Regulation of mitogen-activated protein kinases in cardiac myocytes through the small G protein Rac1.

Small guanine nucleotide-binding proteins of the Ras and Rho (Rac, Cdc42, and Rho) families have been implicated in cardiac myocyte hypertrophy, and this may involve the extracellular signal-related kinase (ERK), c-Jun N-terminal kinase (JNK), and/or p38 mitogen-activated protein kinase (MAPK) cascades. In other systems, Rac and Cdc42 have been particularly implicated in the activation of JNKs and p38-MAPKs. We examined the activation of Rho family small G proteins and the regulation of MAPKs through Rac1 in cardiac myocytes. Endothelin 1 and phenylephrine (both hypertrophic agonists) induced rapid activation of endogenous Rac1, and endothelin 1 also promoted significant activation of RhoA. Toxin B (which inactivates Rho family proteins) attenuated the activation of JNKs by hyperosmotic shock or endothelin 1 but had no effect on p38-MAPK activation. Toxin B also inhibited the activation of the ERK cascade by these stimuli. In transfection experiments, dominant-negative N17Rac1 inhibited activation of ERK by endothelin 1, whereas activated V12Rac1 cooperated with c-Raf to activate ERK. Rac1 may stimulate the ERK cascade either by promoting the phosphorylation of c-Raf or by increasing MEK1 and/or -2 association with c-Raf to facilitate MEK1 and/or -2 activation. In cardiac myocytes, toxin B attenuated c-Raf(Ser-338) phosphorylation (50 to 70% inhibition), but this had no effect on c-Raf activity. However, toxin B decreased both the association of MEK1 and/or -2 with c-Raf and c-Raf-associated ERK-activating activity. V12Rac1 cooperated with c-Raf to increase expression of atrial natriuretic factor (ANF), whereas N17Rac1 inhibited endothelin 1-stimulated ANF expression, indicating that the synergy between Rac1 and c-Raf is potentially physiologically important. We conclude that activation of Rac1 by hypertrophic stimuli contributes to the hypertrophic response by modulating the ERK and/or possibly the JNK (but not the p38-MAPK) cascades.

Signaling pathways mediating cardiac myocyte gene expression in physiological and stress responses

The contractile cells in the heart (the cardiac myocytes) are terminally differentiated. In response to pathophysiological stresses, cardiac myocytes undergo hypertrophic growth or apoptosis, responses associated with the development of cardiac pathologies. There has been much effort expended in gaining an understanding of the stimuli which promote these responses, and in identifying the intracellular signaling pathways which are activated and potentially involved. These signaling pathways presumably modulate gene and protein expression to elicit the end-stage response. For the regulation of gene expression, the signal may traverse the cytoplasm to modulate nuclear-localized transcription factors as occurs with the mitogen-activated protein kinase or protein kinase B/Akt cascades. Alternatively, the signal may promote translocation of transcription factors from the cytoplasm to the nucleus as is seen with the calcineurin/NFAT and JAK/STAT systems. We present an overview of the principal signaling pathways implicated in the regulation of gene expression in cardiac myocyte pathophysiology, and summarize the current understanding of these pathways, the transcription factors they regulate and the changes in gene expression associated with the development of cardiac pathologies. Finally, we discuss how intracellular signaling and gene expression may be integrated to elicit the overall change in cellular phenotype.

Genomic evidence for the Pleistocene and recent population history of Native Americans

How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative “Paleoamerican” relict populations, including the historical Mexican Pericúes and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.

