Design of novel antituberculosis compounds using graph-theoretical and substructural approaches

The increasing resistance of Mycobacterium tuberculosis to the existing drugs has alarmed the worldwide scientific community. In an attempt to overcome this problem, two models for the design and prediction of new antituberculosis agents were obtained. The first used a mixed approach, containing descriptors based on fragments and the topological substructural molecular design approach (TOPS-MODE) descriptors. The other model used a combination of two-dimensional (2D) and three-dimensional (3D) descriptors. A data set of 167 compounds with great structural variability, 72 of them antituberculosis agents and 95 compounds belonging to other pharmaceutical categories, was analyzed. The first model showed sensitivity, specificity, and accuracy values above 80% and the second one showed values higher than 75% for these statistical indices. Subsequently, 12 structures of imidazoles not included in this study were designed, taking into account the two models. In both cases accuracy was 100%, showing that the methodology in silico developed by us is promising for the rational design of antituberculosis drugs.

Conformational differences between the wild type and V30M mutant transthyretin modulate its binding to genistein: Implications to tetramer stability and ligand-binding

Transthyretin (TTR) is a tetrameric beta-sheet-rich transporter protein directly involved in human amyloid diseases. It was recently found that the isoflavone genistein (GEN) potently inhibits TTR amyloid fibril formation (Green et al., 2005) and is therefore a promising candidate for TTR amyloidosis treatment. Here we used structural and biophysical approaches to characterize genistein binding to the wild type (TTRwt) and to its most frequent amyloidogenic variant, the V30M mutant. In a dose-dependent manner, genistein elicited considerable increases in both mutant and TTRwt stability as demonstrated by high hydrostatic pressure (HHP) and acid-mediated dissociation/denaturation assays. TTR:GEN crystal complexes and isothermal titration calorimetry (ITC) experiments showed that the binding mechanisms of genistein to the TTRwt and to V30M are different and are dependent on apoTTR structure conformations. Furthermore, we could also identify potential allosteric movements caused by genistein binding to the wild type TTR that explains, at least in part, the frequently observed negatively cooperative process between the two sites of TTRwt when binding ligands. These findings show that TTR mutants may present different ligand recognition and therefore are of value in ligand design for inhibiting TTR amyloidosis. (C) 2010 Elsevier Inc. All rights reserved.

Learning Grammar : A study of upper secondary level students’ attitudes and beliefs concerning the learning of grammar

The communicative approach to language learning is widely taught in Western education, and yet its predecessor, the grammar-translation method, is still commonly employed in other parts of the world. In Sweden, the increasing popularity of the communicative approach is often justified by the high level of students’ communicative skills (Öhman, 2013). At the same time, students’ written texts and speech contain many grammatical errors (Öhman, 2013). Consequently, being aware of their tendency to produce grammatical errors, some students express beliefs regarding both the explicit and implicit learning of grammar (Sawir, 2005; Boroujeni, 2012). The objective of this thesis is to gain more knowledge regarding students’ beliefs concerning the learning of English grammar at the upper secondary level, in Sweden. With this purpose a survey was conducted in two schools in Sweden, where 49 upper-secondary English students participated. Qualitative and quantitative methods were applied to process the collected data. Despite some difference in the participants’ ages, there were many similarities in their attitudes towards the teaching and learning of grammar. The results show that the participants in both schools believe that only by applying both, explicit and implicit methods, can they obtain a high level of language proficiency. The results of this study can help teachers in planning different activities that enhance the students’ knowledge of grammar.

Towards Qualitative Approaches to Bayesian Evidential Reasoning

A crucial aspect of evidential reasoning in crime investigation involves comparing the support that evidence provides for alternative hypotheses. Recent work in forensic statistics has shown how Bayesian Networks (BNs) can be employed for this purpose. However, the specification of BNs requires conditional probability tables describing the uncertain processes under evaluation. When these processes are poorly understood, it is necessary to rely on subjective probabilities provided by experts. Accurate probabilities of this type are normally hard to acquire from experts. Recent work in qualitative reasoning has developed methods to perform probabilistic reasoning using coarser representations. However, the latter types of approaches are too imprecise to compare the likelihood of alternative hypotheses. This paper examines this shortcoming of the qualitative approaches when applied to the aforementioned problem, and identifies and integrates techniques to refine them.

