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

Analysis of the microcharacteristics of different kinds of asphalt based on different aging conditions

Asphalt aging often leads to rapid degradation of road performance, which seriously affects the service life of asphalt pavement. Exploring the influence of asphalt oil sources, asphalt grades, and filler types on asphalt microcharacteristics in the asphalt aging process can provide an essential reference to guide asphalt pavement maintenance. In this study, we selected seven kinds of asphalt and three fillers commonly used in China for research. The pressurized aging vessel (PAV) and homemade ultraviolet (UV) aging equipment were used to perform thermo-oxidative aging and UV aging tests, respectively, of asphalt. The microcharacteristics of asphalt before and after aging were analyzed via attenuated total reflectance fourier transformation infrared spectroscopy and nuclear magnetic resonance 1H spectroscopy. The results show that the oil source of asphalt exerted the most significant influence on the microcharacteristics of the aged asphalt, while the effect of the asphalt grade was relatively limited. The addition of fillers did not affect the aging mechanism of asphalt. UV and PAV aging generated apparent differences in the changes in the aged asphalt microstructure.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

Fertile sediment and ammonium enrichment decrease the growth and biomechanical strength of submersed macrophyte Myriophyllum spicatum in an experiment

Decline of submersed macrophytes has occurred in eutrophic lakes worldwide. Little is known about effects of nutrient enrichment on biomechanical properties of submersed macrophytes. In a 30-day experiment, Myriophyllum spicatum was cultured in aquaria containing two types of sediment (mesotrophic clay vs. fertile loam) with contrasting water NH4 (+) concentrations (0 vs. 3.0 mg L-1 NH4-N). The plant growth, shoot and root morphology, stem biomechanical properties, and stem total nonstructure carbohydrates content (TNC) were examined. The NH4 (+)-enriched water, particularly combined with the fertile sediment, caused adverse effects on M. spicatum as indicated by reductions in the growth, stem biomechanical properties (tensile force, bending force and structural stiffness), and TNC content. These results indicate that increased sediment fertility and water NH4 (+)-enrichment made the plant more fragile and vulnerable to hydraulic damage, particularly for the upper stem, implying that M. spicatum was prone to uprooting and fracture by hydraulic force, and the broken fragment from parent shoot of M. spicatum might have low-survival potential due to its low-TNC content. This may be a mechanical aspect for the decline of submersed macrophytes and makes it more difficult to restore submersed vegetation in the eutrophic lakes.Decline of submersed macrophytes has occurred in eutrophic lakes worldwide. Little is known about effects of nutrient enrichment on biomechanical properties of submersed macrophytes. In a 30-day experiment, Myriophyllum spicatum was cultured in aquaria containing two types of sediment (mesotrophic clay vs. fertile loam) with contrasting water NH4 (+) concentrations (0 vs. 3.0 mg L-1 NH4-N). The plant growth, shoot and root morphology, stem biomechanical properties, and stem total nonstructure carbohydrates content (TNC) were examined. The NH4 (+)-enriched water, particularly combined with the fertile sediment, caused adverse effects on M. spicatum as indicated by reductions in the growth, stem biomechanical properties (tensile force, bending force and structural stiffness), and TNC content. These results indicate that increased sediment fertility and water NH4 (+)-enrichment made the plant more fragile and vulnerable to hydraulic damage, particularly for the upper stem, implying that M. spicatum was prone to uprooting and fracture by hydraulic force, and the broken fragment from parent shoot of M. spicatum might have low-survival potential due to its low-TNC content. This may be a mechanical aspect for the decline of submersed macrophytes and makes it more difficult to restore submersed vegetation in the eutrophic lakes

Evaluating AlGaN/AlN/GaN heterostructure Schottky barrier heights with flat-band voltage from forward current-voltage characteristics

