Ciliary parathyroid hormone signaling activates transforming growth factor-β to maintain intervertebral disc homeostasis during aging

© 2018 The Author(s). Degenerative disc disease (DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor (PTH1R) to the cilia and enhances parathyroid hormone (PTH) signaling in NP cells. PTH induces transcription of integrin αvβ6 to activate the transforming growth factor (TGF)-β-connective tissue growth factor (CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH (iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1R is expressed in both mouse and human NP cells. Importantly, knockout PTH1R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD

Mass testing of the JUNO experiment 20-inch PMTs readout electronics

The Jiangmen Underground Neutrino Observatory (JUNO) is a multi-purpose, large size, liquid scintillator experiment under construction in China. JUNO will perform leading measurements detecting neutrinos from different sources (reactor, terrestrial and astrophysical neutrinos) covering a wide energy range (from 200 keV to several GeV). This paper focuses on the design and development of a test protocol for the 20-inch PMT underwater readout electronics, performed in parallel to the mass production line. In a time period of about ten months, a total number of 6950 electronic boards were tested with an acceptance yield of 99.1%

Implementation and performances of the IPbus protocol for the JUNO Large-PMT readout electronics

The Jiangmen Underground Neutrino Observatory (JUNO) is a large neutrino detector currently under construction in China. Thanks to the tight requirements on its optical and radio-purity properties, it will be able to perform leading measurements detecting terrestrial and astrophysical neutrinos in a wide energy range from tens of keV to hundreds of MeV. A key requirement for the success of the experiment is an unprecedented 3% energy resolution, guaranteed by its large active mass (20 kton) and the use of more than 20,000 20-inch photo-multiplier tubes (PMTs) acquired by high-speed, high-resolution sampling electronics located very close to the PMTs. As the Front-End and Read-Out electronics is expected to continuously run underwater for 30 years, a reliable readout acquisition system capable of handling the timestamped data stream coming from the Large-PMTs and permitting to simultaneously monitor and operate remotely the inaccessible electronics had to be developed. In this contribution, the firmware and hardware implementation of the IPbus based readout protocol will be presented, together with the performances measured on final modules during the mass production of the electronics

Validation and integration tests of the JUNO 20-inch PMTs readout electronics

The Jiangmen Underground Neutrino Observatory (JUNO) is a large neutrino detector currently under construction in China. JUNO will be able to study the neutrino mass ordering and to perform leading measurements detecting terrestrial and astrophysical neutrinos in a wide energy range, spanning from 200 keV to several GeV. Given the ambitious physics goals of JUNO, the electronic system has to meet specific tight requirements, and a thorough characterization is required. The present paper describes the tests performed on the readout modules to measure their performances.Comment: 20 pages, 13 figure

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Actuator Fault Diagnosis for Discrete-Time Systems via Augmenting State Approach

For the problem of the actuator fault diagnosis in the control systems, this paper presents a novel method by using an interval estimation approach to detect the faults and reconstruct them. In order to make estimations of the unavoidable measurement noise, a descriptor system form is built. Firstly, a full-order interval observer is developed to detect actuator faults for its sensitiveness to them. Then, a reduced-order one, which is robust to actuator faults, is presented. This method does not need the boundary information of faults; thus, the design condition is more relaxed. In order to make the interval observer stable and cooperative, linear matrix inequalities and a time-varying transformation are employed to ensure the error system matrix to be Schur and nonnegative. Based on the interval estimation results of the aforementioned method, an interval reconstruction method of actuator faults is proposed. Finally, results of the two simulation examples verify the proposed methods are effective and accurate

Research of ZnO Arrester Deterioration Mechanism Based on Electrical Performance and Micro Material Test

The traction power supply system of an Electrical Multiple Unit (EMU) often suffers from overvoltage impact. As an important protection device for on-board electrical equipment, the working environment of a roof arrester is worse than that of a power system. In recent years, the explosion failure of the roof arresters of an EMU has occurred from time to time, which seriously endangers the safe operation of high-speed railways. In this paper, the electrical performance test and material micro test of roof arrester in three states of normal, defect, and exploded, are carried out in order to study the internal causes of roof arrester explosion and clarify its deterioration mechanism. Using the DC reference voltage test and leakage current test, the electrical performance differences of normal, defective, and exploded arresters are obtained. By studying the disassembly of an arrester, the appearance characteristics of arrester varistor in three states are obtained. The micro morphology and chemical elements of the varistor are analyzed by Scanning Electron Microscope and Energy Dispersive Spectrometer. The deterioration mechanism of the arrester varistor is then revealed, and preventive measures for the explosion failure of the roof arrester are put forward. The obtained results show that, during the long-term operation of the roof arrester of an EMU, the varistor may be damp, and therefore the aluminum electrode layer and side insulation layer of the varistor may deteriorate. After the deterioration of the aluminum electrode layer, the content of the O element increases, and multiple film structures are formed on the surface. After the deterioration of the side insulating layer, the content of the O element increases, and the surface becomes uneven. Improving the sealing performance requirements of the roof arrester and optimizing the maintenance process can reduce its explosion failure

Transient Elastography in Alcoholic Liver Disease and Nonalcoholic Fatty Liver Disease: A Systemic Review and Meta-Analysis

Background and Aims. Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) have become common chronic liver diseases. Recent evidence has shown the value of transient elastography (TE) in the context of ALD/NAFLD. The aim of this study is to investigate the accuracy of TE for diagnosing steatosis and fibrosis in ALD/NAFLD patients. Methods. We retrieved relevant English studies from the databases of PubMed, Embase, the Web of Science, and the Cochrane Library through March 31st 2019. We included studies regarding the diagnosis or staging of steatosis or fibrosis by using controlled attenuation parameter (CAP) or liver stiffness measurement (LSM) measured by TE in patients with ALD or NAFLD. The reference standard of all included studies was liver biopsy. A random-effects model was applied. Statistical analyses were performed using STATA. Results. A total of 62 articles were included and analyzed in our meta-analysis. In patients with ALD/NAFLD, the pooled results revealed that the sensitivity and specificity of CAP were 0.84, 0.83, and 0.78 and 0.83, 0.71, and 0.62 for steatosis grades ≥S1, ≥S2, and =S3, respectively. The sensitivity and specificity of LSM for identifying fibrosis grades ≥F1, ≥F2, ≥F3, and =F4 were 0.77, 0.77, 0.83, and 0.91 and 0.80, 0.82, 0.84, and 0.86, respectively. Conclusion. In patients with ALD/NAFLD, CAP was feasible for identifying and screening steatosis, and LSM was accurate for diagnosing fibrosis, especially severe fibrosis and cirrhosis