Precambrian geotectonic units of the Rio de La Plata craton

The main Precambrian tectonic units of Uruguay include the Piedra Alta tectonostratigraphic terrane (PATT) and Nico Perez tectonostratigraphic terrane (NPTT), separated by the Sarandi del Yi high-strain zone. Both terranes are well exposed in the Rio de La Plata craton (RPC). Although these tectonic units are geographically small, they record a wide span of geologic time. Therefore improved geological knowledge of this area provides a fuller understanding of the evolution of the core of South America. The PATT is constituted by low-to medium-grade metamorphic belts (ca. 2.1 Ga); its petrotectonic associations such as metavolcanic units, conglomerates, banded iron formations, and turbiditic deposits suggest a back-arc or a trench-basin setting. Also in the PATT, a late to post-orogenic, arc-related layered mafic complex (2.3-1.9 Ga), followed by A-type granites (2.08 Ga), and finally a taphrogenic mafic dike swarm (1.78 Ga) occur. The less thoroughly studied NPTT consists of Palaeoproterozoic high-grade metamorphic sequences (ca. 2.2 Ga), mylonites and postorogenic and rapakivi granites (1.75 Ga). The Brasiliano-Pan African orogeny affected this terrane. Neoproterozoic cover occurs in both tectonostratigraphic terranes, but is more developed in the NPTT. Over the past 15 years, new isotopic studies have improved our recognition of different tectonic events and associated processes, such as reactivation of shear zones and fluids circulation. Transamazonian and Statherian tectonic events were recognized in the RPC. Based on magmatism, deformation, basin development and metamorphism, we propose a scheme for the Precambrian tectonic evolution of Uruguay, which is summarized in the first Palaeoproterozoic tectonic map of the Rio de La Plata craton.

Testing unit root based on partially adaptive estimation

This paper proposes unit tests based on partially adaptive estimation. The proposed tests provide an intermediate class of inference procedures that are more efficient than the traditional OLS-based methods and simpler than unit root tests based on fully adptive estimation using nonparametric methods. The limiting distribution of the proposed test is a combination of standard normal and the traditional Dickey-Fuller (DF) distribution, including the traditional ADF test as a special case when using Gaussian density. Taking into a account the well documented characteristic of heavy-tail behavior in economic and financial data, we consider unit root tests coupled with a class of partially adaptive M-estimators based on the student-t distributions, wich includes te normal distribution as a limiting case. Monte Carlo Experiments indicate that, in the presence of heavy tail distributions or innovations that are contaminated by outliers, the proposed test is more powerful than the traditional ADF test. We apply the proposed test to several macroeconomic time series that have heavy-tailed distributions. The unit root hypothesis is rejected in U.S. real GNP, supporting the literature of transitory shocks in output. However, evidence against unit roots is not found in real exchange rate and nominal interest rate even haevy-tail is taken into a account.

Ensaios em macroeconometria e finanças

This thesis is composed of three essays referent to the subjects of macroeconometrics and Önance. In each essay, which corresponds to one chapter, the objective is to investigate and analyze advanced econometric techniques, applied to relevant macroeconomic questions, such as the capital mobility hypothesis and the sustainability of public debt. A Önance topic regarding portfolio risk management is also investigated, through an econometric technique used to evaluate Value-at-Risk models. The Örst chapter investigates an intertemporal optimization model to analyze the current account. Based on Campbell & Shillerís (1987) approach, a Wald test is conducted to analyze a set of restrictions imposed to a VAR used to forecast the current account. The estimation is based on three di§erent procedures: OLS, SUR and the two-way error decomposition of Fuller & Battese (1974), due to the presence of global shocks. A note on Granger causality is also provided, which is shown to be a necessary condition to perform the Wald test with serious implications to the validation of the model. An empirical exercise for the G-7 countries is presented, and the results substantially change with the di§erent estimation techniques. A small Monte Carlo simulation is also presented to investigate the size and power of the Wald test based on the considered estimators. The second chapter presents a study about Öscal sustainability based on a quantile autoregression (QAR) model. A novel methodology to separate periods of nonstationarity from stationary ones is proposed, which allows one to identify trajectories of public debt that are not compatible with Öscal sustainability. Moreover, such trajectories are used to construct a debt ceiling, that is, the largest value of public debt that does not jeopardize long-run Öscal sustainability. An out-of-sample forecast of such a ceiling is also constructed, and can be used by policy makers interested in keeping the public debt on a sustainable path. An empirical exercise by using Brazilian data is conducted to show the applicability of the methodology. In the third chapter, an alternative backtest to evaluate the performance of Value-at-Risk (VaR) models is proposed. The econometric methodology allows one to directly test the overall performance of a VaR model, as well as identify periods of an increased risk exposure, which seems to be a novelty in the literature. Quantile regressions provide an appropriate environment to investigate VaR models, since they can naturally be viewed as a conditional quantile function of a given return series. An empirical exercise is conducted for daily S&P500 series, and a Monte Carlo simulation is also presented, revealing that the proposed test might exhibit more power in comparison to other backtests.

