Targeting IRE1 with small molecules counteracts progression of atherosclerosis

Metaflammation, an atypical, metabolically induced, chronic lowgrade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory network that responds to ER stress, is a hallmark of all stages of atherosclerotic plaque formation. The most conserved ERresident UPR regulator, the kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1), is activated in lipid-laden macrophages that infiltrate the atherosclerotic lesions. Using RNA sequencing in macrophages, we discovered that IRE1 regulates the expression of many proatherogenic genes, including several important cytokines and chemokines. We show that IRE1 inhibitors uncouple lipid-induced ER stress from inflammasome activation in both mouse and human macrophages. In vivo, these IRE1 inhibitors led to a significant decrease in hyperlipidemia-induced IL-1β and IL-18 production, lowered T-helper type-1 immune responses, and reduced atherosclerotic plaque size without altering the plasma lipid profiles in apolipoprotein E-deficient mice. These results show that pharmacologic modulation of IRE1 counteracts metaflammation and alleviates atherosclerosis

Design and construction of the MicroBooNE Cosmic Ray Tagger system

The MicroBooNE detector utilizes a liquid argon time projection chamber (LArTPC) with an 85 t active mass to study neutrino interactions along the Booster Neutrino Beam (BNB) at Fermilab. With a deployment location near ground level, the detector records many cosmic muon tracks in each beam-related detector trigger that can be misidentified as signals of interest. To reduce these cosmogenic backgrounds, we have designed and constructed a TPC-external Cosmic Ray Tagger (CRT). This sub-system was developed by the Laboratory for High Energy Physics (LHEP), Albert Einstein center for fundamental physics, University of Bern. The system utilizes plastic scintillation modules to provide precise time and position information for TPC-traversing particles. Successful matching of TPC tracks and CRT data will allow us to reduce cosmogenic background and better characterize the light collection system and LArTPC data using cosmic muons. In this paper we describe the design and installation of the MicroBooNE CRT system and provide an overview of a series of tests done to verify the proper operation of the system and its components during installation, commissioning, and physics data-taking

Limits on muon-neutrino to tau-neutrino oscillations induced by a sterile neutrino state obtained by OPERA at the CNGS beam

The OPERA experiment, exposed to the CERN to Gran Sasso $\nu_\mu$ beam, collected data from 2008 to 2012. Four oscillated $\nu_\tau$ Charged Current interaction candidates have been detected in appearance mode, which are consistent with $\nu_\mu \to \nu_\tau$ oscillations at the atmospheric $\Delta m^2$ within the "standard" three-neutrino framework. In this paper, the OPERA $\nu_\tau$ appearance results are used to derive limits on the mixing parameters of a massive sterile neutrino.Comment: 11 pages, 4 figures; reference to Planck result updated in the Introduction. Submitted to JHE

Determination of the muon charge sign with the dipolar spectrometers of the OPERA experiment

The OPERA long-baseline neutrino-oscillation experiment has observed the direct appearance of $\nu_\tau$ in the CNGS $\nu_\mu$ beam. Two large muon magnetic spectrometers are used to identify muons produced in the $\tau$ leptonic decay and in $\nu_\mu^{CC}$ interactions by measuring their charge and momentum. Besides the kinematic analysis of the $\tau$ decays, background resulting from the decay of charmed particles produced in $\nu_\mu^{CC}$ interactions is reduced by efficiently identifying the muon track. A new method for the charge sign determination has been applied, via a weighted angular matching of the straight track-segments reconstructed in the different parts of the dipole magnets. Results obtained for Monte Carlo and real data are presented. Comparison with a method where no matching is used shows a significant reduction of up to 40\% of the fraction of wrongly determined charges.Comment: 10 pages. Improvements in the tex

Procedure for short-lived particle detection in the OPERA experiment and its application to charm decays

The OPERA experiment, designed to perform the first observation of $\nu_\mu \rightarrow \nu_\tau$ oscillations in appearance mode through the detection of the $\tau$ leptons produced in $\nu_\tau$ charged current interactions, has collected data from 2008 to 2012. In the present paper, the procedure developed to detect $\tau$ particle decays, occurring over distances of the order of 1 mm from the neutrino interaction point, is described in detail. The results of its application to the search for charmed hadrons are then presented as a validation of the methods for $\nu_\tau$ appearance detection

