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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
571

DNA damage response activated by anti-cancer agent, irofulven

Wiltshire, Timothy D. January 2007 (has links)
Thesis (Ph. D.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains ix, 227 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.
572

Systems Health Management and Prognosis using Physics Based Modeling and Machine Learning

January 2016 (has links)
abstract: There is a concerted effort in developing robust systems health monitoring/management (SHM) technology as a means to reduce the life cycle costs, improve availability, extend life and minimize downtime of various platforms including aerospace and civil infrastructure. The implementation of a robust SHM system requires a collaborative effort in a variety of areas such as sensor development, damage detection and localization, physics based models, and prognosis models for residual useful life (RUL) estimation. Damage localization and prediction is further complicated by geometric, material, loading, and environmental variabilities. Therefore, it is essential to develop robust SHM methodologies by taking into account such uncertainties. In this research, damage localization and RUL estimation of two different physical systems are addressed: (i) fatigue crack propagation in metallic materials under complex multiaxial loading and (ii) temporal scour prediction near bridge piers. With little modifications, the methodologies developed can be applied to other systems. Current practice in fatigue life prediction is based on either physics based modeling or data-driven methods, and is limited to predicting RUL for simple geometries under uniaxial loading conditions. In this research, crack initiation and propagation behavior under uniaxial and complex biaxial fatigue loading is addressed. The crack propagation behavior is studied by performing extensive material characterization and fatigue testing under in-plane biaxial loading, both in-phase and out-of-phase, with different biaxiality ratios. A hybrid prognosis model, which combines machine learning with physics based modeling, is developed to account for the uncertainties in crack propagation and fatigue life prediction due to variabilities in material microstructural characteristics, crack localization information and environmental changes. The methodology iteratively combines localization information with hybrid prognosis models using sequential Bayesian techniques. The results show significant improvements in the localization and prediction accuracy under varying temperature. For civil infrastructure, especially bridges, pier scour is a major failure mechanism. Currently available techniques are developed from a design perspective and provide highly conservative scour estimates. In this research, a fully probabilistic scour prediction methodology is developed using machine learning to accurately predict scour in real-time under varying flow conditions. / Dissertation/Thesis / Doctoral Dissertation Mechanical Engineering 2016
573

Dano injusto como pressuposto do dever de indenizar / The unfair damage as a presupposition of the duty to indemnify

Karinne Ansiliero Angelin 10 May 2013 (has links)
O objetivo desta dissertação é demonstrar que a responsabilidade civil aquiliana, no ordenamento jurídico brasileiro, tem como pressuposto fundamental a causação de dano injusto. Esse objetivo justifica-se porque existem posições doutrinárias, conhecidas como direito de danos, que defendem a desnecessidade do dano injusto para que seja deflagrada a estrutura de responsabilização civil. Analisam-se, para tanto, a estrutura e a finalidade da responsabilidade civil, bem como o seu enquadramento no sistema jurídico brasileiro. / The aim of this dissertation is to show that the non-contractual civil liability in the Brazilian legal order has as a fundamental presupposition the causation of the unfair damage. This aim is justifiable because there are doctrinaire opinion, known as damage law, that advocate the unnecessariness of the unfair damage to be triggered the structure of civil liability. It analyzes, therefore, the structure and the goal of the civil liability, as well as its fitting into the Brazilian legal system.
574

