A variety of genes that influence aging have been identified in a broad selection of organisms including Saccharomyces cerevisiae (yeast), Caenorhabditis elegans (worms), Drosophila (fruit flies), Macaca Mulatta (rhesus monkeys), and even Homo sapiens. Many of these genes, such the TOR’s, FOXO’s, AKT’s, and S6K’s are conserved across different organisms. All of these genes participate in nutrient sensing networks. Other conserved genetic networks may similarly affect lifespan. In this thesis, I explored genes from an iron metabolism family and a heat shock protein (HSP) gene family that have been identified, but not confirmed, to influence lifespan. Yeast is a reliable model for mitotic (replicative) aging. Using yeast, I tested whether the FET-genes, encoding a family of iron importer-related genes, are required for mitotic lifespan. I also tested whether another family of genes, the yeast SSA HSP70- encoding genes, related to mammalian HSP70s, influence mitotic aging. I primarily used the replicative lifespan (RLS) assay, in which I measured the mitotic capacity of multiple FET and SSA yeast mutants. I hypothesize that aging occurs when iron transport is misregulated, which may lead to an over-reliance on HSPs for lifespan maintenance. The results presented in this thesis support the hypothesis. First, FET3 was primarily involved in lifespan maintenance under normal conditions (2% glucose), while FET5 was primarily involved in the cellular lifespan extension characteristic of caloric restriction (0.01% glucose), a known anti-aging intervention. In addition, SSA2 appeared to facilitate lifespan maintenance in the absence of FET4, while the presence of SSA1 limited lifespan length. That the aging genes identified in this study are involved in iron metabolism or heat stress suggests that protein aggregation or reactive oxidative species production are common processes through which these genes interact.

A produção de fundidos com baixo nível de defeitos e com propriedades mecânicas adequadas é facilmente alcançada com a previsão do comportamento do metal durante a solidificação. A transferência de calor entre o metal-líquido e o molde, nos primeiros instantes de contato, compromete definitivamente as propriedades mecânicas e a qualidade do produto final. O comportamento da transferência de calor entre o metal e o molde foi explorado através da análise térmica experimental e confrontado com o Modelo de Schwarz Modificado (MSM). Para comprovar experimentalmente os fenômenos previstos no MSM tais como: superesfriamento aparente, posição das interfaces líquido-superaquecido/líquido- superesfriado e da sólido/líquido durante a solidificação foram realizados experimentos com alumínio puro, gálio puro e estanho. Para a análise térmica foram utilizados dois sistemas de solidificação vertical descendente (Griffiths et al., 1993; Jinho et al., 1996; Jamgotchian et al., 1987). O sistema A e o sistema B, sendo que o sistema B também permitia a solidificação vertical ascendente. Em ambos os casos, o fluxo de calor foi direcionado através de uma barra de alumínio (na temperatura ambiente) que foi inserida verticalmente no banho (técnica do “dedo frio”). A barra extrai calor do líquido em função da diferença de temperatura entre a massa líquida e a massa sólida e simula o choque térmico do metal líquido com as paredes de um molde. Os resultados experimentais e os obtidos pela simulação foram confrontados. Apresenta-se a relação experimental entre o superesfriamento e a taxa de solidificação. Discute-se o redimensionamento da Ti (temperatura de interface) na solução de Schwarz e a comprovação experimental da solução do MSM. / The production of casting with low level of defects and adjusted mechanical properties can be obtained with the previous knowledge of the metal solidification behavior. The transference of heat between the metal-liquid and the mold, in the first instants of the contact, compromises definitively the mechanical properties and the final product quality. The behavior of the transference of heat between the metal and the mold was carried out through the experimental thermal analysis and the results were compared with the Modified Schwarz Model (MSM). To experimentally prove, the cooled phenomena in the MSM such as: apparent supercooling, liquid superheated/liquid supercooled interfaces position and of the liquid/solid during the solidification experiments had been carried out with pure aluminum, pure gallium and tins. Two systems A and B, one of descending vertical solidification and another one of descending and ascending solidification, had been used for the thermal analysis. In both systems, the heat flow was directed through a bar of aluminum (in the ambient temperature) that was inserted vertically in the bath (“cold finger” technique). The bar extracts heat of the liquid, had the difference of temperature between the liquid mass and the solid mass, and simulates the thermal shock of the metal with the mold walls. The experimental results were compared with simulated data. In this work are presented experimental relation between the supercooling and the rate of solidification. The new dimension of the Ti (temperature of interface) in the Schwarz equation and the experimental evidence of MSM solution, are considered.

