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.

C programs for solving the time-dependent Gross-Pitaevskii equation in a fully anisotropic trap

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

PhotoLin: a program to identify and analyze linear structures in aerial photographs, satellite images and maps

A computer program, PhotoLin, written for an IBM-PC-compatible microcomputer is described which detects linear features in aerial photographs, satellite images and topographic maps. The program accepts images saved to PCX files as input and applies noise correction and smoothing filters and thinning routines. The output consists of a skeleton containing the median lines of linear features which can be represented on a map. The branches of the skeleton can be broken into sections of constant length for which the mean orientations are obtained for the preparation of rose diagrams. (C) 2001 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.

Tensor3D: A computer graphics program to simulate 3D real-time deformation and visualization of geometric bodies

Tensor3D is a geometric modeling program with the capacity to simulate and visualize in real-time the deformation, specified through a tensor matrix and applied to triangulated models representing geological bodies. 3D visualization allows the study of deformational processes that are traditionally conducted in 2D, such as simple and pure shears. Besides geometric objects that are immediately available in the program window, the program can read other models from disk, thus being able to import objects created with different open-source or proprietary programs. A strain ellipsoid and a bounding box are simultaneously shown and instantly deformed with the main object. The principal axes of strain are visualized as well to provide graphical information about the orientation of the tensor's normal components. The deformed models can also be saved, retrieved later and deformed again, in order to study different steps of progressive strain, or to make this data available to other programs. The shape of stress ellipsoids and the corresponding Mohr circles defined by any stress tensor can also be represented. The application was written using the Visualization ToolKit, a powerful scientific visualization library in the public domain. This development choice, allied to the use of the Tcl/Tk programming language, which is independent on the host computational platform, makes the program a useful tool for the study of geometric deformations directly in three dimensions in teaching as well as research activities. (C) 2007 Elsevier Ltd. All rights reserved.

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

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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.

Study of water and dimethylformamide interaction by computer simulation

Monte Carlo simulations of water-dimethylformamide (DMF) mixtures were performed in the isothermal and isobaric ensemble at 298.15 K and 1 atm. The intermolecular interaction energy was calculated using the classical 6-12 Lennard-Jones pairwise potential plus a Coulomb term. The TIP4P model was used for simulating water molecules, and a six-site model previously optimised by us was used to represent DMF. The potential energy for the water-DMF interaction was obtained via standard geometric combining rules using the original potential parameters for the pure liquids. The radial distribution functions calculated for water-DMF mixtures show well characterised hydrogen bonds between the oxygen site of DMF and hydrogen of water. A structureless correlation curve was observed for the interaction between the hydrogen site of the carbonyl group and the oxygen site of water. Hydration effects on the stabilisation of the DMF molecule in aqueous solution have been investigated using statistical perturbation theory. The results show that energetic changes involved in the hydration process are not strong enough to stabilise another configuration of DMF than the planar one.