Testes empíricos da eficiência do mercado acionário brasileiro

Este trabalho tem por objetivo avaliar a eficiência do mercado acionário brasileiro a partir de testes estatísticos, para posterior modelagem das séries de retorno das ações, utilizando os modelos ARMA, ARCH, GARCH, Modelo de Decomposição e, por final, VAR. Para este trabalho foram coletados dados intradiários, que são considerados dados de alta freqüência e menos suscetíveis a possíveis alterações na estrutura de mercado, tanto micro como macroeconômicos. Optou-se por trabalhar com dados coletados a cada cinco minutos, devido à baixa liquidez dos ativos no mercado financeiro (que poderia acarretar em dados ausentes para intervalos de tempo inferiores). As séries escolhidas foram: Petrobrás PN, Gerdau PN, Bradesco PN, Vale do Rio Doce PN e o índice Ibovespa, que apresentam grande representatividade do mercado acionário brasileiro para o período analisado. Com base no teste de Dickey-Fuller, verificou-se indícios que o mercado acionário brasileiro possa ser eficiente e, assim foi proposto modelos para as séries de retorno das ações anteriormente citadas.

Pairs trading : aplicação no mercado acionário brasileiro

Esta dissertação estuda a aplicação da estratégia Pairs Trading no mercado acionário brasileiro. Envolve basicamente a identificação de pares de ações que tenham movimentos de preço semelhantes e posteriormente a operação do diferencial entre seus preços. É possível observar no mercado a existência de um valor de equilíbrio de longo prazo para alguns pares de ações e quando o diferencial divergir de certa quantidade pré-definida opera-se o diferencial no intuito de que o mesmo retorne ao seu valor de equilíbrio de longo prazo, ou seja, espera-se que ocorra uma reversão à média do diferencial. A metodologia para a identificação desses pares de ações que descrevem movimentos semelhantes vem do conceito de cointegração. Essa metodologia é aplicada sobre as ações do índice Bovespa de 04-Jan-1993 a 30-Jun-2005. Inicialmente é feita uma pré-seleção dos pares de ações via correlação, ou medida de distância. Para a seleção final é feito o teste de cointegração, onde é utilizado o método de Dickey-Fuller aumentado (Augmented Dickey-Fuller test – ADF) para verificar a existência de raiz unitária da série de resíduo da combinação linear do logaritmo dos preços. Após a seleção, os pares são simulados historicamente (backtesting) para se analisar a performance dos retornos dos pares de ações, incluindo também os custos operacionais.

As mudanças da indústria automobilística brasileira a partir da década de 90 : as principais políticas setoriais e a nova distribuição geográfica do segmento

Esta dissertação tem como objetivo analisar se determinadas políticas setoriais realizadas na indústria automobilística brasileira na década de 90 provocaram impacto na série de produção de veículos. Para tanto são aplicados o teste de Dickey-Fuller Aumentado, para verificar a presença de raiz unitária, e o teste de Zivot-Andrews, para verificar endogenamente a existência de quebra estrutural da série. Após a aplicação desses testes, observa-se a presença de quebra estrutural ao final de 1997, quando acontece alteração de intercepto na série, porém devido a fatores sem relação com as políticas adotadas. Também a partir de 1997 tem início um novo ciclo de investimentos na indústria montadora, sendo que se verifica que esses novos investimentos acontecem principalmente em locais que não possuíam tradição no segmento, como era o caso dos Estados de São Paulo e Minas Gerais na época. Após estudo da evolução das principais teorias de Geografia Econômica, o trabalho identifica e explora três importantes variáveis que impactaram a definição por essas novas regiões, sendo elas: mão-de-obra, custos de transporte e incentivos governamentais.

