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

Research Note: Near-surface layer replacement for sparse data: Is interpolation needed?

Near-surface problem is a common challenge faced by land seismic data processing, where often, due to near-surface anomalies, events of interest are obscured. One method to handle this challenge is near-surface layer replacement, which is a wavefield reconstruction process based on downward wavefield extrapolation with the near-surface velocity model and upward wavefield extrapolation with a replacement velocity model. This requires, in theory, that the original wavefield should be densely sampled. In reality, data acquisition is always sparse due to economic reasons, and as a result in the near-surface layer replacement data interpolation should be resorted to. For datasets with near-surface challenges, because of the complex event behaviour, a suitable interpolation scheme by itself is a challenging problem, and this, in turn, makes it difficult to carry out the near-surface layer replacement. In this research note, we first point out that the final objective of the near-surface layer replacement is not to obtain a newly reconstructed wavefield but to obtain a better final image. Next, based upon this finding, we propose a new thinking, interpolation-free near-surface layer replacement, which can handle complex datasets without any interpolation. Data volume expansion is the key idea, and with its help, the interpolation-free near-surface layer replacement is capable of preserving the valuable information of areas of interest in the original dataset. Two datasets, i.e., a two-dimensional synthetic dataset and a three-dimensional field dataset, are used to demonstrate this idea. One conclusion that can be drawn is that an attempt to interpolate data before layer replacement may deteriorate the final image after layer replacement, whereas interpolation-free near-surface layer replacement preserves all image details in the subsurface.ImPhys/Acoustical Wavefield Imagin

[[alternative]]The Effect of Self-Regulating Task Difficulty in Learning the Roller ball Task

[[abstract]]Base on the framework of the self-controlled learning, this study investigated the differences between the practice schedule of progressively increasing difficulty and the self-controlled task difficulty in learning the Roller ball Task. There were 27 volunteers participated in this study who were evenly divided into three groups. One group practiced the task with a “Self-Controlled Task Difficulty” strategy (SCTD), the others practiced following a “Progressively Increasing Difficulty by 5% and 20%” strategy (PID5, PID20). All participants went through 30 trials pre test, followed by 250 practice trials over 5 days, and an immediate retention test and a two-week retention test. The success rates and improvement rates in three groups were analyzed using one way ANOVA and mixed design two way ANOVA, respectively. The results showed that the SCTD group had a higher success rate during practice and also had better improvement rate for the retention tests. The 2-week retention performance was better than the immediate retention performance. From the different strategies observed in the SCTD group along with the corresponding improvement rates in the post tests, several principles for improvement are proposed. First, enough practice trials and high success rate are the bases to improvement. Second, do not fall into a groove of unsuccessful trials for too long, prolonged unsuccessful experience may induce negative influence to the “to-be-learned” dynamics. Third, make sure to end a practice session with successful performances in order to let the positive consolidation/integration continue during the following break. Self-controlled learning strategy may not always be optimal. The helpful characteristics of the self-controlled strategy that were uncovered in the study may be used in constructing practice plan for the learners so that they do not have to explore too long to benefit from the self-controlled learning strategy.

Green Approach for Post-industrial Urban Regeneration: A case of Economic and Technical Development Zone, China

For cities facing post-industrial transition, urban greenways are proven strategies to activate urban spaces and improve the sustainability of cities. However, significant challenges remain when seeking to link greenways as a greenway network and integrate greenway networks to urban spaces. Given this shortcoming, Yantai National Economic and Technical Development Zone (YEDZ) was selected as a representative case. This paper analyzed the potential role of greenway network and requirements of post-industrial development for the urban environment. It seeks to develop a regeneration approach that integrating urban greenway planning with overall urban reform. Our priorities are providing a pedestrian network with non-utilitarian rhythms by activating former industrial spaces, restructuring urban green spaces, and integrating greenway networks into diverse urban spaces. In this way, it reveals the comprehensive benefits of the urban greenway network and improves overall urban form - multiple benefits, including economic development and social rewards, be created in the regeneration.Housing Quality and Process Innovatio

Comparison of the addiction levels, sociodemographics and buying behaviours of three main types of lottery buyers in China

Objective: To compare the addiction levels, sociodemographic characteristics and buying behaviours of the buyers of the three main types of lottery in China

Insights into the roles of non-catalytic residues in the active site of a GH10 xylanase with activity on cellulose

