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Plastic deformation and failure mechanisms in nano-scale notched metallic glass specimens under tensile loading
No full textIn this work, numerical simulations using molecular dynamics and non-local plasticity based finite element analysis are carried out on tensile loading of nano-scale double edge notched metallic glass specimens. The effect of acuteness of notches as well as the metallic glass chemical composition or internal material length scale on the plastic deformation response of the specimens are studied. Both MD and FE simulations, in spite of the fundamental differences in their nature, indicate near-identical deformation features. Results show two distinct transitions in the notch tip deformation behavior as the acuity is increased, first from single shear band dominant plastic flow localization to ligament necking, and then to double shear banding in notches that are very sharp. Specimens with moderately blunt notches and composition showing wider shear bands or higher material length scale characterizing the interaction stress associated with flow defects display profuse plastic deformation and failure by ligament necking. These results are rationalized from the role of the interaction stress and development of the notch root plastic zones. (C) 2017 Elsevier Ltd. All rights reserved
Structural and biophysical characterization of Rv3716c, a hypothetical protein from Mycobacterium tuberculosis
No full textLatent tuberculosis (TB) is the main hurdle in reaching the goal of ``Stop TB 2050''. Tuberculin skin and Interferon-gamma release assay tests used currently for the diagnosis of TB infection cannot distinguish between active disease and latent tuberculosis infection (LTBI) and hence new and sensitive protein markers need to be identified for the diagnosis. A protein Rv3716c from Mycobacterium tuberculosis (MtbRv3716c) has been identified as a potential surrogate marker for the diagnosis of LTBI. Here, we present characterization of MtbRv3716c (similar to 13 kDa) using both biophysical and X-Ray crystallographic methods. EMSA study showed that MtbRv3716c binds to double stranded DNA. X-ray diffraction data collected on a crystal of MtbRv3716c at 1.9 angstrom resolution was used for structure determination using the molecular replacement method. Significant electron density was not observed for the N-terminal 21 and C-terminal 41 residues in the final electron density map. The C- terminal disordered region is proline rich and displays characteristics of intrinsically disordered proteins. Although the crystal asymmetric unit contained a protomer, a tight dimer could be generated by the application of the crystal two-fold symmetry parallel to the b axis. Packing of dimers in the crystal is mediated by a cadmium ion (Cd2+) occurring at the interface of two dimers. Molecular packing analysis reveals large cavities that are probably occupied by the disordered segments of the N- and C-termini. Structural comparison with other homologous hypothetical DNA binding proteins (PDB codes: 1PUG, 1YBX) highlights structural features that might be significant for DNA binding. (C) 2017 Elsevier Inc. All rights reserved
High-efficiency broad-bandwidth subwavelength grating-based fiber-chip coupler in silicon-on-insulator
No full textWe report a comprehensive study on the performance of uniform and nonuniform-based subwave-length grating couplers in a silicon-on-insulator. The two performance metrics, coupling efficiency, bandwidth enhancement, and tradeoffs are presented. We also present design parameters to achieve high-efficiency and broadband operation based on the detailed study of various loss mechanisms in the grating. Based on a detailed analysis, subwavelength grating coupler designs with efficiency as high as 84% with a 1-dB bandwidth of 50-nm and 98% with a 44-nm 1-dB bandwidth is presented. (C) 2018 Society of Photo-Optical Instrumentation Engineers (SPIE
A Trimeric HIV-1 Envelope gp120 Immunogen Induces Potent and Broad Anti-V1V2 Loop Antibodies against HIV-1 in Rabbits and Rhesus Macaques
No full textTrimeric HIV-1 envelope (Env) immunogens are attractive due to their ability to display quaternary epitopes targeted by broadly neutralizing antibodies (bNAbs) while obscuring unfavorable epitopes. Results from the RV144 trial highlighted the importance of vaccine-induced HIV-1 Env V1V2-directed antibodies, with key regions of the V2 loop as targets for vaccine-mediated protection. We recently reported that a trimeric JRFL-gp120 immunogen, generated by inserting an N-terminal trimerization domain in the V1 loop region of a cyclically permuted gp120 (cycP-gp120), induces neutralizing activity against multiple tier-2 HIV-1 isolates in guinea pigs in a DNA prime/protein boost approach. Here, we tested the immunogenicity of cycPgp120 in a protein prime/boost approach in rabbits and as a booster immunization to DNA/modified vaccinia Ankara (MVA)-vaccinated rabbits and rhesus macaques. In rabbits, two cycP-gp120 protein immunizations induced 100-fold higher titers of high-avidity gp120-specific IgG than two gp120 immunizations, with four total gp120 immunizations