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.

Nonlinear formulation based on FEM, Mazars damage criterion and Fick's law applied to failure assessment of reinforced concrete structures subjected to chloride ingress and reinforcements corrosion

Structural durability is an important design criterion, which must be assessed for every type of structure. In this regard, especial attention must be addressed to the durability of reinforced concrete (RC) structures. When RC structures are located in aggressive environments, its durability is strongly reduced by physical/chemical/mechanical processes that trigger the corrosion of reinforcements. Among these processes, the diffusion of chlorides is recognized as one of major responsible of corrosion phenomenon start. To accurate modelling the corrosion of reinforcements and to assess the durability of RC structures, a mechanical model that accounts realistically for both concrete and steel mechanical behaviour must be considered. In this context, this study presents a numerical nonlinear formulation based on the finite element method applied to structural analysis of RC structures subjected to chloride penetration and reinforcements corrosion. The physical nonlinearity of concrete is described by Mazars damage model whereas for reinforcements elastoplastic criteria are adopted. The steel loss along time due to corrosion is modelled using an empirical approach presented in literature and the chloride concentration growth along structural cover is represented by Fick's law. The proposed model is applied to analysis of bended structures. The results obtained by the proposed numerical approach are compared to responses available in literature in order to illustrate the evolution of structural resistant load after corrosion start. (C) 2014 Elsevier Ltd. All rights reserved.

Análise morfotectônica do Planalto Ocidental Paulista, ao sul do Rio Tietê: indicadores de deformações neotectônicas na fisiografia da paisagem

Pós-graduação em Geologia Regional - IGCE

Susceptibility of Clinical Isolates of Candida to Photodynamic Effects of Curcumin

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

Genetic variability of porcine parvovirus isolates revealed by analysis of partial sequences of the structural coding gene VP2

The 3'-terminal 853 nt (and the putative 283 aa) sequence of the VP2-encoding gene from 29 field strains of porcine parvovirus (PPV) were determined and compared both to each other and with other published sequences. Sequences were examined using maximum-parsimony and statistical analyses for nucleotide diversity and sequence variability. Among the nucleotide sequences of the PPV field strains, 26 polymorphic sites were encountered; 22 polymorphic sites were detected in the putative amino acid sequence. Mapping polymorphic sites of protein data onto the three-dimensional (3D) structure of PPV VP2 revealed that almost all substitutions were located on the external surface of the viral capsid. Mapping amino acid substitutions to the alignment between PPV VP2 sequences and the 3D structure of canine parvovirus (CPV) capsid, many PPV substitutions were observed to map to regions of recognized antigenicity and/or to contain phenotypically important residues for CPV and other parvoviruses. In spite of the high sequence similarity, genetic analysis has shown the existence of at least two virus lineages among the samples. In conclusion, these results highlight the need for close surveillance on PPV genetic drift, with an assessment of its potential ability to modify the antigenic make-up of the virus.

Analysis and design of constant-frequency peak-current-controlled high-power-factor boost rectifier with slope compensation

This paper presents the analysis and the design of a peak-current-controlled high-power-factor boost rectifier, with slope compensation, operating at constant frequency. The input current shaping is achieved, with continuous inductor current mode, with no multiplier to generate a current reference. The resulting overall circuitry is very simple, in comparison with the average-current-controlled boost rectifier. Experimental results are presented, taken from a laboratory prototype rated at 370 W and operating at 67 kHz. The measured power factor was 0.99, with a input current THD equal to 5.6%, for an input voltage THD equal to 2.26%.

Structural changes induced by ultrasound during aging of the boehmite phase

Structural changes induced by ultrasound during the aging of the aluminum monohydroxide (boehmite) were studied by means of X-ray diffraction (XRD) and nitrogen adsorption. The BET surface area and the pore volume of the ultrasound stimulated hydroxide (HU) are about 40% less than those of the non-stimulated one (HS). The mean pore size practically does not change, while the mean crystallite size (L) is about 25% greater in the HU system. The increase of L alone is not enough to account for the surface area diminution, suggesting that the sonication also induces compaction by elimination of some porosity. The sonication of the precursor hydroxide does not seem to play an apparent role in the structural properties of the resulting calcinated γ-alumina. © 1997 Elsevier Science B.V.

