Pharmacophore Model of Cruzain Inhibitors

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the most serious amongst the so-called neglected diseases in Latin America, specially in Brazil. So far there has been no effective treatment for the chronic phase of this disease. Cruzain is a major cysteine protease of T cruzi and it is recognized as a valid target for Chagas disease chemotherapy. The mechanism of cruzain action is associated with the nucleophilic attack of an activated sulfur atom towards electrophilic groups. In this report, features of a putative pharmacophore model of the enzyme, developed as a virtual screening tool for the selection of potential cruzain inhibitors, are described. The final proposed model was applied to the ZINC v.7 database and afterwards experimentally validated by an enzymatic inhibition assay. One of the compounds selected by the model showed cruzain inhibition in the low micromolar range.

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.

Integration of Ligand- and Target-Based Virtual Screening for the Discovery of Cruzain Inhibitors

A myriad of methods are available for virtual screening of small organic compound databases. In this study we have successfully applied a quantitative model of consensus measurements, using a combination of 3D similarity searches (ROCS and EON), Hologram Quantitative Structure Activity Relationships (HQSAR) and docking (FRED, FlexX, Glide and AutoDock Vina), to retrieve cruzain inhibitors from collected databases. All methods were assessed individually and then combined in a Ligand-Based Virtual Screening (LBVS) and Target-Based Virtual Screening (TBVS) consensus scoring, using Receiving Operating Characteristic (ROC) curves to evaluate their performance. Three consensus strategies were used: scaled-rank-by-number, rank-by-rank and rank-by-vote, with the most thriving the scaled-rank-by-number strategy, considering that the stiff ROC curve appeared to be satisfactory in every way to indicate a higher enrichment power at early retrieval of active compounds from the database. The ligand-based method provided access to a robust and predictive HQSAR model that was developed to show superior discrimination between active and inactive compounds, which was also better than ROCS and EON procedures. Overall, the integration of fast computational techniques based on ligand and target structures resulted in a more efficient retrieval of cruzain inhibitors with desired pharmacological profiles that may be useful to advance the discovery of new trypanocidal agents.

Using an animated pedagogical agent to interact affectively with the student

This work proposes an animated pedagogical agent that has the role of providing emotional support to the student: motivating and encouraging him, making him believe in his self-ability, and promoting a positive mood in him, which fosters learning. This careful support of the agent, its affective tactics, is expressed through emotional behaviour and encouragement messages of the lifelike character. Due to human social tendency of anthropomorphising software, we believe that a software agent can accomplish this affective role. In order to choose the adequate affective tactics, the agent should also know the student’s emotions. The proposed agent recognises the student’s emotions: joy/distress, satisfaction/disappointment, anger/gratitude, and shame, from the student’s observable behaviour, i. e. his actions in the interface of the educational system. The inference of emotions is psychologically grounded on the cognitive theory of emotions. More specifically, we use the OCC model which is based on the cognitive approach of emotion and can be computationally implemented. Due to the dynamic nature of the student’s affective information, we adopted a BDI approach to implement the affective user model and the affective diagnosis. Besides, in our work we profit from the reasoning capacity of the BDI approach in order for the agent to deduce the student’s appraisal, which allows it to infer the student’s emotions. As a case study, the proposed agent is implemented as the Mediating Agent of MACES: an educational collaborative environment modelled as a multi-agent system and pedagogically based on the sociocultural theory of Vygotsky.

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.

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.

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.

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.

Mapa de Conteúdos e Mapa de Dependências:Ferramentas Pedagógicas para uma Metodologia de Planejamento baseada em Objetivos Educacionais e sua Implementação em um Ambiente Virtual de Aprendizagem

Furthered mainly by new technologies, the expansion of distance education has created a demand for tools and methodologies to enhance teaching techniques based on proven pedagogical theories. Such methodologies must also be applied in the so-called Virtual Learning Environments. The aim of this work is to present a planning methodology based on known pedagogical theories which contributes to the incorporation of assessment in the process of teaching and learning. With this in mind, the pertinent literature was reviewed in order to identify the key pedagogical concepts needed to the definition of this methodology and a descriptive approach was used to establish current relations between this conceptual framework and distance education. As a result of this procedure, the Contents Map and the Dependence Map were specified and implemented, two teaching tools that promote the planning of a course by taking into account assessment still in this early stage. Inserted on Moodle, the developed tools were tested in a course of distance learning for practical observation of the involved concepts. It could be verified that the methodology proposed by the above-mentioned tools is in fact helpful in course planning and in strengthening educational assessment, placing the student as central element in the process of teaching and learning

Uso de renderização volumétrica e realidade virtual para problemas de percolação na engenharia

In the recovering process of oil, rock heterogeneity has a huge impact on how fluids move in the field, defining how much oil can be recovered. In order to study this variability, percolation theory, which describes phenomena involving geometry and connectivity are the bases, is a very useful model. Result of percolation is tridimensional data and have no physical meaning until visualized in form of images or animations. Although a lot of powerful and sophisticated visualization tools have been developed, they focus on generation of planar 2D images. In order to interpret data as they would be in the real world, virtual reality techniques using stereo images could be used. In this work we propose an interactive and helpful tool, named ZSweepVR, based on virtual reality techniques that allows a better comprehension of volumetric data generated by simulation of dynamic percolation. The developed system has the ability to render images using two different techniques: surface rendering and volume rendering. Surface rendering is accomplished by OpenGL directives and volume rendering is accomplished by the Zsweep direct volume rendering engine. In the case of volumetric rendering, we implemented an algorithm to generate stereo images. We also propose enhancements in the original percolation algorithm in order to get a better performance. We applied our developed tools to a mature field database, obtaining satisfactory results. The use of stereoscopic and volumetric images brought valuable contributions for the interpretation and clustering formation analysis in percolation, what certainly could lead to better decisions about the exploration and recovery process in oil fields

