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

Turbidity maximum formation in a well-mixed macrotidal estuary: The role of tidal pumping

Traditionally, vertical circulation (induced by gravity circulation and tidal straining), tidal pumping, and resuspension are suggested as the major processes for the formation and maintenance of the estuarine turbidity maximum (ETM). Due to strong mixing, tidal pumping is considered as the dominating process in macrotidal estuaries. To analyze field observation data, the classical empirical decomposition method is commonly suggested, but the tidal pumping flux (TPF) based on this method may lead to erroneous conclusions about the mechanisms of ETM formation because the effects of advection induced by the horizontal SSC gradient and fine bed sediment supply are ignored. If these effects are included, the TPF clearly reproduces the convergence patterns and thus demonstrates its role in the formation of the ETM. By a simplified analytical solution, the TPF is the result of the competition between the downstream flux induced by the river current together with the lag in sediment response and the upstream flux induced by tidal asymmetry and the lag. Field observations in the well-mixed macrotidal Yalu River estuary (located between China and North Korea) were analyzed. Tidal pumping is identified as the dominant mechanism of its ETM formation, and the position of the ETM for different river discharges and sediment settling velocities can be predicted by the concept of tidal pumping by numerical and analytical procedures. The present study provides a typical example of how to evaluate the tidal pumping contributions on ETM formation using the combined information provided by field data, numerical modeling results, and analytical solutions.Hydraulic EngineeringCivil Engineering and Geoscience

Interactions between a magnon mode and a cavity photon mode mediated by traveling photons

We systematically study the indirect interaction between a magnon mode and a cavity photon mode mediated by traveling photons of a waveguide. From a general Hamiltonian, we derive the effective coupling strength between two separated modes, and obtain the theoretical expression of the system's transmission. Accordingly, we design an experimental setup consisting of a shield cavity photon mode, a microstrip line, and a magnon system to test our theoretical predictions. From measured transmission spectra, indirect interaction, as well as mode hybridization, between two modes can be observed. All experimental observations support our theoretical predictions. In this work we clarify the mechanism of traveling photon mediated interactions between two separate modes. Even without spatial mode overlap, two separated modes can still couple with each other through their correlated dissipations into a mutual traveling photon bus. This conclusion may help us understand the recently discovered dissipative coupling effect in cavity magnonics systems. Additionally, the physics and technique developed in this work may benefit us in designing new hybrid systems based on the waveguide magnonics.QN/Bauer Grou

Coherent control of magnon radiative damping with local photon states

A magnon, the collective excitation of ordered spins, can spontaneously radiate a travelling photon to an open system when decaying to the ground state. However, in contrast to electric dipoles, magnetic dipoles by magnons are more isolated from the environment, limiting their radiation and coherent communication with photons. The recent progresses in strongly coupled magnon-photon system have stimulated the manipulation of magnon radiation via tailoring the photon states. Here, by loading an yttrium iron garnet sphere in a one-dimensional waveguide cavity supporting both the travelling and standing photon modes, we demonstrate a significant magnon radiative damping that is proportional to the local density of photon states (LDOS). By modulating the magnitude and/or polarization of LDOS, we can flexibly tune the photon emission and magnon radiative damping. Our findings provide a way to manipulate photon emission from magnon radiation, which could help harness angular momentum generation, transfer, and storage in magnonics.QN/Bauer Grou

Reliability assessment for corroded pipelines in series considering length-scale effects

This paper presents a method for assessing the reliability of a corroded pipeline placed in series, with special consideration given to the effect of the length scale imposed by each segment of the pipe. The features of corrosion in different pipe segments are statistically correlated; thus, a failure in one section may impact the adjacent sections. Herein, using a correlation distance parameter, such statistical correlation is described considering the length-scale effects. The reliability of the corroded pipeline is presented in the form of a failure probability. The results show that analysing a corroded pipeline by considering length-scale effects produces a higher failure probability compared with the case where such effects are excluded, even when the parameters that govern corrosion in a pipeline are included in the analysis.Safety and Security Scienc

