Estrogen receptor: Structural differences and potential implications on selectivity examined by the GRID/CPCA approach

Selective Estrogen Receptor Modulators ( SERMs) have been developed, but the selectivity towards the subtypes ( ER or ER is not well understood. Based on three-dimensional structural properties of ligand binding domains, a model that takes into account this aspect was developed via molecular interaction fields and consensus principal component analysis (GRID/CPCA).

Métodos computacionales para visco-hiperelasticidad anisótropa en grandes deformaciones

El comportamiento mecánico de muchos materiales biológicos y poliméricos en grandes deformaciones se puede describir adecuadamente mediante formulaciones isocóricas hiperelásticas y viscoelásticas. Las ecuaciones de comportamiento elástico y viscoelástico y las formulaciones computacionales para materiales incompresibles isótropos en deformaciones finitas están ampliamente desarrolladas en la actualidad. Sin embargo, el desarrollo de modelos anisótropos no lineales y de sus correspondientes formulaciones computacionales sigue siendo un tema de investigación de gran interés. Cuando se consideran grandes deformaciones, existen muchas medidas de deformación disponibles con las que poder formular las ecuaciones de comportamiento. Los modelos en deformaciones cuadráticas facilitan la implementación en códigos de elementos finitos, ya que estas medidas surgen de forma natural en la formulación. No obstante, pueden dificultar la interpretación de los modelos y llevar a resultados pocos realistas. El uso de deformaciones logarítmicas permite el desarrollo de modelos más simples e intuitivos, aunque su formulación computacional debe ser adaptada a las exigencias del programa. Como punto de partida, en esta tesis se demuestra que las deformaciones logarítmicas representan la extensión natural de las deformaciones infinitesimales, tanto axiales como angulares, al campo de las grandes deformaciones. Este hecho permite explicar la simplicidad de las ecuaciones resultantes. Los modelos hiperelásticos predominantes en la actualidad están formulados en invariantes de deformaciones cuadráticas. Estos modelos, ya sean continuos o microestructurales, se caracterizan por tener una forma analítica predefinida. Su expresión definitiva se calcula mediante un ajuste de curvas a datos experimentales. Un modelo que no sigue esta metodología fue desarrollado por Sussman y Bathe. El modelo es sólo válido para isotropía y queda definido por una función de energía interpolada con splines, la cual reproduce los datos experimentales de forma exacta. En esta tesis se presenta su extensión a materiales transversalmente isótropos y ortótropos utilizando deformaciones logarítmicas. Asimismo, se define una nueva propiedad que las funciones de energía anisótropas deben satisfacer para que su convergencia al caso isótropo sea correcta. En visco-hiperelasticidad, aparte de las distintas funciones de energía disponibles, hay dos aproximaciones computational típicas basadas en variables internas. El modelo original de Simó está formulado en tensiones y es válido para materiales anisótropos, aunque sólo es adecuado para pequeñas desviaciones con respecto al equilibrio termodinámico. En cambio, el modelo basado en deformaciones de Reese y Govindjee permite grandes deformaciones no equilibradas pero es, en esencia, isótropo. Las formulaciones anisótropas en este último contexto son microestructurales y emplean el modelo isótropo para cada uno de los constituyentes. En esta tesis se presentan dos formulaciones fenomenológicas viscoelásticas definidas mediante funciones hiperelásticas anisótropas y válidas para grandes desviaciones con respecto al equilibrio termodinámico. El primero de los modelos está basado en la descomposición multiplicativa de Sidoroff y requiere un comportamiento viscoso isótropo. La formulación converge al modelo de Reese y Govindjee en el caso especial de isotropía elástica. El segundo modelo se define a partir de una descomposición multiplicativa inversa. Esta formulación está basada en una descripción co-rotacional del problema, es sustancialmente más compleja y puede dar lugar a tensores constitutivos ligeramente no simétricos. Sin embargo, su rango de aplicación es mucho mayor ya que permite un comportamiento anisótropo tanto elástico como viscoso. Varias simulaciones de elementos finitos muestran la gran versatilidad de estos modelos cuando se combinan con funciones hiperelásticas formadas por splines. ABSTRACT The mechanical behavior of many polymeric and biological materials may be properly modelled be means of isochoric hyperelastic and viscoelastic formulations. These materials may sustain large strains. The viscoelastic computational formulations for isotropic incompressible materials at large strains may be considered well established; for example Ogden’s hyperelastic function and the visco-hyperelastic model of Reese and Govindjee are well known models for isotropy. However, anisotropic models and computational procedures both for hyperelasticity and viscohyperelasticity are still under substantial research. Anisotropic hyperelastic models are typically based on structural invariants obtained from quadratic strain measures. These models may be microstructurallybased or phenomenological continuum formulations, and are characterized by a predefined analytical shape of the stored energy. The actual final expression of the stored energy depends on some material parameters which are obtained from an optimization algorithm, typically the Levenberg-Marquardt algorithm. We present in this work anisotropic spline-based hyperelastic stored energies in which the shape of the stored energy is obtained as part of the procedure and which (exactly in practice) replicates the experimental data. These stored energies are based on invariants obtained from logarithmic strain measures. These strain measures preserve the metric and the physical meaning of the trace and deviator operators and, hence, are interesting and meaningful for anisotropic formulations. Furthermore, the proposed stored energies may be formulated in order to have material-symmetries congruency both from a theoretical and from a numerical point of view, which are new properties that we define in this work. On the other hand, visco-hyperelastic formulations for anisotropic materials are typically based on internal stress-like variables following a procedure used by Sim´o. However, it can be shown that this procedure is not adequate for large deviations from thermodynamic equilibrium. In contrast, a formulation given by Reese and Govindjee is valid for arbitrarily large deviations from thermodynamic equilibrium but not for anisotropic stored energy functions. In this work we present two formulations for visco-hyperelasticity valid for anisotropic stored energies and large deviations from thermodynamic equilibrium. One of the formulations is based on the Sidoroff multiplicative decomposition and converges to the Reese and Govindjee formulation for the case of isotropy. However, the formulation is restricted to isotropy for the viscous component. The second formulation is based on a reversed multiplicative decomposition. This last formulation is substantially more complex and based on a corotational description of the problem. It can also result in a slightly nonsymmetric tangent. However, the formulation allows for anisotropy not only in the equilibrated and non-equilibrated stored energies, but also in the viscous behavior. Some examples show finite element implementation, versatility and interesting characteristics of the models.

