Rearrangements of ATP5L-KMT2A in acute lymphoblastic leukaemia

Recent genomic studies have identified a wide range of novel genetic alterations that have substantially increased our knowledge of the biology of B- and T-progenitor acute lymphoblastic leukaemia (B-ALL, T-ALL) and defined new subtypes with prognostic and therapeutic relevance.1-4 Thanks to the use of transcriptome sequencing approaches, new cryptic fusion transcripts have been described, such as the ATP5L-KMT2A gene fusion, described by Gestrich et al. in a 14-month-old patient with aggressive B-ALL.5 ATP5L or ATP5MG (ATP Synthase Membrane Subunit G) catalyzes ATP synthesis during oxidative phosphorylation.6 This protein has recently been reported to interact with a SARS-CoV-2 protein.7 The histone lysine [K]-methyl transferase 2A (KMT2A) gene is a transcriptional coactivator that plays an essential role in regulating gene expression during early development and haematopoiesis. It is frequently rearranged to over 135 translocation partner genes in acute leukaemias.8 ATP5L is a novel KMT2A fusion partner not detectable by fluorescent in situ hybridization (FISH) or karyotype, due to the closeness of the two genes on chromosome 11q23. The Cleveland Medical Centre team found a reciprocal out-of-frame ATP5L-KMT2A rearrangement that juxtaposes the ATP5L exon 1 to the KMT2A exon 2, with the insertion of an extra nucleotide (G) at the fusion site.5 We sequenced leukaemic cells from eight adult ALL patients (two T-ALL, five B-ALL Philadelphia negative (Ph−) and one B-ALL Ph+; Table I) by a 199 gene RNA-sequencing panel (RNA-seq; Pan-Heme FusionPlex, ArcherDx Inc., Boulder, CO, USA).The study was supported by European Union Seventh Framework Programme (FP7/2007-2013) (GA 306242-NGS-PTL) and Associazione Italiana Leucemie (AIL)

The commissioning of the CUORE experiment: the mini-tower run

CUORE is a ton-scale experiment approaching the data taking phase in Gran Sasso National Laboratory. Its primary goal is to search for the neutrinoless double-beta decay in 130Te using 988 crystals of tellurim dioxide. The crystals are operated as bolometers at about 10 mK taking advantage of one of the largest dilution cryostat ever built. Concluded in March 2016, the cryostat commissioning consisted in a sequence of cool down runs each one integrating new parts of the apparatus. The last run was performed with the fully configured cryostat and the thermal load at 4 K reached the impressive mass of about 14 tons. During that run the base temperature of 6.3 mK was reached and maintained for more than 70 days. An array of 8 crystals, called mini-tower, was used to check bolometers operation, readout electronics and DAQ. Results will be presented in terms of cooling power, electronic noise, energy resolution and preliminary background measurements

Results from the Cuore Experiment

The Cryogenic Underground Observatory for Rare Events (CUORE) is the first bolometric experiment searching for neutrinoless double beta decay that has been able to reach the 1-ton scale. The detector consists of an array of 988 TeO2 crystals arranged in a cylindrical compact structure of 19 towers, each of them made of 52 crystals. The construction of the experiment was completed in August 2016 and the data taking started in spring 2017 after a period of commissioning and tests. In this work we present the neutrinoless double beta decay results of CUORE from examining a total TeO2 exposure of 86.3kg yr, characterized by an effective energy resolution of 7.7 keV FWHM and a background in the region of interest of 0.014 counts/ (keV kg yr). In this physics run, CUORE placed a lower limit on the decay half- life of neutrinoless double beta decay of 130Te > 1.3.1025 yr (90% C. L.). Moreover, an analysis of the background of the experiment is presented as well as the measurement of the 130Te 2vo3p decay with a resulting half- life of T2 2. [7.9 :- 0.1 (stat.) :- 0.2 (syst.)] x 10(20) yr which is the most precise measurement of the half- life and compatible with previous results

Epileptic EEG discharges and short non-convulsive crisis: Influence on cognitive and psychobehavioural functions in youths

Purpose: Learning and behavioural difficulties often occur in benign childhood epilepsy. In recent years, several electroencephalogram (EEG) characteristics have been related to the occurrence of learning and behavioral problems. We determined if the cognitive characteristics of epileptic children depend exclusively on illness factors, or if epileptic electroencephalogram discharges during the crisis contribute to these changes. Methods: We studied a randomly selected group of 150 youths with short non-convulsive crises, who completed cognitive testing and electroencephalographic studies. The inclusion criteria were: undefined crisis, variations in cognitive function and/or frequent epileptiform discharges on the electroencephalogram. Results: Previous research indicates that the type of epilepsy and the patient&#8217;s educational level can influence cognitive functioning. The electroencephalographic epileptic discharges during the crisis has been found to influence cognitive transitory functions such as vigilance or swiftness of mental functions. The type of epilepsy is correlated statistically with impairment of learning ability tests: reading (F, 5.487, P = 0.005) and mathematics (F, 3.007, P &#8804; 0.05). In addition, 40% of the epileptic patients had behavioural disordered versus 16% for the control group (P < 0.02)

Double beta decay search with CUPID-0: Results and Perspectives

International audienceCUPID-0 is the first large mass experiment based on cryogenic calorimeters (bolometers) that implements the dual read-out of light and heat for background rejection. The detector, consisting of 24 enriched Zn$^{82}$Se crystals (5.28 kg of $^{82}$Se), is taking data in the underground LNGS (Italy) from March 2017. In this contribution we present the analysis that allowed to set the most stringent limit on the half-life of neutrino-less double beta decay of $^{82}$Se. We prove that the particle identification, enabled by the simultaneous read-out of heat and light, provides an unprecedented background level for cryogenic calorimeters of few 10$^{−3}$ counts/keV/kg/y. Finally, we discuss the impact of these results on next generation projects

CUORE: first results and prospects

International audienceCUORE is the first bolometric tonne-scale experiment aiming at the investigation of neutrinoless double-beta (0$\nu$2$\beta$) decay of $^{130}$Te. The cryogenic commissioning followed by the detector installation and cool down took place during 2016. After the optimisation of all the detectors, the data-taking started in spring 2017. We report about the results of the first dataset acquired in May, which led to a limit on the 0$\nu$2$\beta$ half-life of $^{130}$Te of 6.6$\times$10$^{24}$ yr. An upgrade of CUORE, named CUPID, is planned to improve the 0$\nu$2$\beta$-decay sensitivity via passive and active background reduction and crystal enrichment. Some technologies for CUPID are currently under study and two of them are presented here, involving the detection of Cherenkov and scintillation light emitted by enriched $^{130}$TeO$_2$ and Li$^{100}_2$MoO$_4$ crystals respectively. This will allow us to reject the currently dominant a background

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume I Introduction to DUNE

International audienceThe preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE's physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology