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

Spatial and temporal reconstruction of unsteady rotating forces through an inverse acoustic method

An inverse acoustic method is presented in this work, which allows to determine the spatial and temporal distribution of unsteady rotating forces from microphone array measurements. The method is based on the usage of a space–time regularization with a mixed norm. The proposed method can take advantage of a prior knowledge of the space–time characteristics of the unsteady rotating forces to ensure an accurate force reconstruction in real-time, using a smaller number of input signals compared to more conventional inverse methods. Different properties of the proposed method are initially investigated by using synthetic acoustic signals radiated from rotating point sources and computed via an acoustic analogy formulation. Finally, the method is validated by using experimental acoustic signals radiated from the rotor of an unmanned aerial vehicle.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.Wind Energ

Real-time reconstruction of unsteady rotating forces acting by rotor blades in moving medium

A time-domain inverse aeroacoustic method based on the convective Ffowcs Williams–Hawkings equation is presented. The method allows to determine, in real-time, the unsteady forces exerted on rotating blades in the presence of a moving medium. The inversion procedure is based on a space-time regularization with a mixed l1,2-norm, which guarantees accuracy and smoothness of the solution. The method is initially verified through synthetic acoustic signals emitted by rotating sources in a constant flow, up to a convective Mach number of about 0.88. Then the method is validated through signals generated by a propeller immersed in a wind-tunnel jet flow, up to a Mach number of 0.06. Due to the reduced convective Mach number, the leading aeroacoustic effect is derived from a variation of the blade loading. It is argued that the onset of flow separation at high values of the rotor advance ratio is responsible for the onset of force fluctuations that the inverse method is able to retrieve both qualitatively and quantitatively.Wind Energ

Built environment and travel behavior in rural areas: A scientometric literature review

With the rise of global urbanization, the rural built environment has undergone tremendous changes. As such, the rural built environment impacts on residents’ daily travel behavior is getting more researchers’ attention. To date, most of the research focuses on urban areas in developed countries. To understand the state-of-the-art of interplay between the rural built environment and travel behaviors and to identify future research directions, this study adopts a science mapping approach to identify the relevant topics, authors, journals, and countries of the research done. This study proceeds through bibliometric retrieval of articles from 2005, followed by scientometric analysis and qualitative discussion. 37 documents are found to compare urban and rural domains, with 28 on the rural built environment. Research gaps and the research trends are discussed, of which the main themes are multi-dimensional correlation comparison of rural transportation service systems and emerging transportation modes, the influence of rural social and cultural factors on travel behavior, and low-carbon sustainable transportation. This review provides empirical foundation for current state-of-the-art and identifies the future research directions, specifically for rural built environment impact on travel behavior.Design & Construction Managemen

Degradation behaviors and in-vivo biocompatibility of a rare earth- and aluminum-free magnesium-based stent

Biodegradable stents can provide scaffolding and anti-restenosis benefits in the short term and then gradually disappear over time to free the vessel, among which the Mg-based biodegradable metal stents have been prosperously developed. In the present study, a Mg-8.5Li (wt.%) alloy (RE- and Al-free) with high ductility (> 40%) was processed into mini-tubes, and further fabricated into finished stent through laser cutting and electropolishing. In-vitro degradation test was performed to evaluate the durability of this stent before and after balloon dilation. The influence of plastic deformation and residual stress (derived from the dilation process) on the degradation was checked with the assistance of finite element analysis. In addition, in-vivo degradation behaviors and biocompatibility of the stent were evaluated by performing implantation in iliac artery of minipigs. The balloon dilation process did not lead to deteriorated degradation, and this stent exhibited a decent degradation rate (0.15 mm/y) in vitro, but divergent result (> 0.6 mm/y) was found in vivo. The stent was almost completely degraded in 3 months, revealing an insufficient scaffolding time. Meanwhile, it did not induce possible thrombus, and it was tolerable by surrounding tissues in pigs. Besides, endothelial coverage in 1 month was achieved even under the severe degradation condition. In the end, the feasibility of this stent for treatment of benign vascular stenosis was generally discussed, and perspectives on future improvement of Mg-Li-based stents were proposed.Accepted Author ManuscriptBiomaterials & Tissue Biomechanic

The 'Typhoon Eye Effect': determinants of distress during the SARS epidemic

This study examined the effect of the SARS crisis on the level of distress in people both in and around epidemic areas of China during the time of the crisis. We designed a questionnaire to measure personality factors, beliefs regarding SARS, behavioral responses to SARS, and distress levels. The level of exposure to SARS was not a primary determinant of experienced anxiety; indeed, nearness to the center of the epidemic was negatively related to anxiety levels. Instead, more subjective interpretations of the situation were the primary determinants of distress. We propose a 'Typhoon Eye Effect' metaphor to describe the spread of psychological distress

Developing equations to explore relationships between aggregate stability and erodibility in Ultisols of subtropical China

A soil aggregate represents a key soil structural unit that influences several physical soil properties such as water infiltration, runoff and erosion. The relationships between soil aggregate stability and interrill and rill erodibility are critical to process-based erosion prediction models yet remain unclear, likely due to the difficulty of distinguishing between interrill and rill-eroded sediment during the erosion process. This study was designed to partition interrill and sill erosion rates and relate them to the aggregate stability of Ultisols in subtropical China. Six kinds of rare earth elements (REEs) were applied as tracers mixed with two cultivated soils developed over Quaternary red clay or shale at six slope positions. Soil aggregate stability was determined by the Le Bissonnais (LB)-method. Simulated rainfall of three intensities (60, 90 and 120 mm h(-1)) was applied to a soil plot (2.25 m long, 0.5 m wide, 0.2 m deep) at three slope gradients (10 degrees, 20 degrees and 30 degrees) for a duration of 30 min after runoff initiation. The results indicated that rill and interrill erosion rates in the soil developed over shale were considerably greater than those in the soil developed over Quaternary red clay. Equations using an aggregate stability index A(s) to replace the erodibility factor of interrill and rill erosion in the Water Erosion Prediction Project (WEPP) model were constructed after analysing the relationships between estimated and measured rill and interrill erosion data. The results show that these equations based on A, have the potential to improve methods for assessing interrill and rill erosion erodibility synchronously for subtropical Ultisols by using an REE tracing method

Quantifying contributions of slaking and mechanical breakdown of soil aggregates to splash erosion for different soils from the Loess plateau of China

The information of aggregate disintegration mechanisms during splash erosion is scant. This study was conducted to quantify contributions of the mechanisms of aggregate disintegration to splash erosion. Six soils with five soil textures were used. Soil aggregate stability was determined by the Le Bissonnais (LB) method. Deionized water was used to simulate the combined effect of slaking and mechanical disaggregation, while ethanol was used to estimate the sole contribution of the mechanical breakdown. Simulated rainfall with intensity of 60 mm h(-1) was applied at five fall heights (0.5 m, 1 m, 1.5 m, 2 m and 2.5 m) to achieve different levels of rainfall kinetic energy. The results indicated that slaking caused the most severe aggregate breakdown, and followed by mechanical breakdown, while chemical dispersion in slow wetting with deionized water was the weakest breakdown mechanism. The splash erosion rates due to the effects of slaking and mechanical breakdown increased with an increase in rainfall kinetic energy. The contributions of the slaking (mechanical breakdown) to splash erosion decreased (increased) as rainfall kinetic energy increased. The contribution of mechanical breakdown had a power function relation with rainfall kinetic energy, and had the most significant correlation with RSI (relative slaking index)/RMI (relative mechanical breakdown index). A power and a linear function could be used to describe the relationships between the contributions of mechanical breakdown with rainfall kinetic energy and RSI/RMI, respectively, which could be used to estimate the contribution of mechanical breakdown. The results of this research would be helpful to improving the soil erosion prediction models

A new anti-cancer strategy of damaging mitochondria by pro-apoptotic peptide functionalized gold nanoparticles

Gold nanoparticles functionalized with pro-apoptotic peptide (PAP-AuNPs) were fabricated, which were able to lead to programmed cell-death by damaging mitochondria.Gold nanoparticles functionalized with pro-apoptotic peptide (PAP-AuNPs) were fabricated, which were able to lead to programmed cell-death by damaging mitochondria

Holocene erosion triggered by climate change in the central Loess Plateau of China

Understanding changes in Holocene erosion is essential for predicting soil erosion in the future. However, the quantitative response of natural erosion to Holocene climate change is limited for the Loess Plateau of China. In this study, two soil profiles were investigated on the Luochuan and Yanchang sites in the central Loess Plateau of China; and four climate indicators, i.e. magnetic susceptibility, calcium carbonate content, total organic carbon content, and clay content (< 0.005 mm), were analyzed to describe climate change. The equations fitted using modern pedogenic susceptibility, precipitation, and temperature were used to quantitatively reconstruct paleoprecipitation and paleotemperature in the Holocene. The current relationship between soil erosion intensity and precipitation was determined and used to estimate historical erosion. Results indicated that climate was coldest and driest between 12,000 and 8500 cal. yr BP, and became wanner and wetter during 8500 to 5500 cal. yr BP. The warmest and wettest climate was from 5500 to 3000 cal. yr BP and was getting colder and dryer over the last 3000 years. Holocene erosion intensity changed with fluctuation of mean annual precipitation, and these changes were different on both sites. The peak erosion values were 20,966 t.km(-2.)yr(-1) in 7500 cal. yr BP and 21,148 t.km(-2.)yr(-1) in 3300 cal. yr BP on the Luochuan and Yanchang sites, respectively. Furthermore, more severe soil erosion with a faster increase was estimated on the Yanchang site than Luochuan site with a range between 6547 and 11,177 t.km(-2.)yr(-1) during the last 1800 years. This study proposed a new method to quantify historical soil erosion triggered by climate change, which not only can derive detailed soil erosion intensity change with variation of climate, but also provide a way to compare soil losses between different areas