Background: This article presents prospective lower bound estimations of findings on prevalence, incidence, clinical correlates, severity markers, co-morbidity and course stability of threshold and subthreshold recurrent brief depressive disorder (RBD) and other mood disorders in a community sample of 3021 adolescents. Method: Data were collected at baseline (age 14–17) and at two follow-up interviews within an observation period of 42 months. Diagnostic assessment was based on the Munich Composite International Diagnostic Interview (M-CIDI). Results: Our data suggest that RBD is a prevalent (2.6%) clinical condition among depressive disorders (21.3%) being at least as prevalent as dysthymia (2.3%) in young adults over lifetime. Furthermore, RBD is associated with significant clinical impairment sharing many features with major depressive disorder (MDD). Suicide attempts were reported in 7.8% of RBD patients, which was similar to MDD (11.9%). However, other features, like gender distribution or co-morbidity patterns, differ essentially from MDD. Furthermore, the lifetime co-occurrence of MDD and RBD or combined depression represents a severe psychiatric condition. Conclusions: This study provides further independent support for RBD as a clinically significant syndrome that could not be significantly explained as a prodrome or residual of major affective disorders.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23089号 / 医博第4716号 / 新制||医||1050(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 高橋 淳, 教授 浅野 雅秀, 教授 伊佐 正 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-07-11T12:45:47Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) AVALIAÇÃO DA DISPONIBILIDADE DE VIDEO SURVEILLANCE AS A SERVICE (VSAAS) - CarlosMagno_vFinal_.pdf: 9082644 bytes, checksum: c59974ef3892ac2c00ead6db128cf7f6 (MD5) / Made available in DSpace on 2016-07-11T12:45:47Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) AVALIAÇÃO DA DISPONIBILIDADE DE VIDEO SURVEILLANCE AS A SERVICE (VSAAS) - CarlosMagno_vFinal_.pdf: 9082644 bytes, checksum: c59974ef3892ac2c00ead6db128cf7f6 (MD5) Previous issue date: 2015-09-04 / CNPq / Nos últimos anos, sistemas de Video Surveillance as a Service (VSaaS) apresentam um aumento significativo na demanda por técnicas de segurança que elevem os níveis de confiabilidade do serviço. Em paralelo, o paradigma de Computação em Nuvem tornou-se uma importante ferramenta para serviços remotos da computação. O VSaaS entrega armazenamento de grande quantidade de dados. Em 2012, 50% do armazenamento em big data que necessitou serem analisados foram de vídeo de vigilância. Em geral, os vídeos têm um alto significado para seus proprietários, não permitindo longos períodos de interrupção. Com o objetivo de evitar baixos desempenhos e ampliar a qualidade dos serviços de vídeo são necessários mecanismos para garantir alta disponibilidade em VSaaS. Entretanto, esta tarefa é difícil sem gerar impacto no custo. O presente trabalho propõe dois sistemas de VSaaS que foram submetidos a análise de disponibilidade, por meio de modelos analíticos (RBD, CTMC e SPN). O primeiro sistema, denominado doméstico, foi caracterizado pelos elementos essenciais para uma estrutura básica do VSaaS para ser utilizado em casas e pequenos comércios. Estes sistemas geraram três arquiteturas que foram modeladas para a obtenção de fórmulas fechadas, elas são importantes para realização de análises. O modelo da arquitetura 1 foi validado e as outras arquiteturas variaram dessas. A arquitetura 3 teve a maior disponibilidade entre as outras arquiteturas, por possuir a quantidade maior de componentes replicados. O downtime (em horas) desta arquitetura comparada com a sem replicações foi em 36,89%. Por ela ter a maior disponibilidade, foi realizada uma análise de sensibilidade que mostrou o componente “Node” como o de maior impacto. No segundo sistema, foi apresentado um VSaaS de uma empresa, chamado empresarial, gerando 18 (dezoito) arquiteturas, uma delas comparada a arquitetura A1 (sem redundância), obteve uma redução significativa do downtime de 30% com um pequeno aumento no custo na ordem de 7%. Caso um determinado serviço exija um downtime menor, outra análise apontou uma arquitetura com redução de 80% ao aumentar 30% do custo. Diante desse panorama foram propostas e analisadas arquiteturas que podem auxiliar administradores a tomar importantes decisões na