Multiscale Modeling of Heterogeneous Material Systems

January 2014 (has links)
abstract: Damage detection in heterogeneous material systems is a complex problem and requires an in-depth understanding of the material characteristics and response under varying load and environmental conditions. A significant amount of research has been conducted in this field to enhance the fidelity of damage assessment methodologies, using a wide range of sensors and detection techniques, for both metallic materials and composites. However, detecting damage at the microscale is not possible with commercially available sensors. A probable way to approach this problem is through accurate and efficient multiscale modeling techniques, which are capable of tracking damage initiation at the microscale and propagation across the length scales. The output from these models will provide an improved understanding of damage initiation; the knowledge can be used in conjunction with information from physical sensors to improve the size of detectable damage. In this research, effort has been dedicated to develop multiscale modeling approaches and associated damage criteria for the estimation of damage evolution across the relevant length scales. Important issues such as length and time scales, anisotropy and variability in material properties at the microscale, and response under mechanical and thermal loading are addressed. Two different material systems have been studied: metallic material and a novel stress-sensitive epoxy polymer. For metallic material (Al 2024-T351), the methodology initiates at the microscale where extensive material characterization is conducted to capture the microstructural variability. A statistical volume element (SVE) model is constructed to represent the material properties. Geometric and crystallographic features including grain orientation, misorientation, size, shape, principal axis direction and aspect ratio are captured. This SVE model provides a computationally efficient alternative to traditional techniques using representative volume element (RVE) models while maintaining statistical accuracy. A physics based multiscale damage criterion is developed to simulate the fatigue crack initiation. The crack growth rate and probable directions are estimated simultaneously. Mechanically sensitive materials that exhibit specific chemical reactions upon external loading are currently being investigated for self-sensing applications. The "smart" polymer modeled in this research consists of epoxy resin, hardener, and a stress-sensitive material called mechanophore The mechanophore activation is based on covalent bond-breaking induced by external stimuli; this feature can be used for material-level damage detections. In this work Tris-(Cinnamoyl oxymethyl)-Ethane (TCE) is used as the cyclobutane-based mechanophore (stress-sensitive) material in the polymer matrix. The TCE embedded polymers have shown promising results in early damage detection through mechanically induced fluorescence. A spring-bead based network model, which bridges nanoscale information to higher length scales, has been developed to model this material system. The material is partitioned into discrete mass beads which are linked using linear springs at the microscale. A series of MD simulations were performed to define the spring stiffness in the statistical network model. By integrating multiple spring-bead models a network model has been developed to represent the material properties at the mesoscale. The model captures the statistical distribution of crosslinking degree of the polymer to represent the heterogeneous material properties at the microscale. The developed multiscale methodology is computationally efficient and provides a possible means to bridge multiple length scales (from 10 nm in MD simulation to 10 mm in FE model) without significant loss of accuracy. Parametric studies have been conducted to investigate the influence of the crosslinking degree on the material behavior. The developed methodology has been used to evaluate damage evolution in the self-sensing polymer. / Dissertation/Thesis / Doctoral Dissertation Mechanical Engineering 2014
575

Contribuição à formulação matemática de modelos constitutivos para materiais com dano contínuo / Contribution to mathematic formulation of continuum damage materials constitutive models

Antonio Roberto Balbo 02 June 1998 (has links)
A Mecânica do Dano Contínuo é atualmente uma poderosa ferramenta para se modelar o comportamento não-linear de vários materiais decorrente da evolução de um processo de microfissuração. A perda de rigidez causada pelo processo físico tem sido considerada em modelos constitutivos através de variáveis de dano escalar, vetorial ou tensorial. Quando o carregamento é proporcionalmente crescente as deformações residuais podem ser ignoradas e relações constitutivas simples podem ser obtidas, onde os efeitos do dano aparecem por uma penalização direta das propriedades elásticas. Por outro lado, efeitos de dano podem ser acoplados com deformações residuais levando a relações constitutivas mais gerais. Esse trabalho está relacionado a esses tipos de modelos assumindo que o meio ideal apresenta um comportamento elástico linear com danificação ou elastoplástico com danificação. Um dos principais aspectos discutido relaciona-se à formulação variacional, a qual está baseada em conceitos de Análise Convexa e Não-Convexa. Explorando o fato que a evolução do dano tem correspondência com a idealização de regime de encruamento negativo, a teoria de localização de deformação é abordada e um estudo da condição necessária de singularidade ou perda da condição de elipticidade é realizado. Na sequência, uma proposta preliminar para uma análise de pós-singularidade, baseada na Teoria de Bifurcação, é feita no sentido de caracterizar pontos limite ou pontos de bifurcação de solução, em sistemas conservativos. / Continuum Damage Mechanics is nowadays a powerful tool to model the non-linear behaviour of several materials due to evolution of a microcracking process. The lost of rigidity caused by such physical process has been accounted in the constitutive models through a scalar, vectorial or tensorial damage variables. When proportional loading is considered the residuals strains can be ignored and simple constitutive relations can be obtained in which damage effects appear by direct penalization of the elastic properties. On the other hand, damage effects can be coupled with residual strains leading to more general constitutive relations. This work is related to such kind of models assuming that the ideal medium presents a linear elastic-damage or an elastoplastic-damage behaviour. One of the main topics discussed is related to the variational formulation which is based on Convex and Non-Convex Analysis concepts. Exploring the fact that damage evolution has correspondence with a softening idealised regime, the strain localization theory is treated and a study of a necessary condition for singularity or ellipticity tose condition is developed. In the sequence, a introductory poscritical analysis is proposed, based in the bifurcation theory and aiming to detect if the singularity corresponds to a limit or a bifurcation point solution, in conservative systems.
576

