22 research outputs found

    Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

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    [This corrects the article DOI: 10.1186/s13054-016-1208-6.]

    Pan-cancer analysis of whole genomes

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    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

    An advection-based model to increase the temporal resolution of PIV time series

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    A numerical implementation of the advection equation is proposed to increase the temporal resolution of PIV time series. The method is based on the principle that velocity fluctuations are transported passively, similar to Taylor’s hypothesis of frozen turbulence. In the present work, the advection model is extended to unsteady three-dimensional flows. The main objective of the method is that of lowering the requirement on the PIV repetition rate from the Eulerian frequency toward the Lagrangian one. The local trajectory of the fluid parcel is obtained by forward projection of the instantaneous velocity at the preceding time instant and backward projection from the subsequent time step. The trajectories are approximated by the instantaneous streamlines, which yields accurate results when the amplitude of velocity fluctuations is small with respect to the convective motion. The verification is performed with two experiments conducted at temporal resolutions significantly higher than that dictated by Nyquist criterion. The flow past the trailing edge of a NACA0012 airfoil closely approximates frozen turbulence, where the largest ratio between the Lagrangian and Eulerian temporal scales is expected. An order of magnitude reduction of the needed acquisition frequency is demonstrated by the velocity spectra of super-sampled series. The application to three-dimensional data is made with time-resolved tomographic PIV measurements of a transitional jet. Here, the 3D advection equation is implemented to estimate the fluid trajectories. The reduction in the minimum sampling rate by the use of super-sampling in this case is less, due to the fact that vortices occurring in the jet shear layer are not well approximated by sole advection at large time separation. Both cases reveal that the current requirements for time-resolved PIV experiments can be revised when information is poured from space to time. An additional favorable effect is observed by the analysis in the frequency domain whereby the spectrum becomes significantly less prone to aliasing error for the super-sampled data series.Aerospace Engineerin

    Benger Swamp Nature Reserve management plan 1987-1992

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    Experiments on the Flow Field and Acoustic Properties of a Mach number 0·75 Turbulent Air Jet at a Low Reynolds Number

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    In this paper we present the experimental results of a detailed investigation of the flow and acoustic properties of a turbulent jet with Mach number 0·75 and Reynolds number 3·5 103. We describe the methods and experimental procedures followed during the measurements, and subsequently present the flow field and acoustic field. The experiment presented here is designed to provide accurate and reliable data for validation of Direct Numerical Simulations of the same flow. Mean Mach number surveys provide detailed information on the centreline mean Mach number distribution, radial development of the mean Mach number and the evolution of the jet mixing layer thickness both downstream and in the early stages of jet development. Exit conditions are documented by measuring the mean Mach number profile immediately above the nozzle exit. The fluctuating flow field is characterised by means of a hot-wire, which produced radial profiles of axial turbulence at several stations along the jet axis and the development of flow fluctuations through the jet mixing layer. The axial growth rate of the jet instabilities are determined as function of Strouhal number, and the axial development of several spectral components is documented. The directivity of the overall sound pressure level and several spectral components were investigated. The spectral content of the acoustic far field is shown to be compatible with findings of hot-wire experiments in the mixing layer of the jet. In addition, the measured acoustic spectra agree with Tam’s large-scale similarity and fine-scale similarity spectra (Tam et al., AIAA Pap 96, 1996).Aerospace Design, Integration and OperationsAerospace Engineerin

    J2: An evaluation of new estimates from GPS, GRACE, and load models compared to SLR

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    Changes in J2, resulting from past and present changes in Earth's climate, are traditionally observed by Satellite Laser ranging (SLR). Assuming an elastic Earth, it is possible to infer changes in J2 from changes in Earth's shape observed by GPS. We compare estimates of non-secular J2 changes from GPS, SLR, GRACE, and a load model. The GPS and SLR annual signals agree but are different (16%) to the load model. Subtraction of the load model removes the annual variation from GPS, SLR, and GRACE, and the semi-annual variation in GPS. The GPS and SLR long-term signals are highly correlated, but GPS is better correlated with the loading model. Subtraction of the load model removes the 1998 anomaly from the GPS J2 series but not completely from the SLR J2 series, suggesting that the SLR anomaly may not be entirely due to mass re-distribution as has been presumed.Aerospace Engineerin

