Orientador: Willian Fernando Zambuzzi / Resumo: Mudanças nas forças tensionais do shear-stress estão associadas a um repertório de cascatas de sinalização celular, as quais modulam em conjunto o fenótipo vascular tornando o tecido endotelial susceptível a variações patofisiológica e, portanto, compreensão do repertório molecular neste cenário é necessária. Com este propósito, nós submetemos células endoteliais de veia umbilical humana (HUVEC) a um circuito de diferentes forças tensionais in vitro, considerando os grupos seguintes: 1. condição de fluxo de shear-stress fisiológico (nomeado Normo); 2. fluxo de shear-stress hipertenso (nomeado Hyper), e 3. células do grupo 2 foram retornadas para a condição Normo (nomeado Return). As amostras foram apropriadamente coletadas para seguir em diferentes metodologias. Nossos resultados mostraram um forte envolvimento de c-Src no controle da cascata de mecanotransdução modulando sinalização necessária para o fenótipo de adesão, sobrevivência (PI3K/AKT) e proliferação celulares. Além disso, c-Src parece desenvolver importante papel durante o remodelamento da Matriz Extracelular (MEC), cujo performance de matriz metaloproteinases (MMPs) mostrou mudanças significativas. Além disso, através de análise proteômica, mostramos um forte envolvimento de Heat Shock Protein 70 (HSP70) nas células estressadas de modo Hyper, reduzindo significativamente no grupo Return. Esse resultado levou-nos a investigar o proteassoma 20S como uma alternativa proteolítica intracelular para promover o turnover ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Shear-stress changes are associated with a repertory of signaling cascade, modulating vascular phenotype. As shear stress-related tensional forces might be associated with pathophysiological susceptibility, a more comprehensive molecular map needs to be addressed. Thus, we subjected human umbilical vein endothelial cells (HUVECs) to a circuit of different tensional forces in vitro considering the following three groups: one in a physiological blood flow shear-stress condition (named Normo), another in which these cells followed to a hypertensive blood flow shear-stress (named Hyper), and finally one that these hyper-stressed cells were returned to Normo condition (named Return). The samples were properly collected to allow different methodologies analysis. Our data showed a pivotal involvement of c-Src on driving the mechanotransduction cascade by modulating signaling related with adhesion, survival (PI3K/Akt) and proliferative phenotype. Moreover, c-Src seems to develop important role during Extracellular Matrix (ECM) remodeling, which showed significative changes. Additionally, proteomic analysis showed strong involvement of Heat Shock Protein 70 (HSP70) in the hypertensive-stressed cells; it being significantly decreased in Return phenotype. This result prompted us to investigate 20S proteasome as an intracellular proteolytic alternative to promote the turnover of those proteins. Surprisingly, our data reveled significant over expression of sets of proteasome subunit α-typ... (Complete abstract click electronic access below) / Mestre

Orientador: Willian Fernando Zambuzzi / Resumo: As células endoteliais (ECs) e células musculares lisas (AoSMCs) são os principais componentes celulares do endotélio. As interações entre estes tipos celulares desempenham funções na homeostase e na estrutura vascular. Como uma interface entre o sangue e a parede do vaso, as ECs ocupam um local único diretamente exposto ao shear stress (SS), a força mecânica de atrito lateral produzido pelo fluxo de sangue na membrana apical da célula endotelial, que pode influenciar o comportamento de ambas ECs e AoSMCs. Geralmente, AoSMCs não sofrem diretamente às forcas de cisalhamento, no entanto, estas são diretamente expostas ao fluxo sanguíneo quando ocorre alguma injúria vascular, como por exemplo em algumas lesões ateroscleróticas ou por técnicas invasivas, como a angioplastia. As forças hemodinâmicas influenciam as propriedades funcionais do endotélio, porém estas não são profundamente compreendidas quanto aos mecanismos bioquímicos de respostas de células endoteliais e de musculatura lisa. Assim, a proposta desta dissertação foi estabelecer um modelo de cultivo in vitro que mimetize as forças tensionais de cisalhamento (shear stress), buscando compreender mecanismos celulares, bioquímicos e epigenéticos. Cultura de células primárias endoteliais e de musculatura lisa humanas foram obtidas da empresa LONZA e mantidas conforme recomendações do fabricante. Estas células foram mantidas rotineiramente em condições convencionais em incubadora de CO2. Para mimetizar o fluxo sanguíneo, esta... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