Family needs following adult traumatic brain injury

Van der Merwe, Jó-Marié January 2004 (has links)
Traumatic brain injury (TBI) represents a significant and growing type of disability in South Africa. Coping with the impact of traumatic brain injury is one of the most difficult tasks that can confront a family, and family members experience a wide range of needs as the injured person progresses through rehabilitation. In South Africa, research on family needs following traumatic brain injury has thus far been neglected and rehabilitation resources are sadly lacking. For this reason it is necessary to accumulate knowledge about these families’ needs so as to assist with the planning of future rehabilitation programmes. The study aimed to explore and describe the needs of a sample of families with adult traumatic brain injury individuals in the Eastern Cape utilizing the Family Needs Questionnaire (FNQ). The research approach followed could be described as descriptive and exploratory in nature and was conducted within a quantitative framework. A biographical questionnaire and the FNQ were administered to a heterogeneous sample of 32 family members, including significant others and primary caregivers, of 16 adult traumatically brain-injured individuals, who sustained the TBI one to three years previously, and who underwent rehabilitation treatment at a private rehabilitation hospital in Port Elizabeth. A non-probability, purposive, and convenient sampling method was used. Descriptive statistics were computed to determine the importance and the perceived fulfillment of the needs. The results of the present study indicated that all 40 needs were endorsed by at least half the sample as being important to very important. Furthermore, 52.50% of the needs were endorsed by more than two-thirds of the sample as being important to very important. The needs were rank-ordered according to their importance ratings and the 10 mostly rated as important or very important were identified. These 10 needs were endorsed by between 84.38% and 93.75% of the family members as being important to very important. Six of the important or very important needs related to health information, two to professional support, one to community support, and one to emotional support. The relation between various participant, traumatically brain-injured individual and brain injury characteristics and the 10 important or very important needs, as well as the 10 needs more frequently rated as met were investigated and found to either have a limited or varied relationship. The 10 needs most often rated as met were endorsed by between 43.75% and 56.25% of the family members. Six of the met needs related to health information, two to community support, one to instrumental support, and one to treatment decisions. The highest unmet need was endorsed by 46.88% of the participants and related to the need to discuss their feelings with someone who has gone through the same experience. Based on the findings of the present study, further research on family needs following traumatic brain injury is suggested. It is also recommended that the Family Needs Questionnaire be used to evaluate existing rehabilitation programmes so as to make suggestions as to how to improve them. The results of this study suggested that family members would benefit from receiving educational information material, as well as referrals to professionals for advice and support.
577

Interaction fontionnelle entre le système de tolérance des lésions et le checkpoint des dommages à l'ADN : conséquences sur la stabilité du génome et l'oncogenèse / Functional interaction between the DNA damage tolerance pathway and the DNA damage checkpoint : implications for genome stability and oncogenesis

