Inhibition of HSP90 attenuates porcine reproductive and respiratory syndrome virus production in vitro

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) infection leads to substantial economic losses to the swine industry worldwide. However, no effective countermeasures exist to combat this virus infection so far. The most common antiviral strategy relies on directly inhibiting viral proteins. However, this strategy invariably leads to the emergence of drug resistance due to the error-prone nature of viral ploymerase. Targeting cellular proteins required for viral infection for developing new generation of antivirals is gaining concern. Recently, heat shock protein 90 (HSP90) was found to be an important host factor for the replication of multiple viruses and the inhibition of HSP90 showed significant antiviral effects. It is thought that the inhibition of HSP90 could be a promising broad-range antiviral approach. However, the effects of HSP90 inhibition on PRRSV infection have not been evaluated. In the current research, we tried to inhibit HSP90 and test whether the inhibition affect PRRSV infection. METHODS: We inhibit the function of HSP90 with two inhibitors, geldanamycin (GA) and 17- allylamono-demethoxygeldanamycin (17-AAG), and down-regulated the expression of endogenous HSP90 with specific small-interfering RNAs (siRNAs). Cell viability was measured with alamarBlue. The protein level of viral N was determined by western blotting and indirect immunofluorescence (IFA). Besides, IFA was employed to examine the level of viral double-stranded RNA (dsRNA). The viral RNA copy number and the level of IFN-β mRNA were determined by quantitative real-time PCR (qRT-PCR). RESULTS: Our results indicated that both HSP90 inhibitors showed strong anti-PRRSV activity. They could reduce viral production by preventing the viral RNA synthesis. These inhibitory effects were not due to the activation of innate interferon response. In addition, we observed that individual knockdown targeting HSP90α or HSP90β did not show dramatic inhibitory effect. Combined knockdown of these two isoforms was required to reduce viral infection. CONCLUSIONS: Our results shed light on the possibility of developing potential therapeutics targeting HSP90 against PRRSV infection

Using a coherent hydrophone array for observing sperm whale range, classification, and shallow-water dive profiles

Sperm whales in the New England continental shelf and slope were passively localized, in both range and bearing, and classified using a single low-frequency (<2500 Hz), densely sampled, towed horizontal coherent hydrophone array system. Whale bearings were estimated using time-domain beamforming that provided high coherent array gain in sperm whale click signal-to-noise ratio. Whale ranges from the receiver array center were estimated using the moving array triangulation technique from a sequence of whale bearing measurements. Multiple concurrently vocalizing sperm whales, in the far-field of the horizontal receiver array, were distinguished and classified based on their horizontal spatial locations and the inter-pulse intervals of their vocalized click signals. The dive profile was estimated for a sperm whale in the shallow waters of the Gulf of Maine with 160 m water-column depth located close to the array's near-field where depth estimation was feasible by employing time difference of arrival of the direct and multiply reflected click signals received on the horizontal array. By accounting for transmission loss modeled using an ocean waveguide-acoustic propagation model, the sperm whale detection range was found to exceed 60 km in low to moderate sea state conditions after coherent array processing.National Science Foundation (U.S.)United States. Office of Naval Researc

Advantageous grain boundaries in iron pnictide superconductors

High critical temperature superconductors have zero power consumption and could be used to produce ideal electric power lines. The principal obstacle in fabricating superconducting wires and tapes is grain boundaries-the misalignment of crystalline orientations at grain boundaries, which is unavoidable for polycrystals, largely deteriorates critical current density. Here, we report that High critical temperature iron pnictide superconductors have advantages over cuprates with respect to these grain boundary issues. The transport properties through well-defined bicrystal grain boundary junctions with various misorientation angles (thetaGB) were systematically investigated for cobalt-doped BaFe2As2 (BaFe2As2:Co) epitaxial films fabricated on bicrystal substrates. The critical current density through bicrystal grain boundary (JcBGB) remained high (> 1 MA/cm2) and nearly constant up to a critical angle thetac of ~9o, which is substantially larger than the thetac of ~5o for YBCO. Even at thetaGB > thetac, the decay of JcBGB was much smaller than that of YBCO.Comment: to appear in Nature Communication

Bipolar Magnetic Semiconductors: A New Class of Spintronics Materials

Electrical control of spin polarization is very desirable in spintronics, since electric field can be easily applied locally in contrast with magnetic field. Here, we propose a new concept of bipolar magnetic semiconductor (BMS) in which completely spin-polarized currents with reversible spin polarization can be created and controlled simply by applying a gate voltage. This is a result of the unique electronic structure of BMS, where the valence and conduction bands possess opposite spin polarization when approaching the Fermi level. Our band structure and spin-polarized electronic transport calculations on semi-hydrogenated single-walled carbon nanotubes confirm the existence of BMS materials and demonstrate the electrical control of spin-polarization in them.Comment: 20 pages, 6 figures, accepted by Nanoscal

Magnetization Dynamics in Synthetic Antiferromagnets with Perpendicular Magnetic Anisotropy

Understanding the rich physics of magnetization dynamics in perpendicular synthetic antiferromagnets (p-SAFs) is crucial for developing next-generation spintronic devices. In this work, we systematically investigate the magnetization dynamics in p-SAFs combining time-resolved magneto-optical Kerr effect (TR-MOKE) measurements with theoretical modeling. These model analyses, based on a Landau-Lifshitz-Gilbert approach incorporating exchange coupling, provide details about the magnetization dynamic characteristics including the amplitudes, directions, and phases of the precession of p-SAFs under varying magnetic fields. These model-predicted characteristics are in excellent quantitative agreement with TR-MOKE measurements on an asymmetric p-SAF. We further reveal the damping mechanisms of two procession modes co-existing in the p-SAF and successfully identify individual contributions from different sources, including Gilbert damping of each ferromagnetic layer, spin pumping, and inhomogeneous broadening. Such a comprehensive understanding of magnetization dynamics in p-SAFs, obtained by integrating high-fidelity TR-MOKE measurements and theoretical modeling, can guide the design of p-SAF-based architectures for spintronic applications.Comment: 24 pages, 5 figure

Guaranteed Verification of Finite Element Solutions of Heat Conduction

This dissertation addresses the accuracy of a-posteriori error estimators for finite element solutions of problems with high orthotropy especially for cases where rather coarse meshes are used, which are often encountered in engineering computations. We present sample computations which indicate lack of robustness of all standard residual estimators with respect to high orthotropy. The investigation shows that the main culprit behind the lack of robustness of residual estimators is the coarseness of the finite element meshes relative to the thickness of the boundary and interface layers in the solution. With the introduction of an elliptic reconstruction procedure, a new error estimator based on the solution of the elliptic reconstruction problem is invented to estimate the exact error measured in space-time C-norm for both semi-discrete and fully discrete finite element solutions to linear parabolic problem. For a fully discrete solution, a temporal error estimator is also introduced to evaluate the discretization error in the temporal field. In the meantime, the implicit Neumann subdomain residual estimator for elliptic equations, which involves the solution of the local residual problem, is combined with the elliptic reconstruction procedure to carry out a posteriori error estimation for the linear parabolic problem. Numerical examples are presented to illustrate the superconvergence properties in the elliptic reconstruction and the performance of the bounds based on the space-time C-norm. The results show that in the case of L^2 norm for smooth solution there is no superconvergence in elliptic reconstruction for linear element, and for singular solution the superconvergence does not exist for element of any order while in the case of energy norm the superconvergence always exists in elliptic reconstruction. The research also shows that the performance of the bounds based on space-time C-norm is robust, and in the case of fully discrete finite element solution the bounds for the temporal error are sharp