Historical and Instrumental Seismicity of the Sansepolcro Basin, Northern Apennines, Italy

In this work we analyse the most important earthquakes of the 20th century occurred in the Altotiberina Valley in 1917, 1918, 1919 and 1948; in particular instrumental relocation and Ms magnitude estimation are re-evaluated. The area investigated, the Sansepolcro basin, is characterized by the presence of important earthquakes in the past with estimated intensity even larger than IX MCS (the 1352 Monterchi earthquake, the 1389 Boccaserriola, the 1458 Citta' di Castello, the 1781 Cagliese and the 1917 Monterchi-Citerna earthquakes, CPTI Working Group, 2004) and by a surprisingly scarce instrumental seismicity compared to the adjacent areas struck by high seismicity (Castello et al., 2005; Ciaccio et al., 2006). In particular, the area north of Sansepolcro has been struck in recent years by four minor sequences, occurred between 1987 and 2001 with magnitude ranging from Ml3.0 to Mw4.7. The relocation of these earthquakes is particularly critical and in an important issue. An instrumental and precise location is critical for the complexity of the problems associated with the study of seismograms prior to the rst half of the twentieth century and is relevant because in the surrounding regions higher seismicity is observed. Regarding this peculiarity of the area, it’s very important to detect the localization of the historical earthquakes: in particular, the 1917 event is often associated to the possibility that the regional low angle Altotiberina Fault (Barchi et al., 1998) is able or not to nucleate large- or moderate-magnitude events, being historically located close to its surface (Boncio and Lavecchia, 2000)

Testing the performance of a blind burst statistic

In this work we estimate the performance of a method for the detection of burst events in the data produced by interferometric gravitational wave detectors. We compute the receiver operating characteristics in the specific case of a simulated noise having the spectral density expected for Virgo, using test signals taken from a library of possible waveforms emitted during the collapse of the core of Type II Supernovae.Comment: 8 pages, 6 figures, Talk given at the GWDAW2002 worksho

Otx015 epi‐drug exerts antitumor effects in ovarian cancer cells by blocking gnl3‐mediated radioresistance mechanisms: Cellular, molecular and computational evidence

Ovarian cancer (OC) is the most aggressive gynecological tumor worldwide and, notwithstanding the increment in conventional treatments, many resistance mechanisms arise, this leading to cure failure and patient death. So, the use of novel adjuvant drugs able to counteract these pathways is urgently needed to improve patient overall survival. A growing interest is focused on epigenetic drugs for cancer therapy, such as Bromodomain and Extra‐Terminal motif inhibitors (BETi). Here, we investigate the antitumor effects of OTX015, a novel BETi, as a single agent or in combination with ionizing radiation (IR) in OC cellular models. OTX015 treatment significantly reduced tumor cell proliferation by triggering cell cycle arrest and apoptosis that were linked to nucleolar stress and DNA damage. OTX015 impaired migration capacity and potentiated IR effects by reducing the expression of different drivers of cancer resistance mechanisms, including GNL3 gene, whose expression was found to be significantly higher in OC biopsies than in normal ovarian tissues. Gene specific knocking down and computational network analysis confirmed the centrality of GNL3 in OTX015‐mediated OC antitumor effects. Altogether, our findings suggest OTX015 as an effective option to improve therapeutic strategies and overcome the development of resistant cancer cells in patients with OC

Discovery of chemotherapy-associated ovarian cancer antigens by interrogating memory T cells

According to the immunogenic cell death hypothesis, clinical chemotherapy treatments may result in CD8(+) and CD4(+) T-cell responses against tumor cells. To discover chemotherapy-associated antigens (CAAs), T cells derived from ovarian cancer (OC) patients (who had been treated with appropriate chemotherapy protocols) were interrogated with proteins isolated from primary OC cells. We screened for immunogenicity using two-dimensional electrophoresis gel-eluted OC proteins. Only the selected immunogenic antigens were molecularly characterized by mass-spectrometry-based analysis. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were correlated with prolonged survival in response to chemotherapy, supporting the model of chemotherapy-induced apoptosis as an adjuvant of anti-tumor immunity. The strength of both memory CD4(+) and CD8(+) T cells producing either IFN- or IL-17 in response to apoptotic OC antigens was also significantly greater in Responders to chemotherapy than in nonresponders. Immunogenicity of some of these antigens was confirmed using recombinant proteins in an independent set of patients. The T-cell interrogation system represents a strategy of reverse tumor immunology that proposes to identify CAAs, which may then be validated as possible prognostic tumor biomarkers or cancer vaccines

