Au cours de la dernière décennie, la complexité des applications a considérablement évolué afin de répondre aux besoins métiers émergeants. Leur conception implique une composition distribuée de composants logiciels. Ces applications fournissent des services à travers les interactions métiers maintenues par leurs composants. De telles applications sont intrinsèquement en évolution dynamique en raison de la dynamicité de leurs contextes. En effet, elles évoluent dans des environnements qui changent tout en présentant des conditions très dynamiques durant leur cycle de vie d’exécution. De tels contextes représentent une lourde charge pour les développeurs aussi bien pour leurs tâches de conception que de gestion. Cela a motivé́ le besoin de renforcer l’autonomie de gestion des applications pour les rendre moins dépendantes de l’intervention humaine en utilisant les principes de l’Informatique Autonomique. Les Systèmes Informatiques Autonomes (SIA) impliquent l’utilisation des boucles autonomiques, dédiées aux systèmes afin de les aider à accomplir leurs tâches de gestion. Ces boucles ont pour objectif d’adapter leurs systèmes à la dynamicité de leurs contextes, en se basant sur une logique d’adaptation intégrée. Cette logique est souvent donnée par des règles statiques codées manuellement. La construction de ces règles demande beaucoup de temps tout en exigeant une bonne expertise. En fait, elles nécessitent une compréhension approfondie de la dynamicité du système afin de prédire les adaptations précises à apporter à celui-ci. Par ailleurs, une telle logique ne peut envisager tous les scénarios d’adaptation possibles, donc, ne sera pas en mesure de prendre en compte des adaptations pour des situations précédemment inconnues. Les SIA devraient donc être assez sophistiqués afin de pouvoir faire face à la nature dynamique de leurs contextes et de pouvoir apprendre par eux-mêmes afin d’agir correctement dans des situations inconnues. Les SIA devraient également être capables d’apprendre de leur propre expérience passée afin de modifier leur logique d’adaptation en fonction de la dynamicité de leurs contextes. Dans ce manuscrit, nous abordons les lacunes décrites en utilisant les techniques d’Apprentissage par Renforcement (AR) afin de construire notre logique d’adaptation. Cependant, les approches fondées sur l’AR sont connues pour leur mauvaise performance lors des premières phases d’apprentissage. Cette mauvaise performance entrave leur utilisation dans le monde réel des systèmes déployés. Par conséquent, nous avons amélioré cette logique d’adaptation avec des capacités d’apprentissage plus performantes avec une approche AR en multi-pas. Notre objectif est d’optimiser la performance de l’apprentissage et de le rendre plus efficace et plus rapide, en particulier durant les premières phases d’apprentissage. Nous avons aussi proposé́ un cadriciel générique visant à aider les développeurs dans la construction d’applications auto-adaptatives. Nous avons donc proposé de transformer des applications existantes en ajoutant des capacités d’autonomie et d’apprentissage à leurs composants. La transformation consiste en l’encapsulation des composants dans des conteneurs autonomiques pour les doter du comportement auto-adaptatif nécessaire. Notre objectif est d’alléger la charge des tâches de gestion des développeurs et de leur permettre de se concentrer plus sur la logique métier de leurs applications. Les solutions proposées sont destinées à être génériques, granulaires et basées sur un standard connu, à savoir l’Architecture de Composant de Service. Enfin, nos propositions ont été évaluées et validées avec des résultats expérimentaux. Ils ont démontré leur efficacité en montrant un ajustement dynamique des applications transformées face aux dynamicités de leurs contextes en un temps beaucoup plus court comparé aux approches existantes / During the past decade, the complexity of applications has significantly scaled to satisfy the emerging business needs. Their design entails a composition of distributed and interacting software components. They provide services by means of the business interactions maintained by their components. Such applications are inherently in a dynamic evolution due to their context dynamics. Indeed, they evolve in changing environments while exhibiting highly dynamic conditions during their execution life-cycle (e.g., their load, availability, performance, etc.). Such contexts have burdened the applications developers with their design and management tasks. Subsequently, motivated the need to enforce the autonomy of their management to be less dependent on human interventions with the Autonomic Computing principles. Autonomic Computing Systems (ACS) implies the usage of autonomic loops, dedicated to help the system to achieve its management tasks. These loops main role is to adapt their associated systems to the dynamic of their contexts by acting upon an embedded adaptation logic. Most of time, this logic is given by static hand-coded rules, often concern-specific and potentially error-prone. It is undoubtedly time and effort-consuming while demanding a costly expertise. Actually, it requires a thorough understanding of the system design and dynamics to predict the accurate adaptations to bring to the system. Furthermore, such logic cannot envisage all the possible adaptation scenarios, hence, not able to take appropriate adaptations for previously unknown situations. ACS should be sophisticated enough to cope with the dynamic nature of their contexts and be able to learn on their own to properly act in unknown situations. They should also be able to learn from their past experiences and modify their adaptation logic according to their context dynamics. In this thesis manuscript, we address the described shortcomings by using Reinforcement Learning (RL) techniques to build our adaptation logic. Nevertheless, RL-based approaches are known for their poor performance during the early stages of learning. This poor performance hinders their usage in real-world deployed systems. Accordingly, we enhanced the adaptation logic with sophisticated and