Bj-PRO-5a, a natural angiotensin-converting enzyme inhibitor, promotes vasodilatation mediated by both bradykinin B(2) and M1 muscarinic acetylcholine receptors

Bradykinin-potentiating peptides (BPPs) or proline-rich oligopeptides (PROs) isolated from the venom glands of Bothrops jararaca (Bj) were the first natural inhibitors of the angiotensin-converting enzyme (ACE) described. Bj-PRO-5a (< EKWAP), a member of this structurally related peptide family, was essential for the development of captopril, the first site-directed ACE inhibitor used for the treatment of human hypertension. Nowadays, more Bj-PROs have been identified with higher ACE inhibition potency compared to Bj-PRO-5a. However, despite its modest inhibitory effect of ACE inhibition, Bj-PRO-5a reveals strong bradykinin-potentiating activity, suggesting the participation of other mechanisms for this peptide. In the present study, we have shown that Bj-PRO-5a induced nitric oxide (NO) production depended on muscarinic acetylcholine receptor M1 subtype (mAchR-M1) and bradykinin B(2) receptor activation, as measured by a chemiluminescence assay using a NO analyzer. Intravital microscopy based on transillumination of mice cremaster muscle also showed that both bradykinin B(2) receptor and mAchR-M1 contributed to the vasodilatation induced by Bj-PRO-5a. Moreover, Bj-PRO-5a-mediated vasodilatation was completely blocked in the presence of a NO synthase inhibitor. The importance of this work lies in the definition of novel targets for Bj-PRO-5a in addition to ACE, the structural model for captopril development. (C) 2011 Elsevier Inc. All rights reserved.

Enhancement of the citrulline-nitric oxide cycle in astroglioma cells by the proline-rich peptide-10c from Bothrops jararaca venom

The biological activity of the proline rich decapeptde Bj PRO 10c a processing product of the C type natriuretic peptide precursor protein, expressed in the brain and the venom gland of the pit viper Bothrops jararaca, was originally attributed to the inhibition of the somatic angiotensm converting enzyme activity with subsequent ant hypertensive effect However recent results suggest broader biological activity may also be involved in the cardiovascular effects of this peptide Here we show that Bj PRO 10c enhances and sustains the generation of nitric made (NO) by regulating argininosuccinate synthase activity and thereby velocity of the citrulline NO cycle Bj PRO 10c-mediated effects not restricted to the cardiovascular system since NO production was also induced in cells of astroglial origin Bj PRO 10c was internalized by C6 astroglioma cells where it induces NO production and upregulation of the citrulline NO cycle cells in a dose dependent fashion In view of that, astroglial cells function as L arginine pool for NO production in neighboring neurons, we suggest a regulatory function for Bj PRO-10c on the metabolism of this gaseous neurotransmitter in the CNS Moreover, proliferation of astroglial cells was reduced in the presence of Bj PRO 10c however, cell death was not induced Since NO donors have been studied for the treatment of solid cancers Bj PRO 10c may serve as structural model for developing drugs to improve the effects of cancer therapy based on the peptide`s ability to augment NO production (C) 2010 Elsevier B V All rights reserved

A pointcut-based coverage analysis approach for aspect-oriented programs

Aspect-oriented programming (AOP) is a promising technology that supports separation of crosscutting concerns (i.e., functionality that tends to be tangled with, and scattered through the rest of the system). In AOP, a method-like construct named advice is applied to join points in the system through a special construct named pointcut. This mechanism supports the modularization of crosscutting behavior; however, since the added interactions are not explicit in the source code, it is hard to ensure their correctness. To tackle this problem, this paper presents a rigorous coverage analysis approach to ensure exercising the logic of each advice - statements, branches, and def-use pairs - at each affected join point. To make this analysis possible, a structural model based on Java bytecode - called PointCut-based Del-Use Graph (PCDU) - is proposed, along with three integration testing criteria. Theoretical, empirical, and exploratory studies involving 12 aspect-oriented programs and several fault examples present evidence of the feasibility and effectiveness of the proposed approach. (C) 2010 Elsevier Inc. All rights reserved.

