678 research outputs found

    Improvement of adhesive-bonded structural joints

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    Investigation is described of methods for obtaining uniform shear stress distribution in adhesives used in double-lap bonded joints. Design rules for reducing adhesive peak shear stresses are listed. Test results of an analysis of straight-lap joint design and stepped-lap joint design are given

    Promising born/graphite/resin composites

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    Lightweight composite has high specific strength and stiffness and remains effective under extreme environmental conditions. Use as engineering material is feasible because it has excellent mechanical properties and is easily produced within small tolerances on constituent volume fractions. Main benefit of composite is its improved longitudinal strength and modulus

    Evaluating Data Assimilation Algorithms

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    Data assimilation leads naturally to a Bayesian formulation in which the posterior probability distribution of the system state, given the observations, plays a central conceptual role. The aim of this paper is to use this Bayesian posterior probability distribution as a gold standard against which to evaluate various commonly used data assimilation algorithms. A key aspect of geophysical data assimilation is the high dimensionality and low predictability of the computational model. With this in mind, yet with the goal of allowing an explicit and accurate computation of the posterior distribution, we study the 2D Navier-Stokes equations in a periodic geometry. We compute the posterior probability distribution by state-of-the-art statistical sampling techniques. The commonly used algorithms that we evaluate against this accurate gold standard, as quantified by comparing the relative error in reproducing its moments, are 4DVAR and a variety of sequential filtering approximations based on 3DVAR and on extended and ensemble Kalman filters. The primary conclusions are that: (i) with appropriate parameter choices, approximate filters can perform well in reproducing the mean of the desired probability distribution; (ii) however they typically perform poorly when attempting to reproduce the covariance; (iii) this poor performance is compounded by the need to modify the covariance, in order to induce stability. Thus, whilst filters can be a useful tool in predicting mean behavior, they should be viewed with caution as predictors of uncertainty. These conclusions are intrinsic to the algorithms and will not change if the model complexity is increased, for example by employing a smaller viscosity, or by using a detailed NWP model

    On dimension reduction in Gaussian filters

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    A priori dimension reduction is a widely adopted technique for reducing the computational complexity of stationary inverse problems. In this setting, the solution of an inverse problem is parameterized by a low-dimensional basis that is often obtained from the truncated Karhunen-Loeve expansion of the prior distribution. For high-dimensional inverse problems equipped with smoothing priors, this technique can lead to drastic reductions in parameter dimension and significant computational savings. In this paper, we extend the concept of a priori dimension reduction to non-stationary inverse problems, in which the goal is to sequentially infer the state of a dynamical system. Our approach proceeds in an offline-online fashion. We first identify a low-dimensional subspace in the state space before solving the inverse problem (the offline phase), using either the method of "snapshots" or regularized covariance estimation. Then this subspace is used to reduce the computational complexity of various filtering algorithms - including the Kalman filter, extended Kalman filter, and ensemble Kalman filter - within a novel subspace-constrained Bayesian prediction-and-update procedure (the online phase). We demonstrate the performance of our new dimension reduction approach on various numerical examples. In some test cases, our approach reduces the dimensionality of the original problem by orders of magnitude and yields up to two orders of magnitude in computational savings

    Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci

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    <p>Abstract</p> <p>Background</p> <p>Estimates suggest that up to 30% of colorectal cancers (CRC) may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV) (Roche NimbleGen, 385 000 oligo CGH array) in microsatellite stable (MSS) tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53) and 17 elderly patients with median age 79 years (range: 69-87). Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list.</p> <p>Results</p> <p>The total fraction of the genome with aberrant copy number, the overall genomic profile and the <it>TP53 </it>mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, <it>CLC, EIF4E</it>, <it>LTBP4, PLA2G12A, PPAT</it>, <it>RG9MTD2</it>, and <it>ZNF574</it>, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups.</p> <p>Conclusions</p> <p>Ten genomic loci, containing more than 500 protein coding genes, are identified as more often altered in tumors from early onset versus late onset CRC. Integration of genome and transcriptome data identifies seven novel candidate genes with the potential to identify an increased risk for CRC.</p

    Inpatient versus outpatient acute venous thromboembolism management: Trends and postacute healthcare utilization from 2011 to 2018

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    Background - Acute outpatient management of venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), is perceived to be as safe as inpatient management in some settings. How widely this strategy is used is not well documented. Methods and Results - Using MarketScan administrative claims databases for years 2011 through 2018, we identified patients with International Classification of Diseases (ICD) codes indicating incident VTE and trends in the use of acute outpatient management. We also evaluated healthcare utilization and hospitalized bleeding events in the 6 months following the incident VTE event. A total of 200 346 patients with VTE were included, of whom 50% had evidence of PE. Acute outpatient management was used for 18% of those with PE and 57% of those with DVT only, and for both DVT and PE its use increased from 2011 to 2018. Outpatient management was less prevalent among patients with cancer, higher Charlson comorbidity index scores, and whose primary treatment was warfarin as compared with a direct oral anticoagulant. Healthcare utilization in the 6 months following the incident VTE event was generally lower among patients managed acutely as outpatients, regardless of initial presentation. Acute outpatient management was associated with lower hazard ratios of incident bleeding risk for both patients who initially presented with PE (0.71 [95% CI, 0.61, 0.82]) and DVT only (0.59 [95% CI, 0.54, 0.64]). Conclusions - Outpatient management of VTE is increasing. In the present analysis, it was associated with lower subsequent healthcare utilization and fewer bleeding events. However, this may be because healthier patients were managed on an outpatient basis

    The evolution of the ISOLDE control system

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    The ISOLDE on-line mass separator facility is operating on a Personal Computer based control system since spring 1992. Front End Computers accessing the hardware are controlled from consoles running Microsoft WindowsTM through a Novell NetWare4TM local area network. The control system is transparently integrated in the CERN wide office network and makes heavy use of the CERN standard office application programs to control and to document the running of the ISOLDE isotope separators. This paper recalls the architecture of the control system, shows its recent developments and gives some examples of its graphical user interface
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