2,200 research outputs found

    Coupling of D2R Short but not D2R Long receptor isoform to the Rho/ROCK signaling pathway renders striatal neurons vulnerable to mutant huntingtin.

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    Huntington's disease, an inherited neurodegenerative disorder, results from abnormal polyglutamine extension in the N-terminal region of the huntingtin protein. This mutation causes preferential degeneration of striatal projection neurons. We previously demonstrated, in vitro, that dopaminergic D2 receptor stimulation acted in synergy with expanded huntingtin to increase aggregates formation and striatal death through activation of the Rho/ROCK signaling pathway. In vivo, in a lentiviral-mediated model of expanded huntingtin expression in the rat striatum, we found that the D2 antagonist haloperidol protects striatal neurons against expanded huntingtin-mediated toxicity. Two variant transcripts are generated by alternative splicing of the of D2 receptor gene, the D2R-Long and the D2R-Short, which are thought to play different functional roles. We show herein that overexpression of D2R-Short, but not D2R-Long in cell lines is associated with activation of the RhoA/ROCK signaling pathway. In striatal neurons in culture, the selective D2 agonist Quinpirole triggers phosphorylation of cofilin, a downstream effector of ROCK, which is abrogated by siRNAs that knockdown both D2R-Long and D2R-Short, but not by siRNAs targeting D2R-Long alone. Aggregate formation and neuronal death induced by expanded huntingtin, were potentiated by Quinpirole. This D2 agonist-mediated effect was selectively inhibited by the siRNA targeting both D2R-Long and D2R-Short but not D2R-Long alone. Our data provide evidence for a specific coupling of D2R-Short to the RhoA/ROCK/cofilin pathway, and its involvement in striatal vulnerability to expanded huntingtin. A new route for targeting Rho-ROCK signaling in Huntington's disease is unraveled with our findings

    Continuous Entanglement Distribution from an AlGaAs-on-Insulator Microcomb for Quantum Communications

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    Using an aluminum gallium arsenide microring resonator, we demonstrate a bright quantum optical microcomb with >300>300 nm bandwidth and more than 20 sets of time-energy entangled modes, enabling spectral demultiplexing with simple, off-the-shelf commercial telecom components. We report high-rate continuous entanglement distribution for two sets of entangled-photon pair frequency modes exhibiting up to 2020 GHz/mW2^2 pair generation rate. As an illustrative example of entanglement distribution, we perform a continuous-wave time-bin quantum key distribution protocol with 8 kbps raw key rates while maintaining less than 10%\% error rate and sufficient two-photon visibility to ensure security of the channel. When the >>20 frequency modes are multiplexed, we estimate >>100 kbps entanglement-based key rates or the creation of a multi-user quantum communications network. The entire system requires less than 110 μ\muW of on-chip optical power, demonstrating an efficient source of entangled frequency modes for quantum communications. As a proof of principle, a quantum key is distributed across 12 km of deployed fiber on the UCSB campus and used to transmit a 21 kB image with <9%<9\% error.Comment: 14 pages, 8 figure

    Performances of Anode-resistive Micromegas for HL-LHC

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    Micromegas technology is a promising candidate to replace Atlas forward muon chambers -tracking and trigger- for future HL-LHC upgrade of the experiment. The increase on background and pile-up event probability requires detector performances which are currently under studies in intensive RD activities. We studied performances of four different resistive Micromegas detectors with different read-out strip pitches. These chambers were tested using \sim120 GeV momentum pions, at H6 CERN-SPS beam line in autumn 2010. For a strip pitch 500 micrometers we measure a resolution of \sim90 micrometers and a efficiency of ~98%. The track angle effect on the efficiency was also studied. Our results show that resistive techniques induce no degradation on the efficiency or resolution, with respect to the standard Micromegas. In some configuration the resistive coating is able to reduce the discharge currents at least by a factor of 100.Micromegas technology is a promising candidate to replace Atlas forward muon chambers -tracking and trigger- for future HL-LHC upgrade of the experiment. The increase on background and pile-up event probability requires detector performances which are currently under studies in intensive RD activities. We studied performances of four different resistive Micromegas detectors with different read-out strip pitches. These chambers were tested using \sim120 GeV momentum pions, at H6 CERN-SPS beam line in autumn 2010. For a strip pitch 500 micrometers we measure a resolution of \sim90 micrometers and a efficiency of \sim98%. The track angle effect on the efficiency was also studied. Our results show that resistive techniques induce no degradation on the efficiency or resolution, with respect to the standard Micromegas. In some configuration the resistive coating is able to reduce the discharge currents at least by a factor of 100.Comment: "Presented at the 2011 Hadron Collider Physics symposium (HCP-2011), Paris, France, November 14-18 2011, 3 pages, 6 figures.

    Neutron spectroscopy with the Spherical Proportional Counter

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    A novel large volume spherical proportional counter, recently developed, is used for neutron measurements. Gas mixtures of N2N_{2} with C2H6C_{2}H_{6} and pure N2N_{2} are studied for thermal and fast neutron detection, providing a new way for the neutron spectroscopy. The neutrons are detected via the 14N(n,p)C14{}^{14}N(n, p)C^{14} and 14N(n,α)B11{}^{14}N(n, \alpha)B^{11} reactions. Here we provide studies of the optimum gas mixture, the gas pressure and the most appropriate high voltage supply on the sensor of the detector in order to achieve the maximum amplification and better resolution. The detector is tested for thermal and fast neutrons detection with a 252Cf{}^{252}Cf and a 241Am9Be{}^{241}Am-{}^{9}Be neutron source. The atmospheric neutrons are successfully measured from thermal up to several MeV, well separated from the cosmic ray background. A comparison of the spherical proportional counter with the current available neutron counters is also given.Comment: 7 pages, 10 figure
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