Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity

Virus infection of mammalian cells is sensed by pattern recognition receptors and leads to an innate immune response that restricts virus replication and induces adaptive immunity. In response, viruses have evolved many countermeasures that enable them to replicate and be transmitted to new hosts, despite the host innate immune response. Poxviruses, such as vaccinia virus (VACV), have large DNA genomes and encode many proteins that are dedicated to host immune evasion. Some of these proteins are secreted from the infected cell, where they bind and neutralize complement factors, interferons, cytokines and chemokines. Other VACV proteins function inside cells to inhibit apoptosis or signalling pathways that lead to the production of interferons and pro-inflammatory cytokines and chemokines. In this review, these VACV immunomodulatory proteins are described and the potential to create more immunogenic VACV strains by manipulation of the gene encoding these proteins is discussed

Gamma-Ray Burst and Relativistic Shells: The Surface Filling Factor

The variability observed in many complex gamma-ray bursts (GRBs) is inconsistent with causally connected variations in a single, symmetric, relativistic shell interacting with the ambient material ("external shocks"). Rather, the symmetry of the shell must be broken on an angular scale much smaller than Gamma^{-1} where Gamma is the bulk Lorentz factor for the shell. The observed variability in the external shock models arises from the number of causally connected regions that (randomly) become active. We define the "surface filling factor" to be the ratio of the area of causally connected regions that become active to the observable area of the shell. From the observed variability in 52 BATSE bursts, we estimate the surface filling factor to be typically 0.005 although some values are near unity. We find that the surface filling factor is about 0.1 Delta T/T in both the constant Gamma phase (which probably produces the GRB) and the deaccelerating phase (which probably produces the x-ray afterglows). Here, \Delta T is a typical time scale of variability and T is the time since the initial signal. We analyze the 2 hr flare seen by ASCA 36 hr after the GRB and conclude that the surface filling factor must be small (0.001) in the x-ray afterglow phase as well. Explanations for low surface filling factor can either require more or less energy (by a factor of about 1000) compared to that expected for a symmetric shell.Comment: 26 pages, 5 embedded figures, Latex, revised version as in press, ApJ, added figure to show the possible expanding shell geometries that can give low filling facto

A prospective study of resuscitative outcomes at a downtown Greenville SC hospital using Connect Care versus CodeNet for cardiac arrest documentation

Our study was looks at the difference between 2 systems used to document cardiac arrests in a hospital setting. One is a new machine that is called CodeNet. This documentation device was compared to the documentation system at Saint Francis Hospital in downtown Greenville, SC. When the details of a cardiac arrest are recorded (e.g., time it began, how many shocks were given, and what interval the shocks were given), this information can be used to look for patterns that predict survival. This can hopefully be used to create new protocols that will increase the patient\u27s chance of survival. This is being accomplished through chart review (cardiac arrest sheet) of cardiopulmonary arrest for 12 months and data collected with the CodeNet from cardiac arrests that occur in theIntensive Care UnitandCritical Care Unit. More data is being collected, but the preliminary results seem to indicate that CodeNet isa much moreefficient way to document the details of a cardiac arrest

RANS simulations of wind flow at the Bolund experiment

As part of their development, the predictions of numerical wind flow models must be compared with measurements in order to estimate the uncertainty related to their use. Of course, the most rigorous such comparison is under blind conditions. The following paper includes a detailed description of three different wind flow models, all based on a Reynolds-averaged Navier-Stokes approach and two-equation k-ε closure, that were tested as part of the Bolund blind comparison (itself based on the Bolund experiment which measured the wind around a small coastal island). The models are evaluated in terms of predicted normalized wind speed and turbulent kinetic energy at 2 m and 5 m above ground level for a westerly wind direction. Results show that all models predict the mean velocity reasonably well; however accurate prediction of the turbulent kinetic energy remains achallenge

Modulation of linguistic prediction by TDCS of the right lateral cerebellum

AbstractIt has been postulated recently that the cerebellum contributes the same prediction and learning functions to linguistic processing as it does towards motor control. For example, repetitive TMS over posterior-lateral cerebellum caused a significant loss in predictive language processing, as assessed by the latency of saccades to target items of spoken sentences, using the Visual World task. We aimed to assess the polarity-specific effects of cerebellar TDCS, hypothesising that cathodal TDCS should impair linguistic prediction, and anodal TDCS facilitate it. Our design also tested whether TDCS modulated associative learning in this task. A between groups (sham, anodal, cathodal) design was used, with concurrent stimulation during performance of a manual variation of the Visual World paradigm, and with assessment of latency reduction over repeated presentations of the spoken sentences. Mixed model ANOVA was used to analyse change in response latency. Cathodal TDCS decreased participants’ response time advantage for the predictable sentence items without change for non-predictable items, consistent with the previous TMS results. Furthermore, anodal stimulation enhanced the response time advantage for the predictable items, again without change in latencies for non-predictive items. We found a clear practice-based effect over 4 blocks. However, this difference was not significantly modulated by either anodal or cathodal stimulation. Our results therefore support the hypothesis that cerebellum contributes to predictive language processing, mirroring its predictive role in motor control, but we do not yet have evidence that the learning process was affected by cerebellar TDCS

Characterization of disturbance sources for LISA: torsion pendulum results

A torsion pendulum allows ground-based investigation of the purity of free-fall for the LISA test masses inside their capacitive position sensor. This paper presents recent improvements in our torsion pendulum facility that have both increased the pendulum sensitivity and allowed detailed characterization of several important sources of acceleration noise for the LISA test masses. We discuss here an improved upper limit on random force noise originating in the sensor. Additionally, we present new measurement techniques and preliminary results for characterizing the forces caused by the sensor's residual electrostatic fields, dielectric losses, residual spring-like coupling, and temperature gradients.Comment: 11 pages, 8 figures, accepted for publication Classical and Quantum Gravit

