The CNGS Neutrino Beam

The CERN to Gran Sasso Neutrino beam (CNGS) was commissioned at CERN in early August 2006 and was first sent at low intensity to Gran Sasso on August 17, 2006. The Borexino, LVD and OPERA experiments continued the commissioning of their detectors and started taking data with practically no dead time. The CNGS collected several hundred events with clean time distributions.Comment: 11 pages, 14 EPS figures. Lecture given at the 2nd Latin American School on Cosmic Rays and Astrophysics, Puebla, Mexico, 30th August - 8th September 200

Fast automated scanning of OPERA emulsion films

The use of nuclear emulsions to record tracks of charged particles with an accuracy of better than 1 micron is possible in large physics experiments thanks to the recent improvements in the industrial production of emulsions and to the development of fast automated microscopes. The European Scanning System (ESS) is a fast automatic system developed for the mass scanning of the emulsions of the OPERA experiment, which requires microscopes with scanning speeds of about 20 cm$^2$/h. Recent improvements in the technique and measurements with ESS are reported.Comment: 3 pages, 5 figures, presented at the 10th Topical Seminar on Innovative Particle and Radiation Detectors, 1-5 October 2006, Siena, Ital

Systemic Treatment for Metastatic Biliary Tract Cancer: State of the Art and a Glimpse to the Future

Recent years have seen some breakthroughs in the therapeutic landscape of advanced biliary tract cancer (BTC). Firstly, a better understanding of the molecular background of BTC has led to important improvements in the management of these hepatobiliary malignancies, with the advent of targeted agents representing an unprecedented paradigm shift, as witnessed by the FDA approval of pemigatinib and infigratinib for FGFR2-rearranged and ivosidenib in IDH1-mutant cholangiocarci-noma. In addition, several novel treatments are under assessment, including immune checkpoint inhibitors and combination chemotherapies. In the current review, we provide an overview of systemic treatment for metastatic BTC, summarizing recent clinical data on chemotherapy as well as the main results of targeted therapies and immunotherapy

MKRN3 and KISS1R mutations in precocious and early puberty

Background Pubertal timing is known to be influenced by interactions among various genetic, nutritional, environmental and socio-economic factors, although the ultimate mechanisms underlying the increase in pulsatile GnRH secretion at puberty have yet to be fully elucidated. The aim of our research was to verify the role of KISSR1 (previously named GPR54) and MKRN3 genes on pubertal timing. Methods We analyzed the DNA sequence of these genes in 13 girls affected by central precocious puberty (CPP) who showed onset of puberty before 8 years of age, and in 6 girls affected by early puberty (EP) between 8 and 10 years of age. Results Direct sequencing of the KISS1R (GPR54) gene revealed two SNPs. One SNP is a missense variant (rs 350,132) that has been previously reported in connection to CPP in Korean girls. The other variant that we found in the GPR54 gene (rs764046557) was a missense SNP located in exon 5 at position 209 of the aminoacid. We identified this variant in only one CPP patient. Automatic sequencing of MKRN3 in all patients revealed three variants in eight subjects. In 6 out of 19 (31.5%) patients (3/13 CPP patients and 3/6 EP patients) we found the synonymous variant c.663C > T (rs2239669). Another synonymous variant (rs140467331) was found in one of our CPP patients, as well as one missense variant (rs760981395) in another CPP patient. Conclusion In conclusion, we identified sequence variations of the KISS1R and MKRN3 genes, two of the most frequent genetic causes of ICPP. Our results suggest that these variants might be inducible factors in the pathogenesis of CPP

