A series of 39 (a training set of 29 and a test set of 10) interphenylene 7-oxabicyclo [2.2.1]heptane oxazole thromboxane A2 (TXA2) receptor antagonists were studied using four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis. Two thousand conformations of each analogue were sampled to generate a conformational energy profile (CEP) from a molecular dynamic simulation (MDS) of 100,000 trajectory states. Each conformation was placed in a grid cell lattice for each of six trial alignments. Cubic grid cell sizes of 1 and 2 A were considered. The frequency of occupation of each grid cell was computed for each of seven types of pharmacophoric group classes of atoms of each compound. These grid cell occupancy descriptors (GCODs) were then used as independent variables in constructing three-dimensional (3D)-QSAR models after data reduction. The types of data reduction included doing no reducing, reduction based on individual GCOD correlation with activity, and reduction from minimum variance constraints over the GCOD population. The 3D-QSAR models were generated and evaluated by a scheme that combines a genetic algorithm (GA) optimization with partial least squares (PLS) regression. The 3D-QSAR models were evaluated by cross-validation using the leave-one-out technique. The cross-validated correlation coefficient, Q2, ranged from 0.27 to 0.86. The models are not from chance correlation because a scrambled data set was generated and evaluated (Q2 = 0.25-0.37). A composite 3D-QSAR model was constructed using the best models derived from GCODs of both 1 and 2 A grid cell size lattices. The 3D-QSAR models provide detailed 3D pharmacophore requirements in terms of atom types and corresponding locations needed for high TXA2 inhibition activity. Specific sites in space that should not be occupied by an active inhibitor are also specified. The GCOD measures for the compounds in the training set permit reference points regarding which pharmacophore sites can provide the largest boosts in inhibition activity relative to the existing analogues.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Resumo Este artigo ressalta a diferença de comportamento da China no Conselho de Segurança nos períodos entre 1971 e 2006, e entre 2007 e 2012. O primeiro período, marcado pela presença mais discreta do país entre os membros permanentes, e o segundo caracterizado por um comportamento mais ativo, resultado direto de seu novo papel na ordem e no sistema internacional, e com potencial para reconfigurar a política entre potências e a geopolítica mundial.
Sensual, quente, fácil e disponível são palavras que constroem a narrativa da mulher brasileira em seus padrões de identificação no exterior. Esses padrões imagéticos criam imagens pré-concebidas, que interferem na experiência que tais mulheres vivem e sentem ao estarem em outro território. O objetivo do artigo, portanto, é mostrar, por meio das teorias feministas e pós-coloniais das Relações Internacionais, como tal narrativa foi construída por meio de termos e imagens que associam a mulher brasileira, enquanto “mulher do Terceiro Mundo”, a um duplo sistema de opressões. Para tal, serão apresentados discursos e imagens, reforçados pelo Estado brasileiro, além de dados obtidos por meio de pesquisa de survey com alunas da Universidade Federal Fluminense (UFF) que sofreram situações de opressão durante intercambio acadêmico na Europa relacionadas às características de gênero e origem. A fim de ilustrar o argumento, relatos anônimos das experiências das intercambistas são apresentados, de forma a demonstrar os efeitos do duplo sistema de opressões na prática.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.