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Adams, Daniel Lewis. "Functional organisation of the monkey visual cortex for stereoscopic depth". Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268000.
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Thompson, Helen Louise. "Molecular architecture and functional group effects on segregation in polymers". Thesis, Durham University, 1998. http://etheses.dur.ac.uk/5000/.
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The properties of a polymer surface can be manipulated by the addition of a small quantity of surface active functionalised polymer to the bulk. On annealing above the glass transition these low surface energy functional groups attach to the air/polymer interface forming a brush like layer. To quantify this effect perdeuterated polystyrenes with fluoroalkane groups at specific locations in the polymer have been blended with unmodified polystyrene. Three key areas have been studied; effect of molecular architecture; effect of the molecular weight of the matrix polymer; and the rate of formation of the segregating layer. The complementary techniques of neutron reflectometry and nuclear reaction analysis have been used to determine the near surface depth profile of the deuterated polymer. Architectures studied were linear polystyrene with functional groups at both ends of the polymer chain, a 3-armed star with a functional core and linear polystyrene with functional groups evenly spaced along the chain. The architecture affected the shape of the composition profile but had little effect on the surface volume fraction and surface excess values obtained for the same bulk volume fraction. Self-consistent field theory simulations were carried out to determine the 'sticking energy' of the functional groups and good comparisons were obtained between the experimental volume fraction profiles and those predicted. Some segregation of functional polymer was observed during sample preparation and equilibrium segregation was obtained in less than one hour for 50000 M(_W) linear polymer up to eight hours for the 3-armed star after annealing under vacuum at 413K. For the difunctional polystyrene the functional groups did not have a significant affect on the rate of diffusion compared to non-functional polystyrene and diffusion coefficients obtained ranged from 6x10(^-16) to 9x10(^-15) cm(^2)s(^-1) The 3-armed star had the lowest diffusion coefficient value of 2xl0(^-16) cm(^-2)s(^-1) because of the inability for branched molecules to diffuse by reptation.
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Sood, Kanika. "Comparison of Functional Dependency Extraction Methods and an Application of Depth First Search". Thesis, University of Oregon, 2014. http://hdl.handle.net/1794/18413.
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Extracting functional dependencies from existing databases is a useful technique in relational theory, database design and data mining.
Functional dependencies are a key property of relational schema design. A functional dependency is a database constraint between two sets of attributes. In this study we present a comparative study over TANE, FUN, FD_Mine, FastFDs and Dep_Miner, and we propose a new technique, KlipFind, to extract dependencies from relations efficiently. KlipFind employs a depth-first, heuristic driven approach as a solution. Our study indicates that KlipFind is more space efficient than any of the existing solutions and highly efficient in finding keys for relations.
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Obrová, Klára [Verfasser] y Michael [Akademischer Betreuer] Lanzer. "In depth functional characterization of Plasmodium berghei ferlin-like protein / Klara Obrova ; Betreuer: Michael Lanzer". Heidelberg : Universitätsbibliothek Heidelberg, 2018. http://d-nb.info/1177044218/34.
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Risterucci, Paul. "Coupling of electron spectroscopies for high resolution elemental depth distribution profiles in complex architectures of functional materials". Thesis, Ecully, Ecole centrale de Lyon, 2015. http://www.theses.fr/2015ECDL0047/document.
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Ce travail de thèse est focalisé sur la détermination, de manière non-destructive, d'interfaces profondément enterrées dans des empilements multi-couches utilisés dans les conditions de technologie réelles au travers d'une méthode innovante basée sur la photoémission avec utilisation de rayons-x de haute énergie (HAXPES) et l'analyse du fond continu inélastique. Au cours de cette thèse, une procédure numérique a été développée pour quantifier la correspondance entre la mesure du fond continu faite par HAXPES et la simulation du fond continu représentative d'une distribution en profondeur donnée. Cette méthode permet de trouver la distribution en profondeur d'un élément grâce à une procédure semi automatisée. Dans un premier temps cette méthode a été testée en étudiant une couche ultra fine de lanthane enterrée à une profondeur >50 nm dans un dispositif de grille métallique high-k. L'influence des paramètres utilisés lors de l'analyse y est étudiée et révèle l'importance principale d'un paramètre en particulier, la section efficace de diffusion inélastique. La combinaison de mesures HAXPES avec l'analyse du fond continu inélastique utilisant cette nouvelle méthode permet d'augmenter la profondeur de sonde jusqu'à un niveau sans précédent. Ainsi l'échantillon peut être sondé jusqu'à 65 nm sous la surface avec une haute sensibilité à une couche nanométrique. Dans un second temps, la méthode précédemment validée d'analyse de fond continu inélastique est combinée avec une étude haute résolution des niveaux de cœur dans un échantillon servant de source dans un transistor à haute mobilité. Les deux analyses sont complémentaires puisqu'elles permettent d'obtenir la distribution en profondeur des éléments ainsi que leur environnement chimique. Le résultat donne une description complète des diffusions élémentaires dans l'échantillon suivant les différentes conditions de recuitThis thesis tackles the challenge of probing in a non-destructive way deeply buried interfaces in multilayer stacks used in technologically-relevant devices with an innovative photoemission method based on Hard X-ray PhotoElectron Spectroscopy (HAXPES) and inelastic background analysis. In this thesis, a numerical procedure has been implemented to quantify the matching between a HAXPES measured inelastic background and a simulated inelastic background that is representative of a given depth distribution of the chemical elements. The method allows retrieving depth distributions at large depths via a semi-automated procedure. First, this method has been tested by studying an ultra-thin layer of lanthanum buried at depth >50 nm in a high-k metal gate sample. The influence of the parameters involved in the analysis is studied unraveling the primary importance of the inelastic scattering cross section. The combination of HAXPES with inelastic background analysis using this novel method maximizes the probing depth to an unprecedented level, allowing to probe the sample up to 65 nm below the surface with a high sensitivity to a nm-thick layer. Second, the previously-checked inelastic background analysis is combined with that of high resolution core-level spectra in the case of the source part of a high electron mobility transistor. The two analyses are complementary as they allow retrieving the elemental depth distribution and the chemical state, respectively. The result gives a complete picture of the elemental intermixing within the sample when it is annealed at various temperatures
Denne afhandling omhandler problemet med at probe dybt begravede grænseflader i multilags stacks, som bruges i teknologisk relevante devices, med en innovativ fotoemissions metode, der er baseret på Hard X-ray PhotoElectron Spectroscopy (HAXPES) og analyse af den uelastiske baggrund. I afhandlingen er en numerisk procedure blevet implementeret til at kvantificere forskellen mellem en HAXPES målt uelastisk baggrund og en modelleret baggrund, som svarer til en given dybdefordeling af atomerne. Metoden muliggør, med en halv-automatisk procedure, at bestemme dybdefordelingen i store dybder. Metoden er først blevet testet ved at studere et ultra-tyndt lag af lanthan, som er begravet i en dybde > 50 nm i en high-k-metal-gate prøve. Indflydelsen af parametrene der ingår i analysen er blevet studeret for at opklare den primære betydning af det anvendte uelastiske spredningstværsnit. Kombinationen af HAXPES med analyse af den uelastiske baggrund og brug af den nye numeriske metode giver en hidtil uset probe-dybde, som giver mulighed for at probe den atomare sammens ætning i op til 65 nm dybde under overfladen og med høj følsomhed af et kun nm tykt lag. Dernæst er den uelastiske baggrundsanalyse blevet kombineret med højopløst core-level spektroskopi for at studere de aktive dele i en høj-elektronmobilitets transistor. De to analyser er komplementære, idet de henholdsvis bestemmer den atomare fordeling og atomernes kemiske bindingstilstand. Resultatet giver et fuldstændigt billede af atomernes omfordeling i prøven når denne opvarmes til forskellige temperaturer
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Staerman, Guillaume. "Functional anomaly detection and robust estimation". Electronic Thesis or Diss., Institut polytechnique de Paris, 2022. http://www.theses.fr/2022IPPAT021.
