Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents

In previous studies, we identified promising anti-Trypanosoma cruzi cruzain inhibitors based on thiazolylhydrazones. To optimize this series, a number of medicinal chemistry directions were explored and new thiazolylhydrazones and thiosemicarbazones were thus synthesized. Potent cruzain inhibitors were identified, such as thiazolylhydrazones 3b and 3j, which exhibited IC(50) of 200-400 nM. Furthermore, molecular docking studies showed concordance with experimentally derived structure-activity relationships (SAR) data. In the course of this work, lead compounds exhibiting in vitro activity against both the epimastigote and trypomastigote forms of T. cruzi were identified and in vivo general toxicity analysis was subsequently performed. Novel SAR were documented, including the importance of the thiocarbonyl carbon attached to the thiazolyl ring and the direct comparison between thiosemicarbazones and thiazolylhydrazones. (C) 2010 Elsevier Ltd. All rights reserved.

A dislocation based theory for the deformation hardening behavior of DP steels : Impact of martensite content and ferrite grain size

A dislocation model, accurately describing the uniaxial plastic stress-strain behavior of dual phase (DP) steels, is proposed and the impact of martensite content and ferrite grain size in four commercially produced DP steels is analyzed. It is assumed that the plastic deformation process is localized to the ferrite. This is taken into account by introducing a non-homogeneity parameter, f(e), that specifies the volume fraction of ferrite taking active part in the plastic deformation process. It is found that the larger the martensite content the smaller the initial volume fraction of active ferrite which yields a higher initial deformation hardening rate. This explains the high energy absorbing capacity of DP steels with high volume fractions of martensite. Further, the effect of ferrite grain size strengthening in DP steels is important. The flow stress grain size sensitivity for DP steels is observed to be 7 times larger than that for single phase ferrite.

The asymmetric behavior of the U.S public debt

Our main goal in this paper was to measure how e¢ cient is risk sharing between countries. In order to do so, we have used a international risk sharIn this paper we re-analyze the question of the U.S. public debt sustainability by using a quantile autoregression model. This modeling allows for testing whether the behavior of U.S. public debt is asymmetric or not. Our results provide evidence of a band of sustainability. Outside this band, the U.S. public debt is unsustainable. We also nd scal policy to be adequate in the sense that occasional episodes in which the public debt moves out of the band do not pose a threat to long run sustainability.

The asymmetric behavior of the U.S. public debt

In this paper we re-analyze the question of the U.S. public debt sustainability by using a quantile autoregression model. This modeling allows for testing whether the behavior of U.S. public debt is asymmetric or not. Our results provide evidence of a band of sustainability. Outside this band, the U.S. public debt is unsustainable. We also find fiscal policy to be adequate in the sense that occasional episodes in which the public debt moves out of the band do not pose a threat to long run sustainability.

The behavior of temporary sales in a macroeconomic context

Nós investigamos promoções temporárias usando uma base de dados detalhada de 13 anos sobre preços ao consumidor no Brasil, com cotações de preços coletadas decendialmente. Nós encontramos forte evidências da existência de relação entre a frequência e tamanho de promoções e as variáveis macroeconômicas. A crença comum na literatura de que promoções não reagem a mudanças nas variáveis macroeconômicas pode ser devido a baixa volatilidade do cenário macro- econômico nos países analisados até o presente momento.

Structural analysis of the place of wine in Brazil

With the constant decrease of the wine consumption in traditional winemaking countries, more and more Brazil is seen as an appealing market. But the country also pretends to become an international player of winemaking in its own right. Both the participants of the Brazilian wine industry and the foreigners trying to get advantage of this promising market are facing new challenges to develop the consumption of wine in the world’s fifth largest country. Among all the possible actions to be taken in that sense, it also is worth taking time for a collective thought on the place of wine in the country, as well as the factors that shape it. What are these factors, which ones really make the difference, and what is their respective impact on the evolution of the place of wine in the country? After drawing the big picture of the wine market situation, this thesis tries to identify the levers of the evolution of the place of wine in Brazil. Using the tools of prospective, it aims at putting into perspective the different driving forces that influence its development, and in particular the relative influence of the political drivers. This paper also intends to be a first step of a prospective study as it constitutes a solid base for scenario planning. This paper is divided in five chapters starting with “introduction”, followed by chapter 2 “Theoretical framework”. Chapter 3 is “Methodology”, followed by chapter 4 “Description and analysis of the results”. Finally the results are discussed and concluded in the last part “Conclusions and implications for future studies”.

