Identification of structural protein–protein interactions of herpes simplex virus type 1

AbstractIn this study we have defined protein–protein interactions between the structural proteins of herpes simplex virus type 1 (HSV-1) using a LexA yeast two-hybrid system. The majority of the capsid, tegument and envelope proteins of HSV-1 were screened in a matrix approach. A total of 40 binary interactions were detected including 9 out of 10 previously identified tegument–tegument interactions (Vittone, V., Diefenbach, E., Triffett, D., Douglas, M.W., Cunningham, A.L., and Diefenbach, R.J., 2005. Determination of interactions between tegument proteins of herpes simplex virus type 1. J. Virol. 79, 9566–9571). A total of 12 interactions involving the capsid protein pUL35 (VP26) and 11 interactions involving the tegument protein pUL46 (VP11/12) were identified. The most significant novel interactions detected in this study, which are likely to play a role in viral assembly, include pUL35–pUL37 (capsid–tegument), pUL46–pUL37 (tegument–tegument) and pUL49 (VP22)–pUS9 (tegument–envelope). This information will provide further insights into the pathways of HSV-1 assembly and the identified interactions are potential targets for new antiviral drugs

New solution procedures for the order picker routing problem in U-shaped pick areas with a movable depot

This paper develops new solution procedures for the order picker routing problem in U-shaped order picking zones with a movable depot, which has so far only been solved using simple heuristics. The paper presents the frst exact solution approach, based on combinatorial Benders decomposition, as well as a heuristic approach based on dynamic programming that extends the idea of the venerable sweep algorithm. In a computational study, we demonstrate that the exact approach can solve small instances well, while the heuristic dynamic programming approach is fast and exhibits an average optimality gap close to zero in all test instances. Moreover, we investigate the infuence of various storage assignment policies from the literature and compare them to a newly derived policy that is shown to be advantageous under certain circumstances. Secondly, we investigate the efects of having a movable depot compared to a fxed one and the infuence of the efort to move the depot

A36-dependent actin filament nucleation promotes release of vaccinia virus

Cell-to-cell transmission of vaccinia virus can be mediated by enveloped virions that remain attached to the outer surface of the cell or those released into the medium. During egress, the outer membrane of the double-enveloped virus fuses with the plasma membrane leaving extracellular virus attached to the cell surface via viral envelope proteins. Here we report that F-actin nucleation by the viral protein A36 promotes the disengagement of virus attachment and release of enveloped virus. Cells infected with the A36YdF virus, which has mutations at two critical tyrosine residues abrogating localised actin nucleation, displayed a 10-fold reduction in virus release. We examined A36YdF infected cells by transmission electron microscopy and observed that during release, virus appeared trapped in small invaginations at the plasma membrane. To further characterise the mechanism by which actin nucleation drives the dissociation of enveloped virus from the cell surface, we examined recombinant viruses by super-resolution microscopy. Fluorescently-tagged A36 was visualised at sub-viral resolution to image cell-virus attachment in mutant and parental backgrounds. We confirmed that A36YdF extracellular virus remained closely associated to the plasma membrane in small membrane pits. Virus-induced actin nucleation reduced the extent of association, thereby promoting the untethering of virus from the cell surface. Virus release can be enhanced via a point mutation in the luminal region of B5 (P189S), another virus envelope protein. We found that the B5P189S mutation led to reduced contact between extracellular virus and the host membrane during release, even in the absence of virus-induced actin nucleation. Our results posit that during release virus is tightly tethered to the host cell through interactions mediated by viral envelope proteins. Untethering of virus into the surrounding extracellular space requires these interactions be relieved, either through the force of actin nucleation or by mutations in luminal proteins that weaken these interactions. © 2013 Horsington et al

THE ROLE OF DENTISTRY IN FEDERAL-STATE-LOCAL COMPREHENSIVE HEALTH PLANNING *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65702/1/j.1752-7325.1968.tb01419.x.pd

