Insights into mechanism kinematics for protein motion simulation

Background: The high demanding computational requirements necessary to carry out protein motion simulations make it difficult to obtain information related to protein motion. On the one hand, molecular dynamics simulation requires huge computational resources to achieve satisfactory motion simulations. On the other hand, less accurate procedures such as interpolation methods, do not generate realistic morphs from the kinematic point of view. Analyzing a protein's movement is very similar to serial robots; thus, it is possible to treat the protein chain as a serial mechanism composed of rotational degrees of freedom. Recently, based on this hypothesis, new methodologies have arisen, based on mechanism and robot kinematics, to simulate protein motion. Probabilistic roadmap method, which discretizes the protein configurational space against a scoring function, or the kinetostatic compliance method that minimizes the torques that appear in bonds, aim to simulate protein motion with a reduced computational cost. Results: In this paper a new viewpoint for protein motion simulation, based on mechanism kinematics is presented. The paper describes a set of methodologies, combining different techniques such as structure normalization normalization processes, simulation algorithms and secondary structure detection procedures. The combination of all these procedures allows to obtain kinematic morphs of proteins achieving a very good computational cost-error rate, while maintaining the biological meaning of the obtained structures and the kinematic viability of the obtained motion. Conclusions: The procedure presented in this paper, implements different modules to perform the simulation of the conformational change suffered by a protein when exerting its function. The combination of a main simulation procedure assisted by a secondary structure process, and a side chain orientation strategy, allows to obtain a fast and reliable simulations of protein motion.

A regulação das patentes farmacêuticas no Brasil: entre saúde pública, política e direito

O objetivo geral da tese é aprofundar a reflexão sobre a regulação e o exame de qualidade de patentes farmacêuticas no Brasil, em um contexto de implantação de dispositivos legais conhecidos como TRIPS-Plus ao redor do mundo. Para isso, são discutidos os mecanismos jurídicos e políticos de proteção à saúde relacionados à propriedade intelectual. Analisam-se especificamente do ponto de vista sociológico as experiências de anuência prévia para pedidos de patentes envolvendo produtos e processos farmacêuticos da Agência Nacional de Vigilância Sanitária (Anvisa) e o uso do subsídio ao exame técnico. Em termos metodológicos, consideram-se as ações do Governo brasileiro entre 1996 a 2012, propostas de mudança da Lei de Propriedade Industrial brasileira e controvérsias ligadas a algumas modalidades de reivindicação, como polimorfos, patentes de seleção e segundo uso médico. As técnicas de pesquisa utilizadas também incluem o levantamento de material de imprensa, textos de leis, documentos e decretos relativos a medicamentos e propriedade intelectual, assim como de pedidos de patentes e de decisões judiciais concernindo à temática. Optou-se ainda por realizar entrevistas com gestores, examinadores de patentes, juristas e membros de ONGs. As conclusões indicam que as práticas regulatórias ligadas ao setor saúde não podem ser reduzidas ao simples corpo de regras formais presentes neste domínio, mas sim entendidas como agenciamentos entre atores, tipos distintos de saberes e de ferramentas de intervenção. A regulação dos direitos de propriedade intelectual relativos a produtos e processos farmacêuticos no Brasil está ligada a um processo, onde se verifica a disputa em torno de diferentes projetos e visões de mundo de grupos com maior ou menor poder para direcionar este processo. Os dispositivos da anuência prévia e do subsídio ao exame técnico apresentam-se como elementos reguladores da propriedade intelectual de medicamentos e de impacto sobre exame de qualidade de patentes farmacêuticas, contribuindo para a consideração de questões de saúde pública ao longo da concessão destas patentes.

Thermodynamic damage mechanism of transparent films caused by a low-power laser

A new model for analyzing the laser-induced damage process is provided. In many damage pits, the melted residue can been found. This is evidence of the phase change of materials. Therefore the phase change of materials is incorporated into the mechanical damage mechanism of films. Three sequential stages are discussed: no phase change, liquid phase change, and gas phase change. To study the damage mechanism and process, two kinds of stress have been considered: thermal stress and deformation stress. The former is caused by the temperature gradient and the latter is caused by high-pressure drive deformation. The theory described can determine the size of the damage pit. (c) 2006 Optical Society of America.

Development in laser induced extrinsic absorption damage mechanism of dielectric films

Absorption of host and the temperature-dependence of absorption coefficient have been considered in evaluating temperatures distribution in films, when laser pulse irradiates on films. Absorption of dielectric materials experience three stages with the increase of temperature: multi-photon absorption; single photon absorption; metallic absorption. These different absorption mechanisms correspond to different band gap energies of materials, which will decrease when the temperature of materials increases. evaluating results indicate that absorption of host increases rapidly when the laser pulse will be over. If absorption of host and the temperature-dependence of absorption are considered, the material temperatures in films will be increased by a factor of four.

Mechanism initiated by nanoabsorber for UV nanosecond-pulse-driven damage of dielectric coatings

A model of plasma formation induced by UV nanosecond pulselaser interaction with SiO2 thin film based on nanoabsorber is proposed. The model considers the temperature dependence of band gap. The numerical results show that during the process of nanosecond pulsed-laser interaction with SiO2 thin film, foreign inclusion which absorbs a fraction of incident radiation heats the surrounding host material through heat conduction causing the decrease of the band gap and consequently, the transformation of the initial transparent matrix into an absorptive medium around the inclusion, thus facilitates optical damage. Qualitative comparison with experiments is also provided. (C) 2008 Optical Society of America.

Study on the activation mechanism of BCL-2 related ovarian killer (BOK)

BCL-2 family proteins are key regulators of the mitochondrial apoptotic machinery, controlling the mitochondrial outer membrane (MOM) permeabilization (MOMP). BCL-2 related Ovarian Killer (BOK) is a poorly understood pro-apoptotic member of this protein family. It has been reported that BOK localizes predominantly (although not exclusively) at membranes of the endoplasmic reticulum and of the Golgi apparatus. However, it is unclear whether BOK also operates at the MOM to promote apoptosis, as other pro-apoptotic BCL-2 family members do. Basing on the fact that the other two BAX-like pro-apoptotic members have been reported to oligomerize in order to induce MOMP, site-directed mutagenesis was used to generate two point mutations that predictably eliminated BOK’s oligomerization capacity. Then, the effect of such mutations on BOK’s membrane activity was examined using fluorescence spectroscopy.

As joint ventures na indústria do petróleo: um olhar crítico sobre a intervenção do Estado na autonomia privada

A atividade empresarial requer dos agentes econômicos soluções práticas para a transposição dos riscos inerentes ao exercício da empresa. A engenhosidade dos homens de negócio tem visualizado nos denominados contratos associativos um importante mecanismo para o sucesso do empreendimento. Na indústria do petróleo, especificamente no setor do upstream, as parcerias empresariais mostram-se como importante meio para compartilhamento dos riscos geológico, financeiro e político inerentes a esta atividade. Neste sentido o trabalho desenvolvido busca efetuar uma análise das associações empresariais, especialmente aquelas consagradas na prática como joint ventures, especificando suas peculiaridades, para posteriormente analisar a situação destas dentro do novo marco regulatório que se firma para exploração de petróleo, gás natural e outros hidrocarbonetos na região denominada de pré-sal e outras áreas estratégicas. Nesse sentido, foram analisadas as mudanças instituídas pela Lei n. 12.351/2010, a qual instituiu o modelo de partilha de produção, no qual se observou uma mudança do Estado que deixa de ser mero regulador para atuar mais diretamente, de modo a influenciar a atuação empresarial, limitando a autonomia privada no referido setor.