3,681 research outputs found

    Aggregation of Lipid Rafts Accompanies Signaling via the T Cell Antigen Receptor

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    The role of lipid rafts in T cell antigen receptor (TCR) signaling was investigated using fluorescence microscopy. Lipid rafts labeled with cholera toxin B subunit (CT-B) and cross-linked into patches displayed characteristics of rafts isolated biochemically, including detergent resistance and colocalization with raft-associated proteins. LCK, LAT, and the TCR all colocalized with lipid patches, although TCR association was sensitive to nonionic detergent. Aggregation of the TCR by anti-CD3 mAb cross-linking also caused coaggregation of raft-associated proteins. However, the protein tyrosine phosphatase CD45 did not colocalize to either CT-B or CD3 patches. Cross-linking of either CD3 or CT-B strongly induced tyrosine phosphorylation and recruitment of a ZAP-70(SH2)2–green fluorescent protein (GFP) fusion protein to the lipid patches. Also, CT-B patching induced signaling events analagous to TCR stimulation, with the same dependence on expression of key TCR signaling molecules. Targeting of LCK to rafts was necessary for these events, as a nonraft- associated transmembrane LCK chimera, which did not colocalize with TCR patches, could not reconstitute CT-B–induced signaling. Thus, our results indicate a mechanism whereby TCR engagement promotes aggregation of lipid rafts, which facilitates colocalization of LCK, LAT, and the TCR whilst excluding CD45, thereby triggering protein tyrosine phosphorylation

    Low temperature transport on surface conducting diamond

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    Magneto-transport measurements were performed on surface conducting hydrogen-terminated diamond (100) hall bars at temperatures between 0.1-5 K in magnetic fields up to 8T.Comment: 2 pages Optoelectronic and Microelectronic Materials & Devices (COMMAD), 2012 Conferenc

    Design, synthesis, and biological evaluation of an allosteric inhibitor of HSET that targets cancer cells with supernumerary centrosomes

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    Centrosomes associate with spindle poles; thus, the presence of two centrosomes promotes bipolar spindle assembly in normal cells. Cancer cells often contain supernumerary centrosomes, and to avoid multipolar mitosis and cell death, these are clustered into two poles by the microtubule motor protein HSET. We report the discovery of an allosteric inhibitor of HSET, CW069, which we designed using a methodology on an interface of chemistry and biology. Using this approach, we explored millions of compounds in silico and utilized convergent syntheses. Only compound CW069 showed marked activity against HSET in vitro. The inhibitor induced multipolar mitoses only in cells containing supernumerary centrosomes. CW069 therefore constitutes a valuable tool for probing HSET function and, by reducing the growth of cells containing supernumerary centrosomes, paves the way for new cancer therapeutics

    Forecasting the European carbon market

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    In an effort to meet its obligations under the Kyoto Protocol, in 2005 the European Union introduced a cap-and-trade scheme where mandated installations are allocated permits to emit CO2. Financial markets have developed that allow companies to trade these carbon permits. For the EU to achieve reductions in CO2 emissions at a minimum cost, it is necessary that companies make appropriate investments and policymakers design optimal policies. In an effort to clarify the workings of the carbon market, several recent papers have attempted to statistically model it. However, the European carbon market (EU ETS) has many institutional features that potentially impact on daily carbon prices (and associated …nancial futures). As a consequence, the carbon market has properties that are quite di¤erent from conventional financial assets traded in mature markets. In this paper, we use dynamic model averaging (DMA) in order to forecast in this newly-developing market. DMA is a recently-developed statistical method which has three advantages over conventional approaches. First, it allows the coefficients on the predictors in a forecasting model to change over time. Second, it allows for the entire forecasting model to change over time. Third, it surmounts statistical problems which arise from the large number of potential predictors that can explain carbon prices. Our empirical results indicate that there are both important policy and statistical benefits with our approach. Statistically, we present strong evidence that there is substantial turbulence and change in the EU ETS market, and that DMA can model these features and forecast accurately compared to conventional approaches. From a policy perspective, we discuss the relative and changing role of different price drivers in the EU ETS. Finally, we document the forecast performance of DMA and discuss how this relates to the efficiency and maturity of this market

    Positronium Hyperfine Splitting in Non-commutative Space at the Order α6\alpha^6

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    We obtain positronium Hyperfine Splitting owing to the non-commutativity of space and show that, in the leading order, it is proportional to θα6\theta \alpha^6 where, θ\theta is the parameter of non-commutativity. It is also shown that spatial non-commutativity splits the spacing between n=2n=2 triplet excited levels E(23S1)→E(23P2)E(2^3S_1)\to E(2^3P_2) which provides an experimental test on the non-commutativity of space.Comment: 7 pages, 2 figures, to appear in Phys. Rev.

    Mangroves enhance the biomass of coral reef fish communities in the Caribbean

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    Mangrove forests are one of the world's most threatened tropical ecosystems with global loss exceeding 35% (ref. 1). Juvenile coral reef fish often inhabit mangroves, but the importance of these nurseries to reef fish population dynamics has not been quantified. Indeed, mangroves might be expected to have negligible influence on reef fish communities: juvenile fish can inhabit alternative habitats and fish populations may be regulated by other limiting factors such as larval supply or fishing. Here we show that mangroves are unexpectedly important, serving as an intermediate nursery habitat that may increase the survivorship of young fish. Mangroves in the Caribbean strongly influence the community structure of fish on neighbouring coral reefs. In addition, the biomass of several commercially important species is more than doubled when adult habitat is connected to mangroves. The largest herbivorous fish in the Atlantic, Scarus guacamaia, has a functional dependency on mangroves and has suffered local extinction after mangrove removal. Current rates of mangrove deforestation are likely to have severe deleterious consequences for the ecosystem function, fisheries productivity and resilience of reefs. Conservation efforts should protect connected corridors of mangroves, seagrass beds and coral reefs

    Connection Between Type A and E Factorizations and Construction of Satellite Algebras

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    Recently, we introduced a new class of symmetry algebras, called satellite algebras, which connect with one another wavefunctions belonging to different potentials of a given family, and corresponding to different energy eigenvalues. Here the role of the factorization method in the construction of such algebras is investigated. A general procedure for determining an so(2,2) or so(2,1) satellite algebra for all the Hamiltonians that admit a type E factorization is proposed. Such a procedure is based on the known relationship between type A and E factorizations, combined with an algebraization similar to that used in the construction of potential algebras. It is illustrated with the examples of the generalized Morse potential, the Rosen-Morse potential, the Kepler problem in a space of constant negative curvature, and, in each case, the conserved quantity is identified. It should be stressed that the method proposed is fairly general since the other factorization types may be considered as limiting cases of type A or E factorizations.Comment: 20 pages, LaTeX, no figure, to be published in J. Phys.

    Quantum Communication with Phantom Photons

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    We show that quantum information may be transferred between atoms in different locations by using ``phantom photons'': the atoms are coupled through electromagnetic fields, but the corresponding field modes do not have to be fully populated. In the case where atoms are placed inside optical cavities, errors in quantum information processing due to photon absorption inside the cavity are diminished in this way. This effect persists up to intercavity distances of about a meter for the current levels of cavity losses, and may be useful for distributed quantum computing.Comment: 6 pages RevTex, 4 eps figures included. Revised calculation with more details about mode structure calculation and the introduction of losse

    The TAM-TB Assay—A Promising TB Immune-Diagnostic Test With a Potential for Treatment Monitoring

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    Tuberculosis (TB) epidemiology is changing in Western and Central Europe due to the rise in immigration and refugees fleeing high-TB-burden areas of war and devastation. The change in local demography and the lack of sensitive and specific TB diagnostic and monitoring tools, especially for cases of childhood TB, leads to either missed cases or over-treatment of this group. Here we present a promising new diagnostic approach, the T cell activation marker (TAM)-TB assay, and its performance in a case of extra-pulmonary TB occurring in a 16 year old refugee from Afghanistan. This assay is based on the characterization of 3 activation markers (CD38, HLA-DR, and Ki67) and one maturation marker (CD27) on M. tuberculosis-specific CD4 T cells. It was performed at time-points TO (10 days), T1 (1 month), T2 (6 months), and T3 (12 months) post-treatment initiation. All markers were able to detect active tuberculosis (aTB) within this patient at T0 and reverted to a healthy/LTBI phenotype at the end of treatment. Tantalizingly, there was a clear trend toward the healthy/LTBI phenotype for the markers at T1 and T2, indicating a potential role in monitoring anti-TB treatment in the future. This assay may therefore contribute to improved TB diagnostic algorithms and TB treatment monitoring, potentially allowing for individualization of TB treatment duration in the future
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