Autoantigenic properties of the aminoacyl tRNA synthetase family in idiopathic inflammatory myopathies

Objectives: Autoantibodies are thought to play a key role in the pathogenesis of idiopathic inflammatory myopathies (IIM). However, up to 40% of IIM patients, even those with clinical manifestations of anti-synthetase syndrome (ASSD), test seronegative to known myositis-specific autoantibodies. We hypothesized the existence of new potential autoantigens among human cytoplasmic aminoacyl tRNA synthetases (aaRS) in patients with IIM. Methods: Plasma samples from 217 patients with IIM according to 2017 EULAR/ACR criteria, including 50 patients with ASSD, 165 without, and two with unknown ASSD status were identified retrospectively, as well as age and gender-matched sera from 156 population controls, and 219 disease controls. Patients with previously documented ASSD had to test positive for at least one of the five most common anti-aaRS autoantibodies (anti-Jo1, -PL7, -PL12, -EJ, and -OJ) and present with one or more of the following clinical manifestations: interstitial lung disease, myositis, arthritis, Raynaud's phenomenon, fever, or mechanic's hands. Demographics, laboratory, and clinical data of the IIM cohort (ASSD and non-ASSD) were compared. Samples were screened using a multiplex bead array assay for presence of autoantibodies against a panel of 117 recombinant protein variants, representing 33 myositis-related proteins, including all nineteen cytoplasmic aaRS. Prospectively collected clinical data for the IIM cohort were retrieved and compared between groups within the IIM cohort and correlated with the results of the autoantibody screening. Principal component analysis was used to analyze clinical manifestations between ASSD, non-ASSD groups, and individuals with novel anti-aaRS autoantibodies. Results: We identified reactivity towards 16 aaRS in 72 of the 217 IIM patients. Twelve patients displayed reactivity against nine novel aaRS. The novel autoantibody specificities were detected in four previously seronegative patients for myositis-specific autoantibodies and eight with previously detected myositis-specific autoantibodies. IIM individuals with novel anti-aaRS autoantibodies (n = 12) all had signs of myositis, and they had either muscle weakness and/or muscle enzyme elevation, 2/12 had mechanic's hands, 3/12 had interstitial lung disease, and 2/12 had arthritis. The individuals with novel anti-aaRS and a pathological muscle biopsy all presented widespread up-regulation of major histocompatibility complex class I. The reactivities against novel aaRS could be confirmed in ELISA and western blot. Using the multiplex bead array assay, we could confirm previously known reactivities to four of the most common aaRS (Jo1, PL12, PL7, and EJ (n = 45)) and identified patients positive for anti-Zo, -KS, and -HA (n = 10) that were not previously tested. A low frequency of anti-aaRS autoantibodies was also detected in controls. Conclusion: Our results suggest that most, if not all, cytoplasmic aaRS may become autoantigenic. Autoantibodies against new aaRS may be found in plasma of patients previously classified as seronegative with potential high clinical relevance.publishedVersio

Status of the Super-B factory Design

The SuperB international team continues to optimize the design of an electron-positron collider, which will allow the enhanced study of the origins of flavor physics. The project combines the best features of a linear collider (high single-collision luminosity) and a storage-ring collider (high repetition rate), bringing together all accelerator physics aspects to make a very high luminosity of 10$^{36}$ cm$^{-2}$ sec$^{-1}$. This asymmetric-energy collider with a polarized electron beam will produce hundreds of millions of B-mesons at the $\Upsilon$(4S) resonance. The present design is based on extremely low emittance beams colliding at a large Piwinski angle to allow very low $\beta_y^\star$ without the need for ultra short bunches. Use of crab-waist sextupoles will enhance the luminosity, suppressing dangerous resonances and allowing for a higher beam-beam parameter. The project has flexible beam parameters, improved dynamic aperture, and spin-rotators in the Low Energy Ring for longitudinal polarization of the electron beam at the Interaction Point. Optimized for best colliding-beam performance, the facility may also provide high-brightness photon beams for synchrotron radiation applications