Fractal Holography: a geometric re-interpretation of cosmological large scale structure

The fractal dimension of large-scale galaxy clustering has been demonstrated to be roughly $D_F \sim 2$ from a wide range of redshift surveys. If correct, this statistic is of interest for two main reasons: fractal scaling is an implicit representation of information content, and also the value itself is a geometric signature of area. It is proposed that the fractal distribution of galaxies may thus be interpreted as a signature of holography (``fractal holography''), providing more support for current theories of holographic cosmologies. Implications for entropy bounds are addressed. In particular, because of spatial scale invariance in the matter distribution, it is shown that violations of the spherical entropy bound can be removed. This holographic condition instead becomes a rigid constraint on the nature of the matter density and distribution in the Universe. Inclusion of a dark matter distribution is also discussed, based on theoretical considerations of possible universal CDM density profiles.Comment: 13 pp, LaTeX. Revised version; to appear in JCA

Polyphenism in social insects: insights from a transcriptome-wide analysis of gene expression in the life stages of the key pollinator, Bombus terrestris

Background: Understanding polyphenism, the ability of a single genome to express multiple morphologically and behaviourally distinct phenotypes, is an important goal for evolutionary and developmental biology. Polyphenism has been key to the evolution of the Hymenoptera, and particularly the social Hymenoptera where the genome of a single species regulates distinct larval stages, sexual dimorphism and physical castes within the female sex. Transcriptomic analyses of social Hymenoptera will therefore provide unique insights into how changes in gene expression underlie such complexity. Here we describe gene expression in individual specimens of the pre-adult stages, sexes and castes of the key pollinator, the buff-tailed bumblebee Bombus terrestris. Results: cDNA was prepared from mRNA from five life cycle stages (one larva, one pupa, one male, one gyne and two workers) and a total of 1,610,742 expressed sequence tags (ESTs) were generated using Roche 454 technology, substantially increasing the sequence data available for this important species. Overlapping ESTs were assembled into 36,354 B. terrestris putative transcripts, and functionally annotated. A preliminary assessment of differences in gene expression across non-replicated specimens from the pre-adult stages, castes and sexes was performed using R-STAT analysis. Individual samples from the life cycle stages of the bumblebee differed in the expression of a wide array of genes, including genes involved in amino acid storage, metabolism, immunity and olfaction. Conclusions: Detailed analyses of immune and olfaction gene expression across phenotypes demonstrated how transcriptomic analyses can inform our understanding of processes central to the biology of B. terrestris and the social Hymenoptera in general. For example, examination of immunity-related genes identified high conservation of important immunity pathway components across individual specimens from the life cycle stages while olfactory-related genes exhibited differential expression with a wider repertoire of gene expression within adults, especially sexuals, in comparison to immature stages. As there is an absence of replication across the samples, the results of this study are preliminary but provide a number of candidate genes which may be related to distinct phenotypic stage expression. This comprehensive transcriptome catalogue will provide an important gene discovery resource for directed programmes in ecology, evolution and conservation of a key pollinator

Measuring random force noise for LISA aboard the LISA Pathfinder mission

The LTP (LISA Testflight Package), to be flown aboard the ESA / NASA LISA Pathfinder mission, aims to demonstrate drag-free control for LISA test masses with acceleration noise below 30 fm/s^2/Hz^1/2 from 1-30 mHz. This paper describes the LTP measurement of random, position independent forces acting on the test masses. In addition to putting an overall upper limit for all source of random force noise, LTP will measure the conversion of several key disturbances into acceleration noise and thus allow a more detailed characterization of the drag-free performance to be expected for LISA.Comment: 7 pages, 3 figures. To be published in Classical and Quantum Gravity with the proceedings of the 2003 Amaldi Meetin

Serine Phosphorylation of HIV-1 Vpu and Its Binding to Tetherin Regulates Interaction with Clathrin Adaptors

HIV-1 Vpu prevents incorporation of tetherin (BST2/ CD317) into budding virions and targets it for ESCRT-dependent endosomal degradation via a clathrin-dependent process. This requires a variant acidic dileucine-sorting motif (ExxxLV) in Vpu. Structural studies demonstrate that recombinant Vpu/tetherin fusions can form a ternary complex with the clathrin adaptor AP-1. However, open questions still exist about Vpu's mechanism of action. Particularly, whether endosomal degradation and the recruitment of the E3 ubiquitin ligase SCFβTRCP1/2 to a conserved phosphorylated binding site, DSGNES, are required for antagonism. Re-evaluation of the phenotype of Vpu phosphorylation mutants and naturally occurring allelic variants reveals that the requirement for the Vpu phosphoserine motif in tetherin antagonism is dissociable from SCFβTRCP1/2 and ESCRT-dependent tetherin degradation. Vpu phospho-mutants phenocopy ExxxLV mutants, and can be rescued by direct clathrin interaction in the absence of SCFβTRCP1/2 recruitment. Moreover, we demonstrate physical interaction between Vpu and AP-1 or AP-2 in cells. This requires Vpu/tetherin transmembrane domain interactions as well as the ExxxLV motif. Importantly, it also requires the Vpu phosphoserine motif and adjacent acidic residues. Taken together these data explain the discordance between the role of SCFβTRCP1/2 and Vpu phosphorylation in tetherin antagonism, and indicate that phosphorylation of Vpu in Vpu/tetherin complexes regulates promiscuous recruitment of adaptors, implicating clathrin-dependent sorting as an essential first step in tetherin antagonism