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| 3. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 5. |
- Speakman, John R., et al.
(författare)
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Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure
- 2023
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Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5:4, s. 579-588
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Obesity is caused by a prolonged positive energy balance(1,2). Whether reduced energy expenditure stemming from reduced activity levels contributes is debated(3,4). Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.
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| 6. |
- Rudolph, M., et al.
(författare)
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On the population density of the argon excited levels in a high power impulse magnetron sputtering discharge
- 2022
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 29:2, s. 023506-
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Tidskriftsartikel (refereegranskat)abstract
- Population densities of excited states of argon atoms in a high power impulse magnetron sputtering (HiPIMS) discharge are examined using a global discharge model and a collisional-radiative model. Here, the ionization region model (IRM) and the Orsay Boltzmann equation for electrons coupled with ionization and excited states kinetics (OBELIX) model are combined to obtain the population densities of the excited levels of the argon atom in a HiPIMS discharge. The IRM is a global plasma chemistry model based on particle and energy conservation of HiPIMS discharges. OBELIX is a collisional-radiative model where the electron energy distribution is calculated self-consistently from an isotropic Boltzmann equation. The collisional model constitutes 65 individual and effective excited levels of the argon atom. We demonstrate that the reduced population density of high-lying excited argon states scales with (p*)(-6), where p * is the effective quantum number, indicating the presence of a multistep ladder-like excitation scheme, also called an excitation saturation. The reason for this is the dominance of electron impact processes in the population and de-population of high-lying argon states in combination with a negligible electron-ion recombination.
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| 7. |
- Antunes, V. G., et al.
(författare)
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Influence of the magnetic field on the extension of the ionization region in high power impulse magnetron sputtering discharges
- 2023
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Ingår i: Plasma sources science & technology. - : IOP Publishing. - 0963-0252 .- 1361-6595. ; 32:7
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Tidskriftsartikel (refereegranskat)abstract
- The high power impulse magnetron sputtering (HiPIMS) discharge brings about increased ionization of the sputtered atoms due to an increased electron density and efficient electron energization during the active period of the pulse. The ionization is effective mainly within the electron trapping zone, an ionization region (IR), defined by the magnet configuration. Here, the average extension and the volume of the IR are determined based on measuring the optical emission from an excited level of the argon working gas atoms. For particular HiPIMS conditions, argon species ionization and excitation processes are assumed to be proportional. Hence, the light emission from certain excited atoms is assumed to reflect the IR extension. The light emission was recorded above a 100 mm diameter titanium target through a 763 nm bandpass filter using a gated camera. The recorded images directly indicate the effect of the magnet configuration on the average IR size. It is observed that the shape of the IR matches the shape of the magnetic field lines rather well. The IR is found to expand from 10 and 17 mm from the target surface when the parallel magnetic field strength 11 mm above the racetrack is lowered from 24 to 12 mT at a constant peak discharge current.
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| 8. |
- Rudolph, M., et al.
(författare)
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Influence of the magnetic field on the discharge physics of a high power impulse magnetron sputtering discharge
- 2022
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Ingår i: Journal of Physics D. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- The magnetic field is a key feature that distinguishes magnetron sputtering from simple diode sputtering. It effectively increases the residence time of electrons close to the cathode surface and by that increases the energy efficiency of the discharge. This becomes apparent in high power impulse magnetron sputtering (HiPIMS) discharges, as small changes in the magnetic field can result in large variations in the discharge characteristics, notably the peak discharge current and/or the discharge voltage during a pulse. Here, we analyze the influence of the magnetic field on the electron density and temperature, how the discharge voltage is split between the cathode sheath and the ionization region, and the electron heating mechanism in a HiPIMS discharge. We relate the results to the energy efficiency of the discharge and discuss them in terms of the probability of target species ionization. The energy efficiency of the discharge is related to the fraction of pulse power absorbed by the electrons. Ohmic heating of electrons in the ionization region leads to higher energy efficiency than electron energization in the sheath. We find that the electron density and ionization probability of the sputtered species depend largely on the discharge current. The results suggest ways to adjust electron density and electron temperature using the discharge current and the magnetic field, respectively, and how they influence the ionization probability.
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| 9. |
- Babu, Swetha Suresh, et al.
(författare)
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Modeling of high power impulse magnetron sputtering discharges with tungsten target
- 2022
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Ingår i: Plasma sources science & technology. - : IOP Publishing. - 0963-0252 .- 1361-6595. ; 31:6, s. 065009-
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Tidskriftsartikel (refereegranskat)abstract
- The ionization region model (IRM) is applied to model a high power impulse magnetron sputtering discharge with a tungsten target. The IRM gives the temporal variation of the various species and the average electron energy, as well as internal discharge parameters such as the ionization probability and the back-attraction probability of the sputtered species. It is shown that an initial peak in the discharge current is due to argon ions bombarding the cathode target. After the initial peak, the W+ ions become the dominating ions and remain as such to the end of the pulse. We demonstrate how the contribution of the W+ ions to the total discharge current at the target surface increases with increased discharge voltage for peak discharge current densities J (D,peak) in the range 0.33-0.73 A cm(-2). For the sputtered tungsten the ionization probability increases, while the back-attraction probability decreases with increasing discharge voltage. Furthermore, we discuss the findings in terms of the generalized recycling model and compare to experimentally determined deposition rates and find good agreement.
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| 10. |
- Brenning, Nils, et al.
(författare)
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HiPIMS optimization by using mixed high-power and low-power pulsing
- 2021
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Ingår i: Plasma sources science & technology. - : IOP Publishing. - 0963-0252 .- 1361-6595. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- The possibility to optimize a high-power impulse magnetron sputtering (HiPIMS) discharge through mixing two different power levels in the pulse pattern is investigated. Standard HiPIMS pulses are used to create the ions of the film-forming material. After each HiPIMS pulse an off-time follows, during which no voltage (or, optionally, a reversed voltage) is applied, letting the remaining ions in the magnetic trap escape towards the substrate. After these off-times, a long second pulse with lower amplitude, in the dc magnetron sputtering range, is applied. During this pulse, which is continued up to the following HiPIMS pulse, mainly neutrals of the film-forming material are produced. This pulse pattern makes it possible to achieve separate optimization of the ion production, and of the neutral atom production, that constitute the film-forming flux to the substrate. The optimization process is thereby separated into two sub-problems. The first sub-problem concerns minimizing the energy cost for ion production, and the second sub-problem deals with how to best split a given allowed discharge power between ion production and neutral production. The optimum power split is decided by the lowest ionized flux fraction that gives the desired film properties for a specific application. For the first sub-problem we describe a method where optimization is achieved by the selection of five process parameters: the HiPIMS pulse amplitude, the HiPIMS pulse length, the off-time, the working gas pressure, and the magnetic field strength. For the second sub-problem, the splitting of power between ion and neutral production, optimization is achieved by the selection of the values of two remaining process parameters, the HiPIMS pulse repetition frequency and the discharge voltage of the low-power pulse.
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