QSAR e dinâmica molecular no estudo de sistemas biomoleculares: predição da atividade biológica de antagonistas do receptor sigma-1 e simulações de bicamadas lipídicas

Diferentes abordagens teóricas têm sido utilizadas em estudos de sistemas biomoleculares com o objetivo de contribuir com o tratamento de diversas doenças. Para a dor neuropática, por exemplo, o estudo de compostos que interagem com o receptor sigma-1 (Sig-1R) pode elucidar os principais fatores associados à atividade biológica dos mesmos. Nesse propósito, estudos de Relações Quantitativas Estrutura-Atividade (QSAR) utilizando os métodos de regressão por Mínimos Quadrados Parciais (PLS) e Rede Neural Artificial (ANN) foram aplicados a 64 antagonistas do Sig-1R pertencentes à classe de 1-arilpirazóis. Modelos PLS e ANN foram utilizados com o objetivo de descrever comportamentos lineares e não lineares, respectivamente, entre um conjunto de descritores e a atividade biológica dos compostos selecionados. O modelo PLS foi obtido com 51 compostos no conjunto treinamento e 13 compostos no conjunto teste (r² = 0,768, q² = 0,684 e r²teste = 0,785). Testes de leave-N-out, randomização da atividade biológica e detecção de outliers confirmaram a robustez e estabilidade dos modelos e mostraram que os mesmos não foram obtidos por correlações ao acaso. Modelos também foram gerados a partir da Rede Neural Artificial Perceptron de Multicamadas (MLP-ANN), sendo que a arquitetura 6-12-1, treinada com as funções de transferência tansig-tansig, apresentou a melhor resposta para a predição da atividade biológica dos compostos (r²treinamento = 0,891, r²validação = 0,852 e r²teste = 0,793). Outra abordagem foi utilizada para simular o ambiente de membranas sinápticas utilizando bicamadas lipídicas compostas por POPC, DOPE, POPS e colesterol. Os estudos de dinâmica molecular desenvolvidos mostraram que altas concentrações de colesterol induzem redução da área por lipídeo e difusão lateral e aumento na espessura da membrana e nos valores de parâmetro de ordem causados pelo ordenamento das cadeias acil dos fosfolipídeos. As bicamadas lipídicas obtidas podem ser usadas para simular interações entre lipídeos e pequenas moléculas ou proteínas contribuindo para as pesquisas associadas a doenças como Alzheimer e Parkinson. As abordagens usadas nessa tese são essenciais para o desenvolvimento de novas pesquisas em Química Medicinal Computacional.

Surface wind-stress threshold for glacial Atlantic overturning

Using a coupled model of intermediate complexity the sensitivity of the last glacial maximum (LGM) Atlantic meridional overturning circulation (AMOC) to the strength of surface wind-stress is investigated. A threshold is found below which North Atlantic deep water formation (DWF) takes place south of Greenland and the AMOC is relatively weak. Above this threshold, DWF occurs north of the Greenland-Scotland ridge, leading to a vigorous AMOC. This nonlinear behavior is explained through enhanced salt transport by the wind-driven gyre circulation and the overturning itself. Both pattern and magnitude of the Nordic Sea's temperature difference between strong and weak AMOC states are consistent with those reconstructed for abrupt climate changes of the last glacial period. Our results thus point to a potentially relevant role of surface winds in these phenomena.

Um modelo multiescala concorrente para representar o processo de fissuração do concreto.

