Anti-fibroblast antibodies detected by cell-based ELISA in systemic sclerosis enhance the collagenolytic activity and matrix metalloproteinase-1 production in dermal fibroblasts

Objectives. Antibodies binding to the surface of fibroblasts (anti-fibroblast antibodies: AFA) have been described in systemic sclerosis (SSc). We aimed to assess the effect of AFA on extracellular matrix (ECM) turnover and whether AFA were associated with anti-topoisomerase-I antibody. Methods. IgG were purified from AFA-positive and AFA-negative sera selected within 20 SSc and 20 healthy individuals, and tested on normal dermal fibroblasts, at protein and mRNA level, for their capacity to induce collagen deposition or degradation. Results. Fibroblasts stimulated with AFA-positive but not with AFA-negative and control IgG showed an increased capacity to digest collagen matrix and produce metalloproteinase-1 (MMP-1) while their production of total collagen, type I collagen and tissue inhibitor of metalloproteinase-1 (TIMP-1) was unaffected. The steady-state mRNA levels of MMP-1, COL1A1 and TIMP-1 paralleled the protein levels. AFA-positive IgG did not induce Smad 2/3 phosphorylation, indicating that this transforming growth factor-β signalling pathway was not involved. IL-1 and tumour necrosis factor (TNF) neutralization did not reverse the enhanced production of MMP-1, suggesting a direct effect of AFA on fibroblasts. Finally, anti-topoisomerase-I antibodies were present in 11 of 12 AFA-negative IgG, and an anti-topoisomerase-I monoclonal antibody failed to enhance MMP-1 production, thus indicating a lack of correlation between AFA and anti-topoisomerase-I antibody. Conclusions. These results indicate that SSc antibodies binding to fibroblasts enhance matrix degradation and MMP production events that may favour inflammation but do not directly impact on fibrosis developmen

New experimental limits on the Pauli forbidden transitions in 12^{12}C nuclei obtained with 485 days Borexino data

The Pauli exclusion principle (PEP) has been tested for nucleons ($n,p$) in $^{12}C$ with the Borexino detector.The approach consists of a search for $\gamma$, $n$, $p$ and $\beta^\pm$ emitted in a non-Paulian transition of 1$P_{3/2}$- shell nucleons to the filled 1$S_{1/2}$ shell in nuclei. Due to the extremely low background and the large mass (278 t) of the Borexino detector, the following most stringent up-to-date experimental bounds on PEP violating transitions of nucleons have been established: $\tau({^{12}\rm{C}}\to{^{12}\widetilde{\rm{C}}}+\gamma) \geq 5.0\cdot10^{31}$ y, $\tau({^{12}\rm{C}}\to{^{11}\widetilde{\rm{B}}}+ p) \geq 8.9\cdot10^{29}$ y, $\tau({^{12}\rm{C}}\to{^{11}\widetilde{\rm{C}}}+ n) \geq 3.4 \cdot 10^{30}$ y, $\tau({^{12}\rm{C}}\to{^{12}\widetilde{\rm{N}}}+ e^- + \widetilde{\nu_e}) \geq 3.1\cdot 10^{30}$ y and $\tau({^{12}\rm{C}}\to{^{12}\widetilde{\rm{B}}}+ e^+ + \nu_e) \geq 2.1 \cdot 10^{30}$ y, all at 90% C.L. The corresponding upper limits on the relative strengths for the searched non-Paulian electromagnetic, strong and weak transitions have been estimated: $\delta^2_{\gamma} \leq 2.2\cdot10^{-57}$, $\delta^2_{N} \leq 4.1\cdot10^{-60}$ and $\delta^2_{\beta} \leq 2.1\cdot10^{-35}$.Comment: 9 pages, 6 figure

New limits on heavy sterile neutrino mixing in 8B{^{8}\rm{B}}-decay obtained with the Borexino detector

