Computer-aided design of a novel ligand for retinoic acid receptor in cancer chemotherapy

The isotypes of RAR and RXR are retinoic acid and retinoid X acid receptors, respectively, whose ligand-binding domain contains the ligand-dependent activation function, with distinct pharmacological targets for retinoids, involved in the treatment of various cancers and skin diseases. Due to the major challenge which cancer treatment and cure still imposes after many decades to the international scientific community, there is actually considerable interest in new ligands with increased bioactivity. We have focused on the retinoid acid receptor, which is considered an interesting target for drug design. In this work, we carried out density functional geometry optimizations, and different docking procedures. We performed screening in a large database (hundreds of thousands of molecules which we optimized at the AM1 level) yielding a set of potential bioactive ligands. A new ligand was selected and optimized at the B3LYP/6-31G* level. A flexible docking program was used to investigate the interactions between the receptor and the new ligand. The result of this work is compared with several crystallographic ligands of RAR. Our theoretically more bioactive new-ligand indicates stronger and more hydrogen bonds as well as hydrophobic interactions with the receptor. (c) 2005 Wiley Periodicals, Inc.

Alternative method of smearing samples on slides facilitate visualization of hemoglobin H inclusion bodies in alpha thalassemia

Nas talassemias alfa, a HbH pode ser detectada, nos eritrócitos do sangue periférico como inclusões celulares quando coradas com azul crezil brillante. Este teste simples é útil para o diagnóstico de talassemia alfa, no entanto, a identificação dos corpos de inclusão de HbH é um processo laborioso e os resultados são altamente dependentes do observador. No intuito de melhorar a identificação das inclusões, foi testado um método alternativo para espalhar as amostras nas lâminas. Amostras de sangue foram espalhadas nas lâminas usando-se o método clássico e o método alternativo. O método alternativo permitiu uma melhor identificação das inclusões de HbH do que o método clássico. Nossos resultados mostraram que o método alternativo é uma opção útil para a pesquisa dos corpúsculos de inclusão de HbH naquelas amostras onde o método clássico não o permite.

Construção de conceitos de física moderna e sobre a natureza da ciência com o suporte da hipermídia

Apresentam-se os resultados de uma pesquisa sobre a construção de conceitos de Física Moderna e sobre a natureza da Ciência com o apoio da hipermídia, que envolveu a produção e avaliação de um software educacional. A proposta didática fundamentou-se na Teoria da Aprendizagem de Ausubel, em orientações para a implementação de sistemas hipermídia educacionais e em abordagens derivadas da pesquisa em Ensino de Ciências, dentre as quais o enfoque Ciência-Tecnologia-Sociedade, ponderações quanto à importância pedagógica da História e Filosofia da Ciência e considerações sobre a inserção de Física Moderna no Ensino Médio. O programa foi avaliado por pesquisadores de Ensino de Física e licenciandos de Física e, após a incorporação de algumas sugestões realizadas, foi testado por estudantes do terceiro ano do Ensino Médio de uma escola pública. Obtiveram-se indícios de que o uso do computador foi fator de motivação dos estudantes; a diversidade de elementos de mídia auxiliou-os a fixar a atenção sobre o conteúdo e favoreceu a visualização e interpretação dos fenômenos, facilitando ainda o raciocínio; o hipertexto estruturado em conformidade com princípios ausubelianos contribuiu para a percepção da relação entre os conceitos e ajudou no desenvolvimento de subsunçores para apoiar a aprendizagem subseqüente. Constatou-se que a proposta didática avaliada favoreceu a evolução das concepções da maior parte dos estudantes quanto ao conceito de equivalência massa-energia e suas implicações; às relações entre Ciência, Tecnologia e Sociedade, incluindo aspectos ambientais e políticos; ao papel da Ética no desenvolvimento e aplicação dos conhecimentos científicos; ao progresso da Ciência ao longo do tempo.

