Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Editorial

EditorialGreen Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Structural Design & Mechanic

Challenging glass: the sequel

Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Applied MechanicsStructural Design & Mechanic

Challenging glass in challenging times

EditorialEditorial Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Structural Design & Mechanic

Glass engineering!

EditorialGreen Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Structural Design & Mechanic

Glass and the energy crisis

Civil Engineering & GeosciencesArchitectural Technolog

Glass performance

Structural Design & Mechanic

Glass and digital transformation

Structural Design & Mechanic

The Aresys FF-SAR Service for Cryosat-2 at ESA GPOD

The Fully-Focused SAR (FF-SAR) processing, introduced in Egido and Smith (2016) allows obtaining a maximum resolution of 0.5 m in the along-track direction. It provides significant benefits for inland water altimetry investigations allowing the successful investigation of very small rivers and canals (Kleinherenbrink, 2020) that are typically harder to be analysed by using unfocused Delay-Doppler SAR (DD-SAR) data (about 300 m resolution in the along-track direction).In its development, two major limitations were associated with the FF-SAR processing: 1) the presence of evenly spaced high sidelobes in the Point Target Response (PTR) due to the closed-loop burst mode implemented in Sentinel-3 & Cryosat-2 altimeter payloads, used for initial FF-SAR investigations, and 2) the heavy computational burden with respect to the unfocused DD-SAR processing. The first limitation can be overcome by designing the radar system differently adopting an open-loop transmission scheme as, for instance, the one implemented in the altimeter payload of the Sentinel-6 Michael Freilich mission, launched on 21 November 2020. The second limitation has been addressed in research works following Egido and Smith (2016) indicating that an improvement in terms of computational burden can be achieved by adopting algorithms in the frequency domain (Guccione et al., 2018).Being the role of FF-SAR for future inland water altimetry well understood, along with the possibility to see it implemented with reduced drawbacks during the Sentinel-6 Michael Freilich mission, a collaboration has started between the ESA GPOD Team, already hosting the successful SARvatore services portfolio for unfocused SAR & SARin altimetry, and Aresys. Aresys has developed a generic FF-SAR prototype processor, that is able to process data acquisition from different instruments and exploiting the frequency-domain Omega-K algorithm (Guccione et al., 2018 & Scagliola et al., 2018). The Aresys's FFSAR prototype processor for CryoSat-2 allows users to process, on line and on demand, low-level CryoSat FBR products in SAR mode up to FF-SAR Level-1 products with self-customized options. Additionally a wide set of processing parameters is configurable, allowing as an example to select the along-track resolution or to obtain FFSAR multilooked waveforms at the desired posting rate. The collaboration led to the creation of a new service for the processing of CryoSat Baseline D data in FF-SAR mode. Users will be able to select the following options: 1) range oversampling factor, 2) bandwidth factor (responsible for the along-track resolution value) and 3) multilook posting rate (1Hz-500Hz). Geophysical corrections and L2 estimates from both a threshold peak retracker and an ALES-like subwaveform retracker are part of the output package. In preliminary open ocean analyses, very good results on SSH noise have been obtained by the ALES-like subwaveform retracker.In this presentation, the Aresys FF-SAR prototype processor is described and the outcome of some preliminary validation activities, performed by a group of altimetry researchers, is reported. The service is scheduled to open to all GPOD/SARvatore users in the first semester of 2021. Future evolutions should include the extension of the service to Sentinel-3 and Sentinel-6 data.Astrodynamics & Space Mission

Challenging glass

EditorialGreen Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Structural Design & MechanicsApplied Mechanic