2,360 research outputs found

    The role of the cancer stem cell marker CD271 in DNA damage response and drug resistance of melanoma cells

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    Several lines of evidence have suggested that stemness and acquired resistance to targeted inhibitors or chemotherapeutics are mechanistically linked. Here we observed high cell surface and total levels of nerve growth factor receptor/CD271, a marker of melanoma-initiating cells, in sub-populations of chemoresistant cell lines. CD271 expression was increased in drug-sensitive cells but not resistant cells in response to DNA-damaging chemotherapeutics etoposide, fotemustine and cisplatin. Comparative analysis of melanoma cells engineered to stably express CD271 or a targeting short hairpin RNA by expression profiling provided numerous genes regulated in a CD271-dependent manner. In-depth analysis of CD271-responsive genes uncovered the association of CD271 with regulation of DNA repair components. In addition, gene set enrichment analysis revealed enrichment of CD271-responsive genes in drug- resistant cells, among them DNA repair components. Moreover, our comparative screen identified the fibroblast growth factor 13 (FGF13) as a target of CD271, highly expressed in chemoresistant cells. Further we show that levels of CD271 determine drug response. Knock-down of CD271 in fotemustine-resistant cells decreased expression of FGF13 and at least partly restored sensitivity to fotemustine. Together, we demonstrate that expression of CD271 is responsible for genes associated with DNA repair and drug response. Further, we identified 110 CD271-responsive genes predominantly expressed in melanoma metastases, among them were NEK2, TOP2A and RAD51AP1 as potential drivers of melanoma metastasis. In addition, we provide mechanistic insight in the regulation of CD271 in response to drugs. We found that CD271 is potentially regulated by p53 and in turn is needed for a proper p53-dependent response to DNA-damaging drugs. In summary, we provide for the first time insight in a CD271-associated signaling network connecting CD271 with DNA repair, drug response and metastasis

    Constraining the Hadronic Contributions to the Muon Anomalous Magnetic Moment

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    The mini-proceedings of the Workshop on "Constraining the hadronic contributions to the muon anomalous magnetic moment" which included the "13th meeting of the Radio MonteCarLow WG" and the "Satellite meeting R-Measurements at BES-III" held in Trento from April 10th to 12th, 2013, are presented. This collaboration meeting aims to bring together the experimental e+e- collider communities from BaBar, Belle, BESIII, CMD2, KLOE, and SND, with theorists working in the fields of meson transitions form factors, hadronic contributions to (g-2)_\mu and effective fine structure constant, and development of Monte Carlo generator and Radiative Corrections for precision e+e- and tau physics.Comment: 45 pages, 17 contributions. Editors: P. Masjuan and G. Venanzon

    Impact Ionization in ZnS

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    The impact ionization rate and its orientation dependence in k space is calculated for ZnS. The numerical results indicate a strong correlation to the band structure. The use of a q-dependent screening function for the Coulomb interaction between conduction and valence electrons is found to be essential. A simple fit formula is presented for easy calculation of the energy dependent transition rate.Comment: 9 pages LaTeX file, 3 EPS-figures (use psfig.sty), accepted for publication in PRB as brief Report (LaTeX source replaces raw-postscript file

    MesonNet 2013 International Workshop. Mini-proceedings

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    The mini-proceedings of the MesonNet 2013 International Workshop held in Prague from June 17th to 19th, 2013, are presented. MesonNet is a research network within EU HadronPhysics3 project (1/2012 -- 12/2014). The web page of the conference, which contains all talks, can be found at http://ipnp.mff.cuni.cz/mesonnet13Comment: 106 pages, 53 contributions. Mini-proceedings of the MesonNet 2013 International Workshop. Editors: K. Kampf, A. Kupsc, and P. Masjua

    Measurement of the pnppπ0πpn \to pp\pi^0\pi^- Reaction in Search for the Recently Observed Resonance Structure in dπ0π0d\pi^0\pi^0 and dπ+πd\pi^+\pi^- systems