Analytical study of the nonlinear behavior of a shape memory oscillator: Part II-resonance secondary

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Analytical study of the nonlinear behavior of a shape memory oscillator: Part I-primary resonance and free response at low temperatures

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

An analytical tool that quantifies cellular morphology changes from three-dimensional fluorescence images

The most common software analysis tools available for measuring fluorescence images are for two-dimensional (2D) data that rely on manual settings for inclusion and exclusion of data points, and computer-aided pattern recognition to support the interpretation and findings of the analysis. It has become increasingly important to be able to measure fluorescence images constructed from three-dimensional (3D) datasets in order to be able to capture the complexity of cellular dynamics and understand the basis of cellular plasticity within biological systems. Sophisticated microscopy instruments have permitted the visualization of 3D fluorescence images through the acquisition of multispectral fluorescence images and powerful analytical software that reconstructs the images from confocal stacks that then provide a 3D representation of the collected 2D images. Advanced design-based stereology methods have progressed from the approximation and assumptions of the original model-based stereology(1) even in complex tissue sections(2). Despite these scientific advances in microscopy, a need remains for an automated analytic method that fully exploits the intrinsic 3D data to allow for the analysis and quantification of the complex changes in cell morphology, protein localization and receptor trafficking. Current techniques available to quantify fluorescence images include Meta-Morph (Molecular Devices, Sunnyvale, CA) and Image J (NIH) which provide manual analysis. Imaris (Andor Technology, Belfast, Northern Ireland) software provides the feature MeasurementPro, which allows the manual creation of measurement points that can be placed in a volume image or drawn on a series of 2D slices to create a 3D object. This method is useful for single-click point measurements to measure a line distance between two objects or to create a polygon that encloses a region of interest, but it is difficult to apply to complex cellular network structures. Filament Tracer (Andor) allows automatic detection of the 3D neuronal filament-like however, this module has been developed to measure defined structures such as neurons, which are comprised of dendrites, axons and spines (tree-like structure). This module has been ingeniously utilized to make morphological measurements to non-neuronal cells(3), however, the output data provide information of an extended cellular network by using a software that depends on a defined cell shape rather than being an amorphous-shaped cellular model. To overcome the issue of analyzing amorphous-shaped cells and making the software more suitable to a biological application, Imaris developed Imaris Cell. This was a scientific project with the Eidgenössische Technische Hochschule, which has been developed to calculate the relationship between cells and organelles. While the software enables the detection of biological constraints, by forcing one nucleus per cell and using cell membranes to segment cells, it cannot be utilized to analyze fluorescence data that are not continuous because ideally it builds cell surface without void spaces. To our knowledge, at present no user-modifiable automated approach that provides morphometric information from 3D fluorescence images has been developed that achieves cellular spatial information of an undefined shape (Figure 1). We have developed an analytical platform using the Imaris core software module and Imaris XT interfaced to MATLAB (Mat Works, Inc.). These tools allow the 3D measurement of cells without a pre-defined shape and with inconsistent fluorescence network components. Furthermore, this method will allow researchers who have extended expertise in biological systems, but not familiarity to computer applications, to perform quantification of morphological changes in cell dynamics.

Constitutive modeling of shape memory alloy wire with non-local rate kinetics

A constitutive modeling approach for shape memory alloy (SMA) wire by taking into account the microstructural phase inhomogeneity and the associated solid-solid phase transformation kinetics is reported in this paper. The approach is applicable to general thermomechanical loading. Characterization of various scales in the non-local rate sensitive kinetics is the main focus of this paper. Design of SMA materials and actuators not only involve an optimal exploitation of the hysteresis loops during loading-unloading, but also accounts for fatigue and training cycle identifications. For a successful design of SMA integrated actuator systems, it is essential to include the microstructural inhomogeneity effects and the loading rate dependence of the martensitic evolution, since these factors play predominant role in fatigue. In the proposed formulation, the evolution of new phase is assumed according to Weibull distribution. Fourier transformation and finite difference methods are applied to arrive at the analytical form of two important scaling parameters. The ratio of these scaling parameters is of the order of 10(6) for stress-free temperature-induced transformation and 10(4) for stress-induced transformation. These scaling parameters are used in order to study the effect of microstructural variation on the thermo-mechanical force and interface driving force. It is observed that the interface driving force is significant during the evolution. Increase in the slopes of the transformation start and end regions in the stress-strain hysteresis loop is observed for mechanical loading with higher rates.

Analytical solutions for protective filters based on soil-retention and permeability criteria with respect to the phenomenon of soil boiling

For the successful performance of a granular filter medium, existing design guidelines, which are based on the particle size distribution (PSD) characteristics of the base soil and filter medium, require two contradictory conditions to be satisfied, viz., soil retention and permeability. In spite of the wider applicability of these guidelines, it is well recognized that (i) they are applicable to a particular range of soils tested in the laboratory, (ii) the design procedures do not include performance-based selection criteria, and (iii) there are no means to establish the sensitivity of the important variables influencing performance. In the present work, analytical solutions are developed to obtain a factor of safety with respect to soil-retention and permeability criteria for a base soil - filter medium system subjected to a soil boiling condition. The proposed analytical solutions take into consideration relevant geotechnical properties such as void ratio, permeability, dry unit weight, effective friction angle, shape and size of soil particles, seepage discharge, and existing hydraulic gradient. The solution is validated through example applications and experimental results, and it is established that it can be used successfully in the selection as well as design of granular filters and can be applied to all types of base soils.

A note on the inverse mode shape problem for bars, beams, and plates

Motivated by the idea of designing a structure for a desired mode shape, intended towards applications such as resonant sensors, actuators and vibration confinement, we present the inverse mode shape problem for bars, beams and plates in this work. The objective is to determine the cross-sectional profile of these structures, given a mode shape, boundary condition and the mass. The contribution of this article is twofold: (i) A numerical method to solve this problem when a valid mode shape is provided in the finite element framework for both linear and nonlinear versions of the problem. (ii) An analytical result to prove the uniqueness and existence of the solution in the case of bars. This article also highlights a very important question of the validity of a mode shape for any structure of given boundary conditions.

