L'ischémie cérébrale est une pathologie complexe impliquant une cascade de mécanismes cellulaires qui conduisent, entre autres, à une augmentation de l’autophagie dans les neurones. Bien que l’activation de l’autophagie dans l’AVC ischémique soit aujourd’hui un fait avéré, le rôle de l'activateur tissulaire du plasminogène (tPA ; médicament utilisé dans la phase aigüe de l’AVC ischémique et neuromodulateur du système nerveux central) n’a jamais été décrit. Le tPA est une sérine protéase initialement découverte dans le compartiment vasculaire jouant un rôle important dans la fibrinolyse. Mais le tPA est aussi exprimé dans le parenchyme cérébral où il intervient dans le système glutamatergique, la plasticité synaptique et la survie neuronale. Afin de mieux comprendre les effets moléculaires du tPA dans l’autophagie, nous avons utilisé un modèle in vitro d'ischémie cérébrale consistant à sevrer en oxygène et en glucose (OGD) puis à réoxygéner des neurones corticaux primaires murins avec ou sans tPA. Nous avons confirmé, dans un premier temps, que l’OGD induit une autophagie délétère via une diminution de l’axe PI3K/Akt/mTORC1. Nous avons ensuite étudié l’effet du tPA sur l’autophagie induite par l’OGD. Nos résultats démontrent que le tPA protège les neurones de la mort induite par l’OGD en réduisant l’autophagie via l’activation du récepteur du facteur de croissance à l'insuline (IGF-1R, un récepteur tyrosine kinase) et de la voie PI3K/Akt/mTOR. Ce travail de thèse a donc permis de décrire le rôle neuroprotecteur et anti-autophagique du tPA, et d’identifier un nouveau récepteur cible du tPA : IGF-1R. / Cerebral ischemia is a complex pathology involving a cascade of cellular mechanisms leading, among other things, to an increase of neuronal autophagy. The activation of autophagy in ischemic stroke conditions is now well accepted, but the role of tissue-type plasminogen activator (tPA, a drug used in the acute phase of ischemic stroke, and a neuromodulator) on this pathway has never been studied. tPA is a serine protease originally discovered in the vascular compartment, that plays an important role in fibrinolysis. Interestingly, tPA is also expressed in the cerebral parenchyma where it is involved in the glutamatergic neurotransmission, synaptic plasticity and neuronal survival. To better understand molecular effects of tPA on autophagy, we used an in vitro model of cerebral ischemia consisting in an oxygen and glucose deprivation (OGD) followed by reoxygenation, on murine primary cortical neurons with or without tPA. First we reported that OGD enhances deleterious autophagy through the decrease of PI3K/Akt/mTOR pathways. Then, we investigated the effect of tPA on OGD-induced autophagy. Our results demonstrate that tPA protects neurons from OGD-induced death by reducing autophagy through Insulin Growth Factor Receptor (IGF-1R, a tyrosine kinase receptor) and an increase of PI3K/Akt/mTOR pathways. This thesis has made it possible to describe the neuroprotective and anti-autophagic effect of tPA, and to identify a new target receptor for tPA: IGF-1R.

