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- 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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- Teixeira, J., et al.
(författare)
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Tropical and Subtropical Cloud Transitions in Weather and Climate Prediction Models : The GCSS/WGNE Pacific Cross-Section Intercomparison (GPCI)
- 2011
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Ingår i: Journal of Climate. - 0894-8755 .- 1520-0442. ; 24:20, s. 5223-5256
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Tidskriftsartikel (refereegranskat)abstract
- A model evaluation approach is proposed in which weather and climate prediction models are analyzed along a Pacific Ocean cross section, from the stratocumulus regions off the coast of California, across the shallow convection dominated trade winds, to the deep convection regions of the ITCZ-the Global Energy and Water Cycle Experiment Cloud System Study/Working Group on Numerical Experimentation (GCSS/WGNE) Pacific Cross-Section Intercomparison (GPCI). The main goal of GPCI is to evaluate and help understand and improve the representation of tropical and subtropical cloud processes in weather and climate prediction models. In this paper, a detailed analysis of cloud regime transitions along the cross section from the subtropics to the tropics for the season June-July-August of 1998 is presented. This GPCI study confirms many of the typical weather and climate prediction model problems in the representation of clouds: underestimation of clouds in the stratocumulus regime by most models with the corresponding consequences in terms of shortwave radiation biases; overestimation of clouds by the 40-yr ECMWF Re-Analysis (ERA-40) in the deep tropics (in particular) with the corresponding impact in the outgoing longwave radiation; large spread between the different models in terms of cloud cover, liquid water path and shortwave radiation; significant differences between the models in terms of vertical cross sections of cloud properties (in particular), vertical velocity, and relative humidity. An alternative analysis of cloud cover mean statistics is proposed where sharp gradients in cloud cover along the GPCI transect are taken into account. This analysis shows that the negative cloud bias of some models and ERA-40 in the stratocumulus regions [as compared to the first International Satellite Cloud Climatology Project (ISCCP)] is associated not only with lower values of cloud cover in these regimes, but also with a stratocumulus-to-cumulus transition that occurs too early along the trade wind Lagrangian trajectory. Histograms of cloud cover along the cross section differ significantly between models. Some models exhibit a quasi-bimodal structure with cloud cover being either very large (close to 100%) or very small, while other models show a more continuous transition. The ISCCP observations suggest that reality is in-between these two extreme examples. These different patterns reflect the diverse nature of the cloud, boundary layer, and convection parameterizations in the participating weather and climate prediction models.
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- Harwit, M., et al.
(författare)
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Polarisation observations of VY Canis Majoris H2O 5(32)-4(41) 620.701 GHz maser emission with HIFI
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L51-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Water vapour maser emission from evolved oxygen-rich stars remains poorly understood. Additional observations, including polarisation studies and simultaneous observation of different maser transitions may ultimately lead to greater insight. Aims. We have aimed to elucidate the nature and structure of the VY CMa water vapour masers in part by observationally testing a theoretical prediction of the relative strengths of the 620.701 GHz and the 22.235 GHz maser components of ortho H2O. Methods. In its high-resolution mode (HRS) the Herschel Heterodyne Instrument for the Far Infrared (HIFI) offers a frequency resolution of 0.125 MHz, corresponding to a line-of-sight velocity of 0.06 km s(-1), which we employed to obtain the strength and linear polarisation of maser spikes in the spectrum of VY CMa at 620.701 GHz. Simultaneous ground based observations of the 22.235 GHz maser with the Max-Planck-Institut fur Radioastronomie 100-m telescope at Effelsberg, provided a ratio of 620.701 GHz to 22.235 GHz emission. Results. We report the first astronomical detection to date of H2O maser emission at 620.701 GHz. In VY CMa both the 620.701 and the 22.235 GHz polarisation are weak. At 620.701 GHz the maser peaks are superposed on what appears to be a broad emission component, jointly ejected from the star. We observed the 620.701 GHz emission at two epochs 21 days apart, both to measure the potential direction of linearly polarised maser components and to obtain a measure of the longevity of these components. Although we do not detect significant polarisation levels in the core of the line, they rise up to approximately 6% in its wings.
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| 10. |
- Harwit, M., et al.
(författare)
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Polarisation observations of VY Canis Majoris H2O 532-441 620.701 GHz maser emission with HIFI
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L51-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Water vapour maser emission from evolved oxygen-rich stars remains poorly understood. Additional observations, including polarisation studies and simultaneous observation of different maser transitions may ultimately lead to greater insight. Aims. We have aimed to elucidate the nature and structure of the VY CMa water vapour masers in part by observationally testing a theoretical prediction of the relative strengths of the 620.701 GHz and the 22.235 GHz maser components of ortho H2O. Methods. In its high-resolution mode (HRS) the Herschel Heterodyne Instrument for the Far Infrared (HIFI) offers a frequency resolution of 0.125 MHz, corresponding to a line-of-sight velocity of 0.06 km s(-1), which we employed to obtain the strength and linear polarisation of maser spikes in the spectrum of VY CMa at 620.701 GHz. Simultaneous ground based observations of the 22.235 GHz maser with the Max-Planck-Institut fur Radioastronomie 100-m telescope at Effelsberg, provided a ratio of 620.701 GHz to 22.235 GHz emission. Results. We report the first astronomical detection to date of H2O maser emission at 620.701 GHz. In VY CMa both the 620.701 and the 22.235 GHz polarisation are weak. At 620.701 GHz the maser peaks are superposed on what appears to be a broad emission component, jointly ejected from the star. We observed the 620.701 GHz emission at two epochs 21 days apart, both to measure the potential direction of linearly polarised maser components and to obtain a measure of the longevity of these components. Although we do not detect significant polarisation levels in the core of the line, they rise up to approximately 6% in its wings.
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