SerpinB3 promotes pro-fibrogenic responses in activated hepatic stellate cells

SerpinB3 is a hypoxia- and hypoxia-inducible factor-2\u3b1-dependent cystein protease inhibitor that is up-regulated in hepatocellular carcinoma and in parenchymal cells during chronic liver diseases (CLD). SerpinB3 up-regulation in CLD patients has been reported to correlate with the extent of liver fibrosis and the production of transforming growth factor-\u3b21, but the actual role of SerpinB3 in hepatic fibrogenesis is still poorly characterized. In the present study we analyzed the pro-fibrogenic action of SerpinB3 in cell cultures and in two different murine models of liver fibrosis. "In vitro" experiments revealed that SerpinB3 addition to either primary cultures of human activated myofibroblast-like hepatic stellate cells (HSC/MFs) or human stellate cell line (LX2 cells) strongly up-regulated the expression of genes involved in fibrogenesis and promoted oriented migration, but not cell proliferation. Chronic liver injury by CCl4 administration or by feeding a methionine/choline deficient diet to transgenic mice over-expressing human SerpinB3 in hepatocytes confirmed that SerpinB3 over-expression significantly increased the mRNA levels of pro-fibrogenic genes, collagen deposition and \u3b1SMA-positive HSC/MFs as compared to wild-type mice, without affecting parenchymal damage. The present study provides for the first time evidence that hepatocyte release of SerpinB3 during CLD can contribute to liver fibrogenesis by acting on HSC/MFs

Neutron irradiation test on ATLAS MDT chambers

Abstract The Monitored Drift Tubes (MDT) chambers of the ATLAS muon spectrometer are crucial for the identification of high-momentum final-state muons, which represent very promising and robust signatures of physics at the LHC. They will operate in a high rate and high background environment and therefore their performances should not significantly degrade for the whole ATLAS data taking. The maximum expected total flux, mainly consisting of neutrons and photons in the MeV range, is of the order of 5 kHz/cm 2 for the barrel MDTs, while at SLHC, with machine working at higher luminosity, fluxes can be 10 times higher. To test detector robustness, a MDT test chamber was exposed to intensive neutron irradiation at the TAPIRO ENEA-Casaccia Research Center facility

Transcatheter aortic valve implantation with the novel-generation Navitor device. Procedural and early outcomes

Transcatheter aortic valve implantation (TAVI) has proved beneficial in patients with severe aortic stenosis, especially when second-generation devices are used. We aimed at reporting our experience with Navitor, a third-generation device characterized by intrannular, large cell, and cuffed design, as well as high deliverability and minimization of paravalvular leak. Between June and December 2021, a total of 39 patients underwent TAVI with Navitor, representing 20% of all TAVI cases. Mean age was 80.0 +/- 6.7 years, and 14 (36.8%) women were included. Severe aortic stenosis was the most common indication to TAVI (37 [97.4%] cases), whereas 2 (5.3%) individuals were at low surgical risk. Device and procedural success was obtained in all patients, with a total hospital stay of 6.6 +/- 4.5 days. One (2.9%) patient required permanent pacemaker implantation, but no other hospital events occurred. At 1-month follow-up, a cardiac death was adjudicated in an 87-year-old man who had been at high surgical risk. Echocardiographic follow-up showed no case of moderate or severe aortic regurgitation, with mild regurgitation in 18 (47%), and none or trace regurgitation in 20 (53%). The Navitor device, thanks to its unique features, is a very promising technology suitable to further expand indications and risk-benefit profile of TAVI

Measurement of {\eta} meson production in {\gamma}{\gamma} interactions and {\Gamma}({\eta}-->{\gamma}{\gamma}) with the KLOE detector

We present a measurement of {\eta} meson production in photon-photon interactions produced by electron-positron beams colliding with \sqrt{s}=1 GeV. The measurement is done with the KLOE detector at the \phi-factory DA{\Phi}NE with an integrated luminosity of 0.24 fb^{-1}. The e^+e^- --> e^+e^-{\eta} cross section is measured without detecting the outgoing electron and positron, selecting the decays {\eta}-->{\pi}^+{\pi}^-{\pi}^0 and {\eta}-->{\pi}^0{\pi}^0{\pi}^0. The most relevant background is due to e^+e^- --> {\eta}{\gamma} when the monochromatic photon escapes detection. The cross section for this process is measured as {\sigma}(e^+e^- -->{\eta}{\gamma}) = (856 \pm 8_{stat} \pm 16_{syst}) pb. The combined result for the e^+e^- -->e^+e^-{\eta} cross section is {\sigma}(e^+e^- -->e^+e^-{\eta}) = (32.72 \pm 1.27_{stat} \pm 0.70_{syst}) pb. From this we derive the partial width {\Gamma}({\eta}-->{\gamma}{\gamma}) = (520 \pm 20_{stat} \pm 13_{syst}) eV. This is in agreement with the world average and is the most precise measurement to date.Comment: Version accepted by JHE