Kermi, Chames 14 December 2016 (has links)
Notre génome subit constamment les effets néfastes des agents endommageant de l'ADN. Afin de se protéger de ces effets délétères, les cellules disposent d’un système de détection des dommages à l’ADN (point de contrôle ou « checkpoint »). Certaines lésions peuvent persister quand les cellules entrent en phase S et inhiber ainsi la synthèse de l’ADN en interférant avec les ADN polymérases réplicatives. Ceci peut provoquer des arrêts prolongés des fourches de réplication ce qui fragilise l’ADN. Pour préserver l’intégrité de l’information génétique, les cellules ont développé une voie de tolérance qui implique des ADN polymérases spécialisées dans la réplication des lésions, appelées ADN Polymérases translésionnelles (Pols TLS). Dans ce processus, PCNA joue le rôle de facteur d’échafaudage pour de nombreuses protéines impliquées dans le métabolisme de l'ADN. Les mécanismes de régulation des échanges entre les différents partenaires de PCNA ne sont pas très bien compris. Parmi les protéines qui interagissent avec PCNA, CDT1, p21 ou encore PR-Set7/Set8 sont caractérisées par une forte affinité pour cette protéine. Ces dernières possèdent un motif d’interaction particulier avec PCNA, nommé « PIP degron », qui favorise leur protéolyse d'une manière dépendante de l’E3 ubiquitine ligase CRL4Cdt2. Après irradiation aux UV-C, le facteur d’initiation de la réplication CDT1 est rapidement détruit d’une manière dépendante de son PIP degron, Dans la première partie de mon travail, j’ai contribué à comprendre le rôle fonctionnel de cette dégradation. Les résultats obtenus ont fourni des évidences expérimentales qui montrent que l’inhibition de la dégradation de CDT1 par CRL4Cdt2 dans les cellules de mammifères compromet la relocalisation des TLS Pol eta et Pol kappaen foyers nucléaires induits par les irradiations UV-C. On a constaté que seules les protéines qui contiennent un PIP degron interfèrent avec la formation de foyers de Pol eta. La mutagenèse du PIP degron de CDT1 a révélé qu'un résidu de thréonine conservé parmi les PIP degrons est essentiel pour l'inhibition de la formation des foyers des TLS Polymérases. Les résultats obtenus suggèrent que l’élimination de protéines contenant des PIP degrons par la voie CRL4Cdt2 régule le recrutement de TLS Polymérases au niveau des sites des dommages induits par les UV-C.Dans un second temps, on s’est intéressé à l’étude du checkpoint des dommages à l’ADN au cours de l’embryogénèse. En effet, dans les embryons précoces, le checkpoint est silencieux jusqu'à la transition de mid-blastula (MBT), en raison de facteurs maternels limitants. Dans ce travail, nous avons montré, aussi bien in vitro qu’in vivo, que l’ubiquitine ligase de type E3 RAD18, un régulateur majeur de la translésion, est un facteur limitant pour l’activation du checkpoint dans les embryons de xénope. Nous avons montré que l'inactivation de la fonction de l’ubiquitine ligase RAD18 conduit à l'activation du checkpoint par un mécanisme qui implique l’arrêt des fourches de réplication en face des lésions produites par les UV-C. De plus, nous avons montré que l'abondance de RAD18 et de PCNA monoubiquitiné (PCNAmUb) est régulée au cours de l’embryogénèse. À l’approche de la MBT, l’abondance de l'ADN limite la disponibilité de RAD18, réduisant ainsi la quantité de PCNAmUb et induisant la dé-répression du checkpoint. En outre, nous avons montré que cette régulation embryonnaire peut être réactivée dans les cellules somatiques de mammifères par l'expression ectopique de RAD18, conférant une résistance aux agents qui causent des dommages à l'ADN. Enfin, nous avons trouvé que l'expression de RAD18 est élevée dans les cellules souches cancéreuses de glioblastome hautement résistantes aux dommages de l'ADN. En somme, ces données proposent RAD18 comme un facteur embryonnaire critique qui inhibe le point de contrôle des dommages de l’ADN et suggèrent que le dérèglement de l’expression de RAD18 peut avoir un potentiel oncogénique inattendu / Our genome is continuously exposed to DNA damaging agents. In order to preserve the integrity of their genome, cells have evolved a DNA damage signalling pathway known as checkpoint. Some lesions may persist when cells enter the S-phase and halt the progression of replicative DNA polymerases. This can cause prolonged replication forks stalling which threaten the stability of the genome. To preserve the integrity of genetic information, cells have developed a tolerance pathway which involves specialized DNA polymerases, called translesion DNA polymerases (TLS Pols). These polymerases have the unique ability to accommodate the damaged bases thanks to their catalytic site. In this process, PCNA acts as a scaffold for many proteins involved in DNA metabolism. The mechanisms governing the exchanges between different PCNA partners are not well understood. Among the proteins that interact with PCNA, CDT1, p21 and PR-Set7/set8 are characterized by a high binding affinity. These proteins have a particular interaction domain with PCNA, called "PIP degron", which promotes their proteasomal degradation via the E3 ubiquitin ligase CRL4Cdt2. After UV-C irradiation, the replication initiation factor CDT1 is rapidly degraded in a PIP degron-dependent manner. During the first part of my work, we wanted to understand the functional role of this degradation. Our results have shown that inhibition of CDT1 degradation by CRL4Cdt2 in mammalian cells, compromises the relocalisation of TLS Pol eta and Pol kappato nuclear foci after UV-C irradiation. We also found that only the proteins which contain a PIP degron interfere with the formation of Pol eta foci. Mutagenesis experiments on CDT1 PIP degron revealed that a threonine residue conserved among PIP degrons is essential for inhibiting foci formation of at least two TLS polymerases. This results suggest that CRL4Cdt2-dependent degradation of proteins containing PIP degrons regulates the recruitment of TLS polymerases at sites of UV-induced DNA damage.During the second part of my thesis, we studied DNA damage checkpoint regulation during embryogenesis. Indeed, in early embryos, the DNA damage checkpoint is silent until the mid-blastula transition (MBT) due to maternal inhibiting factors. In this work, we have shown, both in vitro and in vivo, that the E3 ubiquitin ligase RAD18, a major regulator of translesion DNA synthesis, is a limiting factor for the checkpoint activation in Xenopus embryos. We have also shown that RAD18 depletion leads to the activation of DNA damage checkpoints by inducing replication fork uncoupling in front of the lesions. Furthermore, we showed that the abundance of RAD18 and PCNA monoubiquitination (PCNAmUb) is regulated during embryonic development. Near the MBT, the increased abundance of DNA limits the availability of RAD18, thereby reducing the amount of PCNAmUb and inducing the de-repression of the checkpoint. Moreover, we have shown that this embryonic-like regulation can be reactivated in somatic mammalian cells by ectopic expression of RAD18, conferring resistance to DNA damaging. Finally, we found high RAD18 levels in glioblastoma cancer stem cells highly resistant to DNA damage. All together, these data propose RAD18 as a critical factor that inhibits DNA damage checkpoint in early embryos and suggests that dysregulation of RAD18 expression may have an unexpected oncogenic potential
578

