396 research outputs found
Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy
Degenerative diseases of the retina are responsible for the death of photoreceptors and subsequent loss of vision in patients. Nevertheless, the inner retinal layers remain intact over an extended period of time, enabling the restoration of light sensitivity in blind retinas via the expression of optogenetic tools in the remaining retinal cells. The chimeric Opto-mGluR6 protein represents such a tool. With exclusive ON-bipolar cell expression, it combines the light-sensitive domains of melanopsin and the intracellular domains of the metabotropic glutamate receptor 6 (mGluR6), which naturally mediates light responses in these cells. Albeit vision restoration in blind mice by Opto-mGluR6 delivery was previously shown, much is left to be explored in regard to the effects of the timing of the treatment in the degenerated retina. We performed a functional evaluation of Opto-mGluR6-treated murine blind retinas using multi-electrode arrays (MEAs) and observed long-term functional preservation in the treated retinas, as well as successful therapeutical intervention in later stages of degeneration. Moreover, the treatment decreased the inherent retinal hyperactivity of the degenerated retinas to levels undistinguishable from healthy controls. Finally, we observed for the first time micro electroretinograms (mERGs) in optogenetically treated animals, corroborating the origin of Opto-mGluR6 signalling at the level of mGluR6 of ON-bipolar cells
Bipolar cell targeted optogenetic gene therapy restores parallel retinal signaling and high-level vision in the degenerated retina.
Optogenetic gene therapies to restore vision are in clinical trials. Whilst current clinical approaches target the ganglion cells, the output neurons of the retina, new molecular tools enable efficient targeting of the first order retinal interneurons, the bipolar cells, with the potential to restore a higher quality of vision. Here we investigate retinal signaling and behavioral vision in blind mice treated with bipolar cell targeted optogenetic gene therapies. All tested tools, including medium-wave opsin, Opto-mGluR6, and two new melanopsin based chimeras restored visual acuity and contrast sensitivity. The best performing opsin was a melanopsin-mGluR6 chimera, which in some cases restored visual acuities and contrast sensitivities that match wild-type animals. Light responses from the ganglion cells were robust with diverse receptive-field types, inferring elaborate inner retinal signaling. Our results highlight the potential of bipolar cell targeted optogenetics to recover high-level vision in human patients with end-stage retinal degenerations
ALICE Central Trigger System for LHC Run 3
A major upgrade of the ALICE experiment is in progress and will result in
high-rate data taking during LHC Run 3 (2022-2024). The LHC interaction rate at
Point 2 where the ALICE experiment is located will be increased to $50\
\mathrm{kHz}1\ \mathrm{MHz}$ in pp collisions. The
ALICE experiment will be able to read out data at these interaction rates
leading to an increase of the collected luminosity by a factor of up to about
100 with respect to LHC Runs 1 and 2. To satisfy these requirements, a new
readout system has been developed for most of the ALICE detectors, allowing the
full readout of the data at the required interaction rates without the need for
a hardware trigger selection. A novel trigger and timing distribution system
will be implemented, based on Passive Optical Network (PON) and GigaBit
Transceiver (GBT) technology. To assure backward compatibility a triggered mode
based on RD12 Trigger-Timing-Control (TTC) technology, as used in the previous
LHC runs, will be maintained and re-implemented under the new Central Trigger
System (CTS). A new universal ALICE Trigger Board (ATB) based on the Xilinx
Kintex Ultrascale FPGA has been designed to function as a Central Trigger
Processor (CTP), Local Trigger Unit (LTU), and monitoring interfaces.
In this paper, this new hybrid multilevel system with continuous readout will
be described, together with the triggering mechanism and algorithms. An
overview of the CTS, the design of the ATB and the different communication
protocols will be presented.Comment: 10 pages, 6 figures, submitted as a proceedings paper for 25th
International Conference on Computing in High-Energy and Nuclear Physics
(vCHEP 2021) to European Physical Journal (EPJ) Web of Conferences, May
17th-2th 2021, v2: corrected institution lis
New results from the NA57 experiment
We report results from the experiment NA57 at CERN SPS on hyperon production
at midrapidity in Pb-Pb collisions at 158 GeV/ and 40 GeV/.
, and yields are compared with those from the STAR
experiment at the higher energy of the BNL RHIC. , , \
and preliminary transverse mass spectra are presented and interpreted
within the framework of a hydro-dynamical blast wave model.Comment: 8 pages, 3 figures, contribution to the proceedings of The XXXVIIIth
Rencontres de Moriond "QCD and High Energy Hadronic Interactions
Strange particle production in 158 and 40 GeV/ Pb-Pb and p-Be collisions
Results on strange particle production in Pb-Pb collisions at 158 and 40
GeV/ beam momentum from the NA57 experiment at CERN SPS are presented.
Particle yields and ratios are compared with those measured at RHIC.
Strangeness enhancements with respect to p-Be reactions at the same beam
momenta have been also measured: results about their dependence on centrality
and collision energy are reported and discussed.Comment: Contribution to the proceedings of the "Hot Quarks 2004" Conference,
July 18-24 2004, New Mexico, USA, submitted to Journal of Physics G 7 pages,
5 figure
Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions
We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe
Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV
Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe
Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV
Peer reviewe
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