752 research outputs found

    Onco-miR-155 targets SHIP1 to promote TNFalpha-dependent growth of B cell lymphomas.

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    Non-coding microRNAs (miRs) are a vital component of post-transcriptional modulation of protein expression and, like coding mRNAs harbour oncogenic properties. However, the mechanisms governing miR expression and the identity of the affected transcripts remain poorly understood. Here we identify the inositol phosphatase SHIP1 as a bonafide target of the oncogenic miR-155. We demonstrate that in diffuse large B cell lymphoma (DLBCL) elevated levels of miR-155, and consequent diminished SHIP1 expression are the result of autocrine stimulation by the pro-inflammatory cytokine tumour necrosis factor a (TNFalpha). Anti-TNFalpha regimen such as eternacept or infliximab were sufficient to reduce miR-155 levels and restored SHIP1 expression in DLBCL cells with an accompanying reduction in cell proliferation. Furthermore, we observed a substantial decrease in tumour burden in DLBCL xenografts in response to eternacept. These findings strongly support the concept that cytokine-regulated miRs can function as a crucial link between inflammation and cancer, and illustrate the feasibility of anti-TNFalpha therapy as a novel and immediately accessible (co)treatment for DLBCL

    Neutral Radius Value Determination by Numerical Simulation Method at Ring Upsetting Test

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    Ring upsetting represents a basic operation for bulk forming process and has particular significance since it is used for contact friction determination. At ring upsetting by flat dies, metal flow depends upon tribological conditions present at contact surface. Thereby, two variants of metal flow are possible: a) two-way flow from neutral radius that is present at lower friction coefficient values, followed by ring’s inner radius reduction and ring’s outer radius increase. In such circumstances, neutral radius is found between inner and outer radius. b) one-way flow that occurs at higher friction coefficient values, where neutral radius is lower than ring’s inner radius. This paper is presenting the results of determination of relation between neutral radius value and friction coefficient. Such relation is determined by numerical simulation, by using Simufact.Forming software. Experimental verification of neutral radius position is conducted by metallographic analysis, for two friction coefficient values. Friction coefficient values are determined by ring upsetting by using dies, where in one case of ring upsetting, contact surfaces were ion implanted with nitroge

    AC Stark-shift in CPT-based Cs miniature atomic clocks

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    We report on studies on the light-shift in caesium miniature atomic clocks based on coherent population trapping (CPT) using a micro-fabricated buffer-gas cell (MEMS cell). The CPT signal is observed on the Cs D1-line by coupling the two hyperfine ground-state Zeeman sublevels involved in the clock transition to a common excited state, using two coherent electromagnetic fields. These light fields are created with a distributed feedback laser and an electro-optical modulator. We study the light-shift phenomena at different cell temperatures and laser wavelengths around 894.6nm. By adjusting the cell temperature, conditions are identified where a miniature CPT atomic clock can be operated with simultaneously low temperature coefficient and suppressed light-shift. The impact of the light-shift on the clock frequency stability is evaluated. These results are relevant for improving the long-term frequency stability of CPT-based Cs vapour-cell clock

    Quadratic dependence on temperature of Cs 0-0 hyperfine resonance frequency in single Ne buffer gas microfabricated vapour cell

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    Presented is the observation of a quadratic temperature dependence of the Cs 0-0 ground state hyperfine resonance frequency in a single Neon (Ne) buffer gas vapour microcell. The inversion temperature, expected to be theoretically independent of the buffer gas pressure, is measured to be about 80-C for two different samples. A proposal to develop chip scale atomic clocks with improved long-term frequency stability, simpler configuration (a single buffer gas instead of a buffer gas mixture) and then relaxed constraints on pressure accuracy during the cell filling procedure is presented

    A compact ultra-clean system for deploying radioactive sources inside the KamLAND detector

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    We describe a compact, ultra-clean device used to deploy radioactive sources along the vertical axis of the KamLAND liquid-scintillator neutrino detector for purposes of calibration. The device worked by paying out and reeling in precise lengths of a hanging, small-gauge wire rope (cable); an assortment of interchangeable radioactive sources could be attached to a weight at the end of the cable. All components exposed to the radiopure liquid scintillator were made of chemically compatible UHV-cleaned materials, primarily stainless steel, in order to avoid contaminating or degrading the scintillator. To prevent radon intrusion, the apparatus was enclosed in a hermetically sealed housing inside a glove box, and both volumes were regularly flushed with purified nitrogen gas. An infrared camera attached to the side of the housing permitted real-time visual monitoring of the cable's motion, and the system was controlled via a graphical user interface.Comment: Revised author affiliations, corrected typos, made minor improvements to text, and revised reference

    Measurement of the 8B Solar Neutrino Flux with the KamLAND Liquid Scintillator Detector

