Interação heparina-antitrombina : reconhecimento molecular caracterizado por ferramentas de modelagem molecular

A heparina foi isolada no início do século XX e permanece, até os dias atuais, como um dos mais importantes e eficientes agentes terapêuticos de ação antitrombótica. Sua atividade anticoagulante deve-se à ativação da antitrombina (AT), uma serpina responsável pela inibição fisiológica de serino-proteinases plasmáticas, tais como fIIa e fXa. Os esforços no sentido da elucidação dos aspectos estruturais e dinâmicos associados ao reconhecimento molecular da heparina pela AT, em nível atômico, vêm encontrando diversas dificuldades, principalmente associadas aos compostos sacarídicos. Em decorrência de sua elevada polaridade e flexibilidade, glicosaminoglicanos como a heparina são difíceis de estudar e modelar. Soma-se a isto o fato de que os resíduos de iduronato presentes na heparina (IdoA) apresentam um incomum equilíbrio conformacional entre estados de cadeira (1C4) e bote-torcido (2SO), sendo esta última estrutura postulada como a possível conformação bioativa. Sendo assim, este trabalho apresenta um estudo de modelagem molecular do perfil conformacional da heparina, tanto em solução quanto complexada à AT, utilizando cálculos ab initio e simulações de dinâmica molecular (DM) Em decorrência da ausência de parâmetros capazes de descrever polissacarídeos nos campos de força atualmente disponíveis, cargas atômicas foram geradas, utilizando-se os esquemas de Mulliken, Löwdin e cargas ajustadas ao Potencial Eletrostático, através de cálculos quantum-mecânicos na base 6-31G** e testadas na simulação de DM da heparina. Diversas condições de simulação, tais como modelos de água, concentrações de sais e as conformações 1C4 e 2SO do IdoA, foram avaliadas de forma a identificar as melhores condições para a descrição conformacional da heparina em solução. O protocolo de DM obtido foi então utilizado no estudo do complexo AT-heparina. Os resultados obtidos estão de acordo com os dados experimentais atualmente disponíveis acerca da conformação da heparina e da contribuição energética de cada resíduo de aminoácido da AT para a formação do complexo com a heparina. A partir dos cálculos ab initio realizados, foi proposto um refinamento na estrutura da heparina determinada por RMN, enquanto que as simulações de DM permitiram reinterpretar aspectos da estrutura tridimensional da AT determinada por cristalografia de raios-X. Adicionalmente, os dados obtidos sugerem que não há requerimento conformacional para a interação do IdoA com a AT Globalmente, os dados indicam que simulações de DM podem ser utilizadas para representar adequadamente a conformação da heparina, assim como para caracterizar e quantificar suas interações com a AT. Assim sendo, propomos o uso de simulações de DM do complexo entre a AT e a heparina, ou entre a AT e compostos derivados da heparina, como uma ferramenta útil no processo de desenvolvimento de novos agentes antitrombóticos e anticoagulantes.

Modelagem de previsões econômicas em cenários prospectivos

A estabilidade econômica que o Brasil atualmente experimenta permite resgatar a tradição de construção e análises prospectivas de médio e longo prazos. Isto remete à necessidade de se pensar mais profundamente acerca da possível evolução da economia brasileira, sendo mister o conhecimento de ferramentas de previsão. O objetivo deste trabalho é contribuir com este propósito. Avanços significativos têm sido observados na modelagem de previsões macro econômicas. Para se avaliar como os modelos de previsão estarão se desenvolvendo no futuro próximo, é necessário entender a evolução das abordagens dos modelos de previsão não-estruturais e estruturais. Como dependem da teoria econômica, os modelos estruturais ganham importância e descaso na medida em que a teoria evolui e cai em desuso. A marca registrada das previsões macroeconômicas nos próximos anos será o casamento das melhores abordagens estruturais e não-estruturais, facilitadas por avanços em técnicas numéricas e de simulação. Para ilustrar o trabalho de forma empírica, três cenários para a economia brasileira foram desenvolvidos, utilizando-se como base o arcabouço teórico resumido em uma das seções deste trabalho. Cenários potencialmente têm um valor muito grande na gestão de uma empresa ou de uma instituição. Cenários são a oitava ferramenta gerencial mais utilizada nas empresas em todo o mundo1 e esta dissertação é mais uma contribuição para este rico campo.

