26 research outputs found

    Coherent π0 photoproduction on the deuteron up to 4 GeV

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    The differential cross section for 2H(γ,d)π0 has been measured at deuteron center-of-mass angles of 90° and 136°. This work reports the first data for this reaction above a photon energy of 1 GeV, and permits a test of the apparent constituent counting rule and reduced nuclear amplitude behavior as observed in elastic ed scattering. Measurements were performed up to a photon energy of 4.0 GeV, and are in good agreement with previous lower energy measurements. Overall, the data are inconsistent with both constituent-counting rule and reduced nuclear amplitude predictions

    Measurements of Deuteron Photodisintegration up to 4.0 GeV

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    The first measurements of the differential cross section for the d(γ,p)n reaction up to 4.0 GeV were performed at the Continuous Electron Beam Accelerator Facility (CEBAF) at Thomas Jefferson Laboratory. We report the cross sections at the proton center-of-mass angles of 36°, 52°, 69°, and 89°. These results are in reasonable agreement with previous measurements at lower energy. The 89° and 69° data show constituent-counting-rule behavior up to 4.0 GeV photon energy. The 52° and 36° data disagree with the counting-rule behavior. The quantum chromodynamics (QCD) model of nuclear reactions involving reduced amplitudes disagrees with the present data.U.S. Department of Energy, National Science Foundatio

    Antibodies against endogenous retroviruses promote lung cancer immunotherapy

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    B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

    Lung adenocarcinoma promotion by air pollutants

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    A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden

    Peddling or Creating? Investigating the Role of Twitter in News Reporting

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    © Springer-Verlag Berlin Heidelberg 2011. The widespread use of social media is regarded by many as the emergence of a new highway for information and news sharing promising a new information-driven “social revolution”. In this paper, we analyze how this idea transfers to the news reporting domain. To analyze the role of social media in news reporting, we ask whether citizen journalists tend to create news or peddle (re-report) existing content. We introduce a framework for exploring divergence between news sources by providing multiple views on corpora in comparison. The results of our case study comparing Twitter and other news sources suggest that a major role of Twitter authors consists of neither creating nor peddling, but extending them by commenting on news.acceptance rate 20%status: publishe

    Effects of Differential Glycosylation of Glycodelins on Lymphocyte Survival*S⃞

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    Glycodelin is a human glycoprotein with four reported glycoforms, namely glycodelin-A (GdA), glycodelin-F (GdF), glycodelin-C (GdC), and glycodelin-S (GdS). These glycoforms have the same protein core and appear to differ in their N-glycosylation. The glycosylation of GdA is completely different from that of GdS. GdA inhibits proliferation and induces cell death of T cells. However, the glycosylation and immunomodulating activities of GdF and GdC are not known. This study aimed to use ultra-high sensitivity mass spectrometry to compare the glycomes of GdA, GdC, and GdF and to study the relationship between the immunological activity and glycosylation pattern among glycodelin glycoforms. Using MALDI-TOF strategies, the glycoforms were shown to contain an enormous diversity of bi-, tri-, and tetra-antennary complex-type glycans carrying Galβ1–4GlcNAc (lacNAc) and/or GalNAcβ1–4GlcNAc (lacdiNAc) antennae backbones with varying levels of fucose and sialic acid substitution. Interestingly, they all carried a family of Sda (NeuAcα2–3(GalNAcβ1–4)Gal)-containing glycans, which were not identified in the earlier study because of less sensitive methodologies used. Among the three glycodelins, GdA is the most heavily sialylated. Virtually all the sialic acid on GdC is located on the Sda antennae. With the exception of the Sda epitope, the GdC N-glycome appears to be the asialylated counterpart of the GdA/GdF glycomes. Sialidase activity, which may be responsible for transforming GdA/GdF to GdC, was detected in cumulus cells. Both GdA and GdF inhibited the proliferation, induced cell death, and suppressed interleukin-2 secretion of Jurkat cells and peripheral blood mononuclear cells. In contrast, no immunosuppressive effect was observed for GdS and GdC
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