Both circular and rectangular Ni Schottky contacts on AlGaN/AlN/GaN heterostructures have been fabricated. Both of the Schottky barrier heights were measured by internal photoemission. The flat-band voltage (V(0)) for the AlGaN/AlN/GaN heterostructure Schottky contacts was analyzed and obtained from the forward current-voltage (I-V) characteristics. Based on the forward I-V characteristics and with the obtained flat-band voltage, the Schottky barrier heights for the circular and rectangular diodes have been analyzed and calculated by self-consistently solving Schrodinger's and Poisson's equations. The evaluated Schottky barrier heights for the prepared circular and rectangular Ni Schottky diodes agree well with the photocurrent measured results. (C) 2011 American Institute of Physics. [doi:10.1063/1.3643139

Effects of moderate ammonium enrichment on three submersed macrophytes under contrasting light availability

1. Increased ammonium concentrations and decreased light availability in a water column have been reported to adversely affect submersed vegetation in eutrophic waters worldwide. 2. We studied the chronic effects of moderate NH(4)(+) enrichment (NH(4)-N: 0.16-0.25 mg L(-1)) on the growth and carbon and nitrogen metabolism of three macrophytes (Ceratophyllum demersum, Myriophyllum spicatum and Vallisneria natans) under contrasting light availability in a 2-month experiment. 3. The NH(4)(+) enrichment greatly increased the contents of free amino acids and nitrogen in the shoot/leaf of the macrophytes. This indicates that NH(4)(+) was the dominant N source for the macrophytes. 4. Soluble carbohydrate contents remained relatively stable in the shoot/leaf of the macrophytes irrespective of the treatments. Under ambient light, the starch contents in the shoot/leaf of C. demersum and M. spicatum increased with NH(4)(+) enrichment, whereas V. natans did not exhibit any change. The starch contents decreased in C. demersum, increased in M. spicatum and remained unchanged in V. natans after the combined treatment of NH(4)(+) enrichment and reduced light. 5. The NH(4)(+) enrichment did not affect the growth of the three macrophytes under the ambient light. However, it did suppress the growth of C. demersum and M. spicatum under the reduced light. The results indicate that a moderate NH(4)(+) enrichment was not directly toxic to the macrophytes although it might change their viability in eutrophic lakes in terms of the carbon and nitrogen metabolism

EFFECTS OF SEDIMENT TYPE ON STEM MECHANICAL PROPERTIES OF THE SUBMERGED MACROPHYTE HYDRILLA VERTICILLATA (L.F.) ROYLE

The decline of submerged macrophytes during the eutrophication progress can be partly attributed to the adverse effects of fertile sediment on morphology and physiology of plants. However, little is known about its effects on mechanical properties, although this has been confirmed in terrestrial plants. In this study, the morphological traits, mechanical properties (tensile force, tensile stress and bending index) and cellulose content of Hydrilla verticillata grown on three types of sediment (sand, clay and loam) with different nutrient levels, were examined experimentally. Results showed that considerable variations in mechanical properties of plants were observed among the three sediments and along the stem, with the highest values in clay sediment and a decreased trend from the lower to upper segment, especially when grown in loam sediment, indicating that mesotrophic sediment benefits to higher mechanical resistance of stems than the other two sediments, and plants were prone to break at the other two segments, rather than the lower segment. Stem cross sectional area and internode length were significantly correlated with tensile force, and tensile stress was a linear function of stem cellulose content. Plants grown in clay sediment showed the shortest plant height and the maximum branch numbers, which are morphologically advantageous to reduce the hydraulic force. In conclusion, fertile sediment stimulated the plant growth at the expense of H. verticillata performance with respect to mechanical resistance. Decrease of mechanical resistance could contribute to the decline of submerged macrophytes with the enrichment of sediment nutrient during the process of eutrophication.The decline of submerged macrophytes during the eutrophication progress can be partly attributed to the adverse effects of fertile sediment on morphology and physiology of plants. However, little is known about its effects on mechanical properties, although this has been confirmed in terrestrial plants. In this study, the morphological traits, mechanical properties (tensile force, tensile stress and bending index) and cellulose content of Hydrilla verticillata grown on three types of sediment (sand, clay and loam) with different nutrient levels, were examined experimentally. Results showed that considerable variations in mechanical properties of plants were observed among the three sediments and along the stem, with the highest values in clay sediment and a decreased trend from the lower to upper segment, especially when grown in loam sediment, indicating that mesotrophic sediment benefits to higher mechanical resistance of stems than the other two sediments, and plants were prone to break at the other two segments, rather than the lower segment. Stem cross sectional area and internode length were significantly correlated with tensile force, and tensile stress was a linear function of stem cellulose content. Plants grown in clay sediment showed the shortest plant height and the maximum branch numbers, which are morphologically advantageous to reduce the hydraulic force. In conclusion, fertile sediment stimulated the plant growth at the expense of H. verticillata performance with respect to mechanical resistance. Decrease of mechanical resistance could contribute to the decline of submerged macrophytes with the enrichment of sediment nutrient during the process of eutrophication

Suppressed growth of the submersed macrophyte Vallisneria natans in a non-rooted suspended state

The growth, morphological traits, and biomass accumulation and allocation pattern of Vallisneria natans grown from buds were observed in a non-rooted suspended state in the laboratory. Submersed anchored V. natans were about 229% higher in height, 208% higher in leaf number, 719% greater in total root length, 64% higher in lacunal root volume, and 1473% greater in total biomass dry weight compared with suspended V. natans. However, insignificant differences existed in root diameter, specific root length, and biomass allocation patterns. These results indicate that when V. natans is not anchored to a substrate in the normal mode, the growth will be markedly suppressed

Variation in stable isotope signatures of the submersed macrophyte Vallisneria natans collected from several shallow lakes in China

We examined the stable carbon and nitrogen isotope variation in the submersed macrophyte Vallisneria natans in several shallow Chinese lakes relative to physicochemical parameters of the lake water and V. natans tissue. Of the parameters examined, the delta(15)N values of V. natans were correlated only with different inorganic nitrogen concentrations in the water column, suggesting that V. natans could be a sensitive bioindicator for monitoring nitrogen input into lakes. The delta(13)C of V. natans varied widely and was correlated only with the inorganic carbon concentration of the water, possibly reflecting complex photosynthetic fixation and adaptations of V. natans to utilize inorganic carbon sources of different types

Isotopic turnover of a submersed macrophyte following transplant: the roles of growth and metabolism in eutrophic conditions

Stable isotopic turnover with isotopic change due to growth and metabolic tissue replacement associated with a change in environmental conditions is a critical aspect of the use of stable isotope analyses as time-integrating tracers of resource-consumer interactions. However, stable isotopic turnover in plants remains poorly understood compared with those of animals, and here we used continuous flow elemental analyzer-isotopic ratio mass spectrometry (EA-IRMS) to analyse the turnover of stable carbon and nitrogen isotopes in a submersed macrophyte (Vallisneria natans) after transplantation to hypereutrophic and mesoeutrophic treatments in a field mesocosm experiment. The direction and magnitude of the isotopic shifts of V. natans were suggested to be determined by the inorganic nutrient availability and its isotopic content in the different treatments. Based on the modelling results of turnover, the contribution of growth to the isotopic turnover was as high as those observed in various aquatic ectotherms. However, the contribution of metabolism was also considerable, especially for nitrogen in the hypereutrophic treatment, which was argued to be a response, co-occurring with growth inhabitation and biochemical disorder of V. natans, to the stress induced by the eutrophication. Our results indicated that isotope turnover in a macrophyte is a feasible technique for estimating its ecophysiological conditions in the natural environment, and that it may facilitate understanding of isotopic data in field studies of food web and habitat restoration under eutrophic conditions. Copyright (C) 2011 John Wiley & Sons, Ltd