Diminished Intracellular Invariant Chain Expression Following Vaccinia Virus Infection

Vaccinia virus (VV) has been used as a vaccine to eradicate smallpox and as a vaccine for HIV and tumors. However, the immunoevasive properties of VV, have raised safety concerns. VV infection of APC perturbs MHC class II-mediated Ag presentation. Exposure of human B cell lines to VV induced a dramatic reduction in cellular expression of the class II chaperone, invariant chain (Ii) during the late stages (i.e. 8–10 h) of infection. Yet, cell viability and surface expression of MHC class II molecules were maintained up to 24 h after exposure to virus. Reductions in Ii and class II mRNA levels were detected as early as 6 h after VV infection of APC. To examine whether VV was acting solely to disrupt host protein synthesis, B cells were treated with an inhibitor of translation, cycloheximide (CHX). Within 1 h of B cell CHX treatment, Ii protein expression decreased coupled with a loss of class II presentation. Analysis of Ii degradation in VV or CHX treated cells, revealed on-going Ii proteolysis contributing to reduced steady state Ii levels in these APC. Yet in contrast with CHX, VV infection of APC altered lysosomal protease expression and Ii degradation. Virus infection induced cellular cathepsin L expression while reducing the levels of other lysosomal proteases. These results demonstrate that at late stages of VV infection, reductions in cellular Ii levels coupled with changes in lysosomal protease activity, contribute in part to defects in class II presentation

Interplay of Spin-Orbit Interaction and Electron Correlation on the Van Vleck Susceptibility in Transition Metal Compounds

We have studied the effects of electron correlation on Van Vleck susceptibility ($\chi_{\rm{VV}}$) in transition metal compounds. A typical crossover behavior is found for the correlation effect on $\chi_{\rm{VV}}$ as sweeping spin-orbit interaction, $\lambda$. For a small $\lambda$, orbital fluctuation plays a dominant role in the correlation enhancement of $\chi_{\rm{VV}}$; however, the enhancement rate is rather small. In contrast, for an intermediate $\lambda$, $\chi_{\rm{VV}}$ shows a substantial increase, accompanied by the development of spin fluctuation. We will discuss the behavior of $\chi_{\rm{VV}}$ in association with the results of Knight-shift experiments on Sr$_2$RuO$_4$ and an anomalously large magnetic susceptibility observed for $5d$ Ir compounds.Comment: 5 pages, 3 figures, to appear in J. Phys. Soc. Jp

Multi-Modes Phonon Softening in Two-Dimensional Electron-Lattice System

Phonon dispersion in a two-dimensional electron-lattice system described by a two-dimensional square-lattice version of Su-Schrieffer-Heeger's model and having the half-filled electronic band is studied theoretically at temperatures higher than the mean field critical temperature of the Peierls transition. When the temperature is lowered from the higher region down to the critical one, softening of multi phonon modes which have wave vectors equal to the nesting vector \vv{Q}=(\pi/a,\pi/a) with $a$ the lattice constant or parallel to \vv{Q} is observed. Although both of the transverse and longitudinal modes are softened at the critical temperature in the case of the wave vector equal to \vv{Q}, only the transverse modes are softened for other wave vectors parallel to \vv{Q}. This behavior is consistent with the Peierls distortions at lower temperatures.Comment: 10 pages, 5 Figure

