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

Germline genetic variation in prostate susceptibility does not predict outcomes in the chemoprevention trials PCPT and SELECT

Background The development of prostate cancer can be influenced by genetic and environmental factors. Numerous germline SNPs influence prostate cancer susceptibility. The functional pathways in which these SNPs increase prostate cancer susceptibility are unknown. Finasteride is currently not being used routinely as a chemoprevention agent but the long term outcomes of the PCPT trial are awaited. The outcomes of the SELECT trial have not recommended the use of chemoprevention in preventing prostate cancer. This study investigated whether germline risk SNPs could be used to predict outcomes in the PCPT and SELECT trial. Methods Genotyping was performed in European men entered into the PCPT trial (n = 2434) and SELECT (n = 4885). Next generation genotyping was performed using Affymetrix® Eureka™ Genotyping protocols. Logistic regression models were used to test the association of risk scores and the outcomes in the PCPT and SELECT trials. Results Of the 100 SNPs, 98 designed successfully and genotyping was validated for samples genotyped on other platforms. A number of SNPs predicted for aggressive disease in both trials. Men with a higher polygenic score are more likely to develop prostate cancer in both trials, but the score did not predict for other outcomes in the trial. Conclusion Men with a higher polygenic risk score are more likely to develop prostate cancer. There were no interactions of these germline risk SNPs and the chemoprevention agents in the SELECT and PCPT trials

The European Large Area ISO Survey - ISOPHOT results using the MPIA-pipeline

The European Large Area ISO Survey (ELAIS) will provide Infrared observations of 4 regions in the sky with ISO. Around 2000 Infrared sources have been detected at 7 and 15 microns (with ISOCAM), 90 and 175 microns (with ISOPHOT)) over 13 square degrees of the sky. We present the source extraction pipeline of the 90 microns ISOPHOT observations, describe and discuss the results obtained and derive the limits of the ELAIS observational strategy.Comment: 4 pages, 5 figures, to appear in the ISO conference "The Universe as seen by ISO", 1998, UNESCO, Pari

First results of the two square meters multilayer glass composite mirror design proposed for the Cherenkov Telescope Array developed at INFN

The Cherenkov Telescope Array (CTA) is a future ground-based gamma-ray astronomy detector that will consist of more than 100 Imaging Atmospheric Cherenkov Telescopes of different sizes. The total reflective surface of roughly 10 000 m$^2$ requires unprecedented technological efforts towards a cost-efficient production of light-weight and reliable mirror substrates at high production rate. We report on a new mirror concept proposed for CTA developed by INFN, which is based on the replication from a spherical convex mold under low pressure. The mirror substrate is an open structure design made by thin glass layers at the mirror's front and rear interspaced by steel cylinders. A first series of nominal size mirrors has been produced, for which we discuss the optical properties in terms of radius of curvature and focusing power

Evidence of widespread selection on standing variation in Europe at height-associated SNPs.

Strong signatures of positive selection at newly arising genetic variants are well documented in humans(1-8), but this form of selection may not be widespread in recent human evolution(9). Because many human traits are highly polygenic and partly determined by common, ancient genetic variation, an alternative model for rapid genetic adaptation has been proposed: weak selection acting on many pre-existing (standing) genetic variants, or polygenic adaptation(10-12). By studying height, a classic polygenic trait, we demonstrate the first human signature of widespread selection on standing variation. We show that frequencies of alleles associated with increased height, both at known loci and genome wide, are systematically elevated in Northern Europeans compared with Southern Europeans (P < 4.3 × 10(-4)). This pattern mirrors intra-European height differences and is not confounded by ancestry or other ascertainment biases. The systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients ∼10(-3)-10(-5) per allele) rather than genetic drift alone (P < 10(-15))

UVMag: stellar formation, evolution, structure and environment with space UV and visible spectropolarimetry

Important insights into the formation, structure, evolution and environment of all types of stars can be obtained through the measurement of their winds and possible magnetospheres. However, this has hardly been done up to now mainly because of the lack of UV instrumentation available for long periods of time. To reach this aim, we have designed UVMag, an M-size space mission equipped with a high-resolution spectropolarimeter working in the UV and visible spectral range. The UV domain is crucial in stellar physics as it is very rich in atomic and molecular lines and contains most of the flux of hot stars. Moreover, covering the UV and visible spectral domains at the same time will allow us to study the star and its environment simultaneously. Adding polarimetric power to the spectrograph will multiply tenfold the capabilities of extracting information on stellar magnetospheres, winds, disks, and magnetic fields. Examples of science objectives that can be reached with UVMag are presented for pre-main sequence, main sequence and evolved stars. They will cast new light onto stellar physics by addressing many exciting and important questions. UVMag is currently undergoing a Research and Technology study and will be proposed at the forthcoming ESA call for M-size missions. This spectropolarimeter could also be installed on a large UV and visible observatory (e.g. NASA's LUVOIR project) within a suite of instruments.Comment: Accepted in ApSS's special volume on UV astronom