If heavy neutrinos with mass $m_{\nu_{H}}\geq$2$m_e$ are produced in the Sun via the decay ${^8\rm{B}} \rightarrow {^8\rm{Be}} + e^+ + \nu_H$ in a side branch of pp-chain, they would undergo the observable decay into an electron, a positron and a light neutrino $\nu_{H}\rightarrow\nu_{L}+e^++e^-$. In the present work Borexino data are used to set a bound on the existence of such decays. We constrain the mixing of a heavy neutrino with mass 1.5 MeV $\leq m_{\nu_{H}} \le$ 14 MeV to be $|U_{eH}|^2\leq (10^{-3}-4\times10^{-6})$ respectively. These are tighter limits on the mixing parameters than obtained in previous experiments at nuclear reactors and accelerators.Comment: 7 pages, 6 figure

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 well as further validation of the LMA-MSW model of neutrino oscillations.Comment: Proceedings from NOW (Neutrino Oscillation Workshop) 201

The Main Results of the Borexino Experiment

The main physical results on the registration of solar neutrinos and the search for rare processes obtained by the Borexino collaboration to date are presented.Comment: 8 pages, 8 figgures, To be published as Proceedings of the Third Annual Large Hadron Collider Physics Conference, St. Petersburg, Russia, 201

Solar neutrino with Borexino: results and perspectives

Borexino is a unique detector able to perform measurement of solar neutrinos fluxes in the energy region around 1 MeV or below due to its low level of radioactive background. It was constructed at the LNGS underground laboratory with a goal of solar $^{7}$Be neutrino flux measurement with 5\% precision. The goal has been successfully achieved marking the end of the first stage of the experiment. A number of other important measurements of solar neutrino fluxes have been performed during the first stage. Recently the collaboration conducted successful liquid scintillator repurification campaign aiming to reduce main contaminants in the sub-MeV energy range. With the new levels of radiopurity Borexino can improve existing and challenge a number of new measurements including: improvement of the results on the Solar and terrestrial neutrino fluxes measurements; measurement of pp and CNO solar neutrino fluxes; search for non-standard interactions of neutrino; study of the neutrino oscillations on the short baseline with an artificial neutrino source (search for sterile neutrino) in context of SOX project.Comment: 15 pages, 4 figure

Borexino calibrations: Hardware, Methods, and Results

Borexino was the first experiment to detect solar neutrinos in real-time in the sub-MeV region. In order to achieve high precision in the determination of neutrino rates, the detector design includes an internal and an external calibration system. This paper describes both calibration systems and the calibration campaigns that were carried out in the period between 2008 and 2011. We discuss some of the results and show that the calibration procedures preserved the radiopurity of the scintillator. The calibrations provided a detailed understanding of the detector response and led to a significant reduction of the systematic uncertainties in the Borexino measurements

CP asymmetry in B→ϕKSB \to \phi K_S in a general two-Higgs-doublet model with fourth-generation quarks

We discuss the time-dependent CP asymmetry of decay $B \to \phi K_S$ in an extension of the Standard Model with both two Higgs doublets and additional fourth-generation quarks. We show that although the Standard Model with two-Higgs-doublet and the Standard model with fourth generation quarks alone are not likely to largely change the effective $\sin 2 \beta$ from the decay of $B \to \phi K_S$, the model with both additional Higgs doublet and fourth-generation quarks can easily account for the possible large negative value of $\sin 2 \beta$ without conflicting with other experimental constraints. In this model, additional large CP violating effects may arise from the flavor changing Yukawa interactions between neutral Higgs bosons and the heavy fourth generation down type quark, which can modify the QCD penguin contributions. With the constraints obtained from $b \to s \bar{s} s$ processes such as $B \to X_s \gamma$ and $\Delta m_{B_s^0}$, this model can lead to the effective $\sin 2 \beta$ to be as large as $- 0.4$ in the CP asymmetry of $B \to \phi K_S$.Comment: 13 pages, 5 figures, references added, to appear in Eur.Phys.J.

Light Sterile Neutrinos: A White Paper

This white paper addresses the hypothesis of light sterile neutrinos based on recent anomalies observed in neutrino experiments and the latest astrophysical data