Convolutional Neural Networks Applied to Neutrino Events in a Liquid Argon Time Projection Chamber

We present several studies of convolutional neural networks applied to data coming from the MicroBooNE detector, a liquid argon time projection chamber (LArTPC). The algorithms studied include the classification of single particle images, the localization of single particle and neutrino interactions in an image, and the detection of a simulated neutrino event overlaid with cosmic ray backgrounds taken from real detector data. These studies demonstrate the potential of convolutional neural networks for particle identification or event detection on simulated neutrino interactions. We also address technical issues that arise when applying this technique to data from a large LArTPC at or near ground level

Observation of nu_tau appearance in the CNGS beam with the OPERA experiment

The OPERA experiment is searching for nu_mu -> nu_tau oscillations in appearance mode i.e. via the direct detection of tau leptons in nu_tau charged current interactions. The evidence of nu_mu -> nu_tau appearance has been previously reported with three nu_tau candidate events using a sub-sample of data from the 2008-2012 runs. We report here a fourth nu_tau candidate event, with the tau decaying into a hadron, found after adding the 2012 run events without any muon in the final state to the data sample. Given the number of analysed events and the low background, nu_mu -> nu_tau oscillations are established with a significance of 4.2sigma.Comment: Submitted to Progress of Theoretical and Experimental Physics (PTEP

Emulsion sheet doublets as interface trackers for the OPERA experiment

New methods for efficient and unambiguous interconnection between electronic counters and target units based on nuclear photographic emulsion films have been developed. The application to the OPERA experiment, that aims at detecting oscillations between mu neutrino and tau neutrino in the CNGS neutrino beam, is reported in this paper. In order to reduce background due to latent tracks collected before installation in the detector, on-site large-scale treatments of the emulsions ("refreshing") have been applied. Changeable Sheet (CSd) packages, each made of a doublet of emulsion films, have been designed, assembled and coupled to the OPERA target units ("ECC bricks"). A device has been built to print X-ray spots for accurate interconnection both within the CSd and between the CSd and the related ECC brick. Sample emulsion films have been extensively scanned with state-of-the-art automated optical microscopes. Efficient track-matching and powerful background rejection have been achieved in tests with electronically tagged penetrating muons. Further improvement of in-doublet film alignment was obtained by matching the pattern of low-energy electron tracks. The commissioning of the overall OPERA alignment procedure is in progress.Comment: 19 pages, 19 figure

Measurement of the atmospheric muon charge ratio with the OPERA detector

The OPERA detector at the Gran Sasso underground laboratory (LNGS) was used to measure the atmospheric muon charge ratio in the TeV energy region. We analyzed 403069 atmospheric muons corresponding to 113.4 days of livetime during the 2008 CNGS run. We computed separately the muon charge ratio for single and for multiple muon events in order to select different energy regions of the primary cosmic ray spectrum and to test the charge ratio dependence on the primary composition. The measured charge ratio values were corrected taking into account the charge-misidentification errors. Data have also been grouped in five bins of the "vertical surface energy". A fit to a simplified model of muon production in the atmosphere allowed the determination of the pion and kaon charge ratios weighted by the cosmic ray energy spectrum.Comment: 14 pages, 10 figure

The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector

The development and operation of Liquid-Argon Time-Projection Chambers for neutrino physics has created a need for new approaches to pattern recognition in order to fully exploit the imaging capabilities offered by this technology. Whereas the human brain can excel at identifying features in the recorded events, it is a significant challenge to develop an automated, algorithmic solution. The Pandora Software Development Kit provides functionality to aid the design and implementation of pattern-recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition, in which individual algorithms each address a specific task in a particular topology. Many tens of algorithms then carefully build up a picture of the event and, together, provide a robust automated pattern-recognition solution. This paper describes details of the chain of over one hundred Pandora algorithms and tools used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE detector. Metrics that assess the current pattern-recognition performance are presented for simulated MicroBooNE events, using a selection of final-state event topologies.Comment: Preprint to be submitted to The European Physical Journal