    High-Strength Liquid Crystal Polymer-Graphene Oxide Nanocomposites from Water

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    We report on the morphology and mechanical properties of nanocomposite films derived from aqueous, hybrid liquid crystalline mixtures of rodlike aggregates of a sulfonated, all-aromatic polyamide, poly(2,2′-disulfonyl-4,4′-benzidine terephthalamide) (PBDT), and graphene oxide (GO) platelets. An isothermal step at 200 °C facilitates in situ partial thermal reduction of GO to reduced GO (rGO) in nanocomposite films. X-ray scattering studies reveal that PBDT-rGO nanocomposites exhibit both higher in-plane alignment of PBDT (the order parameter increases from 0.79 to 0.9 at 1.8 vol % rGO) and alignment along the casting direction (from 0.1 to 0.6 at 1.8 vol % rGO). From dynamic mechanical thermal analysis, the interaction between PBDT and rGO causes the β-relaxation activation energy for PBDT to increase with rGO concentration. Modulus mapping of nanocomposites using atomic force microscopy demonstrates enhanced local stiffness, indicating reinforcement. From stress-strain analysis, the average Young's modulus increases from 16 to 37 GPa at 1.8 vol % rGO and the average tensile strength increases from 210 to 640 MPa. Despite polymer alignment along the casting direction, an average transverse tensile strength of 230 MPa is obtained. 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.ChemE/Advanced Soft MatterNovel Aerospace Material

    Evidence against a charge density wave on Bi(111)

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    The Bi(111) surface was studied by scanning tunneling microscopy (STM), transmission electron microscopy (TEM) and angle-resolved photoemission (ARPES) in order to verify the existence of a recently proposed surface charge density wave (CDW) [Ch. R. Ast and H. Hoechst Phys. Rev. Lett. 90, 016403 (2003)]. The STM and TEM results to not support a CDW scenario at low temperatures. Furthermore, the quasiparticle interference pattern observed in STM confirms the spin-orbit split character of the surface states which prevents the formation of a CDW, even in the case of good nesting. The dispersion of the electronic states observed with ARPES agrees well with earlier findings. In particular, the Fermi contour of the electron pocket at the centre of the surface Brillouin zone is found to have a hexagonal shape. However, no gap opening or other signatures of a CDW phase transition can be found in the temperature-dependent data

    Adjuvant Chemotherapy With Fluorouracil Plus Folinic Acid vs Gemcitabine Following Pancreatic Cancer Resection A Randomized Controlled Trial

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    Context Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer. Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer. Objective To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer. Design, Setting, and Patients The European Study Group for Pancreatic Cancer (ESPAC)-3 trial, an open-label, phase 3, randomized controlled trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan, and Canada. Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection; patients were randomized between July 2000 and January 2007 and underwent at least 2 years of follow-up. Interventions Patients received either fluorouracil plus folinic acid (folinic acid, 20 mg/m(2), intravenous bolus injection, followed by fluorouracil, 425 mg/m(2) intravenous bolus injection given 1-5 days every 28 days) (n=551) or gemcitabine (1000 mg/m2 intravenous infusion once a week for 3 of every 4 weeks) (n=537) for 6 months. Main Outcome Measures Primary outcome measure was overall survival; secondary measures were toxicity, progression-free survival, and quality of life. Results Final analysis was carried out on an intention-to-treat basis after a median of 34.2 (interquartile range, 27.1-43.4) months' follow-up after 753 deaths (69%). Median survival was 23.0 (95% confidence interval [CI], 21.1-25.0) months for patients treated with fluorouracil plus folinic acid and 23.6 (95% CI, 21.4-26.4) months for those treated with gemcitabine (chi(2)(1) = 0.7; P = .39; hazard ratio, 0.94 [95% CI, 0.81-1.08]). Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (P<.001). There were no significant differences in either progression-free survival or global quality-of-life scores between the treatment groups. Conclusion Compared with the use of fluorouracil plus folinic acid, gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer
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