47,725 research outputs found

    DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire

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    The majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire

    Measurement of the ratio of prompt χ c to J / ψ production in pp collisions at √s = 7 TeV

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    The prompt production of charmonium χ c and J / ψ states is studied in proton-proton collisions at a centre-of-mass energy of √s = 7 TeV at the Large Hadron Collider. The χ c and J / ψ mesons are identified through their decays χ c → J / ψ γ and J / ψ → μ + μ - using 36 pb - 1 of data collected by the LHCb detector in 2010. The ratio of the prompt production cross-sections for χ c and J / ψ, σ (χ c → J / ψ γ) / σ (J / ψ), is determined as a function of the J / ψ transverse momentum in the range 2 < p T J / ψ < 15 GeV / c. The results are in excellent agreement with next-to-leading order non-relativistic expectations and show a significant discrepancy compared with the colour singlet model prediction at leading order, especially in the low p T J / ψ region

    Decoding third sector electoral politics: the shaping of the agenda and getting heard in the 2010 general election’

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    Following a period of unprecedented success in policy support from the Labour Government, the uncertain outcome of the 2010 General Election marked a potential watershed for the third sector and required a new kind of engagement if community and voluntary organisations were to maintain political leverage over the longer-term. Hence the sector took a long-term approach to the election, with third sector organisations engaging in political lobbying and manifesto production for a sustained period before the anticipated onset of purdah. This paper draws upon qualitative interviews with key policy players around the time of the election and documentary analysis to consider the relative success of the sector’s methods, measured in terms of policy representation in the political parties’ manifestos and inclusion in the public campaigning agenda once the election was declared. This mapping is complicated by the three main political parties using very different language to talk about the third sector, a difference which reflects ideological differences in how they see its role. It is argued that it is essential to unpick these discourses to understand the story of how an apparently high degree of consensus on sectoral politics actually represented very different attitudes to its future function

    Evidence for the decay B0→J/ψω and measurement of the relative branching fractions of meson decays to J/ψη and J/ψη′

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    First evidence of the B 0 → J / ψ ω decay is found and the B s 0 → J / ψ η and B s 0 → J / ψ η ′ decays are studied using a dataset corresponding to an integrated luminosity of 1.0 fb -1 collected by the LHCb experiment in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV. The branching fractions of these decays are measured relative to that of the B 0 → J / ψ ρ 0 decay:frac(B (B 0 → J / ψ ω), B (B 0 → J / ψ ρ 0)) = 0.89 ± 0.19 (stat) - 0.13 + 0.07 (syst),frac(B (B s 0 → J / ψ η), B (B 0 → J / ψ ρ 0)) = 14.0 ± 1.2 (stat) - 1.5 + 1.1 (syst) - 1.0 + 1.1 (frac(f d, f s)),frac(B (B s 0 → J / ψ η ′), B (B 0 → J / ψ ρ 0)) = 12.7 ± 1.1 (stat) - 1.3 + 0.5 (syst) - 0.9 + 1.0 (frac(f d, f s)), where the last uncertainty is due to the knowledge of f d / f s, the ratio of b-quark hadronization factors that accounts for the different production rate of B 0 and B s 0 mesons. The ratio of the branching fractions of B s 0 → J / ψ η ′ and B s 0 → J / ψ η decays is measured to befrac(B (B s 0 → J / ψ η ′), B (B s 0 → J / ψ η)) = 0.90 ± 0.09 (stat) - 0.02 + 0.06 (syst)

    Predicting the effects of marine climate change on the invertebrate prey of the birds of rocky shores

