Role of Halogen Bonds in Thyroid Hormone Receptor Selectivity: Pharmacophore-Based 3D-QSSR Studies

Most physiological effects of thyroid hormones are mediated by the two thyroid hormone receptor subtypes, TR alpha and TR beta. Several pharmacological effects mediated by TR beta might be beneficial in important medical conditions such as obesity, hypercholesterolemia and diabetes, and selective TR beta activation may elicit these effects while maintaining an acceptable safety profile, To understand the molecular determinants of affinity and subtype selectivity of TR ligands, we have successfully employed a ligand- and structure-guided pharmacophore-based approach to obtain the molecular alignment of a large series of thyromimetics. Statistically reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) and three-dimensional quantitative structure-selectivity relationship (3D-QSSR) models were obtained using the comparative molecular field analysis (CoMFA) method, and the visual analyses of the contour maps drew attention to a number of possible opportunities for the development of analogs with improved affinity and selectivity. Furthermore, the 3D-QSSR analysis allowed the identification of a novel and previously unmentioned halogen bond, bringing new insights to the mechanism of activity and selectivity of thyromimetics.

CoMFA and CoMSIA 3D QSAR Models for a Series of Cyclic Imides with Analgesic Activity

Three-dimensional quantitative structure-activity relationships (3D-QSAR) were performed for a series of analgesic cyclic imides using the CoMFA and CoMSIA methods. Significant correlation coefficients ( CoMFA, r(2) = 0.95 and q(2) = 0.72; CoMSIA, r(2) = 0.96 and q(2) = 0.76) were obtained, and the generated models were externally validated using test sets. The final QSAR models as well as the information gathered from 3D contour maps should be useful for the design of novel cyclic imides having improved analgesic activity.

Structural basis for selective inhibition of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase: Molecular docking and 3D QSAR studies

The glycolytic enzyme glyceraldehyde-3 -phosphate dehydrogenase (GAPDH) is as an attractive target for the development of novel antitrypanosomatid agents. In the present work, comparative molecular field analysis and comparative molecular similarity index analysis were conducted on a large series of selective inhibitors of trypanosomatid GAPDH. Four statistically significant models were obtained (r(2) > 0.90 and q(2) > 0.70), indicating their predictive ability for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results. Molecular modeling studies provided further insight into the structural basis for selective inhibition of trypanosomatid GAPDH.

Pharmacophore-based 3D QSAR studies on a series of high affinity 5-HT(1A) receptor ligands

5-HT(1A) receptor antagonists have been employed to treat depression, but the lack of structural information on this receptor hampers the design of specific and selective ligands. In this study, we have performed CoMFA studies on a training set of arylpiperazines (high affinity 5-HT(1A) receptor ligands) and to produce an effective alignment of the data set, a pharmacophore model was produced using Galahad. A statistically significant model was obtained, indicating a good internal consistency and predictive ability for untested compounds. The information gathered from our receptor-independent pharmacophore hypothesis is in good agreement with results from independent studies using different approaches. Therefore, this work provides important insights on the chemical and structural basis involved in the molecular recognition of these compounds. (C) 2010 Elsevier Masson SAS. All rights reserved.

3D face computational photography using PCA spaces

In this paper, we present a 3D face photography system based on a facial expression training dataset, composed of both facial range images (3D geometry) and facial texture (2D photography). The proposed system allows one to obtain a 3D geometry representation of a given face provided as a 2D photography, which undergoes a series of transformations through the texture and geometry spaces estimated. In the training phase of the system, the facial landmarks are obtained by an active shape model (ASM) extracted from the 2D gray-level photography. Principal components analysis (PCA) is then used to represent the face dataset, thus defining an orthonormal basis of texture and another of geometry. In the reconstruction phase, an input is given by a face image to which the ASM is matched. The extracted facial landmarks and the face image are fed to the PCA basis transform, and a 3D version of the 2D input image is built. Experimental tests using a new dataset of 70 facial expressions belonging to ten subjects as training set show rapid reconstructed 3D faces which maintain spatial coherence similar to the human perception, thus corroborating the efficiency and the applicability of the proposed system.

