1,009 research outputs found
Dual PI3K/mTOR inhibitor NVP-BEZ235 enhances radiosensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines due to suppressed Double-Strand Break (DSB) repair by non-homologous end joining
The PI3K/Akt/mTOR pathway is frequently altered in human papillomavirus (HPV)-positive
and negative squamous cell carcinoma of the head and neck (HNSCC) and overstimulation is associated
with poor prognosis. PI3K drives Akt activation and constitutive signaling acts pro-proliferative,
supports cell survival, DNA repair, and contributes to radioresistance. Since the small molecule
NVP-BEZ235 (BEZ235) is a potent dual inhibitor of this pathway, we were interested whether BEZ235
could be an efficient radiosensitizer. The 50 nM BEZ235 was found to abrogate endogenous and
irradiation-induced phosphorylation of Akt (Ser473). The anti-proliferative capacity of the drug
resulted in an increase in G1-phase cells. Repair of radiation-induced DNA double-strand breaks
(DSBs) was strongly suppressed. Reduction in DSB repair was only apparent in G1- but not in
G2-phase cells, suggesting that BEZ235 primarily affects non-homologous end joining. This finding
was confirmed using a DSB repair reporter gene assay and could be attributed to an impaired
phosphorylation of DNA-PKcs (S2056). Cellular radiosensitivity increased strongly after BEZ235
addition in all HNSCC cell lines used, especially when irradiated in the G0 or G1 phase. Our data
indicate that targeting the PI3K/Akt/mTOR pathway by BEZ235 with concurrent radiotherapy may be
considered an effective strategy for the treatment of HNSCC, regardless of the HPV and Akt status
Scintillation Counters for the D0 Muon Upgrade
We present the results of an upgrade to the D0 muon system. Scintillating
counters have been added to the existing central D0 muon system to provide
rejection for cosmic ray muons and out-of-time background, and to provide
additional fast timing information for muons in an upgraded Tevatron.
Performance and results from the 1994-1996 Tevatron run are presented.Comment: 30 pages, 25 postscript figure
Effective Functional Form of Regge Trajectories
We present theoretical arguments and strong phenomenological evidence that
hadronic Regge trajectories are essentially nonlinear and can be well
approximated, for phenomenological purposes, by a specific square-root form.Comment: 29 pages, LaTeX. Published versio
Crucial Physical Dependencies of the Core-Collapse Supernova Mechanism
We explore with self-consistent 2D F{\sc{ornax}} simulations the dependence
of the outcome of collapse on many-body corrections to neutrino-nucleon cross
sections, the nucleon-nucleon bremsstrahlung rate, electron capture on heavy
nuclei, pre-collapse seed perturbations, and inelastic neutrino-electron and
neutrino-nucleon scattering. Importantly, proximity to criticality amplifies
the role of even small changes in the neutrino-matter couplings, and such
changes can together add to produce outsized effects. When close to the
critical condition the cumulative result of a few small effects (including
seeds) that individually have only modest consequence can convert an anemic
into a robust explosion, or even a dud into a blast. Such sensitivity is not
seen in one dimension and may explain the apparent heterogeneity in the
outcomes of detailed simulations performed internationally. A natural
conclusion is that the different groups collectively are closer to a realistic
understanding of the mechanism of core-collapse supernovae than might have
seemed apparent.Comment: 25 pages; 10 figure
Search for Higgs bosons decaying to tautau pairs in ppbar collisions at sqrt(s) = 1.96 TeV
We present a search for the production of neutral Higgs bosons decaying into
tautau pairs in ppbar collisions at a center-of-mass energy of 1.96 TeV. The
data, corresponding to an integrated luminosity of 5.4 fb-1, were collected by
the D0 experiment at the Fermilab Tevatron Collider. We set upper limits at the
95% C.L. on the product of production cross section and branching ratio for a
scalar resonance decaying into tautau pairs, and we then interpret these limits
as limits on the production of Higgs bosons in the minimal supersymmetric
standard model (MSSM) and as constraints in the MSSM parameter space.Comment: 7 pages, 5 figures, submitted to PL
Measurement of the photon-jet production differential cross section in collisions at \sqrt{s}=1.96~\TeV
We present measurements of the differential cross section dsigma/dpT_gamma
for the inclusive production of a photon in association with a b-quark jet for
photons with rapidities |y_gamma|< 1.0 and 30<pT_gamma <300 GeV, as well as for
photons with 1.5<|y_gamma|< 2.5 and 30< pT_gamma <200 GeV, where pT_gamma is
the photon transverse momentum. The b-quark jets are required to have pT>15 GeV
and rapidity |y_jet| < 1.5. The results are based on data corresponding to an
integrated luminosity of 8.7 fb^-1, recorded with the D0 detector at the
Fermilab Tevatron Collider at sqrt(s)=1.96 TeV. The measured cross
sections are compared with next-to-leading order perturbative QCD calculations
using different sets of parton distribution functions as well as to predictions
based on the kT-factorization QCD approach, and those from the Sherpa and
Pythia Monte Carlo event generators.Comment: 10 pages, 9 figures, submitted to Phys. Lett.
Limits on anomalous trilinear gauge boson couplings from WW, WZ and Wgamma production in pp-bar collisions at sqrt{s}=1.96 TeV
We present final searches of the anomalous gammaWW and ZWW trilinear gauge
boson couplings from WW and WZ production using lepton plus dijet final states
and a combination with results from Wgamma, WW, and WZ production with leptonic
final states. The analyzed data correspond to up to 8.6/fb of integrated
luminosity collected by the D0 detector in pp-bar collisions at sqrt{s}=1.96
TeV. We set the most stringent limits at a hadron collider to date assuming two
different relations between the anomalous coupling parameters
Delta\kappa_\gamma, lambda, and Delta g_1^Z for a cutoff energy scale Lambda=2
TeV. The combined 68% C.L. limits are -0.057<Delta\kappa_\gamma<0.154,
-0.015<lambda<0.028, and -0.008<Delta g_1^Z<0.054 for the LEP parameterization,
and -0.007<Delta\kappa<0.081 and -0.017<lambda<0.028 for the equal couplings
parameterization. We also present the most stringent limits of the W boson
magnetic dipole and electric quadrupole moments.Comment: 10 pages, 5 figures, submitted to PL
Measurement of three-jet differential cross sections d sigma-3jet / d M-3jet in p anti-p collisions at sqrt(s)=1.96 TeV
We present the first measurement of the inclusive three-jet differential
cross section as a function of the invariant mass of the three jets with the
largest transverse momenta in an event in p anti-p collisions at sqrt(s) = 1.96
TeV. The measurement is made in different rapidity regions and for different
jet transverse momentum requirements and is based on a data set corresponding
to an integrated luminosity of 0.7 fb^{-1} collected with the D0 detector at
the Fermilab Tevatron Collider. The results are used to test the three-jet
matrix elements in perturbative QCD calculations at next-to-leading order in
the strong coupling constant. The data allow discrimination between
parametrizations of the parton distribution functions of the proton.Comment: 10 pages, 4 figures, 2 tables, submitted to Phys. Lett. B, corrected
chi2 values for NNPD
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