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L’engouement pour l’apprentissage automatique s’étend à presque tous les domaines comme l’énergie, la médecine ou la finance. L’omniprésence des capteurs met à disposition de plus en plus de données avec une granularité toujours plus fine. Une abondance de nouvelles applications telles que la surveillance d’infrastructures complexes comme les avions ou les réseaux d’énergie, ainsi que la disponibilité d’échantillons de données massives, potentiellement corrompues, ont mis la pression sur la communauté scientifique pour développer de nouvelles méthodes et algorithmes d’apprentissage automatique fiables. Le travail présenté dans cette thèse s’inscrit dans cette ligne de recherche et se concentre autour de deux axes : la détection non-supervisée d’anomalies fonctionnelles et l’apprentissage robuste, tant du point de vue pratique que théorique.La première partie de cette thèse est consacrée au développement d’algorithmes efficaces de détection d’anomalies dans le cadre fonctionnel. Plus précisément, nous introduisons Functional Isolation Forest (FIF), un algorithme basé sur le partitionnement aléatoire de l’espace fonctionnel de manière flexible afin d’isoler progressivement les fonctions les unes des autres. Nous proposons également une nouvelle notion de profondeur fonctionnelle basée sur l’aire de l’enveloppe convexe des courbes échantillonnées, capturant de manière naturelle les écarts graduels de centralité. Les problèmes d’estimation et de calcul sont abordés et diverses expériences numériques fournissent des preuves empiriques de la pertinence des approches proposées. Enfin, afin de fournir des recommandations pratiques, la performance des récentes techniques de détection d’anomalies fonctionnelles est évaluée sur deux ensembles de données réelles liés à la surveillance des hélicoptères en vol et à la spectrométrie des matériaux de construction.La deuxième partie est consacrée à la conception et à l’analyse de plusieurs approches statistiques, potentiellement robustes, mêlant la profondeur de données et les estimateurs robustes de la moyenne. La distance de Wasserstein est une métrique populaire résultant d’un coût de transport entre deux distributions de probabilité et permettant de mesurer la similitude de ces dernières. Bien que cette dernière ait montré des résultats prometteurs dans de nombreuses applications d’apprentissage automatique, elle souffre d’une grande sensibilité aux valeurs aberrantes. Nous étudions donc comment tirer partie des estimateurs de la médiane des moyennes (MoM) pour renforcer l’estimation de la distance de Wasserstein avec des garanties théoriques. Par la suite, nous introduisons une nouvelle fonction de profondeur statistique dénommée Affine-Invariante Integrated Rank-Weighted (AI-IRW). Au-delà de l’analyse théorique effectuée, des résultats numériques sont présentés, confirmant la pertinence de cette profondeur. Les sur-ensembles de niveau des profondeurs statistiques donnent lieu à une extension possible des fonctions quantiles aux espaces multivariés. Nous proposons une nouvelle mesure de similarité entre deux distributions de probabilité. Elle repose sur la moyenne de la distance de Hausdorff entre les régions quantiles, induites par les profondeur de données, de chaque distribution. Nous montrons qu’elle hérite des propriétés intéressantes des profondeurs de données telles que la robustesse ou l’interprétabilité. Tous les algorithmes développés dans cette thèse sont accessible en ligneEnthusiasm for Machine Learning is spreading to nearly all fields such as transportation, energy, medicine, banking or insurance as the ubiquity of sensors through IoT makes more and more data at disposal with an ever finer granularity. The abundance of new applications for monitoring of complex infrastructures (e.g. aircrafts, energy networks) together with the availability of massive data samples has put pressure on the scientific community to develop new reliable Machine-Learning methods and algorithms. The work presented in this thesis focuses around two axes: unsupervised functional anomaly detection and robust learning, both from practical and theoretical perspectives.The first part of this dissertation is dedicated to the development of efficient functional anomaly detection approaches. More precisely, we introduce Functional Isolation Forest (FIF), an algorithm based on randomly splitting the functional space in a flexible manner in order to progressively isolate specific function types. Also, we propose the novel notion of functional depth based on the area of the convex hull of sampled curves, capturing gradual departures from centrality, even beyond the envelope of the data, in a natural fashion. Estimation and computational issues are addressed and various numerical experiments provide empirical evidence of the relevance of the approaches proposed. In order to provide recommendation guidance for practitioners, the performance of recent functional anomaly detection techniques is evaluated using two real-world data sets related to the monitoring of helicopters in flight and to the spectrometry of construction materials.The second part describes the design and analysis of several robust statistical approaches relying on robust mean estimation and statistical data depth. The Wasserstein distance is a popular metric between probability distributions based on optimal transport. Although the latter has shown promising results in many Machine Learning applications, it suffers from a high sensitivity to outliers. To that end, we investigate how to leverage Medians-of-Means (MoM) estimators to robustify the estimation of Wasserstein distance with provable guarantees. Thereafter, a new statistical depth function, the Affine-Invariant Integrated Rank-Weighted (AI-IRW) depth is introduced. Beyond the theoretical analysis carried out, numerical results are presented, providing strong empirical confirmation of the relevance of the depth function proposed. The upper-level sets of statistical depths—the depth-trimmed regions—give rise to a definition of multivariate quantiles. We propose a new discrepancy measure between probability distributions that relies on the average of the Hausdorff distance between the depth-based quantile regions w.r.t. each distribution and demonstrate that it benefits from attractive properties of data depths such as robustness or interpretability. All algorithms developed in this thesis are open-sourced and available online
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Gühmann, Martin [Verfasser] y Gáspár [Akademischer Betreuer] Jékely. "A functional characterization of a Go‑opsin and a ratio-chromatic depth gauge in Platynereis dumerilii / Martin Gühmann ; Betreuer: Gáspár Jékely". Tübingen : Universitätsbibliothek Tübingen, 2017. http://d-nb.info/1167247051/34.
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Dima, Danai. "Investigation of neural correlates of bottom-up and top-down processing with functional magnetic resonance imaging and electroencephalogram. Exemplified by the binocular depth inversion-paradigm". Hannover Bibliothek der Tierärztlichen Hochschule Hannover, 2009. http://d-nb.info/1000116735/34.
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Baldy, Ngayo Christine. "Enabling Conditions for Organizational Change Production by Cross Functional Teams in Multinational Corporations : An In-Depth Multi Cases Study of the Marketing, Sales and Distribution Transformation in Pharmaceutical Multinational Companies". Phd thesis, HEC, 2011. http://pastel.archives-ouvertes.fr/pastel-00708802.
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In today's ever-changing, competitive business environment, cross-functional teams are an increasingly popular mechanism to implement major business transformations within multinationals. Yet empirical data (Kotter, 1995; Beer, Eisenstat and Spector, 1990; Beer, 2000; Stvetena and Damian, 2006) support for the prevailing view that such teams, unless they are well managed, lead to failure. By drawing on an in depth comparative study of one Pilot Team and four teams dedicated to marketing, sales and distribution transformation in two pharmaceutical companies, we examine under which internal conditions cross-functional teams dedicated to organizational change enable or hinder organizational change within multinational corporations. The findings suggest that they succeed best through high level coupling activities with the remainder of the organization during the early and the later phases of a project, when practicing shared leadership and when organized as a semi-structure. This study contributes to the literature on organizational change in transcending the paradoxical relationships between stability and change, to the literature on the practice-based approach in making more explicit the relationships between practices and organizations and provides implications for managers involved in major business transformations in multinational corporations.
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Dima, Danai [Verfasser]. "Investigation of neural correlates of bottom-up and top-down processing with functional magnetic resonance imaging and electroencephalogram : exemplified by the binocular depth inversion-paradigm / Danai Dima". Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2009. http://d-nb.info/1000116735/34.
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Nieto, Reyes Alicia. "Aplicaciones estadísticas de las proyecciones aleatorias". Doctoral thesis, Universidad de Cantabria, 2010. http://hdl.handle.net/10803/10700.
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Dado un conjunto de datos, o una distribución, en un espacio de dimensión mayor a uno, las proyecciones aleatorias consisten en proyectar los datos, o calcular la marginal de la distribución, en un subespacio de menor dimensión que ha sido elegido de forma aleatoria. En nuestro caso de dimensión uno. En esta tesis presentamos dos aplicaciones de las proyecciones aleatorias. La primera es una definición de profundidad, que es computacionalmente efectiva, aproxima a la conocida profundidad de Tukey y es válida tanto en espacios multidimensionales como funcionales. La segunda es un test de Gaussianidad para procesos estrictamente estacionarios, que rechaza procesos no Gaussianos con marginal unidimensional Gaussiana.A random projection consists in projecting a given data set, or in computing the marginal of a distribution, on a randomly chosen lower dimensional subspace. In our case, it is of dimension one.In this thesis, we present two applications of the random projections. The first one is a new definition of depth that is computationally effective, approximates the well-known Tukey depth and works as much in multidimensional spaces as in functional. The second is a test of Gaussianity for strictly stationary processes, which rejects non-Gaussian processes with Gaussian one-dimensional marginal.
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Armaut, Elisabeth. "Estimation d'ensembles de niveau d'une fonction de profondeur pour des données fonctionnelles. Applications au clustering et à la théorie du risque". Electronic Thesis or Diss., Université Côte d'Azur, 2024. http://www.theses.fr/2024COAZ5021.
