Quantitative structure-activity relationships for a series of inhibitors of cruzain from Trypanosoma cruzi: Molecular modeling, CoMFA and CoMSIA studies

Human parasitic diseases are the foremost threat to human health and welfare around the world. Trypanosomiasis is a very serious infectious disease against which the currently available drugs are limited and not effective. Therefore, there is an urgent need for new chemotherapeutic agents. One attractive drug target is the major cysteine protease from Trypanosoma cruzi, cruzain. In the present work, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies were conducted on a series of thiosemicarbazone and semicarbazone derivatives as inhibitors of cruzain. Molecular modeling studies were performed in order to identify the preferred binding mode of the inhibitors into the enzyme active site, and to generate structural alignments for the three-dimensional quantitative structure-activity relationship (3D QSAR) investigations. Statistically significant models were obtained (CoMFA. r(2) = 0.96 and q(2) = 0.78; CoMSIA, r(2) = 0.91 and q(2) = 0.73), indicating their predictive ability for untested compounds. The models were externally validated employing a test set, and the predicted values were in good agreement with the experimental results. The final QSAR models and the information gathered from the 3D CoMFA and CoMSIA contour maps provided important insights into the chemical and structural basis involved in the molecular recognition process of this family of cruzain inhibitors, and should be useful for the design of new structurally related analogs with improved potency. (C) 2009 Elsevier Inc. All rights reserved.

Single Synapse Information Coding in Intraburst Spike Patterns of Central Pattern Generator Motor Neurons

Burst firing is ubiquitous in nervous systems and has been intensively studied in central pattern generators (CPGs). Previous works have described subtle intraburst spike patterns (IBSPs) that, despite being traditionally neglected for their lack of relation to CPG motor function, were shown to be cell-type specific and sensitive to CPG connectivity. Here we address this matter by investigating how a bursting motor neuron expresses information about other neurons in the network. We performed experiments on the crustacean stomatogastric pyloric CPG, both in control conditions and interacting in real-time with computer model neurons. The sensitivity of postsynaptic to presynaptic IBSPs was inferred by computing their average mutual information along each neuron burst. We found that details of input patterns are nonlinearly and inhomogeneously coded through a single synapse into the fine IBSPs structure of the postsynaptic neuron following burst. In this way, motor neurons are able to use different time scales to convey two types of information simultaneously: muscle contraction (related to bursting rhythm) and the behavior of other CPG neurons (at a much shorter timescale by using IBSPs as information carriers). Moreover, the analysis revealed that the coding mechanism described takes part in a previously unsuspected information pathway from a CPG motor neuron to a nerve that projects to sensory brain areas, thus providing evidence of the general physiological role of information coding through IBSPs in the regulation of neuronal firing patterns in remote circuits by the CNS.

Fragment-guided approach to incorporating structural information into a CoMFA study: BACE-1 as an example

Alzheimer`s disease is an ultimately fatal neurodegenerative disease, and BACE-1 has become an attractive validated target for its therapy, with more than a hundred crystal structures deposited in the PDB. In the present study, we present a new methodology that integrates ligand-based methods with structural information derived from the receptor. 128 BACE-1 inhibitors recently disclosed by GlaxoSmithKline R&D were selected specifically because the crystal structures of 9 of these compounds complexed to BACE-1, as well as five closely related analogs, have been made available. A new fragment-guided approach was designed to incorporate this wealth of structural information into a CoMFA study, and the methodology was systematically compared to other popular approaches, such as docking, for generating a molecular alignment. The influence of the partial charges calculation method was also analyzed. Several consistent and predictive models are reported, including one with r (2) = 0.88, q (2) = 0.69 and r (pred) (2) = 0.72. The models obtained with the new methodology performed consistently better than those obtained by other methodologies, particularly in terms of external predictive power. The visual analyses of the contour maps in the context of the enzyme drew attention to a number of possible opportunities for the development of analogs with improved potency. These results suggest that 3D-QSAR studies may benefit from the additional structural information added by the presented methodology.

From Data Snore, to Data Score: Communicating Library Assessment Data Visually through Infographics

This presentation was offered as part of the CUNY Library Assessment Conference, Reinventing Libraries: Reinventing Assessment, held at the City University of New York in June 2014.

