HIV-1 Env sequence and structure contribute to both coreceptor tropism and susceptibility to antibody neutralization

HIV-1 Env is the only viral protein expressed on the surface of the virus, making Env the sole target of selective pressure that favors mutated variants capable of evading the immune response. The surface subunit of Env, gp120, binds CD4 on the surface of the target cell, followed by binding of a coreceptor, usually chemokine receptors CCR5 or CXCR4. The virus that is normally transmitted during infection is a CCR5-using virus (R5-tropic), which can mutate to acquire CXCR4 usage (X4-tropism) later in infection. The coreceptor switch is manifested in some HIV-1 subtypes, whereas other subtypes rarely make the coreceptor switch. env contains regions of conserved and variable sequence, and the variable region 3 (V3) is the major determinant of coreceptor usage. In this dissertation, we describe subtype-specific conformational differences within the V3 region that permit coreceptor switching in subtype B, but not in subtype C. Furthermore, the backbone of Env interacts with V3 to shelter it from immune pressures; when V3 is exposed, Env is hyper-sensitive to neutralization by anti-V3 monoclonal antibodies, suggesting interactions between different regions of Env. In vivo coreceptor usage evolution of subtype B env variants indicates that dual-tropic variants are always generated in the transition to X4-tropism, suggesting that coreceptor evolution begins with R5-monotropic variants, transitions into dual-tropic variants and finally generates X4-monotropic variants. The coreceptor switch is associated with mutations in V3 and other areas of the env backbone, again suggesting the interaction of the entire Env in coreceptor interaction. Finally, the transmembrane subunit of Env, gp41, contains the epitopes of two broadly neutralizing antibodies, 2F5 and 4E10, located in the membrane proximal external region (MPER). A single mutation in the MPER confers increased neutralization sensitivity to both antibodies. The effect of the mutation is contained to the MPER, and there is no apparent effect on expression, folding, infection or the global structure, suggesting that the MPER can be modified for efficient antigen presentation as part of a comprehensive vaccine for long-term control of viremia. Our data collectively suggest that HIV-1 env sequence and structure contribute to both coreceptor tropism and susceptibility to antibody neutralization

Stationary inversion of a two level system coupled to an off-resonant cavity with strong dissipation

We present an off-resonant excitation scheme that realizes pronounced stationary inversion in a two level system. The created inversion exploits a cavity-assisted two photon resonance to enhance the multi-photon regime of nonlinear cavity QED and survives even in a semiconductor environment, where the cavity decay rate is comparable to the cavity-dot coupling rate. Exciton populations of greater than 0.75 are obtained in the presence of realistic decay and pure dephasing. Quantum trajectory simulations and quantum master equation calculations help elucidate the underlying physics and delineate the limitations of a simplified rate equation model. Experimental signatures of inversion and multi-photon cavity QED are predicted in the fluorescence intensity and second-order correlation function measured as a function of drive power.Comment: 4 page lette

Finite Size Effects in Thermal Field Theory

We consider a neutral self-interacting massive scalar field defined in a d-dimensional Euclidean space. Assuming thermal equilibrium, we discuss the one-loop perturbative renormalization of this theory in the presence of rigid boundary surfaces (two parallel hyperplanes), which break translational symmetry. In order to identify the singular parts of the one-loop two-point and four-point Schwinger functions, we use a combination of dimensional and zeta-function analytic regularization procedures. The infinities which occur in both the regularized one-loop two-point and four-point Schwinger functions fall into two distinct classes: local divergences that could be renormalized with the introduction of the usual bulk counterterms, and surface divergences that demand countertems concentrated on the boundaries. We present the detailed form of the surface divergences and discuss different strategies that one can assume to solve the problem of the surface divergences. We also briefly mention how to overcome the difficulties generated by infrared divergences in the case of Neumann-Neumann boundary conditions.Comment: 31 pages, latex, to appear in J. Math. Phy