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Les fonctions de profondeur statistiques jouent un rôle fondamental dans l'analyse et la caractérisation des structures de données complexes. Les profondeurs fournissent une mesure de centralité ou d'excentricité pour une observation individuelle ou pour l'ensemble des données, ce qui aide à comprendre leurs positions relatives et leurs distributions sous-jacentes. Les concepts relatifs à la profondeur, tels qu'ils sont présents dans la littérature, trouvent leur origine dans la notion de profondeur de Tukey, également désignée sous le nom de profondeur médiane. Cette notion a été introduite par le statisticien John W. Tukey dans son article intitulé "Mathematics and the Picturing of Data" publié en 1975 [170]. La principale idée sous-jacente à la profondeur de Tukey consiste à généraliser la médiane univariée d'un jeu de données unidimensionnel en dimension supérieure.Dans un premier temps, nous nous intéressons aux profondeurs multivariées suivies des profondeurs fonctionnelles, pour lesquelles nous construisons une revue générale dans le Chapitre 1.Dans la seconde partie de la thèse, i.e. dans le Chapitre 2, nous entreprenons une étude rigoureuse des ensembles de niveaux des fonctions de profondeur multivariées et établissons plusieurs propriétés analytiques et statistiques. Tout d'abord, nous montrons que lorsque la profondeur multivariée sous-jacente est suffisamment régulière, la différence symétrique entre l'ensemble de niveaux de profondeur estimé et son équivalent théorique converge vers zéro en termes de volume d-dimensionel et de probabilité sous la distribution considérée. Outre ces contributions, la nouveauté du Chapitre 2, dans le cadre de la théorie du risque, réside dans l'introduction d'une mesure de risque basée sur une profondeur appelée Covariate-Conditional-Tail-Expectation (CCTE). Globalement, la CCTE vise à calculer un coût moyen sachant qu'au moins un des facteurs de risque en jeu est 'élevé' suivant une certaine direction. Cette dernière zone de risque est modélisée par un ensemble de niveau de faible profondeur. Contrairement à des mesures de risques fondées sur les queues de distribution, notre définition de CCTE est indépendante de toute direction grâce à l'implication des ensembles de niveaux d'une profondeur. Nous démontrons également que, lorsque la taille de l'échantillon tend vers l'infini, la CCTE basée sur la profondeur empirique est consistante par rapport à sa version théorique. Et nous fournissons les taux de convergence pour la CCTE, pour des niveaux de risque fixes ainsi que lorsque le niveau de risque tend vers zéro quand la taille de l'échantillon tend vers l'infini. Dans ce dernier cas d'étude, nous analysons de même le comportement de la définition originelle de CCTE basée sur une fonction de répartition, cas qui n'a pas été étudié dans [56]. En plus des simulations effectuées sur la CCTE, nous illustrons son utilité sur des données environnementales.La dernière partie de cette thèse, le Chapitre 3, conclut notre travail et consiste à définir une profondeur fonctionnelle générale pour des données fonctionnelles basée sur l'analyse en composantes principales fonctionnelles. Cela implique l'utilisation d'une profondeur multivariée générique. Dans cette optique, nous utilisons la décomposition bien connue de Karhunen-Loève comme outil pour pro- jeter un processus aléatoire centré et de carré intégrable le long d'une combinaison linéaire finie de fonctions orthogonales appelées composantes principales. À notre connaissance, il s'agit d'une approche novatrice dans le cadre des profondeurs fonctionnelles. Naturellement, nous proposons un estimateur de notre profondeur fonctionnelle pour lequel nous démontrons une consistance uniforme. Nous complétons enfin notre étude avec des simulations et des applications sur données réelles dans des problèmes de classifications, où notre nouvelle profondeur se révèle être au moins aussi performante que la plupart des concurrents classiquesStatistical depth functions play a fundamental role in analyzing and characterizing complex data structures. Depth functions provide a measure of centrality or outlyingness for individual observations or entire datasets, aiding in the understanding of their relative positions and underlying distributions. The concepts related to depth, as found in the literature, originate from the notion of Tukey's depth, also known as the median depth. This concept was introduced by the statistician John W. Tukey in his article titled "Mathematics and the Picturing of Data," published in 1975 [170]. The fundamental idea underlying Tukey's depth is to generalize the univariate median of a one-dimensional dataset in higher dimension. First, our interest focuses on multivariate depths followed by functional depths, both of which we build an overall review within Chapter 1. In the second part of this thesis, i.e. in Chapter 2, we undertake a rigorous study of multivariate depth-level sets and establish several analytical and statistical properties. First, we show that, when the underlying multivariate depth is smooth enough, then the symmetric difference between the estimated depth-level set and its theoretical counterpart converges to zero in terms of the d-dimensional volume and of the probability under the unknown distribution. Apart from these contributions, the novelty of Chapter 2 is the introduction and study of a depth-based risk measure called the Covariate-Conditional- Tail-Expectation (CCTE), within a risk theory setup. Roughly, the CCTE aims at computing an average cost knowing that at least one of the risk factors at hand is 'high' in some direction. The latter risk area is modelled by a level-set of low depth value. In contrast to risk measures based on distribution tails, our definition of CCTE is direction-free, owing to the involvement of depth level sets. We establish that, as the sample size goes to infinity the empirical depth-based CCTE is consistent for its theoretical version. We demonstrate consistency and provide rates of convergence for the depth- CCTE, for fixed levels of risk as well as when the risk level goes to zero as the sample size goes to infinity. In this last case of study, we also analyze the behavior of the original CCTE definition based on a distribution function, a case that was not studied in [56]. On top of several simulations performed on the CCTE, we illustrate its usefulness on environmental data.The final part of this thesis, Chapter 3, wraps up our work in which we contribute to defining a new type of depth for functional data based on functional principal component analysis. This includes using a generic multivariate depth. In this view, we use the well known Karhunen-Loève decomposition as a tool to project a centered square-integrable random process along some finite linear combination of orthogonal functions called the principal components. To the best of our knowledge, this is a novel approach in the functional depth literature. In this extent, we involve a multivariate depth function for the vector of the projected principal components. Naturally, we provide an estimator of our functional depth for which we demonstrate uniform consistency with a rate of convergence. We complement our study with several simulations and real data applications to functional classification, where our new depth equals or outperforms most of conventional competitors
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Lok, Wing-sze. "Statistical depth functions and depth-based robustness diagnosis". Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B34838260.
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Lok, Wing-sze y 駱穎思. "Statistical depth functions and depth-based robustness diagnosis". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B34838260.
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Junior, Reinaldo Squillante. "Controle relacionado à segurança nas indústrias de processos: uma abordagem integrada de modelos de acidentes, defesa em profundidade e diagnosticabilidade segura". Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/3/3152/tde-10082017-110852/.
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A questão da segurança funcional das indústrias de processos vem recebendo uma atenção crescente pela comunidade científica mundial, uma vez que se observa a possibilidade de ocorrências de acidentes e as consequências indesejadas que estes acidentes têm provocado. Essas indústrias podem ser consideradas como parte de uma classe de sistemas denominados Sistemas Críticos, que são caracterizados pela possibilidade de ocorrência de falhas críticas, que resultam em acidentes com perdas de vidas humanas, danos ao meio ambiente e perdas financeiras envolvendo custos significativos de equipamentos e propriedades. Estes fatos justificam a necessidade de uma nova abordagem no que se refere ao design de processos, design de controle de processos, análise e controle de riscos e avaliação de riscos. Um dos desafios pertinentes à segurança funcional está associado a como vincular os cenários de acidentes aos requisitos para projetos de sistemas de controle relacionados à segurança das indústrias de processos de forma sistemática. Por sua vez, a possibilidade de ocorrência de eventos críticos e/ou eventos indesejados não observados ou ocultos, como fatores relevantes associados à evolução da sequência de eventos que culmina na ocorrência de um acidente. Neste contexto, o desafio está em aprimorar a eficácia destes sistemas de controle, que envolve o desenvolvimento de uma solução capaz de supervisionar o processo de evolução de falhas críticas, a fim de se garantir um nível de segurança funcional adequado e que esteja em conformidade com as normas internacionais aplicáveis IEC 61508 e IEC 61511. Portanto, estas considerações trazem novos requisitos para o projeto de sistemas de controle desta natureza, capaz de englobar modelos de acidentes e processos de evolução de falhas críticas. Uma solução é a consideração das abordagens de prevenção e mitigação de falhas críticas de forma integrada e interativa. Além disso é necessário abordar novas técnicas e conceitos para que se possa desenvolver um sistema de controle capaz de rastrear e atuar nos processos de evolução de falhas desta natureza. Uma possibilidade consiste em considerar o princípio de defesa em profundidade aliado à propriedade de diagnosticabilidade segura. O atendimento a este novo conjunto de requisitos não é trivial e se faz necessário integrar diferentes formalismos para o desenvolvimento de soluções adequadas. Portanto, este trabalho apresenta uma metodologia para o projeto de um sistema de controle baseado no conceito de segurança funcional para indústrias de processos, e que propõe: (i) uma arquitetura de controle para prevenção e mitigação de falhas críticas, (ii) extensão da classificação de barreiras de segurança focando na automação via sistemas instrumentados de segurança (SIS) (iii) framework para a síntese de sistemas de controle relacionados à segurança baseado em modelos de acidentes e que contempla os seguintes métodos: (a) elaboração do HAZOP, (b) construção de modelos de acidentes, (c) integração dos modelos de acidentes com o HAZOP e (d) geração dos algoritmos de defesa para a prevenção e mitigação de falhas críticas, a partir de técnicas de modelagem usando extensões da rede de Petri: Production Flow Schema (PFS) e Mark Flow Graph (MFG). A metodologia proposta foi verificada, a partir de exemplos de aplicação investigados na literatura.The issue of the functional safety of process industries has been receiving increasing attention from the world scientific community, since it has stated the possibility of occurrences of the accidents and the related undesired consequences. These industries can be considered as part of a system class called critical systems, which are characterized by the occurrence of critical faults, which can result in accidents involving loss of life, damage to the environment, and financial losses involving equipment and property. These facts justify the need for a new approach that addresses: process design, process control design, risk analysis and control, and risk assessment. One of the challenges related to functional safety is associated with how to integrate accident scenarios to the requirements for the design of safety-related control systems of the process industries in a systematic way. Furthermore, there is the possibility of the occurrence of the unobserved or hidden undesired and / or critical events, as relevant factors associated to the evolution of the sequence of the events that corroborates in the occurrence of an accident. In this context, the challenge is to improve the effectiveness of these control systems, which involves the development of a solution capable of supervising the process of evolution of the critical and / or undesired events, in order to guarantee an adequate level of functional safety, and that complies with the applicable international standards IEC 61508 and IEC 61511. Therefore, these considerations bring new requirements for the design of control systems of this nature, capable of encompassing the accident models and the critical fault evolution processes. One solution is to consider critical fault prevention and mitigation approaches in an integrated and interactive way. In addition, it is necessary to addresses new techniques and concepts in order to develop a control system capable of tracking and acting in the evolution processes of faults of this nature. One possibility is to consider the principle of defense-in-depth coupled with the property of safe diagnosability. The fulfillment of this new set of requirements is not trivial and it is necessary to integrate different formalisms for the development of adequate solutions. Therefore, this work presents a methodology for the design of a safety-related control systems based on the concept of functional safety for the process industries, which proposes: (i) a control architecture for the prevention and mitigation of the critical faults, (ii) an extension of the classification of the safety barriers focusing on automation via safety instrumented system (SIS), (iii) a framework for the synthesis of the safety-related control systems based on accident models and which includes the following methods: (a) elaboration of the HAZOP study, (b) construction of the accident models, (c) integration of the accident models with the HAZOP study, and (d) generation of the defense algorithms for the prevention and mitigation of the critical faults, via modeling techniques using extensions of the Petri net: Production Flow Schema (PFS) and Mark Flow Graph (MFG). The proposed methodology was verified, from application examples investigated in the literature.
