928 resultados para Structure modelling
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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The crystallographically determined structure of biologically active 4,4-dichloro-1,3-diphenyl-4-telluraoct-2-en-1-one, 3, shows the coordination geometry for Te to be distorted psi-pentagonal bipyramidal based on a C2OCl3(lone pair) donor set. Notable is the presence of an intramolecular axial Te center dot center dot center dot O (carbonyl) interaction, a design element included to reduce hydrolysis. Raman and molecular modelling studies indicate the persistence of the Te center dot center dot center dot O(carbonyl) interaction in the solution (CHCl3) and gasphases, respectively. Docking studies of 3' (i.e. original 3 less one chloride) with Cathepsin B reveals a change in the configuration about the vinyl C = C bond. i.e. to E from Z (crystal structure). This isomerism allows the optimisation of interactions in the complex which features a covalent Te-SGCys29 bond. Crucially, the E configuration observed for 3' allows for the formation of a hypervalent Te center dot center dot center dot O interaction as well as an O center dot center dot center dot H-O hydrogen bond with the Gly27 and Glu122 residues, respectively. Additional stabilisation is afforded by a combination of interactions spanning the S1, S2, S1' and S2' sub-sites of Cathepsin B. The greater experimental inhibitory activity of 3 compared with analogues is rationalised by the additional interactions formed between 3' and the His110 and His111 residues in the occluding loop, which serve to hinder the entrance to the active site. (C) 2012 Elsevier B.V. All rights reserved.
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Strong regulatory pressure and rising public awareness on environmental issues will continue to influence the market demand for sustainable housing for years to come. Despite this potential, the voluntary uptake rate of sustainable practices is not as high as expected within the new built housing industry. This is in contrast to the influx of emerging building technologies, new materials and innovative designs as showcased in office buildings and exemplar homes worldwide. One of the possible reasons for this under-performance is that key stakeholders such as developers, builders and consumers do not fully understand and appreciate the related challenges, risks and opportunities of pursuing sustainability. Therefore, in their professional and business activities, they may not be able to see the tangible and mutual benefits that sustainable housing may bring. This research investigates the multiple challenges to achieving benefits (CABs) from sustainable housing development, and links these factors to the characteristics of key stakeholders in the housing supply chain. It begins with a comparative survey study among seven stakeholder groups in the Australian housing industry, in order to examine the importance and interrelationships of CABs. In-depth interviews then further explore the survey findings with a focus on stakeholder diversity, which leads to the identification of 12 critical mutual-benefit factors and their interrelationship. Based on such a platform, a mutual-benefit framework is developed with the aid of Interpretive Structure Modelling, to identify the patterns of stakeholder benefit materialisation, suggest the priority of critical factors and provide related stakeholder-specific action guidelines for sustainable housing implementation. The study concludes with a case study of two real-life housing projects to test the application of the mutual-benefit framework for improvement. This framework will lead to a shared value of sustainability among stakeholders and improved stakeholder collaboration, which in turn help to break the "circle of blame" for the current under-performance of sustainable housing implementation.
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The synthesis, electronic absorption and 1H NMR spectra of a suite of novel porphyrinoids derived from meso-bromoporphyrins by palladium-catalysed aminations using ethyl and tert-butylcarbazates are reported. Instead of the expected carbazate-substituted porphyrins, a facile oxidative dearomatisation of the porphyrin ring occurs in high yield, especially for the nickel(II) complexes, resulting in high yields of 5,15-diiminoporphodimethenes (DIPDs). The analogous zinc(II) and free base DIPDs were also characterised, the former by X-ray crystallography. The oxidation and reduction reactions of DIPDs and their precursor carbazate porphyrins were studied. Density Functional Theory (DFT) was used to calculate the optimised geometries and frontier molecular orbitals of DIPD Ni8c and bis(azocarboxylate) 19c, and Time Dependent DFT calculations allowed the prediction of electronic absorption spectra, whose characteristics corresponded well with those of the observed solution spectra. In the latter case, the calculated low-energy absorptions were unlike those of a typical porphyrin, due to the near-degeneracy of the highest filled frontier orbitals, and the wide energy separation between the unfilled orbitals. This feature was present in the observed spectrum.
