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

Synergy of Ni micro-alloying and thermomechanical processing in Al–Mg–Si–Cu–Zn–Fe–Mn alloys with enhanced bendability

Synergy of Ni micro-alloying and thermomechanical processing on the phase distribution, formability and bendability of Al–Mg–Si–Cu–Zn–Fe–Mn alloys was systematically studied in this paper. With the addition of micro-alloying Ni, the Ni-containing Fe-rich phase can be formed, which not only serves as nucleation sites of Mg–Si precipitates (such as, Q phase) during the casting process, but also improves the uniform distribution level of Fe-rich phases after homogenization. The formability and bendability of Ni-containing alloy can be both improved to a certain level due to the positive effect of Ni micro-alloying. In comparison, if increasing the cold rolling deformation between hot rolling and annealing, the distribution of multi-scale Fe-rich phases can be significantly improved based on the synergy of Ni micro-alloying and thermomechanical processing. And finally, this improvement further results in the great improvements in the microstructure, texture, formability (average r = 0.688, △r = −0.09) and bendability of the alloy together. Based on the microstructure evolution, the synergy mechanism of Ni micro-alloying and thermomechanical processing is put forward in this paper.Team Maria Santofimia Navarr

Fast age-hardening response of Al–Mg–Si–Cu–Zn–Fe–Mn alloy via coupling control of quenching rate and pre-aging

The coupling control of quenching rate and pre-aging and its positive effect on the age-hardening response of Al–Mg–Si–Cu–Zn–Fe–Mn alloy was systematically investigated. The larger and more stable solute clusters can be formed in alloy with fast age-hardening response by using the lower quenching rate (5.3 °C/min) and an appropriate pre-aging, in which the deterioration of natural aging also can be obviously suppressed. Additionally, the highest bake hardening increment of the alloy can reach 145.2 MPa, which is much higher than those of traditional Al–Mg–Si–(Cu) alloys (such as, 6016 and 6111 alloys). Based on the detailed precipitation behavior characterization of alloys with different quenching rates and the same pre-aging, the quenching rate change can result in the significant differences in the size, number density of precipitates in the both paint baking and peak aging states, but the type of precipitates basically keeps the same, i.e., Mg–Si precipitates, and no Mg–Zn precipitates can be observed. Finally, the related mechanisms of coupling control of quenching rate and pre-aging were also discussed in this paper. The developed coupling control method shows great potential and could significantly increase applications of Al–Mg–Si–Cu–Zn–Fe–Mn alloys with a fast age-hardening response.Team Maria Santofimia Navarr

Uptake of heavy metal ions in layered double hydroxides and applications in cementitious materials: Experimental evidence and first-principle study

The uptake mechanism of heavy metal ions in layered double hydroxides (LDHs) is investigated in this paper via solid-solution exchange experiments and first principle study. The uptake capacities of C-LDHs for heavy metal ions from solutions are experimentally investigated and the structures of LDHs doped with various heavy metal ions are revealed. The doped structures of LDHs are further re-established with first principle calculations. The results show that Cu2+ or Cr3+ ions are immobilized in the form of isomorphic substitution for Mg2+ and Al3+ in the plate of the layered structure, respectively, during reconstruction of calcined LDHs, forming a non-stoichiometric structure. The structure of the Cu2+ doped LDHs is identified as [Mg2+ (1−x)(1−z)Cu2+ (1−x)zAl3+ x(OH)2] An− x/n·yH2O, where z is the molar ratio of Cu2+ to Mg2+. The structure of Cr3+ doped LDHs is identified as [Mg2+ 1−x Cr3+ xzAl3+ x(1−z)(OH)2] An− (x+z)/n·yH2O, where z is the molar ratio of Cr3+ to Al3+. The Cu2+ or Cr3+ ions in the hardened cement paste modified with calcined Mg-Al LDHs as immobilizing admixture can be efficiently removed from the pore solution and chemically stabilized in the structure of LDHs.Accepted author manuscriptMaterials and Environmen

A 90.6% Efficient, 0.333 W/mm2 Power Density Direct 48V-to-1V Dual Inductor Hybrid Converter with Delay-line Based V2D Controller