better-performing learning abilities with a multi-step RL approach. Our main objective is to optimize the learning performance and render it timely-efficient which considerably improves the ACS performance even during the beginning of learning phase. Thereafter, we pushed further our work by proposing a generic framework aimed to support the application developers in building self-adaptive applications. We proposed to transform existing applications by dynamically adding autonomic and learning abilities to their components. The transformation entails the encapsulation of components into autonomic containers to provide them with the needed self-adaptive behavior. The objective is to alleviate the burden of management tasks on the developers and let them focus on the business logic of their applications. The proposed solutions are intended to be generic, granular and based on a well known standard (i.e., Service Component Architecture). Finally, our proposals were evaluated and validated with experimental results. They demonstrated their effectiveness by showing a dynamic adjustment to the transformed application to its context changes in a shorter time as compared to existing approaches

INTRODUÇÃO: Atualmente, a maior limitação ao transplante cardíaco, em todo o mundo, é a escassez de doadores cujo número está sempre aquém do número de pacientes portadores de doença cardíaca terminal, e esse hiato fica ainda maior pelo fato de cerca de 25 % dos corações doados não serem utilizados, por estarem acometidos por acentuada disfunção. A descarga catecolaminérgica associada à morte encefálica poderia ser um dos elementos implicados nesta disfunção. Assim, intervenções terapêuticas com intuito de minimizar o exacerbado estímulo simpático visam, em última instância, ampliar a oferta de órgãos para o transplante. OBJETIVOS: Investigar a hipótese de que a anestesia peridural torácica seja capaz de bloquear a tempestade autonômica inerente à morte encefálica por hipertensão intracraniana aguda, minimizando as alterações hemodinâmicas, reduzindo a resposta inflamatória e, por conseguinte, melhorando a condição do enxerto. MÉTODOS: Ratos Wistar machos (250-350 g) anestesiados (isoflurano 5 %) e monitorados continuamente para o registro da pressão arterial média foram submetidos à inserção de cateter no espaço peridural em nível torácico e, em seguida, submetidos à morte encefálica por hipertensão intracraniana aguda pela xxi insuflação de um cateter de Fogarty® introduzido por trepanação. Os animais (n = 28) foram alocados em 4 grupos: grupo salina - infusão de 20 uL de solução salina pelo cateter peridural antes da indução da morte encefálica; grupo bupi-pré - infusão de 20 uL de solução de bupivacaína a 0,5 % pelo cateter peridural, antes da indução da morte encefálica; grupo bupi-20 - infusão de 20 uL de solução de bupivacaína a 0,5 % pelo cateter peridural 20 minutos após a indução da morte encefálica; grupo bupi-60 - infusão de 20 ?L de solução de bupivacaína a 0,5 % pelo cateter peridural 60 minutos após a indução da morte encefálica. Após 6 horas os animais foram submetidos à eutanásia por exsanguinação. Foram realizadas dosagens séricas e no tecido cardíaco das citocinas interleucina (IL)-1beta e fator de necrose tumoral (TNF)-alfa pelo método de ELISA. As moléculas de adesão endoteliais, vascular adhesion molecule (VCAM)-1 e intercellular adhesion molecule (ICAM)-1, proteínas envolvidas no processo de apoptose, Bcl-2 e caspase-3, e a alfa-actina foram avaliadas no tecido miocárdico por técnica imunohistoquímica. Cortes longitudinais do coração foram corados com hematoxilina/eosina e avaliados quanto à presença de edema, infiltrado leucocitário e congestão vascular. Contagens totais de leucócitos circulantes foram realizadas antes da indução da morte encefálica e 3 e 6 horas após. RESULTADOS: Logo após a insuflação do cateter de Fogarty® todos animais evoluíram com sinais clínicos de morte encefálica: midríase bilateral fixa e ausência de reflexo corneano. O aumento súbito e efêmero da pressão arterial foi observado em todos os animais, à exceção do grupo que recebeu a bupivacaína previamente à indução da morte encefálica (grupo bupi-pré) (p<0,05). Houve acentuada e progressiva leucopenia em todos os grupos. As citocinas IL-1beta, TNF-alfa, tanto no soro quanto no miocárdio, não apresentaram diferenças significativas entre os grupos. As moléculas de adesão VCAM-1 e ICAM-1, as proteínas Bcl-2 e caspase-3, a alfa-actina, bem como a análise histológica do miocárdio não apresentaram diferenças significativas entre os grupos. CONCLUSÕES: A anestesia peridural torácica foi efetiva em bloquear o pico hipertensivo associado à morte encefálica. Contudo, tal bloqueio não se correlacionou a alterações na concentração de citocinas, expressão de moléculas de adesão, expressão de proteínas envolvidas com o processo apoptótico e alfa-actina, e alterações histológicas e do leucograma. Portanto, a tempestade autonômica não parecer ser a responsável pela ativação da resposta inflamatória e, em última instância, pela disfunção miocárdica associada à morte encefálica / BACKGROUND: Currently, the main limitation to cardiac transplantation, worldwide, is the shortage of donors whose number is always smaller than the number of patients with terminal heart disease, and this gap is even greater because about 25 % of donated hearts are not used due to severe dysfunction of unknown cause. Brain-death associated catecholaminergic storm may be implicated in this dysfunction. Thus, therapeutic interventions aiming to reduce the sympathetic stimulation result, ultimately, in an increase in the number of organs for transplantation. OBJECTIVES: To investigate the hypothesis that thoracic epidural anesthesia is capable of blocking the sympathetic discharge inherent to brain death, by acute intracranial hypertension, minimizing hemodynamic changes, and reducing the inflammatory response improving, therefore, the graft outcome. METHODS: Male Wistar rats (250 - 350 g) anesthetized (5 % isoflurane) and continuously monitored to record mean arterial pressure, underwent insertion of a catheter into the epidural space, at the thoracic level. Brain death was induced by acute intracranial hypertension by inflating an intracranially inserted Fogarty catheter. The animals (n = 28) were divided into 4 groups: saline group - infusion of 20 uL of saline through the epidural catheter before induction of brain death; pre-bup group - infusion of 20 uL of bupivacaine through epidural catheter before induction of brain death; bup-20 group - infusion of 20 uL of bupivacaine through epidural catheter 20 min after induction of brain death; bup-60 group - infusion of 20 uL of bupivacaine through epidural catheter 60 min after induction of brain death. After 6 h the animals were exsanguinated. Serum and cardiac tissue concentrations of cytokines, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alfa, were performed by ELISA. The endothelial adhesion molecules, vascular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1, proteins involved in apoptosis, Bcl-2 and caspase-3, and ?-actin were evaluated in myocardial tissue by immunohistochemistry. Longitudinal sections of the heart were stained with hematoxylin/eosin and evaluated for the presence of edema, vascular congestion and leukocyte infiltration. White blood cell counts were obtained prior to induction of brain death, 3 and 6 h thereafter. RESULTS: Clinical signs of brain death, fixed dilated pupils and absence of corneal reflex, were observed immediately after catheter insuflation. The sudden increase in mean arterial pressure was observed in all animals except in those receiving bupivacaine prior to brain death induction (pre-bup) (p<0.05). There was a marked and progressive leukopenia in all groups. Cytokine levels, IL-1beta and TNF-alfa, in serum and cardiac tissue, showed no significant differences among groups. Adhesion molecules, VCAM-1 and ICAM-1, the proteins, Bcl-2, caspase-3 and ?-actin, and the histological analysis of the myocardium showed no significant differences among groups. CONCLUSIONS: The thoracic epidural anesthesia was effective to block the hypertensive peak associated with brain death. However, this blockage does not correlate to changes in the levels of cytokines, expression of adhesion molecules and expression of apoptosis-linked proteins, and alfa-actin. Furthermore, no changes in histological analysis and white blood cell counts were observed. The autonomic storm does not seem to be responsible for the activation of the inflammatory response and, ultimately, for the myocardial dysfunction associated with brain death

Kwok, Ka Ming. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 124-146). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT / In English --- p.ii / In Chinese --- p.v / LIST OF TABLES --- p.vii / LIST OF FIGURE --- p.ix / ABBREVIATIONS / For Units --- p.x / For Prefixes of the International System of Units --- p.x / For Terms Commonly Used --- p.xi / Role of research workers --- p.xv / Chapter CHAPTER 1 --- Overview of methylmercury / Chapter 1.1 --- Source of methylmercury --- p.1 / Chapter 1.2 --- Toxicokinetics --- p.3 / Chapter 1.2.1 --- Absorption and distribution --- p.3 / Chapter 1.2.2 --- Half-life --- p.5 / Chapter 1.2.3 --- Metabolism/Biotransformation --- p.5 / Chapter 1.2.4 --- Biochemical mechanism of toxicity --- p.7 / Chapter 1.3 --- Health effects of mercury exposure --- p.9 / Chapter 1.3.1 --- Adult central nervous system --- p.10 / Chapter 1.3.2 --- The developing central nervous system --- p.11 / Chapter 1.3.3 --- Cardiovascular effects --- p.13 / Chapter 1.3.4 --- Immunotoxicity --- p.14 / Chapter 1.4 --- Biomarkers for prenatal exposure --- p.15 / Chapter 1.5 --- MeHg exposure in high risk populations in Hong Kong --- p.17 / Chapter CHAPTER 2 --- Neurocognitive performance / Chapter 2.1 --- Introduction --- p.19 / Chapter 2.1.1 --- New Zealand --- p.20 / Chapter 2.1.2 --- Seychelles --- p.21 / Chapter 2.1.3 --- Faroe Islands --- p.22 / Chapter 2.1.4 --- The Hong Kong situation --- p.23 / Chapter 2.2 --- Method --- p.23 / Chapter 2.2.1 --- Subjects and study design --- p.23 / Chapter 2.2.2 --- Questionnaires --- p.24 / Chapter 2.2.3 --- Hg concentration measurement --- p.25 / Chapter 2.2.4 --- Neurocognitive measurements --- p.26 / Chapter 2.2.4.1 --- Hong Kong - Wechsler Intelligence Scale for Children --- p.27 / Chapter 2.2.4.2 --- Hong King List Learning Test --- p.28 / Chapter 2.2.4.3 --- Test of Everyday Attention for Children --- p.29 / Chapter 2.2.4.4 --- Boston Naming Test --- p.31 / Chapter 2.2.4.5 --- Grooved Pegboard Test --- p.31 / Chapter 2.2.5 --- Statistical analysis --- p.32 / Chapter 2.3 --- Results --- p.33 / Chapter 2.3.1 --- Subject characteristic --- p.33 / Chapter 2.3.2 --- Test results --- p.34 / Chapter 2.3.3 --- Statistical analysis results --- p.35 / Chapter 2.4 --- Discussion --- p.36 / Chapter CHAPTER 3 --- Cardiac autonomic function / Chapter 3.1 --- Introduction --- p.60 / Chapter 3.1.1 --- Mechanism --- p.60 / Chapter 3.1.2 --- The association between HRV and the ANS --- p.61 / Chapter 3.1.3 --- Clinical applications and related studies --- p.63 / Chapter 3.1.4 --- Associations between MeHg exposure & HRV --- p.64 / Chapter 3.2 --- Methods --- p.65 / Chapter 3.2.1 --- Subjects and study design --- p.65 / Chapter 3.2.2 --- Physical and HRV measurement --- p.66 / Chapter 3.2.3 --- Time domain analysis --- p.68 / Chapter 3.2.4 --- Frequency domain analysis --- p.68 / Chapter 3.2.5 --- Non-linear method --- p.69 / Chapter 3.2.6 --- Statistical analysis --- p.70 / Chapter 3.3 --- Results --- p.71 / Chapter 3.3.1 --- Subjects characteristics --- p.71 / Chapter 3.3.2 --- HRV and statistical analysis results --- p.71 / Chapter 3.4 --- Discussion --- p.73 / Chapter CHAPTER 4 --- Immuno-toxicity / Chapter 4.1 --- Introduction --- p.91 / Chapter 4.2 --- Methods --- p.96 / Chapter 4.2.1 --- Subjects and Study Design --- p.96 / Chapter 4.2.2 --- Cytokine measurement --- p.96 / Chapter 4.2.3 --- Reversibility --- p.98 / Chapter 4.2.4 --- Statistical Analysis --- p.99 / Chapter 4.3 --- Results --- p.101 / Chapter 4.3.1 --- Subject Characteristics --- p.101 / Chapter 4.3.2 --- Atopic and non-atopic diseases group --- p.101 / Chapter 4.3.3 --- Cytokine profiles --- p.102 / Chapter 4.3.4 --- Reversibility --- p.103 / Chapter 4.4 --- Discussion --- p.104 / Chapter CHAPTER 5 --- Conclusion --- p.119 / Reference List --- p.124

In this dissertation we describe the event processing autonomic computing reference architecture (EPACRA), an innovative reference architecture that solves many important problems related to adaptive root cause analysis and diagnosis (RCAD). Along with the research progress for defining EPACRA, we also identified a set of autonomic computing architecture patterns and proposed a new information seeking model called net-casting model. EPACRA is important because today, root cause analysis and diagnosis (RCAD) in enterprise systems is still largely performed manually by experienced system administrators. The goal of this research is to characterize, simplify, improve, and automate RCAD processes to ease selected tasks for system administrators and end-users. Research on RCAD processes involves three domains: (1) autonomic computing architecture patterns, (2) information seeking models, and (3) complex event processing (CEP) technologies. These domains as well as existing technologies and standards contribute to the synthesized knowledge of this dissertation. To minimize human involvement in RCAD, we investigated architecture patterns to be utilized in RCAD processes. We identified a set of autonomic computing architecture patterns and analyzed the interactions among the feedback loops in these individual architecture patterns and how the autonomic elements interact with each other. By illustrating the architecture patterns, we recognized ambiguity in the aggregator-escalator-peer pattern. This problem has been solved by adding a new architecture pattern, namely the chain-of-monitors pattern, to the lattice of autonomic computing architecture patterns. To facilitate the autonomic information seeking process, we developed the net-casting information seeking model. After identifying the commonalities among three traditional information seeking models, we defined the net-casting model as a five stage process and then tailored it to describe our automated RCAD process. One of the main contributions of this dissertation is an innovative autonomic computing reference architecture called event processing autonomic computing reference architecture (EPACRA). This reference architecture is based on (1) complex event processing (CEP) concepts, (2) autonomic computing architecture patterns, (3) real use-case workflows, and (4) our net-casting information seeking model. This reference architecture can be leveraged to relieve the system administrator’s burden of routinely performing RCAD tasks in a heterogeneous environment. EPACRA can be viewed as a variant of the IBM ACRA model—extended with CEP to deal with large event clouds in real-time environments. In the middle layer of the reference model, EPACRA introduces an innovative design referred to as use-case-unit—a use case is the scenario of an RCAD process initiated by a symptom—event processing network (EPN) for RCAD. Each use-case-unit EPN reflects our automation approach, including identification of events from the use cases and classifying those events into event types. Apart from defining individual event processing agents (EPAs) to process the different types of events, dynamically constructing use-case unit EPNs is also an innovative approach which may lead to fully autonomic RCAD systems in the future. Finally, this dissertation presents a case study for EPACRA. As a case study we use a prototype of a Web application intrusion detection tool to demonstrate the autonomic mechanisms of our RCAD process. Specifically, this tool recognizes two types of malicious attacks on web application systems and then takes actions to prevent intrusion attempts. This case study validates both our chain-of-monitors autonomic architecture pattern and our net-casting model. It also validates our use-case-unit EPN approach as an innovative approach to realizing RCAD workflows. Hopefully, this research platform will be beneficial for other RCAD projects and researchers with similar interests and goals.

Les applications logicielles sont de plus en plus diversifié et complexe. Avec le développement orageux du Cloud Computing et de ses applications, les applications logicielles deviennent encore plus complexes que jamais. Les applications de cloud computing complexes peuvent contenir un grand nombre de composants logiciels qui nécessitent et consomment une grande quantité de ressources (matériel ou d'autres composants logiciels) répartis en plusieurs niveaux en fonction de la granularité de ces ressources. En outre, ces composants logiciels peuvent être situés sur différents nuages. Les composants logiciels et de leurs ressources requises d'une application Nuage ont des relations complexes dont certains pourraient être résolus au moment de la conception, mais certains sont nécessaires pour faire face au moment de l'exécution. La complexité des logiciels et de l'hétérogénéité de l'environnement Couverture devenir défis que les solutions d'élasticité actuelles ont besoin de trouver des réponses appropriées à résoudre. L'élasticité est l'un des avantages du cloud computing, qui est la capacité d'un système Cloud pour adapter à la charge de travail des changements par des ressources d'approvisionnement et deprovisioning d'une manière autonome. Par conséquent, les ressources disponibles correspondent à la demande actuelle d'aussi près que possible à chaque moment. Pour avoir une solution d'élasticité efficace, qui ne reflète pas seulement la complexité des applications Cloud mais également à déployer et à gérer eux d'une manière autonome, nous proposons une approche d'élasticité roman. Il est appelé à plusieurs niveaux élasticité fine qui comprend deux aspects de la complexité de l'application: plusieurs composants logiciels et la granularité des ressources. Le multi-niveau élasticité fine concerne les objets touchés par les actions d'élasticité et la granularité de ces actions. Dans cette thèse, nous introduisons plateforme Roboconf un système de cloud computing