The effects of Ikea and external shopping centers on regional trade and retail growth : A comparative analysis of Ikea’s establishment in Kalmar and Karlstad

This paper examines the effects of Ikea store establishment in Kalmar and Karlstad on the trade and retail inside the two cities, and as well on the trade and retail in the close neighboring municipalities and in further peripheral municipalities in both regions. After the establishment of Ikea store, Kalmar and Karlstad have experienced significant growth in trade and retail. The question, however, is how big this growth is in both cities? And how different locations on different distances from Ikea have been affected? What impact there was on different segments of the retail? How different business branches have been affected? How large the catchment area for the emerging new large-scale retail locations is? These questions, in addition to few others, are investigated in this paper. The thesis starts with an introduction chapter containing a background of the topic, problem description, the investigated questions, the purpose, and the outline of the paper. The next chapter includes the frame of reference which consists of literature review and theoretical framework about the external shopping centers and their impact on retail and regional trade development. It includes also information gathered from previous studies technical reports and other available sources about the subject. The third chapter includes description for the methods used to collect the primary and secondary data needed for the purpose of this study. Then the empirical framework which demonstrates the results of the conducted research followed by analysis and concluded in discussion and conclusion. Mixed methods are used as research strategy in this thesis, and the method to conduct the research is based on telephone interviews for the primary (qualitative) data, and documents and desk research for the secondary (quantitative) data. The gathered data is analyzed and designed in a way that allows the usage of comparative analysis technique to present the findings and draw conclusions. The results showed that new established Ikea retail store outside the city boundaries results with many effects on the city center and on the neighboring municipalities as well. The city center seems not to be affected negatively, but on the contrary positive effects were witnessed in both regions, these positive effects are linked to the increase inflow of customers from the external retail area which is known as spillover effect. III On the other hand, the neighboring towns and municipalities are more negatively affected especially with the trade of con-convenience goods as the consumers in these towns and municipalities start to go to the area of Ikea and the large external retail center to do their purchasing, the substitution effect is then said to be occurred. Moreover, the further far municipalities do not seem to be significantly affected by the establishment of Ikea. These effects whether positive or negative could be monitored by looking to few trade parameters such as the turnover, the sales index, and the consumers’ expenditure, these parameters can be very useful to measure the developments and changes in the trade and retail in a given place. 

As demonstrações financeiras em US GAAP tomadas como instrumento gerencial da CST: um estudo de caso

A finalidade desta pesquisa é avaliar as demonstrações financeiras da CST preparadas de acordo com os princípios contábeis geralmente aceitos nos Estados Unidos, como um instrumento de tomada de decisões, pela administração da CST, ao invés dos demonstrativos preparados de acordo com os princípios contábeis geralmente aceitos no Brasil. Como estudo de caso da CST, os seus relatórios financeiros, incluindo demonstrações financeiras, relatórios de administração, press release, e outros, relacionados ao periodo de 1994 a 2000, constituem a base desta pesquisa. As informações de tais documentos foram comparadas e analisadas. Também, foi necessário pesqUIsar sobre as principais regras contábeis do Brasil e dos Estados Unidos que afetam o resultado deste estudo. Alguns livros sobre contabilidade e finanças de ambos os paises, Brasil e Estados Unidos, foram também usados como uma base conceitual. A partir dos resultados obtidos foi possível conhecer a influência das diferenças de princípios contábeis e, aSSIm avaliar quaIs demonstrações contábeis, brasileiras ou amencanas, são mats consistentes para finalidades gerenCIatS, considerando as caracteristicas da CST.