Effects of Side-Chain and Electron Exchange Correlation on the Band Structure of Perylene Diimide Liquid Crystals: A Density Functional Study

The structural and electronic properties of perylene diimide liquid crystal PPEEB are studied using ab initio methods based on the density functional theory (I)FT). Using available experimental crystallographic data as a guide, we propose a detailed structural model for the packing of solid PPEEB. We find that due to the localized nature of the band edge wave function, theoretical approaches beyond the standard method, such as hybrid functional (PBE0), are required to correctly characterize the band structure of this material. Moreover, unlike previous assumptions, we observe the formation of hydrogen bonds between the side chains of different molecules, which leads to a dispersion of the energy levels. This result indicates that the side chains of the molecular crystal not only are responsible for its structural conformation but also can be used for tuning the electronic and optical properties of these materials.

Analysis of Agonist and Antagonist Effects on Thyroid Hormone Receptor Conformation by Hydrogen/Deuterium Exchange

Thyroid hormone receptors (TRs) are ligand-gated transcription factors with critical roles in development and metabolism. Although x-ray structures of TR ligand-binding domains (LBDs) with agonists are available, comparable structures without ligand (apo-TR) or with antagonists are not. It remains important to understand apo-LBD conformation and the way that it rearranges with ligands to develop better TR pharmaceuticals. In this study, we conducted hydrogen/deuterium exchange on TR LBDs with or without agonist (T(3)) or antagonist (NH(3)). Both ligands reduce deuterium incorporation into LBD amide hydrogens, implying tighter overall folding of the domain. As predicted, mass spectroscopic analysis of individual proteolytic peptides after hydrogen/deuterium exchange reveals that ligand increases the degree of solvent protection of regions close to the buried ligand-binding pocket. However, there is also extensive ligand protection of other regions, including the dimer surface at H10-H11, providing evidence for allosteric communication between the ligand-binding pocket and distant interaction surfaces. Surprisingly, C-terminal activation helix H12, which is known to alter position with ligand, remains relatively protected from solvent in all conditions suggesting that it is packed against the LBD irrespective of the presence or type of ligand. T(3), but not NH(3), increases accessibility of the upper part of H3-H5 to solvent, and we propose that TR H12 interacts with this region in apo-TR and that this interaction is blocked by T(3) but not NH(3.) We present data from site-directed mutagenesis experiments and molecular dynamics simulations that lend support to this structural model of apo-TR and its ligand-dependent conformational changes. (Molecular Endocrinology 25: 15-31, 2011)

The Secret Aria on Shame : An Analysis of Narrative Structure and Theme in Coetzee's "Diary of a Bad Year"

Coetzee’s last novel Diary of a Bad Year (2007) has an intriguing triple-voiced narrative structure and deals with the grey area of shame. The narrative is divided between a writer, his written contribution to a book called “Strong Opinions”, and his secretary’s thoughts about both the opinions in the manuscript and her employer’s circumstances. This essay explores the relation between form and theme in Diary of a Bad Year; to see in what way these two fundamental elements of the novel intervene and support each other. By doing so the narrative structure is read through Freud’s structural model of personality, whereby each narrator’s voice is related to the notions of the super-ego, the ego and the id. In other words, this essay argues that the specific threefold narrative structure in Diary of a Bad Year, by reflecting the interrelated parts of human identity, helps in creating and developing the theme of shame, which only exists connected to the human psyche. This connection in turn gives special meaning to the entire narratology of the novel.

