715 research outputs found
The EBV-encoded latent membrane proteins, LMP2A and LMP2B, limit the actions of interferon by targeting interferon receptors for degradation
Although frequently expressed in EpsteinâBarr virus (EBV)-positive malignancies, the role that latent membrane protein 2A and 2B (LMP2A and LMP2B) have in the oncogenic process remains obscure. Here we show a novel function for these proteins in epithelial cells, namely, their ability to modulate signalling from type I/II interferon receptors (IFNRs). We show that LMP2A- and LMP2B-expressing epithelial cells show decreased responsiveness to interferon (IFN)α and IFNÎł, as assessed by STAT1 phosphorylation, ISGF3 and GAF-mediated binding to IFN-stimulated response element and IFNÎł-activated factor sequence elements and luciferase reporter activation. Transcriptional profiling highlighted the extent of this modulation, with both viral proteins impacting âgloballyâ on IFN-stimulated gene expression. Although not affecting the levels of cell-surface IFNRs, LMP2A and LMP2B accelerated the turnover of IFNRs through processes requiring endosome acidification. This function may form part of EBV's strategy to limit anti-viral responses and define a novel function for LMP2A and LMP2B in modulating signalling from receptors that participate in innate immune responses
A Comparison of Cosmic Ray Composition Measurements at the Highest Energies
In recent years the Fly's Eye and Akeno groups have presented analyses of the
cosmic ray mass composition at energies above 10^17 eV. While the analysis of
the Fly's Eye group points to a likely change in mass composition from heavy to
light at energies above 10^18 eV, the Akeno analysis favours an unchanging
composition. However, the two groups base their conclusions on simulations
using quite different hadronic models. Here we present a comparison of the
experiments using the same hadronic model and find that the agreement between
the experiments is much improved. Under this model, both experiments measure a
composition rich in iron around 10^17 eV which becomes lighter at higher
energies. However, the agreement is not complete, which indicates scope for
improvement of the interaction model, or perhaps the need for a re-examination
of the experimental results.Comment: 15 pages, uses epsfig.sty with 6 figures. Submitted to Astroparticle
Physics, 25th January 1998. This is a revised version (21st May 1998) which
addresses some referee comments, and which clarifies discussions of our
result
Genomic landscape and actionable mutations of brain metastases derived from nonâsmall cell lung cancer: A systematic review
Background
Brain metastases derived from nonâsmall cell lung cancer (NSCLC) represent a significant clinical problem. We aim to characterize the genomic landscape of brain metastases derived from NSCLC and assess clinical actionability.
Methods
We searched Embase, MEDLINE, Web of Science, and BIOSIS from inception to 18/19 May 2022. We extracted information on patient demographics, smoking status, genomic data, matched primary NSCLC, and programmed cell death ligand 1 expression.
Results
We found 72 included papers and data on 2346 patients. The most frequently mutated genes from our data were EGFR (nâ
=â
559), TP53 (nâ
=â
331), KRAS (nâ
=â
328), CDKN2A (nâ
=â
97), and STK11 (nâ
=â
72). Common missense mutations included EGFR L858R (nâ
=â
80) and KRAS G12C (nâ
=â
17). Brain metastases of ever versus never smokers had differing missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups. Of the top 10 frequently mutated genes that had primary NSCLC data, we found 37% of the specific mutations assessed to be discordant between the primary NSCLC and brain metastases.
Conclusions
To our knowledge, this is the first systematic review to describe the genomic landscape of brain metastases derived from NSCLC. These results provide a comprehensive outline of frequently mutated genes and missense mutations that could be clinically actionable. These data also provide evidence of differing genomic landscapes between ever versus never smokers and primary NSCLC compared to the BM. This information could have important consequences for the selection and development of targeted drugs for these patients
Unparticle Searches Through Gamma Gamma Scattering
We investigate the effects of unparticles on gamma gamma--> gamma gamma
scattering for photon collider mode of the future multi-TeV e^+e^- linear
collider. We show the effects of unparticles on the differential, and total
scattering cross sections for different polarization configurations.
Considering 1-loop Standard Model background contributions from the charged
fermions, and W^{+-} bosons to the cross section, we calculate the upper limits
on the unparticle couplings lambda_0 to the photons for various values of the
scaling dimension d(1<d<2) at sqrt{s}=0.5-5 TeV.Comment: 15 pages, 5 figures, 2 table
Search for Global Dipole Enhancements in the HiRes-I Monocular Data above 10^{18.5} eV
Several proposed source models for Ultra-High Energy Cosmic Rays (UHECRs)
consist of dipole distributions oriented towards major astrophysical landmarks
such as the galactic center, M87, or Centaurus A. We use a comparison between
real data and simulated data to show that the HiRes-I monocular data for
energies above 10^{18.5} eV is, in fact, consistent with an isotropic source
model. We then explore methods to quantify our sensitivity to dipole source
models oriented towards the Galactic Center, M87, and Centaurus A.Comment: 17 pages, 31 figure
Observation of the Ankle and Evidence for a High-Energy Break in the Cosmic Ray Spectrum
We have measured the cosmic ray spectrum at energies above eV using
the two air fluorescence detectors of the High Resolution Fly's Eye experiment
operating in monocular mode. We describe the detector, PMT and atmospheric
calibrations, and the analysis techniques for the two detectors. We fit the
spectrum to models describing galactic and extragalactic sources. Our measured
spectrum gives an observation of a feature known as the ``ankle'' near eV, and strong evidence for a suppression near eV.Comment: 14 pages, 9 figures. To appear in Physics Letters B. Accepted versio
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in âs = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fbâ1 of protonâproton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC
Measurements of inclusive jet suppression in heavy ion collisions at the LHC
provide direct sensitivity to the physics of jet quenching. In a sample of
lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated
luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with
a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the
transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the
anti-kt algorithm with values for the distance parameter that determines the
nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of
the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp.
Jet production is found to be suppressed by approximately a factor of two in
the 10% most central collisions relative to peripheral collisions. Rcp varies
smoothly with centrality as characterized by the number of participating
nucleons. The observed suppression is only weakly dependent on jet radius and
transverse momentum. These results provide the first direct measurement of
inclusive jet suppression in heavy ion collisions and complement previous
measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables,
submitted to Physics Letters B. All figures including auxiliary figures are
available at
http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02
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