TRICUT: a program to clip triangle meshes using the rapid and triangle libraries and the visualization toolkit

An efficient technique to cut polygonal meshes as a step in the geometric modeling of topographic and geological data has been developed. In boundary represented models of outcropping strata and faulted horizons polygonal meshes often intersect each other. TRICUT determines the line of intersection and re-triangulates the area of contact. Along this line the mesh is split in two or more parts which can be selected for removal. The user interaction takes place in the 3D-model space. The intersection, selection and removal are under graphic control. The visualization of outcropping geological structures in digital terrain models is improved by determining intersections against a slightly shifted terrain model. Thus, the outcrop line becomes a surface which overlaps the terrain in its initial position. The area of this overlapping surface changes with respect to the strike and dip of the structure, the morphology and the offset. Some applications of TRICUT on different real datasets are shown. TRICUT is implemented in C+ + using the Visualization Toolkit in conjunction with the RAPID and TRIANGLE libraries. The program runs under LINUX and UNIX using the MESA OpenGL library. This work gives an example of solving a complex 3D geometric problem by integrating available robust public domain software. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

Light microscopy and computer three-dimensional reconstruction of the blood capillaries of the enamel organ of rat molar tooth germs

We performed a light microscope and a computer three-dimensional reconstruction study of serial sections of the molar enamel organ of 3- and 5-day-old rats perfused with Indian ink through the arterial system. The tooth germs were fixed in Bouin's solution, embedded in paraffin, sectioned and stained with haematoxylin and eosin. For the three-dimensional reconstruction, light micrographs of the serial sections were digitized, and aligned using the serial EM Align software downloaded from http://synapses.bu.edu/tools/. After alignment, the boundaries of the India-ink-filled blood vessels were manually traced with a mouse using the software IGL trace (version 1.26b), also downloaded from the above website. After tracing, a three-dimensional representation of the blood vessel contours was generated in a VRML format and visualized with the help of the software Cortona Web3D viewer (version 4.0) downloaded from http://www.parallelgraphics.com/products/cortona. Our results showed that in regions where ameloblasts are polarized the capillaries are arranged in three distinct levels: (1) penetrating and leaving capillaries in relation to the outer enamel epithelium; (2) capillaries crossing and branching inside the stellate reticulum; and (3) capillaries branching and anastomosing profusely within the stratum intermedium, thereby forming an extensive capillary plexus intimately associated with the cells of the stratum intermedium. The existence of a conspicuous capillary plexus intermingled with cells of the stratum intermedium, as shown in our results, suggests that some molecules produced by cells of the stratum intermedium could be released into the capillary plexus and thereafter carried to the dental follicle.

Computer-assisted analysis of cell proliferation markers in oral lesions

Abnormalities in any component of the cell cycle regulatory machine may result in oral. cancer, and markers of cell proliferation have been used to determine the prognosis of tumor progression. The aim of this study was to determine whether silver-stained nucleolar organizer region (AgNOR) and Ki-67 measurements could improve the assessment of growth rates in oral lesions. Eighty-three oral biopsies were studied, 20 of which were classified as fibrous inflammatory hyperplasia (FIH), 40 as leukoplakia (LKP) and 23 as oral. squamous cell carcinoma (OSCC). Within the LKP group, 22 out of 29 biopsies were diagnosed as non-dysplastic leukoplakia (LK) and 18 as dysplastic teukoptakia (DLK), presenting discrete, moderate and severe dysplasia. Ki-67 immunotabeting of the lesions increased steadily in the following order: FIH, DLK, LK and OSCC, indicating that Ki-67 is a good marker for predicting the protiferative fraction among benign, premalignant and malignant oral lesions. The median values of AgNOR parameters indicate that the morphometric index gives better results regarding the proliferative rate than the numerical one. A series of linear regressions between AgNOR parameters and Ki-67 showed positive associations. We conclude that a combination of Ki-67 and morphometric AgNOR analyses could be used as an aid in the determination of the protiferative status of oral epithelial. cells in oral cancer. (C) 2007 Elsevier GmbH. All rights reserved.

Theoretical studies of liquids by computer simulations: the water-acetone mixture.