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Francisci, Giacomo. "Local depth functions and applications to clustering". Doctoral thesis, Università degli studi di Trento, 2022. https://hdl.handle.net/11572/329413.
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Local depth functions (LDFs) are used for describing the local geometric features and mode(s) in multidimensional distributions. In this thesis, we undertake a rigorous systematic study of LDFs and establish several analytical and statistical properties. First, we show that, when the underlying probability distribution is absolutely continuous, scaled versions of LDFs (referred to as τ-approximation) converge, uniformly and in L^q, to the density, when τ converges to zero. Second, we establish that, as the sample size diverges to infinity the centered and scaled sample LDFs converge in distribution to a centered Gaussian process uniformly in the space of bounded functions on H_G, a class of functions yielding LDFs. Third, using the sample version of the τ-approximation and the gradient system analysis, we develop a new clustering algorithm. The validity of this algorithm requires several results concerning the uniform finite difference approximation of the gradient system associated with the sample τ-approximation. For this reason, we establish a Bernstein-type inequality for deviations between the centered and scaled sample LDFs. Finally, invoking the above results, we establish consistency of the clustering algorithm. Applications of the proposed methods to mode estimation and upper level set estimation are also provided.
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Soleimani, Vahid. "Remote depth-based photoplethysmography in pulmonary function testing". Thesis, University of Bristol, 2018. http://hdl.handle.net/1983/f6a6f7b6-943f-43f7-b684-1612161aee1a.
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This thesis introduces several novel, noninvasive lung function assessment approaches in which we incorporate computer vision techniques to remotely compute standard clinical Pulmonary Function Testing (PFT) measures. Using a single depth sensor, a dynamic 3-D model of a subject's chest is reconstructed and used to generate chest volume-time data by estimating the chest volume variation throughout a sequence. Following computation of multiple keypoints and calibration of volume-time data to present real volume of exchanged air, 7 Forced Vital Capacity (FVC) measures and 4 Slow Vital Capacity (SVC) measures are computed. Evaluation on a dataset of 85 patients (529 sequences), attending a respiratory outpatient service for spirometry, shows a high correlation between the proposed depth-based PFT measures and the measures from a spirometer. Trunk motion during PFT affects the accuracy of these results, so the natural reaction of the subject's body to maximal inhalation and exhalation, must be decoupled from the chest-surface breathing motion. We present an automatic, open source data acquisition and calibration pipeline in which two opposing depth sensors are calibrated and used to reconstruct a well-defined dynamic 3-D model of the trunk during PFT performance. Our proposed method is able to reconstruct dynamic 3-D models with accurate temporal frame synchronisation and spatial registration. Then, we propose a whole body depth-based photoplethysmography (dPPG) approach which allows subjects to perform PFT, as in routine spirometry, without restraining their natural trunk reactions. By decoupling the trunk movement and the chest-surface respiratory motion, dPPG obtains more accurate respiratory volume-time data which improves the accuracy of the estimated PFT measures. A dataset spanning 35 subjects (298 sequences) was collected and used to illustrate the superiority of the proposed dPPG method by comparing its measures to those provided by a spirometer and the single Kinect approach. Although dPPG is able to improve the PFT measures accuracy to a significant extent, it is not able to filter complex trunk motions, particularly at the deep forced inhalation-exhalation stage. To effectively correct trunk motion artifacts further, we propose an active trunk shape modelling approach by which the respiratory volume-time data is computed by performing principal component analysis on temporal 3-D geometrical features, extracted from the chest and posterior shape models in R3 space. We validate the method's accuracy at the signal level by computing several comparative metrics between the depth-based and spirometer volume-time data. Evaluating on the dPPG PFT dataset (300 PFT sequences), our trunk shape modelling approach outperforms the single Kinect and dPPG methods.
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Wei, Bei. "Nonparametric statistical methods based on depth function and bootstrap". Click to view the E-thesis via HKUTO, 2010. http://sunzi.lib.hku.hk/hkuto/record/B4414197X.
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Wei, Bei y 魏孛. "Nonparametric statistical methods based on depth function and bootstrap". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B4414197X.
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Lui, Jackey. "A new design for low-depth compression functions from length preserving public random functions". Zurich : ETH, Swiss Federal Institute of Technology, Department of Computer Science, Institute of Theoretical Computer Science, 2009. http://e-collection.ethbib.ethz.ch/show?type=dipl&nr=429.
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Miller, John Gabriel. "The Death and Resurrection of Function". The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1217299779.
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Claxton, Christopher David. "Colour depth-from-defocus incorporating experimental point spread function measurements". Thesis, University of Warwick, 2007. http://wrap.warwick.ac.uk/4461/.
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Depth-From-Defocus (DFD) is a monocular computer vision technique for creating depth maps from two images taken on the same optical axis with different intrinsic camera parameters. A pre-processing stage for optimally converting colour images to monochrome using a linear combination of the colour planes has been shown to improve the accuracy of the depth map. It was found that the first component formed using Principal Component Analysis (PCA) and a technique to maximise the signal-to-noise ratio (SNR) performed better than using an equal weighting of the colour planes with an additive noise model. When the noise is non-isotropic the Mean Square Error (MSE) of the depth map by maximising the SNR was improved by 7.8 times compared to an equal weighting and 1.9 compared to PCA. The fractal dimension (FD) of a monochrome image gives a measure of its roughness and an algorithm was devised to maximise its FD through colour mixing. The formulation using a fractional Brownian motion (mm) model reduced the SNR and thus produced depth maps that were less accurate than using PCA or an equal weighting. An active DFD algorithm to reduce the image overlap problem has been developed, called Localisation through Colour Mixing (LCM), that uses a projected colour pattern. Simulation results showed that LCM produces a MSE 9.4 times lower than equal weighting and 2.2 times lower than PCA. The Point Spread Function (PSF) of a camera system models how a point source of light is imaged. For depth maps to be accurately created using DFD a high-precision PSF must be known. Improvements to a sub-sampled, knife-edge based technique are presented that account for non-uniform illumination of the light box and this reduced the MSE by 25%. The Generalised Gaussian is presented as a model of the PSF and shown to be up to 16 times better than the conventional models of the Gaussian and pillbox.
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Maalouf, Elie. "Contribution to fluorescence microscopy, 3D thick samples deconvolution and depth-variant PSF". Phd thesis, Université de Haute Alsace - Mulhouse, 2010. http://tel.archives-ouvertes.fr/tel-00594247.
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The 3-D fluorescence microscope has become the method of choice in biological sciences for living cells study. However, the data acquired with conventional3-D fluorescence microscopy are not quantitatively significant because of distortions induced by the optical acquisition process. Reliable measurements need the correction of theses distortions. Knowing the instrument impulse response, also known as the PSF, one can consider the backward process of convolution induced by the microscope, known as "deconvolution". However, when the system response is not invariant in the observation field, the classical algorithms can introduce large errors in the results. In this thesis we propose a new approach, which can be easily adapted to any classical deconvolution algorithm, direct or iterative, for bypassing the non-invariance PSF problem, without any modification to the later. Based on the hypothesis that the minimal error in a restored image using non-invariance assumption is located near the used PSF position, the EMMA (Evolutive Merging Masks Algorithm) blends multiple deconvolutions in the invariance assumption using a specific merging mask set. In order to obtain sufficient number of measured PSF at various depths for a better restoration using EMMA (or any other depth-variant deconvolution algorithm) we propose a 3D PSF interpolation algorithm based on the image moments theory using Zernike polynomials as decomposition base. The known PSF are decomposed into Zernike moments set and each moment's variation is fitted into a polynomial function, the resulting functions are then used to interpolate the needed PSF's Zernike moments set to reconstruct the interpolated PSF.
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Yang, Mengta. "Depth Functions, Multidimensional Medians and Tests of Uniformity on Proximity Graphs". Thesis, The George Washington University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3615104.
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We represent the d-dimensional random vectors as vertices of a complete weighted graph and propose depth functions that are applicable to distributions in d-dimensional spaces and data on graphs. We explore the proximity graphs, examine their connection to existing depth functions, define a family of depth functions on the β-skeleton graph, suggest four types of depth functions on the minimal spanning tree (MST) and define depth functions including path depth, path depth of path length at most δ, all paths probability depth, eccentricity depth, peeling depth and RUNT depth. We study their properties, including affine invariance, maximality at the center, monotonicity and vanishing at infinity. We show that the β-skeleton depth is a family of statistical depth functions and define the sample β-skeleton depth function. We show that it has desirable asymptotic properties, including uniform consistency and asymptotic normality. We consider the corresponding multidimensional medians, investigate their robustness, computational complexity, compare them in a simulation study to find the multivariate medians under different distributions and sample sizes and explore the asymptotic properties of β-skeleton median. We generalize the univariate Greenwood statistic and Hegazy-Green statistic using depth induced order statistics and propose two new test statistics based on normal copula and interpoint distances for testing multivariate uniformity. We generalize the path depth under two-sample setting and propose a new multivariate equality of DF test. We study their empirical power against several copula and multivariate Beta alternatives. The topic is complemented with a discussion on the distribution and moments of the interpoint distances (ID) between bivariate uniform random vectors and the IDs between FGM copula random vectors.
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Li, Suk-yee. "Functional changes and differential cell death of retinal ganglion cells after injury". View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B37552612.