In this work, the Shear Transformation Zone (STZ) dynamics model is adapted to capture the transitions between different regimes of flow serration in the deformation map of metallic glass. This was accomplished by scaling the STZ volume with a log-linear fit to the strain rate, and also adjusting the activation energy of an STZ with a log-linear fit to maintain constant yield strength at differing strain rates. Twelve simulations are run at each of six different strain rates ranging from 10-5 to 100 s-1, and statistics are collected on simulation behavior and shear band nucleation and propagation rates. The simulations show shear band nucleation has a positive correlation to strain rate, and shear band propagation has a negative correlation to strain rate. This shows that in STZ dynamics, the regime of reduced flow serration arises due to competing rates of nucleation and propagation, supporting the hypothesis proposed by Schuh. A positive correlation between critical shear band nucleus size and strain rate is proposed as an underlying cause of these rate dependencies.

L’élastographie par ondes de cisaillement consiste essentiellement en deux étapes: d'abord, une onde de cisaillement est générée en appliquant soigneusement une source contrôlée externe (par exemple actionneur mécanique ou force de rayonnement ultrasonore); Alors les déplacements induits sont imagés et l'élasticité tissulaire est déduite de la propagation d'onde de cisaillement mesurée. Cependant, avec les techniques d'élastographie actuellement disponibles, l'estimation quantitative correcte de la viscosité n'est pas possible. Dans ce contexte, le but principal de cette thèse est double: d'abord, développer un outil capable d'estimer simultanément les propriétés viscoélastiques d'un solide souple, notamment en utilisant l'imagerie par cisaillement supersonique, puis de l'appliquer aux certains problèmes rencontrés en médecine et l'industrie alimentaire.La première étape consiste à utiliser la technique SSI pour générer des cartes de vitesses des ondes de cisaillement dans des milieux solides mous et isotropes. Dans ce contexte, cette technique a été utilisée pour évaluer le processus de coagulation du lait. Au cours de cette étape, les limites de la technique SSI pour obtenir une caractérisation rhéologique complète des solides viscoélastiques sont mis en évidence. Pour parvenir à cette caractérisation, la vitesse de propagation ondes de cisaillement et la absorption que l’onde subi en traversant le milieu doivent être évalués à la fois. Compte tenu des caractéristiques de la technique SSI, en raison des effets de diffraction due à la taille finie des sources, l’absorption ne peut pas être obtenue correctement de façon quantitative.La partie centrale de la thèse porte sur l’étude des avantages et des ses limites de la correction des effets de diffraction de la technique SSI à partir d’une approximation cylindrique. Cette étude a été réalisée expérimentalement en comparant les résultats obtenus avec ceux des simulations numériques. L’étude a montré que la correction cylindrique est utile pour estimer l'atténuation provoquée par l'absorption dans certaines conditions. Une fois déterminé la zone de validité de la procédure de correction, des cartes des vitesses et des cartes d'atténuation ont était obtenus. Ces cartes ont permis t la caractérisation rhéologique complète des milieux étudiés.Une fois validé cette correction nous avons procédé à réaliser trois applications d'intérêt pour obtenir les propriétés rhéologiques, une pour l’ industrie alimentaire et deux pour la médecine clinique : a) suivie et étude du processus de coagulation du lait b) suivie et étude de processus de la coagulation du sang in vitro, c) des expériences de caractérisation rhéologique du foie in vivo. Finalement, une étude de la correction cylindrique mis en œuvre a été utilisée pour caractériser rhéologiquement des solides mous avec isotropie transversale. Milieux avec différents degrés d'anisotropie ont été analysés à l'aide de simulations numériques. Les résultats obtenus montrent que pour de faibles niveaux d’anisotropie la correction cylindrique s’avère utile avec une erreur raisonnable. Pour des degrés plus élevés d'anisotropie la correction cylindrique conduit à des erreurs majeures dans l'estimation de l'atténuation. Des mesures des coefficients d’absorption ont été réalisées dans des phantoms de gel anisotropes et dans des échantillons de viande de bœuf avec des tissues musculaire / Shear wave elastography consists essentially of two steps: first, a shear wave is generated by an external controlled source (eg mechanical actuator or ultrasonic radiation force); then the induced displacements are imaged and the tissue elasticity is deduced from the measured shear wave propagation. However, with the currently available elastographic techniques, a quantitative estimation of viscosity is not possible. In this context, the objective of this thesis is twofold: first, to develop a tool capable of estimating the viscoelastic properties of a soft solid, in particular by using supersonic shear imaging (SSI), and then to apply it to some problems encountered in medicine and the food industry.The first stage consisted in using the SSI technique to generate shear wave velocity maps in soft, isotropic solid media. In this context, this technique was used to evaluate the milk coagulation process. During this stage, limitations of the SSI technique to obtain a complete rheological characterization of viscoelastic solids were demonstrated. To achieve this characterization, the velocity of the shear waves and the absorption generated when passing through the medium must be evaluated at the same time. Given the characteristics of the SSI technique, the absorption cannot be directly quantified due to diffraction.The central part of the thesis focuses in the study of the advantages and limitations of using a cylindrical approximation to correct the diffraction effects. This study was carried out experimentally and through numerical simulations. The study showed that cylindrical correction is useful for estimating the attenuation caused by absorption under certain conditions. After determining the validity zone of the correction, velocity and attenuation maps were obtained. These maps allowed the complete rheological characterization of the studied media.Once the correction was validated, three applications of interest were carried out to obtain rheological properties, one for the food industry and two for clinical medicine: a) monitoring the process of milk coagulation through storage and loss moduli maps b) following in vitro blood coagulation processes, c) rheological characterization experiments of the liver in vivo. Finally, the application of the cylindrical correction to characterize transversely isotropic soft solids was studied. Media with different degrees of anisotropy were analyzed through numerical simulations. The results obtained showed that for low levels of anisotropy the cylindrical correction proves useful within a reasonable error. For higher degrees of anisotropy the cylindrical correction leads to major errors in the estimation of the attenuation. Measurements of the absorption coefficients were performed in anisotropic gel phantoms and in beef samples with muscle tissue

