MPO Inhibitors Selected by Virtual Screening

The hemeprotein myeloperoxidase (MPO) participates in innate immune defense through its ability to generate potent microbicidal oxidants. However, these oxidants are also key mediators of the tissue damage associated with many inflammatory diseases. Thus, there is considerable interest in developing therapeutically useful MPO inhibitors. Here, we used structure-based drug design (SBDD) and ligand-based drug design (LBDD) to select for potentially new and selective MPO inhibitors. A pharmacophore model was developed based on the crystal structure of human MPO in complex with salicylhydroxamic acid (SHA), a known inhibitor of the enzyme. The pharmacophore model was used to screen the ZINC database for potential ligands, which were further filtered on the basis of their physical-chemical properties and docking score. The filtered compounds were visually inspected, and nine were purchased for experimental studies. Surprisingly, almost all of the selected compounds belonged to the aromatic hydrazide class, which had been previously described as MPO inhibitors. The compounds selected by virtual screening were shown to inhibit the chlorinating activity of MPO; the top four compounds displayed IC(50) values ranging from 1.0 to 2.8 mM. MPO inactivation by the most effective compound was shown to be irreversible. Overall, our results show that SBDD and LBDD may be useful for the rational development of new MPO inhibitors.

Uncovering false positives on a virtual screening search for cruzain inhibitors

Some unexpected promiscuous inhibitors were observed in a virtual screening protocol applied to select cruzain inhibitors from the ZINC database. Physical-chemical and pharmacophore model filters were used to reduce the database size. The selected compounds were docked into the cruzain active site. Six hit compounds were tested as inhibitors. Although the compounds were designed to be nucleophilically attacked by the catalytic cysteine of cruzain, three of them showed typical promiscuous behavior, revealing that false positives are a prevalent concern in VS programs. (C) 2007 Elsevier Ltd. All rights reserved.

Nyttan med virtuella provrum : En utvärderingsstudie av virtuella provrum för online-shopping, med fokus på användbarhet.

Den relativt nya företeelsen BrandME – I am the brand är en eTjänst som fungerar som ett virtuellt provrum och därmed gör det möjligt att kunna prova på kläder virtuellt. Till sin hjälp har man bland annat använt sig av 3D-grafik samt databaser. BrandME är en produkt av det kanadensiska företaget My Virtual Model, ett företag som har arbetat med att sätta standarder för virtuell identitet sedan år 2000.Då denna företeelse är relativ ny, skapar detta utrymme för undersökning och bedömning om huruvida välutvecklad och välanpassad BrandME är. Undersökningens syfte är att utvärdera BrandME för att sedan kunna fastställa nyttan med denna eTjänst. Under utvärderingen koncentrerar vi oss dels på användbarheten hos BrandME och dels på utformningen av BrandME.

Temperature Dynamics Investigation At Small And Shallow Lakes Using Hydrodynamic Model

A three-dimensional time-dependent hydrodynamic and heat transport model of Lake Binaba, a shallow and small dam reservoir in Ghana, emphasizing the simulation of dynamics and thermal structure has been developed. Most numerical studies of temperature dynamics in reservoirs are based on one- or two-dimensional models. These models are not applicable for reservoirs characterized with complex flow pattern and unsteady heat exchange between the atmosphere and water surface. Continuity, momentum and temperature transport equations have been solved. Proper assignment of boundary conditions, especially surface heat fluxes, has been found crucial in simulating the lake’s hydrothermal dynamics. This model is based on the Reynolds Average Navier-Stokes equations, using a Boussinesq approach, with a standard k − ε turbulence closure to solve the flow field. The thermal model includes a heat source term, which takes into account the short wave radiation and also heat convection at the free surface, which is function of air temperatures, wind velocity and stability conditions of atmospheric boundary layer over the water surface. The governing equations of the model have been solved by OpenFOAM; an open source, freely available CFD toolbox. As its core, OpenFOAM has a set of efficient C++ modules that are used to build solvers. It uses collocated, polyhedral numerics that can be applied on unstructured meshes and can be easily extended to run in parallel. A new solver has been developed to solve the hydrothermal model of lake. The simulated temperature was compared against a 15 days field data set. Simulated and measured temperature profiles in the probe locations show reasonable agreement. The model might be able to compute total heat storage of water bodies to estimate evaporation from water surface.