implementação de VSaaS. / In the last few years, Video Surveillance as a Service VSaaS has shown the significant increase in demand for security mechanisms to ensure reliability higher levels. In parallel, the Cloud Computing paradigm has become an important tool for remote computing services. VSaaS, for example, allows for storage large amounts of data. In 2012, 50% of big data storage were surveillance video and in general, videos have a high significance for their owners, not allowing long periods interruption. To avoid video services with low performance and increase the quality, mechanisms to ensure high availability in VSaaS are required. However, this task is difficult without generating a major impact on cost, so this paper proposes two VSaaS systems who underwent an availability analysis, using analytical models (RBD, CTMC, and SPN). The first system, entitled domestic, was characterized by essential elements of a basic structure VSaaS, for use in homes and small businesses. This system generated three architectures that were modeled to obtain closed formulas; they are important to performing analyzes. The model architecture one was validated, and other architectures vary these. The architecture three had the highest availability of the other architectures, by owning the largest number of replicated components. The downtime (in hours) this architecture compared to a without replication was 36.89%. For having the highest availability, a sensitivity analysis showed the "Node"component as the most relevant. In the second system, was showed a VSaaS in a company and has generated eighteen architectures. One of them compared to a baseline, we obtained a significant reduction in downtime (30%) and a small increase in cost (on the order of 7%). In case, of the service requires less downtime, another analysis pointed an architecture with a reduction 80% of downtime and increased 30% in the cost. We propose and analyze architectures that can help administrators make important decisions in the VSaaS implementation.

Background: This article presents prospective lower bound estimations of findings on prevalence, incidence, clinical correlates, severity markers, co-morbidity and course stability of threshold and subthreshold recurrent brief depressive disorder (RBD) and other mood disorders in a community sample of 3021 adolescents. Method: Data were collected at baseline (age 14–17) and at two follow-up interviews within an observation period of 42 months. Diagnostic assessment was based on the Munich Composite International Diagnostic Interview (M-CIDI). Results: Our data suggest that RBD is a prevalent (2.6%) clinical condition among depressive disorders (21.3%) being at least as prevalent as dysthymia (2.3%) in young adults over lifetime. Furthermore, RBD is associated with significant clinical impairment sharing many features with major depressive disorder (MDD). Suicide attempts were reported in 7.8% of RBD patients, which was similar to MDD (11.9%). However, other features, like gender distribution or co-morbidity patterns, differ essentially from MDD. Furthermore, the lifetime co-occurrence of MDD and RBD or combined depression represents a severe psychiatric condition. Conclusions: This study provides further independent support for RBD as a clinically significant syndrome that could not be significantly explained as a prodrome or residual of major affective disorders.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-07-12T12:58:40Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) avld-tese-2016.pdf: 5797292 bytes, checksum: 0ff6ad41cf04121ad18911a2cc983ef8 (MD5) / Made available in DSpace on 2016-07-12T12:58:40Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) avld-tese-2016.pdf: 5797292 bytes, checksum: 0ff6ad41cf04121ad18911a2cc983ef8 (MD5) Previous issue date: 2015-12-16 / FACEPE / Rede de Sensores Sem Fio (RSSF) é um tipo de rede ad hoc formada tipicamente por centenas de pequenos dispositivos, chamados de nós sensores, os quais cooperam entre si para coletar e enviar informações até um nó sorvedouro. Esses nós sensores possuem recursos limitados de processamento, armazenamento e energia. Geralmente, a RSSF é implantada para coleta de informações em ambientes de difícil acesso, impossibilitando a substituição dos nós sensores caso apresentem alguma falha ou quando a energia acaba. Sendo assim, planejar e estimar o