VV 655 and NGC 4418: Implications of an interaction for the evolution of a LIRG

VV 655, a dwarf irregular galaxy with HI tidal debris, is a companion to the lenticular luminous infrared galaxy (LIRG) NGC 4418. NGC 4418 stands out among nearby LIRGs due to its dense central concentration of molecular gas and the dusty, bi-polar structures along its minor axis suggestive of a wind driven by a central starburst and possible nuclear activity. We seek to understand the consequences of the ongoing minor interaction between VV 655 and NGC 4418 for the evolution of the LIRG, including the origin of the gas supply responsible for its unusual nuclear properties. We investigate the structural, kinematic, and chemical properties of VV 655 and NGC 4418 by analyzing archival imaging data and optical spectroscopic observations from the SDSS-III and new spectra from SALT-RSS. We characterize their gas-phase metal abundances and spatially resolved, ionized gas kinematics, and demonstrate that the gas-phase metallicity in NGC 4418 significantly exceeds that in VV 655. No kinematic disturbances in the ionized gas are observed along the minor axis of NGC 4418, but we see evidence for ionized gas outflows from VV 655 that may increase the cross-section for gas stripping in grazing collisions. A faint, asymmetric outer arm is detected in NGC 4418 of the type normally associated with galaxy-galaxy interactions. The simplest model suggests that the minor interaction between VV 655 and NGC 4418 produced the unusual nuclear properties of the LIRG via tidal torquing of the interstellar medium of NGC 4418 rather than through a significant gas transfer event. In addition to inducing a central concentration of gas in NGC 4418, this interaction also produced an enhanced star formation rate and an outer tidal arm in the LIRG. The VV 655-NGC 4418 system offers an example of the potential for minor collisions to alter the evolutionary pathways of giant galaxies.Comment: 9 pages, 4 figures, accepted for publication in Astronomy & Astrophysic

Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence

Viral immune evasion strategies target key aspects of the host antiviral response. Recently, it has been recognized that Toll-like receptors (TLRs) have a role in innate defense against viruses. Here, we define the function of the vaccinia virus (VV) protein A46R and show it inhibits intracellular signalling by a range of TLRs. TLR signalling is triggered by homotypic interactions between the Toll-like-interleukin-1 resistance (TIR) domains of the receptors and adaptor molecules. A46R contains a TIR domain and is the only viral TIR domain-containing protein identified to date. We demonstrate that A46R targets the host TIR adaptors myeloid differentiation factor 88 (MyD88), MyD88 adaptor-like, TIR domain-containing adaptor inducing IFN-beta (TRIF), and the TRIF-related adaptor molecule and thereby interferes with downstream activation of mitogen-activated protein kinases and nuclear factor kappaB. TRIF mediates activation of interferon (IFN) regulatory factor 3 (IRF3) and induction of IFN-beta by TLR3 and TLR4 and suppresses VV replication in macrophages. Here, A46R disrupted TRIF-induced IRF3 activation and induction of the TRIF-dependent gene regulated on activation, normal T cell expressed and secreted. Furthermore, we show that A46R is functionally distinct from another described VV TLR inhibitor, A52R. Importantly, VV lacking the A46R gene was attenuated in a murine intranasal model, demonstrating the importance of A46R for VV virulence

Coordinate time and proper time in the GPS

The Global Positioning System (GPS) provides an excellent educational example as to how the theory of general relativity is put into practice and becomes part of our everyday life. This paper gives a short and instructive derivation of an important formula used in the GPS, and is aimed at graduate students and general physicists. The theoretical background of the GPS (see \cite{ashby}) uses the Schwarzschild spacetime to deduce the {\it approximate} formula, ds/dt\approx 1+V-\frac{|\vv|^2}{2}, for the relation between the proper time rate $s$ of a satellite clock and the coordinate time rate $t$. Here $V$ is the gravitational potential at the position of the satellite and \vv is its velocity (with light-speed being normalized as $c=1$). In this note we give a different derivation of this formula, {\it without using approximations}, to arrive at ds/dt=\sqrt{1+2V-|\vv|^2 -\frac{2V}{1+2V}(\n\cdot\vv)^2}, where \n is the normal vector pointing outward from the center of Earth to the satellite. In particular, if the satellite moves along a circular orbit then the formula simplifies to ds/dt=\sqrt{1+2V-|\vv|^2}. We emphasize that this derivation is useful mainly for educational purposes, as the approximation above is already satisfactory in practice.Comment: 5 pages, revised, over-over-simplified... Does anyone care that the GPS uses an approximate formula, while a precise one is available in just a few lines??? Physicists don'

