75 resultados para 90-03-PC1


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This work aims at dimensional reduction of non-linear isotropic hyperelastic plates in an asymptotically accurate manner. The problem is both geometrically and materially non-linear. The geometric non-linearity is handled by allowing for finite deformations and generalized warping while the material non-linearity is incorporated through hyperelastic material model. The development, based on the Variational Asymptotic Method (VAM) with moderate strains and very small thickness to shortest wavelength of the deformation along the plate reference surface as small parameters, begins with three-dimensional (3-D) non-linear elasticity and mathematically splits the analysis into a one-dimensional (1-D) through-the-thickness analysis and a two-dimensional (2-D) plate analysis. Major contributions of this paper are derivation of closed-form analytical expressions for warping functions and stiffness coefficients and a set of recovery relations to express approximately the 3-D displacement, strain and stress fields. Consistent with the 2-D non-linear constitutive laws, 2-D plate theory and corresponding finite element program have been developed. Validation of present theory is carried out with a standard test case and the results match well. Distributions of 3-D results are provided for another test case. (c) 2012 Elsevier Ltd. All rights reserved.

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Lattice oxygen of TiO2 is activated by the substitution of Pd ion in its lattice. Ti1-xPdxO2-x (x = 0.01-0.03) have been synthesized by solution combustion method crystallizing in anatase TiO2 structure. Pd is in +2 oxidation state and Ti is in +4 oxidation state in the catalyst. Pd is more ionic in TiO2 lattice compared to Pd in PdO. Oxygen storage capacity defined by ``amount of oxygen that is used reversibly to oxidize CO'' is as high as 5100 mu mol/g of Ti0.97Pd0.03O1.97. Oxygen is extracted by CO to CO2 in absence of feed oxygen even at room temperature which is more than 20 times compared to pure TiO2. Rate of CO oxidation is 2.75 mu mol g(-1) s(-1) at 60 degrees C over Ti0.97Pd0.03O1.97 and C2H2 gets oxidized to CO2 and H2O at room temperature. Catalyst is not poisoned on long time operation of the reactor. Such high catalytic activity is due to activated lattice oxygen created by the substitution of Pd ion as seen from first-principles density functional theory (DFT) calculations with 96 atom supercells of Ti32O64, Ti31Pd1O63, Ti30Pd2O62, and Ti29Pd3O61. The compounds crystallize in anatase TiO2 structure with Pd2+ ion in nearly square planar geometry and TiO6 octahedra are distorted by the creation of weakly bound oxygens. Structural analysis of Ti31Pd1O63 which is close to 3% Pd ion substituted TiO2 shows that oxygens associated with both Ti and Pd ions in the lattice show bond valence sum of 1.87, a low value characteristic of weak oxygen in the lattice compared to oxygens with valence 2 and above in the same lattice. Exact positions of activated oxygens have been identified in the lattice from DFT calculations.

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Combating stress is one of the prime requirements for any organism. For parasitic microbes, stress levels are highest during the growth inside the host. Their survival depends on their ability to acclimatize and adapt to new environmental conditions. Robust cellular machinery for stress response is, therefore, both critical and essential especially for pathogenic microorganisms. Microbes have cleverly exploited stress proteins as virulence factors for pathogenesis in their hosts. Owing to its ability to sense and respond to the stress conditions, Heat shock protein 90 (Hsp90) is one of the key stress proteins utilized by parasitic microbes. There are growing evidences for the critical role played by Hsp90 in the growth of pathogenic organisms like Candida, Giardia, Plasmodium, Trypanosoma, and others. This review, therefore, explores potential of exploiting Hsp90 as a target for the treatment of infectious diseases. This molecular chaperone has already gained attention as an effective anti-cancer drug target. As a result, a lot of research has been done at laboratory, preclinical and clinical levels for several Hsp90 inhibitors as potential anti-cancer drugs. In addition, lot of data pertaining to toxicity studies, pharmacokinetics and pharmacodynamics studies, dosage regime, drug related toxicities, dose limiting toxicities as well as adverse drug reactions are available for Hsp90 inhibitors. Therefore, repurposing/repositioning strategies are also being explored for these compounds which have gone through advanced stage clinical trials. This review presents a comprehensive summary of current status of development of Hsp90 as a drug target and its inhibitors as candidate anti-infectives. A particular emphasis is laid on the possibility of repositioning strategies coupled with pharmaceutical solutions required for fulfilling needs for ever growing pharmaceutical infectious disease market.