Monte Carlo simulation results for pure liquid acetone and water-acetone mixtures calculated in the isothermal and isobaric (NPT) ensemble at T=298K and p=1.0atm are presented. The TIP4P model was used for water and optimized potential for liquid simulation (OPLS) force field parameters used for acetone. The results obtained for the average configurational energy as a function of the mole fraction are in good accord with experimental data. Energy partitioning and co-ordination numbers results calculated for equimolar water-acetone solution are compared to similar data obtained for other water-organic liquid mixtures. These results show an increase in water-water interaction energy and co-ordination numbers when the interaction between water and organic liquid molecules decrease. Distribution functions for pure liquid acetone and water-acetone mixtures are presented. Dipole-dipole angular correlation functions obtained for pure liquid acetone show a predominance of dimers with parallel alignment of dipole moments. Radial distribution functions from water-acetone interaction show characteristic features of hydrogen bonded liquids. Radial and angular distribution functions for water-water correlation calculated in pure water and in equimolar water-acetone mixture are compared, showing very similar features in both systems. (C) 1999 Elsevier B.V. B.V. All rights reserved.

Coordinated views to assist exploration of spatio-temporal data: a case study

In this paper we focus on providing coordinated visual strategies to assist users in performing tasks driven by the presence of temporal and spatial attributes. We introduce temporal visualization techniques targeted at such tasks, and illustrate their use with an application involving a climate classification process. The climate classification requires extensive Processing of a database containing daily rain precipitation values collected along over fifty years at several spatial locations in the São Paulo state, Brazil. We identify user exploration tasks typically conducted as part of the data preparation required in this process, and then describe how such tasks may be assisted by the multiple visual techniques provided. Issues related to the use of the multiple techniques by an end-user are also discussed.

Does spatial visualization ability improve after studying technical drawing?

Two studies were carried out to analyze whether learning technical drawing improves a person's ability for spatial visualization. Visualization and inductive reasoning tests were applied at the beginning and end of a course in technical drawing in samples of first year engineering students. In both studies it was observed that a moderate percentage of students improved their Visualization test execution. The improvement was similar in men and women. There was no improvement on the inductive reasoning test. The results support the conclusion that the spatial visualization ability can be improved with training.

Galectin-3 Overexpression in Invasive Laryngeal Carcinoma, Assessed by Computer-assisted Analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Simulação numérica de trocadores de calor multitubulares equipados com fitas helicoidais externamente aos tubos

Classical shell-and-tube heat exchangers are usually equipped with segmental baffles. These baffles serve two basic functions: (a) they provide tube supports, thereby preventing or reducing mechanical problems, such as sagging or vibration; (b) they direct the fluid flow over the tubes so as to introduce a cross-flow component, thereby increasing the heat transfer. Segmented baffles have several sources of performance loss, some due to various leakage flows and others caused by stagnation zones. A new concept of longitudinal flow heat exchanger - based on placing twisted tapes along the tube bundle subchannels - was developed to mitigate drawbacks of other types of tubular heat exchangers. In this paper, a numerical model has been implemented in order to simulate the thermal-hydraulic feature of tubular heat exchangers equipped either with segmental baffles or with subchannel twisted tapes. The tube bundle has been described by means of an equivalent porous medium type model, allowing a macroscopic description of the shell-side flow. The basic equations - continuity, momentum and energy - have been solved by using the finite volume method. Typical numerical results have been compared with experimental data, reaching a very good agreement. A comparative analysis of different types of heat exchangers has been carried out, revealing the satisfactory thermal-hydraulic efficiency level of the twisted tapes heat exchangers.

Conditional reasoning: A key to assessing computer-based knowledge-building communication processes

This article describes a methodological approach to conditional reasoning in online asynchronous learning environments such as Virtual-U VGroups, developed by SFU, BC, Canada, consistent with the notion of meaning implication: If part of a meaning C is embedded in B and a part of a meaning B is embedded in A, then A implies C in terms of meaning [Piaget 91]. A new transcript analysis technique was developed to assess the flows of conditional meaning implications and to identify the occurrence of hypotheses and connections among them in two human science graduate mixed-mode online courses offered in the summer/spring session of 1997 by SFU. Flows of conditional meaning implications were confronted with Virtual-U VGroups threads and results of the two courses were compared. Findings suggest that Virtual-U VGroups is a knowledge-building environment although the tree-like Virtual-U VGroups threads should be transformed into neuronal-like threads. Findings also suggest that formulating hypotheses together triggers a collaboratively problem-solving process that scaffolds knowledge-building in asynchronous learning environments: A pedagogical technique and an built-in tool for formulating hypotheses together are proposed. © Springer Pub. Co.