Análise da precificação de imóveis na cidade do Rio de Janeiro utilizando Modelagem Hedônica e os efeitos da autocorrelação espacial

A escolha da cidade do Rio de Janeiro como sede de grandes eventos esportivos mundiais, a Copa do Mundo de Futebol de 2014 e os Jogos Olímpicos de 2016, colocou-a no centro de investimentos em infraestrutura, mobilidade urbana e segurança pública, com consequente impacto no mercado imobiliário, tanto de novos lançamentos de empreendimentos, quanto na revenda de imóveis usados. Acredita-se que o preço de um imóvel dependa de uma relação entre suas características estruturais como quantidade de quartos, suítes, vagas de garagem, presença de varanda, tal como sua localização, proximidade com centros de trabalho, entretenimento e áreas valorizadas ou degradadas. Uma das técnicas para avaliar a contribuição dessas características para a formação do preço do imóvel, conhecido na Econométrica como Modelagem Hedônica de Preços, é uma aplicação de regressão linear multivariada onde a variável dependente é o preço e as variáveis independentes, as respectivas características que deseja-se modelar. A utilização da regressão linear implica em observar premissas que devem ser atendidas para a confiabilidade dos resultados a serem analisados, tais como independência e homoscedasticidade dos resíduos e não colinearidade entre as variáveis independentes. O presente trabalho objetiva aplicar a modelagem hedônica de preços para imóveis localizados na cidade do Rio de Janeiro em um modelo de regressão linear multivariada, em conjunto com outras fontes de dados para a construção de variáveis de acessibilidade e socioambiental a fim de verificar a relação de importância entre elas para a formação do preço e, em particular, exploramos brevemente a tendência de preços em função da distância a favelas. Em atenção aos pré-requisitos observados para a aplicação de regressão linear, verificamos que a premissa de independência dos preços não pode ser atestada devido a constatação da autocorrelação espacial entre os imóveis, onde não apenas as características estruturais e de acessibilidade são levadas em consideração para a precificação do bem, mas principalmente a influência mútua que os imóveis vizinhos exercem um ao outro.

Um método de linearização local com passo adaptativo para solução numérica de equações diferenciais estocásticas com ruído aditivo

Neste trabalho apresentamos um novo método numérico com passo adaptativo baseado na abordagem de linearização local, para a integração de equações diferenciais estocásticas com ruído aditivo. Propomos, também, um esquema computacional que permite a implementação eficiente deste método, adaptando adequadamente o algorítimo de Padé com a estratégia “scaling-squaring” para o cálculo das exponenciais de matrizes envolvidas. Antes de introduzirmos a construção deste método, apresentaremos de forma breve o que são equações diferenciais estocásticas, a matemática que as fundamenta, a sua relevância para a modelagem dos mais diversos fenômenos, e a importância da utilização de métodos numéricos para avaliar tais equações. Também é feito um breve estudo sobre estabilidade numérica. Com isto, pretendemos introduzir as bases necessárias para a construção do novo método/esquema. Ao final, vários experimentos numéricos são realizados para mostrar, de forma prática, a eficácia do método proposto, e compará-lo com outros métodos usualmente utilizados.

Modelagem e simulação de um sistema de bombeio mecânico em poços direcionais utilizando parâmetros concentrados

This work aims presenting the development of a model and computer simulation of a sucker rod pumping system. This system take into account the well geometry, the flow through the tubing, the dynamic behavior of the rod string and the use of a induction motor model. The rod string were modeled using concentrated parameters, allowing the use of ordinary differential equations systems to simulate it s behavior

Modelagem matemática para o transporte de partículas sujeitas a múltiplos mecanismos de retenção

Discrepancies between classical model predictions and experimental data for deep bed filtration have been reported by various authors. In order to understand these discrepancies, an analytic continuum model for deep bed filtration is proposed. In this model, a filter coefficient is attributed to each distinct retention mechanism (straining, diffusion, gravity interception, etc.). It was shown that these coefficients generally cannot be merged into an effective filter coefficient, as considered in the classical model. Furthermore, the derived analytic solutions for the proposed model were applied for fitting experimental data, and a very good agreement between experimental data and proposed model predictions were obtained. Comparison of the obtained results with empirical correlations allowed identifying the dominant retention mechanisms. In addition, it was shown that the larger the ratio of particle to pore sizes, the more intensive the straining mechanism and the larger the discrepancies between experimental data and classical model predictions. The classical model and proposed model were compared via statistical analysis. The obtained p values allow concluding that the proposed model should be preferred especially when straining plays an important role. In addition, deep bed filtration with finite retention capacity was studied. This work also involves the study of filtration of particles through porous media with a finite capacity of filtration. It was observed, in this case, that is necessary to consider changes in the boundary conditions through time evolution. It was obtained a solution for such a model using different functions of filtration coefficients. Besides that, it was shown how to build a solution for any filtration coefficient. It was seen that, even considering the same filtration coefficient, the classic model and the one here propposed, show different predictions for the concentration of particles retained in the porous media and for the suspended particles at the exit of the media

Modelagem numérica de estruturas de contenção atirantadas em areia

A numerical study on the behavior of tied-back retaining walls in sand, using the finite element method (FEM) is presented. The analyses were performed using the software Plaxis 2D, and were focused on the development of horizontal displacements, horizontal stresses, shear forces and bending moments in the structure during the construction process. Emphasis was placed on the evaluation of wall embedment, tie-back horizontal spacing, wall thickness, and free anchor length on wall behavior. A representative soil profile of a specific region at the City of Natal, Brazil, was used in the numerical analyses. New facilities built on this region often include retaining structures of the same type studied herein. Soil behavior was modeled using the Mohr-Coulomb constitutive model, whereas the structural elements were modeled using the linear elastic model. Shear strength parameters of the soil layers were obtained from direct shear test results conducted with samples collected at the studied site. Deformation parameters were obtained from empirical correlations from SPT test results carried out on the studied site. The results of the numerical analyses revealed that the effect of wall embedment on the investigated parameters is virtually negligible. Conversely, the tie-back horizontal spacing plays an important role on the investigated parameters. The results also demonstrated that the wall thickness significantly affects the wall horizontal displacements, and the shear forces and bending moments within the retaining structure. However, wall thickness was not found to influence horizontal stresses in the structure

Modelagem de Superfícies Seletivas de Freqüência e Antenas de Microfita utilizando Redes Neurais Artificiais

This work has as main objective the application of Artificial Neural Networks, ANN, in the resolution of problems of RF /microwaves devices, as for example the prediction of the frequency response of some structures in an interest region. Artificial Neural Networks, are presently a alternative to the current methods of analysis of microwaves structures. Therefore they are capable to learn, and the more important to generalize the acquired knowledge, from any type of available data, keeping the precision of the original technique and adding the low computational cost of the neural models. For this reason, artificial neural networks are being increasily used for modeling microwaves devices. Multilayer Perceptron and Radial Base Functions models are used in this work. The advantages/disadvantages of these models and the referring algorithms of training of each one are described. Microwave planar devices, as Frequency Selective Surfaces and microstrip antennas, are in evidence due the increasing necessities of filtering and separation of eletromagnetic waves and the miniaturization of RF devices. Therefore, it is of fundamental importance the study of the structural parameters of these devices in a fast and accurate way. The presented results, show to the capacities of the neural techniques for modeling both Frequency Selective Surfaces and antennas

