2,549 research outputs found

    Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors

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    Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells. © 2010 MacTavish et al

    Geographical information retrieval with ontologies of place

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    Geographical context is required of many information retrieval tasks in which the target of the search may be documents, images or records which are referenced to geographical space only by means of place names. Often there may be an imprecise match between the query name and the names associated with candidate sources of information. There is a need therefore for geographical information retrieval facilities that can rank the relevance of candidate information with respect to geographical closeness of place as well as semantic closeness with respect to the information of interest. Here we present an ontology of place that combines limited coordinate data with semantic and qualitative spatial relationships between places. This parsimonious model of geographical place supports maintenance of knowledge of place names that relate to extensive regions of the Earth at multiple levels of granularity. The ontology has been implemented with a semantic modelling system linking non-spatial conceptual hierarchies with the place ontology. An hierarchical spatial distance measure is combined with Euclidean distance between place centroids to create a hybrid spatial distance measure. This is integrated with thematic distance, based on classification semantics, to create an integrated semantic closeness measure that can be used for a relevance ranking of retrieved objects

    Experimental Induction of Odontoblast Differentiation and Stimulation During Preparative Processes

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    In vivo implantation experiments have shown that ethylenediaminetetraaceticacid(EDTA)-soluble frac tions of dentin stimulate reparative dentinogenesis . When isolated embryonic dental papillae were cultured in the presence of these dentin constituents, odontoblast cytological and functional differentiation could be initiated and maintained in the absence of an enamel organ. These effects were attributed to the presence of TGF-/1- related molecules [TGF-/11 or bone morphogenetic protein -2a (BMP-2a)] which had to be used in combination with an EDT A-soluble fraction of dentin in order to specifically affect competent preodontoblasts . These EDT A-soluble constituents present in dentin could be replaced by heparin or fibronectin which both have been reported to interact with TGF-/1. The association of such defined matrix components with a TGF-/1-related molecule represents a biologically active complex triggering odontoblast functional differentiation. In response to caries, odontoblasts modulate their secretory activity and are stimulated to elaborate reactionary dentin. This might be induced by active molecules such as IGF, TGF-6 or BMP which are liberated from dentin consecutively to the demineralization process. Reparative dentinogenesis is distinct from reactionary dentinogenesis and more complex since it implicates the differentiation of precursor cells present in the dental papilla. The developmental history of these cells is different from that of the physiological predontoblasts in developing teeth. The nature of these stem cells and the mechanism of their induction still remain open questions

    An upper limit on the electron-neutrino flux from the HiRes detector

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    Air-fluorescence detectors such as the High Resolution Fly's Eye (HiRes) detector are very sensitive to upward-going, Earth-skimming ultrahigh energy electron-neutrino-induced showers. This is due to the relatively large interaction cross sections of these high-energy neutrinos and to the Landau-Pomeranchuk-Migdal (LPM) effect. The LPM effect causes a significant decrease in the cross sections for bremsstrahlung and pair production, allowing charged-current electron-neutrino-induced showers occurring deep in the Earth's crust to be detectable as they exit the Earth into the atmosphere. A search for upward-going neutrino-induced showers in the HiRes-II monocular dataset has yielded a null result. From an LPM calculation of the energy spectrum of charged particles as a function of primary energy and depth for electron-induced showers in rock, we calculate the shape of the resulting profile of these showers in air. We describe a full detector Monte Carlo simulation to determine the detector response to upward-going electron-neutrino-induced cascades and present an upper limit on the flux of electron-neutrinos.Comment: 13 pages, 3 figures. submitted to Astrophysical Journa

    Search for Point Sources of Ultra-High Energy Cosmic Rays Above 40 EeV Using a Maximum Likelihood Ratio Test

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    We present the results of a search for cosmic ray point sources at energies above 40 EeV in the combined data sets recorded by the AGASA and HiRes stereo experiments. The analysis is based on a maximum likelihood ratio test using the probability density function for each event rather than requiring an a priori choice of a fixed angular bin size. No statistically significant clustering of events consistent with a point source is found.Comment: 7 pages, 7 figures. Accepted for publication in The Astrophysical Journa

    Search for Correlations between HiRes Stereo Events and Active Galactic Nuclei

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    We have searched for correlations between the pointing directions of ultrahigh energy cosmic rays observed by the High Resolution Fly's Eye experiment and Active Galactic Nuclei (AGN) visible from its northern hemisphere location. No correlations, other than random correlations, have been found. We report our results using search parameters prescribed by the Pierre Auger collaboration. Using these parameters, the Auger collaboration concludes that a positive correlation exists for sources visible to their southern hemisphere location. We also describe results using two methods for determining the chance probability of correlations: one in which a hypothesis is formed from scanning one half of the data and tested on the second half, and another which involves a scan over the entire data set. The most significant correlation found occurred with a chance probability of 24%.Comment: 13 pages, 1 table, 5 figure

    Isotopic Composition of Light Nuclei in Cosmic Rays: Results from AMS-01

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    The variety of isotopes in cosmic rays allows us to study different aspects of the processes that cosmic rays undergo between the time they are produced and the time of their arrival in the heliosphere. In this paper we present measurements of the isotopic ratios 2H/4He, 3He/4He, 6Li/7Li, 7Be/(9Be+10Be) and 10B/11B in the range 0.2-1.4 GeV of kinetic energy per nucleon. The measurements are based on the data collected by the Alpha Magnetic Spectrometer, AMS-01, during the STS-91 flight in 1998 June.Comment: To appear in ApJ. 12 pages, 11 figures, 6 table
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