tempo de vida (consumo de energia) e a qualidade do serviço (confiabilidade) de uma RSSF antes de implantá-la são atividades cruciais. Existem duas deficiências quando se observam soluções para o problema mencionado: elas se concentram na avaliação do consumo da aplicação ou apenas da infraestrutura de comunicação( e.g., protocolos de comunicação); e, quando os trabalhos avaliam os dois juntos, eles avaliam ou o consumo de energia ou a confiabilidade, e não ambas. Tais deficiências devem ser resolvidas para se ter um bom planejamento da RSSF. Neste cenário, esta tese propõe uma metodologia para guiar o usuário no desenvolvimento de RSSFs levando em consideração o consumo de energia e a confiabilidade das aplicações e da infraestrutura. A metodologia orienta o usuário no planejamento, codificação, otimização, validação e implantação da RSSF. Com relação à avaliação, a metodologia inclui quatro conjuntos de modelos formais baseados em Coloured Petri Ned (CPN) e em Reliability Block Diagram (RBD) para avaliar o consumo de energia e a confiabilidade, respectivamente. Esses quatro conjuntos de modelos são criados através de um processo de composição usando pequenos modelos reusáveis. Todas as atividades da metodologia são suportadas por um conjunto de ferramentas que automatiza a avaliação das RSSFs. Os modelos CPN e RBD foram validados através de experimentos, comparando os resultados obtidos a medições e dados encontrados na literatura. Uma análise de sensibilidade foi realizada para identificar quais fatores tem maior impacto sobre o consumo de energia e a confiabilidade das RSSFs. As contribuições foram a metodologia, unindo o planejamento da aplicação com da infraestrutura da RSSF e avaliando o consumo de energia e a confiabilidade de forma integrada; os modelos formais baseados nas instâncias da RSSF; o conjunto de ferramentas para suportar a metodologia proposta; e a análise de sensibilidade, que mostrou quais fatores afetam mais o consumo e a confiabilidade da RSSF. / Wireless Sensor Network (WSN) is an ad hoc network typically formed by hundreds of small devices called sensor nodes, which cooperate to collect and send information to a sink node. These sensor nodes have limited processing, storage and energy resources. Generally, the WSN is deployed to collect information in inaccessible environments, making it impossible to replace the sensors if they have any failure or when the energy is over. In this way, planning and estimating the lifetime (power consumption) and quality of service (reliability) of a WSN, considering the application and infrastructure before deploying are crucial activities. There are two deficiencies when looking at solutions for the mentioned problem: they focus on evaluating the power consumption of the application or just the infrastructure of WSN; and, when the studies evaluate both together, either they evaluate power consumption and reliability, not both. These deficiencies should be addressed to enable a good WSN planning. In this scenario, this thesis proposes a methodology to guide the user in the WSNs development, considering the power consumption and reliability of the application and the infrastructure of the WSN. The methodology guides the user in the design, coding, optimization, validation and deployment of a WSN. Regarding the evaluation, the methodology includes four sets of formal models based on Coloured Petri Ned (CPN) and Reliability Block Diagram (RBD) to evaluate the power consumption and reliability of the WSN, respectively. These four models are created by a process of composition using small reusable models. All activities of the methodology are supported by a set of tools that automates the WSN evaluation. CPN and RBD models were validated by experiments, comparing the results obtained by the models with results of the measurements or study in the literature. A sensitivity analysis was performed to identify which factors impact on power consumption and reliability of the WSN using the proposed models. The contributions were the methodology, combining the planning of the application with the WSN infrastructure and evaluating power consumption and reliability in an integrated way; formal models based on WSN instances; the set of tools to support the proposed methodology; and the sensitivity analysis, which showed the factors that most affect the consumption and reliability of WSN.

