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- van Rheenen, W, et al.
(författare)
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Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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- Ahmadi, M., et al.
(författare)
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Antihydrogen accumulation for fundamental symmetry tests
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Antihydrogen, a positron bound to an antiproton, is the simplest anti-atom. Its structure and properties are expected to mirror those of the hydrogen atom. Prospects for precision comparisons of the two, as tests of fundamental symmetries, are driving a vibrant programme of research. In this regard, a limiting factor in most experiments is the availability of large numbers of cold ground state antihydrogen atoms. Here, we describe how an improved synthesis process results in a maximum rate of 10.5 +/- 0.6 atoms trapped and detected per cycle, corresponding to more than an order of magnitude improvement over previous work. Additionally, we demonstrate how detailed control of electron, positron and antiproton plasmas enables repeated formation and trapping of antihydrogen atoms, with the simultaneous retention of atoms produced in previous cycles. We report a record of 54 detected annihilation events from a single release of the trapped anti-atoms accumulated from five consecutive cycles.
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- Ahmadi, M., et al.
(författare)
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Observation of the 1S-2S transition in trapped antihydrogen
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 541:7638, s. 506-510
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Tidskriftsartikel (refereegranskat)abstract
- The spectrum of the hydrogen atom has played a central part in fundamental physics over the past 200 years. Historical examples of its importance include the wavelength measurements of absorption lines in the solar spectrum by Fraunhofer, the identification of transition lines by Balmer, Lyman and others, the empirical description of allowed wavelengths by Rydberg, the quantum model of Bohr, the capability of quantum electrodynamics to precisely predict transition frequencies, and modern measurements of the 1S-2S transition by Hansch1 to a precision of a few parts in 10(15). Recent technological advances have allowed us to focus on antihydrogen-the antimatter equivalent of hydrogen(2-4). The Standard Model predicts that there should have been equal amounts of matter and antimatter in the primordial Universe after the Big Bang, but today's Universe is observed to consist almost entirely of ordinary matter. This motivates the study of antimatter, to see if there is a small asymmetry in the laws of physics that govern the two types of matter. In particular, the CPT (charge conjugation, parity reversal and time reversal) theorem, a cornerstone of the Standard Model, requires that hydrogen and antihydrogen have the same spectrum. Here we report the observation of the 1S-2S transition in magnetically trapped atoms of antihydrogen. We determine that the frequency of the transition, which is driven by two photons from a laser at 243 nanometres, is consistent with that expected for hydrogen in the same environment. This laser excitation of a quantum state of an atom of antimatter represents the most precise measurement performed on an anti-atom. Our result is consistent with CPT invariance at a relative precision of about 2 x 10(-10).
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- Ahmadi, M., et al.
(författare)
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Observation of the hyperfine spectrum of antihydrogen
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 548:7665, s. 66-
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Tidskriftsartikel (refereegranskat)abstract
- The observation of hyperfine structure in atomic hydrogen by Rabi and co-workers(1-3) and the measurement(4) of the zero-field ground-state splitting at the level of seven parts in 10(13) are important achievements of mid-twentieth-century physics. The work that led to these achievements also provided the first evidence for the anomalous magnetic moment of the electron(5-8), inspired Schwinger's relativistic theory of quantum electrodynamics(9,10) and gave rise to the hydrogen maser(11), which is a critical component of modern navigation, geo-positioning and very-long-baseline interferometry systems. Research at the Antiproton Decelerator at CERN by the ALPHA collaboration extends these enquiries into the antimatter sector. Recently, tools have been developed that enable studies of the hyperfine structure of antihydrogen(12)-the antimatter counterpart of hydrogen. The goal of such studies is to search for any differences that might exist between this archetypal pair of atoms, and thereby to test the fundamental principles on which quantum field theory is constructed. Magnetic trapping of antihydrogen atoms(13,14) provides a means of studying them by combining electromagnetic interaction with detection techniques that are unique to antimatter(12,15). Here we report the results of a microwave spectroscopy experiment in which we probe the response of antihydrogen over a controlled range of frequencies. The data reveal clear and distinct signatures of two allowed transitions, from which we obtain a direct, magnetic-field-independent measurement of the hyperfine splitting. From a set of trials involving 194 detected atoms, we determine a splitting of 1,420.4 +/- 0.5 megahertz, consistent with expectations for atomic hydrogen at the level of four parts in 10(4). This observation of the detailed behaviour of a quantum transition in an atom of antihydrogen exemplifies tests of fundamental symmetries such as charge-parity-time in antimatter, and the techniques developed here will enable more-precise such tests.
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- Ahmadi, M., et al.
(författare)
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Enhanced Control and Reproducibility of Non-Neutral Plasmas
- 2018
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 120:2
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Tidskriftsartikel (refereegranskat)abstract
- The simultaneous control of the density and particle number of non-neutral plasmas confined in Penning-Malmberg traps is demonstrated. Control is achieved by setting the plasma's density by applying a rotating electric field while simultaneously fixing its axial potential via evaporative cooling. This novel method is particularly useful for stabilizing positron plasmas, as the procedures used to collect positrons from radioactive sources typically yield plasmas with variable densities and particle numbers; it also simplifies optimization studies that require plasma parameter scans. The reproducibility achieved by applying this technique to the positron and electron plasmas used by the ALPHA antihydrogen experiment at CERN, combined with other developments, contributed to a 10-fold increase in the antiatom trapping rate.
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- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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