autonome (ACCS) pour installer et reconfigurer les applications complexes ainsi que soutenir le multi-niveau élasticité fine. A cet effet, Roboconf est également un gestionnaire d'élasticité autonome. Merci à cette plate-forme, nous pouvons abstraire les applications cloud complexes et automatiser leur installation et de reconfiguration qui peut être de plusieurs centaines d'heures de travail. Nous utilisons également Roboconf à mettre en œuvre les algorithmes de multi-niveau élasticité fine sur ces applications. Les expériences menées indiquent non seulement l'efficacité de l'élasticité fine multi-niveau, mais aussi de valider les caractéristiques de support de cette approche de la plateforme Roboconf. / Software applications are becoming more diverse and complex. With the stormy development of Cloud Computing and its applications, software applications become even more complex than ever. The complex Cloud applications may contain a lot of software components that require and consume a large amount of resources (hardware or other software components) distributed into multiple levels based on granularity of these resources. Moreover these software components might be located on different clouds. The software components and their required resources of a Cloud application have complex relationships which some could be resolved at design time but some are required to tackle at run time. The complexity of software and heterogeneity of Cloud environment become challenges that current elasticity solutions need to find appropriate answers to resolve. Elasticity is one of benefits of Cloud computing, which is capability of a Cloud system to adapt to workload changes by provisioning and deprovisioning resources in an autonomic manner. Hence, the available resources fit the current demand as closely as possible at each point in time. To have an efficient elasticity solution which not only reflects the complexity of Cloud applications but also deploy and manage them in an autonomic manner, we propose a novel elasticity approach. It is called multi-level fine-grained elasticity which includes two aspects of application’s complexity: multiple software components and the granularity of resources. The multi-level fine-grained elasticity concerns objects impacted by elasticity actions and granularity of these actions. In this thesis, we introduce Roboconf platform an autonomic Cloud computing system (ACCS) to install and reconfigure the complex applications as well as support the multi-level fine-grained elasticity. To this end, Roboconf is also an autonomic elasticity manager. Thanks to this platform, we can abstract the complex Cloud applications and automate their installation and reconfiguration that can be up to several hundred hours of labour. We also use Roboconf to implement the algorithms of multi-level fine-grained elasticity on these applications. The conducted experiments not only indicate efficiency of the multi-level fine-grained elasticity but also validate features supporting this approach of Roboconf platform.

Made available in DSpace on 2016-06-02T20:18:15Z (GMT). No. of bitstreams: 1 3878.pdf: 5612737 bytes, checksum: f29d73d585fd4a443e6ecd3e27bbdfa4 (MD5) Previous issue date: 2011-08-12 / A tese constou de 3 estudos descritos a seguir. O estudo I, intitulado: Programa fisioterapêutico hospitalar de curto periodo composto por exercícios físicos supervisionados melhora a função autonômica cardíaca após cirurgia de revascularização do miocárdio - Estudo randomizado e controlado teve como objetivo investigar se um programa fisioterapeutico hospitalar melhora a funcao autonomica cardiaca (FAC) apos a cirurgia de revascularizacao do miocardio (CRM). 47 pacientes pos- CRM, foram randomizados para: grupo de exercicios (GE,n=24) ou cuidados usuais de fisioterapia (GCU, n=23). A avaliacao da FAC incluiu medidas da variabilidade da frequencia cardiaca (VFC). Na alta hospitalar, GE apresentou maiores valores dos indices rMSSD, AF,SD1, STD RR, SD2, DFA &#945;1, DFA &#945;2, entropia aproximada e media RR, p<0,05. Contrariamente, maiores valores da media FC, BF e BF/AF (balanco simpato-vagal) foram encontrados em GCU. Concluimos que um programa fisioterapeutico de exercicios fisicos, realizado durante a internacao pos-CRM, melhora a FAC. Na sequencia, o estudo II, intitulado: Função ventricular esquerda e adaptações autonômicas cardíacas após RC hospitalar em curto período - Estudo clínico prospectivo. objetivou avaliar as adaptacoes autonomicas cardiacas em pacientes com diferenca na funcao do ventriculo esquerdo (FVE) submetidos a CRM e a reabilitacao cardiaca (RC). Em 44 pacientes divididos em grupo FVE normal (FVEN >55%, n=23) e FVE reduzida (FVER= 35-54%,n=21) a FAC foi avaliada antes e apos a RC. Foi encontrada interacao grupo (FVEN vs FVER) vs tempo (efeito da RC) para dimensao de correlacao (CD) e SD2, com melhora significativamente maior para FVER. Pacientes com FVER apresentaram melhor adaptacao autonomica cardiaca frente a RC. Finalmente, o estudo III, intitulado: Respostas autonômicas cardíacas induzidas pelo exercício durante a RC hospitalar em pacientes submetidos a cirurgia cardíaca e com funções ventriculares diferentes. avaliou se os exercicios fisicos realizados na RC hospitalar podem evocar respostas autonomicas diferenciadas em pacientes pos-CRM e FVE diferentes. Nos mesmos pacientes do estudo II foram avaliados os indices da VFC em repouso e durante os exercicios metabolicos e deambulacao no primeiro dia pos-operatorio (PO1) e na alta hospitalar, respectivamente. No PO1 foram observadas diferencas (media RR e media da FC) entre o repouso e exercicio em ambos os grupos. Durante a deambulacao foram encontrados menores valores da VFC (STDRR, TINN, SD2, entropia Shannon e dimensao de correlacao) para FVER, assim como, para a variacao entre repouso e deambulacao para os indices STDRR, RR tri, TINN, SD2, rMSSD e dimensao de correlacao, P<0,05. Concluimos que em pacientes pos-CRM e com FVE normal, o exercicio fisico hospitalar desencadeou resposta autonomica cardiaca mais atenuada comparado a FVEN. / A tese constou de 3 estudos descritos a seguir. O estudo I, intitulado: Programa fisioterapêutico hospitalar de curto periodo composto por exercícios físicos supervisionados melhora a função autonômica cardíaca após cirurgia de revascularização do miocárdio - Estudo randomizado e controlado teve como objetivo investigar se um programa fisioterapeutico hospitalar melhora a funcao autonomica cardiaca (FAC) apos a cirurgia de revascularizacao do miocardio (CRM). 