Electronics design of the RPC system for the OPERA muon spectrometer

The present document describes the front-end electronics of the RPC system that instruments the magnet muon spectrometer of the OPERA experiment. The main task of the OPERA spectrometer is to provide particle tracking information for muon identification and simplify the matching between the Precision Trackers. As no trigger has been foreseen for the experiment, the spectrometer electronics must be self-triggered with single-plane readout capability. Moreover, precision time information must be added within each event frame for off-line reconstruction. The read-out electronics is made of three different stages: the Front-End Boards (FEBs) system, the Controller Boards (CBs) system and the Trigger Boards(TBs) system. The FEB system provides discrimination of the strip incoming signals; a FAST-OR output of the input signals is also available for trigger plane signal generation. FEB signals are acquired by the CB system that provides the zero suppression and manages the communication to the DAQ and Slow Control. A Trigger Board allows to operate in both self-trigger mode (the FEB’s FAST-OR signal starts the plane acquisition) or in external-trigger mode (different conditions can be set on the FAST-OR signals generated from different planes)

Pre- and post-transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia

Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in complete remission (CR). MRD was measured by polymerase chain reaction in bone marrow samples collected pre-HSCT and during the first and third trimesters after HSCT (post-HSCT1 and post-HSCT3). The overall event-free survival (EFS) was 50%. The cumulative incidence of relapse and non-relapse mortality was 41% and 9%. Any degree of detectable pre-HSCT MRD was associated with poor outcome: EFS was 39% and 18% in patients with MRD positivity <1 × 10−3 and ≥1 × 10−3, respectively, versus 73% in MRD-negative patients (P < 0·001). This effect was maintained in different disease remissions, but low-level MRD had a very strong negative impact only in patients transplanted in second or further CR. Also, MRD after HSCT enabled patients to be stratified, with increasing MRD between post-HSCT1 and post-HSCT3 clearly defining cohorts with a different outcome. MRD is an important prognostic factor both before and after transplantation. Given that MRD persistence after HSCT is associated with dismal outcome, these patients could benefit from early discontinuation of immunosuppression, or pre-emptive immuno-therapy

Electron neutrino tagging through tertiary lepton detection

We discuss an experimental technique aimed at tagging electron neutrinos in multi-GeV artificial sources on an event-by-event basis. It exploits in a novel manner calorimetric and tracking technologies developed in the framework of the LHC experiments and of rare kaon decay searches. The setup is suited for slow-extraction, moderate power beams and it is based on an instrumented decay tunnel equipped with tagging units that intercept secondary and tertiary leptons from the bulk of undecayed \pi^+ and protons. We show that the taggers are able to reduce the \nue contamination originating from K_e3 decays by about one order of magnitude. Only a limited suppression (~60%) is achieved for \nue produced by the decay-in-flight of muons; for low beam powers, similar performance as for K_e3 can be reached supplementing the tagging system with an instrumented beam dump.Comment: 19 pages, 7 figures; minor changes, version to appear in EPJ

The OPERA experiment Target Tracker

The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multi-anode photomultiplier tubes. All the elements used in the construction of this detector and its main characteristics are described.Comment: 25 pages, submitted to Nuclear Instrument and Method

Mesenchymal Stromal Cell on Liver Decellularised Extracellular Matrix for Tissue Engineering

Background: In end-stage chronic liver disease, transplantation represents the only curative option. However, the shortage of donors results in the death of many patients. To overcome this gap, it is mandatory to develop new therapeutic options. In the present study, we decellularised pig livers and reseeded them with allogeneic porcine mesenchymal stromal cells (pMSCs) to understand whether extracellular matrix (ECM) can influence and/or promote differentiation into hepatocyte-like cells (HLCs). Methods: After decellularisation with SDS, the integrity of ECM-scaffolds was examined by histological staining, immunofluorescence and scanning electron microscope. DNA quantification was used to assess decellularisation. pMSCs were plated on scaffolds by static seeding and maintained in in vitro culture for 21 days. At 3, 7, 14 and 21 days, seeded ECM scaffolds were evaluated for cellular adhesion and growth. Moreover, the expression of specific hepatic genes was performed by RT-PCR. Results: The applied decellularisation/recellularisation protocol was effective. The number of seeded pMSCs increased over the culture time points. Gene expression analysis of seeded pMSCs displayed a weak induction due to ECM towards HLCs. Conclusions: These results suggest that ECM may address pMSCs to differentiate in hepatocyte-like cells. However, only contact with liver-ECM is not enough to induce complete differentiation