Comparing equilibrium real interest rates : different approaches to measure Brazilian rates

Despite the difficulties involved in the precise determination of equilibrium real interest rates, it seems clear that nominal interest rates has been higher in Brazil than in similar emerging economies. This paper aims to shed light on the possible reasons for this feature of the Brazilian economy. We extend Miranda and Muinhos (2003) one-country study to a sample of 20 countries, using many methods to compare measures of the real interest: (i) extracting equilibrium interest rates from IS curves; (ii) extracting steady state interest rates from marginal product of capital; (iii) capturing relevant variables and the fixed effects having real interest rates as dependent variable in a panel for emerging countries; and (iv) extracting inflation expectation from the spread between fixed rate and inflation-indexed treasure notes.

SSM samba: a survey of brazilian approaches to soft systems methodology (1999-2005)

This paper reports the results of a survey intended to discover the manner in which Soft Systems Methodology (SSM) is understood and used in Brazil. The focus is upon SSM papers published in national and international journals, and conferences, incorporating a refereeing procedure. To be included in the survey, publications had to meet at least one of the following criteria: (a) authorship is clearly of Brazilian nationality; or, (b) authorship is affiliated to a Brazilian institution; or (c) application is set in Brazil. Similar surveys reporting on the United Kingdom, Australia and, to a lesser extent, Spain have been published previously in the literature. This paper, therefore, contributes to the growing international understanding and usage of SSM. Ultimately the paper serves as an initial map of the developing context in Brazilian SSM theory and practice.

Valuing emerging markets companies : new approaches to determine the effective exposure to country risk

The aim of this paper is to propose new methods to measure the effective exposure to country risk of emerging-market companies. Starting from Damodaran (2003), we propose seven new approaches and a revised CAPM for emerging markets companies. The “Prospective Lambda” represents the effective exposure according to analysts’ estimates of growth. The “Relative Lambda” relies on the firm value estimated through a relative valuation. The “Retrospective Lambda” represents the ex-post effective exposure to country risk. The “Company Effective Risk Premium” is a generalization of the Retrospective Lambda, and expresses the premium effectively requested by investors to invest in that specific company in the past year. “The Actual Lambda” and the “Company Actual Risk Premium” represent, respectively, the actual exposure to country risk of a company and the actual premium requested by investors to invest in that specific company. The “Industry Lambda” reflects the median exposure to country risk of the industry in which the company belongs. We tested our new measures of exposure to country risk on the Latin American emerging markets companies according to the classification of the MSCI Emerging Markets Latin America Index. The results confirm that the new approaches can be effectively applied by financial analysts to stable-growth companies that operate in emerging markets and to mature markets companies that operate in emerging markets, providing with a more reliable estimate of both the premium effectively requested by investors in the past and the actual premium. Applying the new approaches, the cost of equity reflects the effective exposure of a company to country risk without being over- or underestimated, as is the case with other existing approaches.

Paradigms in health care and its relationship to the nursing theories: an analytical test

DANTAS, Rodrigo Assis Neves; NÓBREGA, Walkíria Gomes da; MORAIS FILHO, Luiz Alves; MACÊDO, Eurides Araújo Bezerra de ; FONSECA , Patrícia de Cássia Bezerra; ENDERS, Bertha Cruz; MENEZES, Rejane Maria Paiva de; TORRES , Gilson de Vasconcelos. Paradigms in health care and its relationship to the nursing theories: an analytical test . Revista de Enfermagem UFPE on line. v.4,n.2, p.16-24.abr/jun. 2010. Disponível em < http://www.ufpe.br/revistaenfermagem/index.php/revista>.

Environmental temperature and cloacal and surface temperatures of broiler chicks in first week post-hatch

Adequate environmental temperature during the brooding period is very important to future broiler performance. Thus, the objective of this study was to investigate the extent to which environmental temperature affects the body weight and cloacal and surface (back, head, wing, and shank) temperatures. The study also investigated the sensible heat loss by radiation of broiler chicks reared at three environmental temperatures (35, 25, and 20 degrees C) up to 7 days of life. The results showed that chicks raised at low environmental temperature (20 degrees C) had lower body weight at 7 days of age. Birds kept at 20 degrees C also had significantly lower cloacal and surface temperatures than did other birds. The most marked difference was seen in the shanks. These findings revealed that body weight declined in chicks reared at 20 degrees C, and radiant heat loss (W) was nine times higher than for the birds kept at 35 degrees C at 7 days of age.