47 pacientes pos- CRM, foram randomizados para: grupo de exercicios (GE,n=24) ou cuidados usuais de fisioterapia (GCU, n=23). A avaliacao da FAC incluiu medidas da variabilidade da frequencia cardiaca (VFC). Na alta hospitalar, GE apresentou maiores valores dos indices rMSSD, AF,SD1, STD RR, SD2, DFA &#945;1, DFA &#945;2, entropia aproximada e media RR, p<0,05. Contrariamente, maiores valores da media FC, BF e BF/AF (balanco simpato-vagal) foram encontrados em GCU. Concluimos que um programa fisioterapeutico de exercicios fisicos, realizado durante a internacao pos-CRM, melhora a FAC. Na sequencia, o estudo II, intitulado: Função ventricular esquerda e adaptações autonômicas cardíacas após RC hospitalar em curto período - Estudo clínico prospectivo. objetivou avaliar as adaptacoes autonomicas cardiacas em pacientes com diferenca na funcao do ventriculo esquerdo (FVE) submetidos a CRM e a reabilitacao cardiaca (RC). Em 44 pacientes divididos em grupo FVE normal (FVEN >55%, n=23) e FVE reduzida (FVER= 35-54%,n=21) a FAC foi avaliada antes e apos a RC. Foi encontrada interacao grupo (FVEN vs FVER) vs tempo (efeito da RC) para dimensao de correlacao (CD) e SD2, com melhora significativamente maior para FVER. Pacientes com FVER apresentaram melhor adaptacao autonomica cardiaca frente a RC. Finalmente, o estudo III, intitulado: Respostas autonômicas cardíacas induzidas pelo exercício durante a RC hospitalar em pacientes submetidos a cirurgia cardíaca e com funções ventriculares diferentes. avaliou se os exercicios fisicos realizados na RC hospitalar podem evocar respostas autonomicas diferenciadas em pacientes pos-CRM e FVE diferentes. Nos mesmos pacientes do estudo II foram avaliados os indices da VFC em repouso e durante os exercicios metabolicos e deambulacao no primeiro dia pos-operatorio (PO1) e na alta hospitalar, respectivamente. No PO1 foram observadas diferencas (media RR e media da FC) entre o repouso e exercicio em ambos os grupos. Durante a deambulacao foram encontrados menores valores da VFC (STDRR, TINN, SD2, entropia Shannon e dimensao de correlacao) para FVER, assim como, para a variacao entre repouso e deambulacao para os indices STDRR, RR tri, TINN, SD2, rMSSD e dimensao de correlacao, P<0,05. Concluimos que em pacientes pos-CRM e com FVE normal, o exercicio fisico hospitalar desencadeou resposta autonomica cardiaca mais atenuada comparado a FVEN.

INTRODUÇÃO: Atualmente, a maior limitação ao transplante cardíaco, em todo o mundo, é a escassez de doadores cujo número está sempre aquém do número de pacientes portadores de doença cardíaca terminal, e esse hiato fica ainda maior pelo fato de cerca de 25 % dos corações doados não serem utilizados, por estarem acometidos por acentuada disfunção. A descarga catecolaminérgica associada à morte encefálica poderia ser um dos elementos implicados nesta disfunção. Assim, intervenções terapêuticas com intuito de minimizar o exacerbado estímulo simpático visam, em última instância, ampliar a oferta de órgãos para o transplante. OBJETIVOS: Investigar a hipótese de que a anestesia peridural torácica seja capaz de bloquear a tempestade autonômica inerente à morte encefálica por hipertensão intracraniana aguda, minimizando as alterações hemodinâmicas, reduzindo a resposta inflamatória e, por conseguinte, melhorando a condição do enxerto. MÉTODOS: Ratos Wistar machos (250-350 g) anestesiados (isoflurano 5 %) e monitorados continuamente para o registro da pressão arterial média foram submetidos à inserção de cateter no espaço peridural em nível torácico e, em seguida, submetidos à morte encefálica por hipertensão intracraniana aguda pela xxi insuflação de um cateter de Fogarty® introduzido por trepanação. Os animais (n = 28) foram alocados em 4 grupos: grupo salina - infusão de 20 uL de solução salina pelo cateter peridural antes da indução da morte encefálica; grupo bupi-pré - infusão de 20 uL de solução de bupivacaína a 0,5 % pelo cateter peridural, antes da indução da morte encefálica; grupo bupi-20 - infusão de 20 uL de solução de bupivacaína a 0,5 % pelo cateter peridural 20 minutos após a indução da morte encefálica; grupo bupi-60 - infusão de 20 ?L de solução de bupivacaína a 0,5 % pelo cateter peridural 60 minutos após a indução da morte encefálica. Após 6 horas os animais foram submetidos à eutanásia por exsanguinação. Foram realizadas dosagens séricas e no tecido cardíaco das citocinas interleucina (IL)-1beta e fator de necrose tumoral (TNF)-alfa pelo método de ELISA. As moléculas de adesão endoteliais, vascular adhesion molecule (VCAM)-1 e intercellular adhesion molecule (ICAM)-1, proteínas envolvidas no processo de apoptose, Bcl-2 e caspase-3, e a alfa-actina foram avaliadas no tecido miocárdico por técnica imunohistoquímica. Cortes longitudinais do coração foram corados com hematoxilina/eosina e avaliados quanto à presença de edema, infiltrado leucocitário e congestão vascular. Contagens totais de leucócitos circulantes foram realizadas antes da indução da morte encefálica e 3 e 6 horas após. RESULTADOS: Logo após a insuflação do cateter de Fogarty® todos animais evoluíram com sinais clínicos de morte encefálica: midríase bilateral fixa e ausência de reflexo corneano. O aumento súbito e efêmero da pressão arterial foi observado em todos os animais, à exceção do grupo que recebeu a bupivacaína previamente à indução da morte encefálica (grupo bupi-pré) (p<0,05). Houve acentuada e progressiva leucopenia em todos os grupos. As citocinas IL-1beta, TNF-alfa, tanto no soro quanto no miocárdio, não apresentaram diferenças significativas entre os grupos. As moléculas de adesão VCAM-1 e ICAM-1, as proteínas Bcl-2 e caspase-3, a alfa-actina, bem como a análise histológica do miocárdio não apresentaram diferenças