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- Shrine, N, et al.
(författare)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Tidskriftsartikel (refereegranskat)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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- Belyaev, A., et al.
(författare)
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Advancing LHC Probes of Dark Matter from the Inert two-Higgs Doublet Model with the Mono-jet Signal
- 2019
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 99:1
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Tidskriftsartikel (refereegranskat)abstract
- The inert 2-Higgs Doublet Model (i2HDM) is a well-motivated minimal consistent Dark Matter (DM) model, but it is rather challenging to test at the Large Hadron Collider (LHC) in the parameter space allowed by relic density and DM direct detection constraints. This is especially true when considering the latest XENON 1T data on direct DM searches which we use here to present the best current combined limit on the i2HDM parameter space. In this analysis, we present prospects to advance the exploitation of DM mono-jet signatures from the i2HDM at the LHC, by emphasising that a shape analysis of the missing transverse momentum distribution allows one to sizably improve the LHC discovery potential. As a key element of our analysis, we explore the validity of using an effective vertex, Hgg, for the coupling of the Higgs boson to gluons using a full one-loop computation. We have found sizeable differences between the two approaches, especially in the high missing transverse momentum region, and incorporated the respective K-factors to obtain the correct kinematical distributions. As a result, we delineate a realistic search strategy and present the improved current and projected LHC sensitivity to the i2HDM parameter space.
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- Porth, Oliver, et al.
(författare)
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The Event Horizon General Relativistic Magnetohydrodynamic Code Comparison Project
- 2019
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Ingår i: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 243:2
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Tidskriftsartikel (refereegranskat)abstract
- Recent developments in compact object astrophysics, especially the discovery of merging neutron stars by LIGO, the imaging of the black hole in M87 by the Event Horizon Telescope, and high- precision astrometry of the Galactic Center at close to the event horizon scale by the GRAVITY experiment motivate the development of numerical source models that solve the equations of general relativistic magnetohydrodynamics (GRMHD). Here we compare GRMHD solutions for the evolution of a magnetized accretion flow where turbulence is promoted by the magnetorotational instability from a set of nine GRMHD codes: Athena++, BHAC, Cosmos++, ECHO, H-AMR, iharm3D, HARM-Noble, IllinoisGRMHD, and KORAL. Agreement among the codes improves as resolution increases, as measured by a consistently applied, specially developed set of code performance metrics. We conclude that the community of GRMHD codes is mature, capable, and consistent on these test problems.
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