Contribuições da tecnologia da informação e da inovação para a produtividade do trabalho dos magistrados: um estudo de caso no Superior Tribunal de Justiça

Esta dissertação de mestrado teve como objetivo analisar a produtividade do trabalho dos Magistrados do Poder Judiciário Brasileiro. O objetivo específico foi tentar compreender as contribuições da Tecnologia da Informação e da Inovação para a produtividade do trabalho dos Magistrados. A tecnologia da informação e a inovação têm sido responsáveis pela otimização de tarefas nas mais diversas áreas, proporcionando muitos benefícios, que vão desde a economia de tempo na realização das atividades até a redução de custos. Para verificar as contribuições da tecnologia da informação e da inovação na produtividade do trabalho dos magistrados foi adotado a estudo de caso, o qual teve como foco o Superior Tribunal de Justiça (STJ). Nesse sentido, a pesquisa foi conduzida por meio de levantamento e análise de dados provenientes de documentos, da Internet e de entrevistas. Justamente, procurando reconhecer quais são as ferramentas de TI e quais são as inovações colocadas à disposição dos magistrados do STJ para o desempenho de sua função, como se dá o alinhamento com o planejamento estratégico e em que medida a TI e a inovação tem possibilitado o aumento da produtividade do trabalho dos magistrados do STJ. As conclusões depreendidas deste estudo revelam que de fato há um aumento da produtividade do trabalho dos magistrados do STJ com o uso da TI e da Inovação.

As práticas e o processo de diferenciação estratégica no surgimento de novas capacidades organizacionais: uma análise no lançamento de novos produtos

O processo de lançamento de novos produtos e serviços possui etapas significativas caracterizadas por atividades, rotinas e práticas que a define, e busca explorar a estratégia de diferenciação como processo-chave e determinante de sucesso (DEEDS; DECAROLIS; COOMS, 1999). Este estudo investiga como surgem novas capacidades organizacionais a partir do lançamento de novos serviços em busca de diferenciação no mercado. As práticas foram escolhidas como canal para entender de que forma as atividades e competências são direcionadas dentro da organização em atendimento a uma demanda emergente do mercado, fazendo com que a organização se diferencie das demais em um ambiente competitivo e demarcado por rápidas mudanças. O conceito de capacidades dinâmicas se encaixa à medida que o setor em que a organização pesquisada está inserida é carregado por informações que, por sua vez, está exposto a mudanças constantes, o que exige adaptação a todo o momento. A metodologia, qualitativa, foi realizada através da análise de trechos de documentos, vídeo e reportagens disponíveis no mercado a respeito do assunto, complementado por entrevistas em profundidade realizada com os responsáveis pela operação e lançamento deste novo serviço. Como resultado, foi encontrado que as práticas permitem a seleção das melhores atividades, rotinas e do que funciona ou não na organização. Permitem a criação de novas capacidades e a expressão das capacidades absorvitiva, adaptativa e inovativa, envolvidas na criação de um novo serviço para atender a demanda emergente do mercado.

Nematicidal activity of Solanum nigrum and S. sisymbriifolium extracts against the root-lesion nematode Pratylenchus goodeyi and its effects on infection and gene expression

The control of Pratylenchus goodeyi a common nematode parasite of banana crop in Madeira Island can benefit from searching for natural nematicides through plants extracts. With this aim we submitted Solanum nigrum and S. sisymbriifolium dried plants to a sequential extraction in the solvent sequence of dichloromethane, acetone, ethanol and water, and to na aqueous extraction of the fresh and dried plants. Analyses with the extracts at several concentrations were used to assess mobility and mortality on P. goodeyi. Results showed that the water extract and aqueous extracts from both plants at a concentration of 10 mg/mL affected nematode mobility and caused mortality but the acetone extract from S. nigrum was the most efficient, causing 100% mortality whereas dichloromethane had no effect on P. goodeyi. Determination of the lipophilic and phenolic compounds present in the two most effective Solanum extracts (acetone and water) and in dichloromethane extract revealed that some of these compounds had nematicidal activity. S. nigrum acetone extract (10 mg/mL) was used to find out the nematicidal potential following the effect at gene expression level and nematode behaviour. Genes coding for calreticulin and beta-1,4- endoglucanase related to parasitism and translocon-associated protein putatively connected to stress were obtained and its relative expression assessed in nematodes exposed to the extract. Results revealed that expression of Pg-CRT decreased showing to influence the infection, Pg-ENG remained steady and Pg-TRAPδ was induced over time exposure. Biological assays showed that P. goodeyi mobility and ability to infect the banana roots were affected as a decrease in the number of nematodes that reached the roots was obtained with the increased exposure time to the extract being implicated in the infection success. The information obtained from this thesis showed that S. nigrum has potential to be used for the development of a new control strategy against plant-parasitic nematodes.