Software Tools For Large Scale Interactive Hydrodynamic Modeling

Running hydrodynamic models interactively allows both visual exploration and change of model state during simulation. One of the main characteristics of an interactive model is that it should provide immediate feedback to the user, for example respond to changes in model state or view settings. For this reason, such features are usually only available for models with a relatively small number of computational cells, which are used mainly for demonstration and educational purposes. It would be useful if interactive modeling would also work for models typically used in consultancy projects involving large scale simulations. This results in a number of technical challenges related to the combination of the model itself and the visualisation tools (scalability, implementation of an appropriate API for control and access to the internal state). While model parallelisation is increasingly addressed by the environmental modeling community, little effort has been spent on developing a high-performance interactive environment. What can we learn from other high-end visualisation domains such as 3D animation, gaming, virtual globes (Autodesk 3ds Max, Second Life, Google Earth) that also focus on efficient interaction with 3D environments? In these domains high efficiency is usually achieved by the use of computer graphics algorithms such as surface simplification depending on current view, distance to objects, and efficient caching of the aggregated representation of object meshes. We investigate how these algorithms can be re-used in the context of interactive hydrodynamic modeling without significant changes to the model code and allowing model operation on both multi-core CPU personal computers and high-performance computer clusters.

Motivations for knowledge sharing in virtual social networks: a comparative study between Brazil and France

Sociedades pós-modernas caracterizam-se pela transição de economias baseadas em ativos tangíveis para economias de conhecimento, onde indivíduos vivenciam uma imprescindível conectividade, mas ao mesmo tempo, experimentam um enfraquecimento das estruturas sociais, que tem generado uma crescente necessidade de se criar bases cognitivas e afetivas para a vida (Rheingold, 1992; Wasko & Farah, 2005; Arvidsson, 2008). Nesse cenário se desenvolve o fenômeno das redes sociais virtuais, agregando milhões de pessoas que compartilham mensagens de texto, imagens e vídeos todos os dias (Nielsen, 2012) fazendo com que organizações privadas foquem cada vez mais seus investimentos para acompanhar as novas tendências (McWilliam, 2000; Reichheld & Schefter, 2000; Yoo, Suh & Lee, 2002; Arvidsson, 2008). Consequentemente, uma das mais importantes questões que vem ganhando importância no meio academico e entre profissionais da área é justamente: por que as pessoas compartilham conhecimento online? (Monge, Fulk, Kalman, Flanigan, Parnassa & Rumsey, 1998; Lin, 2001) Por meio de uma metodologia de estudo de caso conduzida no Brasil e na França, este estudo objetiva produzir uma relevante revisão teórica acerca do tema, trazendo novas idéias de diferentes contextos, e propondo um modelo para avaliar as principais motivações que conduzem indivíduos a compartilhar conhecimento em redes sociais virtuais. Essas razões foram estruturadas em cinco dimensões: capital estrutural, cognitivo e relacional, motivações pessoais e razões monetárias (Nahapiet & Ghoshal, 1998; Wasko & Faraj, 2005; Chiu et al, 2006). As evidências sugerem que o processo de participar e compartilhar conhecimento em redes sociais virtuais é resultado de uma complexa combinação de motivações de orientação pessoal e coletiva, que parecem variar pouco de acordo com os diferentes objetivos e contextos dessas comunidades, onde as razões financeiras parecem ser secundárias.

A low cost one-camera optical tracking system for indoor wide-area augmented and virtual reality environments

In the last years the number of industrial applications for Augmented Reality (AR) and Virtual Reality (VR) environments has significantly increased. Optical tracking systems are an important component of AR/VR environments. In this work, a low cost optical tracking system with adequate attributes for professional use is proposed. The system works in infrared spectral region to reduce optical noise. A highspeed camera, equipped with daylight blocking filter and infrared flash strobes, transfers uncompressed grayscale images to a regular PC, where image pre-processing software and the PTrack tracking algorithm recognize a set of retro-reflective markers and extract its 3D position and orientation. Included in this work is a comprehensive research on image pre-processing and tracking algorithms. A testbed was built to perform accuracy and precision tests. Results show that the system reaches accuracy and precision levels slightly worse than but still comparable to professional systems. Due to its modularity, the system can be expanded by using several one-camera tracking modules linked by a sensor fusion algorithm, in order to obtain a larger working range. A setup with two modules was built and tested, resulting in performance similar to the stand-alone configuration.