Náhrada škody / Compensation for damage

Smolík, Libor January 2016 (has links)
Resumé This thesis deals with the question of compensation for damage in civil law. Its main task is to acquaint the reader with the basic institutions associated with the prescribed topic from the basic premises of the legislation through the explanation of the main terms to determine the prerequisites for a successful claim for damages and the rules determining the manner and extent of damages including some specific cases of damages. Work is also trying to compare the current, still not so long effective statutory regulation with the previous one. The thesis is divided into four main chapters. The first part discusses the basic concepts of liability for damages and the functions that it has in the legal system and even in society. It also describes the general concepts, such as the limitation period, prevention duties, general and specific, and also lists the entities to which the obligation to pay damages arise. The second chapter deals with the prerequisites for the establishing the liability in damages, which are traditionally a tort, the damage, causation and fault. It also presents the merits of general offenses. Especially acquaints readers with compensation that occurs accidentally. The third part deals with the way in which the damage is replaced and to what extent. Approximations are different...
579

Does the Pareto Distribution of Hurricane Damage Inherit its Fat Tail from a Zipf Distribution of Assets at Hazard?

Hernandez, Javiera I 02 July 2014 (has links)
Tropical Cyclones are a continuing threat to life and property. Willoughby (2012) found that a Pareto (power-law) cumulative distribution fitted to the most damaging 10% of US hurricane seasons fit their impacts well. Here, we find that damage follows a Pareto distribution because the assets at hazard follow a Zipf distribution, which can be thought of as a Pareto distribution with exponent 1. The Z-CAT model is an idealized hurricane catastrophe model that represents a coastline where populated places with Zipf- distributed assets are randomly scattered and damaged by virtual hurricanes with sizes and intensities generated through a Monte-Carlo process. Results produce realistic Pareto exponents. The ability of the Z-CAT model to simulate different climate scenarios allowed testing of sensitivities to Maximum Potential Intensity, landfall rates and building structure vulnerability. The Z-CAT model results demonstrate that a statistical significant difference in damage is found when only changes in the parameters create a doubling of damage.
580

[en] A CONTINUOUS DAMAGE MODEL FOR MATERIALS WITH ELASTIC-PLASTIC BEHAVIOR / [pt] UM MODELO DE DANO CONTÍNUO PARA MATERIAIS COM COMPORTAMENTO ELASTO-PLÁSTICO

FULVIO ENRICO GIACOMO CHIMISSO 08 March 2018 (has links)
[pt] A Mecânica do Dano Contínuo é uma ferramenta promissora para a análise de vida residual em componentes de máquinas e de estruturas. Todavia, não é uma tarefa simples a de se obter uma descrição fisica realística, associada a uma descrição matemática correta, do acoplamento entre a deformação e o amolecimento causado pela degradação da microestrutura. No caso de barras metálicas, a deformação plástica cíclica causa um endurecimento junto com uma degradação na estrutura (dano de fadiga). Por outro lado, a degradação da estrutura induz o amolecimento observado na curva tensão de engenharia vs. deformação. Logo, torna-se importante a modelagem do acoplamento entre plasticidade e dano para que se possa prever de maneira adequada o tempo de vida (ciclos), de um componente estrutural. Muitas tentativas feitas para descrever este tipo de comportamento mostraram-se insatisfatórias. O problema matemático é, em geral, mal posto e uma aproximação numérica da solução é incorreta do ponto de vista fisico. Nestes casos, o fenômeno de localização da deformação é malha-dependente. No presente trabalho, propõe-se uma nova teoria de dano para materiais elasto-plásticos que supera este problema. A teoria tem uma forte base termodinâmica e leva em conta o fenômeno de amolecimento. Uma diferença básica em relação a outros modelos consiste no fato de que a variável escalar D, associada ao dano, é considerada não apenas uma variável de estado mas também uma variável cinemática independente, com abordagem semelhante à apresentada nas teorias de contínuo com microestrutura. As possibilidades de utilização da teoria apresentada são verificadas através da comparação de simulações numéricas com resultados experimentais, para solicitações cíclicas uniaxiais, em barras de almnínioestrutural e em barras de aço austenitico AISI 316 L. / [en] Continuum Damage Mechanics is a promising tool for the failure prediction of structural components. Nevertheless, it is not a simple task to do a mathematically correct and physically realistic description of the strain-softcning behavior due to the degradation of the microstructure. In the case of metallic bars, the cyclic plastic deformation induces a strain-hardening and also a degradation of the structure (fatigue damage). In the other hand, the degradation of the structure induces a softening behavior in the engineering stress-strain curve. Hence, it is very important to model the coupling between plasticity and damage in order to perform an adequate lifetime prevision. Many attempts to describe this type of behavior have been unsatisfatory. The mathematical problem is, in general, ill posed and a numerical approximation of the solution is incorrect from the physical point of view. In this cases the phenomenon of strain localization due to strain-soflzening is mesh dependent. In the present work a new Damage theory for elasto-plastic materials that overcome this problem is proposed. The theory has a strong thermodynarnic basis and take into account the softening behavior. One basic difference from the others models is that the scalar variable D related with damage is taken as an independent kinematic variable, similarly as in the theories of continua with microstructure. The effectiveness and usefulness of the theory is checked by comparing numerical simulations of cyclic uniaxial tests in Aluminiun bars and 316L stainless steel bars with experimental results.

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