Diante do cenário de crise econômica vivenciado no Brasil nos últimos anos, a preocupação em minimizar os seus efeitos na vida financeira da população tornou-se fundamental. Assim, evidenciar fatores que possam ter contribuído para um maior nível de impacto pelo choque é importante para que se formule campanhas de conscientização financeira, visando maior bem estar da população. Com base nisso, este trabalho testa, através de uma regressão logística ordinal, a influência do comportamento do indivíduo no nível de impacto por choques econômicos. Para isso foram utilizados 366 questionários aplicados na região da Grande Porto Alegre. Foram, assim, analisadas e comparadas as principais características de quatro categorias de impacto: não afetados pelo choque financeiro, afetados de forma fraca, moderada e forte. Os principais resultados apontaram diferenças de comportamento significativas entre as pessoas menos afetadas e aquelas mais impactadas no que se refere a lócus de controle e comportamento financeiro, confirmando que as variáveis testadas podem ajudar a explicar o nível de impacto. / Given the economic crisis scenario that Brazil has been facing in recent years, the concern to minimize its effects in the financial life of the population has increased greatly. Therefore, to evidence factors that might have contributed to a higher level of impact caused by its shock is important to create campaigns promoting financial awareness which aim to improve the population's well-being. Thus, the present work aims to analyze, through an ordinal logistic regression, the powerful influence of the behavior in the impact of economic shocks on people. To achieve this purpose, 366 questionnaires were applied in the region of great Porto Alegre. The main characteristics of four impact categories were analyzed and compared: those not affected by the financial shock, those who were weakly affected, those who were partially affected and those who were strongly affected by the financial shock. The main results showed significant differences in behavior among the least affected people and those most impacted regarding the control locus and financial behavior, confirming that the variables tested can help to explain the levels of impact.

For many years, terrorism has threatened life, property and business. Targets are largely in urban areas where there is a greater density of life and economic value. Governments, insurers and engineers have sought to mitigate these threats through understanding the effects of urban bombings, increasing the resilience of buildings and improving estimates of financial loss for insurance purposes. This has led to a desire for an improved approach to the prediction of blast propagation in urban cityscapes. Urban geometry has a significant impact on blast wave propagation. Presently, only computational fluid dynamics (CFD) methods adequately simulate these effects. However, for large-scale urban domains, these methods are both challenging to use and are computationally expensive. Adaptive mesh refinement (AMR) methods alleviate the problem, but are difficult to use for the non-expert and require significant tuning. We aim to make CFD urban blast simulation a primary choice for governments, insurers and engineers through improvements to AMR and by studying the performance of CFD in relation to other methods used by the industry. We present a new AMR flagging approach based on a second derivative error norm for compressive shocks (ENCS). This is compared with existing methods and is shown to lead to a reduction in overall refinement without affecting solution quality. Significant improvements to feature tracking over long distances are demonstrated, making the method easier to tune and less obtuse to non-experts. In the chapter that follows, we consider blast damage in urban areas. We begin with a validation and a numerical study, investigating the effects of simple street geometry on blast resultants. We then investigate the sensitivity of their distribution to the location of the charge. We find that moving the charge by a small distance can lead to a significant change in peak overpressures and creates a highly localised damage field due to interactions between the blast wave and the geometry. We then extend the investigation to the prediction of insured losses following a large-scale bombing in London. A CFD loss model is presented and compared with simpler approaches that do not account for urban geometry. We find that the simpler models lead to significant over-predictions of loss, equivalent to several hundred million pounds for the scenario considered. We use these findings to argue for increased uptake of CFD methods by the insurance industry. In the final chapter, we investigate the influence of urban geometry on the propagation of blast waves. An earlier study on the confinement effects of narrow streets is repeated at a converged resolution and we corroborate the findings. We repeat the study, this time introducing a variable porosity into the building facade. We observe that the effect of this porosity is as significant as the confinement effect, and we recommend to engineers that they consider porosity effects in certain cases. We conclude the study by investigating how alterations to building window layout can improve the protective effects of a facade. Maintaining the window surface area constant, we consider a range of layouts and observe how some result in significant reductions to blast strength inside the building.