Realtime calibration of the A4 electromagnetic lead fluoride calorimeter

Sufficient energy resolution is the key issue for the calorimetry in particle and nuclear physics. The calorimeter of the A4 parity violation experiment at MAMI is a segmented calorimeter where the energy of an event is determined by summing the signals of neighbouring channels. In this case the precise matching of the individual modules is crucial to obtain a good energy resolution. We have developped a calibration procedure for our total absorbing electromagnetic calorimeter which consists of 1022 lead fluoride (PbF_2) crystals. This procedure reconstructs the the single-module contributions to the events by solving a linear system of equations, involving the inversion of a 1022 x 1022-matrix. The system has shown its functionality at beam energies between 300 and 1500 MeV and represents a new and fast method to keep the calorimeter permanently in a well-calibrated state

Measurement of the Transverse Beam Spin Asymmetry in Elastic Electron Proton Scattering and the Inelastic Contribution to the Imaginary Part of the Two-Photon Exchange Amplitude

We report on a measurement of the asymmetry in the scattering of transversely polarized electrons off unpolarized protons, A$_\perp$, at two Q$^2$ values of \qsquaredaveragedlow (GeV/c)$^2$ and \qsquaredaveragedhighII (GeV/c)$^2$ and a scattering angle of $30^\circ < \theta_e < 40^\circ$. The measured transverse asymmetries are A$_{\perp}$(Q$^2$ = \qsquaredaveragedlow (GeV/c)$^2$) = (\experimentalasymmetry alulowcorr $\pm$ \statisticalerrorlow$_{\rm stat}$ $\pm$ \combinedsyspolerrorlowalucor$_{\rm sys}$) $\times$ 10$^{-6}$ and A$_{\perp}$(Q$^2$ = \qsquaredaveragedhighII (GeV/c)$^2$) = (\experimentalasymme tryaluhighcorr $\pm$ \statisticalerrorhigh$_{\rm stat}$ $\pm$ \combinedsyspolerrorhighalucor$_{\rm sys}$) $\times$ 10$^{-6}$. The first errors denotes the statistical error and the second the systematic uncertainties. A$_\perp$ arises from the imaginary part of the two-photon exchange amplitude and is zero in the one-photon exchange approximation. From comparison with theoretical estimates of A$_\perp$ we conclude that $\pi$N-intermediate states give a substantial contribution to the imaginary part of the two-photon amplitude. The contribution from the ground state proton to the imaginary part of the two-photon exchange can be neglected. There is no obvious reason why this should be different for the real part of the two-photon amplitude, which enters into the radiative corrections for the Rosenbluth separation measurements of the electric form factor of the proton.Comment: 4 figures, submitted to PRL on Oct.

Measurement of Strange Quark Contributions to the Nucleon's Form Factors at Q^2=0.230 (GeV/c)^2

We report on a measurement of the parity-violating asymmetry in the scattering of longitudinally polarized electrons on unpolarized protons at a $Q^2$ of 0.230 (GeV/c)^2 and a scattering angle of \theta_e = 30^o - 40^o. Using a large acceptance fast PbF_2 calorimeter with a solid angle of \Delta\Omega = 0.62 sr the A4 experiment is the first parity violation experiment to count individual scattering events. The measured asymmetry is A_{phys} =(-5.44 +- 0.54_{stat} +- 0.27_{\rm sys}) 10^{-6}. The Standard Model expectation assuming no strangeness contributions to the vector form factors is $A_0=(-6.30 +- 0.43) 10^{-6}$. The difference is a direct measurement of the strangeness contribution to the vector form factors of the proton. The extracted value is G^s_E + 0.225 G^s_M = 0.039 +- 0.034 or F^s_1 + 0.130 F^s_2 = 0.032 +- 0.028.Comment: 5 pages, 3 figures, submitted to Phys. Rev. Letters on Dec 11, 200