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In this article, we have reported the controlled synthesis of uniformly grown zinc oxide nanoparticles (ZnO NPs) films by a simple, low-cost, and scalable pulsed spray pyrolysis technique. From the surface analysis it is noticed that the as-deposited films have uniformly dispersed NPs-like morphology. The structural studies reveal that these NPs films have highly crystalline hexagonal crystal structure, which are preferentially orientated along the (001) planes. The size of the NPs varied between 5 and 100 nm, and exhibited good stoichiometric chemical composition. Raman spectroscopic analysis reveals that these ZnO NPs films have pure single phase and hexagonal crystal structure. These unique nanostructured films exhibited a low electrical resistivity (5 Omega cm) and high light transmittance (90 %) in visible region.

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Cytosolic heat shock protein 90 (Hsp90) has been shown to be essential for many infectious pathogens and is considered a potential target for drug development. In this study, we have carried out biochemical characterization of Hsp90 from a poorly studied protozoan parasite of clinical importance, Entamoeba histolytica. We have shown that Entamoeba Hsp90 can bind to both ATP and its pharmacological inhibitor, 17-AAG (17-allylamino-17-demethoxygeldanamycin), with K-d values of 365.2 and 10.77 mu M, respectively, and it has a weak ATPase activity with a catalytic efficiency of 4.12 x 10(-4) min(-1) mu M-1. Using inhibitor 17-AAG, we have shown dependence of Entamoeba on Hsp90 for its growth and survival. Hsp90 function is regulated by various co-chaperones. Previous studies suggest a lack of several important co-chaperones in E. histolytica. In this study, we describe the presence of a novel homologue of co-chaperone Aha1 (activator of Hsp90 ATPase), EhAha1c, lacking a canonical Aha1 N-terminal domain. We also show that EhAha1c is capable of binding and stimulating ATPase activity of EhHsp90. In addition to highlighting the potential of Hsp90 inhibitors as drugs against amoebiasis, our study highlights the importance of E. histolytica in understanding the evolution of Hsp90 and its co-chaperone repertoire. (C) 2014 Elsevier Ltd. All rights reserved.

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Saccharomyces boulardii was encapsulated by layer-by-layer technique (LbL) using oppositely charged polyelectrolytes, chitosan and dextran sulfate to protect from degradation during its gastrointestinal transit. The protective effect of the coating was evaluated by checking viability after subjecting the coated cells to lyophilisation and simulated gastrointestinal conditions. During lyophilization, coated S. boulardii was found to have an enhanced viability of 7.74 +/- 2.00 log CFU/100 mg (5.62 x 10(6) +/- 2.12 CFU/100 mg) and 5.53 +/- 1.85 log CFU/100 mg (3.46 x 10(5) 1.73 CFU/100 mg) for uncoated cells. On sequential treatment with simulated gastric and intestinal juice, the coated cells had a viability of 4.59 +/- 1.52 log CFU/100 mg (3.8 x 104 +/- 1.52 CFU/100 mg) while only 1.90 +/- 0.80 log CFU/100 mg (0.79 x 102 +/- 0.81 CFU/100 mg) of uncoated cells survived. Confocal studies displayed the selective permeability of the coated cells which plays a significant role in maintaining the integrity and viability of the yeast cells. This clearly indicates that LbL is an efficient protective encapsulation technique and it could be potentially used for improving therapeutic applications of yeast. (C) 2014 Elsevier Ltd. All rights reserved.

