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- Schlosser, P, et al.
(author)
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Meta-analyses identify DNA methylation associated with kidney function and damage
- 2021
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7174-
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Journal article (peer-reviewed)abstract
- Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
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- Tin, A, et al.
(author)
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Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
- 2021
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7173-
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Journal article (peer-reviewed)abstract
- Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E–7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
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- Joshi, Siddarth Koduru, et al.
(author)
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Space QUEST mission proposal : experimentally testing decoherence due to gravity
- 2018
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In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 20
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Journal article (peer-reviewed)abstract
- Models of quantum systems on curved space-times lack sufficient experimental verification. Some speculative theories suggest that quantum correlations, such as entanglement, may exhibit different behavior to purely classical correlations in curved space. By measuring this effect or lack thereof, we can test the hypotheses behind several such models. For instance, as predicted by Ralph et al [5] and Ralph and Pienaar [1], a bipartite entangled system could decohere if each particle traversed through a different gravitational field gradient. We propose to study this effect in a ground to space uplink scenario. We extend the above theoretical predictions of Ralph and coworkers and discuss the scientific consequences of detecting/failing to detect the predicted gravitational decoherence. We present a detailed mission design of the European Space Agency's Space QUEST (Space-Quantum Entanglement Space Test) mission, and study the feasibility of the mission scheme.
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- Oswald, S. M, et al.
(author)
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Coupling of urban energy balance model with 3-D radiation model to derive human thermal (dis)comfort
- 2019
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In: International journal of biometeorology. - : Springer Science and Business Media LLC. - 0020-7128 .- 1432-1254. ; 63:6, s. 711-722
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Journal article (peer-reviewed)abstract
- While capabilities in urban climate modeling have substantially increased in recent decades, the interdependency of changes in environmental surface properties and human (dis)comfort have only recently received attention. The open-source solar long-wave environmental irradiance geometry (SOLWEIG) model is one of the state-of-the-art models frequently used for urban (micro-)climatic studies. Here, we present updated calculation schemes for SOLWEIG allowing the improved prediction of surface temperatures (wall and ground). We illustrate that parameterizations based on measurements of global radiation on a south-facing vertical plane obtain better results compared to those based on solar elevation. Due to the limited number of ground surface temperature parameterizations in SOLWEIG, we implement the two-layer force-restore method for calculating ground temperature for various soil conditions. To characterize changes in urban canyon air temperature (Tcan), we couple the calculation method as used in the Town Energy Balance (TEB) model. Comparison of model results and observations (obtained during field campaigns) indicates a good agreement between modeled and measured Tcan, with an explained variance of R2 =0.99. Finally, we implement an energy balance model for vertically mounted PV modules to contrast different urban surface properties. Specifically, we consider (i) an environment comprising dark asphalt and a glass facade and (ii) an environment comprising bright concrete and a PV facade. The model results show a substantially decreased Tcan (by up to − 1.65°C) for the latter case, indicating the potential of partially reducing/mitigating urban heat island effects.
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