Within the safety analysis industry there are a variety of tools used to ensure reliability and security of systems, ranging from mostly qualitative approaches to mostly quantitative. One safety analysis method that lies in between these two is called Layers Of Protection Analysis (LOPA). LOPA is known as a “semi-quantitative” approach that uses a mix of quantitative and qualitative approaches to draw conclusions. In this masters thesis the LOPA approach is demonstrated, in addition to being developed into two alternate LOPA approaches, known as MarkovLOPA and RBDLOPA. These two developed approaches use the concept of Markov chains and Reliability block diagram (RBD) respectively, to extend the applicability of the traditional LOPA methodology. Furthermore, a conventional hydraulic braking system (CHB), which includes ABS/TCS- and ESP functionality was analysed by these three methodologies. The results of the analysis show that in the analysis by LOPA and RBDLOPA 4- and 3 out of 10 scenarios need slight improvements and only 1 scenario for MarkovLOPA. Additionally, the validity of the alternative approaches are analysed by a sensitivity analysis, showing irregularities in the results, leading to the conclusion that further research and development is required prior to industrial applications of the approaches.

Les protéines DOCK180 et ELMO coopèrent ensemble biochimiquement et génétiquement afin d’activer la GTPase Rac1 lors de plusieurs évènements biologiques. Toutefois, le rôle que jouent ces protéines dans la signalisation par Rac est encore mal compris. Nous émettons l’hypothèse que Dock180 agit comme activateur de Rac, alors que ELMO est requis pour l’intégration de la signalisation de Rac plutôt que son activation per se. Nous postulons que ELMO agit comme signal de localisation intracellulaire afin de restreindre de façon spatio-temporelle la signalisation de Rac en aval de Dock180, et/ou que ELMO agit comme protéine d’échafaudage entre Rac et ses effecteurs pour amplifier la migration cellulaire. Dans l’objectif nº 1, nous démontrons que le domaine PH atypique de ELMO1 est le site d’interaction principal entre cette protéine et DOCK180. De plus, nous démontrons que la liaison entre ELMO et DOCK180 n’est pas nécessaire pour l’activation de Rac, mais est plutôt essentielle pour faciliter la réorganisation du cytosquelette induite par l’activation de Rac en aval de Dock180. Ces résultats impliquent que ELMO pourrait jouer des rôles additionnels dans la signalisation par Rac. Dans l’objectif nº 2, nous avons découvert l’existence d’une homologie structurelle entre ELMO et un module d’autorégulation de la formine Dia1, et avons identifié trois nouveaux domaines dans la protéine ELMO : les domaines RBD, EID et EAD. De façon analogue à Dia1, nous avons découvert que ELMO à l’état basal est autoinhibé grâce à des intéractions intramoléculaires. Nous proposons que l’état d’activation des protéines ELMO est régulé de façon similaire aux formines de la famille Dia, c’est-à-dire grâce à des interactions avec d’autres protéines. Dans l’objectif nº 3, nous identifions un domaine RBD polyvalent chez ELMO. Ce domaine possède une double spécificité pour les GTPases de la famille Rho et Arf. Nous avons découvert que Arl4A agit comme signal de recrutement membranaire pour le module ELMO/DOCK180/Rac. Nos résultats nous permettent de supposer que d’autres GTPases pourraient être impliquées dans l’activation et la localisation de cette voie de signalisation. Nous concluons qu’à l’état basal, ELMO et DOCK180 forment un complexe dans lequel ELMO est dans sa conformation autoinhibée. Bien que le mécanisme d’activation de ELMO ne soit pas encore bien compris, nous avons découvert que, lorsqu’il y a stimulation cellulaire, certaines GTPases liées au GTP peuvent intéragir avec le domaine RBD de ELMO pour relâcher les contacts intramoléculaires et/ou localiser le complexe à la membrane. Ainsi, les GTPases peuvent servir d’ancrage au complexe ELMO/DOCK180 pour assurer une regulation spatiotemporelle adequate de l’activation et de la signalisation de Rac. / DOCK180 and ELMO cooperate biochemically and genetically to activate Rac in several biological events. However, the role of these proteins in Rac signaling is still poorly understood. We hypothesize that DOCK180 functions as a RacGEF, with ELMO binding to DOCK180 being required for integration of proper Rac signaling rather than Rac activation per se. We postulate that ELMO acts