232 research outputs found
Natural compound Tetrocarcin-A downregulates Junctional Adhesion Molecule-A in conjunction with HER2 and inhibitor of apoptosis proteins and inhibits tumor cell growth.
Overexpression of the tight junction protein Junctional Adhesion Molecule-A (JAM-A) has been linked to aggressive disease in breast and other cancers, but JAM-targeting drugs remain elusive. Screening of a natural compound library identified the antibiotic Tetrocarcin-A as a novel downregulator of JAM-A and human epidermal growth factor receptor-2 (HER2) protein expression in breast cancer cells. Lysosomal inhibition partially rescued the downregulation of JAM-A and HER2 caused by Tetrocarcin-A, and attenuated its cytotoxic activity. Tetrocarcin-A treatment or JAM-A silencing reduced AKT and ERK phosphorylation, inhibited c-FOS phosphorylation at Threonine-232 (its transcriptional regulation site), inhibited nuclear localization of c-FOS, and downregulated expression of the inhibitor of apoptosis proteins (IAP). This was accompanied by Tetrocarcin-A-induced caspase-dependent apoptosis. To begin evaluating the potential clinical relevance of our findings, we extended our studies to other models. Encouragingly, Tetrocarcin-A downregulated JAM-A expression and caused cytotoxicity in primary breast cells and lung cancer stem cells, and inhibited the growth of xenografts in a semi-in vivo model involving invasion across the chicken egg chorioallantoic membrane. Taken together, our data suggest that Tetrocarcin-A warrants future evaluation as a novel cancer therapeutic by virtue of its ability to downregulate JAM-A expression, reduce tumorigenic signaling and induce apoptosis
ZFOURGE catalogue of AGN candidates: an enhancement of 160-Όm-derived star formation rates in active galaxies to z  = 3.2
We investigate active galactic nuclei (AGN) candidates within the FourStar Galaxy Evolution Survey (ZFOURGE) to determine the impact they have on star formation in their host galaxies. We first identify a population of radio, X-ray, and infrared-selected AGN by cross-matching the deep Ks-band imaging of ZFOURGE with overlapping multiwavelength data. From this, we construct a mass-complete (log(Mâ/MâMâ/Mâ) â„9.75), AGN luminosity limited sample of 235 AGN hosts over z = 0.2â3.2. We compare the rest-frame U â V versus V â J (UVJ) colours and specific star formation rates (sSFRs) of the AGN hosts to a mass-matched control sample of inactive (non-AGN) galaxies. UVJ diagnostics reveal AGN tend to be hosted in a lower fraction of quiescent galaxies and a higher fraction of dusty galaxies than the control sample. Using 160 ÎŒm Herschel PACS data, we find the mean specific star formation rate of AGN hosts to be elevated by 0.34 ± 0.07 dex with respect to the control sample across all redshifts. This offset is primarily driven by infrared-selected AGN, where the mean sSFR is found to be elevated by as much as a factor of âŒ5. The remaining population, comprised predominantly of X-ray AGN hosts, is found mostly consistent with inactive galaxies, exhibiting only a marginal elevation. We discuss scenarios that may explain these findings and postulate that AGN are less likely to be a dominant mechanism for moderating galaxy growth via quenching than has previously been suggested
Ramond-Ramond Fields, Fractional Branes and Orbifold Differential K-Theory
We study D-branes and Ramond-Ramond fields on global orbifolds of Type II
string theory with vanishing H-flux using methods of equivariant K-theory and
K-homology. We illustrate how Bredon equivariant cohomology naturally realizes
stringy orbifold cohomology. We emphasize its role as the correct cohomological
tool which captures known features of the low-energy effective field theory,
and which provides new consistency conditions for fractional D-branes and
Ramond-Ramond fields on orbifolds. We use an equivariant Chern character from
equivariant K-theory to Bredon cohomology to define new Ramond-Ramond couplings
of D-branes which generalize previous examples. We propose a definition for
groups of differential characters associated to equivariant K-theory. We derive
a Dirac quantization rule for Ramond-Ramond fluxes, and study flat
Ramond-Ramond potentials on orbifolds.Comment: 46 pages; v2: typos correcte
Constraining Very Heavy Dark Matter Using Diffuse Backgrounds of Neutrinos and Cascaded Gamma Rays
We consider multi-messenger constraints on very heavy dark matter (VHDM) from
recent Fermi gamma-ray and IceCube neutrino observations of isotropic
background radiation. Fermi data on the diffuse gamma-ray background (DGB)
shows a possible unexplained feature at very high energies (VHE), which we have
called the "VHE Excess" relative to expectations for an attenuated power law
extrapolated from lower energies. We show that VHDM could explain this excess,
and that neutrino observations will be an important tool for testing this
