Dielectric response features and oxygen migration on rare earth modified lead titanate ferroelectric ceramics

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

Structural alterations in the seminiferous tubules of rats treated with immunosuppressor tacrolimus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Structural and functional characterization of an acidic platelet aggregation inhibitor and hypotensive phospholipase A(2) from Bothrops jararacussu snake venom

An acidic (pI similar to 4.5) phospholipase A(2) (BthA-I-PLA(2)) was isolated from Bothrops jararacussu snake venom by ion-exchange chromatography on a CM-Sepharose column followed by reverse phase chromatography on an RP-HPLC C-18 column. It is an similar to13.7 kDa single chain Asp49 PLA(2) with approximately 122 amino acid residues, 7 disulfide bridges, and the following N-terminal sequence: 'SLWQFGKMINYVMJGESGVLQYLSYGCYCGLGGQGQPTDATDRCCFVHDCC(51). Crystals of this acidic protein diffracted beyond 2.0 Angstrom resolution. These crystals are monoclinic and have unit cell dimensions of a = 33.9, b = 63.8, c = 49.1 Angstrom, and beta = 104.0degrees. Although not myotoxic, cytotoxic, or lethal, the protein was catalytically 3-4 tithes more active than BthTX-II, a basic D49 myotoxic PLA(2) from the same venom and other Bothrops venoms. Although it showed no toxic activity, it was able to induce time-independent edema, this activity being inhibited by EDTA. In addition, BthA-I-PLA(2) caused a hypotensive response in the rat and inhibited platelet aggregation, Catalytic, antiplatelet and other activities were abolished by chemical modification with 4-bromophenacyl bromide, which is known to covalently bind to His48 of the catalytic site. Antibodies raised against crude B. jararacussu venom recognized this acidic PLA(2), while anti-Asp49-BthTX-II recognized it weakly and anti-Lys49-BthTX-I showed the least cross-reaction. These data confirm that myotoxicity does not necessarily correlate with catalytic activity in native PLA(2) homologues and that either of these two activities may exist alone. BthA-I-PLA(2), in addition to representing a relevant molecular model of catalytic activity, is also a promising hypotensive agent and platelet aggregation inhibitor for further studies. (C) 2002 Elsevier B.V. All rights reserved.

Structural basis of nuclear import of flap endonuclease 1 (FEN1)

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

Determining the structural basis for specificity of ligands using crystallographic screening

Crystallographic screening has been used to identify new inhibitors for potential target for drug development. Here, we describe the application of the crystallographic screening to assess the structural basis of specificity of ligands against a protein target. The method is efficient and results in detailed crystallographic information. The utility of the method is demonstrated in the study of the structural basis for specificity of ligands for human purine nucleoside phosphorylase (PNP). Purine nucleoside phosphorylase catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. This enzyme is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. This methodology may help in the future development of a new generation of PNP inhibitors.

Structural basis for inhibition of human PNP by immucillin-H

Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation. This work reports on the crystallographic study of the complex of human PNP-immucillin-H (HsPNP-ImmH) solved at 2.6 Angstrom resolution using synchrotron radiation. Immucillin-H (ImmH) inhibits the growth of malignant T-cell lines in the presence of deoxyguanosine without affecting non-T-cell tumor lines. ImmH inhibits activated normal human T cells after antigenic stimulation in vitro. These biological effects of ImmH suggest that this agent may have utility in the treatment of certain human diseases characterized by abnormal T-cell growth or activation. This is the first structural report of human PNP complexed with immucillin-H. The comparison of the complex HsPNP-ImmH with recent crystallographic structures of human PNP explains the high specificity of immucillin-H for human PNP. (C) 2003 Elsevier B.V. All rights reserved.

Crystal Structures of Xanthomonas Small Heat Shock Protein Provide a Structural Basis for an Active Molecular Chaperone Oligomer

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

Electrochemical and structural characterization of heat-treated Cr3C2-NiCr coatings

The influence of heat-treatments on the electrochemical behavior of thermal spray Cr3C2-NiCr coatings prepared by high velocity oxygen fuel (HVOF) was studied in NaCl solution, at 25 degrees C, using open-circuit potential (E-OC) and electrochemical impedance spectroscopy (EIS) measurements. Coating characterization were performed before and after the heat-treatments and electrochemical tests by scanning electron microscopy, X-ray diffraction, and Auger electron spectroscopy. In addition to the changes in the original powder composition occurring during HVOF process, heat-treatment performed at 450 degrees C caused no significant changes in electrochemical response compared with untreated sample, and at 760 degrees C the main difference was the formation of a thin and defective layer of Cr2O3 at the coating surface, which increased the total impedance at the first day of immersion. Higher influence on the electrochemical was noted for samples treated at 880 degrees C, which also showed higher E-OC and total impedance, and lower corrosion current. This behavior was interpreted considering the formation of a chromium oxide layer on the coating surface, dissolution and decomposition of smaller carbide particles and their surface enrichment with Cr due to C diffusion and dissolution into the matrix, and possible Ni, Cr, and Fe diffusion to coating/substrate interface. (c) 2006 the Electrochemical Society.