Modelagem numérica de escoamento em padrão anular com transferência de calor e massa

Annular flow is the prevailing pattern in transport and energy conversion systems and therefore, one of the most important patterns in multiphase flow in ducts. The correct prediction of the pressure gradient and heat transfer coefficient is essential for optimizing the system s capacity. The objective of this work is to develop and implement a numerical algorithm capable of predicting hydrodynamic and thermal characteristics for upflow, vertical, annular flow. The numerical algorithm is then complemented with the physical modeling of phenomena that occurs in this flow pattern. These are, turbulence, entrainment and deposition and phase change. For the development of the numerical model, axial diffusion of heat and momentum is neglected. In this way the time-averaged equations are solved in their parabolic form obtaining the velocity and temperature profiles for each axial step at a time, together with the global parameters, namely, pressure gradient, mean film thickness and heat transfer coefficient, as well as their variation in the axial direction. The model is validated for the following conditions: fully-developed laminar flow with no entrainment; fully developed laminar flow with heat transfer, fully-developed turbulent flow with entrained drops, developing turbulent annular flow with entrained drops, and turbulent flow with heat transfer and phase change

Modelagem e simulação de um separador bifásico com inversão de fases induzida

The present work has the main goal to study the modeling and simulation of a biphasic separator with induced phase inversion, the MDIF, with the utilization of the finite differences method for the resolution of the partial differencial equations which describe the transport of contaminant s mass fraction inside the equipment s settling chamber. With this aim, was developed the deterministic differential model AMADDA, wich was admensionalizated and then semidiscretizated with the method of lines. The integration of the resultant system of ordinary differential equations was realized by means of a modified algorithm of the Adam-Bashfort- Moulton method, and the sthocastic optimization routine of Basin-Hopping was used in the model s parameter estimation procedure . With the aim to establish a comparative referential for the results obtained with the model AMADDA, were used experimental data presented in previous works of the MDIF s research group. The experimental data and those obtained with the model was assessed regarding its normality by means of the Shapiro-Wilk s test, and validated against the experimental results with the Student s t test and the Kruskal-Wallis s test, depending on the result. The results showed satisfactory performance of the model AMADDA in the evaluation of the MDIF s separation efficiency, being possible to determinate that at 1% significance level the calculated results are equivalent to those determinated experimentally in the reference works

Modelagem e simulação da solubilização da parafina em tubos circulares e em regime laminar

O óleo produzido nos novos campos de petróleo está cada vez mais parafínico e viscoso, com isso, à medida que o óleo é escoado, parafinas são depositadas sobre as paredes internas do tubo, e ao longo do tempo, tendem a reduzir drasticamente a área transversal ao escoamento. Visando estudar o processo de solubilização da parafina em dutos, esse trabalho objetiva desenvolver modelos matemáticos que represente o processo, com base nos fenômenos envolvidos no mesmo tais como transferência de massa, transferência de energia e equilíbrio sólido-líquido, implementando-os em um ambiente de desenvolvimento VBA (Visual Basic) for Excel ®. O presente trabalho foi realizado em quatro etapas: i) modelagem dos fenômenos de transferência de calor e massa, ii) modelagem da rotina dos coeficientes de atividade através do modelo UNIFAC e modelagem do sistema de equilíbrio sólido-líquido; iii) modelagem matemática do processo de solubilização e cálculo da espessura da parafina ao longo do tempo; iv) implementação dos modelos em um ambiente de desenvolvimento VBA for Excel® e criação de um simulador com uma interface gráfica, para simular o processo de solubilização da parafina depositada em dutos e sua otimização. O simulador conseguiu produzir soluções bastante adequadas, mantendo continuidade das equações diferenciáveis do balanço de energia e de massa, com uma interpretação física viável, sem a presença de dissipação de oscilações nos perfis de temperatura e massa. Além disso, esse simulador visa permitir a simulação nas diversas condições de escoamento, bem como compreender a importância das variáveis (vazão, temperatura de entrada, temperatura externa, cadeia carbônica do solvente). Através dos resultados foram possíveis verificar os perfis de temperatura, fração molar e o de solubilização