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    We report a measurement of the neutrino-electron elastic scattering rate from 8B solar neutrinos based on a 123 kton-day exposure of KamLAND. The background-subtracted electron recoil rate, above a 5.5 MeV analysis threshold is 1.49+/-0.14(stat)+/-0.17(syst) events per kton-day. Interpreted as due to a pure electron flavor flux with a 8B neutrino spectrum, this corresponds to a spectrum integrated flux of 2.77+/-0.26(stat)+/-0.32(syst) x 10^6 cm^-2s^-1. The analysis threshold is driven by 208Tl present in the liquid scintillator, and the main source of systematic uncertainty is due to background from cosmogenic 11Be. The measured rate is consistent with existing measurements and with Standard Solar Model predictions which include matter enhanced neutrino oscillation.Comment: 6 pages, 3 figure

    7Be Solar Neutrino Measurement with KamLAND

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    We report a measurement of the neutrino-electron elastic scattering rate of 862 keV 7Be solar neutrinos based on a 165.4 kton-day exposure of KamLAND. The observed rate is 582 +/- 90 (kton-day)^-1, which corresponds to a 862 keV 7Be solar neutrino flux of (3.26 +/- 0.50) x 10^9 cm^-2s^-1, assuming a pure electron flavor flux. Comparing this flux with the standard solar model prediction and further assuming three flavor mixing, a nu_e survival probability of 0.66 +/- 0.14 is determined from the KamLAND data. Utilizing a global three flavor oscillation analysis, we obtain a total 7Be solar neutrino flux of (5.82 +/- 0.98) x 10^9 cm^-2s^-1, which is consistent with the standard solar model predictions.Comment: 8 pages, 6 figures, submitted to Phys. Rev.

    Search for extraterrestrial antineutrino sources with the KamLAND detector

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    We present the results of a search for extraterrestrial electron antineutrinos (νˉe\bar{\nu}_{e}'s) in the energy range 8.3MeV<Eνˉe<31.8MeV8.3 MeV < E_{\bar{\nu}_{e}} < 31.8 MeV using the KamLAND detector. In an exposure of 4.53 kton-year, we identify 25 candidate events. All of the candidate events can be attributed to background, most importantly neutral current atmospheric neutrino interactions, setting an upper limit on the probability of 8^{8}B solar νe\nu_{e}'s converting into νˉe\bar{\nu}_{e}'s at 5.3×1055.3 \times 10^{-5} (90% C.L.), if we assume an undistorted νˉe\bar{\nu}_{e} shape. This limit corresponds to a solar νˉe\bar{\nu}_{e} flux of 93cm2s193 cm^{-2} s^{-1} or an event rate of 1.6events(ktonyear)11.6 events (kton-year)^{-1} above the energy threshold (Eνˉe>8.3MeV)(E_{\bar{\nu}_{e}} > 8.3 MeV). The present data also allows us to set more stringent limits on the diffuse supernova neutrino flux and on the annihilation rates for light dark matter particles.Comment: 22 pages, 6 figure

    Measurement of Neutrino Oscillation with KamLAND: Evidence of Spectral Distortion

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    We present results of a study of neutrino oscillation based on a 766 ton-year exposure of KamLAND to reactor anti-neutrinos. We observe 258 \nuebar\ candidate events with energies above 3.4 MeV compared to 365.2 events expected in the absence of neutrino oscillation. Accounting for 17.8 expected background events, the statistical significance for reactor \nuebar disappearance is 99.998%. The observed energy spectrum disagrees with the expected spectral shape in the absence of neutrino oscillation at 99.6% significance and prefers the distortion expected from \nuebar oscillation effects. A two-neutrino oscillation analysis of the KamLAND data gives \DeltaMSq = 7.90.5+0.6×105^{+0.6}_{-0.5}\times10^{-5} eV2^2. A global analysis of data from KamLAND and solar neutrino experiments yields \DeltaMSq = 7.90.5+0.6×105^{+0.6}_{-0.5}\times10^{-5} eV2^2 and \ThetaParam = 0.400.07+0.10^{+0.10}_{-0.07}, the most precise determination to date.Comment: 5 pages, 4 figures; submitted to Phys.Rev.Letter

    First Results from KamLAND: Evidence for Reactor Anti-Neutrino Disappearance

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    KamLAND has been used to measure the flux of νˉe\bar{\nu}_e's from distant nuclear reactors. In an exposure of 162 ton\cdotyr (145.1 days) the ratio of the number of observed inverse β\beta-decay events to the expected number of events without disappearance is 0.611±0.085(stat)±0.041(syst)0.611\pm 0.085 {\rm (stat)} \pm 0.041 {\rm (syst)} for νˉe\bar{\nu}_e energies >> 3.4 MeV. The deficit of events is inconsistent with the expected rate for standard νˉe\bar{\nu}_e propagation at the 99.95% confidence level. In the context of two-flavor neutrino oscillations with CPT invariance, these results exclude all oscillation solutions but the `Large Mixing Angle' solution to the solar neutrino problem using reactor νˉe\bar{\nu}_e sources.Comment: 6 pages, 6 figure
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