5,566 research outputs found

    Testing ultrafast mode-locking at microhertz relative optical linewidth

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    We report new limits on the phase coherence of the ultrafast mode-locking process in an octave-spanning Ti:sapphire comb. We find that the mode-locking mechanism correlates optical phase across a full optical octave with less than 2.5 micro Hz relative linewidth. This result is at least two orders of magnitude below recent predictions for quantum-limited individual comb-mode linewidths, verifying that the mode-locking mechanism strongly correlates quantum noise across the comb spectrum.Comment: Expanded discussion to include correlated noise terms, made minor formatting changes, added a reference, and fixed typographical errors. 10 pages, 5 figure

    Down-Regulation of the Interferon Signaling Pathway in T Lymphocytes from Patients with Metastatic Melanoma

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    BACKGROUND: Dysfunction of the immune system has been documented in many types of cancers. The precise nature and molecular basis of immune dysfunction in the cancer state are not well defined. METHODS AND FINDINGS: To gain insights into the molecular mechanisms of immune dysfunction in cancer, gene expression profiles of pure sorted peripheral blood lymphocytes from 12 patients with melanoma were compared to 12 healthy controls. Of 25 significantly altered genes in T cells and B cells from melanoma patients, 17 are interferon (IFN)-stimulated genes. These microarray findings were further confirmed by quantitative PCR and functional responses to IFNs. The median percentage of lymphocytes that phosphorylate STAT1 in response to interferon-α was significantly reduced (Δ = 16.8%; 95% confidence interval, 0.98% to 33.35%) in melanoma patients (n = 9) compared to healthy controls (n = 9) in Phosflow analysis. The Phosflow results also identified two subgroups of patients with melanoma: IFN-responsive (33%) and low-IFN-response (66%). The defect in IFN signaling in the melanoma patient group as a whole was partially overcome at the level of expression of IFN-stimulated genes by prolonged stimulation with the high concentration of IFN-α that is achievable only in IFN therapy used in melanoma. The lowest responders to IFN-α in the Phosflow assay also showed the lowest gene expression in response to IFN-α. Finally, T cells from low-IFN-response patients exhibited functional abnormalities, including decreased expression of activation markers CD69, CD25, and CD71; T(H)1 cytokines interleukin-2, IFN-γ, and tumor necrosis factor α, and reduced survival following stimulation with anti-CD3/CD28 antibodies compared to controls. CONCLUSIONS: Defects in interferon signaling represent novel, dominant mechanisms of immune dysfunction in cancer. These findings may be used to design therapies to counteract immune dysfunction in melanoma and to improve cancer immunotherapy

    Analysis of expression profiles of MAGE-A antigens in oral squamous cell carcinoma cell lines

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    <p>Abstract</p> <p>Background</p> <p>The immunological response to solid tumours is insufficient. Therefore, tumour specific antigens have been explored to facilitate the activation of the immune system. The cancer/testis antigen class of MAGE-A antigens is a possible target for vaccination. Their differential expression profiles also modulate the course of the cancer disease and its response to antineoplastic drugs.</p> <p>Methods</p> <p>The expression profiles of MAGE-A2, -A3, -A4, -A6 and -A10 in five own oral squamous cell carcinoma cell lines were characterised by rt-PCR, qrt-PCR and immunocytochemistry with a global MAGE-A antibody (57B) and compared with those of an adult keratinocyte cell line (NHEK).</p> <p>Results</p> <p>All tumour cell lines expressed MAGE-A antigens. The antigens were expressed in groups with different preferences. The predominant antigens expressed were MAGE-A2, -A3 and -A6. MAGE-A10 was not expressed in the cell lines tested. The MAGE-A gene products detected in the adult keratinocyte cell line NHEK were used as a reference.</p> <p>Conclusion</p> <p>MAGE-A antigens are expressed in oral squamous cell carcinomas. The expression profiles measured facilitate distinct examinations in forthcoming studies on responses to antineoplastic drugs or radiation therapy. MAGE-A antigens are still an interesting aim for immunotherapy.</p

    Apparent Temperature and Cause-Specific Emergency Hospital Admissions in Greater Copenhagen, Denmark

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    One of the key climate change factors, temperature, has potentially grave implications for human health. We report the first attempt to investigate the association between the daily 3-hour maximum apparent temperature (Tappmax) and respiratory (RD), cardiovascular (CVD), and cerebrovascular (CBD) emergency hospital admissions in Copenhagen, controlling for air pollution. The study period covered 1 January 2002−31 December 2006, stratified in warm and cold periods. A case-crossover design was applied. Susceptibility (effect modification) by age, sex, and socio-economic status was investigated. For an IQR (8°C) increase in the 5-day cumulative average of Tappmax, a 7% (95% CI: 1%, 13%) increase in the RD admission rate was observed in the warm period whereas an inverse association was found with CVD (−8%, 95% CI: −13%, −4%), and none with CBD. There was no association between the 5-day cumulative average of Tappmax during the cold period and any of the cause-specific admissions, except in some susceptible groups: a negative association for RD in the oldest age group and a positive association for CVD in men and the second highest SES group. In conclusion, an increase in Tappmax is associated with a slight increase in RD and decrease in CVD admissions during the warmer months

    Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

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    The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

    Observation of two new Ξb\Xi_b^- baryon resonances

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    Two structures are observed close to the kinematic threshold in the Ξb0π\Xi_b^0 \pi^- mass spectrum in a sample of proton-proton collision data, corresponding to an integrated luminosity of 3.0 fb1^{-1} recorded by the LHCb experiment. In the quark model, two baryonic resonances with quark content bdsbds are expected in this mass region: the spin-parity JP=12+J^P = \frac{1}{2}^+ and JP=32+J^P=\frac{3}{2}^+ states, denoted Ξb\Xi_b^{\prime -} and Ξb\Xi_b^{*-}. Interpreting the structures as these resonances, we measure the mass differences and the width of the heavier state to be m(Ξb)m(Ξb0)m(π)=3.653±0.018±0.006m(\Xi_b^{\prime -}) - m(\Xi_b^0) - m(\pi^{-}) = 3.653 \pm 0.018 \pm 0.006 MeV/c2/c^2, m(Ξb)m(Ξb0)m(π)=23.96±0.12±0.06m(\Xi_b^{*-}) - m(\Xi_b^0) - m(\pi^{-}) = 23.96 \pm 0.12 \pm 0.06 MeV/c2/c^2, Γ(Ξb)=1.65±0.31±0.10\Gamma(\Xi_b^{*-}) = 1.65 \pm 0.31 \pm 0.10 MeV, where the first and second uncertainties are statistical and systematic, respectively. The width of the lighter state is consistent with zero, and we place an upper limit of Γ(Ξb)<0.08\Gamma(\Xi_b^{\prime -}) < 0.08 MeV at 95% confidence level. Relative production rates of these states are also reported.Comment: 17 pages, 2 figure

    Search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓

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    A search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓ is performed with a data sample, corresponding to an integrated luminosity of 1.0  fb-1 of pp collisions at √s=7  TeV, collected by the LHCb experiment. The observed number of Bs0→e±μ∓ and B0→e±μ∓ candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be B(Bs0→e±μ∓)101  TeV/c2 and MLQ(B0→e±μ∓)>126  TeV/c2 at 95% C.L., and are a factor of 2 higher than the previous bounds

    Observation of the decay BcJ/ψK+Kπ+B_c \rightarrow J/\psi K^+ K^- \pi^+

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    The decay BcJ/ψK+Kπ+B_c\rightarrow J/\psi K^+ K^- \pi^+ is observed for the first time, using proton-proton collisions collected with the LHCb detector corresponding to an integrated luminosity of 3fb1^{-1}. A signal yield of 78±1478\pm14 decays is reported with a significance of 6.2 standard deviations. The ratio of the branching fraction of \B_c \rightarrow J/\psi K^+ K^- \pi^+ decays to that of BcJ/ψπ+B_c \rightarrow J/\psi \pi^+ decays is measured to be 0.53±0.10±0.050.53\pm 0.10\pm0.05, where the first uncertainty is statistical and the second is systematic.Comment: 18 pages, 2 figure

    Observation of associated production of a ZZ boson with a DD meson in the~forward region

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    A search for associated production of a ZZ boson with an open charm meson is presented using a data sample, corresponding to an integrated luminosity of 1.0fb1.0\,\mathrm{fb}^{-`} of proton--proton collisions at a centre-of-mass energy of 7\,TeV, collected by the LHCb experiment. %% Seven candidate events for associated production of a ZZ boson with a D0D^0 meson and four candidate events for a ZZ boson with a D+D^+ meson are observed with a combined significance of 5.1standard deviations. The production cross-sections in the forward region are measured to be σZμ+μ ⁣,D0=2.50±1.12±0.22pb\sigma_{Z\rightarrow\mu^+\mu^-\!,D^0} = 2.50\pm1.12\pm0.22pb σZμ+μ ⁣,D+=0.44±0.23±0.03pb,\sigma_{Z\rightarrow\mu^+\mu^-\!,D^+} = 0.44\pm0.23\pm0.03pb, where the first uncertainty is statistical and the second systematic.Comment: 18 pages, 2 figure

    Measurement of the mass and lifetime of the Ωb\Omega_b^- baryon

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    A proton-proton collision data sample, corresponding to an integrated luminosity of 3 fb1^{-1} collected by LHCb at s=7\sqrt{s}=7 and 8 TeV, is used to reconstruct 63±963\pm9 ΩbΩc0π\Omega_b^-\to\Omega_c^0\pi^-, Ωc0pKKπ+\Omega_c^0\to pK^-K^-\pi^+ decays. Using the ΞbΞc0π\Xi_b^-\to\Xi_c^0\pi^-, Ξc0pKKπ+\Xi_c^0\to pK^-K^-\pi^+ decay mode for calibration, the lifetime ratio and absolute lifetime of the Ωb\Omega_b^- baryon are measured to be \begin{align*} \frac{\tau_{\Omega_b^-}}{\tau_{\Xi_b^-}} &= 1.11\pm0.16\pm0.03, \\ \tau_{\Omega_b^-} &= 1.78\pm0.26\pm0.05\pm0.06~{\rm ps}, \end{align*} where the uncertainties are statistical, systematic and from the calibration mode (for τΩb\tau_{\Omega_b^-} only). A measurement is also made of the mass difference, mΩbmΞbm_{\Omega_b^-}-m_{\Xi_b^-}, and the corresponding Ωb\Omega_b^- mass, which yields \begin{align*} m_{\Omega_b^-}-m_{\Xi_b^-} &= 247.4\pm3.2\pm0.5~{\rm MeV}/c^2, \\ m_{\Omega_b^-} &= 6045.1\pm3.2\pm 0.5\pm0.6~{\rm MeV}/c^2. \end{align*} These results are consistent with previous measurements.Comment: 11 pages, 5 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-008.htm
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