Design, Construction, Operation and Performance of a Hadron Blind Detector for the PHENIX Experiment

A Hadron Blind Detector (HBD) has been developed, constructed and successfully operated within the PHENIX detector at RHIC. The HBD is a Cherenkov detector operated with pure CF4. It has a 50 cm long radiator directly coupled in a window- less configuration to a readout element consisting of a triple GEM stack, with a CsI photocathode evaporated on the top surface of the top GEM and pad readout at the bottom of the stack. This paper gives a comprehensive account of the construction, operation and in-beam performance of the detector.Comment: 51 pages, 39 Figures, submitted to Nuclear Instruments and Method

Calibration of Photomultiplier Tubes for the Fluorescence Detector of Telescope Array Experiment using a Rayleigh Scattered Laser Beam

We performed photometric calibration of the PhotoMultiplier Tube (PMT) and readout electronics used for the new fluorescence detectors of the Telescope Array (TA) experiment using Rayleigh scattered photons from a pulsed nitrogen laser beam. The experimental setup, measurement procedure, and results of calibration are described. The total systematic uncertainty of the calibration is estimated to be 7.2%. An additional uncertainty of 3.7% is introduced by the transport of the calibrated PMTs from the laboratory to the TA experimental site.Comment: 43 pages, 15 figure

The JAK2-STAT3 pathway is necessary and sufficient to induce reactivity in astrocytes

International audienceAstrocyte reactivity is a hallmark of neurological diseases. This response has been observed for over a century; yet, its functional consequences are still unclear, and the signaling cascades that control reactive astrocytes are not established. Several pathways are classically associated with astrocyte reactivity but their direct contribution is often not demonstrated or the reactive phenotype characterization is limited. Here, we used viral vectors targeting astrocytes to express elements or reporter systems of the JAK2-STAT3 pathway in several mouse models of neurodegenerative diseases (ND) in vivo. To explore the involvement of this cascade in astrocyte reactivity, we performed histological, biochemical analysis as well as astrocyte-specific transcriptomics. We found that STAT3 accumulated in the nucleus of reactive astrocytes in multiple animal models of ND. We developed a viral vector-based reporter system to monitor STAT3 activation in situ. Using this STAT3-reporter in selected murine models of ND, we confirmed that the JAK-STAT3 pathway is activated in reactive astrocytes. Expression of the pathway-specific inhibitor SOCS3 by viral gene transfer, prevented reactivity in mouse models of ND. SOCS3-expressing astrocytes expressed low levels of GFAP and vimentin, recovered a normal morphology and displayed a transcriptional profile of resting astrocytes. Mirror experiments were performed by overexpressing a constitutively active form of JAK2 (JAK2ca) in astrocytes of WT mice to activate the JAK2-STAT3 pathway in the absence of any pathological context. JAK2ca expression in striatal and hippocampal astrocytes activated STAT3, as demonstrated by an increased activity of the STAT3-reporter, enhanced STAT3 phosphorylation and nuclear accumulation. JAK2ca-expressing astrocytes were hypertrophic and they overexpressed GFAP along with many transcripts characteristics of reactive astrocytes. Our results show that the JAK-STAT3 pathway is necessary and sufficient for astrocyte reactivity in various disease contexts. This core cascade can be targeted to modulate reactive astrocytes and better understand their roles in ND

Performance of a prototype RICH detector using hybrid photo-diodes

A prototype Ring-Imaging Cherenkov detector has been operated in a charged particle test beam. Cherenkov photons are imaged onto a plane of hybrid photo-diode detectors. The geometrical arrangement of the prototype and data-taking conditions are described. An analysis of the detector performance, using silica aerogel, air and C4F10 gas radiators, is presented. The photon yields and observed Cherenkov angle resolutions are found to be in good agreement with Monte Carlo simulation and satisfy the requirements of the RICH 1 detector in the LHCb experiment

The JAK2-STAT3 pathway controls a beneficial proteostasis response of reactive astrocytes in Huntington’s disease

Huntington’s disease (HD) is a fatal neurodegenerative disease characterized by striatal neurodegeneration, aggregation of mutant Huntingtin (mHTT) and the presence of reactive astrocytes. Astrocytes are important partners for neurons and engage in a specific reactive response in HD that involves morphological, molecular and functional changes. How reactive astrocytes contribute to HD is still an open question, especially because their reactive state is poorly reproduced in mouse models. Here, we show that the JAK2-STAT3 pathway, a central cascade controlling the reactive response of astrocytes, is activated in the putamen of HD patients. Selective activation of this cascade in astrocytes reduces the number and size of neuronal mHTT aggregates and improves neuronal features in two HD mouse models. Moreover, activation of the JAK2-STAT3 pathway in astrocytes coordinates a transcriptional program that increases their intrinsic proteolytic capacity, through the lysosomes and the ubiquitin-proteasome system, and enhances their production of the co-chaperone DNAJB1, which is released in exosomes. Together, our results show that the JAK2-STAT3 pathway controls a beneficial proteostasis response in reactive astrocytes in HD, which involves bi-directional signalling with neurons to reduce mHTT aggregation and toxicity

Modulation of astrocyte reactivity improves functional deficits in mouse models of Alzheimer’s disease

Abstract Astrocyte reactivity and neuroinflammation are hallmarks of CNS pathological conditions such as Alzheimer’s disease. However, the specific role of reactive astrocytes is still debated. This controversy may stem from the fact that most strategies used to modulate astrocyte reactivity and explore its contribution to disease outcomes have only limited specificity. Moreover, reactive astrocytes are now emerging as heterogeneous cells and all types of astrocyte reactivity may not be controlled efficiently by such strategies. Here, we used cell type-specific approaches in vivo and identified the JAK2-STAT3 pathway, as necessary and sufficient for the induction and maintenance of astrocyte reactivity. Modulation of this cascade by viral gene transfer in mouse astrocytes efficiently controlled several morphological and molecular features of reactivity. Inhibition of this pathway in mouse models of Alzheimer’s disease improved three key pathological hallmarks by reducing amyloid deposition, improving spatial learning and restoring synaptic deficits. In conclusion, the JAK2-STAT3 cascade operates as a master regulator of astrocyte reactivity in vivo. Its inhibition offers new therapeutic opportunities for Alzheimer’s disease

Performance of a cluster of multi-anode photomultipliers equipped with lenses for use in a prototype RICH detector

A cluster of multi-anode photomultiplier tubes (MaPMTs) equipped with focusing lenses in front of the tubes was tested in a prototype ring imaging Cherenkov (RICH) detector in a charged particle beam. The readout electronics were capable of capturing the data at 40 MHz. The effects due to charged particles and magnetic field on the MaPMT performance were also studied. The results are used to evaluate the MaPMT as a possible photodetector for the LHCb RICH detectors