Recorte volumétrico usando técnicas de interação 2D e 3D

A visualização de conjuntos de dados volumétricos é comum em diversas áreas de aplicação e há já alguns anos os diversos aspectos envolvidos nessas técnicas vêm sendo pesquisados. No entanto, apesar dos avanços das técnicas de visualização de volumes, a interação com grandes volumes de dados ainda apresenta desafios devido a questões de percepção (ou isolamento) de estruturas internas e desempenho computacional. O suporte do hardware gráfico para visualização baseada em texturas permite o desenvolvimento de técnicas eficientes de rendering que podem ser combinadas com ferramentas de recorte interativas para possibilitar a inspeção de conjuntos de dados tridimensionais. Muitos estudos abordam a otimização do desempenho de ferramentas de recorte, mas muito poucos tratam das metáforas de interação utilizadas por essas ferramentas. O objetivo deste trabalho é desenvolver ferramentas interativas, intuitivas e fáceis de usar para o recorte de imagens volumétricas. Inicialmente, é apresentado um estudo sobre as principais técnicas de visualização direta de volumes e como é feita a exploração desses volumes utilizando-se recorte volumétrico. Nesse estudo é identificada a solução que melhor se enquadra no presente trabalho para garantir a interatividade necessária. Após, são apresentadas diversas técnicas de interação existentes, suas metáforas e taxonomias, para determinar as possíveis técnicas de interação mais fáceis de serem utilizadas por ferramentas de recorte. A partir desse embasamento, este trabalho apresenta o desenvolvimento de três ferramentas de recorte genéricas implementadas usando-se duas metáforas de interação distintas que são freqüentemente utilizadas por usuários de aplicativos 3D: apontador virtual e mão virtual. A taxa de interação dessas ferramentas é obtida através de programas de fragmentos especiais executados diretamente no hardware gráfico. Estes programas especificam regiões dentro do volume a serem descartadas durante o rendering, com base em predicados geométricos. Primeiramente, o desempenho, precisão e preferência (por parte dos usuários) das ferramentas de recorte volumétrico são avaliados para comparar as metáforas de interação empregadas. Após, é avaliada a interação utilizando-se diferentes dispositivos de entrada para a manipulação do volume e ferramentas. A utilização das duas mãos ao mesmo tempo para essa manipulação também é testada. Os resultados destes experimentos de avaliação são apresentados e discutidos.

Engajamento do consumidor em uma comunidade virtual de marca

O estudo objetivou a investigação do fenômeno de engajamento do consumidor em uma comunidade virtual de marca, tendo a Fan Page da L'Oréal Paris Brasil como contexto de observação. Para isso, por meio de método netnográfico, foram coletadas as interações entre os membros da comunidade ao longo de três meses e analisadas sob a perspectiva do modelo conceitual apresentado por Brodie et al. (2011b). Durante a análise de conteúdo, considerando as técnicas propostas por Bardin (2007), foram identificadas as dimensões, os processos e sub-processos do engajamento do consumidor, conforme proposto pelo modelo conceitual. Além disso, os resultados encontrados apontam para a validação do modelo e reforçam a perspectiva de que a simples participação ou envolvimento não pressupõe engajamento, pois este reflete um estado psicológico complexo, dependente de contexto e que necessita de processos antecedentes e consequentes. Com base nos achados, são discutidas as implicações teóricas e práticas, assim como sugestão para futuros estudos sobre o tema.