Avaliação e modelagem da absorção de H2S do gás natural em coluna de leito estagnado

Natural gas, although basically composed by light hydrocarbons, also presents contaminant gases in its composition, such as CO2 (carbon dioxide) and H2S (hydrogen sulfide). The H2S, which commonly occurs in oil and gas exploration and production activities, causes damages in oil and natural gas pipelines. Consequently, the removal of hydrogen sulfide gas will result in an important reduction in operating costs. Also, it is essential to consider the better quality of the oil to be processed in the refinery, thus resulting in benefits in economic, environmental and social areas. All this facts demonstrate the need for the development and improvement in hydrogen sulfide scavengers. Currently, the oil industry uses several processes for hydrogen sulfide removal from natural gas. However, these processes produce amine derivatives which can cause damage in distillation towers, can cause clogging of pipelines by formation of insoluble precipitates, and also produce residues with great environmental impact. Therefore, it is of great importance the obtaining of a stable system, in inorganic or organic reaction media, able to remove hydrogen sulfide without formation of by-products that can affect the quality and cost of natural gas processing, transport, and distribution steps. Seeking the study, evaluation and modeling of mass transfer and kinetics of hydrogen removal, in this study it was used an absorption column packed with Raschig rings, where the natural gas, with H2S as contaminant, passed through an aqueous solution of inorganic compounds as stagnant liquid, being this contaminant gas absorbed by the liquid phase. This absorption column was coupled with a H2S detection system, with interface with a computer. The data and the model equations were solved by the least squares method, modified by Levemberg-Marquardt. In this study, in addition to the water, it were used the following solutions: sodium hydroxide, potassium permanganate, ferric chloride, copper sulfate, zinc chloride, potassium chromate, and manganese sulfate, all at low concentrations (»10 ppm). These solutions were used looking for the evaluation of the interference between absorption physical and chemical parameters, or even to get a better mass transfer coefficient, as in mixing reactors and absorption columns operating in counterflow. In this context, the evaluation of H2S removal arises as a valuable procedure for the treatment of natural gas and destination of process by-products. The study of the obtained absorption curves makes possible to determine the mass transfer predominant stage in the involved processes, the mass transfer volumetric coefficients, and the equilibrium concentrations. It was also performed a kinetic study. The obtained results showed that the H2S removal kinetics is greater for NaOH. Considering that the study was performed at low concentrations of chemical reagents, it was possible to check the effect of secondary reactions in the other chemicals, especially in the case of KMnO4, which shows that your by-product, MnO2, acts in H2S absorption process. In addition, CuSO4 and FeCl3 also demonstrated to have good efficiency in H2S removal

Métodos numéricos para resolução de equações diferenciais ordinárias lineares baseados em interpolação por spline

In this work we have elaborated a spline-based method of solution of inicial value problems involving ordinary differential equations, with emphasis on linear equations. The method can be seen as an alternative for the traditional solvers such as Runge-Kutta, and avoids root calculations in the linear time invariant case. The method is then applied on a central problem of control theory, namely, the step response problem for linear EDOs with possibly varying coefficients, where root calculations do not apply. We have implemented an efficient algorithm which uses exclusively matrix-vector operations. The working interval (till the settling time) was determined through a calculation of the least stable mode using a modified power method. Several variants of the method have been compared by simulation. For general linear problems with fine grid, the proposed method compares favorably with the Euler method. In the time invariant case, where the alternative is root calculation, we have indications that the proposed method is competitive for equations of sifficiently high order.