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Background: Hsp90 from Giardia lamblia is expressed by splicing of two independently transcribed RNA molecules, coded by genes named HspN and HspC located 777 kb apart. The reasons underlying such unique trans-splicing based generation of GlHsp90 remain unclear. Principle Finding: In this study using mass-spectrometry we identify the sequence of the unique, junctional peptide contributed by the 5' UTR of HspC ORF. This peptide is critical for the catalytic function of Hsp90 as it harbours an essential ``Arg'' in its sequence. We also show that full length GlHsp90 possesses all the functional hall marks of a canonical Hsp90 including its ability to bind and hydrolyze ATP. Using qRT-PCR as well as western blotting approach we find the reconstructed Hsp90 to be induced in response to heat shock. On the contrary we find GlHsp90 to be down regulated during transition from proliferative trophozoites to environmentally resistant cysts. This down regulation of GlHsp90 appears to be mechanistically linked to the encystation process as we find pharmacological inhibition of GlHsp90 function to specifically induce encystation. Significance: Our results implicate the trans-spliced GlHsp90 from Giardia lamblia to regulate an essential stage transition in the life cycle of this important human parasite.

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Trypanosomiasis is caused by Trypanosoma species which affect both human and animal populations and pose a major threat to developing countries. The incidence of animal trypanosomiasis is on the rise. Surra is a type of animal trypanosomiasis, caused by Trypanosoma evansi, and has been included in priority list B of significant diseases by the World Organization of Animal Health (OIE). Control of surra has been a challenge due to the lack of effective drugs and vaccines and emergence of resistance towards existing drugs. Our laboratory has previously implicated Heat shock protein 90 (Hsp90) from protozoan parasites as a potential drug target and successfully demonstrated efficacy of an Hsp90 inhibitor in cell culture as well as a pre-clinical mouse model of trypanosomiasis. This article explores the role of Hsp90 in the Trypanosoma life cycle and its potential as a drug target. It appears plausible that the repertoire of Hsp90 inhibitors available in academia and industry may have value for treatment of surra and other animal trypanosomiasis.

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We report inelastic light scattering studies on Ca(Fe0.97Co0.03)(2)As-2 in a wide spectral range of 120-5200 cm(-1) from 5 to 300 K, covering the tetragonal to orthorhombic structural transition as well as magnetic transition at T-sm similar to 160 K. The mode frequencies of two first-order Raman modes B-1g and E-g, both involving the displacement of Fe atoms, show a sharp increase below T-sm. Concomitantly, the linewidths of all the first-order Raman modes show anomalous broadening below T-sm, attributed to strong spin-phonon coupling. The high frequency modes observed between 400 and 1200 cm(-1) are attributed to electronic Raman scattering involving the crystal field levels of d-orbitals of Fe2+. The splitting between xz and yz d-orbital levels is shown to be similar to 25 meV, which increases as temperature decreases below T-sm. A broad Raman band observed at similar to 3200 cm(-1) is assigned to two-magnon excitation of the itinerant Fe 3d antiferromagnet.

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Algae grown in outdoor reactors (volume: 10 L and depth: 20 cm) were fed directly with filtered and sterilised municipal wastewater. The nutrient removal efficiencies were 86%, 90%, 89%, 70% and 76% for TOC, TN, NH4-N, TP and OP, respectively, and lipid content varied from 18% to 28.5% of dry algal biomass. Biomass productivity of similar to 122 mg/l/d (surface productivity 24.4 g/m(2)/d) and lipid productivity of similar to 32 mg/l/d were recorded. Gas chromatography and mass spectrometry (GC-MS) analyses of the fatty acid methyl esters (FAME) showed a higher content of desirable fatty acids (bearing biofuel properties) with major contributions from saturates such as palmitic acid C16:0; similar to 40%] and stearic acid C18:0; similar to 34%], followed by unsaturates such as oleic acid C18:1(9); similar to 10%] and linoleic acid C18:2(9,12); similar to 5%]. The decomposition of algal biomass and reactor residues with an exothermic heat content of 123.4 J/g provides the scope for further energy derivation. (C) 2014 Elsevier Ltd. All rights reserved.

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The sensing of relative humidity (RH) at room temperature has potential applications in several areas ranging from biomedical to horticulture, paper, and textile industries. In this paper, a highly sensitive humidity sensor based on carbon nanotubes (CNTs) coated on the surface of an etched fiber Bragg grating (EFBG) sensor has been demonstrated, for detecting RH over a wide range of 20%-90% at room temperature. When water molecules interact with the CNT coated EFBG, the effective refractive index of the fiber core changes, resulting in a shift in the Bragg wavelength. It has been possible to achieve a high sensitivity of similar to 31 pm/% RH, which is the highest compared with many of the existing FBG-based humidity sensors. The limit of detection in the CNT coated EFBG has been found to be similar to 0.03 RH. The experimental data shows a linear response of Bragg wavelength shift with increase in humidity. This novel method of incorporating CNTs on to the FBG sensor for humidity sensing has not been reported before.