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    By the end of the 21st century models of climate change predict that the air temperature over most of the British Isles will increase by between 2 and 3 °C and sea-level will rise by 40–50 cm. Over that period it will become windier and mean wave height will increase, as will the frequency of storms. These changes in climate and weather will impact the intertidal zone of the UK and will cause distribution changes in many of the common invertebrate species that live there. Where these changes are severe they may well impact on patterns of distribution of ducks and wading birds. In the British Isles a number of organisms live close to their geographical limits of distribution. Some of these species might be expected to extend their range as climatic restraints are relaxed. Species currently limited by cool summers or winter cold will move northwards. In most cases the effects on the distribution of waterbirds will be small. For example, the replacement of the Northern Limpet Patella vulgata by the Southern Limpet P. depressa is unlikely to adversely affect Eurasian Oystercatchers Haematopus ostralegus. Of wider concern is the possibility that as climate warms the abundance and productivity of brown algae will decrease. This is likely to have two significant effects for waders. First, it would represent a loss of potentially rich feeding grounds for species such as Ruddy Turnstone Arenaria interpres that feed on small easily desiccated invertebrates living on or below the seaweed. Secondly, as algae die or are broken away the resulting debris is exported to sediment habitats where it considerably boosts the in situ production of bacteria at the base of the food web. An increase in sea-level will only have a major impact on the extent of rocky shore invertebrate communities where shore topography prevents the upward migration of the biota. Where a seawall limits shores, for example, biological production will be curtailed as the area available for colonization decreases. Increases in the size of waves and the frequency of storms will mimic increasing exposure and there will be a significant reduction in algal production in areas that are affected

    Climate signal propagation in southern California aquifers

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    The western United States is marked by limited water resources and a fast-growing population. Increasing climate variability as well as a growing demand on water resources highlights the need for improved understanding of connections between regional climate, surface water dynamics, and groundwater recharge. The current study focuses on the linkages between climate variability and groundwater levels in Calleguas Creek watershed located in southern California. The Calleguas Creek groundwater system serves as a critical source of water supply for agricultural and industrial use. Precipitation time series and groundwater levels were analyzed throughout the Calleguas Creek watershed for the period 1975-2004. Water level variability was analyzed for over 311 individual wells with a subset of 20 wells selected for further analysis. A correlation matrix was computed to establish well locations (or groups) with similar hydrologic behavior. Prewhitening methods were used to evaluate the effect of time series autocorrelation on the test statistics for trend detection using the Mann-Kendall test. Both climate and selected groundwater level (well) data were subjected to frequency analysis using fast Fourier transform. The time series of precipitation, the El Nino-Southern Oscillation (ENSO) index, and well levels were analyzed. A strong persistence was observed in the groundwater level time series, ranging from 66% to 99%. Results suggest the existence of significant periodicities between 2.0 and 7.0 years in both the precipitation and the well level data that are partially coincident with ENSO modes. A decadal oscillation was also observed in the well level data, which partially corresponds with the Pacific Decadal Oscillation. Assessment of the complex interactions between climate variability and groundwater levels will facilitate improved water resources planning and management in water-stressed regions where marginal changes in hydrologic budgets have significant implications

    Frank and Wilma Kendall

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    Frank and Wilma Potter Kendall were married in 1939. Frank is the son of Charles T. and Lucy Kendall. He was born January 21, 1919 and died February 14, 1947. Wilma is the daughter of William and Effie Potter. She was born January 19, 1923 and died July 8, 2009

    J. T. Wiswall papers, W.0011

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    Abstract: Two notebooks, containing mathematical equations and scientific essays, as well as the handwritten manuscripts of J. T. Wiswall's works "The African" and "Iliad of the Family," neither of which were ever published.Scope and Content Note: The collection contains two small, leather notebooks. One contains the handwritten manuscript "The African" and includes a bookplate identifying Caldwell Delaney as the owner. The other contains the handwritten manuscript "Iliad of the Family," as well as mathematical equations and scientific essays.Biographical/Historical Note: A Mobile, Alabama, author, J. T. Wiswall published two books, The Last Crusader in 1861 and Mr. Christopher Katydid (of Casconia) in 1864 (under the pseudonym Mark Heywood). The two handwritten manuscripts in this collection, "The African" and "Iliad of the Family," were never published, although they were listed in Robert E. Bell's Bibliography of Mobile, which noted that Mobile historian Caldwell Delaney held the manuscripts in his private collection
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