1,995 research outputs found
BARD1 mediates TGF-β signaling in pulmonary fibrosis
Background
Idiopathic pulmonary fibrosis (IPF) is a rapid progressive fibro-proliferative disorder with poor prognosis similar to lung cancer. The pathogenesis of IPF is uncertain, but loss of epithelial cells and fibroblast proliferation are thought to be central processes. Previous reports have shown that BARD1 expression is upregulated in response to hypoxia and associated with TGF-β signaling, both recognized factors driving lung fibrosis. Differentially spliced BARD1 isoforms, in particular BARD1β, are oncogenic drivers of proliferation in cancers of various origins. We therefore hypothesized that BARD1 and/or its isoforms might play a role in lung fibrosis.
Methods
We investigated BARD1 expression as a function of TGF-β in cultured cells, in mice with experimentally induced lung fibrosis, and in lung biopsies from pulmonary fibrosis patients.
Results
FL BARD1 and BARD1β were upregulated in response to TGF-β in epithelial cells and fibroblasts in vitro and in vivo. Protein and mRNA expression studies showed very low expression in healthy lung tissues, but upregulated expression of full length (FL) BARD1 and BARD1β in fibrotic tissues.
Conclusion
Our data suggest that FL BARD1 and BARD1β might be mediators of pleiotropic effects of TGF-β. In particular BARD1β might be a driver of proliferation and of pulmonary fibrosis pathogenesis and progression and represent a target for treatment
A new Low Gain Avalanche Diode concept: the double-LGAD
This paper describes the new concept of the double-LGAD. The goal is to
increase the charge at the input of the electronics, keeping a time resolution
equal or better than a standard (single) LGAD; this has been realized by adding
the charges of two coupled LGADs while still using a single front-end
electronics. The study here reported has been done starting from single LGAD
with a thickness of 25 \textmu{m}, 35 \textmu{m} and 50 \textmu{m}.Comment: arXiv admin note: text overlap with arXiv:2208.0571
New Eco-gas mixtures for the Extreme Energy Events MRPCs: results and plans
The Extreme Energy Events observatory is an extended muon telescope array,
covering more than 10 degrees both in latitude and longitude. Its 59 muon
telescopes are equipped with tracking detectors based on Multigap Resistive
Plate Chamber technology with time resolution of the order of a few hundred
picoseconds. The recent restrictions on greenhouse gases demand studies for new
gas mixtures in compliance with the relative requirements. Tetrafluoropropene
is one of the candidates for tetrafluoroethane substitution, since it is
characterized by a Global Warming Power around 300 times lower than the gas
mixtures used up to now. Several mixtures have been tested, measuring
efficiency curves, charge distributions, streamer fractions and time
resolutions. Results are presented for the whole set of mixtures and operating
conditions, %. A set of tests on a real EEE telescope, with cosmic muons, are
being performed at the CERN-01 EEE telescope. The tests are focusing on
identifying a mixture with good performance at the low rates typical of an EEE
telescope.Comment: 8 pages, 6 figures, proceedings for the "XIV Workshop on Resistive
Plate Chambers and Related Detectors" (19-23 February 2018), Puerto Vallarta,
Jalisco State, Mexic
A simulation tool for MRPC telescopes of the EEE project
The Extreme Energy Events (EEE) Project is mainly devoted to the study of the
secondary cosmic ray radiation by using muon tracker telescopes made of three
Multigap Resistive Plate Chambers (MRPC) each. The experiment consists of a
telescope network mainly distributed across Italy, hosted in different building
structures pertaining to high schools, universities and research centers.
Therefore, the possibility to take into account the effects of these structures
on collected data is important for the large physics programme of the project.
A simulation tool, based on GEANT4 and using GEMC framework, has been
implemented to take into account the muon interaction with EEE telescopes and
to estimate the effects on data of the structures surrounding the experimental
apparata.A dedicated event generator producing realistic muon distributions,
detailed geometry and microscopic behavior of MRPCs have been included to
produce experimental-like data. The comparison between simulated and
experimental data, and the estimation of detector resolutions is here presented
and discussed
INFN What Next: Ultra-relativistic Heavy-Ion Collisions
This document was prepared by the community that is active in Italy, within
INFN (Istituto Nazionale di Fisica Nucleare), in the field of
ultra-relativistic heavy-ion collisions. The experimental study of the phase
diagram of strongly-interacting matter and of the Quark-Gluon Plasma (QGP)
deconfined state will proceed, in the next 10-15 years, along two directions:
the high-energy regime at RHIC and at the LHC, and the low-energy regime at
FAIR, NICA, SPS and RHIC. The Italian community is strongly involved in the
present and future programme of the ALICE experiment, the upgrade of which will
open, in the 2020s, a new phase of high-precision characterisation of the QGP
properties at the LHC. As a complement of this main activity, there is a
growing interest in a possible future experiment at the SPS, which would target
the search for the onset of deconfinement using dimuon measurements. On a
longer timescale, the community looks with interest at the ongoing studies and
discussions on a possible fixed-target programme using the LHC ion beams and on
the Future Circular Collider.Comment: 99 pages, 56 figure
Rimeporide as a first- in-class NHE-1 inhibitor: Results of a phase Ib trial in young patients with Duchenne Muscular Dystrophy
Rimeporide, a first-in-class sodium/proton exchanger Type 1 inhibitor (NHE-1 inhibitor) is repositioned by EspeRare for patients with Duchenne Muscular Dystrophy (DMD). Historically, NHE-1 inhibitors were developed for cardiac therapeutic interventions. There is considerable overlap in the pathophysiological mechanisms in Congestive Heart Failure (CHF) and in cardiomyopathy in DMD, therefore NHE-1 inhibition could be a promising pharmacological approach to the cardiac dysfunctions observed in DMD. Extensive preclinical data was collected in various animal models including dystrophin-deficient (mdx) mice to characterise Rimeporide’s anti-fibrotic and anti-inflammatory properties and there is evidence that NHE-1 inhibitors could play a significant role in modifying DMD cardiac and also skeletal pathologies, as the NHE-1 isoform is ubiquitous. We report here the first study with Rimeporide in DMD patients. This 4-week treatment, open label phase Ib, multiple oral ascending dose study, enrolled 20 ambulant boys with DMD (6–11 years), with outcomes including safety, pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers. Rimeporide was safe and well-tolerated at all doses. PK evaluations showed that Rimeporide was well absorbed orally reaching pharmacological concentrations from the lowest dose, with exposure increasing linearly with dose and with no evidence of accumulation upon repeated dosing. Exploratory PD biomarkers showed positive effect upon a 4-week treatment, supporting its therapeutic potential in patients with DMD, primarily as a cardioprotective treatment, and provide rationale for further efficacy studies
Direct detection of charged particles with SiPMs
The direct response of Silicon PhotoMultipliers being traversed by a MIP charged particle have been studied in a systematic way for the first time. Using beam test data, time resolution and the crosstalk probability have been measured. A characterization of the SiPM by means of a laser beam is also reported. The results obtained for different sensors indicate a measured time resolution around 40-70 ps. Although particles are expected to traverse only one SPAD per event, crosstalk measurements on different sensors indicate an unexpected higher value with respect to the one related to the sensor noise
Mechanisms of pulmonary fibrosis: role of activated myofibroblasts and NADPH oxidase
A common feature of pathological fibrosis involving the lung and other organs is the persistent activation of myofibroblasts in injured tissues. Recent evidence supports the role of a member of the NADPH oxidase (NOX) gene family, NOX4, in myofibroblast differentiation, matrix synthesis and contractility. Additionally, NOX4 may contribute directly or indirectly to alveolar epithelial cell death, while myofibroblasts themselves acquire an apoptosis-resistant phenotype. Thus, NOX4 may be responsible for the cardinal features of progressive fibrosis - myofibroblast activation and epithelial cell dysrepair. Therapeutic targeting of NOX4 is likely to be effective in progressive cases of fibrosis involving multiple organs
Beam test results of 25 and 35 μ m thick FBK ultra-fast silicon detectors
This paper presents the measurements on first very thin Ultra-Fast Silicon Detectors (UFSDs) produced by Fondazione Bruno Kessler; the data have been collected in a beam test setup at the CERN PS, using beam with a momentum of 12 GeV/c. UFSDs with a nominal thickness of 25 and 35 mu m and an area of 1 x 1 mm(2) have been considered, together with an additional HPK 50-mu m thick sensor, taken as reference. Their timing performances have been studied as a function of the applied voltage and gain. A time resolution of about 25 ps and of 22 ps at a voltage of 120 and 240 V has been obtained for the 25 and 35 mu m thick UFSDs, respectively
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