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

The dependence of light extraction improvement on optimized surface microstructure for AlGaN-based UVC-LEDs considering TM-polarized emission

In order to improve the light extraction of AlGaN-based short wavelength ultraviolet light emitting diodes (DUC-LEDs), a type of microstructure with high aspect ratio is introduced and optimized on the AlN substrate surface. And, particle swarm optimization (PSO) algorithm is used to inverse design of the surface microstructure to maximize the light extraction efficiency (LEE). Considering that the propagation characteristics of TM-polarized light are different from that of TE-polarized light, the optical field distribution and LEE is analyzed for the UVC-LEDs with different TE-polarized component when the optimized surface microstructure is applied. Furthermore, the preparation process tolerance of the high aspect ratio structure is discussed by calculating the LED's LEE when the structural deviation occurs or morphology changes. Simulation results show that, by using the optimized surface microstructure based on parabola cone array, the LEDs' LEE is increased from 4.4% to 8.7% and from 0.4% to 3.7% for TE-polarized and TM-polarized emission, respectively. In addition, it is demonstrated that the light extraction improvement by the surface microstructure has a good tolerance to the structural deviation and morphology. The results are significant for improving light extraction and realizing high efficient short wavelength AlGaN-based UVC-LEDs by designing surface microstructures.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.ImPhys/Esmaeil Zadeh grou

Investigating Effects of Heterogeneity and Fracture Distribution on Two-Phase Flow in Fractured Reservoir with adaptive time strategy

Modeling of fluid flow in porous media is a pillar in geoscience applications. Previous studies have revealed that heterogeneity and fracture distribution have considerable influence on fluid flow. In this work, a numerical investigation of two-phase flow in heterogeneous fractured reservoir is presented. First, the discrete fracture model is implemented based on a hybrid-dimensional modeling approach, and an equivalent continuum approach is integrated in the model to reduce computational cost. A multilevel adaptive strategy is devised to improve the numerical robustness and efficiency. It allows up to 4-levels adaption, where the adaptive factors can be modified flexibly. Then, numerical tests are conducted to verify the the proposed method and to evaluate its performance. Different adaptive strategies with 3-levels, 4-levels and fixed time schemes are analyzed to evaluate the computational cost and convergence history. These evaluations demonstrate the merits of this method compared to the classical method. Later, the heterogeneity in permeability field, as well as initial saturation, is modeled in a layer model, where the effect of layer angle and permeability on fluid flow is investigated. A porous medium containing multiple length fractures with different distributions is simulated. The fine-scale fractures are upscaled based on the equivalent approach, while the large-scale fractures are retained. The conductivity of the rock matrix is enhanced by the upscaled fine-scale fractures. The difference of hydraulic property between homogeneous and heterogeneous situations is analyzed. It reveals that the heterogeneity may influence fluid flow and production, while these impacts are also related to fracture distribution and permeability.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.Delft Institute of Applied Mathematic

Influence of surface pretreatment on phosphate conversion coating on AZ91 Mg alloy

Surface pretreatment is generally applied before application of protective coatings on Mg alloys, which influences surface microstructure and electrochemical activity of the substrate and has an effect on the coating properties. The effect of various pretreatment processes (sand-blasting, grinding and polishing) on the microstructure and corrosion protection performance of phosphate conversion coating (PCC) on AZ91D Mg alloy was investigated in the present study. Sand-blasting cleaning significantly increases the surface roughness and electrochemical activity of the substrate, leading to formation of a porous PCC with inferior corrosion protection performance. In the case of ground/polished Mg alloy, the uniformity and corrosion resistance of the resultant conversion coating are mainly related to the surface roughness. Relatively low surface roughness of the substrate facilitates formation of a corrosion protective PCC.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.(OLD) MSE-

The dynamic behavior of gas hydrate dissociation by heating in tight sandy reservoirs: A molecular dynamics simulation study

Knowledge on the kinetics of gas hydrate dissociation in microporous sediments is very important for developing safe and efficient approaches to gas recovery from natural gas hydrate (NGH) deposits. Herein, molecular dynamics (MD) simulations are used to study the dissociation kinetics in microporous sediments. The hydrate phase occupies a confined sandy nanopore formed by two hydroxylated silica surfaces with a buffering water layer between the hydrate and silica phase, meanwhile, this system is in contact with the bulk phase outside the pore. The hydrates in this sediment system dissociate layer-by-layer in a shrinking core manner. The released methane molecules aggregate and eventually evolve into nanobubbles, most of which are spherical cap-shaped on the hydroxylated silica surfaces. At high initial temperatures, a faster decomposition of the hydrate phase is observed, however, fewer methane molecules migrate to the bulk phase from the pore phase. These phenomena may occur because more methane molecules are released from the hydrate phase and facilitate the formation of nanobubbles with large heat injection; these nanobubbles can stably adsorb on the surface of silica and capture the surrounding methane molecules, thereby decreasing the number of methane molecules in the water phase. In addition, the injection speed of heat flow should be significantly increased at high dissociation temperatures when using the thermal stimulation method to extract gas from hydrates in tight sediments. This study provides molecular level insight into the kinetic mechanism of hydrate dissociation and theoretical guidance for gas production by thermal injection from sediments with low permeabilities.Accepted Author ManuscriptEngineering Thermodynamic

The Relative Biological Effect of Spread-Out Bragg Peak Protons in Sensitive and Resistant Tumor Cells