being required to induce comparable titers. cycP-gp120 also induced markedly enhanced neutralizing activity against tier-1A and -1B HIV-1 isolates, substantially higher binding and breadth to gp70-V1V2 scaffolds derived from a multiclade panel of global HIV-1 isolates, and antibodies targeting key regions of the V2-loop region associated with reduced risk of infection in RV144. Similarly, boosting MVA-or DNA/MVA-primed rabbits or rhesus macaques with cycP-gp120 showed a robust expansion of gp70-V1V2-specific IgG, neutralization breadth to tier-1B HIV-1 isolates, and antibody-dependent cellular cytotoxicity activity. These results demonstrate that cycP-gp120 serves as a robust HIV Env immunogen that induces broad anti-V1V2 antibodies and promotes neutralization breadth against HIV-1. IMPORTANCE Recent focus in HIV-1 vaccine development has been the design of trimeric HIV-1 Env immunogens that closely resemble native HIV-1 Env, with a major goal being the induction of bNAbs. While the generation of bNAbs is considered a gold standard in vaccine-induced antibody responses, results from the RV144 trial showed that nonneutralizing antibodies directed toward the V1V2 loop of HIV-1 gp120, specifically the V2 loop region, were associated with decreased risk of infection, demonstrating the need for the development of Env immunogens that induce a broad anti-V1V2 antibody response. In this study, we show that a novel trimeric gp120 protein, cycP-gp120, generates high titers of high-avidity and broadly cross-reactive anti-V1V2 antibodies, a result not found in animals immunized with monomeric gp120. These results reveal the potential of cycP-gp120 as a vaccine candidate to induce antibodies associated with reduced risk of HIV-1 infection in humans
A natural small molecule inhibitor corilagin blocks HCV replication and modulates oxidative stress to reduce liver damage
No full textHepatitis C virus (HCV) infection causes chronic liver disease, which often leads to hepatocellular carcinoma. Earlier, we have demonstrated anti-HCV property of the methanolic extract of Phyllanthus amarus, an age-old folk-medicine against viral hepatitis. Here, we report identification of a principal bioactive component `corilagin', which showed significant inhibition of the HCV key enzymes, NS3 protease and NS5B RNA-dependent-RNA-polymerase. This pure compound could effectively inhibit viral replication in the infectious cell culture system, displayed strong antioxidant activity by blocking HCV induced generation of reactive oxygen species and suppressed up-regulation of NOX4 and TGF-beta mRNA levels. Oral administration of corilagin in BALB/c mice demonstrated its better tolerability and systemic bioavailability. More importantly, corilagin could restrict serum HCV RNA levels, decrease collagen deposition and hepatic cell denaturation in HCV infected chimeric mice harbouring human hepatocytes. Taken together, results provide a basis towards developing a pure natural drug as an alternate therapeutic strategy for restricting viral replication and prevent liver damage towards better management of HCV induced pathogenesis
Optimized peptide based inhibitors targeting the dihydrofolate reductase pathway in cancer
No full textWe report the first peptide based hDHFR inhibitors designed on the basis of structural analysis of dihydrofolate reductase (DHFR). A set of peptides were rationally designed and synthesized using solid phase peptide synthesis and characterized using nuclear magnetic resonance and enzyme immunoassays. The best candidate among them, a tetrapeptide, was chosen based on molecular mechanics calculations and evaluated in human lung adenocarcinoma cell line A549. It showed a significant reduction of cell proliferation and an IC50 of 82 mu M was obtained. The interaction of the peptide with DHFR was supported by isothermal calorimetric experiments revealing a dissociation constant K-d of 0.7 mu M and Delta G of -34 +/- 1 kJ mol(-1). Conjugation with carboxylated polystyrene nanoparticles improved further its growth inhibitory effects. Taken together, this opens up new avenues to design, develop and deliver biocompatible peptide based anti-cancer agents
Influence of silver nanoparticles on titanium oxide and nitrogen doped titanium oxide thin films for sun light photocatalysis
No full textDecreasing recombination of photogenerated charge carriers in photocatalysts is a critical issue for enhancing the efficiency of dye degradation. It is one of the greatest challenges to reduce the recombination of photo generated charge carriers in semiconductor. In this paper, we report that there is an enhancement of photocatalytic activity in presence of Sun light, by introducing Plasmon (silver nanoparticles (Ag)) onto the titanium oxide (TiO2) and nitrogen incorporated titanium oxide (N-TiO2) films. These silver nanoparticles facilitate the charge transport and separation of charge carriers. In this paper we find that the phase transformation accurse from rutile to anatase with increase of nitrogen flow rates. The FESEM analysis showed the micro structure changes to dense columnar growth with increase of nitrogen flow rates. XPS studies of the N-TiO2 thin films revealed that the substitution of N atoms within the O sites plays a crucial role in narrowing the band gap of the TiO2. This enables the absorption of visible light radiation and leads to operation of the film as a highly reactive and effective photocatalysis. The synergetic effect of silver nanoparticles on TiO2 and N-TiO2 films tailored the photocatalytic acitivity, charge transfer mechanism, and photocurrent studies. The silver nanoparticle loaded N-TiO2 films showed highest degradation of 95% compare to the N-TiO2 films. The photo degradation rate constant of Ag/N-TiO2 film was larger than the N-TiO2 films. (C) 2017 Elsevier B.V. All rights reserved