scenario. More conservatively, we derive new constraints on the properties of
VHDM for masses of 10^3-10^10 GeV. These generic bounds follow from cosmic
energy budget constraints for gamma rays and neutrinos that we developed
elsewhere, based on detailed calculations of cosmic electromagnetic cascades
and also neutrino detection rates. We show that combining both gamma-ray and
neutrino data is essential for making the constraints on VHDM properties both
strong and robust. In the lower mass range, our constraints on VHDM
annihilation and decay are comparable to other results; however, our
constraints continue to much higher masses, where they become relatively
stronger.Comment: 33 pages, 21 figures, accepted for publication in JCA
Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya
Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV
A search for a Higgs boson decaying into two photons is described. The
analysis is performed using a dataset recorded by the CMS experiment at the LHC
from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an
integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross
section of the standard model Higgs boson decaying to two photons. The expected
exclusion limit at 95% confidence level is between 1.4 and 2.4 times the
standard model cross section in the mass range between 110 and 150 GeV. The
analysis of the data excludes, at 95% confidence level, the standard model
Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The
largest excess of events above the expected standard model background is
observed for a Higgs boson mass hypothesis of 124 GeV with a local significance
of 3.1 sigma. The global significance of observing an excess with a local
significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is
estimated to be 1.8 sigma. More data are required to ascertain the origin of
this excess.Comment: Submitted to Physics Letters
Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV
The Lambda(b) differential production cross section and the cross section
ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum
pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7
TeV using data collected by the CMS experiment at the LHC. The measurements are
based on Lambda(b) decays reconstructed in the exclusive final state J/Psi
Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and
Lambda to proton pion, using a data sample corresponding to an integrated
luminosity of 1.9 inverse femtobarns. The product of the cross section times
the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls
faster than that of b mesons. The measured value of the cross section times the
branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06
+/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for
anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are
statistical and systematic, respectively.Comment: Submitted to Physics Letters
Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV
A search is presented for physics beyond the standard model (BSM) in final
states with a pair of opposite-sign isolated leptons accompanied by jets and
missing transverse energy. The search uses LHC data recorded at a
center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to
an integrated luminosity of approximately 5 inverse femtobarns. Two
complementary search strategies are employed. The first probes models with a
specific dilepton production mechanism that leads to a characteristic kinematic
edge in the dilepton mass distribution. The second strategy probes models of
dilepton production with heavy, colored objects that decay to final states
including invisible particles, leading to very large hadronic activity and
missing transverse energy. No evidence for an event yield in excess of the
standard model expectations is found. Upper limits on the BSM contributions to
the signal regions are deduced from the results, which are used to exclude a
region of the parameter space of the constrained minimal supersymmetric
extension of the standard model. Additional information related to detector
efficiencies and response is provided to allow testing specific models of BSM
physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO
Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV
Isolated photon production is measured in proton-proton and lead-lead
collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the
pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80
GeV with the CMS detector at the LHC. The measured ET spectra are found to be
in good agreement with next-to-leading-order perturbative QCD predictions. The
ratio of PbPb to pp isolated photon ET-differential yields, scaled by the
number of incoherent nucleon-nucleon collisions, is consistent with unity for
all PbPb reaction centralities.Comment: Submitted to Physics Letters
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