significativas entre os grupos. CONCLUSÕES: A anestesia peridural torácica foi efetiva em bloquear o pico hipertensivo associado à morte encefálica. Contudo, tal bloqueio não se correlacionou a alterações na concentração de citocinas, expressão de moléculas de adesão, expressão de proteínas envolvidas com o processo apoptótico e alfa-actina, e alterações histológicas e do leucograma. Portanto, a tempestade autonômica não parecer ser a responsável pela ativação da resposta inflamatória e, em última instância, pela disfunção miocárdica associada à morte encefálica / BACKGROUND: Currently, the main limitation to cardiac transplantation, worldwide, is the shortage of donors whose number is always smaller than the number of patients with terminal heart disease, and this gap is even greater because about 25 % of donated hearts are not used due to severe dysfunction of unknown cause. Brain-death associated catecholaminergic storm may be implicated in this dysfunction. Thus, therapeutic interventions aiming to reduce the sympathetic stimulation result, ultimately, in an increase in the number of organs for transplantation. OBJECTIVES: To investigate the hypothesis that thoracic epidural anesthesia is capable of blocking the sympathetic discharge inherent to brain death, by acute intracranial hypertension, minimizing hemodynamic changes, and reducing the inflammatory response improving, therefore, the graft outcome. METHODS: Male Wistar rats (250 - 350 g) anesthetized (5 % isoflurane) and continuously monitored to record mean arterial pressure, underwent insertion of a catheter into the epidural space, at the thoracic level. Brain death was induced by acute intracranial hypertension by inflating an intracranially inserted Fogarty catheter. The animals (n = 28) were divided into 4 groups: saline group - infusion of 20 uL of saline through the epidural catheter before induction of brain death; pre-bup group - infusion of 20 uL of bupivacaine through epidural catheter before induction of brain death; bup-20 group - infusion of 20 uL of bupivacaine through epidural catheter 20 min after induction of brain death; bup-60 group - infusion of 20 uL of bupivacaine through epidural catheter 60 min after induction of brain death. After 6 h the animals were exsanguinated. Serum and cardiac tissue concentrations of cytokines, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alfa, were performed by ELISA. The endothelial adhesion molecules, vascular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1, proteins involved in apoptosis, Bcl-2 and caspase-3, and ?-actin were evaluated in myocardial tissue by immunohistochemistry. Longitudinal sections of the heart were stained with hematoxylin/eosin and evaluated for the presence of edema, vascular congestion and leukocyte infiltration. White blood cell counts were obtained prior to induction of brain death, 3 and 6 h thereafter. RESULTS: Clinical signs of brain death, fixed dilated pupils and absence of corneal reflex, were observed immediately after catheter insuflation. The sudden increase in mean arterial pressure was observed in all animals except in those receiving bupivacaine prior to brain death induction (pre-bup) (p<0.05). There was a marked and progressive leukopenia in all groups. Cytokine levels, IL-1beta and TNF-alfa, in serum and cardiac tissue, showed no significant differences among groups. Adhesion molecules, VCAM-1 and ICAM-1, the proteins, Bcl-2, caspase-3 and ?-actin, and the histological analysis of the myocardium showed no significant differences among groups. CONCLUSIONS: The thoracic epidural anesthesia was effective to block the hypertensive peak associated with brain death. However, this blockage does not correlate to changes in the levels of cytokines, expression of adhesion molecules and expression of apoptosis-linked proteins, and alfa-actin. Furthermore, no changes in histological analysis and white blood cell counts were observed. The autonomic storm does not seem to be responsible for the activation of the inflammatory response and, ultimately, for the myocardial dysfunction associated with brain death

Submitted by Pedro Silva Filho (pfsilva@ipen.br) on 2017-11-22T17:22:11Z No. of bitstreams: 0 / Made available in DSpace on 2017-11-22T17:22:11Z (GMT). No. of bitstreams: 0 / A crotamina, um peptídeo catiônico que possui 42 aminoácidos e 4,88 kDa, é proveniente do veneno de Crotalus durissus terrificus. Ela apresenta características que permitem sua forte interação com alvos moleculares e membranas biológicas e assim foi o primeiro peptídeo de veneno a ser classificado como um CPP (cell penetrating peptide), justificando seus importantes efeitos biológicos e suas diversas atividades farmacológicas. A crotamina é descrita por sua atividade miotóxica, tendo como efeito a paralisia e espasmos das patas traseiras de ratos e camundongos. Esse fenômeno é descrito por ações em canais de Na+ e/ou K+ e consequente aumento do influxo intracelular dos níveis do íon Ca2+. Estudos a descrevem como um agente despolarizante utilizando a musculatura esquelética como modelo experimental. Outra atividade descrita da crotamina é um aumento na liberação basal de acetilcolina (ACh) e dopamina no sistema nervoso central de ratos. Até o momento, pouco ou nenhum estudo foi realizado em musculatura lisa. A junção neuromuscular autônoma difere em vários aspectos importantes da já conhecida junção neuromuscular esquelética. O ducto deferente de rato (DDR), um órgão par e tubular pertencente à genitália acessória masculina, foi utilizado como modelo experimental por ser um dos órgãos periféricos mais densamente inervados pelo sistema nervoso autônomo simpático. Esse fato, o torna uma importante ferramenta para estudos que envolvam a neurotransmissão e a ação de drogas adrenérgicas. O objetivo do presente trabalho é investigar o efeito da crotamina na contração da musculatura lisa. A crotamina foi isolada a partir do veneno de C. d. terrificus por cromatografia de exclusão molecular seguida de troca iônica. Os estudos em modelos animais foram realizados utilizando o DD (porção prostática) de ratos Wistar com 5 meses de idade