Evolution of replication efficiency following infection with a molecularly cloned feline immunodeficiency virus of low virulence

The development of an effective vaccine against human immunodeficiency virus is considered to be the most practicable means of controlling the advancing global AIDS epidemic. Studies with the domestic cat have demonstrated that vaccinal immunity to infection can be induced against feline immunodeficiency virus (FIV); however, protection is largely restricted to laboratory strains of FIV and does not extend to primary strains of the virus. We compared the pathogenicity of two prototypic vaccine challenge strains of FIV derived from molecular clones; the laboratory strain PET<sub>F14</sub> and the primary strain GL8<sub>414</sub>. PET<sub>F14</sub> established a low viral load and had no effect on CD4<sup>+</sup>- or CD8<sup>+</sup>- lymphocyte subsets. In contrast, GL8<sub>414</sub> established a high viral load and induced a significant reduction in the ratio of CD4<sup>+</sup> to CD8<sup>+</sup> lymphocytes by 15 weeks postinfection, suggesting that PET<sub>F14</sub> may be a low-virulence-challenge virus. However, during long-term monitoring of the PET<sub>F14</sub>-infected cats, we observed the emergence of variant viruses in two of three cats. Concomitant with the appearance of the variant viruses, designated 627<sub>W135</sub> and 628<sub>W135</sub>, we observed an expansion of CD8<sup>+</sup>-lymphocyte subpopulations expressing reduced CD8 ß-chain, a phenotype consistent with activation. The variant viruses both carried mutations that reduced the net charge of the V3 loop (K409Q and K409E), giving rise to a reduced ability of the Env proteins to both induce fusion and to establish productive infection in CXCR4-expressing cells. Further, following subsequent challenge of naïve cats with the mutant viruses, the viruses established higher viral loads and induced more marked alterations in CD8<sup>+</sup>-lymphocyte subpopulations than did the parent F14 strain of virus, suggesting that the E409K mutation in the PET<sub>F14</sub> strain contributes to the attenuation of the virus

Simulating spin-3/2 particles at colliders

Support for interactions of spin-3/2 particles is implemented in the FeynRules and ALOHA packages and tested with the MadGraph 5 and CalcHEP event generators in the context of three phenomenological applications. In the first, we implement a spin-3/2 Majorana gravitino field, as in local supersymmetric models, and study gravitino and gluino pair-production. In the second, a spin-3/2 Dirac top-quark excitation, inspired from compositness models, is implemented. We then investigate both top-quark excitation and top-quark pair-production. In the third, a general effective operator for a spin-3/2 Dirac quark excitation is implemented, followed by a calculation of the angular distribution of the s-channel production mechanism.Comment: 20 pages, 7 figure

Stealth Dark Matter: Dark scalar baryons through the Higgs portal

We present a new model of "Stealth Dark Matter": a composite baryonic scalar of an $SU(N_D)$ strongly-coupled theory with even $N_D \geq 4$. All mass scales are technically natural, and dark matter stability is automatic without imposing an additional discrete or global symmetry. Constituent fermions transform in vector-like representations of the electroweak group that permit both electroweak-breaking and electroweak-preserving mass terms. This gives a tunable coupling of stealth dark matter to the Higgs boson independent of the dark matter mass itself. We specialize to $SU(4)$, and investigate the constraints on the model from dark meson decay, electroweak precision measurements, basic collider limits, and spin-independent direct detection scattering through Higgs exchange. We exploit our earlier lattice simulations that determined the composite spectrum as well as the effective Higgs coupling of stealth dark matter in order to place bounds from direct detection, excluding constituent fermions with dominantly electroweak-breaking masses. A lower bound on the dark baryon mass $m_B \gtrsim 300$ GeV is obtained from the indirect requirement that the lightest dark meson not be observable at LEP II. We briefly survey some intriguing properties of stealth dark matter that are worthy of future study, including: collider studies of dark meson production and decay; indirect detection signals from annihilation; relic abundance estimates for both symmetric and asymmetric mechanisms; and direct detection through electromagnetic polarizability, a detailed study of which will appear in a companion paper.Comment: 15 pages, 3 figures, citations added, typos fixed, minor clarification

Lattice simulations with eight flavors of domain wall fermions in SU(3) gauge theory

We study an SU(3) gauge theory with Nf=8 degenerate flavors of light fermions in the fundamental representation. Using the domain wall fermion formulation, we investigate the light hadron spectrum, chiral condensate and electroweak S parameter. We consider a range of light fermion masses on two lattice volumes at a single gauge coupling chosen so that IR scales approximately match those from our previous studies of the two- and six-flavor systems. Our results for the Nf=8 spectrum suggest spontaneous chiral symmetry breaking, though fits to the fermion mass dependence of spectral quantities do not strongly disfavor the hypothesis of mass-deformed infrared conformality. Compared to Nf=2 we observe a significant enhancement of the chiral condensate relative to the symmetry breaking scale F, similar to the situation for Nf=6. The reduction of the S parameter, related to parity doubling in the vector and axial-vector channels, is also comparable to our six-flavor results

Cosmic cookery : making a stereoscopic 3D animated movie.

This paper describes our experience making a short stereoscopic movie visualizing the development of structure in the universe during the 13.7 billion years from the Big Bang to the present day. Aimed at a general audience for the Royal Society's 2005 Summer Science Exhibition, the movie illustrates how the latest cosmological theories based on dark matter and dark energy are capable of producing structures as complex as spiral galaxies and allows the viewer to directly compare observations from the real universe with theoretical results. 3D is an inherent feature of the cosmology data sets and stereoscopic visualization provides a natural way to present the images to the viewer, in addition to allowing researchers to visualize these vast, complex data sets. The presentation of the movie used passive, linearly polarized projection onto a 2m wide screen but it was also required to playback on a Sharp RD3D display and in anaglyph projection at venues without dedicated stereoscopic display equipment. Additionally lenticular prints were made from key images in the movie. We discuss the following technical challenges during the stereoscopic production process; 1) Controlling the depth presentation, 2) Editing the stereoscopic sequences, 3) Generating compressed movies in display speci¯c formats. We conclude that the generation of high quality stereoscopic movie content using desktop tools and equipment is feasible. This does require careful quality control and manual intervention but we believe these overheads are worthwhile when presenting inherently 3D data as the result is signi¯cantly increased impact and better understanding of complex 3D scenes

A Double Sigma Model for Double Field Theory

We define a sigma model with doubled target space and calculate its background field equations. These coincide with generalised metric equation of motion of double field theory, thus the double field theory is the effective field theory for the sigma model.Comment: 26 pages, v1: 37 pages, v2: references added, v3: updated to match published version - background and detail of calculations substantially condensed, motivation expanded, refs added, results unchange

The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin

Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18) in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN) in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition