Development of a modular test system for the silicon sensor R&D of the ATLAS Upgrade

High Voltage CMOS sensors are a promising technology for tracking detectors in collider experiments. Extensive R&D studies are being carried out by the ATLAS Collaboration for a possible use of HV-CMOS in the High Luminosity LHC upgrade of the Inner Tracker detector. CaRIBOu (Control and Readout Itk BOard) is a modular test system developed to test Silicon based detectors. It currently includes five custom designed boards, a Xilinx ZC706 development board, FELIX (Front-End LInk eXchange) PCIe card and a host computer. A software program has been developed in Python to control the CaRIBOu hardware. CaRIBOu has been used in the testbeam of the HV-CMOS sensor AMS180v4 at CERN. Preliminary results have shown that the test system is very versatile. Further development is ongoing to adapt to different sensors, and to make it available to various lab test stands

Heterocycle-containing tranylcypromine derivatives endowed with high anti-LSD1 activity

As regioisomers/bioisosteres of 1a, a 4-phenylbenzamide tranylcypromine (TCP) derivative previously disclosed by us, we report here the synthesis and biological evaluation of some (hetero)arylbenzoylamino TCP derivatives 1b-6, in which the 4-phenyl moiety of 1a was shifted at the benzamide C3 position or replaced by 2- or 3-furyl, 2- or 3-thienyl, or 4-pyridyl group, all at the benzamide C4 or C3 position. In anti-LSD1-CoREST assay, all the meta derivatives were more effective than the para analogues, with the meta thienyl analogs 4b and 5b being the most potent (IC50 values = 0.015 and 0.005 μM) and the most selective over MAO-B (selectivity indexes: 24.4 and 164). When tested in U937 AML and prostate cancer LNCaP cells, selected compounds 1a,b, 2b, 3b, 4b, and 5a,b displayed cell growth arrest mainly in LNCaP cells. Western blot analyses showed increased levels of H3K4me2 and/or H3K9me2 confirming the involvement of LSD1 inhibition in these assays

Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies

Belief, Credence and Statistical Evidence

According to the Rational Threshold View, a rational agent believes p if and only if her credence in p is equal to or greater than a certain threshold. One of the most serious challenges for this view is the problem of statistical evidence: statistical evidence is often not sufficient to make an outright belief rational, no matter how probable the target proposition is given such evidence. This indicates that rational belief is not as sensitive to statistical evidence as rational credence. The aim of this paper is twofold. First, we argue that, in addition to playing a decisive role in rationalizing outright belief, non-statistical evidence also plays a preponderant role in rationalizing credence. More precisely, when both types of evidence are present in a context, non-statistical evidence should receive a heavier weight than statistical evidence in determining rational credence. Second, based on this result, we argue that a modified version of the Rational Threshold View can avoid the problem of statistical evidence. We conclude by suggesting a possible explanation of the varying sensitivity to different types of evidence for belief and credence based on the respective aims of these attitudes

Progress on development of the new FDIRC PID detector

International audienceWe present a progress status of a new concept of PID detector called FDIRC, intended to be used at the SuperB experiment, which requires π/K separation up to a few GeV/c. The new photon camera is made of the solid fused-silica optics with a volume 25× smaller and speed increased by a factor of 10 compared to the BaBar DIRC, and therefore will be much less sensitive to electromagnetic and neutron background

Testbeam results of irradiated ams H18 HV-CMOS pixel sensor prototypes

HV-CMOS pixel sensors are a promising option for the tracker upgrade of the ATLAS experiment at the LHC, as well as for other future tracking applications in which large areas are to be instrumented with radiation-tolerant silicon pixel sensors. We present results of testbeam characterisations of the 4th generation of Capacitively Coupled Pixel Detectors (CCPDv4) produced with the ams H18 HV-CMOS process that have been irradiated with different particles (reactor neutrons and 18 MeV protons) to fluences between 1× 1014 and 5× 1015 1−MeV− neq. The sensors were glued to ATLAS FE-I4 pixel readout chips and measured at the CERN SPS H8 beamline using the FE-I4 beam telescope. Results for all fluences are very encouraging with all hit efficiencies being better than 97% for bias voltages of 85 V. The sample irradiated to a fluence of 1× 1015 neq—a relevant value for a large volume of the upgraded tracker—exhibited 99.7% average hit efficiency. The results give strong evidence for the radiation tolerance of HV-CMOS sensors and their suitability as sensors for the experimental HL-LHC upgrades and future large-area silicon-based tracking detectors in high-radiation environments

Administration of intrapulmonary sodium polyacrylate to induce lung injury for the development of a porcine model of early acute respiratory distress syndrome.

BACKGROUND: The loss of alveolar epithelial and endothelial integrity is a central component in acute respiratory distress syndrome (ARDS); however, experimental models investigating the mechanisms of epithelial injury are lacking. The purpose of the present study was to design and develop an experimental porcine model of ARDS by inducing lung injury with intrapulmonary administration of sodium polyacrylate (SPA). METHODS: The present study was performed at the Centre for Comparative Medicine, University of British Columbia, Vancouver, British Columbia. Human alveolar epithelial cells were cultured with several different concentrations of SPA; a bioluminescence technique was used to assess cell death associated with each concentration. In the anesthetized pig model (female Yorkshire X pigs (n = 14)), lung injury was caused in 11 animals (SPA group) by injecting sequential aliquots (5 mL) of 1% SPA gel in aqueous solution into the distal airway via a rubber catheter through an endotracheal tube. The SPA was dispersed throughout the lungs by manual bag ventilation. Three control animals (CON group) underwent all experimental procedures and measurements with the exception of SPA administration. RESULTS: The mean (± SD) ATP concentration after incubation of human alveolar epithelial cells with 0.1% SPA (0.92 ± 0.27 μM/well) was approximately 15% of the value found for the background control (6.30 ± 0.37 μM/well; p < 0.001). Elastance of the respiratory system (E RS) and the lung (E L) increased in SPA-treated animals after injury (p = 0.003 and p < 0.001, respectively). Chest wall elastance (E CW) did not change in SPA-treated animals. There were no differences in E RS, E L, or E CW in the CON group when pre- and post-injury values were compared. Analysis of bronchoalveolar lavage fluid showed a significant shift toward neutrophil predominance from before to after injury in SPA-treated animals (p < 0.001) but not in the CON group (p = 0.38). Necropsy revealed marked consolidation and congestion of the dorsal lung lobes in SPA-treated animals, with light-microscopy evidence of bronchiolar and alveolar spaces filled with neutrophilic infiltrate, proteinaceous debris, and fibrin deposition. These findings were absent in animals in the CON group. Electron microscopy of lung tissue from SPA-treated animals revealed injury to the alveolar epithelium and basement membranes, including intra-alveolar neutrophils and fibrin on the alveolar surface and intravascular fibrin (microthrombosis). CONCLUSIONS: In this particular porcine model, the nonimmunogenic polymer SPA caused a rapid exudative lung injury. This model may be useful to study ARDS caused by epithelial injury and inflammation

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13