The HSV-1 Latency-Associated Transcript Functions to Repress Latent Phase Lytic Gene Expression and Suppress Virus Reactivation from Latently Infected Neurons

open access articleHerpes simplex virus 1 (HSV-1) establishes life-long latent infection within sensory neurons, during which viral lytic gene expression is silenced. The only highly expressed viral gene product during latent infection is the latency-associated transcript (LAT), a non-protein coding RNA that has been strongly implicated in the epigenetic regulation of HSV-1 gene expression. We have investigated LAT-mediated control of latent gene expression using chromatin immunoprecipitation analyses and LAT-negative viruses engineered to express firefly luciferase or β-galactosidase from a heterologous lytic promoter. Whilst we were unable to determine a significant effect of LAT expression upon heterochromatin enrichment on latent HSV-1 genomes, we show that reporter gene expression from latent HSV-1 genomes occurs at a greater frequency in the absence of LAT. Furthermore, using luciferase reporter viruses we have observed that HSV-1 gene expression decreases during long-term latent infection, with a most marked effect during LAT-negative virus infection. Finally, using a fluorescent mouse model of infection to isolate and culture single latently infected neurons, we also show that reactivation occurs at a greater frequency from cultures harbouring LAT-negative HSV-1. Together, our data suggest that the HSV-1 LAT RNA represses HSV-1 gene expression in small populations of neurons within the mouse TG, a phenomenon that directly impacts upon the frequency of reactivation and the maintenance of the transcriptionally active latent reservoir

Renormalization of the mass gap

The full gluon propagator relevant for the description of the truly non-perturbative QCD dynamics, the so-called intrinsically non-perturbative gluon propagator has been derived in our previous work. It explicitly depends on the regularized mass gap, which dominates its structure at small gluon momentum. It is automatically transversal in a gauge invariant way. It is characterized by the presence of severe infrared singularities at small gluon momentum, so the gluons remain massless, and this does not depend on the gauge choice. In this paper we have shown how precisely the renormalization program for the regularized mass gap should be performed. We have also shown how precisely severe infrared singularities should be correctly treated. This allowed to analytically formulate the exact and gauge-invariant criteria of gluon and quark confinement. After the renormalization program is completed, one can derive the gluon propagator applicable for the calculation of physical observables processes, etc., in low-energy QCD from first principles.Comment: 16 pages, no figures, no tables, some minor changes are introduce

System for prostate brachytherapy and biopsy in a standard 1.5 T MRI scanner

A technique for transperineal high-dose-rate (HDR) prostate brachytherapy and needle biopsy in a standard 1.5 T MRI scanner is demonstrated. In each of eight procedures (in four patients with intermediate to high risk localized prostate cancer), four MRI-guided transperineal prostate biopsies were obtained followed by placement of 14-15 hollow transperineal catheters for HDR brachytherapy. Mean needle-placement accuracy was 2.1 mm, 95% of needle-placement errors were less than 4.0 mm, and the maximum needle-placement error was 4.4 mm. In addition to guiding the placement of biopsy needles and brachytherapy catheters, MR images were also used for brachytherapy treatment planning and optimization. Because 1.5 T MR images are directly acquired during the interventional procedure, dependence on deformable registration is reduced and online image quality is maximized

Non-linear response of a Kondo system: Perturbation approach to the time dependent Anderson impurity model

Nonlinear tunneling current through a quantum dot (an Anderson impurity system) subject to both constant and alternating electric fields is studied in the Kondo regime. A systematic diagram technique is developed for perturbation study of the current in physical systems out of equilibrium governed by time - dependent Hamiltonians of the Anderson and the Kondo models. The ensuing calculations prove to be too complicated for the Anderson model, and hence, a mapping on an effective Kondo problem is called for. This is achieved by constructing a time - dependent version of the Schrieffer - Wolff transformation. Perturbation expansion of the current is then carried out up to third order in the Kondo coupling J yielding a set of remarkably simple analytical expressions for the current. The zero - bias anomaly of the direct current differential conductance is shown to be suppressed by the alternating field while side peaks develop at finite source - drain voltage. Both the direct component and the first harmonics of the time - dependent response are equally enhanced due to the Kondo effect, while amplitudes of higher harmonics are shown to be relatively small. A zero alternating bias anomaly is found in the alternating current differential conductance, that is, it peaks around zero alternating bias. This peak is suppressed by the constant bias. No side peaks show up in the differential alternating - conductance but their counterpart is found in the derivative of the alternating current with respect to the direct bias. The results pertaining to nonlinear response are shown to be valid also below the Kondo temperature.Comment: 55 latex pages 11 ps figure

On the influence of a Coulomb-like potential induced by the Lorentz symmetry breaking effects on the Harmonic Oscillator

In this work, we obtain bound states for a nonrelativistic spin-half neutral particle under the influence of a Coulomb-like potential induced by the Lorentz symmetry breaking effects. We present a new possible scenario of studying the Lorentz symmetry breaking effects on a nonrelativistic quantum system defined by a fixed space-like vector field parallel to the radial direction interacting with a uniform magnetic field along the z-axis. Furthermore, we also discuss the influence of a Coulomb-like potential induced by Lorentz symmetry violation effects on the two-dimensional harmonic oscillator.Comment: 14 pages, no figure, this work has been accepted for publication in The European Physical Journal Plu

Research review: young people leaving care

This paper reviews the international research on young people leaving care. Set in the context of a social exclusion framework, it explores young people's accelerated and compressed transitions to adulthood, and discusses the development and classification of leaving care services in responding to their needs. It then considers the evidence from outcome studies and argues that adopting a resilience framework suggests that young people leaving care may fall into three groups: young people 'moving on', 'survivors' and 'victims'. In concluding, it argues that these three pathways are associated with the quality of care young people receive, their transitions from care and the support they receive after care

Renormalized Path Integral for the Two-Dimensional Delta-Function Interaction

A path-integral approach for delta-function potentials is presented. Particular attention is paid to the two-dimensional case, which illustrates the realization of a quantum anomaly for a scale invariant problem in quantum mechanics. Our treatment is based on an infinite summation of perturbation theory that captures the nonperturbative nature of the delta-function bound state. The well-known singular character of the two-dimensional delta-function potential is dealt with by considering the renormalized path integral resulting from a variety of schemes: dimensional, momentum-cutoff, and real-space regularization. Moreover, compatibility of the bound-state and scattering sectors is shown.Comment: 26 pages. The paper was significantly expanded and numerous equations were added for the sake of clarity; the main results and conclusions are unchange

Statistics of the gravitational force in various dimensions of space: from Gaussian to Levy laws

We discuss the distribution of the gravitational force created by a Poissonian distribution of field sources (stars, galaxies,...) in different dimensions of space d. In d=3, it is given by a Levy law called the Holtsmark distribution. It presents an algebraic tail for large fluctuations due to the contribution of the nearest neighbor. In d=2, it is given by a marginal Gaussian distribution intermediate between Gaussian and Levy laws. In d=1, it is exactly given by the Bernouilli distribution (for any particle number N) which becomes Gaussian for N>>1. Therefore, the dimension d=2 is critical regarding the statistics of the gravitational force. We generalize these results for inhomogeneous systems with arbitrary power-law density profile and arbitrary power-law force in a d-dimensional universe