Casimir forces in a T operator approach

We explore the scattering approach to Casimir forces. Our main tool is the description of Casimir energy in terms of transition operators, as presented in Kenneth and Klich, Phys. Rev. Lett. 97, 160401 (2006). We study the convergence properties of the formula and how to utilize it, together with scattering data to compute the force. We illustrate the approach by describing the force between scatterers in 1d and 3d,, and in particular show how it may be applied in order to study the interaction between two spherical bodies at all distances

Superluminal pulse reflection from a weakly absorbing dielectric slab

Group delay for a reflected light pulse from a weakly absorbing dielectric slab is theoretically investigated, and large negative group delay is found for weak absorption near a resonance of the slab ($Re(kd)=m\pi$). The group delays for both the reflected and transmitted pulses will be saturated with the increase of the absorption.Comment: 13pages, 3figure

Diffraction in the Semiclassical Approximation to Feynman's Path Integral Representation of the Green Function

We derive the semiclassical approximation to Feynman's path integral representation of the energy Green function of a massless particle in the shadow region of an ideal obstacle in a medium. The wavelength of the particle is assumed to be comparable to or smaller than any relevant length of the problem. Classical paths with extremal length partially creep along the obstacle and their fluctuations are subject to non-holonomic constraints. If the medium is a vacuum, the asymptotic contribution from a single classical path of overall length L to the energy Green function at energy E is that of a non-relativistic particle of mass E/c^2 moving in the two-dimensional space orthogonal to the classical path for a time \tau=L/c. Dirichlet boundary conditions at the surface of the obstacle constrain the motion of the particle to the exterior half-space and result in an effective time-dependent but spatially constant force that is inversely proportional to the radius of curvature of the classical path. We relate the diffractive, classically forbidden motion in the "creeping" case to the classically allowed motion in the "whispering gallery" case by analytic continuation in the curvature of the classical path. The non-holonomic constraint implies that the surface of the obstacle becomes a zero-dimensional caustic of the particle's motion. We solve this problem for extremal rays with piecewise constant curvature and provide uniform asymptotic expressions that are approximately valid in the penumbra as well as in the deep shadow of a sphere.Comment: 37 pages, 5 figure

Quantum Radiation of a Uniformly Accelerated Refractive Body

We study quantum radiation generated by an accelerated motion of a small body with a refractive index n which differes slightly from 1. To simplify calculations we consider a model with a scalar massless field. We use the perturbation expansion in a small parameter n-1 to obtain a correction to the vacuum Hadamard function for a uniformly accelerated motion of the body. We obtain the vacuum expectation for the energy density flux in the wave zone and discuss its properties.Comment: 16 pages, 1 figur

Quantum Effects in the Presence of Expanding Semi-Transparent Spherical Mirrors

We study quantum effects in the presence of a spherical semi-transparent mirror or a system of two concentric mirrors which expand with a constant acceleration in a flat D-dimensional spacetime. Using the Euclidean approach, we obtain expressions for fluctuations and the renormalized value of stress-energy tensor for a scalar non-minimally coupled massless field. Explicit expressions are obtained for the energy fluxes at the null infinity generated by such mirrors in the physical spacetime and their properties are discussed.Comment: 28 pages, Paper is slightly reorganized, additional references are adde

Perturbations of Noise: The origins of Isothermal Flows

We make a detailed analysis of both phenomenological and analytic background for the "Brownian recoil principle" hypothesis (Phys. Rev. A 46, (1992), 4634). A corresponding theory of the isothermal Brownian motion of particle ensembles (Smoluchowski diffusion process approximation), gives account of the environmental recoil effects due to locally induced tiny heat flows. By means of local expectation values we elevate the individually negligible phenomena to a non-negligible (accumulated) recoil effect on the ensemble average. The main technical input is a consequent exploitation of the Hamilton-Jacobi equation as a natural substitute for the local momentum conservation law. Together with the continuity equation (alternatively, Fokker-Planck), it forms a closed system of partial differential equations which uniquely determines an associated Markovian diffusion process. The third Newton law in the mean is utilised to generate diffusion-type processes which are either anomalous (enhanced), or generically non-dispersive.Comment: Latex fil