| 1. |
- Wang, Z., et al.
(författare)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Tidskriftsartikel (refereegranskat)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 2. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 3. |
- Knyazev, A., et al.
(författare)
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Simulations of light collection in long tapered CsI(Tl) scintillators using real crystal surface data and comparisons to measurement
- 2021
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Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 1003
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Tidskriftsartikel (refereegranskat)abstract
- Simulation results for light transport in long tapered CsI(Tl) crystals using look-up tables (LUTs) are presented. The LUTs were derived from the topography of a polished and a lapped surface of a CsI(Tl) crystal measured with atomic force microscopy. Simulations with different combinations of polished and lapped surfaces were performed, to extract the non-uniformity of light collection depending on the interaction point, and compared to experimental results. The simulations reproduce the general trend given by the measurements, and show that more homogeneous light collection is attained when all lateral sides of the crystal are lapped. For the lapped crystal the simulation model is most sensitive to the reflectivity of the enhanced specular reflector (ESR) foil surrounding the crystal, which is one of several properties influencing the light transport examined in this study. The sensitivity of the light-output non-uniformity to variations in the absorption length observed in a batch of CsI(Tl) crystals in a previous study is also discussed. Residual differences between the simulation and the measurements can potentially be attributed to the scattering of scintillation photons inside the materials used. Additional measurements to further advance the construction of the simulation model are suggested.
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| 4. |
- Knyazev, A., et al.
(författare)
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Tl concentration and its variation in a CsI(Tl) crystal for the CALIFA detector
- 2020
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Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 975
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Tidskriftsartikel (refereegranskat)abstract
- One of the factors that can contribute to the resolution of long, doped inorganic scintillators used for nuclear spectroscopy is the variation of the dopant concentration over the length the detector crystal. In this work an investigation of such potential variations in one of the CsI(Tl) scintillators used in the calorimeter, CALIFA, of the R3B experiment at FAIR, has been performed using particle induced X-ray emission. No statistically significant gradient in doping level was found along the long axis of the investigated sample crystal and the mean value of the Tl concentration was measured to be 0.0839(38)% by weight. This corresponds to a light output of 97.3−1.7 +1.3% relative to the maximum attainable light output according to previously published work. By taking the ±1σ bounds, the 3% statistical spread in the relative light output provides a good reference value of the minimum light-output non-uniformity observed for the CALIFA crystals. If the relative light output is estimated pointwise from a set of Tl concentration measurements a light-output non-uniformity of 4.6(2.4)% results. For a γ-ray energy of 662 keV the deduced variation in Tl concentration contributes with 0.48(6)% to the typical resolution of 7.74(6)% measured with a collimated source along the crystal main axis. The result is of interest for the characterization of the detector system performance and for realistic simulations of the light collection process in detector systems that are used for nuclear spectroscopy and calorimetry.
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