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Li, Suk-yee y 李淑儀. "Functional changes and differential cell death of retinal ganglion cells after injury". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38597731.
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Dieken, Ellen Sue. "Functional characterization of glucocorticoid receptor sequences required for steroid-induced cell death". Diss., The University of Arizona, 1991. http://hdl.handle.net/10150/185651.
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Glucocorticoid induction of cell death (apoptosis) in mouse lymphoma S49 cells has long been studied as a molecular genetic model of steroid hormone action. The research described in this dissertation focuses on understanding the transcriptional control of apoptosis in two steroid resistant ntⁱ S49 mutant cell lines (S49.55r and S49.143r). These studies extend earlier biochemical analysis of the mutant ntⁱ glucocorticoid receptor (ntⁱ GR) to the molecular level by isolating and characterizing GR cDNA from the two ntⁱ S49 cell lines, S49.55r and S49.143r, and the wild type (wt) parental line, S49.A2. This analysis revealed that ntⁱ GR transcripts encode intact steroid and DNA binding domains but lack 404 amino-terminal (N-terminal) residues as a result of aberrant RNA splicing between exons 1 and 3. Results from transient co-transfection experiments into CV1 cells using ntⁱ receptor expression plasmids and a glucocorticoid responsive reporter gene demonstrate that the truncated ntⁱ receptor is capable of inducing transcription to only 10% the level of wt GR. Gene fusions containing portions of both the wt and ntⁱ GR coding sequences were constructed and used to functionally map the ntⁱ receptor mutation. It was found that the loss of the N-terminal domain alone is sufficient to cause the observed defect in ntⁱ transcriptional transactivation. In addition, a complementation assay utilizing stable transfection of wt and mutant GR cDNA constructs into a GR-deficient cell line (7r) was developed. By measuring steroid-sensitivity of various 7r derivatives, it was determined that GR is rate-limiting for S49 apoptosis and moreover, that the GR N-terminus is absolutely required for complementation in this system. These data also indicate that at physiological levels of receptor, the GR N-terminus plays a crucial role in controlling lymphocyte apoptosis, even though this portion of the receptor seems to be dispensable for low-level induction of mouse mammary tumor virus (MMTV) transcription. The smallest functionally defined transactivation region in the GR N-terminus has a net negative charge and has been named enh2, tau1 or acidic activation domain (AAD). Results from experiments designed to test whether similar activating sequences from the herpes simplex virus-1 (HSV-1) VP16 protein can substitute for the GR N-terminus demonstrate that 7r cells expressing VP-GR fusions are indeed steroid-sensitive, suggesting that S49 apoptosis requires transcriptional induction of specific genes.
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Ibrahim, MohD, Omer sheikh, Pratyksha Sankhyan, Qaryoute Ayah Al, Abdulrahman Ibrahim, Akilesh Mahajan, Nilesh Mahajan, Mohsen Pourmoteza y Jason Mckinney. "Terbinafine induced fulminant hepatic failure and patient death". Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/108.
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A 72 year-old-patient without known past medical history presented to the hospital with worsening cough, dyspnea on exertion, decreased appetite, weight loss for two months. Prior to admission, he was treated with a 10- day course of levofloxacin and prednisone as a case of bronchitis with minimal improvement. Then he started to develop red urine with marked changes in mental status. On physical examination, the patient had notifiable scleral icterus, confusion and abdominal tenderness in the right upper quadrant. On admission his labs were significant for alkaline phosphatase 541, aspartate transaminase 557, alanine transaminase 94, total bilirubin 8.6, lactate 11.7. CT scan of abdomen showed hepatosplenomegaly, mild ascites and trace bilateral pleural effusion. Work up with Viral hepatitis serology, cryptococcal antigen, histoplasma antigen, respiratory virus panel, Epstein Barr virus tests were negative. Anti-nuclear antibodies (ANA) and anti-mitochondrial antibody were also negative. Blood level of amylase, lipase, acetaminophen and alcohol were negative at admission too. The patient was started initially on broad spectrum antibiotics, N-acetyl cysteine empirically and aggressive intravenous fluid hydration. Patient condition rapidly worsened and he developed profound shock requiring mechanical ventilation and started on stress dose steroid and pressor support. Upon further investigation, patient was noted to take terbinafine for toe onychomycosis (day 112). Ferritin level was elevated to 1596 with 93% iron saturation. Ceruloplasmin level was normal. Patient was not a transplant candidate due to multiple organ failure. As per family request, patient was palliatively extubated and died.
Terbinafine is a fungicidal drug with activity against dermatophytes including Epidermophyton flccosum and trichophyton rubrum. It works by inhibition of squalene epoxidase with a resultant accumulation of squalene in the fungal cell and killing it as a result. Commonly used orally to treat onychomycosis and other fingernails and toenails infections. Shortly after its introduction to the market, DILI had been reported with elevation with serum aminotransferases elevation that was usually self-limited. Usually presents within first 6 weeks of therapy with either hepatocellular or cholestatic initially with sings of hypersensitivity. Mechanism of injury entails hypersensitivity reaction, though the full pathogenesis was not elucidated yet, but genetic polymorphism is implicated in the variable presentation especially among HLA-A 33:01 allele carriers. Terbinafine DILI resolves usually within 6 months of stopping the medication but can lead to death or need liver transplantation in some cases.
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Aryal, Puruswottam. "Optical and Photovoltaic Properties of Copper Indium-Gallium Diselenide Materials and Solar Cells". University of Toledo / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404679981.
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Kurland, Brenda F. "Analysis of binary longitudinal data with dropout and death /". Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/9593.
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Farndon, Lisa Jane. "The function and purpose of core podiatry : an in-depth analysis of practice". Thesis, Sheffield Hallam University, 2006. http://shura.shu.ac.uk/20198/.
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The function and purpose of podiatry and podiatrists in the UK were investigated with specific regard to the core role whilst considering current health policy and sociopolitical issues influencing the profession. A survey of 9.6% working members of The Society of Chiropodists and Podiatrists from both the private, commercial and public sectors, identified the constituents of current practice in the UK. Traditional podiatry was still being carried out over 50% of the time despite developments in education and training. Although the term traditional podiatry is in current use to describe long-established tasks associated with care, respondents disagreed about its role, which suggest that it is poorly conceptualised and understood. Consequently, the term core podiatry was adopted. Some NHS departments are reducing the provision of core podiatry care which is linked to cost improvement initiatives, as there is little evidence of its effectiveness. Patients were interviewed to determine the value of core podiatry to them and it was found to sustain foot health whilst offering some emotional support and reassurance. Utilising data provided by practitioners and patients and reappraising the literature using concept analysis, a new definition and model of core podiatry was produced. This was then assimilated into The Chronic Care Model to propose a new strategy for the design and delivery of core podiatry services within the NHS.The findings confirm that core podiatry preserves individuals' foot health and the mobility of elderly patients in particular. Withdrawal of services is therefore a false economy. This new definition offers a consolidated view of practice and denotes areas that require further advancement or reorganisation. Developing the role of assistant practitioners to carry out some of the core work is proposed, whilst increasing treatments that can offer a cure. There is also an urgent need to introduce foot health promotion strategies at both national and local levels with the aim of preventing foot problems, thus contributing to the longer-term picture of improving and sustaining foot health.
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Wildsmith, G. C. "Structural and functional investigation of the cytoplasmic domain of the Fas death receptor". Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1462353/.
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Activation of the transmembrane death receptor Fas (CD95/APO-1) by a membrane bound ligand (FasL/CD95L) activates the extrinsic pathway of apoptosis. Intracellular Fas death domains (DDs) are induced to oligomerise enabling binding to the adaptor protein FADD, thereby leading to the recruitment of procaspase 8 and other proteins to form the death inducing signalling complex (DISC).This thesis describes an investigation of the structure and function of the cytoplasmic Fas-DD. A model for the solution structure of the Fas-DD was published in 1996, it has since been reported that the death domain can form at least one other conformation when in complex with FADD. As a foundation to the work in this thesis, modern multidimensional NMR techniques have been used to solve the structure of the FasDD, to further probe the potential for alternative conformations. It has previously been reported that Fas can be phosphorylated at Tyr291, providing a platform for the recruitment of binding partners that can affect non-apoptotic signalling. The second part of this thesis details the development of an expressed protein ligation methodology to prepare a Tyr291 phosphorylated Fas DD to provide a basis for in vitro studies of the structural, dynamic and functional effects of phosphorylation. It is widely accepted that Fas is palmitoylated at Cys199 and recognised by the membrane cytoskeletal protein, ezrin. Fas palmitoylation is important for clathrinmediated internalisation of the DISC, and amplification of the caspase cascade. There are multiple reports detailing the binding of ezrin to Fas, but it is not clear whether this interaction occurs in a palmitoylation-dependent manner. Efforts to characterise an interaction between bacterially expressed intracellular Fas and ezrin proteins were carried out using a number of biophysical assays, described in the third part of this thesis. Building upon this, the fourth section explores the preparation of a palmitoylated Fas construct suitable for biophysical analysis by incubating recombinant Fas with palmitoyl-CoA.
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Burling, John William. "The function of culturally-created symbolic systems in the reduction of death anxiety". Diss., The University of Arizona, 1988. http://hdl.handle.net/10150/184349.
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Several studies have attempted to assess the effects of death anxiety upon personality and behavior. However, only recently has research on this topic begun to develop a larger theoretical context within which many behaviors and intrapsychic mechanisms can be explained. The present study was conducted to test the hypothesis that people's symbolic investments, such as religious beliefs and status, are inflated when an individual is faced with events which make their personal mortality salient. Theoretically this inflation would help them buffer their anxieties about death. Subjects were selected for participation on the basis of scores on measures of status concern and religiosity, and were assigned to a mortality salience treatment or control condition. Results suggest limited support for the hypothesis. Though all predictions were not confirmed, some intriguing findings are noted. Implications of these findings are discussed.
