Monoclonal Antibodies against Hepatitis C Genotype 3a Virus Like Particle Inhibit Virus Entry in Cell Culture System

The envelope protein (E1-E2) of Hepatitis C virus (HCV) is a major component of the viral structure. The glycosylated envelope protein is considered to be important for initiation of infection by binding to cellular receptor(s) and also known as one of the major antigenic targets to host immune response. The present study was aimed at identifying mouse monoclonal antibodies which inhibit binding of virus like particles of HCV to target cells. The first step in this direction was to generate recombinant HCV-like particles (HCV-LPs) specific for genotypes 3a of HCV (prevalent in India) using the genes encoding core, E1 and E2 envelop proteins in a baculovirus expression system. The purified HCV-LPs were characterized by ELISA and electron microscopy and were used to generate monoclonal antibodies (mAbs) in mice. Two monoclonal antibodies (E8G9 and H1H10) specific for the E2 region of envelope protein of HCV genotype 3a, were found to reduce the virus binding to Huh7 cells. However, the mAbs generated against HCV genotype 1b (D2H3, G2C7, E1B11) were not so effective. More importantly, mAb E8G9 showed significant inhibition of the virus entry in HCV JFH1 cell culture system. Finally, the epitopic regions on E2 protein which bind to the mAbs have also been identified. Results suggest a new therapeutic strategy and provide the proof of concept that mAb against HCV-LP could be effective in preventing virus entry into liver cells to block HCV replication.

Supersymmetry of classical solutions in Chern-Simons higher spin supergravity

We construct and study classical solutions in Chern-Simons supergravity based on the superalgebra sl(N vertical bar N = 1). The algebra for the N = 3 case is written down explicitly using the fact that it arises as the global part of the super conformal W-3 superalgebra. For this case we construct new classical solutions and study their supersymmetry. Using the algebra we write down the Killing spinor equations and explicitly construct the Killing spinor for conical defects and black holes in this theory. We show that for the general sl(N|N - 1) theory the condition for the periodicity of the Killing spinor can be written in terms of the products of the odd roots of the super algebra and the eigenvalues of the holonomy matrix of the background. Thus the supersymmetry of a given background can be stated in terms of gauge invariant and well defined physical observables of the Chern-Simons theory. We then show that for N >= 4, the sl(N|N - 1) theory admits smooth supersymmetric conical defects.

Mechanistic Insights into a Non-Classical Diffusion Pathway for the Formation of Hollow Intermetallics: A Route to Multicomponent Hollow Structures

Hollow nanostructures are used for various applications including catalysis, sensing, and drug delivery. Methods based on the Kirkendall effect have been the most successful for obtaining hollow nanostructures of various multicomponent systems. The classical Kirkendall effect relies on the presence of a faster diffusing species in the core; the resultant imbalance in flux results in the formation of hollow structures. Here, an alternate non-Kirkendall mechanism that is operative for the formation of hollow single crystalline particles of intermetallic PtBi is demonstrated. The synthesis method involves sequential reduction of Pt and Bi salts in ethylene glycol under microwave irradiation. Detailed analysis of the reaction at various stages indicates that the formation of the intermetallic PtBi hollow nanoparticles occurs in steps. The mechanistic details are elucidated using control experiments. The use of microwave results in a very rapid synthesis of intermetallics PtBi that exhibits excellent electrocatalytic activity for formic acid oxidation reaction. The method presented can be extended to various multicomponent systems and is independent of the intrinsic diffusivities of the species involved.

Large deviation function and fluctuation theorem for classical particle transport

We analytically evaluate the large deviation function in a simple model of classical particle transfer between two reservoirs. We illustrate how the asymptotic long-time regime is reached starting from a special propagating initial condition. We show that the steady-state fluctuation theorem holds provided that the distribution of the particle number decays faster than an exponential, implying analyticity of the generating function and a discrete spectrum for its evolution operator.

Genomic mapping of cAMP receptor protein (CRPMt) in Mycobacterium tuberculosis: relation to transcriptional start sites and the role of CRPMt as a transcription factor

Chromatin immunoprecipitation identified 191 binding sites of Mycobacterium tuberculosis cAMP receptor protein (CRPMt) at endogenous expression levels using a specific alpha-CRPMt antibody. Under these native conditions an equal distribution between intragenic and intergenic locations was observed. CRPMt binding overlapped a palindromic consensus sequence. Analysis by RNA sequencing revealed widespread changes in transcriptional profile in a mutant strain lacking CRPMt during exponential growth, and in response to nutrient starvation. Differential expression of genes with a CRPMt-binding site represented only a minor portion of this transcriptional reprogramming with similar to 19% of those representing transcriptional regulators potentially controlled by CRPMt. The subset of genes that are differentially expressed in the deletion mutant under both culture conditions conformed to a pattern resembling canonical CRP regulation in Escherichia coli, with binding close to the transcriptional start site associated with repression and upstream binding with activation. CRPMt can function as a classical transcription factor in M. tuberculosis, though this occurs at only a subset of CRPMt-binding sites.

