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

Improving Energy Efficiency for All: Lessons on sustainable building retrofits from Shanghai, China

Improving the energy efficiency of existing buildings is a critical part of action on climate change. Retrofitting in particular provides benefits to the economy, the environment and society, as well as making significant reductions to operational greenhouse gas emissions. This policy brief looks in detail at the impact of retrofitting schemes adopted in Changning District, Shanghai, China, and highlights ways other cities can learn from Shanghai’s experience.Urban Development Managemen

Continuous Fatty Acid Decarboxylation using an Immobilized Photodecarboxylase in a Membrane Reactor

The realm of photobiocatalytic alkane biofuel synthesis has burgeoned recently; however, the current dearth of well-established and scalable production methodologies in this domain remains conspicuous. In this investigation, we engineered a modified form of membrane-associated fatty acid photodecarboxylase sourced from Micractinium conductrix (McFAP). This endeavour resulted in creating an innovative assembled photoenzyme-membrane (protein load 5 mg cm−2), subsequently integrated into an illuminated flow apparatus to achieve uninterrupted generation of alkane biofuels. Through batch experiments, the photoenzyme-membrane exhibited its prowess in converting fatty acids spanning varying chain lengths (C6–C18). Following this, the membrane-flow mesoscale reactor attained a maximum space-time yield of 1.2 mmol L−1 h−1 (C8) and demonstrated commendable catalytic proficiency across eight consecutive cycles, culminating in a cumulative runtime of eight hours. These findings collectively underscored the photoenzyme-membrane's capability to facilitate the biotransformation of diverse fatty acids, furnishing valuable benchmarks for the conversion of biomass via photobiocatalysis.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.BT/Biocatalysi

Hybrid Plasmonics Slot THz Waveguide for Subwavelength Field Confinement and Crosstalk between Two Waveguides

The slot waveguide has attracted considerable attention because of its ability to confine and guide electromagnetic energy at the subwavelength scale beyond the diffraction limit. We propose a novel terahertz slot waveguide structure to achieve a better tradeoff between propagation length and field confinement capacity, the novel waveguide consisting of a two slot structure. The performances of terahertz waveguides were investigated using the finite-element method. The results demonstrated that the hybrid slot waveguide (HSW) provides significantly enhanced field confinement in low index slot regions: more than five times that of traditional low index slot waveguides (LISWs). An optimized HSW structure was achieved by tuning the tradeoff between mode confinement and propagation length. We also showed that its integration in conventional planar waveguide circuits was greatly improved compared with the LISWs, by comparing their crosstalk. The proposed new HSW structure has great potential to enable THz production of compact integration and could lead to true semiconductor-basedTHz applications with high performance.Electronic Components, Technology and Material

Thickness-Independent Capacitive Performance of Holey Ti₃C₂T_x Film Prepared through a Mild Oxidation Strategy

The Ti3C2Tx film with metallic conductivity and high pseudo-capacitance holds profound promise in flexible high-rate supercapacitors. However, the restacking of Ti3C2Tx sheets hinders ion access to thick film electrodes. Herein, a mild yet green route has been developed to partially oxidize Ti3C2Tx to TiO2/Ti3C2Tx by introducing O2 molecules during refluxing the Ti3C2Tx suspension. The subsequent etching away of these TiO2 nanoparticles by HF leaves behind numerous in-plane nanopores on the Ti3C2Tx sheets. Electrochemical impedance spectroscopy shows that longer oxidation time of 40 min yields holey Ti3C2Tx (H-Ti3C2Tx) with a much shorter relax time constant of 0.85 s at electrode thickness of 25 µm, which is 89 times smaller than that of the pristineTi3C2Tx film (75.58 s). Meanwhile, H-Ti3C2Tx film with 25 min oxidation exhibits less-dependent capacitive performance in film thickness range of 10–84 µm (1.63–6.41 mg cm−2) and maintains around 60% capacitance as the current density increases from 1 to 50 A g−1. The findings clearly demonstrate that in-plane nanopores not only provide more electrochemically active sites, but also offer numerous pathways for rapid ion impregnation across the thick Ti3C2Tx film. The method reported herein would pave way for fabricating porous MXene materials toward high-rate flexible supercapacitor applications.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.RST/Storage of Electrochemical Energ

A CMOS-Compatible Hybrid Plasmonic Slot Waveguide With Enhanced Field Confinement

The emerging field of nanophotonics requires plasmonic devices to be fully compatible with semiconductor fabrication techniques. However, very few feasible practical structures exist at present. Here, we propose a CMOS-compatible hybrid plasmonic slot waveguide (HPSW) with enhanced field confinement. Our simulation results show that the HPSW exhibits significantly enhanced field confinement as compared with the traditional low-index slot waveguides and the hybrid metal dielectric slot waveguides. By controlling the thicknesses of different layers, an optimized HPSW structure with a better tradeoff between field confinement and propagation length has been simultaneously achieved.Electronic Components, Technology and Material