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The startling increase in the occurrence of rifampicin (Rif) resistance in the clinical isolates of Mycobacterium tuberculosis worldwide is posing a serious concern to tuberculosis management. The majority of Rif resistance in bacteria arises from mutations in the RpoB subunit of the RNA polymerase. We isolated M. smegmatis strains harbouring either an insertion (6 aa) or a deletion (10 aa) in their RpoB proteins. Although these strains showed a compromised fitness for growth in 7H9 Middlebrook medium, their resistance to Rif was remarkably high. The attenuated growth of the strains correlated with decreased specific activities of the RNA polymerases from the mutants. While the RNA polymerases from the parent or a mutant strain (harbouring a frequently occurring mutation, H442Y, in RpoB) were susceptible to Rif-mediated inhibition of transcription from calf thymus DNA, those from the insertion and deletion mutants were essentially refractory to such inhibition. Three-dimensional structure modelling revealed that the RpoB amino acids that interact with Rif are either deleted or unable to interact with Rif due to their unsuitable spatial positioning in these mutants. We discuss possible uses of the RpoB mutants in studying transcriptional regulation in mycobacteria and as potential targets for drug design.
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As a kind of mood, depression is one of the emotions which people experienced usually. Depressive disorder is one of the common mental diseases. There are about 100 million people in the world be disturbed by depression every year. So it is long history that depression is investigated widely in medicine, psychology, and sociology. There are many theorial problems remain to be solved. Viewed from latest vocuments, the development of depression theory is tending to become more complicated. Most of the prior depression theory focused on relation between one factor and depression. Because depressed individuls have various characteristics and factors that cause depression are different, and each factor can explain only part of depression variance, these prior depression theories are defected. As the knowledge about depression accumulated, the view that depression be caused by multifactor is clearer. There is tendency to integrate these cooperational factor into a model while developing a depression theory. In the present study, depression status of 1625 middle school students from junior 1 to senior 3 are measured using Depression Scale of Middle-school Student which is developed by ourselves. From approach of depressive mood, the present study explored depressive diathesis including attributional style, personality, coping style, and self. The relation among depressive diathesis, stress and depression is analysed. The relation between depression and school life adaptation, depression and cohesion, adaptation in family are also analysed from environmental view. At last, relation among environment, stress, depressive diathesis is examined by using covariance structure modelling. Synthesizing the results from the present study, the following conclusions were drawn: (1) There is grade-characteristics in development of depression in middle school students. Depression degree increased with grade. The main reason may be that the stress middle-school students experience increase and self-acceptance decrease with grade; (2) High depressive diathesis is different from low depressive diathesis. the features of high depressive diathesis are that attributing failure to ability or background, low capacity for status, low sociability, low independence, low self-blame, more illusion. The features of low depressive diathesis are that not attributing failure to ability or background, high capacity for status, high sociability, high independence, high self-acceptance, while facing difficulties, using problem-resolving coping strategy, less self-blame, less illusion. Individuals who have high depressive diathesis showed serious depression, and individuals who have low depressive diathesis showed light depression; (3) Depressive diathesis had accumulative effect on depression. More low depressive diathesis, more light is depression. More high depressive diathesis, more serious is depression; (4) Depressive diathesis can predict present depression and future depression. Predicting present depression is more effective than predicting future depression; (5) Individual who has different depressive diathesis experiences different level of stress. Higher the depressive diathesis individual has, higher stress he will experience. Lower the depressive diathesis individual has, lower stress will he experience; (6) There is correlation between life event pressure and depression. Life event pressure can predict a part of variance of depression. Life event pressure has accumulative effect on depression. More life event and higher life event pressure, more serious depression individual will experience; (7) There exits high correlation between depression and school life adaptation which can predict depression; (8) There is high correlative relation between depression and cohesion, adaptation in family which can predict depression; and (9) Environment have more effect on diathesis than on stress. Diathesis has more effect on depression than stress does. The past depression can predict future depression. This study had enlarged the domain of depressive diathesis such as attributional style, personality, coping style, and self, which are analysed wholly. This study had also enriched the connotation of diathesis=stress theory. Above two aspects are theoretical significance of the study. This study provide a framework of mental health educational curriculum in high school and provide the guideline for prevention and cure of depression. It is the practical significance of this study.