This brief presents a 48V-to-1V 10-level dual inductor hybrid converter (DIHC) containing 11 on-chip switches and an off-chip gallium nitride (GaN) switch. Thanks to the 10-level Dickson switched-capacitor (SC) circuit, most of the voltage stress will be taken over by off-chip capacitors, which reduces the voltage stress of each switch to 4.8 V and takes full advantage of the voltage pressure on the 5-V on-chip transistors. This proposed structure is implemented in a 0.18- $\mu \text{m}$ BCD process to convert 48-V input to 1-V output with up to 18-A current load. The post-layout simulations show that a peak power efficiency of 90.6% can be achieved at 5.2-A loading and the power density is about 0.333 $W/mm^{2}$ considering the power stage area.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.Electronic Instrumentatio

Water-Soluble Anthraquinone Photocatalysts Enable Methanol-Driven Enzymatic Halogenation and Hydroxylation Reactions

Peroxyzymes simply use H2O2 as a cosubstrate to oxidize a broad range of inert C-H bonds. The lability of many peroxyzymes against H2O2 can be addressed by a controlled supply of H2O2, ideally in situ. Here, we report a simple, robust, and water-soluble anthraquinone sulfonate (SAS) as a promising organophotocatalyst to drive both haloperoxidase-catalyzed halogenation and peroxygenase-catalyzed oxyfunctionalization reactions. Simple alcohols, methanol in particular, can be used both as a cosolvent and an electron donor for H2O2 generation. Very promising turnover numbers for the biocatalysts of up to 318 »000 have been achieved. BT/Biocatalysi

A Biocatalytic Platform for the Synthesis of Enantiopure Propargylic Alcohols and Amines

Propargylic alcohols and amines are versatile building blocks in organic synthesis. We demonstrate a straightforward enzymatic cascade to synthesize enantiomerically pure propargylic alcohols and amines from readily available racemic starting materials. In the first step, the peroxygenase from Agrocybe aegerita converted the racemic propargylic alcohols into the corresponding ketones, which then were converted into the enantiomerically pure alcohols using the (R)-selective alcohol dehydrogenase from Lactobacillus kefir or the (S)-selective alcohol dehydrogenase from Thermoanaerobacter brokii. Moreover, an enzymatic Mitsunobu-type conversion of the racemic alcohols into enantiomerically enriched propargylic amines using (R)-selective amine transaminase from Aspergillus terreus or (S)-selective amine transaminase from Chromobacterium violaceum was established. The one-pot two-step cascade reaction yielded a broad range of enantioenriched alcohol and amine products in 70-99% yield. BT/Biocatalysi

Characterization and virus susceptibility of a skin cell line from red-spotted grouper (Epinephelus akaara)

A red-spotted grouper Epinephelus akaara skin (RGS) cell line was established and characterized. RGS cells had a normal diploid chromosome number of 2n = 48, the morphology of which was fibroblastic-like in 3 days and epithelial-like over 5 after 16 passages. The cells multiplied well in Dulbecco's modified Eagle's medium supplemented with 10% of fetal bovine serum at 25A degrees C. Susceptibilities of RGS and grass carp ovary (GCO) cells to two viruses were tested, and the results showed that the titer of an iridovirus Rana grylio virus (RGV) in RGS cells was 10(3.5) TCID50 ml(-1), which was much higher than a rhabdovirus spring viremia of carp virus (SVCV) in the cells (10(0.5) TCID50 ml(-1)). The titers of RGV and SVCV in GCO were 10(6.0) TCID50 ml(-1) and 10(8.0) TCID50 ml(-1), respectively, which were higher than those in RGS cells. The data may imply that RGS cells could be selectively resistible to some viruses during infection. RT-PCR analysis of RGV-infected RGS cells showed that RGV could replicate in RGS cells. Further study of virus replications in RGS cells was conducted by electron microscopy and immunofluorescence microscopy has shown that virus particles scattered in the cytoplasm and virus protein appeared in both the cytoplasm and nucleus. The results suggested that RGS cells could be used as a potential in vitro model to study the cutaneous barrier function against virus infection.A red-spotted grouper Epinephelus akaara skin (RGS) cell line was established and characterized. RGS cells had a normal diploid chromosome number of 2n = 48, the morphology of which was fibroblastic-like in 3 days and epithelial-like over 5 after 16 passages. The cells multiplied well in Dulbecco's modified Eagle's medium supplemented with 10% of fetal bovine serum at 25A degrees C. Susceptibilities of RGS and grass carp ovary (GCO) cells to two viruses were tested, and the results showed that the titer of an iridovirus Rana grylio virus (RGV) in RGS cells was 10(3.5) TCID50 ml(-1), which was much higher than a rhabdovirus spring viremia of carp virus (SVCV) in the cells (10(0.5) TCID50 ml(-1)). The titers of RGV and SVCV in GCO were 10(6.0) TCID50 ml(-1) and 10(8.0) TCID50 ml(-1), respectively, which were higher than those in RGS cells. The data may imply that RGS cells could be selectively resistible to some viruses during infection. RT-PCR analysis of RGV-infected RGS cells showed that RGV could replicate in RGS cells. Further study of virus replications in RGS cells was conducted by electron microscopy and immunofluorescence microscopy has shown that virus particles scattered in the cytoplasm and virus protein appeared in both the cytoplasm and nucleus. The results suggested that RGS cells could be used as a potential in vitro model to study the cutaneous barrier function against virus infection