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Heat-shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone that is essential for the normal functioning of eukaryotic cells. It plays crucial roles in cell signalling, cell-cycle control and in maintaining proteome integrity and protein homeostasis. In plants, Hsp90s are required for normal plant growth and development. Hsp90s are observed to be upregulated in response to various abiotic and biotic stresses and are also involved in immune responses in plants. Although there are several studies elucidating the physiological role of Hsp90s in plants, their molecular mechanism of action is still unclear. In this study, biochemical characterization of an Hsp90 protein from rice (Oryza sativa; OsHsp90) has been performed and the crystal structure of its N-terminal domain (OsHsp90-NTD) was determined. The binding of OsHsp90 to its substrate ATP and the inhibitor 17-AAG was studied by fluorescence spectroscopy. The protein also exhibited a weak ATPase activity. The crystal structure of OsHsp90-NTD was solved in complex with the nonhydrolyzable ATP analogue AMPPCP at 3.1 angstrom resolution. The domain was crystallized by cross-seeding with crystals of the N-terminal domain of Hsp90 from Dictyostelium discoideum, which shares 70% sequence identity with OsHsp90-NTD. This is the second reported structure of a domain of Hsp90 from a plant source.

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Enteric protozoan Entamoeba histolytica is a major cause of debilitating diarrheal infection worldwide with high morbidity and mortality. Even though the clinical burden of this parasite is very high, this infection is categorized as a neglected disease. Parasite is transmitted through feco-oral route and exhibit two distinct stages namely - trophozoites and cysts. Mechanism and regulation of encystation is not clearly understood. Previous studies have established the role of Heat shock protein 90 (Hsp90) in regulating stage transition in various protozoan parasites like Giardia, Plasmodium, Leishmania, and Toxoplasma. Our study for the first time reports that Hsp90 plays a crucial role in life cycle of Entamoeba as well. We identify Hsp90 to be a negative regulator of encystation in Entamoeba. We also show that Hsp90 inhibition interferes with the process of phagocytosis in Entamoeba. Overall, we show that Hsp90 plays an important role in virulence and transmission of Entamoeba.

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The involvement of Hsp90 in progression of diseases like cancer, neurological disorders and several pathogen related conditions is well established. Hsp90, therefore, has emerged as an attractive drug target for many of these diseases. Several small molecule inhibitors of Hsp90, such as geldanamycin derivatives, that display antitumor activity, have been developed and are under clinical trials. However, none of these tested inhibitors or drugs are peptide-based compounds. Here we report the first crystal structure of a peptide bound at the ATP binding site of the N-terminal domain of Hsp90. The peptide makes several specific interactions with the binding site residues, which are comparable to those made by the nucleotide and geldanamycin. A modified peptide was designed based on these interactions. Inhibition of ATPase activity of Hsp90 was observed in the presence of the modified peptide. This study provides an alternative approach and a lead peptide molecule for the rational design of effective inhibitors of Hsp90 function.

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The complexity associated with local structures continues to pose challenges with regard to the understanding of the structure-property relationship in Na1/2Bi1/2TiO3-based lead-free piezoceramics. (1-x)Na1/2Bi1/2TiO3-(x)BaTiO3 is an extensively studied system because of its interesting piezoelectric properties. Recently, a room temperature phase boundary was reported at x = 0.03 in this system Ma et al., Adv. Funct. Mater. 23, 5261 (2013)]. In the present work we have examined this subtle phase boundary using x-ray diffraction, neutron diffraction, dielectric measurements as a function of composition (x < 0.06), temperature, and electric field. Our results show that this boundary separates an R3c + Cc-like structural state for x < 0.03 from an R3c+ cubiclike structural state for 0.03 <= x <= 0.05 in the unpoled specimens. This phase boundary is characterized by an anomalous reduction in the depolarization temperature, and a suppression of the tetragonal distortion of the high temperature P4bm phase. Our results also provide the clue to understand the pathway leading to the cubiclike structure of the critical composition x = 0.06, known for its highest piezoelectric response.