Modelagem Matemática e Computacional de fenômenos eletrocinéticos em meios porosos carregados eletricamente

In this work we present a mathematical and computational modeling of electrokinetic phenomena in electrically charged porous medium. We consider the porous medium composed of three different scales (nanoscopic, microscopic and macroscopic). On the microscopic scale the domain is composed by a porous matrix and a solid phase. The pores are filled with an aqueous phase consisting of ionic solutes fully diluted, and the solid matrix consists of electrically charged particles. Initially we present the mathematical model that governs the electrical double layer in order to quantify the electric potential, electric charge density, ion adsorption and chemical adsorption in nanoscopic scale. Then, we derive the microscopic model, where the adsorption of ions due to the electric double layer and the reactions of protonation/ deprotanaç~ao and zeta potential obtained in modeling nanoscopic arise in microscopic scale through interface conditions in the problem of Stokes and Nerst-Planck equations respectively governing the movement of the aqueous solution and transport of ions. We developed the process of upscaling the problem nano/microscopic using the homogenization technique of periodic structures by deducing the macroscopic model with their respectives cell problems for effective parameters of the macroscopic equations. Considering a clayey porous medium consisting of kaolinite clay plates distributed parallel, we rewrite the macroscopic model in a one-dimensional version. Finally, using a sequential algorithm, we discretize the macroscopic model via the finite element method, along with the interactive method of Picard for the nonlinear terms. Numerical simulations on transient regime with variable pH in one-dimensional case are obtained, aiming computational modeling of the electroremediation process of clay soils contaminated

Desenvolvimento de dobras e falhas em ambiente distensional: Aplicação da modelagem física

The geological modeling allows, at laboratory scaling, the simulation of the geometric and kinematic evolution of geological structures. The importance of the knowledge of these structures grows when we consider their role in the creation of traps or conduits to oil and water. In the present work we simulated the formation of folds and faults in extensional environment, through physical and numerical modeling, using a sandbox apparatus and MOVE2010 software. The physical modeling of structures developed in the hangingwall of a listric fault, showed the formation of active and inactive axial zones. In consonance with the literature, we verified the formation of a rollover between these two axial zones. The crestal collapse of the anticline formed grabens, limited by secondary faults, perpendicular to the extension, with a curvilinear aspect. Adjacent to these faults we registered the formation of transversal folds, parallel to the extension, characterized by a syncline in the fault hangingwall. We also observed drag folds near the faults surfaces, these faults are parallel to the fault surface and presented an anticline in the footwall and a syncline hangingwall. To observe the influence of geometrical variations (dip and width) in the flat of a flat-ramp fault, we made two experimental series, being the first with the flat varying in dip and width and the second maintaining the flat variation in width but horizontal. These experiments developed secondary faults, perpendicular to the extension, that were grouped in three sets: i) antithetic faults with a curvilinear geometry and synthetic faults, with a more rectilinear geometry, both nucleated in the base of sedimentary pile. The normal antithetic faults can rotate, during the extension, presenting a pseudo-inverse kinematics. ii) Faults nucleated at the top of the sedimentary pile. The propagation of these faults is made through coalescence of segments, originating, sometimes, the formation of relay ramps. iii) Reverse faults, are nucleated in the flat-ramp interface. Comparing the two models we verified that the dip of the flat favors a differentiated nucleation of the faults at the two extremities of the mater fault. V These two flat-ramp models also generated an anticline-syncline pair, drag and transversal folds. The anticline was formed above the flat being sub-parallel to the master fault plane, while the syncline was formed in more distal areas of the fault. Due the geometrical variation of these two folds we can define three structural domains. Using the physical experiments as a template, we also made numerical modeling experiments, with flat-ramp faults presenting variation in the flat. Secondary antithetic, synthetic and reverse faults were generated in both models. The numerical modeling formed two folds, and anticline above the flat and a syncline further away of the master fault. The geometric variation of these two folds allowed the definition of three structural domains parallel to the extension. These data reinforce the physical models. The comparisons between natural data of a flat-ramp fault in the Potiguar basin with the data of physical and numerical simulations, showed that, in both cases, the variation of the geometry of the flat produces, variation in the hangingwall geometry