A Note on Proxy Variables and Instrument Variable Regression

This is a note about proxy variables and instruments for identification of structural parameters in regression models. We have experienced that in the econometric textbooks these two issues are treated separately, although in practice these two concepts are very often combined. Usually, proxy variables are inserted in instrument variable regressions with the motivation they are exogenous. Implicitly meaning they are exogenous in a reduced form model and not in a structural model. Actually if these variables are exogenous they should be redundant in the structural model, e.g. IQ as a proxy for ability. Valid proxies reduce unexplained variation and increases the efficiency of the estimator of the structural parameter of interest. This is especially important in situations when the instrument is weak. With a simple example we demonstrate what is required of a proxy and an instrument when they are combined. It turns out that when a researcher has a valid instrument the requirements on the proxy variable is weaker than if no such instrument exists

Review of the literature on credit risk modeling : development of the past 10 years

This paper traces the developments of credit risk modeling in the past 10 years. Our work can be divided into two parts: selecting articles and summarizing results. On the one hand, by constructing an ordered logit model on historical Journal of Economic Literature (JEL) codes of articles about credit risk modeling, we sort out articles which are the most related to our topic. The result indicates that the JEL codes have become the standard to classify researches in credit risk modeling. On the other hand, comparing with the classical review Altman and Saunders(1998), we observe some important changes of research methods of credit risk. The main finding is that current focuses on credit risk modeling have moved from static individual-level models to dynamic portfolio models.

Estimation of genetic variance for macro- and micro-environmental sensitivity using double hierarchical generalized linear models

Background: Genetic variation for environmental sensitivity indicates that animals are genetically different in their response to environmental factors. Environmental factors are either identifiable (e.g. temperature) and called macro-environmental or unknown and called micro-environmental. The objectives of this study were to develop a statistical method to estimate genetic parameters for macro- and micro-environmental sensitivities simultaneously, to investigate bias and precision of resulting estimates of genetic parameters and to develop and evaluate use of Akaike’s information criterion using h-likelihood to select the best fitting model. Methods: We assumed that genetic variation in macro- and micro-environmental sensitivities is expressed as genetic variance in the slope of a linear reaction norm and environmental variance, respectively. A reaction norm model to estimate genetic variance for macro-environmental sensitivity was combined with a structural model for residual variance to estimate genetic variance for micro-environmental sensitivity using a double hierarchical generalized linear model in ASReml. Akaike’s information criterion was constructed as model selection criterion using approximated h-likelihood. Populations of sires with large half-sib offspring groups were simulated to investigate bias and precision of estimated genetic parameters. Results: Designs with 100 sires, each with at least 100 offspring, are required to have standard deviations of estimated variances lower than 50% of the true value. When the number of offspring increased, standard deviations of estimates across replicates decreased substantially, especially for genetic variances of macro- and micro-environmental sensitivities. Standard deviations of estimated genetic correlations across replicates were quite large (between 0.1 and 0.4), especially when sires had few offspring. Practically, no bias was observed for estimates of any of the parameters. Using Akaike’s information criterion the true genetic model was selected as the best statistical model in at least 90% of 100 replicates when the number of offspring per sire was 100. Application of the model to lactation milk yield in dairy cattle showed that genetic variance for micro- and macro-environmental sensitivities existed. Conclusion: The algorithm and model selection criterion presented here can contribute to better understand genetic control of macro- and micro-environmental sensitivities. Designs or datasets should have at least 100 sires each with 100 offspring.

Stock Markets and Household Wealth: Can a Stock Market Crash Cause a Recession in The U.S. Economy?

Stock market wealth effects on the level of consumption in the United States economy have been constantly debated; there is evidence for arguments for and against its prominence and its symmetry. This paper seeks to investigate the strength of its negative effect by creating models to analyze unexpected shocks to the Standard and Poor's 500 index. First, a transmission mechanism between the stock market and GDP is established through the use of second-order vector autoregressive models. Following which, theory from the life cycle model and adaptations of previous researchers' models are used to create a structural model. This paper finds that stock market wealth effects are small, but important to consider, especially if markets are overpriced; this claim is corroborated by evidence from simulation of 'alternative scenarios' and the historical experiences of 1987 and 2001.