Lattice Boltzmann simulations of a pitch-up and pitch-down maneuver of a chord-wise flexible wing in a free stream flow

A rapid pitch-up and pitch-down maneuver of a chord-wise flexible wing in a steady free stream is studied by using a lattice Boltzmann flexible particle method in a three-dimensional space at a chord based Reynolds number of 100. The pitching rates, flexibility, and wing density are systematically varied, and their effects on aerodynamic forces are investigated. It is demonstrated that the flexibility can be utilized to significantly improve lift forces. The flexible wing has a larger angular momentum due to elasticity and inertia and generates a larger leading edge vortex as compared with a rigid wing. Such lift enhancement occurs mainly during the pitch-down motion while a large stall angle is produced during the pitch-up motion. At a low pitch rate, the flexibility cannot improve lift. (C) 2014 AIP Publishing LLC.A rapid pitch-up and pitch-down maneuver of a chord-wise flexible wing in a steady free stream is studied by using a lattice Boltzmann flexible particle method in a three-dimensional space at a chord based Reynolds number of 100. The pitching rates, flexibility, and wing density are systematically varied, and their effects on aerodynamic forces are investigated. It is demonstrated that the flexibility can be utilized to significantly improve lift forces. The flexible wing has a larger angular momentum due to elasticity and inertia and generates a larger leading edge vortex as compared with a rigid wing. Such lift enhancement occurs mainly during the pitch-down motion while a large stall angle is produced during the pitch-up motion. At a low pitch rate, the flexibility cannot improve lift. (C) 2014 AIP Publishing LLC

Growth, morphological and physiological responses of alfalfa (Medicago sativa) to phosphorus supply in two alkaline soils

Phosphorus (P) deficiency is a major problem for alfalfa (Medicago sativa) productivity on alkaline soils on the Loess Plateau, China. Our aim was to investigate growth, morphological and physiological responses of alfalfa to P supply in two alkaline soils when water supply is limited. A pot experiment was carried out to grow alfalfa in two alkaline soils supplied with different rates of P. Parameters of plant growth and root morphology, rhizosphere pH and carboxylates, and plant concentrations of mineral nutrients were measured. Plant growth and nutrient uptake were enhanced by supplying P, but shoot growth was not further increased when P supply was > 20 mu g P g(-1) soil. Specific root length was only responsive to changes in soil P when P supply was low in the loessial soil. The rhizosphere carboxylate amount was significantly greater when no P was supplied than when P was supplied to the loessial soil. The rhizosphere pH was lower than the bulk soil pH, but did not vary with soil P. A P supply of 20 mu g P g(-1) soil was optimal for alfalfa growth. The responses of specific root length and rhizosphere carboxylates depended on soil type

Brain-derived neurotrophic factor signalling mediates antidepressant effects of lamotrigine

The anticonvulsant drug lamotrigine has been shown to produce antidepressant effects in patients with bipolar disorder. To date, only a few preclinical studies have been conducted using lamotrigine treatment in the forced swim test (FST), an animal model of depression with low face validity. The underlying mechanisms by which lamotrigine works have not been well characterized either. This study extends earlier work on the role of brain-derived neurotrophic factor (BDNF) in regulating the antidepressant actions of lamotrigine. We showed that in rats subjected to chronic unpredictable stress, chronic administration of 30 mg/kg lamotrigine ameliorates behavioural deficits of stressed rats in both sucrose preference test (SPT) and novelty-suppressed feeding test (NSFT). In parallel, chronic lamotrigine treatment up-regulates frontal and hippocampal BDNF protein expression in both naive and stressed animals, and restores the stress-induced down-regulation of BDNF levels. In addition, inhibition of BDNF signalling by infusion of K252a, an inhibitor of the BDNF receptor TrkB, blocks the antidepressant effects of lamotrigine in SPT, NSFT and FST. Taken together, this study provides further evidence that BDNF is an essential mediator for the antidepressant effects of lamotrigine

A Constrained Particle Dynamics for Continuum-Particle Hybrid Method in Micro- and Nano-Fluidics

A hybrid method of continuum and particle dynamics is developed for micro- and nano-fluidics, where fluids are described by a molecular dynamics (MD) in one domain and by the Navier-Stokes (NS) equations in another domain. In order to ensure the continuity of momentum flux, the continuum and molecular dynamics in the overlap domain are coupled through a constrained particle dynamics. The constrained particle dynamics is constructed with a virtual damping force and a virtual added mass force. The sudden-start Couette flows with either non-slip or slip boundary condition are used to test the hybrid method. It is shown that the results obtained are quantitatively in agreement with the analytical solutions under the non-slip boundary conditions and the full MD simulations under the slip boundary conditions