Interplay between NS3 protease and human La protein regulates translation-replication switch of Hepatitis C virus

HCV NS3 protein plays a central role in viral polyprotein processing and RNA replication. We demonstrate that the NS3 protease (NS3(pro)) domain alone can specifically bind to HCV-IRES RNA, predominantly in the SLIV region. The cleavage activity of the NS3 protease domain is reduced upon HCV-RNA binding. More importantly, NS3(pro) binding to the SLIV hinders the interaction of La protein, a cellular IRES-trans acting factor required for HCV IRES-mediated translation, resulting in inhibition of HCV-IRES activity. Although overexpression of both NS3(pro) as well as the full length NS3 protein decreased the level of HCV IRES mediated translation, replication of HCV replicon RNA was enhanced significantly. These observations suggest that the NS3(pro) binding to HCV IRES reduces translation in favor of RNA replication. The competition between the host factor (La) and the viral protein (NS3) for binding to HCV IRES might regulate the molecular switch from translation to replication of HCV.

Weakening of charge order and antiferromagnetic to ferromagnetic switch over in Pr0.5Ca0.5MnO3 nanowires

We have prepared crystalline nanowires (diameter ∼ 50 nm, length ∼ a few microns) of the charge-ordering manganite Pr0.5Ca0.5MnO3 using a low reaction temperature hydrothermal method and characterized them using x-ray diffraction, transmission electron microscopy, superconducting quantum interference device (SQUID) magnetometry and electron magnetic resonance measurements. While the bulk sample shows a charge ordering transition at 245 K and an antiferromagnetic transition at 175 K, SQUID magnetometry and electron magnetic resonance experiments reveal that in the nanowires phase, a ferromagnetic transition occurs at ∼ 105 K. Further, the antiferromagnetic transition disappears and the charge ordering transition is suppressed. This result is particularly significant since the charge order in Pr0.5Ca0.5MnO3 is known to be very robust, magnetic fields as high as 27 T being needed to melt it.

Magnetic arm-switch-based three-phase series-shunt compensated quality AC power supply

This study presents a novel magnetic arm-switch-based integrated magnetic circuit for a three-phase series-shunt compensated uninterruptible power supply (UPS). The magnetic circuit acts as a common interacting field for a number of energy ports, viz., series inverter, shunt inverter, grid and load. The magnetic arm-switching technique ensures equivalent series or shunt connection between the inverters. In normal grid mode (stabiliser mode), the series inverter is used for series voltage correction and the shunt one for current correction. The inverters and the load are effectively connected in parallel when the grid power is not available. These inverters are then used to share the load power. The operation of the inverters in parallel is ensured by the magnetic arm-switching technique. This study also includes modelling of the magnetic circuit. A graphical technique called bond graph is used to model the system. In this model, the magnetic circuit is represented in terms of gyrator-capacitors. Therefore the model is also termed as gyrator-capacitor model. The model is used to extract the dynamic equations that are used to simulate the system using MATLAB/SIMULINK. This study also discusses a synchronously rotating reference frame-based control technique that is used for the control of the series and shunt inverters in different operating modes. Finally, the gyrator-capacitor model is validated by comparing the simulated and experimental results.

The Hinge Region of Human Thyroid-Stimulating Hormone (TSH) Receptor Operates as a Tunable Switch between Hormone Binding and Receptor Activation

The mechanism by which the hinge regions of glycoprotein hormone receptors couple hormone binding to activation of downstream effecters is not clearly understood. In the present study, agonistic (311.62) and antagonistic (311.87) monoclonal antibodies (MAbs) directed against the TSH receptor extracellular domain were used to elucidate role of the hinge region in receptor activation. MAb 311.62 which identifies the LRR/Cb-2 junction (aa 265-275), increased the affinity of TSHR for the hormone while concomitantly decreasing its efficacy, whereas MAb 311.87 recognizing LRR 7-9 (aa 201-259) acted as a non-competitive inhibitor of Thyroid stimulating hormone (TSH) binding. Binding of MAbs was sensitive to the conformational changes caused by the activating and inactivating mutations and exhibited differential effects on hormone binding and response of these mutants. By studying the effects of these MAbs on truncation and chimeric mutants of thyroid stimulating hormone receptor (TSHR), this study confirms the tethered inverse agonistic role played by the hinge region and maps the interactions between TSHR hinge region and exoloops responsible for maintenance of the receptor in its basal state. Mechanistic studies on the antibody-receptor interactions suggest that MAb 311.87 is an allosteric insurmountable antagonist and inhibits initiation of the hormone induced conformational changes in the hinge region, whereas MAb 311.62 acts as a partial agonist that recognizes a conformational epitope critical for coupling of hormone binding to receptor activation. The hinge region, probably in close proximity with the alpha-subunit in the hormone-receptor complex, acts as a tunable switch between hormone binding and receptor activation.

