| 1. |
- Koettgen, Anna, et al.
(författare)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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| 2. |
- Assimes, Themistocles L., et al.
(författare)
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Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
- 2010
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:19, s. 1552-1563
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Tidskriftsartikel (refereegranskat)abstract
- Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
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| 3. |
- Malerba, L., et al.
(författare)
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Ab initio calculations and interatomic potentials for iron and iron alloys : Achievements within the Perfect Project
- 2010
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 406:1, s. 7-18
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the FP6 Perfect Project was to develop a first example of integrated multiscale computational models, capable of describing the effects of irradiation in nuclear reactor components, namely vessel and internals. The use of ab initio techniques to study, in the most reliable way currently possible, atomic-level interactions between species and defects, and the transfer of this knowledge to interatomic potentials, of use for large scale dynamic simulations, lie at the core of this effort. The target materials of the Project were bainitic steels (vessel) and austenitic steels (internals), i.e. iron alloys. In this article, the advances made within the Project in the understanding of defect properties in Fe alloys, by means of ab initio calculations, and in the development of interatomic potentials for Fe and Fe alloys are overviewed, thereby providing a reference basis for further progress in the field. Emphasis is put in showing how the produced data have enhanced our level of understanding of microstructural processes occurring under irradiation in model alloys and steels used in existing nuclear power plants.
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| 4. |
- Djurabekova, F., et al.
(författare)
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Kinetics versus thermodynamics in materials modeling : The case of the di-vacancy in iron
- 2010
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Ingår i: Philosophical Magazine. - : Informa UK Limited. - 1478-6435 .- 1478-6443. ; 90:19, s. 2585-2595
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Tidskriftsartikel (refereegranskat)abstract
- Monte Carlo models are widely used for the study of microstructural and microchemical evolution of materials under irradiation. However, they often link explicitly the relevant activation energies to the energy difference between local equilibrium states. We provide a simple example (di-vacancy migration in iron) in which a rigorous activation energy calculation, by means of both empirical interatomic potentials and density functional theory methods, clearly shows that such a link is not granted, revealing a migration mechanism that a thermodynamics-linked activation energy model cannot predict. Such a mechanism is, however, fully consistent with thermodynamics. This example emphasizes the importance of basing Monte Carlo methods on models where the activation energies are rigorously calculated, rather than deduced from widespread heuristic equations.
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| 5. |
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| 6. |
- Malerba, L., et al.
(författare)
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Comparison of empirical interatomic potentials for iron applied to radiation damage studies
- 2010
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 406:1, s. 19-38
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Tidskriftsartikel (refereegranskat)abstract
- The performance of four recent semi-empirical interatomic potentials for iron, developed or used within the FP6 Perfect Project, is evaluated by comparing them between themselves and with available experimental or, more often, density functional theory data. The quantities chosen for the comparison are of specific interest for radiation damage studies, i.e. they concern mainly properties of point-defects and their clusters, as well as dislocations. For completeness, an earlier, widely used (also within the Project) iron potential is included in the comparison exercise as well. This exercise allows conclusions to be drawn about the reliability of the available potentials, while providing a snapshot of the state-of-the-art concerning fundamental properties of iron, thereby being also useful as a kind of handbook and as a framework for the validation of future semi-empirical interatomic potentials for iron. It is found that Mendelev-type potentials are currently the best choice in order to "extend density functional theory" to larger scales and this justifies their widespread use, also for the development of iron alloy potentials. However, a fully reliable description of self-interstitial atom clusters and dislocations with interatomic potentials remains largely an elusive objective, that calls for further effort within the concerned scientific community.
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| 7. |
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| 8. |
- Terentyev, D., et al.
(författare)
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Further development of large-scale atomistic modelling techniques for Fe-Cr alloys
- 2011
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 409:2, s. 167-175
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we review the current status of our efforts to model the Fe-Cr system, which is a model alloy for high-Cr ferritic-martensitic steels, using large-scale atomistic methods. The core of such methods are semi-empirical interatomic potentials. Here we discuss their performance with respect to the features that are important for an accurate description of radiation effects in Fe-Cr alloys. We describe their most recent improvements regarding macroscopic thermodynamic properties as well as microscopic point-defect properties. Furthermore we describe a new type of large-scale atomistic kinetic Monte Carlo (AKMC) approach driven by an artificial neural network (ANN) regression method to generate the local migration barrier for a defect accounting for the local chemistry around it. The results of the thermal annealing of the Fe-20Cr alloy modelled using this AKMC approach, parameterized by our newly developed potential, were found to be in very good agreement with experimental data. Furthermore the interaction of a 1/2 (1 1 1) screw dislocation with Cr precipitates as obtained from the AKMC simulations was studied using the same potential. In summary, we critically discuss our current achievements, findings and outline issues to be addressed in the near future development.
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