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Zur numerischen L\"osung von Algebro-Differentialgleichungen (ADGln) m\"ussen konsistente Anfangswerte berechnet werden. Diese Arbeit befasst sich mit einem Ansatz zur Behandlung dieses Problems f\"ur Index-2 DAEs unter Verwendung von Projektoren auf die zur DAE zugeh\"origen Unterr\"aume. Die Arbeit hat zwei Schwerpunkte.\\ Zum einen werden neue Struktureigenschaften aus schwachen Voraussetzungen hergeleitet. Anschlie{\ss}end wird eine Vorgehensweise zur Auswahl von geeigneten Gleichungen einer Index-2 ADGln vorgeschlagen, deren Differentiation zu einer Indexreduktion f\"uhrt. Diese Indexreduktion liefert neue Existenz- und Eindeutigkeitsergebnisse f\"ur L\"osungen von Index-2 ADGln. Die Ergebnisse umfassen eine allgemeinere Aufgabenklasse als die bisherigen Resultate. Beruhend auf dieser Vorgehensweise wird ein stufenweiser Ansatz zur Berechnung konsistenter Anfangswerte hergeleitet. Auf diese Weise werden neue Einsichten hinsichtlich der Ausnutzung von Struktureigenschaften von Index-2 ADGln gewonnen. Insbesondere stellt sich heraus, dass im Vergleich zu Index-1 ADGln der zus\"atzliche Schritt oft in der L\"osung eines linearen Systems besteht. Die sich hieraus ergebenden numerischen Folgen werden f\"ur zwei in der Schaltungssimulation h\"aufig verwendete Verfahren, das implizite Eulerverfahren und die Trapezregel, erl\"autert. \\ Zum anderen wird die Anwendung der erhaltenen Ergebnisse auf die Gleichungen, die bei der Schaltungssimulation mittels modifizierter Knotenanalyse entstehen, ausgearbeitet. Abschlie{\ss}end wird eine kurze \"Ubersicht der durchgef\"uhrten Umsetzung gegeben.\\ / For solving DAEs numerically, consistent initial values have to be calculated. This thesis deals with an approach for handling this problem for index-2 DAEs by considering projectors onto the spaces related to the DAE. There are two major aspects in this work.\\ On the one hand, new structural properties are deduced from weak assumptions. Subsequently, a method is proposed to choose suitable equations of an index-2 DAE, whose differentiation leads to an index reduction. This index reduction yields new theoretical results for the existence and uniqueness of solutions of index-2 DAEs which apply to a wider class of applications than previous results. Based on this method, a step-by-step approach to compute consistent initial values is developed. In this way, we gain new insights about how to deal with structural properties of index-2 DAEs. In particular, it turns out that, in comparison to index-1 DAEs, the additional step that has to be undertaken in practice often consists in solving a linear system. The numerical consequences of this fact are exemplified for two methods commonly used in circuit simulation, the implicit Euler method and the trapezoidal rule.\\ On the other hand, the application of the obtained results to the equations arising in circuit simulation by means of the modified nodal analysis (MNA) is worked out. Finally, a short overview of the specifics of their realization is given.