First AGILE Catalog of High Confidence Gamma-Ray Sources

We present the first catalog of high-confidence gamma-ray sources detected by the AGILE satellite during observations performed from July 9, 2007 to June 30, 2008. Catalogued sources are detected by merging all the available data over the entire time period. AGILE, launched in April 2007, is an ASI mission devoted to gamma-ray observations in the 30 MeV - 50 GeV energy range, with simultaneous X-ray imaging capability in the 18-60 keV band. This catalog is based on Gamma-Ray Imaging Detector (GRID) data for energies greater than 100 MeV. For the first AGILE catalog we adopted a conservative analysis, with a high-quality event filter optimized to select gamma-ray events within the central zone of the instrument Field of View (radius of 40 degrees). This is a significance-limited (4 sigma) catalog, and it is not a complete flux-limited sample due to the non-uniform first year AGILE sky coverage. The catalog includes 47 sources, 21 of which are associated with confirmed or candidate pulsars, 13 with Blazars (7 FSRQ, 4 BL Lacs, 2 unknown type), 2 with HMXRBs, 2 with SNRs, 1 with a colliding-wind binary system, 8 with unidentified sources.Comment: Revised version, 15 pages, 3 figures, 3 tables. To be published in Astronomy and Astrophysics. Text improved and clarified. Refined analysis of complex regions of the Galactic plane yields a new list of high-confidence sources including 47 sources (compared with the 40 sources appearing in the first version

Integrating the BeppoSAX Gamma-Ray Burst Monitor into the 3rd Interplanetary Network

We have added the BeppoSAX Gamma-Ray Burst Monitor to the 3rd Interplanetary Network of burst detectors. We analyze 16 bursts whose positions are known to good accuracy from measurements at other wavelengths. We show that there is excellent agreement between the Ulysses/BeppoSAX triangulation annuli and the known positions of these events, and that these annuli can in many cases provide useful constraints on the positions of bursts detected by the BeppoSAX Wide Field Camera and Narrow Field Instruments.Comment: 16 pages, 18 figures, submitted to the Astrophysical Journa

Baseline Design of the SuperB Factory Injection System

TUPPR088International audienceThe injection complex of the SuperB, B-factory project of INFN consists of a polarized electron gun, a positron production system, electron and positron linac sections, a positron damping ring and the transfer lines connecting these systems and the collider main rings. To keep the ultra high luminosity nearly constant, continuous injection of 4 GeV electrons and 7 GeV positrons in both Low Energy Ring (LER) and High Energy Ring (HER) is necessary. In this paper we describe the baseline design and the beam dynamics studies performed to evaluate the system performance

AGILE detection of delayed gamma-ray emission from GRB 080514B

GRB 080514B is the first gamma ray burst (GRB), since the time of EGRET, for which individual photons of energy above several tens of MeV have been detected with a pair-conversion tracker telescope. This burst was discovered with the Italian AGILE gamma-ray satellite. The GRB was localized with a cooperation by AGILE and the interplanetary network (IPN). The gamma-ray imager (GRID) estimate of the position, obtained before the SuperAGILE-IPN localization, is found to be consistent with the burst position. The hard X-ray emission observed by SuperAGILE lasted about 7 s, while there is evidence that the emission above 30 MeV extends for a longer duration (at least ~13 s). Similar behavior was seen in the past from a few other GRBs observed with EGRET. However, the latter measurements were affected, during the brightest phases, by instrumental dead time effects, resulting in only lower limits to the burst intensity. Thanks to the small dead time of the AGILE/GRID we could assess that in the case of GRB 080514B the gamma-ray to X-ray flux ratio changes significantly between the prompt and extended emission phase.Comment: A&A letters, in pres

Multiwavelength observations of 3C 454.3. I. The AGILE 2007 November campaign on the "Crazy Diamond"

[Abridged] We report on a multiwavelength observation of the blazar 3C 454.3 (which we dubbed "crazy diamond") carried out on November 2007 by means of the astrophysical satellites AGILE, INTEGRAL, Swift, the WEBT Consortium, and the optical-NIR telescope REM. 3C 454.3 is detected at a $\sim 19-\sigma$ level during the 3-week observing period, with an average flux above 100 MeV of $F_{\rm E>100MeV} = (170 \pm 13) \times 10^{-8}$ \phcmsec. The gamma-ray spectrum can be fit with a single power-law with photon index $\Gamma_{\rm GRID} = 1.73 \pm 0.16$ between 100 MeV and 1 GeV. We detect significant day-by-day variability of the gamma-ray emission during our observations, and we can exclude that the fluxes are constant at the 99.6% ($\sim 2.9 \sigma$) level. The source was detected typically around 40 degrees off-axis, and it was substantially off--axis in the field of view of the AGILE hard X-ray imager. However, a 5-day long ToO observation by INTEGRAL detected 3C 454.3 at an average flux of about $F_{\rm 20-200 keV} = 1.49 \times 10^{-3}$ \phcmsec with an average photon index of $\Gamma_{\rm IBIS} = 1.75 \pm 0.24$ between 20--200 keV. Swift also detected 3C 454.3 with a flux in the 0.3--10 keV energy band in the range $(1.23-1.40) \times 10^{-2}$ \phcmsec{} and a photon index in the range $\Gamma_{\rm XRT} = 1.56-1.73$. In the optical band, both WEBT and REM show an extremely variable behavior in the $R$ band. A correlation analysis based on the entire data set is consistent with no time-lags between the gamma-ray and the optical flux variations. Our simultaneous multifrequency observations strongly indicate that the dominant emission mechanism between 30 MeV and 30 GeV is dominated by inverse Compton scattering of relativistic electrons in the jet on the external photons from the broad line region.Comment: Accepted for publication in ApJ. Abridged Abstract. 37 pages, 14 Figures, 3 Table