Este trabalho propõe uma técnica de modelagem multiescala concorrente do concreto considerando duas escalas distintas: a mesoescala, onde o concreto é modelado como um material heterogêneo, e a macroescala, na qual o concreto é tratado como um material homogêneo. A heterogeneidade da estrutura mesoscópica do concreto é idealizada considerando três fases distintas, compostas pelos agregados graúdos e argamassa (matriz), estes considerados materiais homogêneos, e zona de transição interfacial (ZTI), tratada como a parte mais fraca entre as três fases. O agregado graúdo é gerado a partir de uma curva granulométrica e posicionado na matriz de forma aleatória. Seu comportamento mecânico é descrito por um modelo constitutivo elástico-linear, devido a sua maior resistência quando comparado com as outras duas fases do concreto. Elementos finitos contínuos com alta relação de aspecto em conjunto com um modelo constitutivo de dano são usados para representar o comportamento não linear do concreto, decorrente da iniciação de fissuras na ZTI e posterior propagação para a matriz, dando lugar à formação de macrofissuras. Os elementos finitos de interface com alta relação de aspecto são inseridos entre todos os elementos regulares da matriz e entre os da matriz e agregados, representando a ZTI, tornando-se potenciais caminhos de propagação de fissuras. No estado limite, quando a espessura do elemento de interface tende a zero (h ?0) e, consequentemente, a relação de aspecto tende a infinito, estes elementos apresentam a mesma cinemática da aproximação contínua de descontinuidades fortes (ACDF), sendo apropriados para representar a formação de descontinuidades associados a fissuras, similar aos modelos coesivos. Um modelo de dano à tração é proposto para representar o comportamento mecânico não linear das interfaces, associado à formação de fissuras, ou até mesmo ao eventual fechamento destas. A fim de contornar os problemas causados pela malha de elementos finitos de transição entre as malhas da macro e da mesoescala, que, em geral, apresentam diferenças expressivas 5 de refinamento, utiliza-se uma técnica recente de acoplamento de malhas não conformes. Esta técnica é baseada na definição de elementos finitos de acoplamento (EFAs), os quais são capazes de estabelecer a continuidade de deslocamento entre malhas geradas de forma completamente independentes, sem aumentar a quantidade total de graus de liberdade do problema, podendo ser utilizados tanto para acoplar malhas não sobrepostas quanto sobrepostas. Para tornar possível a análise em multiescala em casos nos quais a região de localização de deformações não pode ser definida a priori, propõe-se uma técnica multiescala adaptativa. Nesta abordagem, usa-se a distribuição de tensões da escala macroscópica como um indicador para alterar a modelagem das regiões críticas, substituindo-se a macroescala pela mesoescala durante a análise. Consequentemente, a malha macroscópica é automaticamente substituída por uma malha mesoscópica, onde o comportamento não linear está na iminência de ocorrer. Testes numéricos são desenvolvidos para mostrar a capacidade do modelo proposto de representar o processo de iniciação e propagação de fissuras na região tracionada do concreto. Os resultados numéricos são comparados com os resultados experimentais ou com aqueles obtidos através da simulação direta em mesoescala (SDM).

Strength analysis of steel-concrete composite beams in combined bending and shear

Despite experimental evidences, the contributions of the concrete slab and composite action to the vertical shear strength of simply supported steel-concrete composite beams are not considered in current design codes, which lead to conservative designs. In this paper, the finite element method is used to investigate the flexural and shear strengths of simply supported composite beams under combined bending and shear. A three-dimensional finite element model has been developed to account for geometric and material nonlinear behavior of composite beams, and verified by experimental results. The verified finite element model is than employed to quantify the contributions of the concrete slab and composite action to the moment and shear capacities of composite beams. The effect of the degree of shear connection on the vertical shear strength of deep composite beams loaded in shear is studied. Design models for vertical shear strength including contributions from the concrete slab and composite action and for the ultimate moment-shear interaction ate proposed for the design of simply supported composite beams in combined bending and shear. The proposed design models provide a consistent and economical design procedure for simply supported composite beams.

Analysis of chaotic instabilities in a rotating body with internal energy dissipation

Melnikov's method is used to analytically predict the onset of chaotic instability in a rotating body with internal energy dissipation. The model has been found to exhibit chaotic instability when a harmonic disturbance torque is applied to the system for a range of forcing amplitude and frequency. Such a model may be considered to be representative of the dynamical behavior of a number of physical systems such as a spinning spacecraft. In spacecraft, disturbance torques may arise under malfunction of the control system, from an unbalanced rotor, from vibrations in appendages or from orbital variations. Chaotic instabilities arising from such disturbances could introduce uncertainties and irregularities into the motion of the multibody system and consequently could have disastrous effects on its intended operation. A comprehensive stability analysis is performed and regions of nonlinear behavior are identified. Subsequently, the closed form analytical solution for the unperturbed system is obtained in order to identify homoclinic orbits. Melnikov's method is then applied on the system once transformed into Hamiltonian form. The resulting analytical criterion for the onset of chaotic instability is obtained in terms of critical system parameters. The sufficient criterion is shown to be a useful predictor of the phenomenon via comparisons with numerical results. Finally, for the purposes of providing a complete, self-contained investigation of this fundamental system, the control of chaotic instability is demonstated using Lyapunov's method.