Estudo de polimorfismos em genes relacionados ao metabolismo do ácido fólico e sua associação com o desenvolvimento de fendas orais não-sindrômicas

The congenital facial clefts are characterized by incomplete formation of the structures that separate the oral and nasal cavity. It is known that several environmental and genetic factors are involved in its development, among these, polymorphisms associated with folic acid metabolism have been investigated. In this sense, the objective was to observe the frequency of polymorphisms C677T and A1298C methylenetetrahydrofolate reductase gene (MTHFR), methionine synthase A2756G of (MTR), A66G of methionine synthase reductase (MTRR) A80G and the reduced folate carrier (RFC1) in patients with non-syndromic oral clefts, trying to match them with their development. Methods: We studied 140 patients with non-syndromic oral clefts and their mothers and 175 control subjects with their mothers, who underwent a questionnaire to obtain family information. Were collecting blood for DNA extraction from patients and their mothers to identify the genotypes of both by PCRRFLP, in addition to carrying out the determination of glucose, AST, ALT and serum creatinine, folic acid and vitamin B12 Serum and plasma homocysteine, and the hemogram. Results: Most patients have cleft lip and palate (55.8%), followed by isolated cleft palate (24.2%) and cleft lip (20%). Regarding gender, 62% of patients were male and 48% female and, after subdivision of the type of screwdriver according to sex was found a prevalence of males in the cracks of the type lip and palate (69 %) and lip (69.2%) and in the case of cleft palate was a female predominance (59%). The average concentration of serum folate in the group of mothers of cleft patients was significantly lower (13.8 ± 2.4 ng / mL) compared with the group of mothers of control subjects (18.8 ± 3.4 ng / mL) This was also observed for the group of cleft children as compared to controls, the dosage of folic acid had a significant difference with values of 15.6 ± 0.6 (ng / mL) and 17.9 ± 0.6 (ng / mL), respectively. For the biochemical measurements of glucose, AST, ALT and creatinine were not statistically different, nor was observed for haematological parameters performed. In assessing the frequency of polymorphisms C677T and A1298C MTHFR, A2756G MTR, MTRR A66G and A80G of the RFC1 there was no statistically significant difference in genotype distribution between cases and controls both for mothers and in the cleft. Conclusion: Although not observed association of polymorphisms with the development of cracks, the decrease in serum folate in the group of cleft patients and their mothers may reflect a disturbance in the metabolism of this metabolite, necessitating further studies such as studies methylation and expression to further elucidate the involvement of folate in the development of oral clefts

Extração semi-automática de rodovia baseada em um par estéreo de imagens aéreas e em otimização por programação dinâmica no espaço-objeto

This article proposes a method for 3D road extraction from a stereopair of aerial images. The dynamic programming (DP) algorithm is used to carry out the optimization process in the object-space, instead of usually doing it in the image-space such as the DP traditional methodologies. This means that road centerlines are directly traced in the object-space, implying that a mathematical relationship is necessary to connect road points in object and image-space. This allows the integration of radiometric information from images into the associate mathematical road model. As the approach depends on an initial approximation of each road, it is necessary a few seed points to coarsely describe the road. Usually, the proposed method allows good results to be obtained, but large anomalies along the road can disturb its performance. Therefore, the method can be used for practical application, although it is expected some kind of local manual edition of the extracted road centerline.

Optimization of acid hydrolysis from the hemicellulosic fraction of Eucalyptus grandis residue using response surface methodology

