| 1. |
- Morris, John A, et al.
(författare)
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An atlas of genetic influences on osteoporosis in humans and mice.
- 2019
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 51, s. 258-266
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR)=58, P=1 × 10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P<0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.
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| 2. |
- Pithan, Felix, et al.
(författare)
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Select strengths and biases of models in representing the Arctic winter boundary layer over sea ice : the Larcform 1 single column model intercomparison
- 2016
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Ingår i: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 8:3, s. 1345-1357
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Tidskriftsartikel (refereegranskat)abstract
- Weather and climate models struggle to represent lower tropospheric temperature and moisture profiles and surface fluxes in Arctic winter, partly because they lack or misrepresent physical processes that are specific to high latitudes. Observations have revealed two preferred states of the Arctic winter boundary layer. In the cloudy state, cloud liquid water limits surface radiative cooling, and temperature inversions are weak and elevated. In the radiatively clear state, strong surface radiative cooling leads to the build-up of surface-based temperature inversions. Many large-scale models lack the cloudy state, and some substantially underestimate inversion strength in the clear state. Here, the transformation from a moist to a cold dry air mass is modeled using an idealized Lagrangian perspective. The trajectory includes both boundary layer states, and the single-column experiment is the first Lagrangian Arctic air formation experiment (Larcform 1) organized within GEWEX GASS (Global atmospheric system studies). The intercomparison reproduces the typical biases of large-scale models: some models lack the cloudy state of the boundary layer due to the representation of mixed-phase microphysics or to the interaction between micro- and macrophysics. In some models, high emissivities of ice clouds or the lack of an insulating snow layer prevent the build-up of surface-based inversions in the radiatively clear state. Models substantially disagree on the amount of cloud liquid water in the cloudy state and on turbulent heat fluxes under clear skies. Observations of air mass transformations including both boundary layer states would allow for a tighter constraint of model behavior.
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| 3. |
- Caron, Louis-Philippe, et al.
(författare)
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On the relationship between cloud-radiation interaction, atmospheric stability and Atlantic tropical cyclones in a variable-resolution climate model
- 2013
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 40:5-6, s. 1257-1269
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Tidskriftsartikel (refereegranskat)abstract
- We compare two 28-year simulations performed with two versions of the Global Environmental Multiscale model run in variable-resolution mode. The two versions differ only by small differences in their radiation scheme. The most significant modification introduced is a reduction in the ice effective radius, which is observed to increase absorption of upwelling infrared radiation and increase temperature in the upper troposphere. The resulting change in vertical lapse rate is then observed to drive a resolution-dependent response of convection, which in turn modifies the zonal circulation and induces significant changes in simulated Atlantic tropical cyclone activity. The resulting change in vertical lapse rate and its implication in the context of anthropogenic climate change are discussed.
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