Gene amplification-associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis

The introduction of new therapies against particular genetic mutations in non-small-cell lung cancer is a promising avenue for improving patient survival, but the target population is small. There is a need to discover new potential actionable genetic lesions, to which end, non-conventional cancer pathways, such as RNA editing, are worth exploring. Herein we show that the adenosine-toinosine editing enzyme ADAR1 undergoes gene amplification in non-small cancer cell lines and primary tumors in association with higher levels of the corresponding mRNA and protein. From a growth and invasion standpoint, the depletion of ADAR1 expression in amplified cells reduces their tumorigenic potential in cell culture and mouse models, whereas its overexpression has the opposite effects. From a functional perspective, ADAR1 overexpression enhances the editing frequencies of target transcripts such as NEIL1 and miR-381. In the clinical setting, patients with early-stage lung cancer, but harboring ADAR1 gene amplification, have poor outcomes. Overall, our results indicate a role for ADAR1 as a lung cancer oncogene undergoing gene amplification-associated activation that affects downstream RNA editing patterns and patient prognosis.This work was supported by the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 268626—EPINORC project, the Grant agreement number HEALTH-F2-2010-258677—CURELUNG project, the Spanish Ministry of Economy and Competitiveness (MINECO Projects no. SAF2011-22803, PI13-01339 and SAF2014-55000- R), the Institute of Health Carlos III (ISCIII)—PI10/02992, Ministerio de Educación, Ciencia e Innovación Grant SAF2010-14935, the Cellex Foundation, the National Cancer Center Research and Development Fund (NCC Biobank: 23 A-1) and the Health and Science Departments of the Catalan Government (Generalitat de Catalunya) AGAUR—project no. 2009SGR1315 and 2014SGR633.Peer Reviewe

Radon and material radiopurity assessment for the NEXT double beta decay experiment

The Neutrino Experiment with a Xenon TPC (NEXT), intended to investigate the neutrinoless double beta decay using a high-pressure xenon gas TPC filled with Xe enriched in 136Xe at the Canfranc Underground Laboratory in Spain, requires ultra-low background conditions demanding an exhaustive control of material radiopurity and environmental radon levels. An extensive material screening process is underway for several years based mainly on gamma-ray spectroscopy using ultra-low background germanium detectors in Canfranc but also on mass spectrometry techniques like GDMS and ICPMS. Components from shielding, pressure vessel, electroluminescence and high voltage elements and energy and tracking readout planes have been analyzed, helping in the final design of the experiment and in the construction of the background model. The latest measurements carried out will be presented and the implication on NEXT of their results will be discussed. The commissioning of the NEW detector, as a first step towards NEXT, has started in Canfranc; in-situ measurements of airborne radon levels were taken there to optimize the system for radon mitigation and will be shown too.Comment: Proceedings of the Low Radioactivity Techniques 2015 workshop (LRT2015), Seattle, March 201

NEXT-100 Technical Design Report (TDR). Executive Summary

In this Technical Design Report (TDR) we describe the NEXT-100 detector that will search for neutrinoless double beta decay (bbonu) in Xe-136 at the Laboratorio Subterraneo de Canfranc (LSC), in Spain. The document formalizes the design presented in our Conceptual Design Report (CDR): an electroluminescence time projection chamber, with separate readout planes for calorimetry and tracking, located, respectively, behind cathode and anode. The detector is designed to hold a maximum of about 150 kg of xenon at 15 bar, or 100 kg at 10 bar. This option builds in the capability to increase the total isotope mass by 50% while keeping the operating pressure at a manageable level. The readout plane performing the energy measurement is composed of Hamamatsu R11410-10 photomultipliers, specially designed for operation in low-background, xenon-based detectors. Each individual PMT will be isolated from the gas by an individual, pressure resistant enclosure and will be coupled to the sensitive volume through a sapphire window. The tracking plane consists in an array of Hamamatsu S10362-11-050P MPPCs used as tracking pixels. They will be arranged in square boards holding 64 sensors (8 times8) with a 1-cm pitch. The inner walls of the TPC, the sapphire windows and the boards holding the MPPCs will be coated with tetraphenyl butadiene (TPB), a wavelength shifter, to improve the light collection.Comment: 32 pages, 22 figures, 5 table

Electrical, morphological and structural properties of RF magnetron sputtered Mo thin films for application in thin film photovoltaic solar cells

Molybdenum (Mo) thin films were deposited using radio frequency magnetron sputtering, for application as a metal back contact material in ‘‘substrate configuration’’ thin film solar cells. The variations of the electrical, morphological, and structural properties of the deposited films with sputtering pressure, sputtering power and post-deposition annealing were determined. The electrical conductivity of the Mo films was found to increase with decreasing sputtering pressure and increasing sputtering power. X-ray diffraction data showed that all the films had a (110) preferred orientation that became less pronounced at higher sputtering power while being relatively insensitive to process pressure. The lattice stress within the films changed from tensile to compressive with increasing sputtering power and the tensile stress increased with increasing sputtering pressure. The surface morphology of the films changed from pyramids to cigar-shaped grains for a sputtering power between 100 and 200 W, remaining largely unchanged at higher power. These grains were also observed to decrease in size with increasing sputtering pressure. Annealing the films was found to affect the resistivity and stress of the films. The resistivity increased due to the presence of residual oxygen and the stress changed from tensile to compressive. The annealing step was not found to affect the crystallisation and grain growth of the Mo films

Evaluation of turbulent dissipation rate retrievals from Doppler Cloud Radar

Turbulent dissipation rate retrievals from cloud radar Doppler velocity measurements are evaluated using independent, in situ observations in Arctic stratocumulus clouds. In situ validation data sets of dissipation rate are derived using sonic anemometer measurements from a tethered balloon and high frequency pressure variation observations from a research aircraft, both flown in proximity to stationary, ground-based radars. Modest biases are found among the data sets in particularly low- or high-turbulence regimes, but in general the radar-retrieved values correspond well with the in situ measurements. Root mean square differences are typically a factor of 4-6 relative to any given magnitude of dissipation rate. These differences are no larger than those found when comparing dissipation rates computed from tetheredballoon and meteorological tower-mounted sonic anemometer measurements made at spatial distances of a few hundred meters. Temporal lag analyses suggest that approximately half of the observed differences are due to spatial sampling considerations, such that the anticipated radar-based retrieval uncertainty is on the order of a factor of 2-3. Moreover, radar retrievals are clearly able to capture the vertical dissipation rate structure observed by the in situ sensors, while offering substantially more information on the time variability of turbulence profiles. Together these evaluations indicate that radar-based retrievals can, at a minimum, be used to determine the vertical structure of turbulence in Arctic stratocumulus clouds