Beyond classical dynamic structural plasticity using mesh-free modelling techniques

The problem of modelling the transient response of an elastic-perfectly-plastic cantilever beam, carrying an impulsively loaded tip mass, is,often referred to as the Parkes cantilever problem 25]; The permanent deformation of a cantilever struck transversely at its tip, Proc. R. Soc. A., 288, pp. 462). This paradigm for classical modelling of projectile impact on structures is re-visited and updated using the mesh-free method, smoothed particle hydrodynamics (SPH). The purpose of this study is to investigate further the behaviour of cantilever beams subjected to projectile impact at its tip, by considering especially physically real effects such as plastic shearing close to the projectile, shear deformation, and the variation of the shear strain along the length and across the thickness of the beam. Finally, going beyond macroscopic structural plasticity, a strategy to incorporate physical discontinuity (due to crack formation) in SPH discretization is discussed and explored in the context of tip-severance of the cantilever beam. Consequently, the proposed scheme illustrates the potency for a more refined treatment of penetration mechanics, paramount in the exploration of structural response under ballistic loading. The objective is to contribute to formulating a computational modelling framework within which transient dynamic plasticity and even penetration/failure phenomena for a range of materials, structures and impact conditions can be explored ab initio, this being essential for arriving at suitable tools for the design of armour systems. (C) 2014 Elsevier Ltd. All rights reserved.

Metastable monoclinic and orthorhombic phases and electric field induced irreversible phase transformation at room temperature in the lead-free classical ferroelectric BaTiO3

For decades it has been a well-known fact that among the few ferroelectric compounds in the perovskite family, namely, BaTiO3, KNbO3, PbTiO3, and Na1/2Bi1/2TiO3, the dielectric and piezoelectric properties of BaTiO3 are considerably higher than the others in polycrystalline form at room temperature. Further, similar to ferroelectric alloys exhibiting morphotropic phase boundary, single crystals of BaTiO3 exhibit anomalously large piezoelectric response when poled away from the direction of spontaneous polarization at room temperature. These anomalous features in BaTiO3 remained unexplained so far from the structural standpoint. In this work, we have used high-resolution synchrotron x-ray powder diffraction, atomic resolution aberration-corrected transmission electron microscopy, in conjunction with a powder poling technique, to reveal that at 300 K (i) the equilibrium state of BaTiO3 is characterized by coexistence of metastable monoclinic Pm and orthorhombic (Amm2) phases along with the tetragonal phase, and (ii) strong electric field switches the polarization direction from the 001] direction towards the 101] direction. These results suggest that BaTiO3 at room temperature is within an instability regime, and that this instability is the fundamental factor responsible for the anomalous dielectric and piezoelectric properties of BaTiO3 as compared to the other homologous ferroelectric perovskite compounds at room temperature. Pure BaTiO3 at room temperature is therefore more akin to lead-based ferroelectric alloys close to the morphotropic phase boundary where polarization rotation and field induced ferroelectric-ferroelectric phase transformations play a fundamental role in influencing the dielectric and piezoelectric behavior.

Si nanowire growth on sapphire: Classical incubation, reverse reaction, and steady state supersaturation

Si nanowire growth on sapphire substrates by the vapor-liquid-solid (VLS) method using Au catalyst particles has been studied. Sapphire was chosen as the substrate to ensure that the vapor phase is the only source of Si. Three hitherto unreported observations are described. First, an incubation period of 120-480 s, which is shown to be the incubation period as defined in classical nucleation theory, is reported. This incubation period permits the determination of a desolvation energy of Si from Au-Si alloys of 15 kT. Two, transmission electron microscopy studies of incubation, point to Si loss by reverse reaction as an important part of the mechanism of Si nanowire growth by VLS. Three, calculations using these physico-chemical parameters determined from incubation and measured steady state growth rates of Si nanowires show that wire growth happens from a supersaturated catalyst droplet. (C) 2015 AIP Publishing LLC.