Switching and release dynamics of an electrostatically actuated MEMS switch under the influence of squeeze-film damping

This paper reports analytical modeling, simulation and experimental validation for switching and release times of an electrostatically actuated micromachined switch. Presented work is an extension of our earlier work [1] that analytically argued, and numerically and experimentally demonstrated, why pull-in time is larger that pull-up time when the actuation voltage is less than twice of the pull-in voltage. In this paper, switching dynamics is investigated under the influence of squeeze-film damping. Tests were performed on SOI (silicon-on-insulator) based parallel beams structures.Typical voltage requirement for actuation is in the range of 10-30 V. All the experiments were performed in normal atmospheric pressure. Measurement results confirm that the quality factor Q has appreciable effect on the release time compared to the switching time. The quality factor Q is extracted from the response measurement and compared with the ANSYS simulation result. In addition, the dynamic pull-in effect has also been studied and reported in this paper. A contribution of this work includes the effect of various phenomena such as squeeze-film damping, dynamic pull-in, and frequency pull-in effects on the switching dynamics of a MEMS switch.

Enhancement in threshold voltage with thickness in memory switch fabricated using GeSe1.5S0.5 thin films

Investigations on the electrical switching, structural, optical and photoacoustic analysis have been undertaken on chalcogenide GeSe1.5S0.5 thin films of various thicknesses prepared by vacuum evaporation technique. The decrease of band gap energy with increase in film thickness has been explained using the `density of states model'. The structural units of the films are characterized using Raman spectroscopy and the deconvoluted Raman peaks obtained from Gaussian fit around 188 cm(-1), 204 cm(-1) and 214 cm(-1) favors Ge-chalcogen tetrahedral units forming corner and edge sharing tetrahedra. All the thin films samples have been exhibited memory-type electrical switching behavior. An enhancement in the threshold voltages of GeSe1.5S0.5 thin films have been observed with increase in film thickness. The thickness dependence of switching voltages provide an insight into the switching mechanism and it is explained by the Joule heating effect. (C) 2014 Elsevier B.V. All rights reserved.

Pd-Catalyzed Hydroborylation of Alkynes: A Ligand Controlled Regioselectivity Switch for the Synthesis of alpha- or beta-Vinylboronates

A ligand controlled selective hydroborylation of alkynes to alpha- or beta-vinylboronates has been developed using a Pd catalyst. The high alpha-selectivity displayed by this reaction can be switched to furnish beta-vinylboronates by altering the ligand from a trialkylphosphine to N-heterocyclic carbene. A variety of terminal alkynes are shown to furnish the corresponding alpha- or beta-vinylboronates in good to excellent selectivity and yield. The mechanistic studies suggest that the solvent is the proton source and bromobenzene functions as an important additive in driving this reaction forward.

Reagent-switch controlled metal-free intermolecular geminal diamination and aminooxygenation of vinylarenes

We report here the first general method for the geminal diamination and an intermolecular metal-free, geminal aminooxygenation of vinylarenes using hypervalent iodine reagent. A new m-CPBA mediated geminal aminooxygenation is also reported. A novel reagent-switch for the control of migrating group by controlling the two independent geminal addition paths is developed. Deuterium labelling studies and the control studies have provided unambiguous evidences for the phenyl migration and hydride migration in the oxidative geminal difunctionalization process mediated by Phl(OCOCF3)(2) and m-CPBA, respectively through a semi-pinacol rearrangement. (C) 2016 Elsevier Ltd. All rights reserved.

Pd-Catalyzed Hydroborylation of Alkynes: A Ligand Controlled Regioselectivity Switch for the Synthesis of alpha- or beta-Vinylboronates

A ligand controlled selective hydroborylation of alkynes to alpha- or beta-vinylboronates has been developed using a Pd catalyst. The high alpha-selectivity displayed by this reaction can be switched to furnish beta-vinylboronates by altering the ligand from a trialkylphosphine to N-heterocyclic carbene. A variety of terminal alkynes are shown to furnish the corresponding alpha- or beta-vinylboronates in good to excellent selectivity and yield. The mechanistic studies suggest that the solvent is the proton source and bromobenzene functions as an important additive in driving this reaction forward.

Experimental Investigations on the Pulsed Power Switch of a HIRA based UWB System

The Ultra Wide Band (UWB) system has been a subject of research in the last few years due to its utility in various high power electromagnetic applications. Due to its simplicity in design and fabrication, the Half Impulse Radiating Antenna (HIRA) based UWB system has attracted many researchers. Effectiveness of a UWB system, in terms of the bandwidth of the radiated pulse depends on the duration of the radiated field which is typically of sub nanosecond regime. This duration in turn depends on the closure time of the switch used in the UWB pulsed power source. This paper presents the work carried out on the pressurised gas switch of a 50 kV pulsed power system of a HIRA based UWB system. The aim of the present work is to establish the relationship between the pulser switch breakdown voltage and gas pressure, rise time and gas pressure as well as the dependency of the Pulse Repetition Rate (PRR) on the switch breakdown voltage.