Ca2+ signalling plays a role in celastrol‐mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in rats

Background and purpose Celastrol exhibits anti-arthritic effects in rheumatoid arthritis (RA), but the role of celastrol-mediated Ca2+ mobilization in treatment of RA remains undefined. Here, we describe a regulatory role for celastrol-induced Ca2+ signalling in synovial fibroblasts of RA patients and adjuvant-induced arthritis (AIA) in rats. Experimental approach We used computational docking, Ca2+ dynamics and functional assays to study the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA). In rheumatoid arthritis synovial fibroblasts (RASFs)/rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), mechanisms of Ca2+ -mediated autophagy were analysed by histological, immunohis…

Understanding the Giant Enhancement of Exchange Interaction in Bi2Se3−EuS Heterostructures

A recent experiment indicated that a ferromagnetic EuS film in contact with a topological insulator ${\mathrm{Bi}}_{2}{\mathrm{Se}}_{3}$ might show a largely enhanced Curie temperature and perpendicular magnetic anisotropy [F. Katmis et al., Nature (London) 533, 513 (2016).]. Through systematic density functional calculations, we demonstrate that in addition to the factor that ${\mathrm{Bi}}_{2}{\mathrm{Se}}_{3}$ has a strong spin orbit coupling, the topological surface states are crucial to make these unusual behaviors robust as they hybridize with EuS states and extend rather far into the magnetic layers. The magnetic moments of Eu atoms are nevertheless not much enhanced, unlike what was…

First results on ProtoDUNE-SP liquid argon time projection chamber performance from a beam test at the CERN Neutrino Platform

The ProtoDUNE-SP detector was constructed and operated on the CERN Neutrino Platform. We thank the CERN management for providing the infrastructure for this experiment and gratefully acknowledge the support of the CERN EP, BE, TE, EN, IT and IPT Departments for NP04/ProtoDUNE-SP. This documentwas prepared by theDUNEcollaboration using the resources of the Fermi National Accelerator Laboratory (Fermilab), a U.S. Department of Energy, Office of Science, HEP User Facility. Fermilab is managed by Fermi Research Alliance, LLC (FRA), acting under Contract No. DE-AC02-07CH11359. This work was supported by CNPq, FAPERJ, FAPEG and FAPESP, Brazil; CFI, IPP and NSERC, Canada; CERN; MSMT, Czech Republi…

Neutrino interaction classification with a convolutional neural network in the DUNE far detector

The Deep Underground Neutrino Experiment is a next-generation neutrino oscillation experiment that aims to measure CP-violation in the neutrino sector as part of a wider physics program. A deep learning approach based on a convolutional neural network has been developed to provide highly efficient and pure selections of electron neutrino and muon neutrino charged-current interactions. The electron neutrino (antineutrino) selection efficiency peaks at 90% (94%) and exceeds 85% (90%) for reconstructed neutrino energies between 2–5 GeV. The muon neutrino (antineutrino) event selection is found to have a maximum efficiency of 96% (97%) and exceeds 90% (95%) efficiency for reconstructed neutrino…

Observation of a Near-Threshold Structure in the K+ Recoil-Mass Spectra in e+e−→K+(Ds−D*0+Ds*−D0)

We report a study of the processes of e^{+}e^{-}→K^{+}D_{s}^{-}D^{*0} and K^{+}D_{s}^{*-}D^{0} based on e^{+}e^{-} annihilation samples collected with the BESIII detector operating at BEPCII at five center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7  fb^{-1}. An excess of events over the known contributions of the conventional charmed mesons is observed near the D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0} mass thresholds in the K^{+} recoil-mass spectrum for events collected at sqrt[s]=4.681  GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5_{-2.6}^{+1.8}±2.1)  MeV/c^{2} and (…

Physics reach of the XENON1T dark matter experiment.

The XENON1T experiment is currently in the commissioning phase at the Laboratori Nazionali del Gran Sasso, Italy. In this article we study the experiment's expected sensitivity to the spin-independent WIMP-nucleon interaction cross section, based on Monte Carlo predictions of the electronic and nuclear recoil backgrounds. The total electronic recoil background in $1$ tonne fiducial volume and ($1$, $12$) keV electronic recoil equivalent energy region, before applying any selection to discriminate between electronic and nuclear recoils, is $(1.80 \pm 0.15) \cdot 10^{-4}$ ($\rm{kg} \cdot day \cdot keV)^{-1}$, mainly due to the decay of $^{222}\rm{Rn}$ daughters inside the xenon target. The nu…

Short distance neutrino oscillations with Borexino

International audience; The Borexino detector has convincingly shown its outstanding performances in the low energy, sub-MeV regime through its unprecedented accomplishments in the solar and geo-neutrinos detection. These performances make it the ideal tool to accomplish a state-of-the-art experiment able to test unambiguously the long-standing issue of the existence of a sterile neutrino, as suggested by the several anomalous results accumulated over the past two decades, i.e. the outputs of the LSND and Miniboone experiments, the results of the source calibration of the two Gallium solar neutrino experiments, and the recently hinted reactor anomaly. The SOX project will exploit two source…

The Potential of Serum Exosomal hsa_circ_0028861 as the Novel Diagnostic Biomarker of HBV-Derived Hepatocellular Cancer

Hepatitis B virus (HBV)-derived hepatocellular cancer (HCC) is a serious threat to human health, especially in China. There is no highly sensitive and specific HCC biomarker at present, which makes it difficult to detect HCC at the early stage. Serum exosomal circular RNAs (circRNAs) have been reported as novel diagnostic and prognostic biomarkers of cancers. In the present study, we aimed to explore the diagnostic performance of serum exosomal circRNAs for HBV-derived HCC screening. At first, many circRNAs were found to be differentially expressed in the serum exosomes of HCC individuals by microarray analysis. The validation of dysregulated circRNAs by qRT-PCR revealed that serum exosomal…

First real–time detection of solar pp neutrinos by Borexino

International audience; Solar neutrinos have been pivotal to the discovery of neutrino flavour oscillations and are a unique tool to probe the reactions that keep the Sun shine. Although most of solar neutrino components have been directly measured, the neutrinos emitted by the keystone pp reaction, in which two protons fuse to make a deuteron, have so far eluded direct detection. The Borexino experiment, an ultra-pure liquid scintillator detector running at the Laboratori Nazionali del Gran Sasso in Italy, has now filled the gap, providing the first direct real time measurement of pp neutrinos and of the solar neutrino luminosity.

A test of electric charge conservation with Borexino

Borexino is a liquid scintillation detector located deep underground at the Laboratori Nazionali del Gran Sasso (LNGS, Italy). Thanks to the unmatched radio-purity of the scintillator, and to the well understood detector response at low energy, a new limit on the stability of the electron for decay into a neutrino and a single mono-energetic photon was obtained. This new bound, tau > 6.6 10**28 yr at 90 % C.L., is two orders of magnitude better than the previous limit.

Ultrasensitive and highly specific detection of iodine ions using zirconium (IV)-enhanced oxidation

Nuclear energy has significantly promoted the development of human society. However, nuclear pollution caused by nuclear accidents can lead to significant hazards to the environment and human health. As a major radioactive product, radioactive iodine (mainly existing as I−) detection has attracted significant attentions. In this study, zirconium(IV) is used to enhance the oxidation of environmental I− to form I2. Subsequently, the generated I2 oxidizes the chemical chromogenic substrate 3,3′,5,5′-tetramethylbenzidine, which is used for I− detection and realizes an ultralow limit of detection (LoD) of 0.176 nM. The LoD of our method, to the best of our knowledge, is the lowest among those of…

Erratum: Study of the electromagnetic background in the XENON100 experiment [Phys. Rev. D 83, 082001 (2011)]

The neutron background of the XENON100 dark matter search experiment

TheXENON100 experiment, installed underground at the LaboratoriNazionali del Gran Sasso, aims to directly detect dark matter in the form of weakly interacting massive particles (WIMPs) via their elastic scattering off xenon nuclei. This paper presents a study on the nuclear recoil background of the experiment, taking into account neutron backgrounds from (alpha, n) reactions and spontaneous fission due to natural radioactivity in the detector and shield materials, as well as muon-induced neutrons. Based on MonteCarlo simulations and using measured radioactive contaminations of all detector components, we predict the nuclear recoil backgrounds for the WIMP search results published by theXENO…

Limits on spin-dependent WIMP-nucleon cross sections from 225 live days of XENON100 data

We present new experimental constraints on the elastic, spin-dependent WIMP-nucleon cross section using recent data from the XENON100 experiment, operated in the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 224.6 live days x 34 kg of exposure acquired during 2011 and 2012 revealed no excess signal due to axial-vector WIMP interactions with 129-Xe and 131-Xe nuclei. This leads to the most stringent upper limits on WIMP-neutron cross sections for WIMP masses above 6 GeV, with a minimum cross section of 3.5 x 10^{-40} cm^2 at a WIMP mass of 45 GeV, at 90% confidence level.

Recent Borexino results and prospects for the near future

The Borexino experiment, located in the Gran Sasso National Laboratory, is an organic liquid scintillator detector conceived for the real time spectroscopy of low energy solar neutrinos. The data taking campaign phase I (2007 - 2010) has allowed the first independent measurements of 7Be, 8B and pep fluxes as well as the first measurement of anti-neutrinos from the earth. After a purification of the scintillator, Borexino is now in phase II since 2011. We review here the recent results achieved during 2013, concerning the seasonal modulation in the 7Be signal, the study of cosmogenic backgrounds and the updated measurement of geo-neutrinos. We also review the upcoming measurements from phase…

Implications on inelastic dark matter from 100 live days of XENON100 data

The XENON100 experiment has recently completed a dark matter run with 100.9 live-days of data, taken from January to June 2010. Events in a 48kg fiducial volume in the energy range between 8.4 and 44.6 keVnr have been analyzed. A total of three events have been found in the predefined signal region, compatible with the background prediction of (1.8 \pm 0.6) events. Based on this analysis we present limits on the WIMP-nucleon cross section for inelastic dark matter. With the present data we are able to rule out the explanation for the observed DAMA/LIBRA modulation as being due to inelastic dark matter scattering off iodine at a 90% confidence level.

Observation and applications of single-electron charge signals in the XENON100 experiment

The XENON100 dark matter experiment uses liquid xenon in a time projection chamber (TPC) to measure xenon nuclear recoils resulting from the scattering of dark matter Weakly Interacting Massive Particles (WIMPs). In this paper, we report the observation of single-electron charge signals which are not related to WIMP interactions. These signals, which show the excellent sensitivity of the detector to small charge signals, are explained as being due to the photoionization of impurities in the liquid xenon and of the metal components inside the TPC. They are used as a unique calibration source to characterize the detector. We explain how we can infer crucial parameters for the XENON100 experim…

Dark matter results from 225 live days of XENON100 data

We report on a search for particle dark matter with the XENON100 experiment, operated at the Laboratori Nazionali del Gran Sasso (LNGS) for 13 months during 2011 and 2012. XENON100 features an ultra-low electromagnetic background of (5.3 \pm 0.6) \times 10^-3 events (kg day keVee)^-1 in the energy region of interest. A blind analysis of 224.6 live days \times 34 kg exposure has yielded no evidence for dark matter interactions. The two candidate events observed in the pre-defined nuclear recoil energy range of 6.6-30.5 keVnr are consistent with the background expectation of (1.0 \pm 0.2) events. A Profile Likelihood analysis using a 6.6-43.3 keVnr energy range sets the most stringent limit o…