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Recent track structure modelling studies indicate that radiation induced damage to DNA consists of a spectrum of different lesions of varying complexity. There is considerable evidence to suggest that, in repair-proficient systems, it is only the small proportion of more complex forms that is responsible for most of the biological effect. The complex lesions induced consist initially of clustered radical sites and a knowledge of their special chemistry is important in modelling how they react to form the more stable products that are processed by the repair systems. However, much of the current understanding of the chemical stage of radiation has developed from single-radical systems and there is a need to translate this to the more complex reactions that are likely to occur at the important multiple radical sites. With low LET radiation, DNA dsb may derive either from single-radical attack that damages both strands by a transfer mechanism, or from pairs of radical sites induced in close proximity, with one or more radical on each strand. With high LET radiation, modelling studies indicate that there is an increased probability of dsb arising from sites with more than two radical centres, leading to a greater frequency of more complex types of break. The spectrum of these lesions depends on the overall outcome of consecutive physical and chemical processes. The initial pattern of radical damage is determined by the energy depositions on and around the DNA, according to the type of radiation. This pattern is then modified by scavengers that inhibit the formation of radicals on the DNA, and by agents that either chemically repair (e.g. thiols) or fix (e.g. oxygen) a large fraction of these radicals. The reaction kinetics associated with clustered radical sites will differ from those of single sites: (1) because of the opportunities for interactions between the radicals themselves; and (2) because certain endpoints, e.g. a dsb, may require a combination of the products of two or more radicals. Fast response techniques using pulsed low and high LET irradiation have been established to measure the reactions of radical sites on pBR322 plasmid DNA with oxygen and thiols with a view to obtaining information about cluster size. This paper describes experimental approaches to explore the role of the chemical stage of the radiation effect in relation to lesion complexity.
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WcaJ is an Escherichia coli membrane enzyme catalysing the biosynthesis of undecaprenyl-diphosphate-glucose, the first step in the assembly of colanic acid exopolysaccharide. WcaJ belongs to a large family of polyisoprenyl-phosphate hexose-1-phosphate transferases (PHPTs) sharing a similar predicted topology consisting of an N-terminal domain containing four transmembrane helices (TMHs), a large central periplasmic loop, and a C-terminal domain containing the fifth TMH (TMH-V) and a cytosolic tail. However, the topology of PHPTs has not been experimentally validated. Here, we investigated the topology of WcaJ using a combination of LacZ/PhoA reporter fusions and sulfhydryl
labelling by PEGylation of novel cysteine residues introduced into a cysteine-less WcaJ. The results showed that the large central loop and the C-terminal tail both reside in the cytoplasm and are separated by TMH-V, which does not fully span the membrane, likely forming a "hairpin" structure. Modelling of TMH-V revealed that a highly conserved proline might contribute to a helix-break-helix structure in all PHPT members. Bioinformatic analyses show that all of these features are conserved in PHPT homologues from
Gram-negative and Gram-positive bacteria. Our data demonstrate a novel topological configuration for PHPTs, which is proposed as a signature for all members of this enzyme family
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Trabalho de Projeto para obtenção do grau de Mestre em Engenharia Civil na Área de Especialização de Estruturas
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Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Civil na Área de Especialização estruturas