Selective activation of oxidized PTP1B by the thioredoxin system modulates PDGF-ß receptor tyrosine kinase signaling

The inhibitory reversible oxidation of protein tyrosine phosphatases (PTPs) is an important regulatory mechanism in growth factor signaling. Studies on PTP oxidation have focused on pathways that increase or decrease reactive oxygen species levels and thereby affect PTP oxidation. The processes involved in reactivation of oxidized PTPs remain largely unknown. Here the role of the thioredoxin (Trx) system in reactivation of oxidized PTPs was analyzed using a combination of in vitro and cell-based assays. Cells lacking the major Trx reductase TrxR1 (Txnrd1-/-) displayed increased oxidation of PTP1B, whereas SHP2 oxidation was unchanged. Furthermore, in vivo-oxidized PTP1B was reduced by exogenously added Trx system components, whereas SHP2 oxidation remained unchanged. Trx1 reduced oxidized PTP1B in vitro but failed to reactivate oxidized SHP2. Interestingly, the alternative TrxR1 substrate TRP14 also reactivated oxidized PTP1B, but not SHP2. Txnrd1-depleted cells displayed increased phosphorylation of PDGF-ß receptor, and an enhanced mitogenic response, after PDGF-BB stimulation. The TrxR inhibitor auranofin also increased PDGF-ß receptor phosphorylation. This effect was not observed in cells specifically lacking PTP1B. Together these results demonstrate that the Trx system, including both Trx1 and TRP14, impacts differentially on the oxidation of individual PTPs, with a preference of PTP1B over SHP2 activation. The studies demonstrate a previously unrecognized pathway for selective redox-regulated control of receptor tyrosine kinase signaling

ATHENA Detector Proposal — A Totally Hermetic Electron Nucleus Apparatus Proposed for IP6 at the Electron-Ion Collider

ATHENA has been designed as a general purpose detector capable of delivering the full scientific scope of the Electron-Ion Collider. Careful technology choices provide fine tracking and momentum resolution, high performance electromagnetic and hadronic calorimetry, hadron identification over a wide kinematic range, and near-complete hermeticity. This article describes the detector design and its expected performance in the most relevant physics channels. It includes an evaluation of detector technology choices, the technical challenges to realizing the detector and the R&D required to meet those challenges

Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1

Aberrant transforming growth factor–β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-β signaling activity and that stromal cellconditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-β–induced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment

Transverse-momentum-dependent Multiplicities of Charged Hadrons in Muon-Deuteron Deep Inelastic Scattering

A semi-inclusive measurement of charged hadron multiplicities in deep inelastic muon scattering off an isoscalar target was performed using data collected by the COMPASS Collaboration at CERN. The following kinematic domain is covered by the data: photon virtuality $Q^{2}>1$ (GeV/$c$)$^2$, invariant mass of the hadronic system $W > 5$ GeV/$c^2$, Bjorken scaling variable in the range $0.003 < x < 0.4$, fraction of the virtual photon energy carried by the hadron in the range $0.2 < z < 0.8$, square of the hadron transverse momentum with respect to the virtual photon direction in the range 0.02 (GeV/$c)^2 < P_{\rm{hT}}^{2} < 3$ (GeV/$c$)$^2$. The multiplicities are presented as a function of $P_{\rm{hT}}^{2}$ in three-dimensional bins of $x$, $Q^2$, $z$ and compared to previous semi-inclusive measurements. We explore the small-$P_{\rm{hT}}^{2}$ region, i.e. $P_{\rm{hT}}^{2} < 1$ (GeV/$c$)$^2$, where hadron transverse momenta are expected to arise from non-perturbative effects, and also the domain of larger $P_{\rm{hT}}^{2}$, where contributions from higher-order perturbative QCD are expected to dominate. The multiplicities are fitted using a single-exponential function at small $P_{\rm{hT}}^{2}$ to study the dependence of the average transverse momentum $\langle P_{\rm{hT}}^{2}\rangle$ on $x$, $Q^2$ and $z$. The power-law behaviour of the multiplicities at large $P_{\rm{hT}}^{2}$ is investigated using various functional forms. The fits describe the data reasonably well over the full measured range.Comment: 28 pages, 20 figure

Search for active-sterile neutrino mixing using neutral-current interactions in NOvA

We report results from the first search for sterile neutrinos mixing with active neutrinos through a reduction in the rate of neutral-current interactions over a baseline of 810 km between the NOvA detectors. Analyzing a 14-kton detector equivalent exposure of 6.05 x 10(20) protons-on-target in the NuMI beam at Fermilab, we observe 95 neutral-current candidates at the Far Detector compared with 83.5 +/- 9.7(stat) +/- 9.4(syst) events predicted assuming mixing only occurs between active neutrino species. No evidence for upsilon(mu) -\u3e upsilon(mu) transitions is found. Interpreting these results within a 3 + 1 model, we place constraints on the mixing angles theta(24) \u3c 20.8 degrees and theta(34) \u3c 31.2 degrees at the 90% C.L. for 0.05 eV(2) \u3c= Delta m(41)(2) \u3c= 0.5 eV(2), the range of mass splittings that produce no significant oscillations over the Near Detector baseline