Comportamento de pares de ações no mercado brasileiro sob a ótica da cointegração, para preços intra-diários

Esta dissertação estuda o movimento do mercado acionário brasileiro com o objetivo de testar a trajetória de preços de pares de ações, aplicada à estratégia de pair trading. Os ativos estudados compreendem as ações que compõem o Ibovespa e a seleção dos pares é feita de forma unicamente estatística através da característica de cointegração entre ativos, sem análise fundamentalista na escolha. A teoria aqui aplicada trata do movimento similar de preços de pares de ações que evoluem de forma a retornar para o equilíbrio. Esta evolução é medida pela diferença instantânea dos preços comparada à média histórica. A estratégia apresenta resultados positivos quando a reversão à média se efetiva, num intervalo de tempo pré-determinado. Os dados utilizados englobam os anos de 2006 a 2010, com preços intra-diários para as ações do Ibovespa. As ferramentas utilizadas para seleção dos pares e simulação de operação no mercado foram MATLAB (seleção) e Streambase (operação). A seleção foi feita através do Teste de Dickey-Fuller aumentado aplicado no MATLAB para verificar a existência da raiz unitária dos resíduos da combinação linear entre os preços das ações que compõem cada par. A operação foi feita através de back-testing com os dados intra-diários mencionados. Dentro do intervalo testado, a estratégia mostrou-se rentável para os anos de 2006, 2007 e 2010 (com retornos acima da Selic). Os parâmetros calibrados para o primeiro mês de 2006 puderam ser aplicados com sucesso para o restante do intervalo (retorno de Selic + 5,8% no ano de 2006), para 2007, onde o retorno foi bastante próximo da Selic e para 2010, com retorno de Selic + 10,8%. Nos anos de maior volatilidade (2008 e 2009), os testes com os mesmos parâmetros de 2006 apresentaram perdas, mostrando que a estratégia é fortemente impactada pela volatilidade dos retornos dos preços das ações. Este comportamento sugere que, numa operação real, os parâmetros devem ser calibrados periodicamente, com o objetivo de adaptá-los aos cenários mais voláteis.

O enfoque comunitário: uma visão renovadora das abordagens tradicionais em psicologia e aconselhamento

Nos últimos anos, vem sendo desenvolvido um número significativo de abordagens dos problemas comportamentais e sociais. Todas elas fazem parte de um movimento mais amplo de mudança de funções, papéis, metodologias e programas tradicionais das profissões de ajuda. As novas direções vislumbradas em psicologia, ultrapassam os limites de uma postura profissional passiva e destacam que os modelos intrapessoais da psicologia nem sempre condizem com as realidades sociais. o objetivo deste estudo foi fornecer uma visão geral destas abordagens inovadoras, que refletem um posiconamento novo, não tradicional, nas profissões de ajuda, integrando-as em um conjunto coeso: a abordagem comunitária em psicologia e, mais especificamente, no aconselhamento psicológico. A abordagem comunitária enfatiza a necessidade de se desenvolver modelos preventivos e desenvolvimentistas de amplo alcance, em psicologia, bem como a necessidade de se reconhecer o contexto social no qual ela é praticada. Requer novas definições de muitas e papéis para as atividades de ajuda. Tratou-se, neste estudo, de apresentar definições e de estabelecer um fundamento histórico, ideológico e teórico para esta posição, bem como de ilustra-la através de programas de nível comunitário, que extrapolam a orientação tradicional de ajuda. Tratou-se também, dos muitos problemas enfrentados nestes programas e das perspectivas para o novo campo da psicologia e do aconselhamento comunitário. Concluiu-se que a descrição de tal posição poderá fornecer importantes subsídios para aqueles psicólogos interessados em desempenhar um papel profissional mais completo e em atualizar-se acerca das modalidades preventivas e desenvolvimentistas de prestação de serviços.

