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- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 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
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 2. |
- Persson, Jonas, et al.
(författare)
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Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease
- 2015
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Ingår i: Journal of the American Heart Association. - : WILEY-BLACKWELL. - 2047-9980. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- Background-Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results-Baseline plasma adiponectin concentrationwas tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (beta=-0.018, P<0.001) in men but not in women (beta=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (beta=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82,95% CI0.54 to 1.25). Agenescore of adiponectin-raisingalleles in6loci, reported recently inalarge multi-ethnic metaanalysis, was inversely associated with baseline mean bifurcation IMT in men (beta=-0.0008, P=0.004) but not in women (beta=-0.0003, P=0.522; P for interaction=0.007). Conclusions-This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted.
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| 3. |
- Mohr, Matthias, et al.
(författare)
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Wind power in forests II : Forest wind
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sweden has good conditions for wind power. However, most of Sweden (ca. 70%) is covered by forest. Forests decrease wind speeds and create turbulence, something which is not favourable for wind power. Several Swedish wind maps have shown that forests in Nordic countries can be well suited for wind power (e.g. Bergström and Söderberg 2011, Byrkjedal and Åkervik 2009).At the same time, there is uncertainty over wind conditions over forests at very high altitudes (ca. 150 m above ground). How good do wind resource assessment models agree with measurements? How much energy is a wind turbine in forest going to produce and which loads will a wind turbine in forest experience?This project has investigated all these issues. Work was concentrated in the following work packages:Wind resource at very high heightsTurbulence- and wind measurements at very high heights above forestAnalysis of turbulence data from forestsModel simulations with wind flow modelsModel simulations with very-high-resolution weather forecast modelsModel simulations with Large Eddy Simulation (LES) modelsImproved specification of so-called “synthetic turbulence” over forestAnalysis of airborne laser altimeter measurements over forestForest’s effects on wind turbine energy productionLoad simulations for wind turbines over forestWP1 studies how wind speed and direction varies with height over forest (up to ca 150 m above ground and higher up). Several profile relations are studied here. Frequency distributions of wind shear and veer are presented. WP2 describes turbulence and wind measurements that have been carried out within the project at Hornamossen. Moreover, the measurement campaign that was carried out in a line over the Hornamossen-hill within the New European Wind Atlas project is described. WP3 analyses turbulence data from Hornamossen together with turbulence data from Ryningsnäs. Of special interest is how turbulence intensity decreases with height as well as if the IEC-standard class A, B or C for wind turbines is complied with at different heights. WP4 describes the newly developed linearised wind flow model ORFEUS with a dedicated forest module. WP5 describes model simulations with WRF and the MIUU model, their sensitivity for surface roughness and turbulence parameterisations. Mean wind profiles from the models are compared to Hornamossen. WP6 describes LES simulations with Chalmers LES model and WRF-LES. LES-resultats depend to a large degree on how the turbulent vortices are initialised at the inflow boundaries of the LES model. Several different methods for that are described. WP7 describes a new turbulence model (the Segalini & Arnqvist model) that includes atmospheric stability. This is a further development of the IEC turbulence model (=Mann model) for neutral stability. Coherence of turbulent winds as well as phase profiles are other improvements of the IEC model. WP8 describes a new method to compute leaf/needle/plant area density from laser scans of the Swedish forest and how one estimates surface roughness and zero plane displacement from that. The new method is compared with two other methods. Results are also compared with official forest data (“skoglig grunddata”). The effect on the wind profile is also shown. WP9 describes the new methods for estimating AEP from the Power Curve Working Group and the IEC standard for Power Performance Testing. Effects on estimated AEP are shown. A new simple model for calculating turbulence effects on energy production is developed and compared with data from a wind farm. Within WP10 a new generic open-source wind turbine is developed and used for load simulations with aero-elastic simulations. Results show that the new coherence model for turbulence gives much smaller loads than the turbulence model of the IEC standard.For more information on the different parts of the project the reader is referred to the report’s introduction, the ”Summary and Conclusions” of each chapter as well as the overall summary (”Executive Summary”) at the end of the report.
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| 6. |
- Lötstedt, Per, et al.
(författare)
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Implicit solution of hyperbolic equations with space-time adaptivity
- 2000
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Adaptivity in space and time is introduced to control the error in the numerical solution of hyperbolic partial differential equations. The equations are discretised by a finite volume method in space and an implicit linear multistep method in time. The computational grid is refined in blocks. At the boundaries of the blocks, there may be jumps in the step size. Special treatment is needed there to ensure second order accuracy and stability. The local truncation error of the discretisation is estimated and is controlled by changing the step size and the time step. The global error is obtained by integration of the error equations. In the implicit scheme, the system of linear equations at each time step is solved iteratively by the GMRES method. Numerical examples executed on a parallel computer illustrate the method.
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| 9. |
- Lötstedt, Per, et al.
(författare)
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Preconditioned implicit solution of linear hyperbolic equations with adaptivity
- 2003
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper describes a method for solving hyperbolic partial differential equations using an adaptive grid: the spatial derivatives are discretised with a finite volume method on a grid which is structured and partitioned into blocks which may be refined and derefined as the solution evolves. The solution is advanced in time via a backward differentiation formula. The discretisation used is second order accurate and stable on Cartesian grids. The resulting system of linear equations is solved by GMRES at every time-step with the convergence of the iteration being accelerated by a semi-Toeplitz preconditioner. The efficiency of this preconditioning technique is analysed and numerical experiments are presented which illustrate the behaviour of the method on a parallel computer.
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| 10. |
- Mishra, Yogesh, et al.
(författare)
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Active-site plasticity revealed in the asymmetric dimer of AnPrx6 the 1-Cys peroxiredoxin and molecular chaperone from Anabaena sp. PCC 7120
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Peroxiredoxins (Prxs) are vital regulators of intracellular reactive oxygen species levels in all living organisms. Their activity depends on one or two catalytically active cysteine residues, the peroxidatic Cys (C-P) and, if present, the resolving Cys (C-R). A detailed catalytic cycle has been derived for typical 2-Cys Prxs, however, little is known about the catalytic cycle of 1-Cys Prxs. We have characterized Prx6 from the cyanobacterium Anabaena sp. strain PCC7120 (AnPrx6) and found that in addition to the expected peroxidase activity, AnPrx6 can act as a molecular chaperone in its dimeric state, contrary to other Prxs. The AnPrx6 crystal structure at 2.3 angstrom resolution reveals different active site conformations in each monomer of the asymmetric obligate homo-dimer. Molecular dynamic simulations support the observed structural plasticity. A FSH motif, conserved in 1-Cys Prxs, precedes the active site PxxxTxxCp signature and might contribute to the 1-Cys Prx reaction cycle.
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