A relação entre nacionalidade, valores pessoais e o comportamento do consumidor em shopping centers regionais de Eugene (Estados Unidos), Montevidéu (Uruguai) e Porto Alegre (Brasil)

A globalização e o surgimento dos mercados internacionais têm trazido no bojo de sua evolução o interesse pela compreensão da relação entre a nacionalidade e o comportamento do consumidor ao redor do mundo. Embora a globalização seja um tema em evidência na literatura de marketing (Hadjimarcou, 1998), poucos são os estudos que analisam o comportamento trans -cultural do consumidor em ambientes de varejo na América do Sul. Verifica-se, nesta área, um franco predomínio da produção científica norte-americana, que se restringe a investigar a dinâmica do comportamento do consumidor entre as diversas “nações” existentes nos Estados Unidos (Czinkota e Ronkainen, 2001). Diante do desafio de se compreender a dinâmica existente entre a nacionalidade e o comportamento do consumidor em ambientes de varejo no contexto internacional, elegeu-se como cenário de pesquisa três países que guardam entre si similaridades e distinções marcantes: Brasil, Uruguai e Estados Unidos. Na busca de se colaborar com a consolidação do tema no escopo da área de marketing, este estudo investigou a relação entre a nacionalidade e o comportamento do consumidor nos shopping centers regionais em contextos internacionais. Brasileiros e uruguaios encontram-se imersos num caldo étnico e econômico que se confunde com a própria formação sócio-cultural dos dois países. Os resultados alcançados neste estudo revelam que a proximidade que eiva a relação histórica comum de Brasil e Uruguai manifestam-se valores pessoais e na forma como brasileiros e uruguaios se comportam nos shopping centers. Empregando-se a técnica de modelagem de equações estruturais, revelou-se que a nacionalidade guarda uma relação causal com os valores pessoais e o comportamento do consumidor nos shopping centers regionais dos três países. O modelo estrutural final obteve bons índices de ajustamento, indicando que a nacionalidade exerceu influência indireta sobre comportamento do consumidor nos shopping centers regionais através da mediação dos valores pessoais e atitudes em relação aos atributos daqueles centros de compras. No capítulo de conclusão apresenta-se as implicações dos resultados obtidos, as limitações do estudo e novas possibilidades de pesquisa que surgiram com a realização deste estudo.

Escolariedade, salários e empregabilidade: implicações no mercado de empregos do Rio de Janeiro

The high degree of flexibility has been pointed as one of the outstanding characteristics of the Brazilian job market. Employability is being a frequent discussion issue among the professionals of the human resources area. The Human Capital Theory and the contemporary discussion concerning Employability argue the relationship of the educational practice and of the production practice in a capitalist economical-social structure as a whole. The education consequences in the individuals' life are reflected in several ways, direct and indirectly. Our objective is to evaluate, with statistics methods, and in that universe of consequences, the explanatory events of the relationships between education-wage and education¿job. The main reason of this work is to evaluate the relationship between education, wage and Employability from a structural model perspective, seeking to compare and to contrast two effective theories: the one from the human capital and other from the Employability. To make this analysis, a database of individuals that are working at the formal work market in the Rio de Janeiro Metropolitan Area, had been used. The results showed the education importance on the wage level, as well as, on the Employability factor, whose values and highest taxes correspond to the individuals graduated on the university.

Colecionar: do ideal temático às posses que lhe dão tangibilidade e concretude ao estender o eu (self) do colecionador

Este trabalho procura dar uma resposta à seguinte pergunta de pesquisa: quais variáveis influenciam o comportamento colecionar a partir da perspectiva do consumidor? Para tanto, faz uso de métodos complementares: uso de análise de conteúdo e de modelagem de equações estruturais. As seguintes variáveis foram identificadas: ideal temático, envolvimento, desejo, prazer, permanência, ocupação do espaço e exposição, conhecimento e autoridade. O construto ideal temático foi desenvolvido e escalas para medi-lo e às variáveis permanência, ocupação do espaço e exposição, conhecimento, autoridade e colecionar também foram desenvolvidas. Os resultados sugerem que o modelo estrutural de colecionar aqui desenvolvido é consistente, confiável e válido pelos diversos critérios de análise empregados (índices de adequação do modelo; verificação das hipóteses do modelo; coeficientes de determinação; efeitos diretos, indiretos e totais dos caminhos do modelo e análise de modelos alternativos) e que, portanto, representa uma construção cabível do fenômeno colecionar na área de comportamento do consumidor e que o colecionar é uma forma de estender o eu do colecionador, de uma forma diferenciada, especial. Neste estudo esse fato foi ligado à influência do ideal temático no colecionar.