Bonding of Y-TZP to Dentin: Effects of Y-TZP Surface Conditioning, Resin Cement Type, and Aging

Purpose: To evaluate the effects of two surface treatments, aging, and two resin cements on shear bond strength between dentin and yttrium-stabilized tetragonal zirconia polycrystal ceramic (Y-TZP).Materials and Methods: Eighty human molars were embedded in acrylic resin and sectioned 3 mm below the occlusal plane. These teeth and 80 cylindrical Y-TZP specimens (height, 4 mm; diameter, 3.4 mm) were divided into eight groups (n=10) using the following factors: Y-TZP surface treatment (Vi: low-fusing porcelain [vitrification] + hydrofluoric acid etching + silanization or Si: tribochemical silicatization); cementation strategies (PF: Pan avia or CC: Clearfil); and storage (nonaging or aging). Bonding surfaces of 40 Y-TZP specimens received Vi treatment, and the rest received Si treatment. Half of the ceramic-tooth assemblies were cemented with Panavia, the rest with Clearfil. Shear tests were executed using 0.4-mm-thick wire at 0.5 mm/min. Data were analyzed by three-way analysis of variance and Tukey test (alpha=0.05). Fractures were analyzed.Results: Y-TZP surface treatments did not affect bond strength (p=0.762, Vi = Si), while resin cements (p<0.001, Panavia > Clearfil) and aging (p=0.006, nonaging > aging) showed a significant effect. Most failures were in adhesive at dentin-cement interfaces; no failure occurred between zirconia and cement.Conclusion: When Y-TZP ceramic is bonded to dentin, the weakest interface is that between dentin and resin cement. The resin cement/Y-TZP interface was less susceptible to failures, owing to Y-TZP surface treatments.

Morphometric analysis of long-term dentoskeletal effects induced by treatment with Balters bionator

Objective: To evaluate the long-term effects of the standard (Class II) Balters bionator in growing patients with Class II malocclusion with mandibular retrusion by using morphometrics (thin-plate spline [TPS] analysis). Materials and Methods: Twenty-three Class II patients (8 male, 15 female) were treated consecutively with the Balters bionator (bionator group). The sample was evaluated at T0, start of treatment; T1, end of bionator therapy; and T2, long-term observation (including fixed appliances). Mean age at the start of treatment was 10 years 2 months (T0); at posttreatment, 12 years 3 months (T1); and at long-term follow-up, 18 years 2 months (T2). The control group consisted of 22 subjects (11 male, 11 female) with untreated Class II malocclusion. Lateral cephalograms were analyzed at the three time points for all groups. TPS analysis evaluated statistical differences (permutation tests) in the craniofacial shape and size between the bionator and control groups. Results: TPS analysis showed that treatment with the bionator is able to produce favorable mandibular shape changes (forward and downward displacement) that contribute significantly to the correction of the Class II dentoskeletal imbalance. These results are maintained at a long-term observation after completion of growth. The control group showed no statistically significant differences in the correction of Class II malocclusion. Conclusions: This study suggests that bionator treatment of Class II malocclusion produces favorable results over the long term with a combination of skeletal and dentoalveolar shape changes.

Analysis of tolerance to copper and zinc in Aechmea blanchetiana grown in vitro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Population analysis of susceptibility to propolis in reference strains of Staphylococcus aureus and Escherichia coli

Susceptibility to several ethanolic extracts of propolis (EEP) concentrations was tested with the population analysis technique in reference strains of Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 35218). The results of these tests showed that all bacteria were killed by EEP concentrations approximately equal or higher (2.0% v/v - S. aureus; 10.0% v/v - E. coli) than the respective minimal inhibitory concentrations (MIC). Regarding the susceptibility to propolis, there was a homogeneity of data with the respective time kill curves showing a clear bactericidal effect during 6 to 9 h of exposition.

Allium cepa and Tradescantia pallida bioassays to evaluate effects of the insecticide imidacloprid

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Development and analysis of formulations to the delivery of caffeine for the treatment of gynoid lipodystrophy

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A theoretical and experimental analysis of cold-formed steel shapes subjected to bending - Channel and simple lipped channel

Cold-formed steel shapes have been widely employed in steel construction, where they frequently offer a lower cost solution than do traditional laminated shapes. A classic application of cold-formed steel shapes is purlins in the roof panel of industrial buildings, connected to the roof panel by means of screws. The combined effect of these two elements has been the subject of investigations in some countries. Design criteria were included in the AISI Code in 1991 and 1996. This paper presents and discusses the results obtained from bending tests carried out on shapes commonly used in Brazil, i.e., the channel and the simple lipped channel, Tests were carried out on double shapes with 4.5 and 6.0 meter spans, which were subjected to concentrated loads and braced against each other on the supports and at intermediary points in three different load situations. The panel shape was also analyzed experimentally, simulating the action of wind by means of a vacuum box designed specifically for this purpose. The test results were then compared to those obtained through the theoretical analysis, enabling us to extract important information upon which to base proposed design criteria for the new Brazilian code.