The effect of shear on the evolution of floc properties was investigated to analyse the flocculation mechanisms. Little fundamental attention has been given to the shear influence that often creates compact aggregates, while the floc characteristics might differ in other aggregating conditions. It is thus crucial to understand how flocs evolve to steady state, if their properties are to be 'tailored' to suit subsequent solids-liquid separation processes. In this work, flocculation of monodisperse latex particles of various sizes (60, 380, and 810 nm diameter) via electrolyte addition was carried out in a couette-flow and also in shear fields generated by an axial-flow impeller (Fluid foil A310) and a radial-flow impeller (Rushton R100) in standard mixing tanks. A small-angle light scattering technique was used to acquire information regarding the time variation of floc properties in a non-intrusive manner. The structure was quantified by a measure of fractal dimension, signifying the degree of floc compactness. Estimates of the average floc mass were also obtained from the aggregate scattering patterns. By monitoring the changes in floc structure and mass, corresponding to the size evolution; mechanisms of floc formation, fragmentation, and restructuring were identified. Aggregates of 60 and 380 nm particles were observed to grew larger initially, before decreasing to their equilibrium sizes at moderate shear rates (32 - 100 s-1) in a homogeneous shear environment. Floc restructuring at large length scales occurred extensively, and was responsible for the drop in size, particularly at the early stage of the process. Aggregates of 810 nm particles did not, however, display this behaviour. Flocs of larger primary particles were presumably susceptible to breakage rather than deformation, as they were weaker under comparable conditions. Denser aggregates were found when restructuring transpired, while comparatively tenuous flocs were observed when formation and breakage kinetics were the governing mechanisms. The disparity in floc behaviour at higher shear rates (246 s-1 - 330 s-1) was less apparent. The intense hydrodynamic stresses in those instances inevitably caused fragmentation, regardless of the intrinsic particle properties; hence the observed floc compaction was the product of break-up and re-aggregation. A population balance model, incorporating variation in floc structure, displayed comparable trends in size evolution; verifying that restructuring indeed took an important role under certain flocculation conditions. Similar phenomena were likewise observed with the flocculation in stirred tanks. The results reinforced findings in literature; that while circulation time controlled the process kinetics; the floc size was determined by the turbulent stresses. In addition, the maximum shear levels also influenced the floc structures, with denser aggregates produced in a shear field generated using the radial-flow impeller at equivalent energy dissipation per-unit mass. A correlation between non-dimensional floc factor that embodied the aggregate size and structure, and aggregation factor comprising the significant parameters from flocculation conditions, was proposed. The proposed relationship takes into account aspects such as the aggregate structure, interparticle forces, and particle concentration that are often overlooked in existing relationships, which usually only relate the maximum floc size to the applied energy dissipation rate. It thus provides an improved manner of presenting general flocculation data, as well as a means to predict floc properties produced under a specific aggregation condition. Future studies with increasingly complex systems that resemble real conditions are recommended in order to establish a practical understanding of the flocculation mechanisms, for the purpose of optimising the aggregate properties.