Bifunctional glycoside hydrolases have potential for cost-savings in enzymatic decomposition of plant cell wall polysaccharides for biofuels and bio-based chemicals. The N-terminal GH10 domain of a bifunctional multimodular enzyme CbXyn10C/Cel48B from Caldicellulosiruptor bescii is an enzyme able to degrade xylan and cellulose simultaneously. However, the molecular mechanism underlying its substrate promiscuity has not been elucidated. Herein, we discovered that the binding cleft of CbXyn10C would have at least six sugar-binding subsites by using isothermal titration calorimetry analysis of the inactive E140Q/E248Q mutant with xylo- and cello-oligosaccharides. This was confirmed by determining the catalytic efficiency of the wild-type enzyme on these oligosaccharides. The free form and complex structures of CbXyn10C with xylose- or glucose-configured oligosaccharide ligands were further obtained by crystallographic analysis and molecular modeling and docking. CbXyn10C was found to have a typical (/)(8)-TIM barrel fold and salad-bowl shape of GH10 enzymes. In complex structures with xylo-oligosaccharides, seven sugar-binding subsites were found, and many residues responsible for substrate interactions were identified. Site-directed mutagenesis indicated that 6 and 10 amino acid residues were key residues for xylan and cellulose hydrolysis, respectively. The most important residues are centered on subsites -2 and -1 near the cleavage site, whereas residues playing moderate roles could be located at more distal regions of the binding cleft. Manipulating the residues interacting with substrates in the distal regions directly or indirectly improved the activity of CbXyn10C on xylan and cellulose. Most of the key residues for cellulase activity are conserved across GH10 xylanases. Revisiting randomly selected GH10 enzymes revealed unreported cellulase activity, indicating that the dual function may be a more common phenomenon than has been expected

A reversible functional supramolecular material formed by host-guest inclusion

Humanity has an urgent need to develop more degradable materials for solving environmental pollution. In this study, through host-guest interactions between fatty acids-modified beta-cyclodextrin (Em-beta CD) and polyethylenimine (PEI) oligomer-grafted ferrocene (PEI-Fc), we designed and prepared a supramolecular polymer (PEI-Fc/Em-beta CD complex), which showed polymeric properties and was able to be used as a cushioning material due to its good compressibility. Compared with conventional polymers, a remarkable advantage of the PEI-Fc/Em-beta CD complex is that it can be dismantled into small molecules and rebuilt easily by controlling the dissociation or reformation of beta CD-Fc inclusion complexes. Furthermore, the material also exhibited good self-healing properties

Phosphor-free nanopyramid white light-emitting diodes grown on {10(1)over-bar1} planes using nanospherical-lens photolithography

We reported a high-efficiency and low-cost nano-pattern method, the nanospherical-lens photolithography technique, to fabricate a SiO2 mask for selective area growth. By controlling the selective growth, we got a highly ordered hexagonal nanopyramid light emitting diodes with InGaN/GaN quantum wells grown on nanofacets, demonstrating an electrically driven phosphor-free white light emission. We found that both the quantum well width and indium incorporation increased linearly along the {10 (1) over bar1} planes towards the substrate and the perpendicular direction to the {10 (1) over bar1} planes as well. Such spatial distribution was responsible for the broadband emission. Moreover, using cathodoluminescence techniques, it was found that the blue emission originated from nanopyramid top, resembling the quantum dots, green emission from the InGaN quantum wells layer at the middle of sidewalls, and yellow emission mainly from the bottom of nanopyramid ridges, similar to the quantum wires.We reported a high-efficiency and low-cost nano-pattern method, the nanospherical-lens photolithography technique, to fabricate a SiO2 mask for selective area growth. By controlling the selective growth, we got a highly ordered hexagonal nanopyramid light emitting diodes with InGaN/GaN quantum wells grown on nanofacets, demonstrating an electrically driven phosphor-free white light emission. We found that both the quantum well width and indium incorporation increased linearly along the {10 (1) over bar1} planes towards the substrate and the perpendicular direction to the {10 (1) over bar1} planes as well. Such spatial distribution was responsible for the broadband emission. Moreover, using cathodoluminescence techniques, it was found that the blue emission originated from nanopyramid top, resembling the quantum dots, green emission from the InGaN quantum wells layer at the middle of sidewalls, and yellow emission mainly from the bottom of nanopyramid ridges, similar to the quantum wires. (C) 2013 AIP Publishing LLC

New microbial resource: microbial diversity, function and dynamics in Chinese liquor starter

Traditional Chinese liquor (Baijiu) solid state fermentation technology has lasted for several thousand years. The microbial communities that enrich in liquor starter are important for fermentation. However, the microbial communities are still under-characterized. In this study, 454 pyrosequencing technology was applied to comprehensively analyze the microbial diversity, function and dynamics of two most-consumed liquor starters (Jiang-and Nong-flavor) during production. In total, 315 and 83 bacterial genera and 72 and 47 fungal genera were identified in Jiang-and Nong-flavor liquor starter, respectively. The relatively high diversity was observed when the temperature increased to 70 and 62 degrees C for Jiang-and Nong-flavor liquor starter, respectively. Some thermophilic fungi have already been isolated. Microbial communities that might contribute to ethanol fermentation, saccharification and flavor development were identified and shown to be core communities in correlation-based network analysis. The predictively functional profile of bacterial communities showed significant difference in energy, carbohydrate and amino acid metabolism and the degradation of aromatic compounds between the two kinds of liquor starters. Here we report these liquor starters as a new functionally microbial resource, which can be used for discovering thermophilic and aerobic enzymes and for food and feed preservation