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

Optimizing environmental DNA storage: Comparing DNA detections between low binding and standard polypropylene storage tubes using quantitative PCR

Environmental DNA (eDNA): particles of DNA shed by an organism into their environment eDNA samples are typically stored in polypropylene tubes, which could be affecting detection rates if DNA is binding to the plasti

Seasonal to decadal variability in ice discharge frombreak the Greenland Ice Sheet

Rapid changes in thickness and velocity have been observed at many marine-terminating glaciers in Greenland, impacting the volume of ice they export, or discharge, from the ice sheet. While annual estimates of ice-sheet-wide discharge have been previously derived, higher-resolution records are required to fully constrain the temporal response of these glaciers to various climatic and mechanical drivers that vary in sub-annual scales. Here we sample outlet glaciers wider than 1 km (N=230) to derive the first continuous, ice-sheet-wide record of total ice sheet discharge for the 2000–2016 period, resolving a seasonal variability of 6 %. The amplitude of seasonality varies spatially across the ice sheet from 5 % in the southeastern region to 9 % in the northwest region. We analyze seasonal to annual variability in the discharge time series with respect to both modeled meltwater runoff, obtained from RACMO2.3p2, and glacier front position changes over the same period. We find that year-to-year changes in total ice sheet discharge are related to annual front changes (r2=0.59, p=10 −4 ) and that the annual magnitude of discharge is closely related to cumulative front position changes (r2=0.79), which show a net retreat of >400 km, or an average retreat of >2 km, at each surveyed glacier. Neither maximum seasonal runoff or annual runoff totals are correlated to annual discharge, which suggests that larger annual quantities of runoff do not relate to increased annual discharge. Discharge and runoff, however, follow similar patterns of seasonal variability with near-coincident periods of acceleration and seasonal maxima. These results suggest that changes in glacier front position drive secular trends in discharge, whereas the impact of runoff is likely limited to the summer months when observed seasonal variations are substantially controlled by the timing of meltwater input.Physical and Space Geodes

Comparison between a near-field and a far-field indexing approach for characterization of a polycrystalline sample volume containing more than 1500 grains

A comparison of the performance of X-ray diffraction tomography, a near-field diffraction technique, and a far-field diffraction technique for indexing X-ray diffraction data of polycrystalline materials has been carried out by acquiring two sets of diffraction data from the same polycrystalline sample volume. Both approaches used in this study are variants of the three-dimensional X-ray diffraction (3DXRD) methodology, but they rely on different data-collection and analysis strategies. Previous attempts to assess the quality of 3DXRD indexing results from polycrystalline materials have been restricted to comparisons with two-dimensional electron backscatter diffraction cross sections containing a limited number of grains. In the current work, the relative performance of two frequently used polycrystalline-material indexing algorithms is assessed, comparing the indexing results obtained from a threedimensional sample volume containing more than 1500 grains. The currently achievable accuracy of three-dimensional grain maps produced with these algorithms has been assessed using a statistical analysis of the measurement of the size, position and orientation of the grains in the sample. The material used for this comparison was a polycrystalline commercially pure titanium grade 2 sample, which has a hexagonal close-packed crystal structure. The comparison of the two techniques shows good agreement for the measurements of the grain position, size and orientation. Cross-validation between the indexing results shows that about 99% of the sample volume has been indexed correctly by either of these indexing approaches. The remaining discrepancies have been analysed and the strengths and limitations of both approaches are discussed.Materials Science and EngineeringMechanical, Maritime and Materials Engineerin

Rapid fabrication of MOF-based mixed matrix membranes through digital light processing

3D printing, also known as additive manufacturing technology, has greatly expanded across multiple sectors of technology replacing classical manufacturing methods by combining processing speed and high precision. The scientific interest in this technology lies in the ability to create solid architectures with customized shapes and predetermined properties through the exploration of formulations enriched with multifunctional microporous additives such as metal-organic frameworks (MOFs). The concept of additive manufacturing involving advanced materials could be fruitfully adapted for MOF-based mixed matrix membrane fabrication to be used in gas separation applications. In this work, a digital light processing (DLP) approach for fast prototyping of MOF-based mixed matrix membranes (MOF-MMMs) with full control over the shape, size and thickness of the resulting composite using a conventionally available 3D printer has been explored. MOF-based printable inks have been formulated from a selection of commercially available acrylate oligomers and MIL-53(Al)-NH2 additive post-synthetically modified with methacrylic functionality. The formulations and resulting composites have been extensively characterized to demonstrate the suitability of the inks for DLP processing into free-standing MOF-based membranes. The MOF filler anchored to the polymeric matrix enhances the overall permeability at constant selectivity when applied for H2/CO2 separation. The obtained results confirm the applicability of the 3D DLP technology for fast prototyping of MOF-based MMMs and provide new opportunities for further development.ChemE/Catalysis Engineerin

Spatial, temporal and quantitative assessment of catalyst leaching in continuous flow

Catalyst leaching is a major impediment to the development of commercially-viable processes conducted in a liquid-phase. To date, there is no reliable technique that can accurately identify the extent and dynamics of the leaching process in a quantitative manner. In this work, a tandem flow-reactor system has been developed, which allowed us to distinguish between surface-catalyzed reactions from those occurring in solution by comparing%conversion at the exit of each reactor (S1, S2) corresponding to predominance of heterogeneous/homogeneous reactions (spatial) and two different residence times (temporal). A multiscale model is subsequently established to quantify the two types of reaction rate and simulate the catalyst leaching from a cross-coupling catalyst, PdEncat™ 30; including: (1) a multi-particle sizes model for catalyst scale; and (2) a dispersion model for reactor scale. The results show that catalyst leaching occurs via more than one process, and that the homogeneous Pd-catalyst (leached from the immobilized catalyst and dissolved in the flow) dominates the reaction and possesses a much higher activity than the heterogeneous (immobilized) Pd-catalyst. Additionally, the change of leached Pd stream inside reactors can be predicted along with the axial direction and the reaction time through the reactor-scale dispersion model.ChemE/Product and Process Engineerin

Effects of reclaimed asphalt and warm mix asphalt on the availability of the road network

This repot reviews the EARN project, which was undertaken under CEDR Call2012 in order to investigate the effects of using reclaimed asphalt (RA) and/or lower temperature asphalt on the road network. The work consisted of a review of existing data on service lifetime and availability of road materials and structures, a site trial to evaluate varying proportions of RA, experimental evaluation of moisture damage and ageing in asphalt mixtures and development of an impact assessment model. The site trial involved four different mixtures containing varying proportions of RA and warm mix additive and was monitored for international roughness index, mean profile depth, corrected SCRIM Coefficient, indirect stiffness modulus, water sensitivity and indirect tensile strength, the latter with and without artificial ageing. The monitoring was extended to 40 months with two extensions to the project, when monitoring of the binder mechanical and other properties were also made.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.Pavement Engineerin

Combining satellite altimetry and gravimetry data to improve Antarctic mass balance and gia estimates

This study explores an approach that simultaneously estimates Antarctic mass balance and glacial isostatic adjustment (GIA) through the combination of satellite gravity and altimetry data sets. The results improve upon previous efforts by incorporating reprocessed data sets over a longer period of time, and now include a firn densification model to convert the altimetry volume estimates into mass. When the GIA models created from the combination approach were compared to insitu GPS ground station displacements, the vertical rates estimated showed good agreement after a systematic bias was removed from the computed GIA models. The new models suggest the potential for GIA uplift in the Amundsen Sea Sector, as well as the possible subsidence in large parts of East Antarctica.Geoscience & Remote SensingCivil Engineering and Geoscience