Ultrafast nonlinearity of antimony polyphosphate glasses

We report on the ultrafast nonlinearity of antimony polyphosphate glasses measured using the Kerr shutter technique. The nonlinear refractive index, n(2), was (1.1+/-0.2)x10(-14) cm(2)/W at 800 nm, and enhancement of n(2) by approximate to80% was observed by adding 10% of lead oxide in the glass composition. The full width at half-maximum of the third-order correlation signal was 150 fs, which implies a fast response of the samples (less than or equal to100 fs). Nonlinear absorption was negligible in the range of intensities used. (C) 2003 American Institute of Physics.

Structural and electrical properties of ZnO varistors containing different spinel phases

Structural and electrical properties of ZnO varistors were investigated as a function of spinel composition. Six varistor mixtures differing only in chemical composition of spinel, were prepared by mixing separately synthesized constituent phases (DSCP method). Compositions of constituent phases in sintered samples were investigated by changes of lattice parameters of the phases, as well as by EDS analysis of the constituent phases. It was found that compositions of ZnO, intergranular and spinel phases were partially changed during sintering due to redistribution of additives, that was controlled by starting spinel composition and its stability. Electrical characterization showed significant difference in electrical properties of investigated varistors: nonlinearity coefficients ranging from 22 to 55 and leakage currents differing by the order of magnitude. Activation energies of conduction were obtained from ac impedance spectroscopy measurements. Calculated values of activation energies were in the range 0.61-1.0 eV confirming difference in defect structure of ZnO grain boundaries in varistors containing different spinel phases. (C) 2001 Elsevier B.V. Ltd and Techna S.r.l. All rights reserved.

Whydration effects on DNA double helix stability modulates ligand binding to natural DNA in response to changes in water activity

In this work we present evidence that water molecules are actively involved on the control of binding affinity and binding site discrimination of a drug to natural DNA. In a previous study, the effect of water activity (a(w)) on the energetic parameters of actinomycin-D intercalation to natural DNA was determined using the osmotic stress method (39). This earlier study has shown evidence that water molecules act as an allosteric regulator of ligand binding to DNA via the effect of water activity on the long-range stability of the DNA secondary structure. In this work we have carried out DNA circularization experiments using the plasmid pUC18 in the absence of drugs and in the presence of different neutral solutes to evaluate the contribution of water activity to the energetics of DNA helix unwinding. The contribution of water to these independent reactions were made explicit by the description of how the changes in the free energy of ligand binding to DNA and in the free energy associated with DNA helix torsional deformation are linked to a(w) via changes in structural hydration. Taken together, the results of these studies reveal an extensive linkage between ligand binding affinity and site binding discrimination, and long range helix conformational changes and DNA hydration, This is strong evidence that water molecules work as a classical allosteric regulator of ligand binding to the DNA via its contribution to the stability of the double helix secondary structure, suggesting a possible mechanism by which the biochemical machinery of DNA processing takes advantage of the low activity of water into the cellular milieu.

Quantitative structural analysis of the transition from LT-LixCoO2 to HT-LixCoO2 using the rietveld method: correlation between structure and electrochemical performance

A quantitative phase analysis was made of LiXCoO2 powders obtained by two distinct chemical methodologies at different temperatures (from 400 to 700degreesC). A phase analysis was made using Rietveld refinements based on X-ray diffraction data, considering the LiXCoO2 powders as a multiphase system that simultaneously contained two main phases with distinct, layered and spinel-type structures. The sults showed the coexistence of both structures in LiXCoO2 obtained at low temperature (400 and 500degreesC), although only the layered structure was detected at higher temperatures (600 and 700degreesC, regardless of the chemical powder process employed. The electrochemical performance, evaluated mainly by the cycling reversibility of LiXCoO2 in the form of cathode insertion electrodes, revealed that there is a close correlation between structural features and the electrochemical response, with one of the redox processes (3.3 v/3.9 v) associated only with the presence of the spinel-type structure. (C) 2003 Elsevier B.V. All rights reserved.

Structural and properties of nanocrystalline WO3/TiO2-based humidity sensors elements prepared by high energy activation

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

Functional and Structural Adaptations in the Pancreatic alpha-Cell and Changes in Glucagon Signaling During Protein Malnutrition

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

Quantitative structural analysis of the transition from LT-Li xCoO2 to HT-LixCoO2 using the rietveld method: Correlation between structure and electrochemical performance

A quantitative phase analysis was made of LixCoO2 powders obtained by two distinct chemical methodologies at different temperatures (from 400 to 700°C). A phase analysis was made using Rietveld refinements based on X-ray diffraction data, considering the Li xCoO2 powders as a multiphase system that simultaneously contained two main phases with distinct, layered and spinel-type structures. The results showed the coexistence of both structures in LixCoO 2 obtained at low temperature (400 and 500°C), although only the layered structure was detected at higher temperatures (600 and 700°C), regardless of the chemical powder process employed. The electrochemical performance, evaluated mainly by the cycling reversibility of Li xCoO2 in the form of cathode insertion electrodes, revealed that there is a close correlation between structural features and the electrochemical response, with one of the redox processes (3.3 v/3.9 v) associated only with the presence of the spinel-type structure. © 2003 Elsevier B.V. All rights reserved.