A molecular dynamics study of N–A–S–H gel with various Si/Al ratios

In this paper, the atomic structures of sodium aluminosilicate hydrate (N–A–S–H) gels with different Si/Al ratios are studied by molecular dynamics simulation. An N–A–S–H gel model was obtained from the polymerization of Si(OH)4 and Al(OH)3 monomers with the use of a reactive force field (ReaxFF). The simulated atomic structural features, such as the bond length, bond angle, and simulated X-ray diffraction pattern of the gel structure are in good accordance with the experimental results in the literature. Si–O–Al is found to be preferred over Si–O–Si in the N–A–S–H gel structure according to the amount of T–O–T bond angles and distribution of Si4(mAl). Pentacoordinate Al is identified in all simulated N–A–S–H models. It provides strong support to current knowledge that pentacoordinate Al in geopolymer does not only come from raw material. Furthermore, the structural analysis results also show that N–A–S–H gel with lower Si/Al ratios has a more cross-linked and compacted structure.Materials and Environmen

Solvent-cast 3D printing of magnesium scaffolds

Biodegradable porous magnesium (Mg) scaffolds are promising for application in the regeneration of critical-sized bone defects. Although additive manufacturing (AM) carries the promise of offering unique opportunities to fabricate porous Mg scaffolds, current attempts to apply the AM approach to fabricating Mg scaffolds have encountered some crucial issues, such as those related to safety in operation and to the difficulties in composition control. In this paper, we present a room-temperature extrusion-based AM method for the fabrication of topologically ordered porous Mg scaffolds. It is composed of three steps, namely (i) preparing a Mg powder loaded ink with desired rheological properties, (ii) solvent-cast 3D printing (SC-3DP) of the ink to form scaffolds with 0 °/ 90 °/ 0 ° layers, and (iii) debinding and sintering to remove the binder in the ink and then get Mg powder particles bonded by applying a liquid-phase sintering strategy. A rheological analysis of the prepared inks with 54, 58 and 62 vol% Mg powder loading was performed to reveal their viscoelastic properties. Thermal-gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), carbon/sulfur analysis and scanning electron microscopy (SEM) indicated the possibilities of debinding and sintering at one single step for fabricating pure Mg scaffolds with high fidelity and densification. The resulting scaffolds with high porosity contained hierarchical and interconnected pores. This study, for the first time, demonstrated that the SC-3DP technique presents unprecedented possibilities to fabricate Mg-based porous scaffolds that have the potential to be used as a bone-substituting material. Statement of Significance: Biodegradable porous magnesium scaffolds are promising for application in the regeneration of critical-sized bone defects. Although additive manufacturing (AM) carries the promise of offering unique opportunities to fabricate porous magnesium scaffolds, current attempts to apply the AM approach to fabricating magnesium scaffolds still have some crucial limitations. This study demonstrated that the solvent-cast 3D printing technique presents unprecedented possibilities to fabricate Mg-based porous scaffolds. The judicious chosen of formulated binder system allowed for the negligible binder residue after debinding and the short-time liquid-phase sintering strategy led to a great success in sintering pure magnesium scaffolds. The resulting scaffolds with hierarchical and interconnected pores have great potential to be used as a bone-substituting material.Biomaterials & Tissue Biomechanics(OLD) MSE-3BN/Marie-Eve Aubin-Tam LabChemE/O&O groepPavement Engineerin

Optical properties of strained wurtzite gallium phosphide nanowires

Wurtzite gallium phosphide (WZ GaP) has been predicted to exhibit a direct bandgap in the green spectral range. Optical transitions, however, are only weakly allowed by the symmetry of the bands. While efficient luminescence has been experimentally shown, the nature of the transitions is not yet clear. Here we apply tensile strain up to 6% and investigate the evolution of the photoluminescence (PL) spectrum of WZ GaP nanowires (NWs). The pressure and polarization dependence of the emission together with a theoretical analysis of strain effects is employed to establish the nature and symmetry of the transitions. We identify the emission lines to be related to localized states with significant admixture of Δ7c symmetry and not exclusively related to the Δ8c conduction band minimum (CBM). The results emphasize the importance of strongly bound state-related emission in the pseudodirect semiconductor WZ GaP and contribute significantly to the understanding of the optoelectronic properties of this novel material.QN/Bakkers La

Tailoring precipitation/properties and related mechanisms for a high-strength aluminum alloy plate via low-temperature retrogression and re-aging processes

The retrogression and re-aging (RRA) processes, aimed mainly at tailoring intergranular precipitates, could significantly improve the corrosion resistance (i.e., stress corrosion cracking resistance) without considerably decreasing the strength, which signifies that an efficient control of the size, distribution and evolution of intergranular and intragranular precipitates becomes critical for the integrated properties of the (mid-)thick high-strength Al alloy plates. Compared to RRA process with retrogression at 200 °C (T77), this study investigated the impact of a modified RRA process (MT77) with lower retrogression temperatures (155-175 °C) and first-stage under-aging on the properties of a high-strength AA7050 Al alloy, in combination with detailed precipitate characterization. The study showed that the strength/microhardness of the RRA-treated alloys decreased with raising retrogression temperature and/or prolonging retrogression time, along with the increased electrical conductivity. The rapid responsiveness of microstructure/property typical of retrogression at 200 °C was obviously postponed or decreased by using MT77 process with longer retrogression time that was more suitable for treating the (mid-)thick plates. On the other hand, higher retrogression temperature facilitated more intragranular η precipitates, coarse intergranular precipitates and wide precipitate free zones, which prominently increased the electrical conductivity alongside a considerable strength loss as compared to the MT77-treated alloys. With the preferred MT77 process, the high strength approaching T6 level as well as good corrosion resistance was achieved. However, though a relatively homogeneous through-thickness strength was obtained, some small discrepancies of properties between the central and surface areas of an 86-mm thick 7050 Al alloy plate were observed, possibly related to the quenching sensitivity. The precipitate evolution and mechanistic connection to the properties were discussed and reviewed for high-strength Al alloys along with suggestions for further RRA optimization.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.Team Jilt Sietsm

Ulinastatin activates haem oxygenase 1 antioxidant pathway and attenuates allergic inflammation

Background and PurposeUlinastatin (UTI), a serine protease inhibitor, was recently found to have an anti-inflammatory action. However, the mechanisms mediating this anti-inflammatory effect are not well understood. This study tested the hypothesis that UTI suppresses allergic inflammation by inducing the expression of haem oxygenase 1 (HO1). Experimental ApproachControl mice and mice sensitized (on days 1, 9 and 14) and challenged (on days 21 to 27) with ovalbumin (OVA) were treated with UTI. The effects of UTI on basal expression of HO1 and that induced by OVA challenge were examined. The involvement of UTI-induced HO1 expression in anti-inflammatory and antioxidant effects of UTI was also evaluated. Key ResultsUTI markedly increased basal HO1 protein expression in lungs of control mice in a time- and dose-dependent manner, and augmented HO1 protein expression induced by OVA. The up-regulation of HO1 mediated by UTI in sensitized and OVA-challenged mice was associated with reduced airway inflammation, alleviated tissue injury, reduced oxidant stress and enhanced antioxidant enzyme activities. Inhibition of HO1 activity using HO1 inhibitor, zinc protoporphyrin, attenuated inhibitory effects of UTI on inflammation and oxidant stress, and its stimulant effects on antioxidant enzyme activities. Mechanistic analysis showed that UTI increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), stimulated Nrf2 DNA binding activity and concomitantly up-regulated HO1 mRNA expression. Conclusions and ImplicationsUTI is a potent and naturally occurring inducer of HO1 expression. HO1 up-regulation contributes significantly to the anti-inflammatory and organ-protective effects of UTI, which has important research and therapeutic implications