Criação e teste de uma escala para avaliação da estratégia de gestão do conhecimento : aplicação a um escritório de propriedade intelectual

Esta dissertação objetiva avaliar como as empresas organizam sua estratégia para gestão do conhecimento. Basicamente dois modelos estratégicos são apresentados na literatura: a codificação e a personalização. No entanto, há uma questão que se apresenta na literatura que se refere à importância do foco prioritário em apenas um dos modelos estratégicos citados. Como objetivo principal, pretende-se apresentar uma escala que possa analisar se uma empresa líder em seu segmento realmente possui um foco estratégico com relação à gestão do conhecimento. Durante o desenvolvimento deste trabalho, será percorrido um referencial teórico que busca explicar como a gestão do conhecimento se tomou importante para a estratégia das empresas, tocando em pontos como características da Era da Informação e conceitos básicos da gestão do conhecimento, englobando modelos teóricos que buscam explicar como o conhecimento é criado e transferido dentro das empresas. Um modelo para mensuração do foco estratégico de uma empresa será proposto. Este modelo será composto de indicadores estruturados em forma de um questionário. Para cada indicador haverá uma escala de avaliação e o conjunto do questionário buscará traduzir o foco estratégico citado. Por fim, o questionário será testado em uma empresa de Propriedade Intelectual e serão feitas análises estatísticas para avaliação do mesmo. Para isto será utilizado o procedimento da análise fatorial do tipo confirmatória. Trata-se de uma ferramenta estatística que possibilita uma avaliação tanto do modelo de análise, quanto do modelo estrutural.

Psicologia social, ideológica e meta-ideológica: (psicogênese e sociogênese no modelo dialético)

O presente estudo propõe uma interpretação da Psicologia Social como expressão da relação homem/meio, baseada no modelo dialético genético-estrutural Piagetano. É conceituada uma interdependência entre diferentes níveis de análise teórica e uma continuidade do mais simples ao complexo, mantendo-se a autonomia relativa, em cada nível que, com suas próprias leis, obedecerá ao sistema global da organização vital: níveis biológicos, psicológicos e sociológicos encadeiam-se, sem que se possa definir um limite estrito entre eles. Supera-se assim o problema metodológico de abstração de níveis que leva a consideráveis distorções, especialmente quando se abstrai o nível político-social. Psicologia Social será o estudo da ação que uma estrutura social provoca no indivíduo e a ação recíproca que o indivíduo exerce sobre a estrutura social: o sujeito participa ativamente, em grupo, da construção da estrutura que sobre ele atua. Frente à abordagem psicossocial dominante, empírico-analítica e à abordagem alternativa, histórico-social, e introduzida uma visão interacionista que integra como complementares posições conflitantes, sendo criticadas teorias que pretendem reduzir o comportamento humano ao meio ou ao sujeito. É proposta uma teoria psicobiológica da relação homem/meio que definira o grau de desenvolvimento atingido pelo indivíduo e grupo como função da interação permitida: se o contexto for repressor, ocorrera uma atualização empobrecida de fenótipos culturais. O psicólogo social deverá ter um enfoque do desenvolvimento do indivíduo e sociedade, para poder atuar de forma politicamente relevante. A ideologia ê interpretada como expressa0 de uma função humana mais geral, a função simbólica e será sempre dependente da autorregularão atingida pelo grupo em um contexto sócio-político específico. Como uma ação concreta sempre é ideológica por sua práxis, um nível meta-ideológico só será atingido através da atuação num nível ideológico; apenas através da pesquisa psico e sociogenética se atingirá um dado não-ideológico.