New 3D multi-scale modeling approaches for the structural analysis of native and prosthetic Aortic Valves (AV) are investigated. Three different nonlinear hyperelastic constitutive material models for the mechanical behavior of the AV tissue are introduced. The first is the well-known Holzapfel hyperelastic, anisotropic and homogeneous model. The second model, termed the Collagen Fiber Network (CFN), is a heterogeneous model that recognizes the hyperelastic collagen and elastin layers using different layered finite elements. The third hyperelastic model is implemented using a new nonlinear micromechanical formulation of the High Fidelity Generalized Method of Cells (HFGMC) originally proposed by Aboudi. The latter two material models are heterogeneous and explicitly recognize the in-situ tissue constituents. Initially, a full scale 3D structural model of a polymeric-based prosthetic AV model is studied. This model is verified using deformation metrics obtained from images taken with high speed cameras during in-vitro experiments. The predictions from the proposed polymeric AV model are in good agreement with the test data. Next, the three tissue material models are examined in their ability to predict the anisotropic material behavior of porcine AV leaflet tissue. The Holzapfel model is calibrated from the overall anisotropic uni- and biaxial stress-strain data while the in-situ elastin and collagen constituents in the CFN and HFGMC models are calibrated to match the overall effective responses. Dynamic structural analysis is performed for the porcine AV with applied transvalvular pressure measured from repeated in-vitro tests conducted in this study. Principal stretches are computed from the experimental measurements and compared with the AV material-structural predictions. The proposed multi-scale modeling approach for the native AV is capable of predicting the structural behavior during the entire cardiac cycle without suffering from numerical convergence problems. Finally, new nonlinear micromechanical formulations based on the HFGMC method are developed and applied for various types of tissue materials including the human arterial wall layers and porcine AV leaflets. The proposed hyperelastic HFGMC model is compared to the CFN model and the Holzapfel models. It is shown that the HFGMC is an effective modeling approach for the arteries especially when the collagen fiber network has a periodic microstructure.

O presente trabalho teve por objetivo desenvolver um código computacional com base no método dos elementos finitos, para análises termoestruturais de estruturas de aço aporticadas quando expostas a ações térmicas típicas de situações de incêndio. O código utilizado nas análises estruturais emprega elemento finito de pórtico não linear 3-D de formulação posicional. A formulação posicional utiliza como graus de liberdade as posições dos nós ao invés dos deslocamentos, resultando em uma descrição intrinsecamente não linear do comportamento geométrico das estruturas. Podem ser consideradas seções transversais quaisquer com o elemento finito em questão, e sua representação geral é tridimensional. Adota-se uma lei constitutiva tridimensional completa e a cinemática de Reissner, de modo que o modelo de plasticidade considera o efeito combinado das tensões normais e cisalhantes para verificação do critério 3-D de plasticidade. O código computacional desenvolvido permite que sejam realizadas análises térmicas transientes com base no método dos elementos finitos para se determinar campos de temperatura nas seções transversais dos elementos estruturais sujeitos ao fogo. Assim, a influência da temperatura nas propriedades dos materiais é levada em consideração para se avaliar o desempenho da estrutura em cada instante da análise em situação de incêndio, até que o colapso estrutural seja verificado. Análises de casos presentes na literatura são utilizados para validar os resultados obtidos, os quais comprovam a precisão do código computacional desenvolvido e da formulação posicional quando aplicados a análises de estruturas de aço aporticadas à temperatura ambiente e em situação de incêndio. / The present work deals with the development of a computational code based on the finite element method for thermo-structural analyses of steel framed structures when exposed to typical thermal actions of fire condition. The structural analysis is performed considering a computer code that uses 3-D frame nonlinear finite elements of positional formulation. This formulation is based on the positions of the finite element nodes, instead of displacements, which results in an intrinsically nonlinear description of the geometric behavior of structures. The cross-sections of finite elements can be of any geometry due to the tridimensional representation. A complete tridimensional constitutive law is used and, therefore, the effect of combined normal and shear stresses is taken into account for the tridimensional plasticity evolution. The developed computational code allows performing transient thermal analyses to determine the temperature field over the cross-sections of the structural elements subjected to fire. The influence of temperature on the material properties is considered to evaluate the structure response at each defined instant of the fire analysis, until the collapse occurs. The achieved results, when compared to those found in the literature, allow verifying the precision of the developed computational code when applied to steel frame analysis at ambient temperature and in fire situation.

