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

MetaboSearch: Tool for Mass-Based Metabolite Identification Using Multiple Databases

Searching metabolites against databases according to their masses is often the first step in metabolite identification for a mass spectrometry-based untargeted metabolomics study. Major metabolite databases include Human Metabolome DataBase (HMDB), Madison Metabolomics Consortium Database (MMCD), Metlin, and LIPID MAPS. Since each one of these databases covers only a fraction of the metabolome, integration of the search results from these databases is expected to yield a more comprehensive coverage. However, the manual combination of multiple search results is generally difficult when identification of hundreds of metabolites is desired. We have implemented a web-based software tool that enables simultaneous mass-based search against the four major databases, and the integration of the results. In addition, more complete chemical identifier information for the metabolites is retrieved by cross-referencing multiple databases. The search results are merged based on IUPAC International Chemical Identifier (InChI) keys. Besides a simple list of m/z values, the software can accept the ion annotation information as input for enhanced metabolite identification. The performance of the software is demonstrated on mass spectrometry data acquired in both positive and negative ionization modes. Compared with search results from individual databases, MetaboSearch provides better coverage of the metabolome and more complete chemical identifier information. Availability: The software tool is available at http://omics.georgetown.edu/MetaboSearch.html

Results from the First Science Run of the ZEPLIN-III Dark Matter Search Experiment

The ZEPLIN-III experiment in the Palmer Underground Laboratory at Boulby uses a 12kg two-phase xenon time projection chamber to search for the weakly interacting massive particles (WIMPs) that may account for the dark matter of our Galaxy. The detector measures both scintillation and ionisation produced by radiation interacting in the liquid to differentiate between the nuclear recoils expected from WIMPs and the electron recoil background signals down to ~10keV nuclear recoil energy. An analysis of 847kg.days of data acquired between February 27th 2008 and May 20th 2008 has excluded a WIMP-nucleon elastic scattering spin-independent cross-section above 8.1x10(-8)pb at 55GeV/c2 with a 90% confidence limit. It has also demonstrated that the two-phase xenon technique is capable of better discrimination between electron and nuclear recoils at low-energy than previously achieved by other xenon-based experiments.Comment: 12 pages, 17 figure

Quenching Factor for Low Energy Nuclear Recoils in a Plastic Scintillator

Plastic scintillators are widely used in industry, medicine and scientific research, including nuclear and particle physics. Although one of their most common applications is in neutron detection, experimental data on their response to low-energy nuclear recoils are scarce. Here, the relative scintillation efficiency for neutron-induced nuclear recoils in a polystyrene-based plastic scintillator (UPS-923A) is presented, exploring recoil energies between 125 keV and 850 keV. Monte Carlo simulations, incorporating light collection efficiency and energy resolution effects, are used to generate neutron scattering spectra which are matched to observed distributions of scintillation signals to parameterise the energy-dependent quenching factor. At energies above 300 keV the dependence is reasonably described using the semi-empirical formulation of Birks and a kB factor of (0.014+/-0.002) g/MeVcm^2 has been determined. Below that energy the measured quenching factor falls more steeply than predicted by the Birks formalism.Comment: 8 pages, 9 figure

Measurement of single electron emission in two-phase xenon

We present the first measurements of the electroluminescence response to the emission of single electrons in a two-phase noble gas detector. Single ionization electrons generated in liquid xenon are detected in a thin gas layer during the 31-day background run of the ZEPLIN-II experiment, a two-phase xenon detector for WIMP dark matter searches. Both the pressure dependence and magnitude of the single-electron response are in agreement with previous measurements of electroluminescence yield in xenon. We discuss different photoionization processes as possible cause for the sample of single electrons studied in this work. This observation may have implications for the design and operation of future large-scale two-phase systems.Comment: 11 pages, 6 figure

The Advanced Compton Telescope

The Advanced Compton Telescope (ACT), the next major step in gamma-ray astronomy, will probe the fires where chemical elements are formed by enabling high-resolution spectroscopy of nuclear emission from supernova explosions. During the past two years, our collaboration has been undertaking a NASA mission concept study for ACT. This study was designed to (1) transform the key scientific objectives into specific instrument requirements, (2) to identify the most promising technologies to meet those requirements, and (3) to design a viable mission concept for this instrument. We present the results of this study, including scientific goals and expected performance, mission design, and technology recommendations

WIMP-nucleon cross-section results from the second science run of ZEPLIN-III

We report experimental upper limits on WIMP-nucleon elastic scattering cross sections from the second science run of ZEPLIN-III at the Boulby Underground Laboratory. A raw fiducial exposure of 1,344 kg.days was accrued over 319 days of continuous operation between June 2010 and May 2011. A total of eight events was observed in the signal acceptance region in the nuclear recoil energy range 7-29 keV, which is compatible with background expectations. This allows the exclusion of the scalar cross-section above 4.8E-8 pb near 50 GeV/c^2 WIMP mass with 90% confidence. Combined with data from the first run, this result improves to 3.9E-8 pb. The corresponding WIMP-neutron spin-dependent cross-section limit is 8.0E-3 pb. The ZEPLIN programme reaches thus its conclusion at Boulby, having deployed and exploited successfully three liquid xenon experiments of increasing reach