Divergent mutational processes distinguish hypoxic and normoxic tumours.

Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer

CAMERA – Mobility Report 1

This report is a result of research performed so far in the scope of the CAMERA Coordination and Support Action (CSA). In CAMERA, we investigate research initiatives from the past decade that focus on the European air transport system and its integration with other transport modes, with a special focus on addressing the customer experience and point of view. The focus of this report is the review of the research under FP7 and its successor, H2020, as these have supported a large number of research activities in air mobility in the last decade. Its objective is to analyse 158 selected research initiatives in European mobility research to determine their coverage of mobility challenges, identify potential gaps and form recommendations for future research initiatives. This is the first of four Annual Mobility Reports that CAMERA is planning to publish. It outlines the initial findings and describes the future efforts of this Coordination and Support Action

D4.1: Gaps, bottlenecks and results: the methodology

This deliverable presents the methodology that CAMERA will follow to produce an overview of the European transportation research field. This methodology is based on the analysis carried out, and, planned in WP3, including the output of the cluster analysis presented in D3.1 and D5.3

Large-scale gene-centric analysis identifies novel variants for coronary artery disease

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19); 1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10(-7)). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes

Status of the technologies for the production of the Cherenkov Telescope Array (CTA) mirrors

The Cherenkov Telescope Array (CTA) is the next generation very high-energy gamma-ray observatory, with at least 10 times higher sensitivity than current instruments. CTA will comprise several tens of Imaging Atmospheric Cherenkov Telescopes (IACTs) operated in array-mode and divided into three size classes: large, medium and small telescopes. The total reflective surface could be up to 10,000 m2 requiring unprecedented technological efforts. The properties of the reflector directly influence the telescope performance and thus constitute a fundamental ingredient to improve and maintain the sensitivity. The R&D status of lightweight, reliable and cost-effective mirror facets for the CTA telescope reflectors for the different classes of telescopes is reviewed in this paper.Fil: Pareschi, G.. INAF/Brera Astronomical Observatory; ItaliaFil: Medina, Maria Clementina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto Argentino de Radioastronomia (i); ArgentinaFil: CTA Consortium. No especifíca

Open science resources for the discovery and analysis of Tara Oceans data

Pesant, Stéphane ... et. al.-- 16 pages, 5 figures, 2 tables.-- This article is contribution number 26 of the Tara Oceans ConsortiumThe Tara Oceans expedition (2009–2013) sampled contrasting ecosystems of the world oceans, collecting environmental data and plankton, from viruses to metazoans, for later analysis using modern sequencing and state-of-the-art imaging technologies. It surveyed 210 ecosystems in 20 biogeographic provinces, collecting over 35,000 samples of seawater and plankton. The interpretation of such an extensive collection of samples in their ecological context requires means to explore, assess and access raw and validated data sets. To address this challenge, the Tara Oceans Consortium offers open science resources, including the use of open access archives for nucleotides (ENA) and for environmental, biogeochemical, taxonomic and morphological data (PANGAEA), and the development of on line discovery tools and collaborative annotation tools for sequences and images. Here, we present an overview of Tara Oceans Data, and we provide detailed registries (data sets) of all campaigns (from port-to-port), stations and sampling eventsWe thank the commitment of the following people and sponsors who made this singular expedition possible: CNRS (in particular the Groupement de Recherche GDR3280), European Molecular Biology Laboratory (EMBL), Genoscope/CEA, Fund for Scientific Research—Flanders, VIB, Stazione Zoologica Anton Dohrn, UNIMIB, ANR (projects POSEIDON/ANR-09-BLAN-0348, BIOMARKS/ANR-08-BDVA- 003, PROMETHEUS/ANR-09-GENM-031, PROMETHEUS/ANR-09-PCS-GENM-217, TARAGIRUS/ANR-09-PCS-GENM-218, OCEANOMICS/ANR-11-BTBR-0008, FRANCE GENOMIQUE/ANR-10-INBS-09-08), EU FP7 (MicroB3/No.287589, IHMS/HEALTH-F4-2010-261376, MetaCardis/HEALTH-F4-2012-305312), ERC Advanced Grant Awards to CB (Diatomite: 294823) and PB (CancerBiome: 268985), Spanish Ministry of Science and Innovation grant CGL2011-26848/BOS MicroOcean PANGENOMICS to SGA, JSPS KAKENHI Grant Number 26430184 to HO, FWO, BIO5, Biosphere 2, agne`s b., the Veolia Environment Foundation, Region Bretagne, World Courier, Illumina, Cap L’Orient, the EDF Foundation EDF Diversiterre, FRB, the Prince Albert II de Monaco Foundation, Etienne Bourgois, the Tara schooner and its captain and crew. Tara Oceans would not exist without continuous support from 23 institutes (http://oceans.taraexpeditions.org)Peer Reviewe