A new limit on the CP violating decay KS -> 3pi0 with the KLOE experiment

We have carried out a new direct search for the CP violating decay KS -> 3pi0 with 1.7 fb^-1 of e+e- collisions collected by the KLOE detector at the phi-factory DAFNE. We have searched for this decay in a sample of about 5.9 x 10^8 KS KL events tagging the KS by means of the KL interaction in the calorimeter and requiring six prompt photons. With respect to our previous search, the analysis has been improved by increasing of a factor four the tagged sample and by a more effective background rejection of fake KS tags and spurious clusters. We find no candidates in data and simulated background samples, while we expect 0.12 standard model events. Normalizing to the number of KS -> 2pi0 events in the same sample, we set the upper limit on BR(KS -> 3pi0 < 2.6 x 10^-8 at 90% C.L., five times lower than the previous limit. We also set the upper limit on the eta_000 parameter, |eta_000 | < 0.0088 at 90% C.L., improving by a factor two the latest direct measurement.Comment: Accepted for publication in Physics Letters B (15 pages, 13 figures

Measurement of \Gamma(\eta -> \pi^+\pi^-\gamma)/\Gamma(\eta -> \pi^+\pi^-\pi^0) with the KLOE Detector

The ratio R_{\eta}=\Gamma(\eta -> \pi^+\pi^-\gamma)/\Gamma(\eta -> \pi^+\pi^-\pi^0) has been measured by analyzing 22 million \phi \to \eta \gamma decays collected by the KLOE experiment at DA\PhiNE, corresponding to an integrated luminosity of 558 pb^{-1}. The \eta \to \pi^+\pi^-\gamma proceeds both via the \rho resonant contribution, and possibly a non-resonant direct term, connected to the box anomaly. Our result, R_{\eta}= 0.1856\pm 0.0005_{stat} \pm 0.0028_{syst}, points out a sizable contribution of the direct term to the total width. The di-pion invariant mass for the \eta -> \pi^+\pi^-\gamma decay could be described in a model-independent approach in terms of a single free parameter, \alpha. The determined value of the parameter \alpha is \alpha = (1.32 \pm 0.08_{stat} +0.10/-0.09_{syst}\pm 0.02_{theo}) GeV^{-2}Comment: Paper in press, accepted by PL

KLOE results in kaon physics and prospects for KLOE-2

The phi-factory DAPHNE offers a possibility to select pure kaon beams, charged and neutral ones. In particular, neutral kaons from phi->KS KL are produced in pairs and the detection of a KS (KL) tags the presence of a KL (KS). This allows to perform precise measurements of kaon properties by means of KLOE detector. Another advantage of a phi-factory consists in fact that the neutral kaon pairs are produced in a pure quantum state (J^(PC) = 1^(--)), which allowsto investigate CP and CPT symmetries via quantum interference effects, as well as the basic principles of quantum mechanics.A review of the most recent results of the KLOE experiment at DAPHNE using pure kaon beams or via quantum interferometry is presented together with prospects for kaon physics at KLOE-2.Comment: 5 pages, 4 figures, From Phi To Psi 2011 conference, to be published in Nuclear Physics B (Proceedings Supplements

Cx26 partial loss causes accelerated presbycusis by redox imbalance and dysregulation of Nfr2 pathway.

Mutations in GJB2, the gene that encodes connexin 26 (Cx26), are the most common cause of sensorineural hearing impairment. The truncating variant 35delG, which determines a complete loss of Cx26 protein function, is the prevalent GJB2 mutation in several populations. Here, we generated and analyzed Gjb2+/- mice as a model of heterozygous human carriers of 35delG. Compared to control mice, auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) worsened over time more rapidly in Gjb2+/- mice, indicating they were affected by accelerated age-related hearing loss (ARHL), or presbycusis. We linked causally the auditory phenotype of Gjb2+/- mice to apoptosis and oxidative damage in the cochlear duct, reduced release of glutathione from connexin hemichannels, decreased nutrient delivery to the sensory epithelium via cochlear gap junctions and deregulated expression of genes that are under transcriptional control of the nuclear factor erythroid 2-related factor 2 (Nrf2), a pivotal regulator of tolerance to redox stress. Moreover, a statistically significant genome-wide association with two genes (PRKCE and TGFB1) related to the Nrf2 pathway (p-value &lt; 4\u202f 7 10-2) was detected in a very large cohort of 4091 individuals, originating from Europe, Caucasus and Central Asia, with hearing phenotype (including 1076 presbycusis patients and 1290 healthy matched controls). We conclude that (i) elements of the Nrf2 pathway are essential for hearing maintenance and (ii) their dysfunction may play an important role in the etiopathogenesis of human presbycusis

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal