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

Biomimetic Strain-Stiffening Self-Assembled Hydrogels

Supramolecular structures with strain-stiffening properties are ubiquitous in nature but remain rare in the lab. Herein, we report on strain-stiffening supramolecular hydrogels that are entirely produced through the self-assembly of synthetic molecular gelators. The involved gelators self-assemble into semi-flexible fibers, which thereby crosslink into hydrogels. Interestingly, these hydrogels are capable of stiffening in response to applied stress, resembling biological intermediate filaments system. Furthermore, strain-stiffening hydrogel networks embedded with liposomes are constructed through orthogonal self-assembly of gelators and phospholipids, mimicking biological tissues in both architecture and mechanical properties. This work furthers the development of biomimetic soft materials with mechanical responsiveness and presents potentially enticing applications in diverse fields, such as tissue engineering, artificial life, and strain sensors.Accepted Author ManuscriptChemE/Advanced Soft Matte

Single-Column Model Simulations of Subtropical Marine Boundary-Layer Cloud Transitions Under Weakening Inversions

Results are presented of the GASS/EUCLIPSE single-column model intercomparison study on the subtropical marine low-level cloud transition. A central goal is to establish the performance of state-of-the-art boundary-layer schemes for weather and climate models for this cloud regime, using large-eddy simulations of the same scenes as a reference. A novelty is that the comparison covers four different cases instead of one, in order to broaden the covered parameter space. Three cases are situated in the North-Eastern Pacific, while one reflects conditions in the North-Eastern Atlantic. A set of variables is considered that reflects key aspects of the transition process, making use of simple metrics to establish the model performance. Using this method, some longstanding problems in low-level cloud representation are identified. Considerable spread exists among models concerning the cloud amount, its vertical structure, and the associated impact on radiative transfer. The sign and amplitude of these biases differ somewhat per case, depending on how far the transition has progressed. After cloud breakup the ensemble median exhibits the well-known “too few too bright” problem. The boundary-layer deepening rate and its state of decoupling are both underestimated, while the representation of the thin capping cloud layer appears complicated by a lack of vertical resolution. Encouragingly, some models are successful in representing the full set of variables, in particular, the vertical structure and diurnal cycle of the cloud layer in transition. An intriguing result is that the median of the model ensemble performs best, inspiring a new approach in subgrid parameterization.Atmospheric PhysicsAtmospheric Remote Sensin

CGILS: Results from the first phase of an international project to understand the physical mechanisms of low cloud feedbacks in single column models

CGILS—the CFMIP-GASS Intercomparison of Large Eddy Models (LESs) and single column models (SCMs)—investigates the mechanisms of cloud feedback in SCMs and LESs under idealized climate change perturbation. This paper describes the CGILS results from 15 SCMs and 8 LES models. Three cloud regimes over the subtropical oceans are studied: shallow cumulus, cumulus under stratocumulus, and well-mixed coastal stratus/stratocumulus. In the stratocumulus and coastal stratus regimes, SCMs without activated shallow convection generally simulated negative cloud feedbacks, while models with active shallow convection generally simulated positive cloud feedbacks. In the shallow cumulus alone regime, this relationship is less clear, likely due to the changes in cloud depth, lateral mixing, and precipitation or a combination of them. The majority of LES models simulated negative cloud feedback in the well-mixed coastal stratus/stratocumulus regime, and positive feedback in the shallow cumulus and stratocumulus regime. A general framework is provided to interpret SCM results: in a warmer climate, the moistening rate of the cloudy layer associated with the surface-based turbulence parameterization is enhanced; together with weaker large-scale subsidence, it causes negative cloud feedback. In contrast, in the warmer climate, the drying rate associated with the shallow convection scheme is enhanced. This causes positive cloud feedback. These mechanisms are summarized as the “NESTS” negative cloud feedback and the “SCOPE” positive cloud feedback (Negative feedback from Surface Turbulence under weaker Subsidence—Shallow Convection PositivE feedback) with the net cloud feedback depending on how the two opposing effects counteract each other. The LES results are consistent with these interpretations.Geoscience & Remote SensingCivil Engineering and Geoscience

Comprehensive thermal characterization using ruby R fluorescence lines of sapphire and GaNE(2)-high Raman mode from Raman spectra in high-power flip-chip InGaN/GaN LEDs

A comprehensive temperature characterization method based on the GaNE(2)-high Raman mode and sapphire ruby R fluorescence lines from Raman spectra was developed to analyse the thermal distribution and heat transfer process of high-power flip-chip InGaN/GaN LEDs (FC LEDs). Our analysis demonstrated that in addition to the known problem that the edges of mesa were always the hottest point of FC LEDs, which was due to the current crowding effect, a noteworthy temperature difference was first observed between the sapphire substrate and n-GaN when the injection current was above 300 mA. A 'heat reservoir' was suggested to occur at the interface between the sapphire and n-GaN due to poor thermal conductivity of sapphire when a large amount of heat from the hottest spot cannot be effectively transferred to the Si mount via the active region under high injection currents

The on-orbit calibration of DArk Matter Particle Explorer

The DArk Matter Particle Explorer (DAMPE), a satellite-based cosmic ray and gamma-ray detector, was launched on December 17, 2015, and began its on-orbit operation on December 24, 2015. In this work we document the on-orbit calibration procedures used by DAMPE and report the calibration results of the Plastic Scintillator strip Detector (PSD), the Silicon-Tungsten tracKer-converter (STK), the BGO imaging calorimeter (BGO), and the Neutron Detector (NUD). The results are obtained using Galactic cosmic rays, bright known GeV gamma-ray sources, and charge injection into the front-end electronics of each sub-detector. The determination of the boundary of the South Atlantic Anomaly (SAA), the measurement of the live time, and the alignments of the detectors are also introduced. The calibration results demonstrate the stability of the detectors in almost two years of the on-orbit operation

The on-orbit calibration of DArk Matter Particle Explorer

The DArk Matter Particle Explorer (DAMPE), a satellite-based cosmic ray and gamma-ray detector, was launched on December 17, 2015, and began its on-orbit operation on December 24, 2015. In this work we document the on-orbit calibration procedures used by DAMPE and report the calibration results of the Plastic Scintillator strip Detector (PSD), the Silicon-Tungsten tracKer-converter (STK), the BGO imaging calorimeter (BGO), and the Neutron Detector (NUD). The results are obtained using Galactic cosmic rays, bright known GeV gamma-ray sources, and charge injection into the front-end electronics of each sub-detector. The determination of the boundary of the South Atlantic Anomaly (SAA), the measurement of the live time, and the alignments of the detectors are also introduced. The calibration results demonstrate the stability of the detectors in almost two years of the on-orbit operation

The on-orbit calibration of DArk Matter Particle Explorer

The DArk Matter Particle Explorer (DAMPE), a satellite-based cosmic ray and gamma-ray detector, was launched on December 17, 2015, and began its on-orbit operation on December 24, 2015. In this work we document the on-orbit calibration procedures used by DAMPE and report the calibration results of the Plastic Scintillator strip Detector (PSD), the Silicon-Tungsten tracKer-converter (STK), the BGO imaging calorimeter (BGO), and the Neutron Detector (NUD). The results are obtained using Galactic cosmic rays, bright known GeV gamma-ray sources, and charge injection into the front-end electronics of each sub-detector. The determination of the boundary of the South Atlantic Anomaly (SAA), the measurement of the live time, and the alignments of the detectors are also introduced. The calibration results demonstrate the stability of the detectors in almost two years of the on-orbit operation