Length Sensing and Control in the Virgo Gravitational Wave Interferometer

The gravitational wave detector Virgo is presently being commissioned. A significant part of last year was spent in setting up the cavity length control system. This work was carried out with steps of increasing complexity: locking a simple Fabry-Perot cavity, then a Michelson interferometer with Fabry-Perot cavities in both arms, and finally recycling the light beam into the interferometer. The applied strategy and the main results obtained are describe

Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials

BACKGROUND: Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status. METHODS: STRAP and STRAP-EU were two parallel, open-label, biopsy-driven, stratified, randomised, phase 3 trials done across 26 university centres in the UK and Europe. Biologic-naive patients aged 18 years or older with rheumatoid arthritis based on American College of Rheumatology (ACR)–European League Against Rheumatism classification criteria and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) were included. Following ultrasound-guided synovial biopsy, patients were classified as B cell poor or B cell rich according to synovial B cell signatures and randomly assigned (1:1:1) to intravenous rituximab (1000 mg at week 0 and week 2), subcutaneous tocilizumab (162 mg per week), or subcutaneous etanercept (50 mg per week). The primary outcome was the 16-week ACR20 response in the B cell-poor, intention-to-treat population (defined as all randomly assigned patients), with data pooled from the two trials, comparing etanercept and tocilizumab (grouped) versus rituximab. Safety was assessed in all patients who received at least one dose of study drug. These trials are registered with the EU Clinical Trials Register, 2014-003529-16 (STRAP) and 2017-004079-30 (STRAP-EU). FINDINGS: Between June 8, 2015, and July 4, 2019, 226 patients were randomly assigned to etanercept (n=73), tocilizumab (n=74), and rituximab (n=79). Three patients (one in each group) were excluded after randomisation because they received parenteral steroids in the 4 weeks before recruitment. 168 (75%) of 223 patients in the intention-to-treat population were women and 170 (76%) were White. In the B cell-poor population, ACR20 response at 16 weeks (primary endpoint) showed no significant differences between etanercept and tocilizumab grouped together and rituximab (46 [60%] of 77 patients vs 26 [59%] of 44; odds ratio 1·02 [95% CI 0·47–2·17], p=0·97). No differences were observed for adverse events, including serious adverse events, which occurred in six (6%) of 102 patients in the rituximab group, nine (6%) of 108 patients in the etanercept group, and three (4%) of 73 patients in the tocilizumab group (p=0·53). INTERPRETATION: In this biologic-naive population of patients with rheumatoid arthrtitis, the dichotomic classification into synovial B cell poor versus rich did not predict treatment response to B cell depletion with rituximab compared with alternative treatment strategies. However, the lack of response to rituximab in patients with a pauci-immune pathotype and the higher risk of structural damage progression in B cell-rich patients treated with rituximab warrant further investigations into the ability of synovial tissue analyses to inform disease pathogenesis and treatment response. FUNDING: UK Medical Research Council and Versus Arthritis

Low loss coatings for the VIRGO large mirrors

présentée par L. PinardThe goal of the VIRGO program is to build a giant Michelson type interferometer (3 kilometer long arms) to detect gravitational waves. Large optical components (350 mm in diameter), having extremely low loss at 1064 nm, are needed. Today, the Ion beam Sputtering is the only deposition technique able to produce optical components with such performances. Consequently, a large ion beam sputtering deposition system was built to coat large optics up to 700 mm in diameter. The performances of this coater are described in term of layer uniformity on large scale and optical losses (absorption and scattering characterization). The VIRGO interferometer needs six main mirrors. The first set was ready in June 2002 and its installation is in progress on the VIRGO site (Italy). The optical performances of this first set are discussed. The requirements at 1064 nm are all satisfied. Indeed, the absorption level is close to 1 ppm (part per million), the scattering is lower than 5 ppm and the R.M.S. wavefront of these optics is lower than 8 nm on 150 mm in diameter. Finally, some solutions are proposed to further improve these performances, especially the absorption level (lower than 0.1 ppm) and the mechanical quality factor Q of the mirrors (thermal noise reduction)

The Virgo interferometric gravitational antenna

Submitted to: Class. Quantum Grav.The interferometric gravitational wave detectors represent the ultimate evolution of the classical Michelson interferometer. In order to measure the signal produced by the passage of a gravitational wave, they aim to reach unprecedent sensitivities in measuring the relative displacements of the mirrors. One of them , the 3-km-long Virgo gravitational wave antenna, which will be particularly sensitive in the low frequency range (10-100 Hz), is presently in its commissioning phase. In this paper the various techniques developed in order to reach its target extreme performance are outlined

The status of VIRGO

In this paper the main characteristics of the interferometric gravitational waves detector Virgo are presented as well as its present status and perspectives