abstract: The mechanical behavior of Pb-free solder alloys is important, since they must maintain mechanical integrity under thermomechanical fatigue, creep, and mechanical shock conditions. Mechanical shock, in particular, has become an increasing concern in the electronics industry, since electronic packages can be subjected to mechanical shock by mishandling during manufacture or by accidental dropping. In this study, the mechanical shock behavior of Sn and Sn-Ag-Cu alloys was systematically analyzed over the strain rate range 10-3 - 30 s-1 in bulk samples, and over 10-3 - 12 s-1 on the single solder joint level. More importantly, the influences of solder microstructure and intermetallic compounds (IMC) on mechanical shock resistance were quantified. A thorough microstructural characterization of Sn-rich alloys was conducted using synchrotron x-ray computed tomography. The three-dimensional morphology and distribution of contiguous phases and precipitates was analyzed. A multiscale approach was utilized to characterize Sn-rich phases on the microscale with x-ray tomography and focused ion beam tomography to characterize nanoscale precipitates. A high strain rate servohydraulic test system was developed in conjunction with a modified tensile specimen geometry and a high speed camera for quantifying deformation. The effect of microstructure and applied strain rate on the local strain and strain rate distributions were quantified using digital image correlation. Necking behavior was analyzed using a novel mirror fixture, and the triaxial stresses associated with necking were corrected using a self-consistent method to obtain the true stress-true strain constitutive behavior. Fracture mechanisms were quantified as a function of strain rate. Finally, the relationship between solder microstructure and intermetallic compound layer thickness with the mechanical shock resistance of Sn-3.8Ag-0.7Cu solder joints was characterized. It was found that at low strain rates the dynamic solder joint strength was controlled by the solder microstructure, while at high strain rates it was controlled by the IMC layer. The influences of solder microstructure and IMC layer thickness were then isolated using extended reflow or isothermal aging treatments. It was found that at large IMC layer thicknesses the trend described above does not hold true. The fracture mechanisms associated with the dynamic solder joint strength regimes were analyzed. / Dissertation/Thesis / Ph.D. Materials Science and Engineering 2012

Det pågår en ständig utveckling av normativa teorier om krig för att kunna anpassa sig till nutida konflikter. Nya teorier utvecklas i takt med ny teknologi och nya motståndare. De teorier som utvecklats på senare tid har föranlett till denna jämförelse mellan manöverkrigföring och Shock and Awe, Achieving Rapid Dominance. Uppsatsen syftar till att studera huruvida Shock and Awe, Achieving Rapid Dominance är en egen teori och i vilken utsträckning den grundar sig i manöverkrigföring. Genom en kvalitativ metod där textanalyser har legat till fokus, skapas idealtyper av manöverkrigföringens grundläggande element. Dessa verkar sedan som indikatorer för att urskilja likheter och skillnader med Shock and Awe. Resultatet visar på ett flertal likheter och skillnader som leder till slutsatsen att Shock and Awe inte kan definieras som en originell teori, då likheterna med manöverkrigföringen är allt för stora.

No description available.