L’accident vasculaire cérébral (AVC) est l’une des principales causes de mortalité dans le monde. Sile taux de de mortalité associé à l’AVC a sensiblement diminué dans les dernières décennies, cela estprincipalement du à l’amélioration globale de l’état de santé de la population et non à la découverte d’untraitement thérapeutique contre l’AVC et de nombreux survivants garderont des séquelles. Dans ce contexte,l’influence de la nutrition qui pourrait jouer un rôle central dans la résistance à l’AVC reste très peu étudier.Pourtant de nombreuses études épidémiologiques confèrent des propriétés protectrices à certaines moléculesnaturelles comme les acides gras polyinsaturés oméga-3.Dans un modèle murin d’AVC, notre laboratoire ayant montré que la consommation d’un régimeenrichi en acide a-linolénique (ALA), l’oméga-3 végétal, réduisait le volume d’infarctus cérébral, mestravaux ont porté sur l’effet de la supplémentation nutritionnelle en ALA. J’ai montré que la supplémentationen ALA par voie orale ou intraveineuse favorise la récupération cognitive post-AVC. Ces bénéfices sontassociés à la préservation des neurones de l’hippocampe, une structure cérébrale impliquée dans la mémoire.Par la suite, je me suis intéressé à l’effet de l’ALA sur la réponse inflammatoire pos-AVC, une composantemajeure dans l’étendue des séquelles. J’ai pu ainsi caractériser le rôle neurotoxique de la chimiokine CCL2 etd’identifier la réduction de son expression post-AVC, comme un facteur clé de la protection cérébrale induitepar la supplémentation en ALA. De plus, une étude collaborative nous a permis de mettre en évidencel’implication de la voie de signalisation de cette chimiokine dans la perte de poids induite par uneinflammation du système nerveux central. Mes travaux soulignent l’importance de la supplémentation en ALA pour réduire les conséquences d’un AVC, en ciblant la réponse pro-inflammatoire post-ischémique, apportant une preuve supplémentaire del’intérêt de l’ALA contre l’une des priorités les plus urgentes de la médecine / Stroke is a worldwide major cause of mortality and morbidity without any therapeutic opportunities.While improvements in population health - in the control of major risk factors of stroke - over the pastdecades have contributed to reduced stroke mortality, numerous therapeutics applied acutely after stroke havefailed to improve long-term clinical outcomes. Weirdly, how nutrition may affect stroke damage and recoveryhas not yet been intensely investigated, which is surprising given its great influence as risk factor. Therefore,our lab is investigating an emerging view that is the health potential of a-linolenic acid (ALA is the omega-3contained in plant-derived edible products) in stroke.Our laboratory has previously shown that ALA injections or dietary supplementation reduces strokedamage by direct neuroprotection in rodent models of stroke. As successful translation of putative therapieswill depend on demonstration of efficacy on stroke-induced motor and cognitive deficits, my PhD work hasevaluated the value of ALA supplementation in stroke recovery. I demonstrated that oral and intravenoussupplementation of ALA improved cognitive recovery, which was associated to a better preservation ofhippocampus, a brain structure involved in memory. Looking for mechanistic insights, I also investigated theeffect of ALA supplementation by modification of the daily diet on post-stroke inflammatory response. Wefirst demonstrated a neurotoxic role of the chemokine CCL2 after stroke and identified its reduction, as a keyfactor in brain protection induced by ALA supplementation. In addition, I also contributed to a collaborativestudy deciphering the role of CCL2 in weight loss induced by inflammation of the central nervous system.To conclude, my PhD highlights the importance of ALA supplementation to reduce the consequencesof stroke, targeting post-ischemic pro-inflammatory response and prepare the ground of clinical trial onnutritional interventions that are yet to be evaluated

L’hypertension artérielle chronique représente le premier facteur de risque de l’AVC ischémique, mais elle en est aussi le principal facteur aggravant. Les mécanismes à l’origine du risque ischémique lié à l’hypertension ne sont pas encore entièrement compris. Plusieurs études ont montré l’existence d’une forte composante inflammatoire délétère impliquée dans la physiopathologie de l’hypertension. Au niveau cérébral, la présence d’une intense réactivité microgliale hypothalamique, participant à l’aggravation de la pathologie a été observé. Dans le travail présenté ici, nous nous sommes intéressés à l’impact de l’hypertension artérielle sur l’état inflammatoire du cortex cérébral, une région particulièrement touchée lors d’un AVC ischémique chez le patient. Nous avons tiré parti de la souche transgénique de souris CX3CR1GFP/+ pour l’imagerie de la dynamique microgliale, principal acteur de l’immunité cérébrale. Par une analyse in vivo réalisée en microscopie biphotonique, nous avons montré que l’hypertension induite par infusion chronique d’angiotensine-II altère la morphologie de la microglie, mais surtout sa capacité de surveillance du parenchyme cérébral et sa capacité cicatricielle. Nous avons aussi montré que ce type d’hypertension endommage la structure et la fonctionnalité des vaisseaux corticaux. L’ensemble de ces résultats pourrait expliquer, au moins en partie, la sensibilisation du cerveau aux lésions ischémiques par l’hypertension artérielle, avant même la survenue de l’AVC. / Chronic high blood pressure is ischemic stroke’s leading risk factor, but it is also its main aggravating factor. The mechanisms underlying hypertension-induced ischemic brain lesion exacerbation are not yet fully understood. Several studies highlighted the existence of a strong inflammatory component in the pathophysiology of hypertension. In the brain, the presence of intense hypothalamic microglial reactivity, contributing to the pathology worsening has been shown. In this work, we focused on the impact of high blood pressure on the inflammatory state of the cerebral cortex, a region particularly affected by ischemic stroke in the patient. We took advantage of the CX3CR1GFP/+ mice transgenic strain for imaging microglia dynamics. By using in vivo two-photon microscopy, we have shown that hypertension induced by chronic infusion of angiotensin-II alters the microglia morphology, especially its parenchymal surveilling activity and its cicatricial capacity. We have also shown that this type of hypertension disrupts the structure and the functioning of cortical vessels. All of these results can explain, at least in part, the brain sensitization to ischemic lesions under arterial hypertension, before the onset of stroke.

Chez les patients hémiparétiques chroniques, la tDCS a été testée sur diverses tâches du membre inférieur, montrant des résultats intéressants, mais parfois contradictoires. Cependant, les effets de la tDCS sur la fonction motrice volontaire (extension de genou) et semi-automatique (locomotion) chez des patients hémiparétiques ne sont pas encore totalement connus. L’objet de ce travail était d’évaluer contre placébo les effets de la tDCS en polarité anodale sur les fonctions motrices volontaires et semi-automatiques, chez des patients hémiparétiques. L’étude comporte deux parties : la première a pour but d’évaluer l’effet contre placébo de la tDCS bilatérale sur la force volontaire maximale du quadriceps parétique par isocinétisme, la seconde a pour objectif d’étudier les effets contre placébo des effets de la tDCS unilatérale sur la marche par analyse tridimensionnelle du mouvement. Les résultats ont montré une absence d’effet de la tDCS sur les deux types de mouvements étudiés. De plus, la tDCS n’a pas eu d’effet sur la spasticité du quadriceps ni sur la performance aux tests fonctionnels des patients hémiparétiques. Cela suggère qu’il n’y a pas d’intérêt à l’utilisation de la tDCS bilatérale pour améliorer une performance motrice maximale (l’extension de genou) ni de la tDCS unilatérale pour améliorer un mouvement semi-automatique (la locomotion) chez les patients hémiparétiques chroniques. Les perspectives envisagées sont de reconduire ces expérimentations chez un groupe homogène de patients hémiparétiques en phase aigüe ou subaigüe afin de potentialiser les phénomènes plastiques post-lésionnels. Ceci permettra de renforcer ou non l’intérêt de l’utilisation de la tDCS chez les patients hémiparétiques afin d’améliorer leurs performances motrices. / In chronic hemiparetic patients, the use of tDCS has been tested on various lower limb tasks, showing interesting but sometimes contradictory results. However, the effects of tDCS on voluntary (knee extension) and semi-automatic (locomotion) motor function in hemiparetic patients are not yet fully known. The purpose of this work was to quantify the effects of tDCS in anodal polarity on the voluntary and semi-automatic motor functions in placebo-controlled studies. The study is divided into two parts: the first aims to evaluate the effect against placebo of bilateral tDCS on the maximal voluntary force of the paretic quadriceps by isokinetic assessment, the second aims to study the effects against placebo of unilateral tDCS on the gait of chronic hemiparetic patients, assessed by three-dimensional gait analysis. The results showed an absence of effect of tDCS on the two types of movements studied. In addition, tDCS had no effect on quadriceps spasticity or functional test performance in hemiparetic patients. This suggests that there is no interest in using bilateral tDCS to improve maximal motor performance (knee extension) or unilateral tDCS to improve semi-automatic movement (locomotion) in chronic hemiparetic patients. The envisaged perspectives are to continue these experiments in a homogeneous group of hemiparetic patients in acute or subacute stroke patients in order to potentiate the post-lesional plastic phenomena. This will strengthen or not the interest of the use of tDCS in hemiparetic patients to improve their motor performance.