Glucosyltransferases (GTs) are enzymes that enable transfer of glucose from an activated donor (UDP-glucose) to the acceptor substrates. A flavonol specific glucosyltransferase cloned from Citrus paradisi has strict substrate and regiospecificity (Cp3OGT). The amino acid sequence of Cp3OGT was aligned with a purported anthocyanin GT from Clitorea ternatea and a GT from Vitis vinifera that can glucosylate both flavonols and anthocyanidins. Using homology modeling to identify candidate regions followed by site directed mutagenesis, three double mutations of Cp3OGT were made. Biochemical analysis of the three mutant proteins was performed. S20G+T21S protein retained activity similar to the wildtype (WT- Kmapp-80 µM; Vmax = 16.5 pkat/µg, Mutant- Kmapp-83 µM; Vmax -11 pkat/µg) but the mutant was more thermostable compared to the WT and this mutation broadened its substrate acceptance to include the flavanone, naringenin. S290C+S319A mutant protein retained 40% activity relative to wildtype, had an optimum pH shift, but had no change in substrate specificity (Kmapp-18 µM; Vmax-0.5 pkat/µg). H154Y+Q87I protein was inactive with every class of flavonoid tested. Product identification revealed that the S20G+T21S mutant protein widened the substrate and regio-specificity of CP3OGT. Docking analysis revealed that H154 and Q87 could be involved in orienting the ligand molecules within the acceptor binding site. H363, S20, and S150 were also found to make close contact with the 7-OH, 4-OH and 3’-OH groups, respectively.

O presente trabalho teve por objetivo desenvolver um código computacional com base no método dos elementos finitos, para análises termoestruturais de estruturas de aço aporticadas quando expostas a ações térmicas típicas de situações de incêndio. O código utilizado nas análises estruturais emprega elemento finito de pórtico não linear 3-D de formulação posicional. A formulação posicional utiliza como graus de liberdade as posições dos nós ao invés dos deslocamentos, resultando em uma descrição intrinsecamente não linear do comportamento geométrico das estruturas. Podem ser consideradas seções transversais quaisquer com o elemento finito em questão, e sua representação geral é tridimensional. Adota-se uma lei constitutiva tridimensional completa e a cinemática de Reissner, de modo que o modelo de plasticidade considera o efeito combinado das tensões normais e cisalhantes para verificação do critério 3-D de plasticidade. O código computacional desenvolvido permite que sejam realizadas análises térmicas transientes com base no método dos elementos finitos para se determinar campos de temperatura nas seções transversais dos elementos estruturais sujeitos ao fogo. Assim, a influência da temperatura nas propriedades dos materiais é levada em consideração para se avaliar o desempenho da estrutura em cada instante da análise em situação de incêndio, até que o colapso estrutural seja verificado. Análises de casos presentes na literatura são utilizados para validar os resultados obtidos, os quais comprovam a precisão do código computacional desenvolvido e da formulação posicional quando aplicados a análises de estruturas de aço aporticadas à temperatura ambiente e em situação de incêndio. / The present work deals with the development of a computational code based on the finite element method for thermo-structural analyses of steel framed structures when exposed to typical thermal actions of fire condition. The structural analysis is performed considering a computer code that uses 3-D frame nonlinear finite elements of positional formulation. This formulation is based on the positions of the finite element nodes, instead of displacements, which results in an intrinsically nonlinear description of the geometric behavior of structures. The cross-sections of finite elements can be of any geometry due to the tridimensional representation. A complete tridimensional constitutive law is used and, therefore, the effect of combined normal and shear stresses is taken into account for the tridimensional plasticity evolution. The developed computational code allows performing transient thermal analyses to determine the temperature field over the cross-sections of the structural elements subjected to fire. The influence of temperature on the material properties is considered to evaluate the structure response at each defined instant of the fire analysis, until the collapse occurs. The achieved results, when compared to those found in the literature, allow verifying the precision of the developed computational code when applied to steel frame analysis at ambient temperature and in fire situation.