande av cache-strukturen. Verifiering på verkliga testfall visade på uppsnabbningar på åtminstone 6.75 gånger på en processor med 8 kärnor. De flesta fall visade på en uppsnabbning med en faktor större än 7.2. Optimeringarna gav även en uppsnabbning med en faktor på åtminstone 1.5 vid sekventiell exekvering i en tråd. Slutsatsen är därmed att det är möjligt att uppnå nästan linjär skalning med antalet kärnor för denna typ av händelsestyrd simulering.

Os bisfosfonatos são medicamentos amplamente e efetivamente utilizados para o tratamento de doenças osteolíticas. Entretanto, na cavidade oral, é de particular relevância, pois possuem como efeito adverso a osteonecrose dos maxilares induzida pelo uso de bisfosfonatos. Sua etiopatogenia ainda não é bem estabelecida, os métodos de detecção são insatisfatórios e as terapias recomendadas são por vezes, medidas paliativas e ineficazes. Pouco ainda é sabido sobre o efeito do Ácido Zoledrônico na microestrutura óssea, portanto, propusemo-nos a realizar um estudo em modelo animal que analisasse o trabeculado ósseo da mandíbula através da Micro-CT. Foram utilizados 24 ratos machos (Rattus novergicus, albinus, Wistar), com 12 semanas de vida, divididos em 2 grupos: grupo controle (cloreto de sódio 0,9%) e grupo ácido zoledrônico (ácido zoledrônico 0,6mg/kg). As substâncias foram administradas via intraperitoneal a cada 28 dias em um total de 5 doses. Após 150 dias do início do experimento, foi realizada a eutanásia dos animais e então as amostras foram preparadas e escaneadas (Skyscan 1174) para análise da microestrutura óssea através da Micro- CT. O teste t-student demonstrou diferença estatisticamente significativa (p<0,05) em todos os fatores: volume ósseo, densidade óssea, fator de padrão trabecular, índice de modelo estrutural, espessura trabecular, separação trabecular, porosidade total exceção de número de trabéculas e volume tecidual, demonstrando que há alterações significativas na estrutura trabecular pelo uso de bisfosfonatos. O grupo medicado com ácido zoledrônico comparado ao grupo controle demonstrou trabéculas mais espessas, menos separadas e com menores ligações. / Bisphosphonates are widely and effectively drugs used for the treatment of osteolytic disorders. However, in the oral cavity, this situation is of particular relevance as it can lead to bisphosphonate related osteonecrosis of the jaws. Its etiopathogenesis is still not established, detection methods are unsatisfactory and recommended therapies are sometimes palliative and often ineffective. Little is known about the effect of zoledronic acid on the quality of trabecular bone, therefore, we proposed to conduct a study in an animal model to examine the trabecular bone of the jaw through the Micro-CT. 24 male rats were used (Rattus norvegicus, Albinus, Wistar), with 12 weeks old, divided into 2 groups: control group (sodium chloride 0.9%) and group with zoledronic acid (zoledronic acid 0.6 mg / kg). The substances were administered intraperitoneally every 28 days for a total of 5 doses. After 150 days from the beginning of the experiment, the animals were sacrificed and then the samples were prepared and scanned (Skyscan 1174) for analysis of the bone microstructure through Micro-CT. The \"t-student\" test demonstrated statistically significant differences (p<0.05) in all factors: bone volume, osseous density, trabecular pattern, structure model index, trabecular thickness, trabecular separation, total porosity except trabecular number and tissue volume, demonstrating that there are significant changes in the trabecular structure of the bisphosphonates. Zoledronic Acid compared to control group shows thicker, less separate and lower connected trabeculae.