京都大学 / 0048 / 新制・課程博士 / 博士(情報学) / 甲第19138号 / 情博第584号 / 新制||情||102(附属図書館) / 32089 / 京都大学大学院情報学研究科通信情報システム専攻 / (主査)教授 佐藤 高史, 教授 小野寺 秀俊, 教授 髙木 直史 / 学位規則第4条第1項該当 / Doctor of Informatics / Kyoto University / DFAM

No / Although computer architectures incorporate fast processing hardware resources, high performance real-time implementation of a complex control algorithm requires an efficient design and software coding of the algorithm so as to exploit special features of the hardware and avoid associated architecture shortcomings. This paper presents an investigation into the analysis and design mechanisms that will lead to reduction in the execution time in implementing real-time control algorithms. The proposed mechanisms are exemplified by means of one algorithm, which demonstrates their applicability to real-time applications. An active vibration control (AVC) algorithm for a flexible beam system simulated using the finite difference (FD) method is considered to demonstrate the effectiveness of the proposed methods. A comparative performance evaluation of the proposed design mechanisms is presented and discussed through a set of experiments.

Internet access has evolved in the last decade with the availability of smart handheld devices and high bandwidth offered by mobile networks at reduced costs. Multimedia traffic primarily video became the main share of global Internet traffic due to the popularity of multimedia supported social applications, online gaming, and IPTV. Thus, the success of any network based business model is dependent on service quality and Quality of Experience (QoE) is widely accepted as a means to describe user satisfaction with a service. QoE can be influenced by numerous factors ranging from content liking to system and context-related artifacts. In this thesis, a holistic approach is adopted to evaluate the QoE of an end-user regarding video quality based on system, contextual and human factors. At the system level, an impact of the Maximum Transmission Unit (MTU), and the comparison of widely used video codecs in error-prone networks is investigated by using diverse streaming protocols on an emulated network. It is found that the myth of using small MTU for better performance in high-loss scenarios comes at a cost of increased latency at the intermediate nodes and doesn’t provide any gain in video quality. The performance of the Google royalty-free VP8 codec was also shown to be on par with the widely adopted and proprietary H.264, especially in scenarios involving high jitter. At a human level, user delight towards the shown stimulus, his or her mood along with the frequency of watching online content (contextual), and their impact on quality ratings are investigated. It is found that human-related personality traits tend to influence subjective ratings and highlight the requirement of more cohesive QoE models to estimate user perception.

Yes / This paper presents an investigation into the impact of algorithm design for real-time active control systems. An active vibration control (AVC) algorithm for flexible beam systems is employed to demonstrate the critical design impact for real-time control applications. The AVC algorithm is analyzed, designed in various forms and implemented to explore the impact. Finally, a comparative real-time computing performance of the algorithms is presented and discussed to demonstrate the merits of different design mechanisms through a set of experiments.

Discussions of the armed conflict in Colombia have gained international awareness over the past years. Current events neglect to note the complexities of the civil war conflict that has afflicted Colombia for many decades. The armed soldiers still have a presence in the country, though there have been vast improvements under the current Uribe administration. Since there are only a few existing written accounts of the revolutionary groups this study attempts to contribute to the scholarly discourse. The bulk of this research is dedicated to providing a history of the three dominant illegally armed groups in Colombia, The FARC, the ELN, and the AUC. This study will attempt to provide an accurate analysis of the conflict by describing the groups in their historical context. Conclusions to the Colombian crisis include points of view from all areas. Guerilla and paramilitary ideas include a national convention, government trust in leadership and increasing societal participation. Government actors seek progress in the peace process through the demobilization of the revolutionary groups. As well as defining the conflict, this study sheds light on various possibilities for conflict resolution.