AGILE observation of a gamma-ray flare from the blazar 3C 279

Context. We report the detection by the AGILE satellite of an intense gamma-ray flare from the gamma-ray source 3EG J1255-0549, associated to the Flat Spectrum Radio Quasar 3C 279, during the AGILE pointings towards the Virgo Region on 2007 July 9-13. Aims. The simultaneous optical, X-ray and gamma-ray covering allows us to study the spectral energy distribution (SED) and the theoretical models relative to the flaring episode of mid-July. Methods. AGILE observed the source during its Science Performance Verification Phase with its two co-aligned imagers: the Gamma- Ray Imaging Detector (GRID) and the hard X-ray imager (Super-AGILE) sensitive in the 30 MeV - 50 GeV and 18 - 60 keV respectively. During the AGILE observation the source was monitored simultaneously in optical band by the REM telescope and in the X-ray band by the Swift satellite through 4 ToO observations. Results. During 2007 July 9-13 July 2007, AGILE-GRID detected gamma-ray emission from 3C 279, with the source at ~2 deg from the center of the Field of View, with an average flux of (210+-38) 10^-8 ph cm^-2 s^-1 for energy above 100 MeV. No emission was detected by Super-AGILE, with a 3-sigma upper limit of 10 mCrab. During the observation lasted about 4 days no significative gamma-ray flux variation was observed. Conclusions. The Spectral Energy Distribution is modelled with a homogeneous one-zone Synchrotron Self Compton emission plus the contributions by external Compton scattering of direct disk radiation and, to a lesser extent, by external Compton scattering of photons from the Broad Line Region.Comment: Accepted for publication in Astronomy and Astrophysic

Proposal for taking data with the KLOE-2 detector at the DAΦ\PhiNE collider upgraded in energy

This document reviews the physics program of the KLOE-2 detector at DA$\Phi$NE upgraded in energy and provides a simple solution to run the collider above the $\phi$-peak (up to 2, possibly 2.5 GeV). It is shown how a precise measurement of the multihadronic cross section in the energy region up to 2 (possibly 2.5) GeV would have a major impact on the tests of the Standard Model through a precise determination of the anomalous magnetic moment of the muon and the effective fine-structure constant at the $M_Z$ scale. With a luminosity of about $10^{32}$cm$^{-2}$s$^{-1}$, DA$\Phi$NE upgraded in energy can perform a scan in the region from 1 to 2.5 GeV in one year by collecting an integrated luminosity of 20 pb$^{-1}$ (corresponding to a few days of data taking) for single point, assuming an energy step of 25 MeV. A few years of data taking in this region would provide important tests of QCD and effective theories by $\gamma\gamma$ physics with open thresholds for pseudo-scalar (like the $\eta'$), scalar ($f_0,f'_0$, etc...) and axial-vector ($a_1$, etc...) mesons; vector-mesons spectroscopy and baryon form factors; tests of CVC and searches for exotics. In the final part of the document a technical solution for the energy upgrade of DA$\Phi$NE is proposed.Comment: 19 pages, 8 figure

Instrumentation for Longitudinal Beam Gymnastics in FEL's and at the CLIC Test Facility 3

Built at CERN by an international collaboration, the CLIC Test Facility 3 (CTF3) aims at demonstrating the feasibility of a high luminosity 3 TeV e+-e- collider by the year 2010. One of the main issues to be demonstrated is the generation of a high average current (30 A) high frequency (12 GHz) bunched beam by means of RF manipulation. At the same time, Free Electron Lasers (FEL) are developed in several places all over the world with the aim of providing high brilliance photon sources. These machines rely on the production of high peak current electron bunches. The required performances put high demands on the diagnostic equipment and innovative longitudinal monitors have been developed during the past years. This paper gives an overview of the longitudinal instrumentation developed at ELETTRA and CTF3, where a special effort was made in order to implement at the same time non-intercepting devices for online monitoring, and destructive diagnostics which have the advantage of providing more detailed information