Contribuição ao estudo de treliças não lineares considerando efeitos térmicos

This work presents the numerical analysis of nonlinear trusses summited to thermomechanical actions with Finite Element Method (FEM). The proposed formulation is so-called positional FEM and it is based on the minimum potential energy theorem written according to nodal positions, instead of displacements. The study herein presented considers the effects of geometric and material nonlinearities. Related to dynamic problems, a comparison between different time integration algorithms is performed. The formulation is extended to impact problems between trusses and rigid wall, where the nodal positions are constrained considering nullpenetration condition. In addition, it is presented a thermodynamically consistent formulation, based on the first and second law of thermodynamics and the Helmholtz free-energy for analyzing dynamic problems of truss structures with thermoelastic and thermoplastic behavior. The numerical results of the proposed formulation are compared with examples found in the literature.

Use of active power filter to reduce the effects of harmonics in solid oxide fuel cells

The Solid Oxide Fuel Cell (SOFC) is a class of fuel cells that is capable of generating very high levels of power at high temperatures. SOFCs are used for stationary power generation and as Combined Heat and Power (CHP) systems. In spite of all the beneficial features of the SOFC, the propagation of ripple currents, due to nonlinear loads, is a challenging problem, as it interferes with the physical operation of the fuel cell. The purpose of this thesis is to identify the cause of ripples and attempt to eliminate or reduce the ripple propagation through the use of Active Power Filters (APF). To this end, a systematic approach to modeling the fuel cell to account for its nonlinear behavior in the presence of current ripples is presented. A model of a small fuel cell power system which consists of a fuel cell, a DC-DC converter, a single-phase inverter and a nonlinear load is developed in MATLAB/Simulink environment. The extent of ripple propagation, due to variations in load magnitude and frequency, are identified using frequency spectrum analysis. In order to reduce the effects of ripple propagation, an APF is modeled to remove ripples from the DC fuel cell current. The emphasis of this thesis is based on the idea that small fuel cell systems cannot implement large passive filters to cancel the effects of ripple propagation and hence, the compact APF topology effectively protects the fuel cell from propagating ripples and improves its electrical performance.

Vibrational characteristics of brain magnetic resonance elastography

This thesis aims to investigate vibrational characteristics of magnetic resonance elastography (MRE) of the brain. MRE is a promising, non-invasive methodology for the mapping of shear stiffness of the brain. A mechanical actuator shakes the brain and generates shear waves, which are then imaged with a special MRI sequence sensitive to sub-millimeter displacements. This research focuses on exploring the profile of vibrations utilized in brain elastography from the standpoint of ultimately investigating nonlinear behavior of the tissue. The first objective seeks to demonstrate the effects of encoding off-frequency vibrations using standard MRE methodologies. Vibrations of this nature can arise from nonlinearities in the system and contaminate the results of the measurement. The second objective is to probe nonlinearity in the dynamic brain system using MRE. A non-parametric decomposition technique, novel to the MRE field, is introduced and investigated.

Nonlinear Pile Behavior in Integral Abutment Bridges, HR-227, Part 1, 1982

The highway departments of all fifty states were contacted to find the extent of application of integral abutment bridges, to survey the different guidelines used for analysis and design of integral abutment bridges, and to assess the performance of such bridges through the years. The variation in design assumptions and length limitations among the various states in their approach to the use of integral abutments is discussed. The problems associated with lateral displacements at the abutment, and the solutions developed by the different states for most of the ill effects of abutment movements are summarized in the report. An algorithm based on a state-of-the-art nonlinear finite element procedure was developed and used to study piling stresses and pile-soil interaction in integral abutment bridges. The finite element idealization consists of beam-column elements with geometric and material nonlinearities for the pile and nonlinear springs for the soil. An idealized soil model (modified Ramberg-Osgood model) was introduced in this investigation to obtain the tangent stiffness of the nonlinear spring elements. Several numerical examples are presented in order to establish the reliability of the finite element model and the computer software developed. Three problems with analytical solutions were first solved and compared with theoretical solutions. A 40 ft H pile (HP 10 X 42) in six typical Iowa soils was then analyzed by first applying a horizontal displacement (to simulate bridge motion) and no rotation at the top and then applying a vertical load V incrementally until failure occurred. Based on the numerical results, the failure mechanisms were generalized to be of two types: (a) lateral type failure and (b) vertical type failure. It appears that most piles in Iowa soils (sand, soft clay and stiff clay) failed when the applied vertical load reached the ultimate soil frictional resistance (vertical type failure). In very stiff clays, however, the lateral type failure occurs before vertical type failure because the soil is sufficiently stiff to force a plastic hinge to form in the pile as the specified lateral displacement is applied. Preliminary results from this investigation showed that the vertical load-carrying capacity of H piles is not significantly affected by lateral displacements of 2 inches in soft clay, stiff clay, loose sand, medium sand and dense sand. However, in very stiff clay (average blow count of 50 from standard penetration tests), it was found that the vertical load carrying capacity of the H pile is reduced by about 50 percent for 2 inches of lateral displacement and by about 20 percent for lateral displacement of 1 inch. On the basis of the preliminary results of this investigation, the 265-feet length limitation in Iowa for integral abutment concrete bridges appears to be very conservative.

