Complex interplay of kinetic factors governs the synergistic properties of HIV-1 entry inhibitors.

The homotrimeric HIV-1 envelope glycoprotein (Env) undergoes receptor-triggered structural changes that mediate viral entry through membrane fusion. This process is inhibited by chemokine receptor antagonists (CoRAs) that block Env-receptor interactions and by fusion inhibitors (FIs) that disrupt Env conformational transitions. Synergy between CoRAs and FIs has been attributed to a CoRA-dependent decrease in the rate of viral membrane fusion that extends the lifetime of the intermediate state targeted by FIs. Here, we demonstrated that the magnitude of CoRA/FI synergy unexpectedly depends on FI-binding affinity and the stoichiometry of chemokine receptor binding to trimeric Env. For C-peptide FIs (clinically represented by enfuvirtide), synergy waned as binding strength decreased until inhibitor combinations behaved additively. Curiously, this affinity dependence on synergy was absent for 5-Helix-type FIs. We linked this complex behavior to the CoRA dependence of Env deactivation following FI binding. For both FI classes, reducing chemokine receptor levels on target cells or eliminating competent chemokine receptor-binding sites on Env trimers resulted in a loss of synergistic activity. These data imply that the stoichiometry required for CoRA/FI synergy exceeds that required for HIV-1 entry. Our analysis suggests two distinct roles for chemokine receptor binding, one to trigger formation of the FI-sensitive intermediate state and another to facilitate subsequent conformational transitions. Together, our results could explain the wide variety of previously reported activities for CoRA/FI combinations. These findings also have implications for the combined use of CoRAs and FIs in antiviral therapies and point to a multifaceted role for chemokine receptor binding in promoting HIV-1 entry

Efficient Schemes for Reducing Imperfect Collective Decoherences

We propose schemes that are efficient when each pair of qubits undergoes some imperfect collective decoherence with different baths. In the proposed scheme, each pair of qubits is first encoded in a decoherence-free subspace composed of two qubits. Leakage out of the encoding space generated by the imperfection is reduced by the quantum Zeno effect. Phase errors in the encoded bits generated by the imperfection are reduced by concatenation of the decoherence-free subspace with either a three-qubit quantum error correcting code that corrects only phase errors or a two-qubit quantum error detecting code that detects only phase errors, connected with the quantum Zeno effect again.Comment: no correction, 3 pages, RevTe

Perturbing Around A Warped Product Of AdS_4 and Seven-Ellipsoid

We compute the spin-2 Kaluza-Klein modes around a warped product of AdS_4 and a seven-ellipsoid. This background with global G_2 symmetry is related to a U(N) x U(N) N=1 superconformal Chern-Simons matter theory with sixth order superpotential. The mass-squared in AdS_4 is quadratic in G_2 quantum number and KK excitation number. We determine the dimensions of spin-2 operators using the AdS/CFT correspondence. The connection to N=2 theory preserving SU(3) x U(1)_R is also discussed.Comment: 21pp; The second and last paragraphs of section 2, the footnotes 1 and 2 added and to appear in JHE

Uncorrelated and correlated nanoscale lattice distortions in the paramagnetic phase of magnetoresistive manganites

Neutron scattering measurements on a magnetoresistive manganite La$_{0.75}$(Ca$_{0.45}$Sr$_{0.55}$)$_{0.25}$MnO$_3$ show that uncorrelated dynamic polaronic lattice distortions are present in both the orthorhombic (O) and rhombohedral (R) paramagnetic phases. The uncorrelated distortions do not exhibit any significant anomaly at the O-to-R transition. Thus, both the paramagnetic phases are inhomogeneous on the nanometer scale, as confirmed further by strong damping of the acoustic phonons and by the anomalous Debye-Waller factors in these phases. In contrast, recent x-ray measurements and our neutron data show that polaronic correlations are present only in the O phase. In optimally doped manganites, the R phase is metallic, while the O paramagnetic state is insulating (or semiconducting). These measurements therefore strongly suggest that the {\it correlated} lattice distortions are primarily responsible for the insulating character of the paramagnetic state in magnetoresistive manganites.Comment: 10 pages, 8 figures embedde

Lyman alpha line formation in starbursting galaxies II. Extremely Thick, Dustless, and Static HI Media

