A Shot in the Arm for AIDS Vaccine Research

Why haven't we developed an HIV vaccine yet? And will the new roadmap from the Global HIV/AIDS Vaccine Enterprise help our efforts towards vaccine development? Ho addresses these crucial question

ALMA Observations of Circumnuclear Disks in Early Type Galaxies: 12CO(2-1) and Continuum Properties

We present results from an Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 2 program to map CO(2-1) emission in nearby early-type galaxies (ETGs) that host circumnuclear gas disks. We obtained $\sim0.3''-$resolution Band 6 observations of seven ETGs selected on the basis of dust disks in Hubble Space Telescope images. We detect CO emission in five at high signal-to-noise ratio with the remaining two only faintly detected. All CO emission is coincident with the dust and is in dynamically cold rotation. Four ETGs show evidence of rapid central rotation; these are prime candidates for higher-resolution ALMA observations to measure the black hole masses. In this paper we focus on the molecular gas and continuum properties. Total gas masses and H$_2$ column densities for our five CO-bright galaxies are on average $\sim10^8$ $M_\odot$ and $\sim10^{22.5}$ cm$^{-2}$ over the $\sim$kpc-scale disks, and analysis suggests that these disks are stabilized against gravitational fragmentation. The continuum emission of all seven galaxies is dominated by a central, unresolved source, and in five we also detect a spatially extended component. The $\sim$230 GHz nuclear continua are modeled as power laws ranging from $S_\nu \sim \nu^{-0.4}$ to $\nu^{1.6}$ within the observed frequency band. The extended continuum profiles of the two radio-bright (and CO-faint) galaxies are roughly aligned with their radio jet and suggests resolved synchrotron jets. The extended continua of the CO-bright disks are coincident with optically thick dust absorption and have spectral slopes that are consistent with thermal dust emission.Comment: 20 pages, 10 figures; accepted for publication in Ap

Strategic addition of an N-linked glycan to a monoclonal antibody improves its HIV-1-neutralizing activity

Ibalizumab is a humanized monoclonal antibody that binds human CD4—a key receptor for HIV—and blocks HIV-1 infection. However, HIV-1 strains with mutations resulting in loss of an N-linked glycan from the V5 loop of the envelope protein gp120 are resistant to ibalizumab. Previous structural analysis suggests that this glycan fills a void between the gp120 V5 loop and the ibalizumab L chain, perhaps causing steric hindrance that disrupts viral entry. If this void contributes to HIV-1 resistance to ibalizumab, we reasoned that ‘refilling’ it by engineering an N-linked glycan into the ibalizumab L chain at a position spatially proximal to gp120 V5 may restore susceptibility to ibalizumab. Indeed, one such ibalizumab variant neutralized 100% of 118 tested diverse HIV-1 strains in vitro, including ten strains resistant to parental ibalizumab. These findings demonstrate that the strategic placement of a glycan in the variable region of a monoclonal antibody can substantially enhance its activity

Equilibration through local information exchange in networks

We study the equilibrium states of energy functions involving a large set of real variables, defined on the links of sparsely connected networks, and interacting at the network nodes, using the cavity and replica methods. When applied to the representative problem of network resource allocation, an efficient distributed algorithm is devised, with simulations showing full agreement with theory. Scaling properties with the network connectivity and the resource availability are found.Comment: v1: 7 pages, 1 figure, v2: 4 pages, 2 figures, simplified analysis and more organized results, v3: minor change

Inference and Optimization of Real Edges on Sparse Graphs - A Statistical Physics Perspective

Inference and optimization of real-value edge variables in sparse graphs are studied using the Bethe approximation and replica method of statistical physics. Equilibrium states of general energy functions involving a large set of real edge-variables that interact at the network nodes are obtained in various cases. When applied to the representative problem of network resource allocation, efficient distributed algorithms are also devised. Scaling properties with respect to the network connectivity and the resource availability are found, and links to probabilistic Bayesian approximation methods are established. Different cost measures are considered and algorithmic solutions in the various cases are devised and examined numerically. Simulation results are in full agreement with the theory.Comment: 21 pages, 10 figures, major changes: Sections IV to VII updated, Figs. 1 to 3 replace

Titanium Nitride Films for Ultrasensitive Microresonator Detectors

Titanium nitride (TiNx) films are ideal for use in superconducting microresonator detectors because: a) the critical temperature varies with composition (0 < Tc < 5 K); b) the normal-state resistivity is large, \rho_n ~ 100 $\mu$Ohm cm, facilitating efficient photon absorption and providing a large kinetic inductance and detector responsivity; and c) TiN films are very hard and mechanically robust. Resonators using reactively sputtered TiN films show remarkably low loss (Q_i > 10^7) and have noise properties similar to resonators made using other materials, while the quasiparticle lifetimes are reasonably long, 10-200 $\mu$s. TiN microresonators should therefore reach sensitivities well below 10^-19 WHz^(-1/2).Comment: to be published in AP

Natural Variation in Vif: Differential Impact on APOBEC3G/3F and a Potential Role in HIV-1 Diversification

The HIV-1 Vif protein counteracts the antiviral activity exhibited by the host cytidine deaminases APOBEC3G and APOBEC3F. Here, we show that defective vif alleles can readily be found in HIV-1 isolates and infected patients. Single residue changes in the Vif protein sequence are sufficient to cause the loss of Vif-induced APOBEC3 neutralization. Interestingly, not all the detected defects lead to a complete inactivation of Vif function since some mutants retained selective neutralizing activity against APOBEC3F but not APOBEC3G or vice versa. Concordantly, independently hypermutated proviruses with distinguishable patterns of G-to-A substitution attributable to cytidine deamination induced by APOBEC3G, APOBEC3F, or both enzymes were present in individuals carrying proviruses with completely or partly defective Vif variants. Natural variation in Vif function may result in selective and partial neutralization of cytidine deaminases and thereby promote viral sequence diversification within HIV-1 infected individuals