Análise do modelo troposférico empregado na geração de uma estação de referência virtual utilizando o posicionamento por ponto preciso

In the past few years the interest is accomplishing a high accuracy positioning increasing. One of the methods that has been applied by the scientific community is the network based on positioning. By using multiple reference station data, it is possible to obtain centimetric positioning in a larger coverage area, in addition to gain in reliability, availability and integrity of the service. Besides, using this concept, it is possible to model the atmospheric effects (troposphere refraction and ionosphere effect). Another important question concerning this topic is related to the transmission of the network corrections to the users. There are some possibilities for this fact and an efficient one is the Virtual Reference Station (VRS) concept. In the VRS concept, a reference station is generated near to the rover receiver (user). This provides a short baseline and the user has the possibility of using a single frequency receiver to accomplish the relative positioning. In order to test this kind of positioning method, a software has been developed at São Paulo State University. In this paper, the methodology applied to generate the VRS data is described and the VRS quality is analyzed by using the Precise Point Positioning (PPP) method.

Brazilian Students and Working Capital: An Analysis of Their Decisions When Using Virtual Market Business Games

This study aims to demonstrate that data from business games can be an important resource for improving efficiency and effectiveness of learning. The proposal presented here was developed from preliminary studies of data from Virtual Market games that pointed the possibility of identifying gaps in learning by analyzing the decisions of students. This proposal helps students to refine their learning processes and equips tutors with strategies for teaching and student assessment. The proposal also complements the group discussion and/or debriefing, which are widely used to enhance learning mediated by games. However, from a management perspective the model has the potential to be erroneous and miss opportunities, which cannot be detected because of the dependence on the characteristics of the individual, such as ability to communicate and work together. To illustrate the proposed technique, data sets from two business games were analyzed with the focus on managing working capital and it was found that students had difficulties managing this task. Similar trends were observed in all categories of students in the study-undergraduate, postgraduate and specialization. This discovery led us to the analysis of data for decisions made in the performance of the games, and it was determined that indicators could be developed that were capable of indentifying inconsistencies in the decisions. It was decided to apply some basic concepts of the finance management, such as management of the operational and non-operational expenditures, as well as production management concepts, such as the use of the production capacity. By analyzing the data from the Virtual Market games using the indicator concept, it was possible to detect the lack of domain knowledge of the students. Therefore, these indicators can be used to analyze the decisions of the players and guide them during the game, increasing their effectiveness and efficiency. As these indicators were developed from specific content, they can also be used to develop teaching materials to support learning. Viewed in this light, the proposal adds new possibilities for using business games in learning. In addition to the intrinsic learning that is achieved through playing the games, they also assist in driving the learning process. This study considers the applications and the methodology used.

Proposta metodológica para o imageamento digital e modelagem virtual 3d de um bloco de rochas travertinas

In this paper we present the methodological procedures involved in the digital imaging in mesoscale of a block of travertines rock of quaternary age, originating from the city of Acquasanta, located in the Apennines, Italy. This rocky block, called T-Block, was stored in the courtyard of the Laboratório Experimental Petróleo "Kelsen Valente" (LabPetro), of Universidade Estadual de Campinas (UNICAMP), so that from it were performed Scientific studies, mainly for research groups universities and research centers working in brazilian areas of reservoir characterization and 3D digital imaging. The purpose of this work is the development of a Model Solid Digital, from the use of non-invasive techniques of digital 3D imaging of internal and external surfaces of the T-Block. For the imaging of the external surfaces technology has been used LIDAR (Light Detection and Range) and the imaging surface Interior was done using Ground Penetrating Radar (GPR), moreover, profiles were obtained with a Gamma Ray Gamae-spectômetro laptop. The goal of 3D digital imaging involved the identification and parameterization of surface geological and sedimentary facies that could represent heterogeneities depositional mesoscale, based on study of a block rocky with dimensions of approximately 1.60 m x 1.60 m x 2.70 m. The data acquired by means of terrestrial laser scanner made available georeferenced spatial information of the surface of the block (X, Y, Z), and varying the intensity values of the return laser beam and high resolution RGB data (3 mm x 3 mm), total points acquired 28,505,106. This information was used as an aid in the interpretation of radargrams and are ready to be displayed in rooms virtual reality. With the GPR was obtained 15 profiles of 2.3 m and 2 3D grids, each with 24 sections horizontal of 1.3 and 14 m vertical sections of 2.3 m, both the Antenna 900 MHz to about 2600 MHz antenna. Finally, the use of GPR associated with Laser Scanner enabled the identification and 3D mapping of 3 different radarfácies which were correlated with three sedimentary facies as had been defined at the outset. The 6 profiles showed gamma a low amplitude variation in the values of radioactivity. This is likely due to the fact of the sedimentary layers profiled have the same mineralogical composition, being composed by carbonate sediments, with no clay in siliciclastic pellitic layers or other mineral carrier elements radioactive