Purpose: Variations in the radiosensitivity of tumor cells within and between tumors impact tumor response to radiation, including the dose required to achieve permanent local tumor control. The increased expression of DNA-PKcs, a key component of a major DNA damage repair pathway in tumors treated by radiation, suggests that DNA-PKcs– dependent repair is likely a cause of tumor cell radioresistance. This study evaluates the relative biological effect of spread-out Bragg-peak protons in DNA-PKcs–deficient cells and the same cells transfected with a functional DNA-PKcs gene. Materials and Methods: A cloned radiation-sensitive DNA-PKcs–deficient tumor line and its DNA-PKcs–transfected resistant counterpart were used in this study. Thepresence of functional DNA-PKcs was evaluated by DNA-PKcs autophosphorylation.Cells to be proton irradiated or x-irradiated were obtained from the same single cell suspension and dilution series to maximize precision. Cells were concurrently exposed to 6-MV x-rays or mid 137-MeV spread-out Bragg peak protons and cultured for colony formation. Results: The surviving fraction data were well fit by the linear-quadratic model for each of 8 survival curves. The results suggest that the relative biological effectiveness of mid spread-out Bragg peak protons is approximately 6% higher in DNA-PKcs–mediated resistant tumor cells than in their DNA-PKcs–deficient and radiation-sensitive counterpart.Conclusion: DNA-PKcs–dependent repair of radiation damage is less capable ofrepairing mid spread-out Bragg peak proton lesions than photon-induced lesions, suggesting protons may be more efficient at sterilizing DNA-PKcs–expressing cells that are enriched in tumors treated by conventional fractionated dose x-irradiation.RST/Reactor Physics and Nuclear Material

Molecularly imprinted nanoparticles based potentiometric sensor with a nanomolar detection limit.pdf

Lysozymes are key proteins that play important roles in innate immune defense in many animal phyla by breaking down the bacterial cell-walls. In this study, we report the molecular cloning, sequence analysis and phylogeny of the first caudate amphibian g-lysozyme: a full-length spleen cDNA library from axolotl (Ambystoma mexicanum). A goose-type (g-lysozyme) EST was identified and the full-length cDNA was obtained using RACE-PCR. The axolotl g-lysozyme sequence represents an open reading frame for a putative signal peptide and the mature protein composed of 184 amino acids. The calculated molecular mass and the theoretical isoelectric point (pI) of this mature protein are 21523.0 Da and 4.37, respectively. Expression of g-lysozyme mRNA is predominantly found in skin, with lower levels in spleen, liver, muscle, and lung. Phylogenetic analysis revealed that caudate amphibian g-lysozyme had distinct evolution pattern for being juxtaposed with not only anura amphibian, but also with the fish, bird and mammal. Although the first complete cDNA sequence for caudate amphibian g-lysozyme is reported in the present study, clones encoding axolotl's other functional immune molecules in the full-length cDNA library will have to be further sequenced to gain insight into the fundamental aspects of antibacterial mechanisms in caudate.Lysozymes are key proteins that play important roles in innate immune defense in many animal phyla by breaking down the bacterial cell-walls. In this study, we report the molecular cloning, sequence analysis and phylogeny of the first caudate amphibian g-lysozyme: a full-length spleen cDNA library from axolotl (Ambystoma mexicanum). A goose-type (g-lysozyme) EST was identified and the full-length cDNA was obtained using RACE-PCR. The axolotl g-lysozyme sequence represents an open reading frame for a putative signal peptide and the mature protein composed of 184 amino acids. The calculated molecular mass and the theoretical isoelectric point (pI) of this mature protein are 21523.0 Da and 4.37, respectively. Expression of g-lysozyme mRNA is predominantly found in skin, with lower levels in spleen, liver, muscle, and lung. Phylogenetic analysis revealed that caudate amphibian g-lysozyme had distinct evolution pattern for being juxtaposed with not only anura amphibian, but also with the fish, bird and mammal. Although the first complete cDNA sequence for caudate amphibian g-lysozyme is reported in the present study, clones encoding axolotl's other functional immune molecules in the full-length cDNA library will have to be further sequenced to gain insight into the fundamental aspects of antibacterial mechanisms in caudate

Warm-season Grazing Benefits Species Diversity Conservation and Topsoil Nutrient Sequestration in Alpine Meadow

Seasonal grazing is one way of the moderate grazing regimes, but little information is available on compared study of seasonal grazing in alpine meadow. We studied the aboveground and belowground properties among warm-seasonal grazing meadows and cold-seasonal grazing meadows on the Qinghai-Tibetan Plateau. Results showed that the warm-seasonal grazing increased forb functional group proportion, plant density and evenness index but decreased root biomass, plant height and graminoid functional group proportions. Grazing seasons affected variation in soil bulk density, soil water content, pH and soil nutrient content, and the variations caused the various of soil carbon and nitrogen density. The highest values of soil carbon and nitrogen contents and densities in the warm-season grazing meadow occurred at the top 10-cm soil, while the highest values in the cold-season grazing meadow occurred at the depth of 30- to 50-cm soil. Our results indicated that the warm-season grazing is suitable for the species diversity conservation and the nutrient sequestration at the topsoil. However, the cold-season grazing is suitable for the nutrient sequestration at the deep soil. This study implied that the warm-season and cold-season grazing might be exchanged regularly to practice continuous carbon and nitrogen sequestration. Periodic cold-season and warm-season grazing would be the suitable grazing regime to keep alpine meadow sustainability. Copyright (c) 2016 John Wiley & Sons, Ltd

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