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Rose, Debra Schafer 1958. "Use of Fourier analysis and discriminant function analysis of electroencephalogram to determine anesthetic depth". Thesis, The University of Arizona, 1987. http://hdl.handle.net/10150/276613.
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This study uses statistical techniques to determine anesthetic depths of three females undergoing total abdominal hysterectomies. Spectral analysis of the electronencephalogram is employed to define changes in brain wave activity under different levels of anesthesia after administration of diazepam and isoflurane. The multivariate statistical technique of discriminant function analysis is used to determine which frequencies, or linear combinations of frequencies, yield the most information for classification of the electronencephalogram samples into one of the three anesthetic depths (mild sedation, moderate anesthesia, and anesthetic sleep). Spectral analysis of the electronencephalogram showed similar results for all three patients after administration of diazepam (mild sedation), but widely varying results among patients during anesthesia using isoflurane. The combination of spectral analysis and discriminant function analysis showed reliable discrimination among the three anesthetic depths. The ability to discriminate was significantly improved when only two anesthetic depths were used.
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Gozzelino, Raffaella. "Implication of TNF superfamily receptors and their functional antagonists in neuronal apoptotic cell death". Doctoral thesis, Universitat de Lleida, 2007. http://hdl.handle.net/10803/8087.
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L'apoptosi pot ser induïda a través de nombrosos estímuls, entre els quals hi ha elsreceptors de mort. Per induir apoptosi TNFα necessita la participació d'inhibidors de la
transcripció d'ARN o de la síntesi proteica, com són ActD i CHX. En aquest estudi
demostrem com la citotoxicitat de TNFα en cèl·lules PC12 i en neurones corticals
sensibilitzades amb ActD es dóna a través de l'activació de la caspasa iniciadora 8, de
la generació de tBid i de la conseqüent activació de les pro-caspases-9 i -3. A més, el
tractament amb TNFα/ActD no indueix diferències detectables en l'expressió de
proteïnes involucrades en el complex de senyalització de TNFα. L'anàlisi de les
principals proteïnes antiapoptòtiques, com són FLIP, IAPs i els membres de la família
de Bcl-2, demostra que Bcl-xL endogen és capaç de regular l'apoptosi induïda per
TNFα, sense afectar l'activació de la via del factor de transcripció NF-κB. La
sobreexpressió de Bcl-xL dóna resistència a la mort promoguda per TNFα i ActD, i la
reducció dels seus nivells indueix mort cel·lular per mitjà de TNFα, a través de
l'activació de JNK. Per confirmar la rellevància de Bcl-xL en el senyal promogut per
TNFα, es va avaluar l'efecte de la reducció dels nivells basals de proteïnes
antiapoptòtiques com Bcl-2, Bcl-xL, Bcl-w i Mcl-1, en el model cel·lular HeLa, on
aquestes s'hi troben expressades de forma fisiològica, contràriament al que passa en
les cèl·lules PC12, demostrant que Bcl-xL és la proteïna antiapoptòtica més rellevant
en la protecció de la mort induïda per TNFα.
Per altra banda, l'apoptosi induïda per TNFα pot ser deguda a l'acumulació d'elevats
nivells de hemo lliure. El grup hemo sensibilitza les cèl·lules Hepa a l'acció citotòxica
de TNFα a través de la inducció d'estrès oxidatiu, que provoca un dany cel·lular que
porta a l'activació de la via de JNK y de pro-caspasa-3. La producció de ROS i el dany
induït per estrès oxidatiu, així com la mort induïda per TNFα, conjuntament amb
elevats nivells del grup hemo lliure, poden inhibir-se amb l'expressió de proteïnes
protectores com HO-1 y H-Ferritina.
La apoptosis puede ser inducida a través de numerosos estímulos, entre los cuales los
receptores de muerte. Para promover la apoptosis, TNFα necesita la colaboración de
inhibidores de la trascripción del RNA o de la síntesis proteica, como ActD y CHX. En
este estudio demostramos como la citotoxicidad de TNFα en células PC12 y en
neuronas corticales sensibilizadas con ActD ocurre a través de la activación de la
caspasa iniciadora 8, la generación de tBid y la activación de las pro-caspasas-9 y -3.
Además no se detectan diferencias de expresión, inducidas por TNFα/ActD, de
proteínas involucradas en la formación del complejo de señalización de TNFα. El
análisis de las principales proteínas antiapoptóticas, como FLIP, IAPs y miembros de
la familia de Bcl-2, demuestra que Bcl-xL es la molécula endógena capaz de regular la
apoptosis promovida por TNFα, sin afectar la activación de la vía del factor de
trascripción NF-κB. La sobre-expresión de Bcl-xL confiere resistencia a la muerte
apoptótica mediada por TNFα y ActD, y su disminución forzada es capaz de inducir
muerte celular únicamente tratando con TNFα por activación de JNK. Para confirmar la
relevancia de Bcl-xL en la señal promovida por TNFα, la represión de proteínas antiapoptóticas
como Bcl-2, Bcl-xL, Bcl-w y Mcl-1 ha sido evaluada en el modelo de células
HeLa, donde estas se expresan fisiológicamente al contrario que en las células PC12,
demostrando que Bcl-xL es la proteína anti-apoptótica más importante en la protección
de la muerte inducida por TNFα.
Por otra parte, la apoptosis mediada por TNFα puede ser promovida por la
acumulación de elevados niveles del grupo hemo libre. El grupo hemo sensibiliza las
células Hepa a la acción citotóxica de la citoquina TNFα a través de la inducción de
estrés oxidativo, cuyo daño resulta en la activación de la vía de JNK y de pro-caspasa-
3. La producción de ROS y el daño inducido por estrés oxidativo, así como la muerte
inducida por elevados niveles del grupo hemo libre y de TNFα, pueden inhibirse por la
sobre-expresión de proteínas protectoras como HO-1 y H-Ferritina.
Apoptotic cell death is triggered by several different stimuli, among which death
receptors. To induce apoptosis, TNFα needs the cooperation of RNA transcription or
protein synthesis inhibitor, i.e. ActD and CHX. In this study we demonstrate that ActD
renders rat PC12 cells and primary mouse cortical neurons susceptible to the cytotoxic
effect of TNFα by the activation of the initiator caspase 8, generation of tBid and
activation of pro-caspase-9 and -3. Proteins involved in TNFα receptor signaling
complex are not affected by TNFα/ActD stimulation. However, the analysis of antiapoptotic
proteins, e.g. FLIP, IAPs and Bcl-2 family members, demonstrates that Bcl-xL
is the endogenous regulator of neuronal sensitivity to TNFα-induced apoptosis and that
it operates in a NF-κB-independent manner. Bcl-xL overexpression completely protects
against TNFα/ActD-induced apoptosis, whereas its endogenous decrease sensitizes to
TNFα cytotoxic effect promoting JNK-dependent cell death. To point out the relevance
of Bcl-xL in TNFα signaling pathway, endogenous decrease of the main anti-apoptotic
Bcl-2 family members, e.g. Bcl-2, Bcl-xL, Bcl-w and Mcl-1, was performed in HeLa cell
line in which, contrarily to PC12, these proteins are expressed. The results obtained
demonstrate that Bcl-xL is the most important Bcl-2-cytoprotective protein in regulating
TNFα cytotoxicity.
Moreover, TNFα-induced cell death is promoted by high levels of free heme
accumulation. Heme sensitizes Hepa cell line to TNFα-triggered apoptosis enhancing
ROS production and ROS-mediated damage. This results in JNK and pro-caspase-3
activation. Oxidative stress-promoted apoptosis induced by heme/TNFα treatment is
inhibited by the overexpression of HO-1 and H-Ferritin cytoprotective proteins.
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Thomas, Anne L. "Structural and functional characteristics of novel mRNA isoforms of the death-promoting gene bax". Thesis, University of Nottingham, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285747.
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Peng, Yong. "In-depth accident investigation of pedestrian impact dynamics and development of head injury risk functions". Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAD024.
