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 (NH3). 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, Cterminal 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 NH3, 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 NH3.Wepresent 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). Copyright © 2011 by The Endocrine Society.

Model to design drip hose lateral line using two spacing between emitters

The use of non-pressure compensating drip hose in horticultural and annual cycle fruits is growing in Brazil. In this case, the challenge for designers is getting longer lateral lines with high values of uniformity. The objective of this study was to develop a model to design longer lateral lines using non-pressure compensating drip hose. Using the developed model, the hypotheses to be evaluated were: a) the use of two different spacing between emitters in the same lateral line allows longer length; b) it is possible to get longer lateral lines using high values of pressure variation in the lateral lines since the distribution uniformity stays below allowable limits. A computer program was developed in Delphi based on the model developed and it is able to design lateral lines in level using non-pressure compensating drip hose. The input data are: desired distribution uniformity (DU); initial and final pressure in the lateral line; coefficients of relationship between emitter discharge and pressure head; hose internal diameter; pipe cross-sectional area with the dripper; and roughness coefficient for the Hazen-Williams equation. The program allows calculate the lateral line length with three possibilities: selecting two spacing between emitters and defining the exchange point; using two pre-established spacing between emitters and calculating the length of each section with different spacing; using one emitter spacing. Results showed that the use of two sections with different spacing between drippers in the lateral line didn't allow longer length but got better uniformity when compared with lateral line with one spacing between emitters. The adoption of two spacing increased the flow rate per meter in the final section which represented approximately 80% of the lateral line total length and this justifies their use. The software allowed DU above 90% with pressure head variation of 40% and the use of two spacing between emitters. The developed model/software showed to be accurate, easy to handle and useful for lateral line design using non-pressure compensating drip hose.

The monetary crisis, dollarization and the exchange rate

Includes bibliography

Recovery of pulmonary structure and exercise capacity by treatment with granulocyte-colony stimulating factor (G-CSF) in a mouse model of emphysema

Emphysema is a chronic obstructive pulmonary disease characterized abnormal dilatation of alveolar spaces, which impairs alveolar gas exchange, compromising the physical capacity of a patient due to airflow limitations. Here we tested the effects of G-CSF administration in pulmonary tissue and exercise capacity in emphysematous mice. C57Bl/6 female mice were treated with elastase intratracheally to induce emphysema. Their exercise capacities were evaluated in a treadmill. Lung histological sections were prepared to evaluate mean linear intercept measurement. Emphysematous mice were treated with G-CSF (3 cycles of 200 μg/kg/day for 5 consecutive days, with 7-day intervals) or saline and submitted to a third evaluation 8 weeks after treatment. Values of run distance and linear intercept measurement were expressed as mean ± SD and compared applying a paired t-test. Effects of treatment on these parameters were analyzed applying a Repeated Measures ANOVA, followed by Tukey's post hoc analysis. p < 0.05 was considered statistically significant. Twenty eight days later, animals ran significantly less in a treadmill compared to normal mice (549.7 ± 181.2 m and 821.7 ± 131.3 m, respectively; p < 0.01). Treatment with G-CSF significantly increased the exercise capacity of emphysematous mice (719.6 ± 200.5 m), whereas saline treatment had no effect on distance run (595.8 ± 178.5 m). The PCR cytokines genes analysis did not detect difference between experimental groups. Morphometric analyses in the lung showed that saline-treated mice had a mean linear intercept significantly higher (p < 0.01) when compared to mice treated with G-CSF, which did not significantly differ from that of normal mice. Treatment with G-CSF promoted the recovery of exercise capacity and regeneration of alveolar structural alterations in emphysematous mice. © 2013.

Light front fermion model propagation

In this work we consider the propagation of two fermion fields interacting with each other by the exchange of intermediate scalar bosons in the light front. We obtain the corrections up to fourth order in the coupling constant using hierarchical equations in order to obtain the bound state equation (Bethe - Salpeter equation). © 2013 Chinese Physical Society and IOP Publishing Ltd.

Limite de acoplamento forte da QCD e a interação méson-méson

Pós-graduação em Física - IFT

Exchange-rate variations and the rate of inflation in emerging economies

This paper develops a structural general equilibrium model to analyse the reactions of the nominal exchange rate and the domestic price level to three types of external shock in emerging economies that have limited access to world capital markets. Although the results depend crucially on the type of external shock, each of the two national balance-sheet parameters considered here —the risk premium and the ratio of external indebtedness— exacerbates the reactions of the two endogenous variables without altering the degree of exchange-rate pass-through (erpt). Moreover, flatter Phillips curves, as observed today in many economies, tend to increase erpt. On the basis of these results, the authorities of emerging economies seeking to stabilize markets and limit erpt are advised to minimize the two risk parameters by applying a flexible inflation-targeting regime.

Desorption of heavy metals from ion exchange resin with water and carbon dioxide

Adsorption and regeneration of ion exchange resins were studied using a subcritical solution of a CO₂-H₂O mixture and a fixed bed column. The commercial Amberlite IRC-50/IRC-86 cation exchange resins and Amberlite IRA-67 anion exchange resin were tested for heavy metals (Pb, Cu, Cd) adsorption from a solution with different initial metal concentrations at different temperatures. After adsorption, the loaded resins were regenerated with water and carbon dioxide at different temperatures and a pressure of 25 MPa. The efficiency of the IRC-50 resin was lower than that of the IRC-86 resin for the adsorption of metals like Cd, Cu and Pb. Results obtained for desorption of these metals indicated that the process could be used for Cd and in principle for Cu. Sorption of metal ions depended strongly on feed concentration. Mathematical modeling of the metal desorption process was carried out successfully as an extraction process. For this purpose, the VTII Model, which is applied to extraction from solids using supercritical solvents, was used in this work.

Low mass pseudoscalar dark matter in an extended B - L model

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

Optimized δ expansion for the Walecka model

The optimized δ-expansion is used to study vacuum polarization effects in the Walecka model. The optimized δ-expansion is a nonperturbative approach for field theoretic models which combines the techniques of perturbation theory and the variational principle. Vacuum effects on self-energies and the energy density of nuclear matter are studied up to script O sign(δ2). When exchange diagrams are neglected, the traditional relativistic Hartree approximation (RHA) results are exactly reproduced and, using the same set of parameters that saturate nuclear matter in the RHA, a new stable, tightly bound state at high density is found.

Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary hypertension in a sheep model of acute pulmonary embolism

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

On an energy exchange process and appearance of chaos in a non-ideal portal frame dynamical system

In this paper, we consider non-ideal excitation devices such as DC motors with restrictenergy output capacity. When such motors are attached to structures which needexcitation power levels similar to the source power capacity, jump phenomena and theincrease in power required near resonance characterize the Sommerfeld Effect, actingas a sort of an energy sink. One of the problems often faced by designers of suchstructures is how to drive the system through resonance and avoid this energy sink.Our basic structural model is a simple portal frame driven by a num-ideal powersource-(NIPF). We also investigate the absorption of resonant vibrations (nonlinearand chaotic) by means of a nonlinear sub-structure known as a Nonlinear Energy Sink(NES). An energy exchange process between the NIPF and NES in the passagethrough resonance is investigated, as well the suppression of chaos.

The Cysteine-Rich Protein Thimet Oligopeptidase as a Model of the Structural Requirements for S-glutathiolation and Oxidative Oligomerization

Thimet oligopeptidase (EP24.15) is a cysteine-rich metallopeptidase containing fifteen Cys residues and no intra-protein disulfide bonds. Previous work on this enzyme revealed that the oxidative oligomerization of EP24.15 is triggered by S-glutathiolation at physiological GSSG levels (10-50 mu M) via a mechanism based on thiol-disulfide exchange. In the present work, our aim was to identify EP24.15 Cys residues that are prone to S-glutathiolation and to determine which structural features in the cysteinyl bulk are responsible for the formation of mixed disulfides through the reaction with GSSG and, in this particular case, the Cys residues within EP24.15 that favor either S-glutathiolation or inter-protein thiol-disulfide exchange. These studies were conducted by in silico structural analyses and simulations as well as site-specific mutation. S-glutathiolation was determined by mass spectrometric analyses and western blotting with anti-glutathione antibody. The results indicated that the stabilization of a thiolate sulfhydryl and the solvent accessibility of the cysteines are necessary for S-thiolation. The Solvent Access Surface analysis of the Cys residues prone to glutathione modification showed that the S-glutathiolated Cys residues are located inside pockets where the sulfur atom comes into contact with the solvent and that the positively charged amino acids are directed toward these Cys residues. The simulation of a covalent glutathione docking onto the same Cys residues allowed for perfect glutathione posing. A mutation of the Arg residue 263 that forms a saline bridge to the Cys residue 175 significantly decreased the overall S-glutathiolation and oligomerization of EP24.15. The present results show for the first time the structural requirements for protein S-glutathiolation by GSSG and are consistent with our previous hypothesis that EP24.15 oligomerization is dependent on the electron transfer from specific protonated Cys residues of one molecule to previously S-glutathionylated Cys residues of another one.

CARBON MARKET AND INSTITUTIONS: OPPORTUNITIES IN THE SEARCH OF A NEW MODEL FOR DEVELOPMENT

Seeking alternatives for the economic system to face the several crises it has gone through lately (electrical power, cultural, financing and technological) brought about a new market involving the Kyoto Protocol signatory countries: the carbon market. The present article aims at assessing the carbon market institutional issue in Brazil by identifying the risks and opportunities inherent to the institutional agent characteristics and to that market rules. The research methodology was bibliographic and based on the analysis of the Securities and Exchange Commission of Brazil (Comissao de Valores Mobiliarios and Bolsa Mercantil de Valores) contents. Its theoretical basis rests on concepts of the institution and the new institutional economy. The results show that in spite of the risks and institutional problems it involves, the carbon market is promising due to the opportunities create by new technologies and energies developed to achieve and sustain the capitalist system new cycle, addressed to produce a clean development.

Study of surface free energy on a lattice-gas model applied to Liquid bridge

The pulmonary crackling and the formation of liquid bridges are problems that for centuries have been attracting the attention of scientists. In order to study these phenomena, it was developed a canonical cubic lattice-gas­ like model to explain the rupture of liquid bridges in lung airways [A. Alencar et al., 2006, PRE]. Here, we further develop this model and add entropy analysis to study thermodynamic properties, such as free energy and force. The simulations were performed using the Monte Carlo method with Metropolis algorithm. The exchange between gas and liquid particles were performed randomly according to the Kawasaki dynamics and weighted by the Boltzmann factor. Each particle, which can be solid (s), liquid (l) or gas (g), has 26 neighbors: 6 + 12 + 8, with distances 1, √2 and √3, respectively. The energy of a lattice's site m is calculated by the following expression: Em = ∑k=126 Ji(m)j(k) in witch (i, j) = g, l or s. Specifically, it was studied the surface free energy of the liquid bridge, trapped between two planes, when its height is changed. For that, was considered two methods. First, just the internal energy was calculated. Then was considered the entropy. It was fond no difference in the surface free energy between this two methods. We calculate the liquid bridge force between the two planes using the numerical surface free energy. This force is strong for small height, and decreases as the distance between the two planes, height, is increased. The liquid-gas system was also characterized studying the variation of internal energy and heat capacity with the temperature. For that, was performed simulation with the same proportion of liquid and gas particle, but different lattice size. The scale of the liquid-gas system was also studied, for low temperature, using different values to the interaction Jij.