Pair trading in Bovespa with a quantitative approach: cointegration, Ornstein-Uhlenbeck equation and Kelly criterion.

Pair trading is an old and well-known technique among traders. In this paper, we discuss an important element not commonly debated in Brazil: the cointegration between pairs, which would guarantee the spread stability. We run the Dickey-Fuller test to check cointegration, and then compare the results with non-cointegrated pairs. We found that the Sharpe ratio of cointegrated pairs is greater than the non-cointegrated. We also use the Ornstein-Uhlenbeck equation in order to calculate the half-life of the pairs. Again, this improves their performance. Last, we use the leverage suggested by Kelly Formula, once again improving the results.

Guiana dolphins (Sotalia guianensis) displaying beach hunting behavior in the Cananéia Estuary, Brazil: social context and conservation issues

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

IDENTIFICATION OF A PUTATIVE MEMBRANE-INSERTED SEGMENT IN THE ALPHA-TOXIN OF STAPHYLOCOCCUS-AUREUS

To gain a fuller understanding of the regions of the Staphylococcus aureus alpha-toxin important in pore formation, we have used Forster dipole-dipole energy transfer to demonstrate that a central glycine-rich region of alpha-toxin (the so-called ''hinge'' region) inserts deeply into the bilayer on association of toxin with liposomes. Mutant alpha-toxins with unique cysteine (C) residues at positions 69 and 130 [Palmer, M., et al. (1993) J. Biol. Chem. 268, 11959) were reacted with the C-specific fluorophore acrylodan, which acted as an energy donor. The chosen acceptor was N-(7-nitrobenz-2-oxa-13-diazol-4-yl)-1,2-bis(hexadecanoyl) -sn-glycero-3-phosphoethanolamine (NBD-PE). Measurement of the degree of donor quenching with increasing NBD-PE in the inner bilayer leaflet enables the distance of closest approach between donor and acceptor to be estimated. For toxin labeled with acrylodan at position 130 (in the hinge region), this distance is approximately 5 +/- 2 Angstrom, showing that the probe is close to the inner surface of the liposomes. A second probe labeled at position 69 (in the N-terminal domain) shows negligible energy transfer, indicating a distance of closest approach >40 Angstrom. This implies that this N-terminal region remains ''outside'' the liposome. We propose a model in which the central region of the alpha-toxin inserts into the membrane and possibly participates in forming the wall of the pore.

Camponeses Brazil's Peasant Movement in Historical Perspective (1946-2004)

Comparison of the histories of three leading peasant organizations in the Pontal do Paranapanema region of Brazil-the Partido Comunista do Brasil (PCB) from 1945 to 1964, the Confederacao Nacional de Trabalhadores na Agricultura (CONTAG) from 1964 to 1984, and the Movimento dos Trabalhadores Rurais Sem-Terra (MST) from 1984 to 2004-suggests that continuity is as important as change in understanding Brazilian peasant movements. The MST has been considered a "new social movement" in that it has eschewed partisan politics, incorporated families as members rather than just male heads of household, had a national scope and a participatory decision-making structure, and been attuned to the international struggle over globalization. Placing it in historical perspective makes it clear, however, that this is not the first time that militants have organized around the concept of peasants as a political identity; that while the representation of peasants in the leadership of contemporary rural labor organizations may be greater than in the past, earlier peasant leaders also struggled on behalf of their class; that earlier peasant organizations had, if not a national presence, a substantial presence in the agricultural states of the time; and that attempts at international organization to unite peasant struggles around the globe are not entirely new. This is not to deny the innovative features of contemporary movements but to suggest that the investigation of past achievements will contribute to a fuller appreciation of these movements' conditions and prospects.