Melting transitions in biomembranes

We investigated melting transitions in biological membranes in their native state that include their membrane proteins. These membranes originated from \textit{E. coli}, \textit{B. subtilis}, lung surfactant and nerve tissue from the spinal cord of several mammals. For some preparations, we studied the pressure, pH and ionic strength dependence of the transition. For porcine spine, we compared the transition of the native membrane to that of the extracted lipids. All preparations displayed melting transitions of 10-20 degrees below physiological or growth temperature, independent of the organism of origin and the respective cell type. The position of transitions in \textit{E. coli} membranes depends on the growth temperature. We discuss these findings in the context of the thermodynamic theory of membrane fluctuations that leads to largely altered elastic constants, an increase in fluctuation lifetime and in membrane permeability associated with the transitions. We also discuss how to distinguish lipid transitions from protein unfolding transitions. Since the feature of a transition slightly below physiological temperature is conserved even when growth conditions change, we conclude that the transitions are likely to be of major biological importance for the survival and the function of the cell.Comment: 12 pages, 6 Figures, 1 supplement with 1 figur

Current Status of the High-Efficiency L-band Transmit/Receive Module Development for SAR Systems

Large, lightweight, high power, L-band phased-arrays are required to enable future NASA synthetic aperture radar (SAR) missions. The transmit/receive (T/R) module is a key component in SAR antennas and the T/R module efficiency has direct implications on the power dissipation and power generation requirements of the system. Significant improvements in the efficiency of the T/R module will make SAR missions more feasible and affordable. The efforts described in this paper are part of a three-year on-going task sponsored by the NASA Earth Science Technology Office (ESTO) under the Advanced Component Technology (ACT) program. We will describe the current status and recent results of a novel T/R module technology to achieve ultra-high efficiencies. The T/R module performance goal is to achieve an overall module efficiency greater than 70% with a minimum of 30-Watts output power at L-band frequencies

Long-term patient-important outcomes after septic shock : A protocol for 1-year follow-up of the CLASSIC trial

BackgroundIn patients with septic shock, mortality is high, and survivors experience long-term physical, mental and social impairments. The ongoing Conservative vs Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial assesses the benefits and harms of a restrictive vs standard-care intravenous (IV) fluid therapy. The hypothesis is that IV fluid restriction improves patient-important long-term outcomes. AimTo assess the predefined patient-important long-term outcomes in patients randomised into the CLASSIC trial. MethodsIn this pre-planned follow-up study of the CLASSIC trial, we will assess all-cause mortality, health-related quality of life (HRQoL) and cognitive function 1 year after randomisation in the two intervention groups. The 1-year mortality will be collected from electronic patient records or central national registries in most participating countries. We will contact survivors and assess EuroQol 5-Dimension, -5-Level (EQ-5D-5L) and EuroQol-Visual Analogue Scale and Montreal Cognitive Assessment 5-minute protocol score. We will analyse mortality by logistic regression and use general linear models to assess HRQoL and cognitive function. DiscussionWith this pre-planned follow-up study of the CLASSIC trial, we will provide patient-important data on long-term survival, HRQoL and cognitive function of restrictive vs standard-care IV fluid therapy in patients with septic shock.Peer reviewe

The SuperCam Instrument Suite on the Mars 2020 Rover: Science Objectives and Mast-Unit Description

On the NASA 2020 rover mission to Jezero crater, the remote determination of the texture, mineralogy and chemistry of rocks is essential to quickly and thoroughly characterize an area and to optimize the selection of samples for return to Earth. As part of the Perseverance payload, SuperCam is a suite of five techniques that provide critical and complementary observations via Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), visible and near-infrared spectroscopy (VISIR), high-resolution color imaging (RMI), and acoustic recording (MIC). SuperCam operates at remote distances, primarily 2-7 m, while providing data at sub-mm to mm scales. We report on SuperCam's science objectives in the context of the Mars 2020 mission goals and ways the different techniques can address these questions. The instrument is made up of three separate subsystems: the Mast Unit is designed and built in France; the Body Unit is provided by the United States; the calibration target holder is contributed by Spain, and the targets themselves by the entire science team. This publication focuses on the design, development, and tests of the Mast Unit; companion papers describe the other units. The goal of this work is to provide an understanding of the technical choices made, the constraints that were imposed, and ultimately the validated performance of the flight model as it leaves Earth, and it will serve as the foundation for Mars operations and future processing of the data.In France was provided by the Centre National d'Etudes Spatiales (CNES). Human resources were provided in part by the Centre National de la Recherche Scientifique (CNRS) and universities. Funding was provided in the US by NASA's Mars Exploration Program. Some funding of data analyses at Los Alamos National Laboratory (LANL) was provided by laboratory-directed research and development funds

Radiation and Dust Sensor for Mars Environmental Dynamic Analyzer Onboard M2020 Rover

32 pags., 26 figs., 3 tabs. -- This article belongs to the Section Remote SensorsThe Radiation and Dust Sensor is one of six sensors of the Mars Environmental Dynamics Analyzer onboard the Perseverance rover from the Mars 2020 NASA mission. Its primary goal is to characterize the airbone dust in the Mars atmosphere, inferring its concentration, shape and optical properties. Thanks to its geometry, the sensor will be capable of studying dust-lifting processes with a high temporal resolution and high spatial coverage. Thanks to its multiwavelength design, it will characterize the solar spectrum from Mars' surface. The present work describes the sensor design from the scientific and technical requirements, the qualification processes to demonstrate its endurance on Mars' surface, the calibration activities to demonstrate its performance, and its validation campaign in a representative Mars analog. As a result of this process, we obtained a very compact sensor, fully digital, with a mass below 1 kg and exceptional power consumption and data budget features.This work has been funded with the help of the Spanish National Research, Development and Innovation Program, through the grants RTI2018-099825-B-C31, ESP2016-80320-C2-1-R and ESP2014-54256-C4-3-R. DT acknowledges the financial support from the Comunidad de Madrid for an “Atracción de Talento Investigador” grant (2018-T2/TIC10500). ASL is supported by Grant PID2019-109467GB-I00 funded by MCIN/AEI/10.13039/501100011033/ and by Grupos Gobierno Vasco IT1366-19. The US co-authors performed their work under sponsorship from NASA’s Mars 2020 project, from the Game Changing Development program within the Space Technology Mission Directorate, and from the Human Exploration and Operations Directorate.Peer reviewe

Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis.

Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis

Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available