| 1. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 2. |
- Cook, D. O., et al.
(författare)
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Star cluster catalogues for the LEGUS dwarf galaxies
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 484:4, s. 4897-4919
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Tidskriftsartikel (refereegranskat)abstract
- We present the star cluster catalogues for 17 dwarf and irregular galaxies in the HST Treasury Program 'Legacy ExtraGalactic UV Survey' (LEGUS). Cluster identification and photometry in this sub-sample are similar to that of the entire LEGUS sample, but special methods were developed to provide robust catalogues with accurate fluxes due to low cluster statistics. The colours and ages are largely consistent for two widely used aperture corrections, but a significant fraction of the clusters are more compact than the average training cluster. However, the ensemble luminosity, mass, and age distributions are consistent suggesting that the systematics between the two methods are less than the random errors. When compared with the clusters from previous dwarf galaxy samples, we find that the LEGUS catalogues are more complete and provide more accurate total fluxes. Combining all clusters into a composite dwarf galaxy, we find that the luminosity and mass functions can be described by a power law with the canonical index of -2 independent of age and global SFR binning. The age distribution declines as a power law, with an index of approximate to -0.80 +/- 0.15, independent of cluster mass and global SFR binning. This decline of clusters is dominated by cluster disruption since the combined star formation histories and integrated-light SFRs are both approximately constant over the last few hundred Myr. Finally, we find little evidence for an upper-mass cut-off (< 2 sigma) in the composite cluster mass function, and can rule out a truncation mass below approximate to 10(4.5)M(circle dot) but cannot rule out the existence of a truncation at higher masses.
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| 3. |
- Ahmadi, M., et al.
(författare)
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Investigation of the fine structure of antihydrogen
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7795, s. 375-380
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Tidskriftsartikel (refereegranskat)abstract
- At the historic Shelter Island Conference on the Foundations of Quantum Mechanics in 1947, Willis Lamb reported an unexpected feature in the fine structure of atomic hydrogen: a separation of the 2S(1/2) and 2P(1/2) states(1). The observation of this separation, now known as the Lamb shift, marked an important event in the evolution of modern physics, inspiring others to develop the theory of quantum electrodynamics(2-5). Quantum electrodynamics also describes antimatter, but it has only recently become possible to synthesize and trap atomic antimatter to probe its structure. Mirroring the historical development of quantum atomic physics in the twentieth century, modern measurements on anti-atoms represent a unique approach for testing quantum electrodynamics and the foundational symmetries of the standard model. Here we report measurements of the fine structure in the n = 2 states of antihydrogen, the antimatter counterpart of the hydrogen atom. Using optical excitation of the 1S-2P Lyman-alpha transitions in antihydrogen(6), we determine their frequencies in a magnetic field of 1 tesla to a precision of 16 parts per billion. Assuming the standard Zeeman and hyperfine interactions, we infer the zero-field fine-structure splitting (2P(1/2)-2P(3/2)) in antihydrogen. The resulting value is consistent with the predictions of quantum electrodynamics to a precision of 2 per cent. Using our previously measured value of the 1S-2S transition frequency(6,7), we find that the classic Lamb shift in antihydrogen (2S(1/2)-2P(1/2) splitting at zero field) is consistent with theory at a level of 11 per cent. Our observations represent an important step towards precision measurements of the fine structure and the Lamb shift in the antihydrogen spectrum as tests of the charge-parity-time symmetry(8) and towards the determination of other fundamental quantities, such as the antiproton charge radius(9,10), in this antimatter system. Precision measurements of the 1S-2P transition in antihydrogen that take into account the standard Zeeman and hyperfine effects confirm the predictions of quantum electrodynamics.
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| 4. |
- Ahmadi, M., et al.
(författare)
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Observation of the 1S-2P Lyman-alpha transition in antihydrogen
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 561:7722, s. 211-217
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Tidskriftsartikel (refereegranskat)abstract
- In 1906, Theodore Lyman discovered his eponymous series of transitions in the extreme-ultraviolet region of the atomic hydrogen spectrum(1,2). The patterns in the hydrogen spectrum helped to establish the emerging theory of quantum mechanics, which we now know governs the world at the atomic scale. Since then, studies involving the Lyman-alpha line-the 1S-2P transition at a wavelength of 121.6 nanometres-have played an important part in physics and astronomy, as one of the most fundamental atomic transitions in the Universe. For example, this transition has long been used by astronomers studying the intergalactic medium and testing cosmological models via the so-called 'Lyman-alpha forest('3) of absorption lines at different redshifts. Here we report the observation of the Lyman-alpha transition in the antihydrogen atom, the antimatter counterpart of hydrogen. Using narrow-line-width, nanosecond-pulsed laser radiation, the 1S-2P transition was excited in magnetically trapped antihydrogen. The transition frequency at a field of 1.033 tesla was determined to be 2,466,051.7 +/- 0.12 gigahertz (1 sigma uncertainty) and agrees with the prediction for hydrogen to a precision of 5 x 10(-8). Comparisons of the properties of antihydrogen with those of its well-studied matter equivalent allow precision tests of fundamental symmetries between matter ;and antimatter. Alongside the ground-state hyperfine(4,5) and 1S-2S transitions(6,7) recently observed in antihydrogen, the Lyman-alpha transition will permit laser cooling of antihydrogen(8,9), thus providing a cold and dense sample of anti-atoms for precision spectroscopy and gravity measurements(10). In addition to the observation of this fundamental transition, this work represents both a decisive technological step towards laser cooling of antihydrogen, and the extension of antimatter spectroscopy to quantum states possessing orbital angular momentum.
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| 5. |
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| 6. |
- Baker, C. J., et al.
(författare)
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Laser cooling of antihydrogen atoms
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 592:7852, s. 35-42
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Tidskriftsartikel (refereegranskat)abstract
- The photon-the quantum excitation of the electromagnetic field-is massless but carries momentum. A photon can therefore exert a force on an object upon collision(1). Slowing the translational motion of atoms and ions by application of such a force(2,3), known as laser cooling, was first demonstrated 40 years ago(4,5). It revolutionized atomic physics over the following decades(6-8), and it is now a workhorse in many fields, including studies on quantum degenerate gases, quantum information, atomic clocks and tests of fundamental physics. However, this technique has not yet been applied to antimatter. Here we demonstrate laser cooling of antihydrogen(9), the antimatter atom consisting of an antiproton and a positron. By exciting the 1S-2P transition in antihydrogen with pulsed, narrow-linewidth, Lyman-alpha laser radiation(10,11), we Doppler-cool a sample of magnetically trapped antihydrogen. Although we apply laser cooling in only one dimension, the trap couples the longitudinal and transverse motions of the anti-atoms, leading to cooling in all three dimensions. We observe a reduction in the median transverse energy by more than an order of magnitude-with a substantial fraction of the anti-atoms attaining submicroelectronvolt transverse kinetic energies. We also report the observation of the laser-driven 1S-2S transition in samples of laser-cooled antihydrogen atoms. The observed spectral line is approximately four times narrower than that obtained without laser cooling. The demonstration of laser cooling and its immediate application has far-reaching implications for antimatter studies. A more localized, denser and colder sample of antihydrogen will drastically improve spectroscopic(11-13) and gravitational(14) studies of antihydrogen in ongoing experiments. Furthermore, the demonstrated ability to manipulate the motion of antimatter atoms by laser light will potentially provide ground-breaking opportunities for future experiments, such as anti-atomic fountains, anti-atom interferometry and the creation of antimatter molecules.
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| 7. |
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| 8. |
- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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| 9. |
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| 10. |
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