Current analysis procedures for new reinforced concrete structures are typically based on linear-elastic principles. However, under certain conditions, it may be necessary to analyze a structure to more accurately predict its structural behaviour. Such an analysis can be performed using nonlinear analysis procedures which typically require specialized software. This type of software is limited in number and most available programs do not adequately capture shear-related influences, potentially severely overestimating strength and ductility in shear-critical structures. The purpose of this study is to develop and verify an analytical procedure for the nonlinear analysis of frame structures with the aim of capturing shear-related mechanisms as well as flexural and axial effects. A previously developed analysis program, VecTor5, is further developed for this purpose. Originally formulated in the early 1980s at the University of Toronto, VecTor5 is based on the Modified Compression Field Theory (MCFT) and is capable of performing nonlinear frame analyses under temperature and monotonic loading conditions. Although providing generally satisfactory simulations, there are a number of deficiencies present in its computational algorithms. This study consists of three major parts: improvement of the original analysis procedure for monotonic loading conditions, expansion of the procedure for general loading conditions including the special cases of cyclic and reversed-cyclic loading, and further development of the procedure for dynamic loading conditions including time-varying base accelerations, impulse, impact and blast forces, initial mass velocities, and constant mass accelerations. Each part is supported by verification studies performed on a large number and variety of previously tested structures available in the literature. In addition, considerations in nonlinear modelling are discussed with the aim of providing guidelines for general modelling applications. Analyses of 63 previously tested structures, half of which are shear-critical, demonstrate that the developed analytical procedure is highly successful in simulating the experimental responses in terms of load-deflection response, reinforcement strains, crack widths, failure mode, failure displacement, total energy dissipation, displacement ductility ratio, and post-peak vibrational characteristics.

Current analysis procedures for new reinforced concrete structures are typically based on linear-elastic principles. However, under certain conditions, it may be necessary to analyze a structure to more accurately predict its structural behaviour. Such an analysis can be performed using nonlinear analysis procedures which typically require specialized software. This type of software is limited in number and most available programs do not adequately capture shear-related influences, potentially severely overestimating strength and ductility in shear-critical structures. The purpose of this study is to develop and verify an analytical procedure for the nonlinear analysis of frame structures with the aim of capturing shear-related mechanisms as well as flexural and axial effects. A previously developed analysis program, VecTor5, is further developed for this purpose. Originally formulated in the early 1980s at the University of Toronto, VecTor5 is based on the Modified Compression Field Theory (MCFT) and is capable of performing nonlinear frame analyses under temperature and monotonic loading conditions. Although providing generally satisfactory simulations, there are a number of deficiencies present in its computational algorithms. This study consists of three major parts: improvement of the original analysis procedure for monotonic loading conditions, expansion of the procedure for general loading conditions including the special cases of cyclic and reversed-cyclic loading, and further development of the procedure for dynamic loading conditions including time-varying base accelerations, impulse, impact and blast forces, initial mass velocities, and constant mass accelerations. Each part is supported by verification studies performed on a large number and variety of previously tested structures available in the literature. In addition, considerations in nonlinear modelling are discussed with the aim of providing guidelines for general modelling applications. Analyses of 63 previously tested structures, half of which are shear-critical, demonstrate that the developed analytical procedure is highly successful in simulating the experimental responses in terms of load-deflection response, reinforcement strains, crack widths, failure mode, failure displacement, total energy dissipation, displacement ductility ratio, and post-peak vibrational characteristics.

