1. |
- Lawrenson, Kate, et al.
(author)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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2. |
- Liu, Xiaowan, et al.
(author)
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Measurements and modelling of dynamic stiffness of a railway vehicle primary suspension element and its use in a structure-borne noise transmission model
- 2021
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In: Applied Acoustics. - : Elsevier BV. - 0003-682X .- 1872-910X. ; 182
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Journal article (peer-reviewed)abstract
- The noise inside railway vehicles is transmitted by both structure-borne and airborne paths and, although there are many sources, the rolling noise is often the most important. This paper focuses on the structure-borne transmission of rolling noise in a metro vehicle. Measurements are presented first of the vertical and lateral dynamic stiffness of a primary suspension element consisting of conical rubber/metal elements. Results are presented for various constant preloads over the frequency range 60600 Hz. An analytical model of the suspension element is also developed, based on a mass-spring system and including wave motion within the rubber elements. The dynamic stiffness results are used in a finite element model of the running gear, consisting of the bogie frame, wheelsets and suspension elements. The excitation is provided by the combined wheel/rail roughness at the contact point. This model is used to calculate the blocked forces at the connection points between the secondary suspension elements and the car body. The blocked forces are combined with measured vibro-acoustic transfer functions from these mounting points to the vehicle interior to determine the structure-borne noise inside the vehicle. The proposed methodology is validated against measurements during operation in terms of acceleration levels, blocked forces and structure-borne noise levels inside the vehicle, showing reasonably good agreement. Including the dynamic stiffness for the primary suspension leads to improved agreement between 100 and 500 Hz compared with using a constant stiffness.
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3. |
- Pegourie, B., et al.
(author)
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Deuterium inventory in Tore Supra : Coupled carbon-deuterium balance
- 2013
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In: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 438:Suppl., s. S120-S125
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Journal article (peer-reviewed)abstract
- This paper presents an analysis of the carbon-deuterium circulation and the resulting balance in Tore Supra over the period 2002-2007. Carbon balance combines the estimation of carbon gross erosion from spectroscopy, net erosion and deposition using confocal microscopy, lock-in thermography and SEM, and a measure of the amount of deposits collected in the vacuum chamber. Fuel retention is determined from post-mortem (PM) analyses and gas balance (GB) measurements. Special attention was paid to the deuterium outgassed during the nights and weekends of the experimental campaign (vessel under vacuum, Plasma Facing Components at 120 degrees C) and during vents (vessel at atmospheric pressure, PFCs at room temperature). It is shown that this outgassing is the main process reconciling the PM and GB estimations of fuel retention, closing the coupled carbon-deuterium balance. In particular, it explains why the deuterium concentration in deposits decreases with increasing depth.
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