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    Exclusive measurements of the quasi-free pnppπ0πpn \to pp\pi^0\pi^- reaction have been performed by means of pdpd collisions at TpT_p = 1.2 GeV using the WASA detector setup at COSY. Total and differential cross sections have been obtained covering the energy region s\sqrt s = (2.35 - 2.46) GeV, which includes the region of the ABC effect and its associated resonance structure. No ABC effect, {\it i.e.} low-mass enhancement is found in the π0π\pi^0\pi^--invariant mass spectrum -- in agreement with the constraint from Bose statistics that the isovector pion pair can not be in relative s-wave. At the upper end of the covered energy region tt-channel processes for Roper, Δ(1600)\Delta(1600) and ΔΔ\Delta\Delta excitations provide a reasonable description of the data, but at low energies the measured cross sections are much larger than predicted by such processes. Adding a resonance amplitude for the resonance at mm=~2.37 GeV with Γ\Gamma =~70 MeV and I(JP)= 0(3+)I(J^P)=~0(3^+) observed recently in pndπ0π0pn \to d\pi^0\pi^0 and pndπ+πpn \to d\pi^+\pi^- reactions leads to an agreement with the data also at low energies

    Cross section ratio and angular distributions of the reaction p + d -> 3He + eta at 48.8 MeV and 59.8 MeV excess energy

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    We present new data for angular distributions and on the cross section ratio of the p + d -> 3He + eta reaction at excess energies of Q = 48.8 MeV and Q = 59.8 MeV. The data have been obtained at the WASA-at-COSY experiment (Forschungszentrum J\"ulich) using a proton beam and a deuterium pellet target. While the shape of obtained angular distributions show only a slow variation with the energy, the new results indicate a distinct and unexpected total cross section fluctuation between Q = 20 MeV and Q = 60 MeV, which might indicate the variation of the production mechanism within this energy interval.Comment: 9 pages, 9 figure

    Evidence for a New Resonance from Polarized Neutron-Proton Scattering

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    Exclusive and kinematically complete high-statistics measurements of quasifree polarized np\vec{n}p scattering have been performed in the energy region of the narrow resonance structure dd^* with I(JP)=0(3+)I(J^P) = 0(3^+), MM \approx 2380 MeV/c2c^2 and Γ\Gamma \approx 70 MeV observed recently in the double-pionic fusion channels pndπ0π0pn \to d\pi^0\pi^0 and pndπ+πpn \to d\pi^+\pi^-. The experiment was carried out with the WASA detector setup at COSY having a polarized deuteron beam impinged on the hydrogen pellet target and utilizing the quasifree process dpnp+pspectator\vec{d}p \to np + p_{spectator}. That way the npnp analyzing power AyA_y was measured over a large angular range. The obtained AyA_y angular distributions deviate systematically from the current SAID SP07 NN partial-wave solution. Incorporating the new AyA_y data into the SAID analysis produces a pole in the 3D33G3^3D_3 - ^3G_3 waves as expected from the dd^* resonance hypothesis

    A new limit on the CP violating decay KS -> 3pi0 with the KLOE experiment

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    We have carried out a new direct search for the CP violating decay KS -> 3pi0 with 1.7 fb^-1 of e+e- collisions collected by the KLOE detector at the phi-factory DAFNE. We have searched for this decay in a sample of about 5.9 x 10^8 KS KL events tagging the KS by means of the KL interaction in the calorimeter and requiring six prompt photons. With respect to our previous search, the analysis has been improved by increasing of a factor four the tagged sample and by a more effective background rejection of fake KS tags and spurious clusters. We find no candidates in data and simulated background samples, while we expect 0.12 standard model events. Normalizing to the number of KS -> 2pi0 events in the same sample, we set the upper limit on BR(KS -> 3pi0 < 2.6 x 10^-8 at 90% C.L., five times lower than the previous limit. We also set the upper limit on the eta_000 parameter, |eta_000 | < 0.0088 at 90% C.L., improving by a factor two the latest direct measurement.Comment: Accepted for publication in Physics Letters B (15 pages, 13 figures
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