Multiplicities of charged pions and unidentified charged hadrons from deep-inelastic scattering of muons off an isoscalar target

Multiplicities of charged pions and unidentified hadrons produced in deep-inelastic scattering were measured in bins of the Bjorken scaling variable $x$, the relative virtual-photon energy $y$ and the relative hadron energy $z$. Data were obtained by the COMPASS Collaboration using a 160 GeV muon beam and an isoscalar target ($^6$LiD). They cover the kinematic domain in the photon virtuality $Q^2$ > 1(GeV/c$)^2$, $0.004 < x < 0.4$, $0.2 < z < 0.85$ and $0.1 < y < 0.7$. In addition, a leading-order pQCD analysis was performed using the pion multiplicity results to extract quark fragmentation functions

Journal Staff

We present the first measurements of the differential cross section d sigma/dp(T)(gamma) for the production of an isolated photon in association with at least two b-quark jets. The measurements consider photons with rapidities vertical bar y(gamma)vertical bar &lt; 1.0 and transverse momenta 30 &lt; p(T)(gamma) &lt; 200 GeV. The b-quark jets are required to have p(T)(jet) &gt; 15 GeVand vertical bar y(jet)vertical bar &lt; 1.5. The ratio of differential production cross sections for gamma + 2 b-jets to gamma + b-jet as a function of p(T)(gamma) is also presented. The results are based on the proton-antiproton collision data at root s = 1.96 TeV collected with the D0 detector at the Fermilab Tevatron Collider. The measured cross sections and their ratios are compared to the next- to- leading order perturbative QCD calculations as well as predictions based on the k(T)- factorization approach and those from the sherpa and pythia Monte Carlo event generators

Search for WHWH associated production in ppˉp \bar{p} collisions at s=1.96 TeV\sqrt{s}=1.96\,{\rm TeV}

This report describes a search for associated production of $W$ and Higgs bosons based on data corresponding to an integrated luminosity of $\cal{L}$$\approx 5.3 \rm fb^{-1}$ collected with the D0 detector at the Fermilab Tevatron $p\bar{p}$ Collider. Events containing a $W\rightarrow \ell \nu$ candidate (with $\ell$ corresponding to $e$ or $\mu$) are selected in association with two or three reconstructed jets. One or two of the jets are required to be consistent with having evolved from a $b$ quark. A multivariate discriminant technique is used to improve the separation of signal and backgrounds. Expected and observed upper limits are obtained for the product of the $WH$ production cross section and branching ratios and reported in terms of ratios relative to the prediction of the standard model as a function of the mass of the Higgs boson ($M_{H}$). The observed and expected 95% C.L. upper limits obtained for an assumed $M_{H}=115 \rm GeV$ are, respectively, factors of 4.5 and 4.8 larger than the value predicted by the standard model.Comment: 25 pages, 14 figure

Measurements of single top quark production cross sections and |Vtb| in ppbar collisions at sqrt{s}=1.96 TeV

We present measurements of production cross sections of single top quarks in \ppbar collisions at $\sqrt{s}=1.96\;\rm TeV$ in a data sample corresponding to an integrated luminosity of $5.4\;\rm fb^{-1}$ collected by the D0 detector at the Fermilab Tevatron Collider. We select events with an isolated electron or muon, an imbalance in transverse energy, and two, three, or four jets, with one or two of them containing a bottom hadron. We obtain an inclusive cross section of \sigma({\ppbar}{\rargap}tb+X, tqb+X) = 3.43\pm^{0.73}_{0.74}\;\rm pb and use it to extract the CKM matrix element $0.79 < |V_{tb}| \leq 1$ at the 95% C.L. We also measure \sigma({\ppbar}{\rargap}tb+X) = 0.68\pm^{0.38}_{0.35}\;\rm pb and \sigma({\ppbar}{\rargap}tqb+X) = 2.86\pm^{0.69}_{0.63}\;\rm pb when assuming, respectively, $tqb$ and $tb$ production rates as predicted by the standard model.Comment: 11 pages, 8 figures, submitted to Phys. Rev.

Measurement of Leptonic Asymmetries and Top Quark Polarization in ttbar Production

We present measurements of lepton (l) angular distributions in ttbar -> W+ b W- b -> l+ nu b l- nubar bbar decays produced in ppbar collisions at a center-of-mass energy of sqrt(s)=1.96TeV, where l is an electron or muon. Using data corresponding to an integrated luminosity of 5.4fb^-1, collected with the D0 detector at the Fermilab Collider, we find that the angular distributions of l- relative to anti-protons and l+ relative to protons are in agreement with each other. Combining the two distributions and correcting for detector acceptance we obtain the forward-backward asymmetry A^l_FB = (5.8 +- 5.1(stat) +- 1.3(syst))%, compared to the standard model prediction of A^l_FB (predicted) = (4.7 +- 0.1)%. This result is further combined with the measurement based on the analysis of the l+jets final state to obtain A^l_FB = (11.8 +- 3.2)%. Furthermore, we present a first study of the top-quark polarization.Comment: submitted versio