Made available in DSpace on 2016-03-22T17:26:22Z (GMT). No. of bitstreams: 1 DMII_AndreMarcel.pdf: 2907967 bytes, checksum: 5f3911468dd5affdd2020316f31ee238 (MD5) Previous issue date: 2009-12-11 / The increasing use of digital video on the Internet, devices and also in mobile digital TV has lead to an increasing interest for research in this area, from both industry and academia. This work follows this trend by proposing the investigation of the main aspects of digital video, video compression and also of the H.264/AVC video compression for the implementation of performance efficient dedicated architectures for some modules of the H.264/AVC encoder. In particular, this work presents some architectural alternatives for the increase of performance of two modules of the H.264/AVC, which are: T Module (composed by the Forward Hadamard and Discrete Cosine Transforms) and Motion Estimation (ME). For the implementation of these modules the use of techniques to the increase of performance has been considered, such as the use of efficient adders and pipeline. This efficient adders presents high use of hardware features. Thus, the implemented architectures in this work presented these characteristics too. The main aspect presented by the implemented modules is a large number of arithmetic operations of addition and subtraction for their processing. Thus, the motivation of this work is the increase of performance of these modules, from the use of efficient adder/subtractor circuits that are present in literature. In particular, 4:2, 8:2 and 16:2 adder compressors that perform the simultaneous addition of 4, 8 and 16 operands, respectively, with no penalties in area and the critical path are used. The architectures were described in VHDL and targeted to ASIC technology. The validation of the circuits and the obtained results were performed by using Leonardo Spectrum tool from Mentor Graphics. Comparisons against the solutions of the literature were done and the main results show that the architectures proposed in this work are more efficient. Significant gains in performance are achievable using our solutions for both Forward Transforms and Motion Estimation architectures / A crescente utilização de vídeos digitais na Internet, em dispositivos móveis e também na TV digital faz com que haja um interesse crescente em pesquisas nesta área, tanto na indústria quanto no meio acadêmico. Este trabalho segue esta tendência e tem como proposta estudar aspectos de vídeo digital, compressão de vídeo e também do padrão H.264/AVC de compressão de vídeo para a implementação de arquiteturas dedicadas eficientes em desempenho, isto é, com elevada frequência de operação, dos módulos do codificador do padrão H.264/AVC. Em particular, este trabalho apresenta algumas alternativas arquiteturais para aumento de desempenho de dois módulos do padrão H.264/AVC, que são: Módulo T (composto pelas Transformadas Diretas Transformadas Hadamard e Transformada Discreta do Coseno) e Estimação de Movimento (ME). A implementação destes módulos foi realizada utilizando técnicas para o aumento de desempenho, tais como o uso de somadores eficientes e pipeline. Uma característica dos somadores eficientes utilizados neste trabalho é o uso elevado de recursos de hardware. Assim, as arquiteturas implementadas neste trabalho também apresentaram esta característica. Os módulos implementados apresentam como principal característica um elevado número de operações aritméticas de soma e subtração para o seu processamento. Desta forma, a motivação deste trabalho consiste em aumentar o desempenho destes módulos, a partir da utilização de circuitos somadores/subtratores eficientes presentes na literatura. Em particular, são utilizados circuitos somadores compressores 4:2, 8:2 e 16:2, pois estes realizam a soma simultânea de 4, 8 e 16 operandos, respectivamente, sem penalidades em área e no caminho crítico. As arquiteturas foram descritas em VHDL e direcionadas para tecnologia ASIC, a validação e resultados foram obtidos através da ferramenta Leonardo Spectrum da Mentor Graphics. Para os estudos de caso utilizados neste trabalho (Transformadas Diretas e Estimação de Movimento), foram feitas comparações com soluções apresentadas na literatura e os resultados mostram que as arquiteturas implementadas neste trabalho obtiveram significativos ganhos em desempenho, quando comparadas com soluções apresentadas na literatura