Mapping of transcription termination within the S segment of SFTS phlebovirus facilitated the generation of NSs-deletant viruses

SFTS phlebovirus (severe fever with thrombocytopenia syndrome virus; SFTSV) is an emerging tick-borne bunyavirus that was first reported in China in 2009. Here we report the generation of a recombinant SFTSV (rHB29NSsKO) that cannot express the viral non-structural protein (NSs) upon infection of cells in culture. We show that rHB29NSsKO replication kinetics are greater in interferon (IFN)-incompetent cells and that the virus is unable to suppress IFN induced in response to viral replication. The data confirm for the first time in the context of virus infection that NSs acts as a virally encoded IFN antagonist and that NSs is dispensable for virus replication. Using 3’ RACE we mapped the 3’ -end of the N and NSs mRNAs, showing that the mRNAs terminate within the coding region of the opposite open reading frame. We show that the 3’ end of the N mRNA terminates upstream of a 5’ -GCCAGCC-3’ motif present in the viral genomic RNA. With this knowledge, and using virus-like particles, we could demonstrate that the last 36 nt of the NSs ORF were needed to ensure the efficient termination of the N mRNA and were required for recombinant virus rescue. We demonstrate it is possible to recover viruses lacking NSs, expressing just a 12 amino acid NSs peptide or viruses encoding eGFP or a NSs-eGFP fusion protein in the NSs locus. This opens the possibility for further studies of NSs and potentially the design of attenuated viruses for vaccination studies

Robust continuous-time smoothers without two-sided stochastic integrals

Copyright © 2002 IEEEWe consider the problem of fixed-interval smoothing of a continuous-time partially observed nonlinear stochastic dynamical system. Existing results for such smoothers require the use of two-sided stochastic calculus. The main contribution of the paper is to present a robust formulation of the smoothing equations. Under this robust formulation, the smoothing equations are nonstochastic parabolic partial differential equations (with random coefficients) and, hence, the technical machinery associated with two sided stochastic calculus is not required. Furthermore, the robust smoothed state estimates are locally Lipschitz in the observations, which is useful for numerical simulation. As examples, finite dimensional robust versions of the Benes and hidden Markov model smoothers and smoothers for piecewise linear dynamics are derived; these finite-dimensional smoothers do not involve stochastic integrals.Vikram Krishnamurthy and Robert Elliot

An Improved Limit on Pauli-Exclusion-Principle Forbidden Atomic Transitions

We have examined the atomic theory behind recent constraints on the violation of the Pauli Exclusion Principle derived from experiments that look for x rays emitted from conductors while a large current is present. We also re-examine the assumptions underlying such experiments. We use the results of these studies to assess pilot measurements to develop an improved test of the Principle. We present an improved limit of $(1/2)\beta^2 < 2.6\times10^{-39}$ on the Pauli Exclusion Principle. This limit is the best to date for interactions between a system of fermions and a fermion that has not previously interacted with that given system. That is, for systems that do not obviously violate the Messiah-Greenberg symmetrization-postulate selection rule.Comment: Updated after editorial improvements including a typographical mistake in Table

Immersion microscopy based on photonic crystal materials

Theoretical model of the enhanced optical resolution of the surface plasmon immersion microscope is developed, which is based on the optics of surface plasmon Bloch waves in the tightly bound approximation. It is shown that a similar resolution enhancement may occur in a more general case of an immersion microscope based on photonic crystal materials with either positive or negative effective refractive index. Both signs of the effective refractive index have been observed in our experiments with surface plasmon immersion microscope, which is also shown to be capable of individual virus imaging.Comment: 23 pages, 10 figure

Fast-Neutron Activation of Long-Lived Isotopes in Enriched Ge

We measured the production of \nuc{57}{Co}, \nuc{54}{Mn}, \nuc{68}{Ge}, \nuc{65}{Zn}, and \nuc{60}{Co} in a sample of Ge enriched in isotope 76 due to high-energy neutron interactions. These isotopes, especially \nuc{68}{Ge}, are critical in understanding background in Ge detectors used for double-beta decay experiments. They are produced by cosmogenic-neutron interactions in the detectors while they reside on the Earth's surface. These production rates were measured at neutron energies of a few hundred MeV. We compared the measured production to that predicted by cross-section calculations based on CEM03.02. The cross section calculations over-predict our measurements by approximately a factor of three depending on isotope. We then use the measured cosmic-ray neutron flux, our measurements, and the CEM03.02 cross sections to predict the cosmogenic production rate of these isotopes. The uncertainty in extrapolating the cross section model to higher energies dominates the total uncertainty in the cosmogenic production rate.Comment: Revised after feedback and further work on extrapolating cross sections to higher energies in order to estimate cosmic production rates. Also a numerical error was found and fixed in the estimate of the Co-57 production rat

Large magnetoresistance in the magnetically ordered state as well as in the paramagnetic state near 300 K in an intermetallic compound,Gd7Rh3

We report the response of electrical resistivity $\rho$ to the application of magnetic fields (H) up to 140 kOe in the temperature interval 1.8-300 K for the compound, Gd7Rh3, ordering antiferromagnetically below 150 K. We find that there is an unusually large decrease of $\rho$ for moderate values of H in the close vicinity of room temperature uncharacteristic of paramagnets, with the magnitude of the magnetoresistance increasing with decreasing temperature as though the spin-order contribution to $\rho$ is temperature dependent. In addition, this compound exhibits giant magnetoresistance behaviour at rather high temperatures (above 77 K) in the magnetically ordered state due to a metamagnetic transition.Comment: Europhyics Letters, in pres

Worldwide Exposures to Cardiovascular Risk Factors and Associated Health Effects: Current Knowledge and Data Gaps.

Information on exposure to, and health effects of, cardiovascular disease (CVD) risk factors is needed to develop effective strategies to prevent CVD events and deaths. Here, we provide an overview of the data and evidence on worldwide exposures to CVD risk factors and the associated health effects. Global comparative risk assessment studies have estimated that hundreds of thousands or millions of CVD deaths are attributable to established CVD risk factors (high blood pressure and serum cholesterol, smoking, and high blood glucose), high body mass index, harmful alcohol use, some dietary and environmental exposures, and physical inactivity. The established risk factors plus body mass index are collectively responsible for ≈9.7 million annual CVD deaths, with high blood pressure accounting for more CVD deaths than any other risk factor. Age-standardized CVD death rates attributable to established risk factors plus high body mass index are lowest in high-income countries, followed by Latin America and the Caribbean; they are highest in the region of central and eastern Europe and central Asia. However, estimates of the health effects of CVD risk factors are highly uncertain because there are insufficient population-based data on exposure to most CVD risk factors and because the magnitudes of their effects on CVDs in observational studies are likely to be biased. We identify directions for research and surveillance to better estimate the effects of CVD risk factors and policy options for reducing CVD burden by modifying preventable risk factors.</jats:p