entre 350 g (protocolo CEUA 1261/14). O estudo de neurotransmissão foi feito em sistema de órgão isolado (n=6) por estimulação elétrica transmural com tensão de 70V, 3ms de duração em frequências de 0,05 (30 min) e 1; 5 10 e 20Hz (30 seg). A contração isométrica foi registrada em gramas de tensão. Em todos os experimentos a crotamina (0,1;0,5 e 1g/ml) incubada 30 min antes da estimulação. O efeito máximo de contração (Emax) do componente fásico e tônico foi usado como medida. O componente pós-sináptico foi avaliado por meio de curvas dose-resposta de noradrenalina e dose única de ATP (10-3M) na presença ou ausência da crotamina. A diferença estatística foi avaliada pelo teste-t de student (P0,05). Os ensaios de estimulação elétrica de baixa frequência (0,05Hz) revelaram que a crotamina (0,1 e 0,5g/ml) promoveu uma diminuição da contração do DDR (95,7±4,6% e 85,4±5,9%, respectivamente) enquanto que na dose de 1 g/mL de crotamina este efeito não foi significativo. Na curva de freqüência observamos também com as mesmas concentrações de crotamina uma tendência à diminuição da contração fásica e tônica enquanto que a dose de 1 g/mL promoveu um aumento na contração fásica na freqüência de 20,0Hz ((3,2±0,3) em relação ao controle (2,2±0,2). O componente pós-sináptico não foi alterado pela crotamina conforme evidenciado pela curva concentração-resposta de noradrenalina e concentração única de ATP. Com base nos resultados obtidos, concluímos que a crotamina atua apenas no componente pré-sináptico da contração do DDR, provavelmente interferindo na neuroliberação de ATP e noradrenalina. Ela apresenta um efeito bifásico, dependendo da dose utilizada, inibindo ou potencializando a resposta, efeito semelhante ao da -defensinas, uma proteína cuja estrutura se assemelha bastante com a da crotamina. / Dissertação (Mestrado em Tecnologia Nuclear) / IPEN/D / Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP

Dans le contexte actuel de l’Internet, un enjeu de recherche majeur est de permettre aux applications et à leurs utilisateurs de disposer de systèmes de communication offrant une qualité de service (QdS) optimale. Ceci en fonction des ressources machine et réseau disponibles, dont les capacités et les performances, hétérogènes et variables, ne sont pas connues à l’avance. Le provisionnement optimal de la QdS dans ces futurs systèmes de communication autonomes nécessite d’une part la caractérisation des services et des ressources de communication disponibles, et d’autre part la prise en compte des expressions des besoins et des préférences des différents acteurs du système (utilisateurs, fournisseurs des services, etc.). Le sujet de la thèse porte sur la définition d’un cadre sémantique de QdS basé sur les ontologies pour la caractérisation des ressources et des services de communication dans le but de fournir la meilleure QdS au regard des besoins et des préférences des utilisateurs. Ce cadre sera utilisé dans la définition des objectifs et des contraintes de QdS et dans l’élaboration de modèles de décision. L'ensemble sera utilisé pour la mise en œuvre de QdS dans les systèmes de communication autonomes situés dans un contexte de réseaux domestiques / In the current context of the Internet, a major research challenge is to enable applications and users to have their communications systems with an optimal quality of service (QoS). Indeed, QoS provisioning should take into account the available machine and network resources, which capacities and performances are heterogeneous, variable, and not known in advance. The optimal QoS provisioning for the future autonomous communication systems requires the characterization of available services and communication resources and also taking into account the expressions of needs and preferences of different actors in the system (users, service providers, etc.). The subject of this thesis deals with the definition of a QoS ontology-based semantic framework for the characterization of network resources and communication services in order to provide better QoS according to the needs and preferences of users. This framewor! k will be used in the definition of objectives and QoS constraints as well as in the development of decision models in order to provide QoS for autonomous communication systems located in the context of home networks

Sandvik har utvecklat en teknik för att placera sensorer i rör. Denna teknik har stor marknadspotential och kan effektivisera många industriprocesser. Den färdiga tjänsten ska kunna strömma sensordata till molntjänster för analys och avläsning.Deras nuvarande system kräver idag manuell konfiguration på plats och är komplicerad att installera. Denna uppsats undersöker hur systemets utrustning kan konfigureras automatiskt och hur ett system för underliggande IT-tjänster skulle kunna fungera.En lösning presenteras där många delar av installationsprocessen har automatiserats, samt en skiss för ett underliggande system.Lösningen utvärderas genom att utföra en mätning av konfigureringskomplexitet. Slutsatsen av utvärderingen var att det utvecklade system hade utökad funktionalitet, jämfört med dagens manuella tillvägagångssätt, och var inte mer komplex att konfigurera. I många avseenden mindre komplex. / Sandvik has developed a technique to place sensors inside tubes. This technology has great market potential and can optimize many industrial processes. The finished product should be able to stream sensor data to cloudservices for analysis and reading.The current system requires manual configuration on-site and the installation is labor intensive. This thesis investigates how the system’s hardware can be configured atomically, and how a supporting IT-system could function.A solution is presented where large portion of the installation process has been automated, along with an outline for a supporting system.The solution is evaluated by performing a measurement of the configuration complexity. The evaluation shows that the developed system had increased functionality compared to today’s manual configuration, configuration complexity was not increased. In many aspects, the configuration complexity was reduced.