Benefiting from the constant and significant advancement of wireless communication technologies and networking protocols, Wireless Ad hoc NETwork (WANET) has played a more and more important role in modern communication networks without relying much on existing infrastructures. The past decades have seen numerous applications adopting ad hoc networks for service provisioning. For example, Wireless Sensor Network (WSN) can be widely deployed for environment monitoring and object tracking by utilizing low-cost, low-power and multi-function sensor nodes. To realize such applications, the design and evaluation of communication protocols are of significant importance. Meanwhile, the network performance analysis based on mathematical models is also in great need of development and improvement. This dissertation investigates the above topics from three important and fundamental aspects, including data collection protocol design, protocol modeling and analysis, and physical interference modeling and analysis. The contributions of this dissertation are four-fold. First, this dissertation investigates the synchronization issue in the duty-cycled, pipelined-scheduling data collection of a WSN, based on which a pipelined data collection protocol, called PDC, is proposed. PDC takes into account both the pipelined data collection and the underlying schedule synchronization over duty-cycled radios practically and comprehensively. It integrates all its components in a natural and seamless way to simplify the protocol implementation and to achieve a high energy efficiency and low packet delivery latency. Based on PDC, an Adaptive Data Collection (ADC) protocol is further proposed to achieve dynamic duty-cycling and free addressing, which can improve network heterogeneity, load adaptivity, and energy efficiency. Both PDC and ADC have been implemented in a pioneer open-source operating system for the Internet of Things, and evaluated through a testbed built based on two hardware platforms, as well as through emulations. Second, Linear Sensor Network (LSN) has attracted increasing attention due to the vast requirements on the monitoring and surveillance of a structure or area with a linear topology. Being aware that, for LSN, there is few work on the network modeling and analysis based on a duty-cycled MAC protocol, this dissertation proposes a framework for modeling and analyzing a class of duty-cycled, multi-hop data collection protocols for LSNs. With the model, the dissertation thoroughly investigates the PDC performance in an LSN, considering both saturated and unsaturated scenarios, with and without retransmission. Extensive OPNET simulations have been carried out to validate the accuracy of the model. Third, in the design and modeling of PDC above, the transmission and interference ranges are defined for successful communications between a pair of nodes. It does not consider the cumulative interference from the transmitters which are out of the contention range of a receiver. Since most performance metrics in wireless networks, such as outage probability, link capacity, etc., are nonlinear functions of the distances among communicating, relaying, and interfering nodes, a physical interference model based on distance is definitely needed in quantifying these metrics. Such quantifications eventually involve the Nodal Distance Distribution (NDD) intrinsically depending on network coverage and nodal spatial distribution. By extending a tool in integral geometry and using decomposition and recursion, this dissertation proposes a systematic and algorithmic approach to obtaining the NDD between two nodes which are uniformly distributed at random in an arbitrarily-shaped network. Fourth, with the proposed approach to NDDs, the dissertation presents a physical interference model framework to analyze the cumulative interference and link outage probability for an LSN running the PDC protocol. The framework is further applied to analyze 2D networks, i.e., ad hoc Device-to-Device (D2D) communications underlaying cellular networks, where the cumulative interference and link outage probabilities for both cellular and D2D communications are thoroughly investigated. / Graduate / 0984 / 0544 / tong1987fei@163.com

Introdução: Os linfomas não-Hodgkin de células T periféricas (LCTP) são neoplasias raras caracterizadas pela proliferação monoclonal de linfócitos T maduros. Correspondem a 15% das malignidades linfoides e têm distribuição geográfica peculiar. Compreendem 22 entidades clínico-patológicas distintas, heterogêneas do ponto de vista clínico-epidemiológico, morfológico, fenotípico e molecular. O grupo de apresentação predominantemente nodal compreende as variantes histológicas LGCA/ALK+, LGCA/ALK-, LCTA e LCTP/SOE. Sua terapêutica se baseia em poliquimioterápicos à base de antraciclina e consolidação com transplante de células tronco hematopoiéticas autólogas (TCTH). Com exceção do LGCA/ALK+, apresentam sobrevida global em cinco anos de 30% a 40%. Devido aos desfechos desfavoráveis, estudos de perfil de expressão gênica e de metilação de genes supressores tumorais têm emergido nos últimos anos para refinar o diagnóstico destas neoplasias, melhorar o conhecimento fisiopatológico e o prognóstico e estabelecer possíveis alvos terapêuticos. Estudos preliminares com LCTP nodais indicam valor prognóstico favorável da hiperexpressão de genes de padrão inflamatório NFkB1 e IKBkB e desfavorável nos casos de supraregulação de genes de padrão proliferativo como CCNA2, TOP2A e CHEK1 e do fenótipo metilado de p15INK4b e p16INK4a. Objetivo:Avaliar o impacto da expressão relativa dos genes CCNA2, TOP2A, CHEK1, NFkB1, IKBkB e VEGF1 e da metilação dos genes p15 e p16 em população brasileira com LCTP nodais tratados com quimioterapia CHOP-símile para os desfechos de sobrevida global, sobrevida livre de progressão e sobrevida livre de doença. Métodos: A expressão gênica foi avaliada por qtPCR de amostras fixadas em formol e incluídas em parafina de 63 pacientes. A mediana de expressão dos genes foi comparada com variáveis clínicas e desfechos. PCR qualitativa metilação-específico foi usada avaliar a metilação de p15 e p16. Resultados: Com mediana de seguimento de vinte meses, as SG, SLP e SLD foram, respectivamente, 45,6%, 34,3% e 63,0% e a resposta completa de 46,0%. Em análise multivariada, ECOG >= 2 e a hiperexpressão do gene CCNA2 foram associadas à pior SG em cinco anos, nos LCTP nodais (p=0,008 e p=0,002). Em análise univariada os genes CCNA2, TOP2A e CHEK1 foram associados ao pior prognóstico nos LCTP/SOE e melhor nos LGCA/ALK-. A hiperexpressão do gene VEGF1 se associou ao pior prognóstico no LGCA/ALK- e LCTA. Metilação de p15INK4b não foi encontrada nos LGCA/ALK+ e em análise multivariada foi associada a pior SLP em 5 anos nos LCTP não-ALK+ (HR: 9,88; p=0,03). O painel gênico testado não apresentou poder para discriminar as diferentes variantes histopatólogicas de LCTP nodais, porém demonstrou-se associação direta entre a intensidade de mediana de expressão desses genes e agressividade biológica nesse grupo heterogêneo de neoplasias. O significado prognóstico de imunoexpressão da proteína ALK sofreu influência das variáveis constituintes do IPI nessa coorte. Conclusão: A hiperexpressao dos genes CCNA2, TOP2A e CHEK1 foram associadas a prognóstico desfavorável nos LCTP/SOE e favorável nos LGCA/ALK-. Fenótipo hipermetilado de p15INK4b não foi evento observado em LGCA/ALK+, porém foi associado a pior prognóstico nos LCTP nodais não-ALK+ / Background: Peripheral T-cell non-Hodgkin\'s lymphomas (PTCL) are rare tumors characterized by monoclonal proliferation of mature T lymphocytes; they correspond to 15% of lymphoid malignancies and have specific geographic distribution. PTCL comprise 22 distinct clinicopathologic entities, heterogeneous from the clinical and epidemiological perspective, as well as morphologic, phenotypic and molecular. The group of presentation predominantly nodal comprises the histological variants ALCL/ALK+, ALCL/ALK-, AITL and PTCL/NOS. Its treatment is based on polychemotherapy with anthracycline and consolidation with autologous hematopoietic stem cell transplantation (ASCT). With the exception of ALCL/ALK+, these tumors show overall survival at 5 years from 30% to 40%. Due to unfavorable outcomes, gene expression profile studies, as well as studies of methylation of tumor suppressor genes, have emerged in recent years in order to refine the pathological diagnosis of these cancers, improve the pathophysiological knowledge and prognosis, and establish possible therapeutic targets. Preliminary studies with nodal PTCLs indicate favorable prognostic value of overexpression of inflammatory pattern genes like NFkB1 e IKBkB, and unfavorable in the case of proliferative genes as CCNA2, TOP2A, CHEK1 and the methylated phenotype of suppressor genes p15INK4b e p16INK4a. Objectives: Assess the impact of relative expression of genes CCNA2, TOP2A, CHEK1, NFkB, IKBkB and VEGF1 and the methylation of the genes p15 and p16 in Brazilian population with nodal PTCLs treated with CHOP-like chemotherapy for the outcomes of overall survival, progression-free survival and disease-free survival. Methods: Gene expression was assessed by qtPCR of paraffin samples of 63 patients. The median gene expression was compared with clinical variables and outcomes. Qualitative methylation-specific PCR was used to assess the methylation of p15 and p16. Results: With a segment median of 20 months, the OS, PFS and DFS were, respectively, 45,6%, 34,3% and 63,0% and the complete response (CR) was 46,0%. In multivariate analysis, ECOG >= 2 and overexpression of the gene CCNA2 were associated with worse OS at 5 years in nodal PTCLs (p = 0,008 and p = 0,002). In univariate analysis, the genes CCNA2, TOP2A and CHEK1 were associated with worse prognosis in PTCL/NOS and better in ALCL/ALK negative. The overexpression of the gene VEGF1 was associated with worse prognosis in the variants AITL and ALCL/ALK negative. Methylation of the gene p15INK4b was not found in ALCL/ALK+ group, and in multivariate analysis was associated with worse 5-years PFS in the group of PTCL non-ALK+ (HR: 9,88 and p = 0,03). The gene panel tested showed no power to discriminate the different histopathology of nodal PTCL, but it showed a direct association between the median intensity of expression of these genes and biological aggressiveness in this heterogeneous group of neoplasms. The prognostic significance of immunostaining of ALK protein was influenced by IPI constituents variables in this cohort. Conclusion: The overexpression of genes CCNA2, TOP2A e CHEK1 were associated with poor prognosis in PTCL/NOS and favorable in ALCL/ALK negative. Hypermethylated phenotype of gene p15INK4b was not an observed event in ALCL/ALK+, but it was associated with poor prognosis in nodal PTCL non-ALK+

Perhaps surprisingly, the largest experience in operating nuclear power plants has been in nuclear naval propulsion, particularly submarines. This accumulated experience may become the basis of a proposed new generation of compact nuclear power plant designs. In an effort to de-carbonise commercial freight shipping, there is growing interest in the possibility of using nuclear propulsion systems. Reactor cores for such an application would need to be fundamentally different from land-based power generation systems, which require regular refueling, and from reactors used in military submarines, as the fuel used could not conceivably be as highly enriched. Nuclear-powered propulsion would allow ships to operate with low fuel costs, long refueling intervals, and minimal emissions; however, currently such systems remain largely confined to military vessels. This research project undertakes computational modeling of possible soluble-boron-free (SBF) reactor core designs for this application, with a view to informing design decisions in terms of choices of fuel composition, materials, core geometry and layout. Computational modeling using appropriate reactor physics (e.g. WIMS, MONK, Serpent and PANTHER), thermal-hydraulics etc. codes (e.g. COBRA-EN) is used for this project. With an emphasis on reactor physics, this study investigates possible fuel assembly and core designs for civil marine propulsion applications. In particular, it explores the feasibility of using uranium/thorium-rich fuel in a compact, long-life reactor and seek optimal choices and designs of the fuel composition, reactivity control, assembly geometry, and core loading in order to meet the operational needs of a marine propulsion reactor. In this reactor physics and 3D coupled neutronics/thermal-hydraulics study, we attempt to design a civil marine reactor core that fulfills the objective of providing at least 15 effective full-power-years (EFPY) life at 333 MWth. In order to unleash the benefit of thorium in a long life core, the micro-heterogeneous ThO2-UO2 duplex fuel is well-positioned to be utilized in our proposed civil marine core. Unfortunately, A limited number of studies of duplex fuel are available in the public domain, but its use has never been examined in the context of a SBF environment for long-life small modular rector (SMR) core. Therefore, we assumed micro-heterogeneous ThO2-UO2 duplex fuel for our proposed marine core in order to explore its capability. For the proposed civil marine propulsion core design, this study uses 18% U-235 enriched micro-heterogeneous ThO2-UO2 duplex fuel. To provide a basis for comparison we also evaluate the performance of homogeneously mixed 15% U-235 enriched all-UO2 fuel. This research also attempts to design a high power density core with 14 EFPY while satisfying the neutronic and thermal-hydraulics safety constraints. A core with an average power density of 100 MW/m3 has been successfully designed while obtaining a core life of 14 years. The average core power density for this core is increased by ∼50% compared to the reference core design (63 MW/m3 and is equivalent to Sizewell B PWR (101.6 MW/m3 which means capital costs could be significantly reduced and the economic attractiveness of the marine core commensurately improved. In addition, similar to the standard SMR core, a reference core with a power density of 63 MW/m3 has been successfully designed while obtaining a core life of ∼16 years. One of the most important points that can be drawn from these studies is that a duplex fuel lattice needs less burnable absorber than uranium-only fuel to achieve the same poison performance. The higher initial reactivity suppression and relatively smaller reactivity swing of the duplex can make the task of reactivity control through BP design in a thorium-rich core easier. It is also apparent that control rods have greater worth in a duplex core, reducing the control material requirements and thus potentially the cost of the rods. This research also analyzed the feasibility of using thorium-based duplex fuel in different cases and environments to observe whether this fuel consistently exhibit superior performance compared to the UO2 core in both the assembly and whole-core levels. The duplex fuel/core consistently exhibits superior performance in consideration of all the neutronic and TH constraints specified. It can therefore be concluded from this study that the superior performance of the thorium-based micro-heterogeneous ThO2-UO2 duplex fuel provides enhanced confidence that this fuel can be reliably used in high power density and long-life SBF marine propulsion core systems, offering neutronic advantages compared to the all-UO2 fuel. Last, but not least, considering all these factors, duplex fuel can potentially open the avenue for low-enriched uranium (LEU) SBF cores with different configurations. Motivated by growing environmental concerns and anticipated economic pressures, the overall goal of this study is to examine the technological feasibility of expanding the use of nuclear propulsion to civilian maritime shipping and to identify and propose promising candidate core designs.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Nesta dissertação propomos a utilização do método espectro-nodal SGF, cf. spectral Greens function, para transporte SN de partículas neutras, para determinarmos os fluxos angulares nas interfaces das regiões homogêneas do domínio espacial heterogêneo, com espalhamento linearmente anisotrópico usando preferencialmente altas ordens de quadraturas angulares. As reconstruções espaciais analíticas dos fluxos angulares são feitas no interior das regiões homogêneas, determinando as constantes arbitrárias da solução analítica local das equações SN no interior dos nodos espaciais da grade de dicretização. A seguir, utilizando essas constantes, determinamos as expressões do fluxo escalar e da corrente de nêutrons, que são substituídas na equação de transporte unidimensional em geometria retangular Cartesiana no termo de fonte por espalhamento linearmente anisotrópico. Resolvemos analiticamente a equação de transporte com os termos do fluxo escalar e corrente de nêutrons assim aproximados para estimarmos o perfil do fluxo angular de nêutrons no domínio. Esta reconstrução analítica aproximada da solução da equação de transporte de partículas neutras em geometria unidimensional Cartesiana constitui um problema inverso, na medida em que a partir da solução nodal de malha grossa fazemos primeiramente uma reconstrução analítica espacial do fluxo angular nas direções das ordenadas discretas, para em seguida procedermos à reconstrução analítica aproximada do fluxo no domínio angular. / We describe the application of the spectral Greens function SN nodal method for one-speed neutral particle transport calculations to determine the angular fluxes at the homogeneized regions within heterogeneous domains, for linearly anisotropic scattering, using preferably high-order angular quadratures. The reconstruction scheme in the space variable of the angular flux is carried out within the homogenized regions using uniform spatial grid. We determine the arbitrary constants of the analytical SN general solution inside each spatial node. Then, we determine the SN expression for the scalar flux and total current that we substitute into the analytical slab-geometry transport equation, precisely into its linearly anisotropic scattering source term. Further, we solve analytically the slab-geometry transport equation, so approximated, to obtain the flux profile within the space and angular domains. This approximate analytical reconstruction scheme of the solution of the neutral particle transport equation in slab geometry is an inverse problem, in the sense that we use accurate coarse-mesh SN numerical solution, to recover the SN analytical solution in the space variable, and then reconstruct the solution approximately in the angular domain.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Nesta dissertação propomos a utilização do método espectro-nodal SGF, cf. spectral Greens function, para transporte SN de partículas neutras, para determinarmos os fluxos angulares nas interfaces das regiões homogêneas do domínio espacial heterogêneo, com espalhamento linearmente anisotrópico usando preferencialmente altas ordens de quadraturas angulares. As reconstruções espaciais analíticas dos fluxos angulares são feitas no interior das regiões homogêneas, determinando as constantes arbitrárias da solução analítica local das equações SN no interior dos nodos espaciais da grade de dicretização. A seguir, utilizando essas constantes, determinamos as expressões do fluxo escalar e da corrente de nêutrons, que são substituídas na equação de transporte unidimensional em geometria retangular Cartesiana no termo de fonte por espalhamento linearmente anisotrópico. Resolvemos analiticamente a equação de transporte com os termos do fluxo escalar e corrente de nêutrons assim aproximados para estimarmos o perfil do fluxo angular de nêutrons no domínio. Esta reconstrução analítica aproximada da solução da equação de transporte de partículas neutras em geometria unidimensional Cartesiana constitui um problema inverso, na medida em que a partir da solução nodal de malha grossa fazemos primeiramente uma reconstrução analítica espacial do fluxo angular nas direções das ordenadas discretas, para em seguida procedermos à reconstrução analítica aproximada do fluxo no domínio angular. / We describe the application of the spectral Greens function SN nodal method for one-speed neutral particle transport calculations to determine the angular fluxes at the homogeneized regions within heterogeneous domains, for linearly anisotropic scattering, using preferably high-order angular quadratures. The reconstruction scheme in the space variable of the angular flux is carried out within the homogenized regions using uniform spatial grid. We determine the arbitrary constants of the analytical SN general solution inside each spatial node. Then, we determine the SN expression for the scalar flux and total current that we substitute into the analytical slab-geometry transport equation, precisely into its linearly anisotropic scattering source term. Further, we solve analytically the slab-geometry transport equation, so approximated, to obtain the flux profile within the space and angular domains. This approximate analytical reconstruction scheme of the solution of the neutral particle transport equation in slab geometry is an inverse problem, in the sense that we use accurate coarse-mesh SN numerical solution, to recover the SN analytical solution in the space variable, and then reconstruct the solution approximately in the angular domain.