Novel Application of 2D and 3D-Similarity Searches To Identify Substrates among Cytochrome P450 2C9, 2D6, and 3A4

Cytochrome P450 (CYP450) is a class of enzymes where the substrate identification is particularly important to know. It would help medicinal chemists to design drugs with lower side effects due to drug-drug interactions and to extensive genetic polymorphism. Herein, we discuss the application of the 2D and 3D-similarity searches in identifying reference Structures with higher capacity to retrieve Substrates of three important CYP enzymes (CYP2C9, CYP2D6, and CYP3A4). On the basis of the complementarities of multiple reference structures selected by different similarity search methods, we proposed the fusion of their individual Tanimoto scores into a consensus Tanimoto score (T(consensus)). Using this new score, true positive rates of 63% (CYP2C9) and 81% (CYP2D6) were achieved with false positive rates of 4% for the CYP2C9-CYP2D6 data Set. Extended similarity searches were carried out oil a validation data set, and the results showed that by using the T(consensus) score, not only the area of a ROC graph increased, but also more substrates were recovered at the beginning of a ranked list.

3D roll-forming of hat-profile with variable depth and width

The use of roll-formed products in automotive, furniture, buildings etc. increases every year due to the low part-production cost and the complicated cross-sections that can be produced. The limitation with roll-forming until recent years is that one could only produce profiles with a constant cross-section in the longitudinal direction. About eight years ago ORTIC AB [1] developed a machine in which it was possible to produce profiles with a variable width (“3D roll-forming”) for the building industry. Experimental equipment was recently built for research and prototyping of profiles with variable cross-section in both width and depth for the automotive industry. The objective with the current study is to investigate the new tooling concept that makes it possible to roll-form hat-profiles, made of ultra high strength steel, with variable cross-section in depth and width. The result shows that it is possible to produce 3D roll-formed profiles with close tolerances.

Ökad insikt i den 3D-grafiska arbetsprocessen : Visualisering av interiörmiljöer i stillbilder

Föreliggande studie har haft för avsikt att genom enkäter undersöka likheter och skillnader mellan branschaktiva 3D-grafikers arbetsprocesser. Målet har varit att öka insikten i den 3D-grafiska arbetsprocessen för visualisering av interiörmiljöer. Studien är tänkt att identifiera vilka arbetsmoment som är mest tidskrävande och varför. En ökad insikt i denna process kan leda till förbättrad kommunikation och förståelse mellan kund och byrå. Respondenternas beskrivningar av arbetsprocessen liknade varandra och stämmer till stor del även med beskrivningar i litteraturen. De flesta av respondenterna upplevde modellering som det mest tidskrävande tekniska momentet. God kommunikation med kunden ansåg respondenterna vara viktigt för att undvika onödig korrektur, vilket beskrevs som problematiskt och tidskrävande. Respondenterna hade erfarenhet från referensmaterial av varierande kvalitet, vilket kan påverka ett projekts tidsåtgång.

Metamorphic epiphany -- 3D animation

As far back as I can remember, I have always been interested in studio art. Whether it be painting, drawing, printmaking, or photography, it has consistently been a part of my life. Upon enrolling in Colby, I became interested in computers and decided to major my undergraduate college career in Computer Science. Not forgetting past interests, I continued my studio art education, taking several classes within the Art department. In due time, I began combining interests and began studying Computer Graphics and Design. With limited resources in this field at Colby, the majority of my computer graphic education and experience has been done on my own time apart from regular classroom work. As time progressed, so did my interests. Starting with simple image manipulation of digitally scanned photographs, I moved on to Web Page design, eventually leading to Desktop Publishing. Ultimately, I wanted to take a step further and expand my overall computer graphic knowledge by learning 3D modeling and animation. With even fewer resources in 3D animation at Colby, I perceived having trouble finding the information and tools I would need to gain the necessary skills for this new field. The Senior Scholars program gave me the opponunity to find and acquire the necessary tools to pursue my interest. This program also allowed me to devote the proper amount of time required for learning these new tools.