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Les piétons comptent parmi les usagers de la route les plus vulnérables dans la mesure où ils ne bénéficient d'aucune protection en cas d'impact avec un véhicule automobile. Plus de 1,17 millions de personnes sont tués sur la route de part le monde dont environ 65% ce piétons. Les blessures de la tête, souvent fatales, concernent environ 30 % des blessures enregistrées. Ces blessures conduisent à des incapacités de longue durée avec un coût sociétal et économique immense. Il est par conséquent essentiel de comprendre aussi bien les mécanismes d'accidents que les mécanismes de blessure de la tête afin d'intervenir sur la conception de la face avant des véhicules automobile. Dans ce contexte l'objet de la présente thèse est d'analyser la répons dynamique du piton en cas d'accident et ce contribuer au développement de critères de blessure de la tête. Dans le but d'étudier l'influence de la position du piéton, de la géométrie de la face avant du véhicule et de sa vitesse initiale sur la cinématique du piéton et les conditions d'impact de la tête, une simulation multi-corps a été mise en place. Les résultats de ces simulations donnent la vitesse et l'angle d'impact de la tête et la position de l'impact sur le véhicule. Cette analyse paramètrique a été conduite sur cinq types de véhicules et pour un modèle humain adulte et enfant de 6 ans et a permis de consolider les connaissances sur la conditions d'impact de la tête en comparaison avec les tests normatifs en vigueur.[...]Pedestrians are regarded as an extremely vulnerable and high-risk group of road users since they are unprotected in vehicle impacts. More than 1.17 million people throughout the world are killed in road traffic accidents each year. Where, about 65% of deaths involve pedestrians. The head injuries in vehicle-pedestrian collisions accounted for about 30% of all reported injuries on different body regions, which often resulted in a fatal consequence. Such injuries can result in disabilities and long-term sequence, which lead to significant social costs. It is therefore important to study the characteristics of pedestrian accidents and understand the head injury mechanism of the pedestrian so as to improve vehicle design for pedestrian protection. The aim of this study is to investigate pedestrian dynamic response and develop head injury risk functions.In order to investigate the effect of pedestrian gait, vehicle front geometry and impact velocity on the dynamic responses of the head, the multi-body dynamic (MBD) models were used to simulate the head responses in vehicle to pedestrian collisions with different vehicle types in terms of head impact point measured with Wrap Around Distance (WAD), head relative velocity and impact angle. A simulation matrix is established using five vehicle types, and two mathematical models of the pedestrians represented a 50th male adult and a 6 year old child as well as seven pedestrian gaits based on typical postures in pedestrian accidents. In order to simulate a large range of impact conditions, four vehicle velocities (30 km/h, 40 km/h, 50 km/h and 60 km/h) are considered for each pedestrian position and vehicle type.A total of 43 passenger car versus pedestrian accidents were selected from In-depth Investigation of Vehicle Accidents in Changsha, China (IVAC) and German In-Depth Accident Study (GIDAS) database for simulation study. According to real-world accident investigation, accident reconstructions were conducted using multi-body system (MBS) pedestrian and car models under MADYMO simulation environment to calculate head impact conditions, in terms of head impact velocity, head position and head orientation. In order to study kinematics of adult pedestrian, relationship curves: head impact time, throw distance, head impact velocity and vehicle impact velocity, were computed and logistic regression models: head impact velocity, resultant angular velocity, HIC value, head contact force and head injuries, were developed based on the results from accident reconstructions.The automobile windshield, with which pedestrians come into frequent contact, has been identified as one of the main contact sources for pedestrian head injuries. In order to investigate the mechanical behavior of windshield laminated glass in the caseof pedestrian head impact, windshield FE models were set up using different combination for the modeling of glass and PVB, with various connection types and two mesh sizes (5 mm and 10 mm). Each windshield model was impacted with a standard adult headform impactor in an LS-DYNA simulation environment, and the results were compared with the experimental data reported in the literatures.In order to assess head injury risks of adult pedestrians, accident reconstructions were carried out by using Hybrid III head model based on the real-world pedestrian accidents. The impact conditions were obtained from the MBS simulation, including head impact velocity, head position and head orientation. They were used to set the initial conditions in a simulation of a Hybrid III FE head model striking a windshield FE model. Logistic regression models, Skull Fracture Correlate (SFC), head linear acceleration, Head Impact Power (HIP), HIC value, resultant angular acceleration and head injuries, were developed to study brain injury risk.{...]
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Xue, Peipei. "Soil Microbial Diversity: Relating Microbial Distributions to Soil Functions". Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/28830.
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Soil microbial biodiversity is an essential component of the natural ecosystem. Soil microbes work as decomposers contributing to soil nutrient cycling, primary production, and climate regulation. The heterogeneous edaphic properties lead to the diversity of microbial community structuring and functioning. This thesis investigates microbial community distributions and functions through vertical soil profiles, at the landscape level, and along regional transects. Vertically, soil microbial communities were depicted in soil profiles to a depth of 1 m using the concept of genosoils (soil formed and still under natural vegetation) and phenosoils (the same type of soil that has undergone cultivation). Bacteria community distribution in soil profiles differed by soil types but altered by soil forms. At the local scale, factors of land use and soil types on the microbial communities were evaluated in three soil depth layers through a survey across the Hunter Valley area in NSW, Australia. Topsoil microbial communities were generally regulated by land use, while the subsoil microbial communities were shaped by soil type. Additionally, microbial interactions reveal that soil protists regulate the bacterial and fungal diversity. At the regional scale, microbial functions were investigated across two ~1000 km transects which traversed significant temperature and/or rainfall gradients in NSW. Temperature and rainfall were important drivers of soil microbial functional groups. Paired (genosoils and phenosoils) samples showed that agriculture practices led to a significant shift in microbial functional groups related to particulate organic carbon (POC) degradation. Collectively, this thesis studied the factors of depth, soil type, land use, and environment for the underground microbial community, and demonstrated the significant role of soil biodiversity in the soil ecosystem, especially for soil carbon cycling.
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Le, Vasseur Maxence. "The role of Pannexin 2 in mitochondrial functions and cell death". Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/58297.
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Pannexins constitute a small family of membrane channels homologous to the invertebrate gap junction proteins. Three distinct isoforms, called Panx1, Panx2, and Panx3, are expressed alongside connexins in chordates. Unlike connexins, pannexins do not connect the cytoplasm of adjacent cells but function as unitary channels regulating the exchange of ions and small molecules between the cytoplasm and extracellular milieu. The biochemical properties and functions of Panx1 and Panx3 channels have been investigated, but our understanding on Panx2 channels has progressed at a much slower pace. The first objective of this thesis was to comprehensively map the expression and distribution of Panx2 protein in mammalian tissues. Prior to this work, Panx2 distribution had been studied exclusively by analyzing the expression of its transcript which was found to be largely restricted to the central nervous system (CNS). In this thesis, Panx2 mRNA and protein levels were analyzed in different tissues and Panx2 transcriptional activity was found to poorly predict Panx2 protein abundance. Panx2 protein levels were lower in nervous tissues although transcriptional analysis showed disproportionately high Panx2 mRNA levels in the CNS. Furthermore, endogenous Panx2 channels were found to be sequestered within the endomembrane system of the cell. The second objective focused on characterizing the subcellular localization and biological function of Panx2 channels. Using subcellular fractionation, it was determined that Panx2 co-fractionates with mitochondrial and endoplasmic reticulum (ER) markers thereby suggesting that Panx2-containing compartments can associate, at least transiently, with the ER and mitochondria. The analysis of Panx2 dynamics in living cells combined with immunogold electron microscopy confirmed that Panx2 is not randomly distributed within the cytoplasm but preferentially localizes at membrane contact sites called mitochondria-associated membranes (MAMs) which physically and functionally tether the ER to mitochondria. Finally, the biological function of Panx2 was partially elucidated by showing that Panx2 expression is modulated by the energetic requirements of the cell and can regulate apoptosis.Medicine, Faculty of
Graduate
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Kalynych, Sergei. "Exploring the non-death function of caspase activity during cardiac hypertrophy". Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28061.
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Various pathological conditions that exert stress on cardiac muscle severely compromise the supply of oxygenated blood to peripheral tissues. To maintain steady cardiac output during adverse times, the myocardium is forced to undergo tissue remodeling in a process known as cardiac hypertrophy. The loss of cardiac myocytes during the transition to heart failure has been a subject of intense investigation, and this loss is hypothesized to originate from apoptosis/programmed cell death. In particular, caspase proteases have been implicated as primary components in this process. However, caspase activity has been linked to many cellular remodeling events independent of inducing cell death. Therefore, the possibility that alterations in caspase activity precipitate the cellular alterations that give rise to pathological cardiac hypertrophy was investigated in the current study:
Using cultures of primary neonatal cardiomyocytes and a combination of pharmacological and biological inhibitors it is demonstrated that: (a) Physical growth of a myocyte is not dependant on activity of the apoptotic caspases; (b) Caspase activity is not necessary for the transcriptional control of natriuretic peptide production (ANF and BNP); (c) Transcriptional activity of a general stress-responsive transcription factor Nf-kB is dependent on caspase enzymatic activity in the neonatal cardiomyocyte.
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Wong, Mei Mei. "Effects of Cell Death and Phagocytosis on Mesenchymal Stem Cell Function". Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511852.
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Kaszian, Jonas Verfasser], Kathrin [Gutachter] [Bringmann y Sander [Gutachter] Zwegers. "Indefinite Theta Functions and Higher Depth Mock Modular Forms / Jonas Kaszian ; Gutachter: Kathrin Bringmann, Sander Zwegers". Köln : Universitäts- und Stadtbibliothek Köln, 2019. http://d-nb.info/1196788545/34.
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Daish, Tasman James. "An analysis of DRONC function and its regulation of expression during Drosophila development". Title page, table of contents and abstract only, 2004. http://hdl.handle.net/2440/37707.
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Correct development of multicellular organisms requires the programmed removal of supernumerary, redundant, or damaged cells, a process achieved by apoptosis. Apoptosis, or Programmed Cell Death (PCD) is executed by caspases, a highly conserved family of cysteine proteases. The removal of redundant larval tissues during metamorphosis is controlled by the steroid hormone ecdysone. Ecdysone signalling is mediated by the nuclear receptor heterodimer EcR/Usp, which in turn transcriptionally activates a host of transcription factors which then go on to regulate genes essential for PCD, like caspases. The apical caspase dronc is upregulated in the larval midgut and salivary glands prior to their destruction and is dependent on the BRC and E93 transcription factors. To further understand the role of dronc in development, a dronc mutant fly was generated and a transgenic promoter-reporter strategy was employed to investigate dronc regulation. Larval organs from dronc mutants lack dying cells and, when irradiated, fail to show a radiation-induced PCD response. The midguts from dronc mutants undergo apoptosis and have high caspase activity. These data indicate that a droncindependent caspase activation pathway is active in the midgut. Salivary glands from dronc mutants failed to be removed and have reduced caspase activity. Consequently it is clear that the role of DRONC differs significantly between the midgut and salivary glands. The employment of a transgenic dronc promoter-LacZ reporter system identified promoter regions essential for the correct temporal and spatial expression of dronc. A region of the dronc promoter between 1.1kb and 2.8kb has elements essential for LacZ expression in salivary glands. This region was also dependent on the BR-C and E93 transcription factors for salivary gland expression. A functional ecdysone receptor binding element (EcRBE) was identified in the dronc proximal promoter. The EcR-B1 isoform directly binds this EcRBE and is necessary for correct dronc expression in the larval salivary glands. This work revealed some novel findings regarding the role of DRONC in development and the availability of a specific dronc mutant now makes it possible to explore some of the recently published non- poptotic roles of dronc. This work aids in understanding how nuclear hormones control transcription and shows dronc to be an ideal model gene to explore these molecular and genetic processes.Thesis (Ph.D.)--Department of Medicine, 2004.