Low-energy (anti)neutrino physics with Borexino: Neutrinos from the primary proton-proton fusion process in the Sun

The Sun is fueled by a series of nuclear reactions that produce the energy that makes it shine. The primary reaction is the fusion of two protons into a deuteron, a positron and a neutrino. These neutrinos constitute the vast majority of neutrinos reaching Earth, providing us with key information about what goes on at the core of our star. Several experiments have now confirmed the observation of neutrino oscillations by detecting neutrinos from secondary nuclear processes in the Sun; this is the first direct spectral measurement of the neutrinos from the keystone proton-proton fusion. This observation is a crucial step towards the completion of the spectroscopy of pp-chain neutrinos, as we…

An Early Stage Researcher's Primer on Systems Medicine Terminology

Background: Systems Medicine is a novel approach to medicine, that is, an interdisciplinary field that considers the human body as a system, composed of multiple parts and of complex relationships at multiple levels, and further integrated into an environment. Exploring Systems Medicine implies understanding and combining concepts coming from diametral different fields, including medicine, biology, statistics, modeling and simulation, and data science. Such heterogeneity leads to semantic issues, which may slow down implementation and fruitful interaction between these highly diverse fields. Methods: In this review, we collect and explain more than100 terms related to Systems Medicine. Thes…

Reduced Rivaroxaban Dose Versus Dual Antiplatelet Therapy After Left Atrial Appendage Closure: ADRIFT a Randomized Pilot Study.

Background: Percutaneous left atrial appendage closure (LAAC) exposes to the risk of device thrombosis in patients with atrial fibrillation who frequently have a contraindication to full anticoagulation. Thereby, dual antiplatelet therapy (DAPT) is usually preferred. No randomized study has evaluated nonvitamin K antagonist oral anticoagulant after LAAC, and we decided to evaluate the efficacy and safety of reduced doses of rivaroxaban after LAAC. Methods: ADRIFT (Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure) is a multicenter, phase IIb study, which randomized 105 patients after successful LAAC to eith…

SOX : short distance neutrino oscillations with Borexino

Abstract The Borexino detector has convincingly shown its outstanding performance in the in the sub-MeV regime through its unprecedented accomplishments in the solar and geo-neutrinos detection, which make it the ideal tool to unambiguously test the long-standing issue of the existence of a sterile neutrino, as suggested by several anomalies: the outputs of the LSND and Miniboone experiments, the results of the source calibration of the two Gallium solar ν experiments, and the recently hinted reactor anomaly. The SOX project will exploit two sources, based on chromium and cerium, which deployed under the experiment will emit two intense beams of ν e (Cr) and ν e ‾ (Ce). Interacting in the a…

The distributed Slow Control System of the XENON100 experiment

The XENON100 experiment, in operation at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy, was designed to search for evidence of dark matter interactions inside a volume of liquid xenon using a dual-phase time projection chamber. This paper describes the Slow Control System (SCS) of the experiment with emphasis on the distributed architecture as well as on its modular and expandable nature. The system software was designed according to the rules of Object-Oriented Programming and coded in Java, thus promoting code reusability and maximum flexibility during commissioning of the experiment. The SCS has been continuously monitoring the XENON100 detector since mid 2008, remotely recordi…

Analysis of the XENON100 dark matter search data

The XENON100 experiment, situated in the Laboratori Nazionali del Gran Sasso, aims at the direct detection of dark matter in the form of weakly interacting massive particles (WIMPs), based on their interactions with xenon nuclei in an ultra low background dual-phase time projection chamber. This paper describes the general methods developed for the analysis of the XENON100 data. These methods have been used in the 100.9 and 224.6 live days science runs from which results on spin-independent elastic, spin-dependent elastic and inelastic WIMP-nucleon cross-sections have already been reported.