as a subcellular targeting signal for spatio-temporal restriction of DOCK180-mediated Rac signaling and/or as a scaffold for Rac effectors to enforce cell migration. In Aim #1, we elucidate that the atypical ELMO1 PH is the major DOCK180 binding site. We demonstrate that the binding of ELMO1 to DOCK180 is not necessary for Rac GTP-loading, but is instead required to facilitate Rac-GTP induced cytoskeletal changes following DOCK180 activation. These results imply additional roles for ELMO in mediating Rac signaling. In Aim #2, we reveal structural homology between ELMO and an autoregulatory module in the formin, Dia1, and identify three novel domains in ELMOs: the RBD, EID and EAD. Analogous to Dia1, we uncovered that ELMO is autoinhibited via intramolecular interactions at basal state. We propose that the activation state of ELMO proteins is regulated, much like in Dia-family formins, via interaction with other proteins. Aim #3 identifies a polyvalent RBD in ELMO with dual specificity for Rho and Arf family GTPases. We found Arl4A as a novel membrane recruitment signal for the ELMO/DOCK180/Rac module. Our results may have broad implications in the activation and localization of this pathway by additional GTPases. We conclude that, at basal levels, ELMO/DOCK180 is complexed, with ELMO in an autoinhibited state in the cytosol. Through cell stimulation, certain GTPases will be activated that now bind the ELMO RBD and alleviate the intramolecular contacts. In this way, the GTPase anchors the activated ELMO/DOCK180 module in place for proper spatio-temporal regulation of Rac activation and signaling.

Les protéines DOCK180 et ELMO coopèrent ensemble biochimiquement et génétiquement afin d’activer la GTPase Rac1 lors de plusieurs évènements biologiques. Toutefois, le rôle que jouent ces protéines dans la signalisation par Rac est encore mal compris. Nous émettons l’hypothèse que Dock180 agit comme activateur de Rac, alors que ELMO est requis pour l’intégration de la signalisation de Rac plutôt que son activation per se. Nous postulons que ELMO agit comme signal de localisation intracellulaire afin de restreindre de façon spatio-temporelle la signalisation de Rac en aval de Dock180, et/ou que ELMO agit comme protéine d’échafaudage entre Rac et ses effecteurs pour amplifier la migration cellulaire. Dans l’objectif nº 1, nous démontrons que le domaine PH atypique de ELMO1 est le site d’interaction principal entre cette protéine et DOCK180. De plus, nous démontrons que la liaison entre ELMO et DOCK180 n’est pas nécessaire pour l’activation de Rac, mais est plutôt essentielle pour faciliter la réorganisation du cytosquelette induite par l’activation de Rac en aval de Dock180. Ces résultats impliquent que ELMO pourrait jouer des rôles additionnels dans la signalisation par Rac. Dans l’objectif nº 2, nous avons découvert l’existence d’une homologie structurelle entre ELMO et un module d’autorégulation de la formine Dia1, et avons identifié trois nouveaux domaines dans la protéine ELMO : les domaines RBD, EID et EAD. De façon analogue à Dia1, nous avons découvert que ELMO à l’état basal est autoinhibé grâce à des intéractions intramoléculaires. Nous proposons que l’état d’activation des protéines ELMO est régulé de façon similaire aux formines de la famille Dia, c’est-à-dire grâce à des interactions avec d’autres protéines. Dans l’objectif nº 3, nous identifions un domaine RBD polyvalent chez ELMO. Ce domaine possède une double spécificité pour les GTPases de la famille Rho et Arf. Nous avons découvert que Arl4A agit comme signal de recrutement membranaire pour le module ELMO/DOCK180/Rac. Nos résultats nous permettent de supposer que d’autres GTPases pourraient être impliquées dans l’activation et la localisation de cette voie de signalisation. Nous concluons qu’à l’état basal, ELMO et DOCK180 forment un complexe dans lequel ELMO est dans sa conformation autoinhibée. Bien que le mécanisme d’activation de ELMO ne soit pas encore bien compris, nous avons découvert que, lorsqu’il y a stimulation cellulaire, certaines GTPases liées au GTP peuvent intéragir avec le domaine RBD de ELMO pour relâcher les contacts intramoléculaires et/ou localiser le complexe à la membrane. Ainsi, les GTPases peuvent servir d’ancrage au complexe ELMO/DOCK180 pour assurer une regulation spatiotemporelle adequate de l’activation et de la signalisation de Rac. / DOCK180 and ELMO cooperate biochemically and genetically to activate Rac in several biological