Full instability behavior of N-dimensional dynamical systems with a one-directional nonlinear vector field

We show how certain N-dimensional dynamical systems are able to exploit the full instability capabilities of their fixed points to do Hopf bifurcations and how such a behavior produces complex time evolutions based on the nonlinear combination of the oscillation modes that emerged from these bifurcations. For really different oscillation frequencies, the evolutions describe robust wave form structures, usually periodic, in which selfsimilarity with respect to both the time scale and system dimension is clearly appreciated. For closer frequencies, the evolution signals usually appear irregular but are still based on the repetition of complex wave form structures. The study is developed by considering vector fields with a scalar-valued nonlinear function of a single variable that is a linear combination of the N dynamical variables. In this case, the linear stability analysis can be used to design N-dimensional systems in which the fixed points of a saddle-node pair experience up to N21 Hopf bifurcations with preselected oscillation frequencies. The secondary processes occurring in the phase region where the variety of limit cycles appear may be rather complex and difficult to characterize, but they produce the nonlinear mixing of oscillation modes with relatively generic features

Prediction of dynamical, nonlinear, and unstable process behavior

Process scheduling techniques consider the current load situation to allocate computing resources. Those techniques make approximations such as the average of communication, processing, and memory access to improve the process scheduling, although processes may present different behaviors during their whole execution. They may start with high communication requirements and later just processing. By discovering how processes behave over time, we believe it is possible to improve the resource allocation. This has motivated this paper which adopts chaos theory concepts and nonlinear prediction techniques in order to model and predict process behavior. Results confirm the radial basis function technique which presents good predictions and also low processing demands show what is essential in a real distributed environment.

Experimental characterization of nonlinear systems: a real-time evaluation of the analogous Chua`s circuit behavior

This paper presents an experimental characterization of the behavior of an analogous version of the Chua`s circuit. The electronic circuit signals are captured using a data acquisition board (DAQ) and processed using LabVIEW environment. The following aspects of the time series analysis are analyzed: time waveforms, phase portraits, frequency spectra, Poincar, sections, and bifurcation diagram. The circuit behavior is experimentally mapped with the parameter variations, where are identified equilibrium points, periodic and chaotic attractors, and bifurcations. These analysis techniques are performed in real-time and can be applied to characterize, with precision, several nonlinear systems.

Dependence of the nonlinear electrical behavior of SnO2-based varistors on Cr2O3 addition

Tin dioxide varistors doped with Coo, ZnO, Ta2O5 and Cr2O3 were prepared by the mixed oxide method. Temperature dependent impedance spectroscopy revealed two different activation energies, one at low frequencies and the other at high frequencies. These activation energies were associated with the adsorption and reaction of O-2 species at the grain boundary interface. We show that Cr2O3 improves the varistor properties, generating sites for the adsorption of O' and O at the grain boundary region. The O' and O defects are truly responsible for the barrier formation at the grain boundary interface. (c) 2005 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

The non-ideal problem behavior using a dynamic vibration absorber with nonlinear essential stiffness and timedependent damping properties

The purpose of this study is to develop a dynamic vibration absorber using viscoelastic material with nonlinear essential stiffness and time-dependent damping properties for a non-ideal vibrating system with Sommerfeld effect, resonance capture, and jump phenomenon. The absorber is a mass-bar subsystem that consists of a viscoelastic bar with memory attached to mass, in which the internal dissipative forces depend on current, deformations, and its operational frequency varies with limited temperature. The non-ideal vibrating system consists of a linear (nonlinear) oscillator (plane frame structure) under excitation, via spring connector, of a DC-motor with limited power supply. A viscoelastic dynamic absorber modeled with elastic stiffness essentially nonlinearities was developed to further reduce the Sommerfeld effect and the response of the structure. The numerical results show the performance of the absorber on the non-ideal system response through the resonance curves, time histories, and Poincarésections. Furthermore, the structure responses using the viscoelastic damper with and without memory were studied. © IMechE 2012.