Effect of chemical treatment on surface characteristics of sputter deposited Ti-rich NiTi shape memory alloy thin-films

NiTi thin-films were deposited by DC magnetron sputtering from single alloy target (Ni/Ti: 45/55 aL.%). The rate of deposition and thickness of sputter deposited films were maintained to similar to 35 nm min(-1) and 4 mu m respectively. A set of sputter deposited NiTi films were selected for specific chemical treatment with the solution comprising of de-ionized water, HF and HNO3 respectively. The influence of chemical treatment on surface characteristics of NiTi films before and after chemical treatment was investigated for their structure, micro-structure and composition using different analytical techniques. Prior to chemical treatment, the composition of NiTi films using energy dispersive X-ray dispersive spectroscopy (EDS), were found to be 51.8 atomic percent of Ti and 48.2 atomic percent of Ni. The structure and morphology of these films were investigated by X-ray diffraction (XRD) and scanning electron microscopy (SEM). XRD investigations, demonstrated the presence of dominant Austenite (110) phase along with Martensite phase, for untreated NiTi films whereas some additional diffraction peaks viz. (100), (101), and (200) corresponding to Rutile and Anatase phase of Titanium dioxide (TiO2) along with parent Austenite (110) phase were observed for chemically treated NiTi films. FTIR studies, it can be concluded that chemically treated films have higher tendency to form metal oxide/hydroxide than the untreated NiTi films. XPS investigations, demonstrated the presence of Ni-free surface and formation of a protective metal oxide (TiO2) layer on the surface of the films, in both the cases. The extent of the formation of surface oxide layer onto the surface of NiTi films has enhanced after chemical treatment. (C) 2014 Elsevier B.V. All rights reserved.

Analytical test functions for free vibration analysis of rotating non-homogeneous Timoshenko beams

In this paper, the governing equations for free vibration of a non-homogeneous rotating Timoshenko beam, having uniform cross-section, is studied using an inverse problem approach, for both cantilever and pinned-free boundary conditions. The bending displacement and the rotation due to bending are assumed to be simple polynomials which satisfy all four boundary conditions. It is found that for certain polynomial variations of the material mass density, elastic modulus and shear modulus, along the length of the beam, the assumed polynomials serve as simple closed form solutions to the coupled second order governing differential equations with variable coefficients. It is found that there are an infinite number of analytical polynomial functions possible for material mass density, shear modulus and elastic modulus distributions, which share the same frequency and mode shape for a particular mode. The derived results are intended to serve as benchmark solutions for testing approximate or numerical methods used for the vibration analysis of rotating non-homogeneous Timoshenko beams.

Freeform Skeletal Shape Optimization of Compliant Mechanisms

Compliant mechanisms are elastic continua used to transmit or transform force and motion mechanically. The topology optimization methods developed for compliant mechanisms also give the shape for a chosen parameterization of the design domain with a fixed mesh. However, in these methods, the shapes of the flexible segments in the resulting optimal solutions are restricted either by the type or the resolution of the design parameterization. This limitation is overcome in this paper by focusing on optimizing the skeletal shape of the compliant segments in a given topology. It is accomplished by identifying such segments in the topology and representing them using Bezier curves. The vertices of the Bezier control polygon are used to parameterize the shape-design space. Uniform parameter steps of the Bezier curves naturally enable adaptive finite element discretization of the segments as their shapes change. Practical constraints such as avoiding intersections with other segments, self-intersections, and restrictions on the available space and material, are incorporated into the formulation. A multi-criteria function from our prior work is used as the objective. Analytical sensitivity analysis for the objective and constraints is presented and is used in the numerical optimization. Examples are included to illustrate the shape optimization method.

Interfacial Stresses in Shape Memory Alloy Reinforced Composites

Debonding of Shape Memory Alloy (SMA) wires in SMA reinforced polymer matrix composites is a complex phenomenon compared to other fabric fiber debonding in similar matrix composites. This paper focuses on experimental study and analytical correlation of stress required for debonding of thermal SMA actuator wire reinforced composites. Fiber pull-out tests are carried out on thermal SMA actuator at parent state to understand the effect of stress induced detwinned martensites. An ASTM standard is followed as benchmark method for fiber pull-out test. Debonding stress is derived with the help of non-local shear-lag theory applied to elasto-plastic interface. Furthermore, experimental investigations are carried out to study the effect of Laser shot peening on SMA surface to improve the interfacial strength. Variation in debonding stress due to length of SMA wire reinforced in epoxy are investigated for non-peened and peened SMA wires. Experimental results of interfacial strength variation due to various L/d ratio for non-peened and peened SMA actuator wires in epoxy matrix are discussed.