Made available in DSpace on 2016-08-15T20:31:16Z (GMT). No. of bitstreams: 1 ErickPA_DISSERT.pdf: 4061592 bytes, checksum: 7e51a0e203a6b0a661e28e6402acf1cf (MD5) Previous issue date: 2014-02-28 / The present study aimed to evaluate the effects of acute blood loss in goats, due to the removal of 30% of blood volume. Eight mixed-breed, castrated, adult, healthy goats were used, weighing on average 34.75 + 4.3 kg. Clinical, hemogasometrical, hematological, and biochemical parameters were evaluated; as well as systolic, diastolic and mean blood pressure at the following moments: T0, before sampling, T1, T6, T12, T24, and T72, took place one, six, 12, 24, and 72 hours after sampling, respectively; and T8d, T16d, T24d and T32d, took place eight, 16, 24 and 32 days after sampling. From the total volume of blood 30% were taken. The goats presented tachycardia and tachypnea after the blood removal, a temporary rise in temperature occurred one hour after sampling, returning to normal values already in T6h. Packed cell volume decreased from T1h until T12h. The number of red blood cells, however, was different when compared to T0 only after T12h. Total protein and albumin levels were inferior when compared T0 only an hour after a blood loss, and remained as such until T16d and T8d, respectively. The CRT was high in T1h when compared to T0, but no difference was observed when compared to T12h. There was a decrease in serum calcium levels from T1h up until T24h. Glucose rose in T1h until T6h. At T1h, pH, TCO2, bicarbonate values and base deficit were smaller when compared to T0, while the lactate levels markedly increased at this time. The pO2 and SO2 were not altered. The pCO2 presented decreased values only at T24h. Systolic, diastolic and mean blood pressures showed, immediately after sampling, values lower than half of the observed at T0, however there was no difference at T1h. The concentrations of AST, GGT, urea and creatinine remained within the reference range. The acute loss of 30% of blood volume in goats causes noticeable changes in the clinical, hematological, hemogasometrical, and cardiovascular parameters / O presente estudo objetivou avaliar os efeitos da perda sanguínea aguda em caprinos, com a retirada de 30% do volume sanguíneo. Utilizou-se oito caprinos, SRD, machos, castrados, adultos, hígidos, pesando em media 34,75 + 4,3 kg. Foram avaliados parâmetros clínicos, hemogasométricos, hematológicos, bioquímicos; e pressões sistólica, diastólica e média nos tempos a seguir: T0, antes da coleta, T1, T6, T12, T24, T72, uma, seis, 12, 24, 72 horas após a coleta, respectivamente; e T8d, 16d, 24d e 32d, oito, 16, 24 e 32 dias após a coleta. Foram retirados 30% do volume total de sangue. Houve taquicardia e taquipnéia após retirada de sangue, elevação temporária da temperatura uma hora pós-coleta, voltando a valores normais já no T6h. O volume globular mostrou queda a partir do T1h até o T12h. Já o número de hemácias apresentou diferença em relação ao T0 somente a partir do T12h. A proteína total e albumina mostraram-se inferiores em relação T0 uma hora pós-perda sanguínea, mantendo-se até os tempos T16d e T8d respectivamente. O TPC mostrou-se elevado no T1h em relação ao T0, mas sem diferença em relação ao mesmo no T12h. Observou-se diminuição da concentração sérica do cálcio a partir do T1h até T24h. A glicose elevou-se no T1h até o T6h. No T1h os valores de pH, TCO2, bicarbonato e déficit de base mostraram-se menores em relação ao T0, enquanto o teor de lactato elevou-se marcadamente neste tempo. A pO2 e a SO2 não se alteraram. A pCO2 apresentou menores valores apenas no T24h. As pressões sistólicas, diastólicas e média mostraram imediatamente após a coleta, valores inferiores à metade do observado no T0, porém sem mostrar diferença em relação a este no T1h. As concentrações de AST, GGT, ureia e creatinina, mantiveram-se dentro dos valores de referência. A perda aguda de 30% do volume sanguíneo em caprinos provoca alterações visíveis nos parâmetros clínicos, hematológicos, hemogasométricos e cardiovasculares

A lessor understood co-chaperone, the Hsp70/Hsp90 organising protein (Hop), has been found to play an important role in modulating the activity and co-interaction of two essential chaperones; Hsp90 and Hsp70. The best understood aspects of Hop so far indicate that residues in the concave surfaces of the three tetratricopeptide repeat (TPR) domains in the protein bind selectively to the C-terminal motifs of Hsp70 and Hsp90. Recent research suggests that P. falciparum Hop (PfHop), PfHsp90 and PfHsp70 do interact and form complex in the P. falciparum trophozooite and are overexpressed in this infective stage. However, there has been almost no computational research on malarial Hop protein in complex with other malarial Hsps.The current work has focussed on several aspects of the in-silico characterisation of PfHop, including an in-depth multiple sequence alignment and phylogenetic analysis of the protein; which showed that Hop is very well conserved across a wide range of available phyla (four Kingdoms, 60 species). Homology modelling was employed to predict several protein structures for these interactions in P. falciparum, as well as predict structures of the relevant TPR domains of Human Hop (HsHop) in complex with its own Hsp90 and Hsp70 C-terminal peptide partners for comparison. Protein complex interaction analyses indicate that concave TPR sites bound to the C-terminal motifs of partner proteins are very similar in both species, due to the excellent conservation of the TPR domain’s “double carboxylate binding clamp”. Motif analysis was combined with phylogenetic trees and structure mapping in novel ways to attain more information on the evolutionary conservation of important structural and functional sites on Hop. Alternative sites of interaction between Hop TPR2 and Hsp90’s M and C domains are distinctly less well conserved between the two species, but still important to complex formation, making this a likely interaction site for selective drug targeting. Binding and interaction energies for all modelled complexes have been calculated; indicating that all HsHop TPR domains have higher affinities for their respective C-terminal partners than do their P. falciparum counterparts. An alternate motif corresponding to the C-terminal motif of PfHsp70-x (exported to the infected erythrocyte cytosol) in complex with both human and malarial TPR1 and TPR2B domains was analysed, and these studies suggest that the human TPR domains have a higher affinity for this motif than do the respective PfHop TPR domains. This may indicate potential for a cross species protein interaction to take place, as PfHop is not transported to the human erythrocyte cytosol.