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Mindel, Beth L. "Variation in the structure and function of deep-sea fish assemblages with depth and over time". Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/13277/.
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The deep sea is the largest environment on Earth, but has remained relatively under-studied due to its inaccessibility. In recent years however, technological advances have increased our understanding of this globally important system. In this thesis, I add to this understanding by examining fish assemblage structure along the environmental gradient of the continental slope at depths of 300–2000 m and over a time period (1998–2014) following a reduction in fishing pressure from previous levels. I show that body size is an important factor in structuring deep-sea assemblages along a depth gradient and that it increases at least up to 1500 m. A new metric, fractional size, builds on our knowledge of size structure by accounting for both intra- and interspecific variation in body size and also increases with depth. The Large Fish Indicator, the slope of the biomass spectrum and fractional size have increased over time, signifying recovery of the size structure of deep-sea assemblages, but this increase is depth-dependent. I reveal other depth-related changes by linking morphological traits that relate to function, such as caudal fin aspect ratio and gape size, to the shifting dominance of feeding guilds and patterns in functional diversity. I show that despite the uniqueness of deep-sea ecosystems, the general macroecological pattern of increasing regional occupancy with increasing local abundance still applies. I incorporate the all-pervading importance of depth into these abundance–occupancy relationships by calculating occupancy based on depth distribution as well as spatial distribution. This thesis reveals some surprising characteristics of deep-sea assemblages, such as high biodiversity and the ability to recover from fishing pressure. It further highlights the importance of body size in the marine environment and of depth resolution in deep-sea ecology.
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Baker, Max Owen David Gus. "Tug-of-war: Characterising functional amyloid assemblies that trigger or terminate programmed cell death during viral infection". Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/28074.
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Functional amyloid is an increasingly recognised type of protein assembly that can serve diverse physiological purposes. Functional amyloid is distinct from disease associated amyloid, which plays important aetiological roles in a number of irreversible and degenerative human and animal pathologies. Functional amyloid is a high molecular weight β-sheet rich protein assembly characterised by fibrillar architecture, insolubility, resistance to protease degradation and high stability. An important functional amyloid complex employed by mammals is the necrosome, which is a multi-component higher-order signalling assembly that drives the programmed cell death pathway necroptosis. Necroptosis is a crucial part of the innate immune system and is directly implicated in defense against important human pathogens. Necroptosis is mediated by protein:protein interaction sequences called RHIMs (RIP Homotypic Interaction Motifs). Due to its importance in curtailing infection, necrosome components are targeted for inhibition by pathogens using a suite of immune-evasive strategies. This thesis describes the analysis of RHIM-containing necrosome components associated with cell death signalling and virus RHIM-driven mechanisms to subvert necrosome function. The work in this thesis is divided into three major sections.
In the first section, analysis of the RHIM of TRIF, an innate immune adaptor protein that responds to ligation of Toll like receptors during pathogenic infection, was performed. It is known that when activated, TRIF associates with the kinases RIPK1 and RIPK3 through RHIM-based interactions. The interactions between TRIF and these two proteins can lead to activation of downstream cell death effectors that drive necroptosis. The work in this portion of the thesis describes elucidation of the biophysical characteristics of higher-order assemblies formed by the RHIM from TRIF. TRIF is shown to spontaneously self-assemble into amyloid assemblies with unique morphology dependent on the presence of the RHIM. The residues that comprise the insoluble amyloid core of TRIF were determined by protease digestion and mass spectrometry. Single molecule confocal coincidence spectroscopy was used to demonstrate direct interactions between TRIF and RIPK3 and/or RIPK1. The size and stability of these hetero-assemblies were investigated.
In the second section, a novel mechanism of inhibition of amyloid-driven cell death is described for Varicella Zoster virus, a medically important pathogenic herpesvirus. Herpesviruses can encode proteins that contain RHIM sequences. These virus RHIM sequences mediate protein:protein interactions with human RHIM-containing proteins, leading to human:virus protein hetero-assemblies that render the human proteins unable to signal for programmed cell death, which would otherwise destroy infected cells. A novel virus RHIM is described that is present in the Varicella Zoster virus protein ORF20. The RHIM from ORF20 is shown to be crucial for its infectivity. It is demonstrated that the RHIM from ORF20 is amyloidogenic, like other human and virus RHIMs. ORF20 can interact with the human cell death-associated proteins ZBP1, a nucleic acid sensor that directly responds to cytoplasmic viral ligands, and RIPK3. Interactions between ORF20 and ZBP1 result in the formation of hetero-assemblies that are larger and more stable and have morphology distinct from ZBP1 homo assemblies. These alterations in ZBP1 assembly properties are proposed to underlie the subversion of ZBP1 signalling that occurs during VZV infection.
In the third section, efforts are described to use fluorescent microscopy to detect amyloid necrosomes in cell culture. Despite the growing understanding of functional amyloid in many aspects of biology, there has been limited visualisation of functional amyloid within cells by common microscopy techniques. In particular, no fluorescent microscopy of endogenous RHIM-containing proteins in their amyloid state has been reported. In this project, iterative attempts to image both the identity and amyloid structure of the RIPK1 in the necrosome were performed. These experiments were performed with amyloid staining dyes including Thioflavin T and Thioflavin S, novel amyloid-specific antibodies OC and A11, and protein-specific antibodies for the necroptosis-associated proteins RIPK1 and MLKL. Ultimately, A11 was identified as a potentially useful probe for the detection of endogenous amyloid necrosomes.
Overall, the work in this thesis describes multiple aspects of functional amyloid associated with programmed cell death. Structural characterisation of cell death complexes is described in both physiological and pathological settings which are fundamental for understanding the molecular nature of innate immune signalling.
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Wu, Ling. "Functional Characterization of SCN5A, The Cardiac Sodium Channel Gene Associated With Cardiac Arrhythmias and Sudden Death". Cleveland State University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=csu1206732295.
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Brophy, Victoria Alice. "Investigation of 26S proteasome function in apoptosis and nuclear localisation signal". Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368214.
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Major, Jennifer Lynn. "E2F6: A Unique Regulator of Post-natal Cardiac Growth, Death, and Function". Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36014.
Texto completoResumen
Rationale/Background: The adult mammalian heart has a very limited potential for regeneration due to cardiomyocyte cell cycle withdrawal which occurs shortly after birth. One potential avenue to repair the heart following stress/injury is to reprogram pre-existing cardiomyocytes to re-enter the cell cycle. The E2F family is a group of transcription factors which ubiquitously regulate the cell cycle, but it has previously been difficult to fully appreciate their role in the post-natal myocardium due to either redundancy or embryonic lethality of genetic models. Thus we generated a dominant negative model of the E2F/Rb pathway via expression of the unique transcriptional repressor E2F6 in postnatal myocardium. E2F6 transgenic (Tg) mice developed dose dependent Dilated Cardiomyopathy (DCM) and sudden death without hypertrophy or apoptosis. This was accompanied by the partial loss of E2F3 (critical for cardiac development) and connexin-43 important for metabolic and electrical coupling.
Methods/Results: In this thesis E2F6-Tg mice were examined for markers of cardiac differentiation/ function and exposed to stressors to evaluate the capacity for the E2F pathway to regulate cardiomyocyte growth (isoproterenol) and death (doxorubicin and cobalt chloride). E2F6-Tg mice were twice as sensitive to isoproterenol as their Wt counterparts due to the observed activation of a β2-adrenergic survival pathway. Cardiac hypertrophy in E2F6-Tg mice was accompanied by the rescue of E2F3 expression. Treatment of neonatal cardiomyocytes isolated from Wt and E2F6-Tg pups with cobalt chloride revealed a protective effect for E2F6 against apoptosis. Doxorubicin exposure led to the loss of E2F6 protein and abolished its protective effect. Examination of neonatal hearts and cardiomyocytes isolated from them demonstrated a shift in the cell cycle and metabolic profiles of E2F6-Tg myocardium. Tg cardiomyocytes show decreased glycolysis and a dramatic increase in the regulator of ketolysis, β-hydroxybutyrate dehydrogenase (BDH1), prior to DCM. The substrate of BDH1 (β-hydroxybutyrate) was demonstrated to influence the levels of CX-43 in cardiomyocytes. E2F6 also deregulated expression of T-cap which has been linked to human DCM.
Conclusions: I provide evidence that the E2F pathway can regulate growth, death, and differentiation through a variety of mechanisms which link the cell cycle and metabolism to growth and survival to critically govern post-natal cardiac function. Furthermore, I reveal a new biomarker (BDH1) for early DCM which may be useful in diagnosis/ treatment of idiopathic cases of disease.
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Ebrahimian, Venus. ""Characterization of Red Diamondback Rattlesnake Venom Proteins on Cell Death and Function"". Wright State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=wright1389638004.
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Wong, Grace Kai Wai. "Identification of Cdk5RAP1 as a potential regulator of mitochondrial functions and cell death /". View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?BICH%202007%20WONG.
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