Biotechnological conversion of biomass into fuels and chemicals requires hydrolysis of the polysaccharide fraction into monomeric sugars. Hydrolysis can be performed enzymatically and with dilute or concentrate mineral acids. The present study used dilute sulfuric acid as a catalyst for hydrolysis of Eucalyptus grandis residue. The purpose of this paper was to optimize the hydrolysis process in a 1.41 pilot-scale reactor and investigate the effects of the acid concentration, temperature and residue/acid solution ratio on the hemicellulose removal and consequently on the production of sugars (xylose, glucose and arabinose) as well as on the formation of by-products (furfural, 5-hydroxymethylfurfural and acetic acid). This study was based on a model composition corresponding to a 2 3 orthogonal factorial design and employed the response surface methodology (RSM) to optimize the hydrolysis conditions, aiming to attain maximum xylose extraction from hemicellulose of residue. The considered optimum conditions were: H2SO4 concentration of 0.65%, temperature of 157 degrees C and residue/acid solution ratio of 1/8.6 with a reaction time of 20 min. Under these conditions, 79.6% of the total xylose was removed and the hydrolysate contained 1.65 g/l glucose, 13.65 g/l xylose, 1.55 g/l arabinose, 3.10 g/l acetic acid, 1.23 g/l furfural and 0.20 g/l 5-hydroxymethylfurfural. (c) 2006 Published by Elsevier Ltd.

Spatial electric load forecasting using an evolutionary heuristic

A method for spatial electric load forecasting using elements from evolutionary algorithms is presented. The method uses concepts from knowledge extraction algorithms and linguistic rules' representation to characterize the preferences for land use into a spatial database. The future land use preferences in undeveloped zones in the electrical utility service area are determined using an evolutionary heuristic, which considers a stochastic behavior by crossing over similar rules. The method considers development of new zones and also redevelopment of existing ones. The results are presented in future preference maps. The tests in a real system from a midsized city show a high rate of success when results are compared with information gathered from the utility planning department. The most important features of this method are the need for few data and the simplicity of the algorithm, allowing for future scalability.

Effects of extraction methods on yam (Dioscorea alata) starch characteristics

Starch extraction from roots and tubers uses grating with water and sieves to separate the starch slurry from residual mass. The starch is recovered by decantation or centrifugation. The yam starch extraction is difficult due to high viscosity of the slurry caused by non-starch polysaccharides (NSP). The establishment of an efficient extraction process may turn yam into a competitive raw material. In this paper Dioscorea alata starch extracted by four methods was characterized in order to establish the impact of treatments. When the tubers were digested with an aqueous oxalic acid/ammonium oxalate (OA/AO) 1/1 solution, it was easier to separate the starch slurry from residual mass, because viscosity was reduced. For all the others methods tested, the viscosity remained almost the same. The nitrogen present in yam tubers was removed during the different extractions to a different extent. The largest nitrogen reduction was observed with ONAO followed by the control (water). The spectrum of starch granules sizes obtained also varied according to the treatment. Results proved that NSP carries small starch granules over to the waste water. The smaller starch granules diameter varied from 1.9 mu m (OA/AO extraction) to 13.5 mu m (water and pectinase extractions). The larger diameter varied from 41.0 mu m (NaOH treatment) to 67.7 mu m (ONAO). All starches extracted showed a RVA behavior in agreement with literature for yam starch, but with small differences due to the influence of methods. ONAO extraction showed the best recovery (18 g of starch/100 g tuber yam) and granular variation but it interfered with the rheological behavior of starch.

STOMACH CONTENTS ANALYSIS of WHITE MARLIN (TETRAPTURUS ALBIDUS) CAUGHT OFF SOUTHERN and SOUTHEASTERN BRAZIL: A BAYESIAN ANALYSIS.

This study proposes to ascertain the importance of each alimentary category in the Tetrapturus albidus diet composition, as well as to propose the use of the Bayesian approach for analysis of these data. The stomachs were collected during fishing cruises carried out by the Santos-SP longliner from July 2007 to June 2008. For Bayesian model formulation, each alimentary item was clustered in four food categories as: teleost, cephalopod, crustaceans, and others. To estimate the proportion of each food category, the multinomial model with Dirichlet conjugate prior distribution was used. After the stomach contents analysis, 133 food items were identified, which belonged to 9 taxa. The most important food category is constituted by cephalopod molluscs, followed by teleost fishes. The food category comprised of crustaceans presents a low contribution and in this case it could be considered to be an accidental food item. The Bayesian approach means a distinct view in relation to traditional methods, as it permits one to incorporate information obtained from the literature. It should be useful to analyse great top predators, which are usually caught in small numbers.