L’étude des écoulements compressibles, notamment supersoniques, traversant les chambres de combustion de certains moteurs ramjet et scramjet, requiert la prise en compte de différents dispositifs complexes pour l’amélioration du processus de combustion et en particulier de leur stabilisation. La connaissance des interactions entre la turbulence, les effets de compressibilité, et les interaction fluide-solide dans ce type d’écoulement reste imparfaite. Ce travail de thèse est dédié à l’amélioration de notre compréhension de ce type d’écoulement dans un certain nombre de configurations canoniques par la biais de la simulation numérique directe. L’ensemble des simulations conduites s’appuie sur l’emploi d’un outil de simulation numérique haute fidélité : CREAMS (Compressible REActive Multi-species Solver) développé à l’Institut Pprime. Ce code de calcul met en oeuvre des schémas numériques d’ordre élevé : schéma Runge–Kutta d’ordre 3 pour l’intégration temporelle combiné à un schéma WENO d’ordre 7 et centré d’ordre 8 pour la discrétisation spatiale. Dans un premier temps, nous présentons une nouvelle méthode de frontières immergées pour le calcul d’écoulement d’un fluide visqueux compressible dans des géométries irrégulières. La méthode développée dans le cadre de cette thèse est basée sur la combinaison de l’approche appelée "Direct forcing" et celle de "Ghost-Point-Forcing". L’originalité de cette méthode réside dans sa capacité à simuler des écoulements subsoniques et supersoniques à différents nombres de Reynolds. L’examen de précision de cette méthode a permis d’établir un ordre supérieur à deux et sa robustesse est éprouvée par l’étude d’un bon nombre de cas tests. Dans un second temps, une configuration canonique idéalisée d’interaction choc-turbulence est étudiée pour mettre en lumière les mécanismes physiques fondamentaux caractéristiques du phénomène d’interaction entre une turbulence homogène isotrope et une onde de choc droite. Cette étude est complétée par une étude d’interaction choc-mélange scalaire pour étudier l’impact du choc normal sur le processus du mélange. Ce travail permet de mettre en place une base de données de résultats susceptibles d’être confrontés ultérieurement à des calculs basés sur l’emploi de modèles de turbulence. Enfin, nous nous sommes intéressés à l’effet des propriétés de transport moléculaire, en particulier celles de la viscosité volumique, sur le développement d’une couche de mélange impactée par un choc oblique. Les simulations réalisées dans cette configuration ont permis d’étudier la validité de l’hypothèse de Stokes consistant à négliger l’effet de la viscosité volumique. / The study of compressible flows, especially supersonic, passing through the combustion chambers of ramjet and scramjet engines, requires the consideration of various complex devices for improving the combustion processand in particular its stabilization. Indeed, the knowledge of the interactions between turbulence, compressibility effects, and fluid-solid interactions in this type of flow still remains imperfect. This thesis is dedicated to improving our understanding of this type of flow in a number of canonical flow configurations through direct numerical simulation. All the simulations that have been conducted are based on the use of a high-precision numerical simulations tool, called CREAMS (Compressible REActive Multi-species Solver), developed at the Pprime Institute. This computational solver makes use of high precision numerical schemes: a 3rd order Runge–Kutta scheme for time integration combined with a 7th order WENO and 8th order centered scheme for spatial discretization. In a first step of this study, we present a new immersed boundary method for calculating the flow of compressible viscous fluids in irregular geometries. The method developed in this thesis is based on the combination of the "Directforcing" approach with the "Ghost-Point-Forcing" strategy. The originality of this method lies in its ability to simulate subsonic and supersonic flows at different Reynolds numbers. The accuracy of this method is found to be slightly larger than second order and its robustness is investigated by considering a large set of benchmarks. Ina second step, an idealized canonical configuration of shock-turbulence interaction is studied to highlight the fundamental physical mechanisms that are characteristic of the interaction between an isotropic homogeneous turbulence and a normal shock wave. This analysis is complemented by a scalar shock-mixing interaction study to investigate the impact of normal shock on the mixing process properties. Through this work, a database is made available. It can be used to assess and improve turbulence models. Finally, we investigated the effect of molecular transport properties, more specifically the volume viscosity, on the development of a mixture layer impacted by an oblique shock. The simulations performed in this configuration allow to scrutinize the validity of the Stokes hypothesis that is based on the neglection of the volume viscosity.