events. However, the role of these proteins in Rac signaling is still poorly understood. We hypothesize that DOCK180 functions as a RacGEF, with ELMO binding to DOCK180 being required for integration of proper Rac signaling rather than Rac activation per se. We postulate that ELMO acts as a subcellular targeting signal for spatio-temporal restriction of DOCK180-mediated Rac signaling and/or as a scaffold for Rac effectors to enforce cell migration. In Aim #1, we elucidate that the atypical ELMO1 PH is the major DOCK180 binding site. We demonstrate that the binding of ELMO1 to DOCK180 is not necessary for Rac GTP-loading, but is instead required to facilitate Rac-GTP induced cytoskeletal changes following DOCK180 activation. These results imply additional roles for ELMO in mediating Rac signaling. In Aim #2, we reveal structural homology between ELMO and an autoregulatory module in the formin, Dia1, and identify three novel domains in ELMOs: the RBD, EID and EAD. Analogous to Dia1, we uncovered that ELMO is autoinhibited via intramolecular interactions at basal state. We propose that the activation state of ELMO proteins is regulated, much like in Dia-family formins, via interaction with other proteins. Aim #3 identifies a polyvalent RBD in ELMO with dual specificity for Rho and Arf family GTPases. We found Arl4A as a novel membrane recruitment signal for the ELMO/DOCK180/Rac module. Our results may have broad implications in the activation and localization of this pathway by additional GTPases. We conclude that, at basal levels, ELMO/DOCK180 is complexed, with ELMO in an autoinhibited state in the cytosol. Through cell stimulation, certain GTPases will be activated that now bind the ELMO RBD and alleviate the intramolecular contacts. In this way, the GTPase anchors the activated ELMO/DOCK180 module in place for proper spatio-temporal regulation of Rac activation and signaling.

The doctoral thesis deals with reliability (dependability) analyses of operation and testing data of the Airplanes. Requirements of airworthiness regulations on aircraft hydraulic systems (with a focus on US FAR-23 and European CS-23 regulations) are taken into account. Mentioned regulations include requirements for the structural design, design of systems, etc. They cover wide range of airplanes from small sport airplanes to 19-seats transport aircraft. Also options for predictive reliability analyses (resources) and reliability tests are discussed in the doctoral thesis. Practical application is done on small transport airplane (currently in the development). The failure report is designed. Expected major contribution of the work is selection and practical application of the most suitable procedures for safety assessment on the field of aircraft hydraulic systems, with a focus on the small transport aircraft. Also the comparison to different data source is shown.

The rapid development, approval, and production of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in less than 1 year after the first reports of a new infectious disease was a real game changer, providing 80%–90% efficacy in preventing severe etiopathologies of the coronavirus disease 2019 (COVID-19). These vaccines induce an immune response against the SARS-CoV-2 spike (S) protein located on the surface of the virus particle. Antibodies (Abs) recognizing the S-protein can inhibit binding of the virus via the S-protein to the angiotensin-converting enzyme-2 (ACE-2) receptor expressed on different human cells, especially when these Abs bind to the interaction site, the so-called receptor-binding domain (RBD). We have expressed the RBDs of wild-type SARS-CoV-2 and five variants of concern (VOCs) to test the immune response in people before vaccination with mRNA vaccines BNT162b2 and mRNA-1273 and after up to three vaccinations using in-house ELISA and inhibition assays. The methods of both assays are provided. Both vaccines initiated similarly high IgG titers after two vaccinations against the wild-type and even two VOC-RBDs (alpha and delta) and strongly inhibited the corresponding RBD-ACE-2 binding. The IgG titers and inhibition of ACE-2 binding were lower for beta and gamma RBDs and much lower for omicron RBD. The third vaccination after 6 months strongly increased both the IgG titers and the neutralizing effect against all variants, especially for omicron, leading to 63% ± 13% neutralization potential. Importantly, neutralization linearly increased with the IgG titers.