The Lya line transfer in an extremely thick medium of neutral hydrogen is investigated by adopting an accelerating scheme in our Monte Carlo code to skip a large number of core or resonant scatterings. This scheme reduces computing time significantly with no sacrifice in the accuracy of the results. We applied this numerical method to the Lya transfer in a static, uniform, dustless, and plane-parallel medium. Two types of photon sources have been considered, the midplane source and the uniformly distributed sources. The emergent profiles show double peaks and absorption trough at the line-center. We compared our results with the analytic solutions derived by previous researchers, and confirmed that both solutions are in good agreement with each other. We investigated the directionality of the emergent Lya photons and found that limb brightening is observed in slightly thick media while limb darkening appears in extremely thick media. The behavior of the directionality is noted to follow that of the Thomson scattered radiation in electron clouds, because both Lya wing scattering and Thomson scattering share the same Rayleigh scattering phase function. The mean number of wing scatterings just before escape is in exact agreement with the prediction of the diffusion approximation. The Lya photons constituting the inner part of the emergent profiles follow the relationship derived from the diffusion approximation. We present a brief discussion on the application of our results to the formation of Lya broad absorption troughs and P-Cygni type Lya profiles seen in the UV spectra of starburst galaxies.Comment: 24 papges, 12 figures, The revised version submitted to Ap

Cosmological Lower Bound on Dark Matter Masses from the Soft Gamma-ray Background

Motivated by a recent detection of 511 keV photons from the center of our Galaxy, we calculate the spectrum of the soft gamma-ray background of the redshifted 511 keV photons from cosmological halos. Annihilation of dark matter particles into electron-positron pairs makes a substantial contribution to the gamma-ray background. Mass of such dark matter particles must be <~ 100 MeV so that resulting electron-positron pairs are on-relativistic. On the other hand, we show that in order for the annihilation not to exceed the observed background, the dark matter mass needs to be >~ 20 MeV. We include the contribution from the active galactic nuclei and supernovae. The halo substructures may increase the lower bound to >~ 60 MeV.Comment: 5 pages, 5 figures; accepted for publication in PRD, Rapid Communicatio

Stabilizing the surface morphology of Si1–x–yGexCy/Si heterostructures grown by molecular beam epitaxy through the use of a silicon-carbide source

Si1–x–yGexCy/Si superlattices were grown by solid-source molecular beam epitaxy using silicon carbide as a source of C. Samples consisting of alternating layers of nominally 25 nm Si1–x–yGexCy and 35 nm Si for 10 periods were characterized by high-resolution x-ray diffraction, transmission electron microscopy (TEM), and Rutherford backscattering spectrometry to determine strain, thickness, and composition. C resonance backscattering and secondary ion mass spectrometries were used to measure the total C concentration in the Si1–x–yGexCy layers, allowing for an accurate determination of the substitutional C fraction to be made as a function of growth rate for fixed Ge and substitutional C compositions. For C concentrations close to 1%, high-quality layers were obtained without the use of Sb-surfactant mediation. These samples were found to be structurally perfect to a level consistent with cross-sectional TEM (< 10^7 defects/cm^2) and showed considerably improved homogeneity as compared with similar structures grown using graphite as the source for C. For higher Ge and C concentrations, Sb-surfactant mediation was found to be required to stabilize the surface morphology. The maximum value of substitutional C concentration, above which excessive generation of stacking fault defects caused polycrystalline and/or amorphous growth, was found to be approximately 2.4% in samples containing between 25 and 30% Ge. The fraction of substitutional C was found to decrease from roughly 60% by a factor of 0.86 as the Si1–x–yGexCy growth rate increased from 0.1 to 1.0 nm/s

Sublinear Estimation of Weighted Matchings in Dynamic Data Streams

This paper presents an algorithm for estimating the weight of a maximum weighted matching by augmenting any estimation routine for the size of an unweighted matching. The algorithm is implementable in any streaming model including dynamic graph streams. We also give the first constant estimation for the maximum matching size in a dynamic graph stream for planar graphs (or any graph with bounded arboricity) using $\tilde{O}(n^{4/5})$ space which also extends to weighted matching. Using previous results by Kapralov, Khanna, and Sudan (2014) we obtain a $\mathrm{polylog}(n)$ approximation for general graphs using $\mathrm{polylog}(n)$ space in random order streams, respectively. In addition, we give a space lower bound of $\Omega(n^{1-\varepsilon})$ for any randomized algorithm estimating the size of a maximum matching up to a $1+O(\varepsilon)$ factor for adversarial streams