[pt] Recentes apagões em todo o mundo fazem da confiabilidade de sistemas de potência, no tocante a contingências múltiplas, um tema de pesquisa mundial. Dentro desse contexo, se faz importante investigar métodos eficientes de proteger o sistema contra falhas de alguns de seus componentes, sejam elas dependentes e/ou independentes de outras falhas. Nesse sentido, se tornou crucial a incorporação de critérios de segurança mais rigorosos na operação e planejamento de sistemas de potência. Contingências múltiplas são mais comuns e desastrosas do que falhas naturais e independentes. A principal razão para isso reside na complexidade da estabilidade dinâmica de sistemas de potência. Além disso, o sistema de proteção que opera em paralelo ao sistema de distribuição não é livre de falhas. Portanto, interrupções naturais podem causar contingências em cascata em decorrência do mau funcionamento de mecanismos de proteção ou da instabilidade do sistema elétrico como um todo. Nesse contexto, se dá a motivação pela busca de critérios de segurança mais severos como, por exemplo, o n - K, onde K pode ser maior do que 2. Nesse trabalho, o principal objetivo é incorporar o crtitério de segurança geral n-K para geração e transmissão em modelos de operação e planejamento de sistemas de potência. Além de interrupções em geradores, restrições de rede, bem como falhas em linhas de transmiss˜ao também são modeladas. Esse avanço leva a novos desafios computacionais, para os quais formulamos metodologias de solução eficientes baseadas em decomposição de Benders. Considerando operação, duas abordagens são apresentadas. A primeira propõe um modelo de otimização trinível para decidir o despacho ótimo de energia e reservas sob um critério de segurançaa n - K. Nessa abordagem, a alta dimensionalidade do problema, por contemplar restrições de rede, bem como falhas de geradores e de linhas de transmissão, é contornada por meio da implícita consideração do conjunto de possíveis contingências. No mesmo contexto, a segunda abordagem leva em conta a incerteza da carga a ser suprida e a correlação entre demandas de diferentes barras. Considerando planejamento de expansão da transmissão, outro modelo de otimização trinível é apresentado no intuito de decidir quais linhas de transmissão, dentro de um conjunto de candidatas, devem ser construídas para atender a um critério de segurança n - K e, consequentemente, aumentar a confiabilidade do sistema como um todo. Portanto, as principais contribuições do presente trabalho são as seguintes: 1) modelos de otimização trinível para considerar o critério de segurança n - K em operação e planejamento de sistemas de potência, 2) consideração implícita de todo o conjunto de contingências por meio de uma abordagem de otimização robusta ajustável, 3) otimização conjunta de energia e reserva para operação de sistemas de potência, considerando restrições de rede e garantindo a entregabilidade das reservas em todos os estados pós-contingência considerados, 4) metodologias de solução eficientes baseadas em decomposição de Benders que convergem em passos finitos para o ótimo global e 5) desenvolvimento de restrições válidas que alavancam a eficiência computacional. Estudos de caso ressaltam a eficácia das metodologias propostas em capturar os efeitos econômicos de demanda nodal correlacionada sob um critério de segurançaa n - 1, em reduzir o esfor¸co computacional para considerar os critérios de seguran¸ca convencionais n-1 e n-2 e em considerar critérios de segurança mais rigorosos do que o n - 2, um problema intratável até então. / [en] Recent major blackouts all over the world have been a driving force to make power system reliability, regarding multiple contingencies, a subject of worldwide research. Within this context, it is important to investigate efficient methods of protecting the system against dependent and/or independent failures. In this sense, the incorporation of tighter security criteria in power systems operation and planning became crucial. Multiple contingencies are more common and dangerous than natural independent faults. The main reason for this lies in the complexity of the dynamic stability of power systems. In addition, the protection system, that operates in parallel to the supply system, is not free of failures. Thus, natural faults can cause subsequent contingencies (dependent on earlier contingencies) due to the malfunction of the protection mechanisms or the instability of the overall system. These facts drive the search for more stringent safety criteria, for example, n - K, where K can be greater than 2. In the present work, the main objective is to incorporate the joint generation and transmission general security criteria in power systems operation and planning models. Here, in addition to generators outages, network constraints and transmission lines failures are also accounted for. Such improvement leads to new computational challenges, for which we design efficient solution methodologies based on Benders decomposition. Regarding operation, two approaches are presented. The first one proposes a trilevel optimization model to decide the optimal scheduling of energy and reserve under an n - K security criterion. In such approach, the high dimensionality curse of considering network constraints as well as outages of generators and transmission assets is withstood by implicitly taking into account the set of possible contingencies. The second approach includes correlated nodal demand uncertainty in the same framework. Regarding transmission expansion planning, another trilevel optimization model is proposed to decide which transmission assets should be built within a set of candidates in order to meet an n - K security criterion, and, consequently, boost the power system reliability. Therefore, the main contributions of this work are the following: 1) trilevel models to consider general n - K security criteria in power systems operation and planning, 2) implicit consideration of the whole contingency set by means of an adjustable robust optimization approach, 3) co-optimization of energy and reserves for power systems operation, regarding network constraints and ensuring the deliverability of reserves in all considered post-contingency states, 4) efficient solution methodologies based on Benders decomposition that finitely converges to the global optimal solution, and 5) development of valid constraints to boost computational efficiency. Case studies highlight the effectiveness of the proposed methodologies in capturing the economic effect of nodal demand correlation on power system operation under an n - 1 security criterion, in reducing the computational effort to consider conventional n-1 and n-2 security criteria, and in considering security criteria tighter than n - 2, an intractable problem heretofore.

Introdução: Os linfomas não-Hodgkin de células T periféricas (LCTP) são neoplasias raras caracterizadas pela proliferação monoclonal de linfócitos T maduros. Correspondem a 15% das malignidades linfoides e têm distribuição geográfica peculiar. Compreendem 22 entidades clínico-patológicas distintas, heterogêneas do ponto de vista clínico-epidemiológico, morfológico, fenotípico e molecular. O grupo de apresentação predominantemente nodal compreende as variantes histológicas LGCA/ALK+, LGCA/ALK-, LCTA e LCTP/SOE. Sua terapêutica se baseia em poliquimioterápicos à base de antraciclina e consolidação com transplante de células tronco hematopoiéticas autólogas (TCTH). Com exceção do LGCA/ALK+, apresentam sobrevida global em cinco anos de 30% a 40%. Devido aos desfechos desfavoráveis, estudos de perfil de expressão gênica e de metilação de genes supressores tumorais têm emergido nos últimos anos para refinar o diagnóstico destas neoplasias, melhorar o conhecimento fisiopatológico e o prognóstico e estabelecer possíveis alvos terapêuticos. Estudos preliminares com LCTP nodais indicam valor prognóstico favorável da hiperexpressão de genes de padrão inflamatório NFkB1 e IKBkB e desfavorável nos casos de supraregulação de genes de padrão proliferativo como CCNA2, TOP2A e CHEK1 e do fenótipo metilado de p15INK4b e p16INK4a. Objetivo:Avaliar o impacto da expressão relativa dos genes CCNA2, TOP2A, CHEK1, NFkB1, IKBkB e VEGF1 e da metilação dos genes p15 e p16 em população brasileira com LCTP nodais tratados com quimioterapia CHOP-símile para os desfechos de sobrevida global, sobrevida livre de progressão e sobrevida livre de doença. Métodos: A expressão gênica foi avaliada por qtPCR de amostras fixadas em formol e incluídas em parafina de 63 pacientes. A mediana de expressão dos genes foi comparada com variáveis clínicas e desfechos. PCR qualitativa metilação-específico foi usada avaliar a metilação de p15 e p16. Resultados: Com mediana de seguimento de vinte meses, as SG, SLP e SLD foram, respectivamente, 45,6%, 34,3% e 63,0% e a resposta completa de 46,0%. Em análise multivariada, ECOG >= 2 e a hiperexpressão do gene CCNA2 foram associadas à pior SG em cinco anos, nos LCTP nodais (p=0,008 e p=0,002). Em análise univariada os genes CCNA2, TOP2A e CHEK1 foram associados ao pior prognóstico nos LCTP/SOE e melhor nos LGCA/ALK-. A hiperexpressão do gene VEGF1 se associou ao pior prognóstico no LGCA/ALK- e LCTA. Metilação de p15INK4b não foi encontrada nos LGCA/ALK+ e em análise multivariada foi associada a pior SLP em 5 anos nos LCTP não-ALK+ (HR: 9,88; p=0,03). O painel gênico testado não apresentou poder para discriminar as diferentes variantes histopatólogicas de LCTP nodais, porém demonstrou-se associação direta entre a intensidade de mediana de expressão desses genes e agressividade biológica nesse grupo heterogêneo de neoplasias. O significado prognóstico de imunoexpressão da proteína ALK sofreu influência das variáveis constituintes do IPI nessa coorte. Conclusão: A hiperexpressao dos genes CCNA2, TOP2A e CHEK1 foram associadas a prognóstico desfavorável nos LCTP/SOE e favorável nos LGCA/ALK-. Fenótipo hipermetilado de p15INK4b não foi evento observado em LGCA/ALK+, porém foi associado a pior prognóstico nos LCTP nodais não-ALK+ / Background: Peripheral T-cell non-Hodgkin\'s lymphomas (PTCL) are rare tumors characterized by monoclonal proliferation of mature T lymphocytes; they correspond to 15% of lymphoid malignancies and have specific geographic distribution. PTCL comprise 22 distinct clinicopathologic entities, heterogeneous from the clinical and epidemiological perspective, as well as morphologic, phenotypic and molecular. The group of presentation predominantly nodal comprises the histological variants ALCL/ALK+, ALCL/ALK-, AITL and PTCL/NOS. Its treatment is based on polychemotherapy with anthracycline and consolidation with autologous hematopoietic stem cell transplantation (ASCT). With the exception of ALCL/ALK+, these tumors show overall survival at 5 years from 30% to 40%. Due to unfavorable outcomes, gene expression profile studies, as well as studies of methylation of tumor suppressor genes, have emerged in recent years in order to refine the pathological diagnosis of these cancers, improve the pathophysiological knowledge and prognosis, and establish possible therapeutic targets. Preliminary studies with nodal PTCLs indicate favorable prognostic value of overexpression of inflammatory pattern genes like NFkB1 e IKBkB, and unfavorable in the case of proliferative genes as CCNA2, TOP2A, CHEK1 and the methylated phenotype of suppressor genes p15INK4b e p16INK4a. Objectives: Assess the impact of relative expression of genes CCNA2, TOP2A, CHEK1, NFkB, IKBkB and VEGF1 and the methylation of the genes p15 and p16 in Brazilian population with nodal PTCLs treated with CHOP-like chemotherapy for the outcomes of overall survival, progression-free survival and disease-free survival. Methods: Gene expression was assessed by qtPCR of paraffin samples of 63 patients. The median gene expression was compared with clinical variables and outcomes. Qualitative methylation-specific PCR was used to assess the methylation of p15 and p16. Results: With a segment median of 20 months, the OS, PFS and DFS were, respectively, 45,6%, 34,3% and 63,0% and the complete response (CR) was 46,0%. In multivariate analysis, ECOG >= 2 and overexpression of the gene CCNA2 were associated with worse OS at 5 years in nodal PTCLs (p = 0,008 and p = 0,002). In univariate analysis, the genes CCNA2, TOP2A and CHEK1 were associated with worse prognosis in PTCL/NOS and better in ALCL/ALK negative. The overexpression of the gene VEGF1 was associated with worse prognosis in the variants AITL and ALCL/ALK negative. Methylation of the gene p15INK4b was not found in ALCL/ALK+ group, and in multivariate analysis was associated with worse 5-years PFS in the group of PTCL non-ALK+ (HR: 9,88 and p = 0,03). The gene panel tested showed no power to discriminate the different histopathology of nodal PTCL, but it showed a direct association between the median intensity of expression of these genes and biological aggressiveness in this heterogeneous group of neoplasms. The prognostic significance of immunostaining of ALK protein was influenced by IPI constituents variables in this cohort. Conclusion: The overexpression of genes CCNA2, TOP2A e CHEK1 were associated with poor prognosis in PTCL/NOS and favorable in ALCL/ALK negative. Hypermethylated phenotype of gene p15INK4b was not an observed event in ALCL/ALK+, but it was associated with poor prognosis in nodal PTCL non-ALK+