TV 3D no Brasil: limitações e oportunidades de produção

Dissertação apresentada ao Programa de Pós-graduação em Comunicação da Universidade Municipal de São Caetano do Sul

Gerenciamento de documentação técnica para ambientes de engenharia/CAD com suporte a versões

Ambientes de engenharia apresentam a forte característica da necessidade de cooperação entre projetistas na concepção de projetos CAD, o que provoca uma série de problemas em relação aos ambientes usuais encontrados em aplicações convencionais. Na busca de solucionar tais problemas, vários recursos e mecanismos relativos às gerências de dados e do processo de projeto são apresentados em vários estudos encontrados na literatura. Boa parte desses recursos estão embutidos nesse trabalho, que visa apresentar um sistema gerenciador de documentação técnica para ambientes de engenharia/CAD chamado GerDoc Ábacus. A proposta da construção do GerDoc Ábacus é baseada na busca da solução dos problemas relativos à consistência dos dados de projetos e da integração de tarefas de projetistas que interagem em ambientes distribuídos de projeto. Unindo vários mecanismos, é proposta uma interface totalmente interativa, objetivando manter a harmonia entre projetistas que fazem parte de equipes de projetos que são mantidos em atividade durante longos períodos de tempo, além de documentar todos os passos realizados acerca de cada um desses projetos. Dessa forma, o GerDoc Ábacus é uma ferramenta organizacional e administrativa para projetos de engenharia, sendo de fácil operacionalização, buscando altos níveis de integridade dos dados mantidos.

Um estudo sobre curvas NURBS

O objetivo primordial desse trabalho está concentrado no estudo de Curvas NURBS (B-spline Racional N˜ao-Uniforme). A literatura em português sobre NURBS é escassa, pouco difundida e os textos e artigos existentes tendem a ser rigorosos, longos e teóricos. Assim, o presente estudo está direcionado para os conceitos matemáticos de NURBS, para o qual foi utilizado uma ferramenta chamada DesignMentor com a finalidade de testar os algoritmos desses conceitos. NURBS são funções paramétricas que podem representar qualquer tipo de curva. NURBS são usadas em computação gráfica na indústria de CAD/CAM e estão sendo consideradas um padrão para criar e representar objetos complexos (indústria automobilística, aviação e embarcação). As ferramentas de criação gráfica mais sofisticadas provêem uma interface para usar NURBS, que são flexíveis suficiente para projetar uma grande variedade de formas. Hoje é possível verificar o uso expandido de NURBS, modelando objetos para as artes visuais, arte e escultura; também estão sendo usados para modelar cenas para aplicações de realidade virtual. NURBS trabalha bem em modelagem 3D, permitindo facilidade para manipular e controlar vértices, controlar curvatura e suavidade de contornos. NURBS provêm uma base matemática, unificada para representar formas analíticas e livres além de manter exatidão e independência de resolução matemática.

Um estudo exploratório sobre a utilização de modelos 3D digitais no processo de inovação tecnológica de uma empresa da indústria de manufatura

Através de um estudo de caso, este trabalho apresenta evidências empíricas que reforçam e ampliam as descobertas de trabalhos anteriores sobre as contribuições dos modelos 3D digitais no processo de inovação tecnológica de uma empresa da indústria de manufatura, e oferece contribuições para a academia e para a prática. A inovação tecnológica é um dos fatores essenciais da competição e do desenvolvimento industrial. Na medida em que as mudanças tecnológicas ocorrem em complexidade e ritmo crescentes, as empresas têm procurado aumentar a flexibilidade e a velocidade de suas atividades através de sofisticados sistemas de tecnologia de informação e de comunicações. Na indústria de manufatura, os modelos 3D digitais têm sido cada vez mais utilizados ao longo do ciclo de vida dos produtos das empresas e a sua difusão não apenas tornou-os elementos chave para o processo de inovação tecnológica, mas a sua adoção está forçando muitas empresas a rever a forma como elas conduzem e gerenciam suas atividades de inovação.