Using common features to understand the behavior of metal-commodity prices and forecast them at different horizons

The objective of this article is to study (understand and forecast) spot metal price levels and changes at monthly, quarterly, and annual frequencies. Data consists of metal-commodity prices at a monthly and quarterly frequencies from 1957 to 2012, extracted from the IFS, and annual data, provided from 1900-2010 by the U.S. Geological Survey (USGS). We also employ the (relatively large) list of co-variates used in Welch and Goyal (2008) and in Hong and Yogo (2009). We investigate short- and long-run comovement by applying the techniques and the tests proposed in the common-feature literature. One of the main contributions of this paper is to understand the short-run dynamics of metal prices. We show theoretically that there must be a positive correlation between metal-price variation and industrial-production variation if metal supply is held fixed in the short run when demand is optimally chosen taking into account optimal production for the industrial sector. This is simply a consequence of the derived-demand model for cost-minimizing firms. Our empirical evidence fully supports this theoretical result, with overwhelming evidence that cycles in metal prices are synchronized with those in industrial production. This evidence is stronger regarding the global economy but holds as well for the U.S. economy to a lesser degree. Regarding out-of-sample forecasts, our main contribution is to show the benefits of forecast-combination techniques, which outperform individual-model forecasts - including the random-walk model. We use a variety of models (linear and non-linear, single equation and multivariate) and a variety of co-variates and functional forms to forecast the returns and prices of metal commodities. Using a large number of models (N large) and a large number of time periods (T large), we apply the techniques put forth by the common-feature literature on forecast combinations. Empirically, we show that models incorporating (short-run) common-cycle restrictions perform better than unrestricted models, with an important role for industrial production as a predictor for metal-price variation.

Biological and structural characterization of a new PLA(2) from the Crotalus durissus collilineatus venom

In the present article we report on the biological characterization and amino acid sequence of a new basic Phospholipases A(2) (PLA(2)) isolated from the Crotalus durissus collilineatus venom (Cdcolli F6), which showed the presence of 122 amino acid residues with a pI value of 8.3, molecular mass of 14 kDa and revealed an amino acid sequence identity of 80% with crotalic PLA(2)s such as Mojave B, Cdt F15, and CROATOX. This homology, however, dropped to 50% if compared to other sources of PLA(2)s such as from the Bothrops snake venom. Also, this PLA(2) induced myonecrosis, although this effect was lower than that of BthTx-I or whole crotoxin and it was able to induce a strong blockage effect on the chick biventer neuromuscular preparation, independently of the presence of the acid subunid (crotapotin). The neurotoxic effect was strongly reduced by pre-incubation with heparin or with anhydrous acetic acid and rho-BPB showed a similar reduction. The rho-BPB did not reduce significantly the myotoxic activity induced by the PLA(2), but the anhydrous acetic acid treatment and the pre-incu-bation of PLA(2) with heparin reduced significantly its effects. This protein showed a strong antimicrobial activity against Xanthomonas axonopodis passiflorae (Gram-negative), which was drastically reduced by incubation of this PLA(2) with rho-BPB, but this effect was marginally reduced after treatment with anhydrous acetic acid. Our findings here allow to speculate that basic amino acid residues on the C-terminal and molecular regions near catalytic site regions such as Calcium binding loop or rho-wing region may be involved in the binding of this PLA(2) to the molecular receptor to induce the neurotoxic effect. The bactericidal effect, however, was completely dependent on the enzymatic activity of this protein.

Structural Aspects of the Distinct Biochemical Properties of Glutaredoxin 1 and Glutaredoxin 2 from Saccharomyces cerevisiae

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

The effect of increased light intensity on the aggressive behavior of the Nile tilapia, Oreochromis niloticus (Teleostei: Cichlidae)

Animals show behavioral and physiological changes that emerge in response to environmental perturbations (i.e., emergency life-history stages). In this study, we investigate the effects of light intensity on aggressive encounters and social stability in groups of adult male Nile tilapia, Oreochromis niloticus (Linnaeus, 1758). The study compared the behavior observed under low (280.75 ± 50.60 lx) and high (1394.14 ± 520.32 lx) light intensities, with 12 replicates for each treatment. Adult fish were isolated in 36-L aquaria for 96 hours, and three males were grouped for 11 days in 140-L aquaria. Agonistic behavior was video-recorded (10 min/day) on the 3rd, 5th, 7th, and 9th day to quantify aggressive interactions and social stability. There was an effect of light intensity and day of observation on the total number of agonistic behaviors performed by the fish group. Besides, increased frequency of aggressive interactions (the sum of the four sessions) by the alpha, beta and gamma fish occurred at the higher light intensity. The dominance ranks of the fish remained unchanged across the observation sessions under both the low and high light intensities. We concluded that enhanced light intensity has a cumulative effect that increases the aggressiveness of the Nile tilapia but that this effect is not sufficiently strong to destabilize the social hierarchy.

Structural features of the epididymal region of the domestic duck (Anas plathyrynchos)

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