Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer.

BackgroundHyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understood. Here we used an unbiased approach to identify genomic and epigenomic changes associated with pSTAT3(Y705) expression using data generated by The Cancer Genome Atlas (TCGA).Methods and findingsMutation, mRNA expression, promoter methylation, and copy number alteration data were extracted from TCGA and examined in the context of pSTAT3(Y705) protein expression. mRNA expression levels of 1279 genes were found to be associated with pSTAT3(705) expression. Association of pSTAT3(Y705) expression with caspase-8 mRNA expression was validated by immunoblot analysis in HNSCC cells. Mutation, promoter hypermethylation, and copy number alteration of any gene were not significantly associated with increased pSTAT3(Y705) protein expression.ConclusionsThese cumulative results suggest that unbiased approaches may be useful in identifying the molecular underpinnings of oncogenic signaling, including STAT3 activation, in HNSCC. Larger datasets will likely be necessary to elucidate signaling consequences of infrequent alterations

Spectral Hardness Decay with Respect to Fluence in BATSE Gamma-Ray Bursts

We have analyzed the evolution of the spectral hardness parameter Epk as a function of fluence in gamma-ray bursts. We fit 41 pulses within 26 bursts with the trend reported by Liang & Kargatis (1996) which found that Epk decays exponentially with respect to photon fluence. We also fit these pulses with a slight modification of this trend, where Epk decays linearly with energy fluence. In both cases, we found the set of 41 pulses to be consistent with the trend. For the latter trend, which we believe to be more physical, the distribution of the decay constant is roughly log-normal, with a mean of 1.75 +/- 0.07 and a FWHM of 1.0 +/- 0.1. Regarding an earlier reported invariance in the decay constant among different pulses in a single burst, we found probabilities of 0.49 to 0.84 (depending on the test used) that such invariance would occur by coincidence, most likely due to the narrow distribution of decay constant values among pulses.Comment: 17 pages, 7 figure pages, 2 table pages, submitted to The Astrophysical Journa

Evolution of the Low-Energy Photon Spectra in Gamma-Ray Bursts

We report evidence that the asymptotic low-energy power law slope alpha (below the spectral break) of BATSE gamma-ray burst photon spectra evolves with time rather than remaining constant. We find a high degree of positive correlation exists between the time-resolved spectral break energy E_pk and alpha. In samples of 18 "hard-to-soft" and 12 "tracking" pulses, evolution of alpha was found to correlate with that of the spectral break energy E_pk at the 99.7% and 98% confidence levels respectively. We also find that in the flux rise phase of "hard-to-soft" pulses, the mean value of alpha is often positive and in some bursts the maximum value of alpha is consistent with a value > +1. BATSE burst 3B 910927, for example, has a alpha_max equal to 1.6 +/- 0.3. These findings challenge GRB spectral models in which alpha must be negative of remain constant.Comment: 12 pages (including 6 figures), accepted to Ap

Current Renormalisation Constants with an O(a)-improved Fermion Action

Using chiral Ward identities, we determine the renormalisation constants of bilinear quark operators for the Sheikholeslami-Wohlert action lattice at beta=6.2. The results are obtained with a high degree of accuracy. For the vector current renormalisation constant we obtain Z_V=0.817(2)(8), where the first error is statistical and the second is due to mass dependence of Z_V. This is close to the perturbative value of 0.83. For the axial current renormalisation constant we obtain Z_A = 1.045(+10 -14), significantly higher than the value obtained in perturbation theory. This is shown to reduce the difference between lattice estimates and the experimental values for the pseudoscalar meson decay constants, but a significant discrepancy remains. The ratio of pseudoscalar to scalar renormalisation constants, Z_P/Z_S, is less well determined, but seems to be slightly lower than the perturbative value.Comment: 8 pages uuencoded compressed postscript file. Article to be submitted to Phys.Rev.

Secondary gamma-ray production in a coded aperture mask

The application of the coded aperture mask to high energy gamma-ray astronomy will provide the capability of locating a cosmic gamma-ray point source with a precision of a few arc-minutes above 20 MeV. Recent tests using a mask in conjunction with drift chamber detectors have shown that the expected point spread function is achieved over an acceptance cone of 25 deg. A telescope employing this technique differs from a conventional telescope only in that the presence of the mask modifies the radiation field in the vicinity of the detection plane. In addition to reducing the primary photon flux incident on the detector by absorption in the mask elements, the mask will also be a secondary radiator of gamma-rays. The various background components in a CAMTRAC (Coded Aperture Mask Track Chamber) telescope are considered. Monte-Carlo calculations are compared with recent measurements obtained using a prototype instrument in a tagged photon beam line

Operating characteristics of a prototype high energy gamma-ray telescope

The field of gamma-ray astronomy in the energy range from ten to several hundred MeV is severely limited by the angular resolution that can be achieved by present instruments. The identification of some of the point sources found by the COS-B mission and the resolution of detailed structure existing in those sources may depend on the development of a new class of instrument. The coded aperture mask telescope, used successfully at X-ray energies hold the promise of being such an instrument. A prototype coded aperture telescope was operated in a tagged photon beam ranging in energy from 23 to 123 MeV. The purpose of the experiment was to demonstrate the feasibility of operating a coded aperture mask telescope in this energy region. Some preliminary results and conclusions drawn from some of the data resulting from this experiment are presented

The Relationship between the Optical Depth of the 9.7 micron Silicate Absorption Feature and Infrared Differential Extinction in Dense Clouds

We have examined the relationship between the optical depth of the 9.7 micron silicate absorption feature (tau_9.7) and the near-infrared color excess, E(J-Ks) in the Serpens, Taurus, IC 5146, Chameleon I, Barnard 59, and Barnard 68 dense clouds/cores. Our data set, based largely on Spitzer IRS spectra, spans E(J-Ks)=0.3 to 10 mag (corresponding to visual extinction between about 2 and 60 mag.). All lines of sight show the 9.7 micron silicate feature. Unlike in the diffuse ISM where a tight linear correlation between the 9.7 micron silicate feature optical depth and the extinction (Av) is observed, we find that the silicate feature in dense clouds does not show a monotonic increase with extinction. Thus, in dense clouds, tau_9.7 is not a good measure of total dust column density. With few exceptions, the measured tau_9.7 values fall well below the diffuse ISM correlation line for E(J-Ks) > 2 mag (Av >12 mag). Grain growth via coagulation is a likely cause of this effect.Comment: 11 pages including 2 figures, 1 table. Accepted for publication in ApJ Letters, 23 July 200

Gauge Invariant Smearing and Matrix Correlators using Wilson Fermions at beta=6.2

We present an investigation of gauge invariant smearing for Wilson fermions on a $24^3 \times 48$ lattice at $\beta = 6.2$. We demonstrate a smearing algorithm that allows a substantial improvement in the determination of the baryon spectrum obtained using propagators smeared at both source and sink, at only a small computational cost. We investigate the matrix of correlators constructed from local and smeared operators, and are able to expose excited states of both the mesons and baryons.Comment: at lattice `92. 4 pages latex + 3 postscript figures. Edinburgh preprint: 92/51

GeV Photons from Ultra High Energy Cosmic Rays accelerated in Gamma Ray Bursts

Gamma-ray bursts are produced by the dissipation of the kinetic energy of a highly relativistic fireball, via the formation of a collisionless shock. When this happens, Ultra High Energy Cosmic Rays up to 10^20 eV are produced. I show in this paper that these particles produce, via synchrotron emission as they cross the acceleration region, photons up to 300 GeV which carry away a small, ~0.01, but non-negligible fraction of the total burst energy. I show that, when the shock occurs with the interstellar medium, the optical depth to photon-photon scattering, which might cause energy degradation of the photons, is small. The burst thusly produced would be detected at Earth simultaneoulsy with the parent gamma-ray burst, although its duration may differ significantly from that of the lower energy photons. The expected fluences, ~10^{-5}-10^{-6} erg/cm^2 are well within the range of planned detectors. A new explanation for the exceptional burst GRB 940217 is discussed.Comment: Accepted for publication in The Physical Review Letters. 4 pages, RevTeX needed, no figure