Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: diagnostic and mechanistic relevance

Background & Aims: Serum microRNAs (miRNAs) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages.Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 NAFLD cases representing the complete NAFLD spectrum and 10 population controls). MiRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional NAFLD cases and 15 population controls by quantitative reverse transcriptase-polymerase chain reaction.Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages but miR-193a-5p consistently the showed increased levels in all comparisons. Relative to NAFL/NASH with mild fibrosis (stage 0/1), three miRNAs (miR-193a-5p, miR-378d and miR378d) were increased in cases with NASH and clinically significant fibrosis (stage 2-4), seven (miR193a-5p, miR-378d, miR-378e, miR-320b, c, d & e) increased in cases with NAFLD Activity Score (NAS) 5-8 compared with lower NAS, and three (miR-193a-5p, miR-378d, miR-378e) increased but one (miR-19b-3p) decreased in steatosis, activity, and fibrosis "activity" (SAF-A) score 2-4 compared with lower SAF-A. The significant findings for miR-193a-5p were replicated in the additional NAFLD cohort. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n=80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD

Short Bunch Experiment at EXALT Facility

International audienceNowdays, different applications required short bunches, with low energy spread and low emittances. On EXALT facility, we perform an experiment with a short (few100 femtosecond) laser pulse on a photocathode in a 3 GHz RF gun. We perform the measurement of the single photon emission process with a copper cathode. We show that the longitudinal photoinjector model via transfer matrix is suitable for the reconstruction of the bunch duration even in short pulse mode with an increased accurracy charge below 20 pC. We clearly measure the parabolic profile in the energy spectrum resulting from blow out phenomena at the cathode due to strong space charge forces. Measurements are also compared with the Astra simulations

Characterization of a prototype matrix of Silicon PhotoMultipliers

This work reports on the electrical as well as the optical characterizations of a prototype matrix of Silicon PhotoMultipliers (SiPM). The electrical test consists of the measurement of the static (breakdown voltage, quenching resistance, post-breakdown dark current) as well as the dynamic characteristics (gain, dark count rate). The optical test consists of the estimation of the photon detection efficiency as a function of wavelength as well as operation voltage

Synchronization of a Photo-Injector and a High Power Laser With Independent Clocks

International audienceThe plasma acceleration project ESCULAP (ElectronS CoUrts pour L'Acc\'el\'eration Plasma) aims at studying electrons injection into a laser plasma accelerator. This requires the injection of short electron bunches generated by the photo injector PHIL (Photo injector at LAL) into a plasma wave by the high power femtosecond Laser LASERIX. As a first step we have studied how to synchronize PHIL and LASERIX. As these two machines had not been initially designed to work together, simple synchronization solutions were not available. We detail here the synchronisation scheme that we have tested and the experimental results obtained

A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis : a prospective derivation and global validation study

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Status report of the ESCULAP project at Orsay: External injection of low energy electrons in a Plasma

International audienceThe ESCULAP project aims at studying external injection of low energy (10 MeV) electrons in a plasma in the quasilinear regime. This facility will use the photo injector PHIL and the high power laser LASERIX. We will give a status report of the preliminary work on the facility and the status of the two machines. We will also present the results of simulations showing the expected performances of the facility

Characteristics of a prototype matrix of Silicon PhotoMultipliers (SiPM)

This work reports on the electrical (static and dynamic) as well as on the optical characteristics of a prototype matrix of Silicon Photomultipliers (SiPM). The prototype matrix consists of 4×4 SiPM’s on the same substrate fabricated at FBK-irst (Trento, Italy). Each SiPM of the matrix has an area of 1×1mm2 and it is composed of 625 microcells connected in parallel. Each microcell of the SiPM is a GM-APD (n+/p junction on P+ substrate) with an area of 40×40mm2 connected in series with its integrated polysilicon quenching resistance. The static characteristics as breakdown voltage, quenching resistance, post-breakdown dark current as well as the dynamic characteristics as gain and dark count rate have been analysed. The photon detection efficiency as a function of wavelength and operation voltage has been also estimated

First results in the application of silicon photomultiplier matrices to small animal PET

A very high resolution small animal PET scanner that employs matrices of silicon photomultipliers as photodetectors is under development at the University of Pisa and INFN Pisa. The first SiPM matrices composed of 16 (4x4) 1mmx1mm pixel elements on a common substrate have been produced at FBK-irst, and are being evaluated for this application. The MAROC2 ASIC developed at LAL-Orsay has been employed for the readout of the SiPM matrices. The devices have been tested with pixelated and continuous LYSO crystals. The results show the good performance of the matrices and lead to the fabrication of matrices with 64 SiPM elements