Tailoring the second mode of Euler-Bernoulli beams: an analytical approach

In this paper, we study the inverse mode shape problem for an Euler-Bernoulli beam, using an analytical approach. The mass and stiffness variations are determined for a beam, having various boundary conditions, which has a prescribed polynomial second mode shape with an internal node. It is found that physically feasible rectangular cross-section beams which satisfy the inverse problem exist for a variety of boundary conditions. The effect of the location of the internal node on the mass and stiffness variations and on the deflection of the beam is studied. The derived functions are used to verify the p-version finite element code, for the cantilever boundary condition. The paper also presents the bounds on the location of the internal node, for a valid mass and stiffness variation, for any given boundary condition. The derived property variations, corresponding to a given mode shape and boundary condition, also provides a simple closed-form solution for a class of non-uniform Euler-Bernoulli beams. These closed-form solutions can also be used to check optimization algorithms proposed for modal tailoring.

A Study of Composite Beam with Shape Memory Alloy Arbitrarily Embedded under Thermal and Mechanical Loadings

The constitutive relations and kinematic assumptions on the composite beam with shape memory alloy (SMA) arbitrarily embedded are discussed and the results related to the different kinematic assumptions are compared. As the approach of mechanics of materials is to study the composite beam with the SMA layer embedded, the kinematic assumption is vital. In this paper, we systematically study the kinematic assumptions influence on the composite beam deflection and vibration characteristics. Based on the different kinematic assumptions, the equations of equilibrium/motion are different. Here three widely used kinematic assumptions are presented and the equations of equilibrium/motion are derived accordingly. As the three kinematic assumptions change from the simple to the complex one, the governing equations evolve from the linear to the nonlinear ones. For the nonlinear equations of equilibrium, the numerical solution is obtained by using Galerkin discretization method and Newton-Rhapson iteration method. The analysis on the numerical difficulty of using Galerkin method on the post-buckling analysis is presented. For the post-buckling analysis, finite element method is applied to avoid the difficulty due to the singularity occurred in Galerkin method. The natural frequencies of the composite beam with the nonlinear governing equation, which are obtained by directly linearizing the equations and locally linearizing the equations around each equilibrium, are compared. The influences of the SMA layer thickness and the shift from neutral axis on the deflection, buckling and post-buckling are also investigated. This paper presents a very general way to treat thermo-mechanical properties of the composite beam with SMA arbitrarily embedded. The governing equations for each kinematic assumption consist of a third order and a fourth order differential equation with a total of seven boundary conditions. Some previous studies on the SMA layer either ignore the thermal constraint effect or implicitly assume that the SMA is symmetrically embedded. The composite beam with the SMA layer asymmetrically embedded is studied here, in which symmetric embedding is a special case. Based on the different kinematic assumptions, the results are different depending on the deflection magnitude because of the nonlinear hardening effect due to the (large) deflection. And this difference is systematically compared for both the deflection and the natural frequencies. For simple kinematic assumption, the governing equations are linear and analytical solution is available. But as the deflection increases to the large magnitude, the simple kinematic assumption does not really reflect the structural deflection and the complex one must be used. During the systematic comparison of computational results due to the different kinematic assumptions, the application range of the simple kinematic assumption is also evaluated. Besides the equilibrium study of the composite laminate with SMA embedded, the buckling, post-buckling, free and forced vibrations of the composite beam with the different configurations are also studied and compared.

Modeling Nonlinear Peeling of Ductile Thin Films-Critical Assessment of Analytical Bending Models Using FE Simulations

Three analytical double-parameter criteria based on a bending model and a two-dimensional finite element analysis model are presented for the modeling of ductile thin film undergoing a nonlinear peeling process. The bending model is based on different governing parameters: (1) the interfacial fracture toughness and the separation strength, (2) the interfacial fracture toughness and the crack tip slope angle, and (3) the interfacial fracture toughness and the critical Mises effective strain of the delaminated thin film at the crack tip. Thin film nonlinear peeling under steady-state condition is solved with the different governing parameters. In addition, the peeling test problem is simulated by using the elastic-plastic finite element analysis model. A critical assessment of the three analytical bending models is made by comparison of the bending model solutions with the finite element analysis model solutions. Furthermore, through analyses and comparisons for solutions based on both the bending model and the finite element analysis model, some connections between the bending model and the finite element analysis model are developed. Moreover, in the present research, the effect of different selections for cohesive zone shape on the ductile film peeling solutions is discussed.