Framework para o desenvolvimento e integração de aplicações de realidade virtual, realidade aumentada e multimédia

Os ambientes virtuais têm sido cada vez mais utilizados nas mais diferentes áreas, quer na medicina, engenharia civil ou até mesmo em áreas terapêuticas. Devido à sua emergente utilização foi estabelecido em parceria com o Museu da Baleia, através de várias reuniões, que seria viável a modelação de cenários virtuais, onde se desenvolvessem animações, com o intuito de que representassem o ciclo de vida das baleias cachalotes. Esta escolha foi efectuada de forma a envolver várias temáticas relacionadas com as baleias cachalotes, desde a migração, os problemas relacionados com o lixo no fundo do mar, etc. De seguida, foi construída uma Framework para incorporação destas animações (vídeos) e realização de actividades utilizando diferentes tipos de médias, Realidade Virtual e Realidade Aumentada, tornando desta forma as actividades mais interactivas, estimulantes e atractivas. Para a execução destas etapas do projecto foi decidido utilizar a ferramenta 3ds Max para a modelação dos objectos que iriam compor os cenários virtuais, bem como a sua animação. Para a implementação da Framework foi decidido utilizar o Adobe Flash visto ser uma ferramenta que permite a incorporação de diferentes tipos de médias, de Realidade Virtual, Realidade Aumentada e possibilita a construção de uma interface simples e atractiva. Esta Framework foi desenvolvida para que no futuro seja possível ser modificada, isto é, para que seja capaz de efectuar a incorporação de outros tipos de conteúdos, assim como a edição dos que já estão implementados.

Integrating eye tracking in virtual reality for stroke rehabilitation

This thesis reports on research done for the integration of eye tracking technology into virtual reality environments, with the goal of using it in rehabilitation of patients who suffered from stroke. For the last few years, eye tracking has been a focus on medical research, used as an assistive tool  to help people with disabilities interact with new technologies  and as an assessment tool  to track the eye gaze during computer interactions. However, tracking more complex gaze behaviors and relating them to motor deficits in people with disabilities is an area that has not been fully explored, therefore it became the focal point of this research. During the research, two exploratory studies were performed in which eye tracking technology was integrated in the context of a newly created virtual reality task to assess the impact of stroke. Using an eye tracking device and a custom virtual task, the system developed is able to monitor the eye gaze pattern changes over time in patients with stroke, as well as allowing their eye gaze to function as an input for the task. Based on neuroscientific hypotheses of upper limb motor control, the studies aimed at verifying the differences in gaze patterns during the observation and execution of the virtual goal-oriented task in stroke patients (N=10), and also to assess normal gaze behavior in healthy participants (N=20). Results were found consistent and supported the hypotheses formulated, showing that eye gaze could be used as a valid assessment tool on these patients. However, the findings of this first exploratory approach are limited in order to fully understand the effect of stroke on eye gaze behavior. Therefore, a novel model-driven paradigm is proposed to further understand the relation between the neuronal mechanisms underlying goal-oriented actions and eye gaze behavior.

3D reconstruction through photographs

Humans can perceive three dimension, our world is three dimensional and it is becoming increasingly digital too. We have the need to capture and preserve our existence in digital means perhaps due to our own mortality. We have also the need to reproduce objects or create small identical objects to prototype, test or study them. Some objects have been lost through time and are only accessible through old photographs. With robust model generation from photographs we can use one of the biggest human data sets and reproduce real world objects digitally and physically with printers. What is the current state of development in three dimensional reconstruction through photographs both in the commercial world and in the open source world? And what tools are available for a developer to build his own reconstruction software? To answer these questions several pieces of software were tested, from full commercial software packages to open source small projects, including libraries aimed at computer vision. To bring to the real world the 3D models a 3D printer was built, tested and analyzed, its problems and weaknesses evaluated. Lastly using a computer vision library a small software with limited capabilities was developed.

Comparative analysis between a CAD model design and physical models obtained by manufacturing additive technologies using optical scan

This article presents a detailed study of the application of different additive manufacturing technologies (sintering process, three-dimensional printing, extrusion and stereolithographic process), in the design process of a complex geometry model and its moving parts. The fabrication sequence was evaluated in terms of pre-processing conditions (model generation and model STL SLI), generation strategy and physical model post-processing operations. Dimensional verification of the obtained models was undertook by projecting structured light (optical scan), a relatively new technology of main importance for metrology and reverse engineering. Studies were done in certain manufacturing time and production costs, which allowed the definition of an more comprehensive evaluation matrix of additive technologies.