LHC Signatures of Two-Higgs-Doublets with Fourth Family

On-going Higgs searches in the light mass window are of vital importance for testing the Higgs mechanism and probing new physics beyond the standard model (SM). The latest ATLAS and CMS searches for the SM Higgs boson at the LHC (7TeV) found some intriguing excesses of events in the \gamma\gamma/VV^* channels (V=Z,W) around the mass-range of 124-126 GeV. We explore a possible explanation of the \gamma\gamma and VV^* signals from the light CP-odd Higgs A^0 or CP-even Higgs h^0 from the general two-Higgs-doublet model with fourth-family fermions. We demonstrate that by including invisible decays of the Higgs boson A^0 or h^0 to fourth-family neutrinos, the predicted \gamma\gamma and VV^* signals can explain the observed new signatures at the LHC, and will be further probed by the forthcoming LHC runs in 2012.Comment: 22pp, 10 Figs, JHEP published version, references adde

Asteroseismology of the GW Virginis stars SDSS J0349-0059 and VV 47

We present an asteroseismological study of SDSS J0349-0059 and VV 47 aimed mainly at deriving their total mass on the basis of state-of-the-art PG 1159 evolutionary models. We compute adiabatic nonradial $g$-mode pulsation periods for PG 1159 evolutionary models with stellar masses ranging from $0.515$ to 0.741\ M_{\sun}, that take into account the complete evolution of the progenitor stars. We first estimate a mean period spacing for both SDSS J0349-0059 and VV 47. By comparing the observed period spacing with the asymptotic period spacing we obtain M_{\star}\sim 0.569\ M_{\sun} for SDSS J0349-0059 and M_{\star}\sim 0.523\ M_{\sun} for VV 47. If we compare the observed period spacing with the average of the computed period spacings we found M_{\star}\sim 0.535\ M_{\sun} for SDSS J0349-0059 and M_{\star}\sim 0.528 M_{\sun} for VV 47. Searching for the best period fit we found, in the case of SDSS J0349-0059, an asteroseismological model with $M_{\star}= 0.542\ M_{\sun}$and$T_{\rm eff}= 91\, 255\ $K. For VV 47, we could not find a unique and unambiguous asteroseismological model. Finally, for SDSS J0349-0059, we determined the rotation period as being$P_{\rm rot}= 1/\Omega \sim 0.407$ days. The results presented in this work constitute a further step in the study of GW Vir stars through asteroseismology in the frame of fully evolutionary models of PG 1159 stars. In particular, once again it is shown the potential of asteroseismology to derive stellar masses of PG 1159 stars with an unprecedented precision.Comment: 13 pages, 16 figures, 6 tables. To be published in Astronomy and Astrophysic

Evidence that conflict regarding size of haemodynamic response to interventricular delay optimization of cardiac resynchronization therapy may arise from differences in how atrioventricular delay is kept constant.

Aims: Whether adjusting interventricular (VV) delay changes haemodynamic efficacy of cardiac resynchronization therapy (CRT) is controversial, with conflicting results. This study addresses whether the convention for keeping atrioventricular (AV) delay constant during VV optimization might explain these conflicts. / Method and results: Twenty-two patients in sinus rhythm with existing CRT underwent VV optimization using non-invasive systolic blood pressure. Interventricular optimization was performed with four methods for keeping the AV delay constant: (i) atrium and left ventricle delay kept constant, (ii) atrium and right ventricle delay kept constant, (iii) time to the first-activated ventricle kept constant, and (iv) time to the second-activated ventricle kept constant. In 11 patients this was performed with AV delay of 120 ms, and in 11 at AV optimum. At AV 120 ms, time to the first ventricular lead (left or right) was the overwhelming determinant of haemodynamics (13.75 mmHg at ±80 ms, P < 0.001) with no significant effect of time to second lead (0.47 mmHg, P = 0.50), P < 0.001 for difference. At AV optimum, time to first ventricular lead again had a larger effect (5.03 mmHg, P < 0.001) than time to second (2.92 mmHg, P = 0.001), P = 0.02 for difference. / Conclusion: Time to first ventricular activation is the overwhelming determinant of circulatory function, regardless of whether this is the left or right ventricular lead. If this is kept constant, the effect of changing time to the second ventricle is small or nil, and is not beneficial. In practice, it may be advisable to leave VV delay at zero. Specifying how AV delay is kept fixed might make future VV delay research more enlightening