Reinforced concrete slab-column structures are widely used because of their practicality. However, this type of structures can be subject to punching-shear failure in the slab-column connections. Without shear reinforcement, the slab-column connection can undergo brittle punching failure, especially when the structure is subject to lateral loading in seismic zones. The shear bolts are a new type of transverse reinforcement developed for retrofit of existing structures against punching. This research focuses on how the shear bolts can improve the punching-shear capacity and ductility of the existing slab-column connections under vertical service and lateral seismic loads. A set of nine full-scale reinforced concrete slab-column connection specimens were tested under vertical service and cyclic loads. The vertical (gravity) load for each specimen was kept at a constant value throughout the testing. The cyclic lateral drift with increasing intensity was applied to the columns. The specimens were different in number of bolts, concrete strength, number of openings, and level of gravity punching load. Strains in flexural rebars in the slabs, crack widths, lateral loads, and displacements were obtained. The peak lateral load (moment) and its corresponding drift ratio, connection stiffness, crack width, and ductility were compared among different specimens. The testing results show that shear bolts can increase lateral peak load resisting capacity, lateral drift capacity at peak load, and ductility of the slab-column connections. Shear bolts also change the failure mode of the slab-column connections and increase the energy dissipation capacity. The thesis includes also research on the development of guidelines for shear bolt design for concrete slab retrofitting, including the punching shear design method of concrete slab (with shear bolts), dimensions of bolts, spacing, and influence of bolt layout patterns. Suggestions are given for construction of retrofitting method using shear bolts. Recommendations are also presented for future research.

Reinforced concrete slab-column structures are widely used because of their practicality. However, this type of structures can be subject to punching-shear failure in the slab-column connections. Without shear reinforcement, the slab-column connection can undergo brittle punching failure, especially when the structure is subject to lateral loading in seismic zones. The shear bolts are a new type of transverse reinforcement developed for retrofit of existing structures against punching. This research focuses on how the shear bolts can improve the punching-shear capacity and ductility of the existing slab-column connections under vertical service and lateral seismic loads. A set of nine full-scale reinforced concrete slab-column connection specimens were tested under vertical service and cyclic loads. The vertical (gravity) load for each specimen was kept at a constant value throughout the testing. The cyclic lateral drift with increasing intensity was applied to the columns. The specimens were different in number of bolts, concrete strength, number of openings, and level of gravity punching load. Strains in flexural rebars in the slabs, crack widths, lateral loads, and displacements were obtained. The peak lateral load (moment) and its corresponding drift ratio, connection stiffness, crack width, and ductility were compared among different specimens. The testing results show that shear bolts can increase lateral peak load resisting capacity, lateral drift capacity at peak load, and ductility of the slab-column connections. Shear bolts also change the failure mode of the slab-column connections and increase the energy dissipation capacity. The thesis includes also research on the development of guidelines for shear bolt design for concrete slab retrofitting, including the punching shear design method of concrete slab (with shear bolts), dimensions of bolts, spacing, and influence of bolt layout patterns. Suggestions are given for construction of retrofitting method using shear bolts. Recommendations are also presented for future research.

In this thesis, the relation between shear load and displacement for the lead-free solder (Sn3.0Ag0.5Cu) and the tin-lead solder (63Sn37Pb) are investigated. Except that, a new shear strength of the solder balls is suggested with considering the plastic strain energy of the solder balls. Three diameters of the Sn/Ag/Cu and Sn/Pb solder balls are studied. The variation of the plastic strain energies for the balls undergone different number of thermal cycles is compared. The effect of high temperature aging on the shear strength is also discussed. The difference between the failure fractures of the Sn/Ag/Cu and Sn/Pb solder ball are executed by using SEM. The experimental results show that the failure mechanism for the Sn/Ag/Cu is quite different from the Sn/Pb solder ball. Generally, the lead-free Sn/Ag/Cu solder is much ductile than the Sn/Pb solder ball in the shear test. Also the better fatigue performances are observed for the Sn/Ag/Cu solder balls.