Synthesized Attributes of Water Use by Regional Vegetation: A Key to Cognition of "Water Pump" Viewpoint

Recently, the frequent seasonal drought in Southwest China has brought considerable concerns and continuous heated arguments on the "water pump" viewpoint (i.e., the water demand from Hevea spp. and Eucalyptus spp. can be treated as a water pump) once again. However, such viewpoint just focused on water consumption from vegetation transpiration and its ecoenvironment impacts, which had not considered other attributes of vegetation, namely, water saving and drought resistance, and hydrological regulation (water conservation) into consideration. Thus, in this paper, the synthesized attributes of regional vegetation water use had been mainly discussed. The results showed that the study on such aspects as the characters of water consumption from vegetation transpiration, the potential of water saving and drought resistance, and the effects of hydrological regulation in Southwest China lagged far behind, let alone the report on synthesized attributes of water utilization with the organic combination of the three aspects above or the paralleled analysis. Accordingly, in this paper, the study on the synthesized attributes of water use by regional vegetation in Southwest China was suggested, and the objectives of such a special study were clarified, targeting the following aspects: (i) characters of water consumption from transpiration of regional typical artificial vegetation; (ii) potential of water saving and drought resistance of regional typical artificial vegetation; (iii) effects of hydrological regulation of regional typical artificial vegetation; (iv) synthesized attributes of water use by regional typical artificial vegetation. It is expected to provide a new idea for the scientific assessment on the regional vegetation ecoenvironment effects and theoretical guidance for the regional vegetation reconstruction and ecological restoration.Recently, the frequent seasonal drought in Southwest China has brought considerable concerns and continuous heated arguments on the "water pump" viewpoint (i.e., the water demand from Hevea spp. and Eucalyptus spp. can be treated as a water pump) once again. However, such viewpoint just focused on water consumption from vegetation transpiration and its ecoenvironment impacts, which had not considered other attributes of vegetation, namely, water saving and drought resistance, and hydrological regulation (water conservation) into consideration. Thus, in this paper, the synthesized attributes of regional vegetation water use had been mainly discussed. The results showed that the study on such aspects as the characters of water consumption from vegetation transpiration, the potential of water saving and drought resistance, and the effects of hydrological regulation in Southwest China lagged far behind, let alone the report on synthesized attributes of water utilization with the organic combination of the three aspects above or the paralleled analysis. Accordingly, in this paper, the study on the synthesized attributes of water use by regional vegetation in Southwest China was suggested, and the objectives of such a special study were clarified, targeting the following aspects: (i) characters of water consumption from transpiration of regional typical artificial vegetation; (ii) potential of water saving and drought resistance of regional typical artificial vegetation; (iii) effects of hydrological regulation of regional typical artificial vegetation; (iv) synthesized attributes of water use by regional typical artificial vegetation. It is expected to provide a new idea for the scientific assessment on the regional vegetation ecoenvironment effects and theoretical guidance for the regional vegetation reconstruction and ecological restoration