Os bisfosfonatos são medicamentos amplamente e efetivamente utilizados para o tratamento de doenças osteolíticas. Entretanto, na cavidade oral, é de particular relevância, pois possuem como efeito adverso a osteonecrose dos maxilares induzida pelo uso de bisfosfonatos. Sua etiopatogenia ainda não é bem estabelecida, os métodos de detecção são insatisfatórios e as terapias recomendadas são por vezes, medidas paliativas e ineficazes. Pouco ainda é sabido sobre o efeito do Ácido Zoledrônico na microestrutura óssea, portanto, propusemo-nos a realizar um estudo em modelo animal que analisasse o trabeculado ósseo da mandíbula através da Micro-CT. Foram utilizados 24 ratos machos (Rattus novergicus, albinus, Wistar), com 12 semanas de vida, divididos em 2 grupos: grupo controle (cloreto de sódio 0,9%) e grupo ácido zoledrônico (ácido zoledrônico 0,6mg/kg). As substâncias foram administradas via intraperitoneal a cada 28 dias em um total de 5 doses. Após 150 dias do início do experimento, foi realizada a eutanásia dos animais e então as amostras foram preparadas e escaneadas (Skyscan 1174) para análise da microestrutura óssea através da Micro- CT. O teste t-student demonstrou diferença estatisticamente significativa (p<0,05) em todos os fatores: volume ósseo, densidade óssea, fator de padrão trabecular, índice de modelo estrutural, espessura trabecular, separação trabecular, porosidade total exceção de número de trabéculas e volume tecidual, demonstrando que há alterações significativas na estrutura trabecular pelo uso de bisfosfonatos. O grupo medicado com ácido zoledrônico comparado ao grupo controle demonstrou trabéculas mais espessas, menos separadas e com menores ligações. / Bisphosphonates are widely and effectively drugs used for the treatment of osteolytic disorders. However, in the oral cavity, this situation is of particular relevance as it can lead to bisphosphonate related osteonecrosis of the jaws. Its etiopathogenesis is still not established, detection methods are unsatisfactory and recommended therapies are sometimes palliative and often ineffective. Little is known about the effect of zoledronic acid on the quality of trabecular bone, therefore, we proposed to conduct a study in an animal model to examine the trabecular bone of the jaw through the Micro-CT. 24 male rats were used (Rattus norvegicus, Albinus, Wistar), with 12 weeks old, divided into 2 groups: control group (sodium chloride 0.9%) and group with zoledronic acid (zoledronic acid 0.6 mg / kg). The substances were administered intraperitoneally every 28 days for a total of 5 doses. After 150 days from the beginning of the experiment, the animals were sacrificed and then the samples were prepared and scanned (Skyscan 1174) for analysis of the bone microstructure through Micro-CT. The \"t-student\" test demonstrated statistically significant differences (p<0.05) in all factors: bone volume, osseous density, trabecular pattern, structure model index, trabecular thickness, trabecular separation, total porosity except trabecular number and tissue volume, demonstrating that there are significant changes in the trabecular structure of the bisphosphonates. Zoledronic Acid compared to control group shows thicker, less separate and lower connected trabeculae.

En la última década los ingenieros informáticos se han enfrentado a profundos cambios en el modo en que se diseñan y fabrican los microprocesadores. Los nuevos procesadores no solo deben ser más rápidos que los anteriores, también deben ser factibles en términos de energía y disipación térmica, sobre todo en dispositivos que trabajan con baterías. Los problemas relacionados con consumo y temperatura son muy comunes en estos procesadores. En esta Tesis analizamos el rendimiento, consumo energético y precisión de diferentes mecanismos de reducción de consumo y descubrimos que no son suficientemente buenos para adaptarse a un límite de consumo con una penalización de rendimiento razonable. Para solucionar este problema proponemos diversas técnicas a nivel de microarquitectura que combinan de manera dinámica varios mecanismos de reducción de consumo para obtener una aproximación al límite de consumo mucho más precisa con una penalización de rendimiento mínima. / In the last decade computer engineers have faced changes in the way microprocessors are designed. New microprocessors do not only need to be faster than the previous generation, but also be feasible in terms of energy consumption and thermal dissipation, especially in battery operated devices. In this Thesis we worked in the design, implementation and testing of microarchitecture techniques for accurately adapting the processor performance to power constraints in the single core scenario, multi-core scenario and 3D die-stacked core scenario. We first designed “Power-Tokens”,to approximate the power being consumed by the processor in real time. Later we proposed different mechanisms based on pipeline throttling, confidence estimation, instruction criticality information, to adapt the processor to a predefined power budget . We also propose some layout optimizations for 3D die-stacked vertical designs.

La consommation d'alcool a des effets sur le tissu osseux. L'alcoolisme est une des causes d'ostéoporose secondaire chez l'homme. Dans ce travail nous avons mené différentes expérimentations chez le rat afin d'étudier les effets d'une consommation chronique d'alcool combinée ou non à un entraînement aérobie sur le tissu osseux. Nous avons montré qu'une faible dose d'alcool administrée pendant une période courte peut avoir un effet positif sur la densité minérale osseuse et l'épaisseur trabéculaire. En revanche, la combinaison activité physique et consommation modérée d'alcool n'a pas d'effet additif sur la potentialisation du tissu osseux. Nous avons également démontré un effet dose de l'alcool indiquant des effets délétères majorés sur la densité minérale osseuse (DMO), la microarchitecture corticale et la résistance osseuse avec des apports croissants (25%, 30% et 35% v/v). La modification de DMO s'accompagne d'un changement de composition corporelle et d'une diminution de la leptine systémique. Cependant, le nombre d'adipocytes augmente dans la moelle osseuse. Nous avons mis en évidence dans ce modèle d'ostéoporose secondaire due à l'alcool une augmentation de l'apoptose des ostéocytes, corrélée à la diminution de la DMO et à l'augmentation de l'adiposité médullaire. Nous avons de plus mis en évidence une incorporation de lipides dans les ostéocytes, incorporation fortement corrélée à l'apoptose de ces cellules. Enfin, nos résultats montrent qu'un exercice physique régulier combiné à une consommation chronique et excessive d'alcool permet de prévenir les effets délétères de l'alcool sur les paramètres osseux (porosité corticale, épaisseur corticale) et limite la diminution de la DMO. Cette diminution est associée à une régulation de l'apoptose des ostéocytes.