Vertical distribution and diurnal migration of atlantid heteropods
No full textUnderstanding the vertical distribution and migratory behaviour of shelled holoplanktonic gastropods is essential in determining the environmental conditions to which they are exposed. This is increasingly important in understanding the effects of ocean acidification and climate change. Here we investigated the vertical distribution of atlantid hetero pods by collating data from publications and collections and using the oxygen isotope (delta O-18) composition of single aragonitic shells. Data from publications and collections show 2 patterns of migration behaviour: small species that reside in shallow water at all times, and larger species that make diurnal migrations from the surface at night to deep waters during the daytime. The delta O-18 data show that all species analysed (n = 16) calcify their shells close to the deep chlorophyll maximum. This was within the upper 110 m of the ocean for 15 species, and down to 146 m for a single species. These findings confirm that many atlantid species are exposed to large environmental variations over a diurnal cycle and may already be well adapted to face ocean changes. However, all species analysed rely on aragonite supersaturated waters in the upper < 150 m of the ocean to produce their shells, a region that is projected to undergo the earliest and greatest changes in response to increased anthropogenic CO2
Quantum Phase Transition in Few-Layer NbSe2 Probed through Quantized Conductance Fluctuations
No full textWe present the first observation of dynamically modulated quantum phase transition between two distinct charge density wave (CDW) phases in two-dimensional 2H-NbSe2. There is recent spectroscopic evidence for the presence of these two quantum phases, but its evidence in bulk measurements remained elusive. We studied suspended, ultrathin 2H-NbSe2 devices fabricated on piezoelectric substrates-with tunable flakes thickness, disorder level, and strain. We find a surprising evolution of the conductance fluctuation spectra across the CDW temperature: the conductance fluctuates between two precise values, separated by a quantum of conductance. These quantized fluctuations disappear for disordered and on-substrate devices. With the help of mean-field calculations, these observations can be explained as to arise from dynamical phase transition between the two CDWstates. To affirm this idea, we vary the lateral strain across the device via piezoelectric medium and map out the phase diagram near the quantum critical point. The results resolve a long-standing mystery of the anomalously large spectroscopic gap in NbSe2
Application of 10(13) ohm Faraday cup current amplifiers for boron isotopic analyses by solution mode and laser ablation multicollector inductively coupled plasma mass spectrometry
No full textRationaleBoron isotope ratios (B-11 values) are used as a proxy for seawater paleo-pH, amongst several other applications. The analytical precision can be limited by the detection of low intensity ion beams from limited sample amounts. High-gain amplifiers offer improvements in signal/noise ratio and can be used to increase measurement precision and reduce sample amounts. Methods10(13) ohm amplifier technology has previously been applied to several radiogenic systems, but has thus far not been applied to non-traditional stable isotopes. Here we apply 10(13) ohm amplifier technology for the measurement of boron isotope ratios using solution mode MC-ICP-MS and laser ablation mode (LA-)MC-ICP-MS techniques. Precision is shown for reference materials as well as for low-volume foraminifera samples. ResultsThe baseline uncertainty for a 0.1 pA B-10(+) ion beam is reduced to <0.1 for a typical measurement period. The external precision is better than 0.2 parts per thousand (2SD) for B-11 measurements for solution samples containing as little as 0.8 ng total boron. For in situ microanalyses with LA-MC-ICP-MS, the external precision of B-11/B-10 from an in-house calcite standard was 1 parts per thousand (2SD) for individual spot analyses, and 0.3 parts per thousand for the mean of 10 replicate spot analyses. Conclusions10(13) ohm amplifier technology is demonstrated to offer advantages for the determination of B-11 values by both MC-ICP-MS and LA-MC-ICP-MS for small samples of biogenic carbonates, such as foraminifera shells. 10(13) ohm amplifier technology will also be of benefit to other non-traditional stable isotope measurements