| 1. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 2. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 3. |
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| 4. |
- Kondo, Y., et al.
(författare)
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First observation of 28 O
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 620:7976, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10−21s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called ‘doubly magic’ nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.
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| 5. |
- Revel, A., et al.
(författare)
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Extending the Southern Shore of the Island of Inversion to F-28
- 2020
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 124:15
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Tidskriftsartikel (refereegranskat)abstract
- Detailed spectroscopy of the neutron-unbound nucleus F-28 has been performed for the first time following proton/neutron removal from Ne-29/F-29 beams at energies around 230 MeV=nucleon. The invariant-mass spectra were reconstructed for both the F-27((*)) + n and F-26((*)) + 2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the F-28 ground state, with S-n(F-28) = -199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S-n(F-27) = 1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of F-28. Importantly, in the case of the ground state, the reconstructed F-27 + n momentum distribution following neutron removal from F-29 indicates that it arises mainly from the 1p(3/2) neutron intruder configuration. This demonstrates that the island of inversion around N = 20 includes F-28, and most probably F-29, and suggests that O-28 is not doubly magic.
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| 6. |
- Wang, H., et al.
(författare)
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Intruder configurations in 29 Ne at the transition into the island of inversion: Detailed structure study of 28 Ne
- 2023
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 843
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Tidskriftsartikel (refereegranskat)abstract
- Detailed γ-ray spectroscopy of the exotic neon isotope 28Ne has been performed for the first time using the one-neutron removal reaction from 29Ne on a liquid hydrogen target at 240 MeV/nucleon. Based on an analysis of parallel momentum distributions, a level scheme with spin-parity assignments has been constructed for 28Ne and the negative-parity states are identified for the first time. The measured partial cross sections and momentum distributions reveal a significant intruder p-wave strength providing evidence of the breakdown of the N=20 and N=28 shell gaps. Only a weak, possible f-wave strength was observed to bound final states. Large-scale shell-model calculations with different effective interactions do not reproduce the large p-wave and small f-wave strength observed experimentally, indicating an ongoing challenge for a complete theoretical description of the transition into the island of inversion along the Ne isotopic chain.
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| 7. |
- Holl, Matthias, 1986, et al.
(författare)
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Border of the island of inversion: Unbound states in Ne-29
- 2022
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Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 105:3
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Tidskriftsartikel (refereegranskat)abstract
- The nucleus Ne-29 is situated at the border of the island of inversion. Despite significant efforts, no bound low-lying intruder f(7/2) state, which would place Ne-29 firmly inside the island of inversion, has yet been observed. Here, the first investigation of unbound states of Ne-29 is reported. The states were populated in Ne-30(p, pn) and Na-30(p, 2p) reactions at a beam energy of around 230 MeV/nucleon, and analyzed in terms of their resonance properties, partial cross sections, and momentum distributions. The momentum distributions are compared to calculations using the eikonal, direct reaction model, allowing assignments for the observed states. The lowest lying resonance at an excitation energy of 1.48(4) MeV shows clear signs of a significant l = 3 component, giving first evidence for f(7/2) single particle strength in Ne-29. The excitation energies and strengths of the observed states are compared to shell-model calculations using the SDPF-U-MIX interaction.
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| 8. |
- Duer, M., et al.
(författare)
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Observation of a correlated free four-neutron system
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 606:7915
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Tidskriftsartikel (refereegranskat)abstract
- A long-standing question in nuclear physics is whether chargeless nuclear systems can exist. To our knowledge, only neutron stars represent near-pure neutron systems, where neutrons are squeezed together by the gravitational force to very high densities. The experimental search for isolated multi-neutron systems has been an ongoing quest for several decades(1), with a particular focus on the four-neutron system called the tetraneutron, resulting in only a few indications of its existence so far(2-4), leaving the tetraneutron an elusive nuclear system for six decades. Here we report on the observation of a resonance-like structure near threshold in the four-neutron system that is consistent with a quasi-bound tetraneutron state existing for a very short time. The measured energy and width of this state provide a key benchmark for our understanding of the nuclear force. The use of an experimental approach based on a knockout reaction at large momentum transfer with a radioactive high-energy He-8 beam was key.
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| 9. |
- Hassler, B., et al.
(författare)
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Past changes in the vertical distribution of ozone - Part 1: Measurement techniques, uncertainties and availability
- 2014
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 7:5, s. 1395-1427
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Tidskriftsartikel (refereegranskat)abstract
- Peak stratospheric chlorofluorocarbon (CFC) and other ozone depleting substance (ODS) concentrations were reached in the mid- to late 1990s. Detection and attribution of the expected recovery of the stratospheric ozone layer in an atmosphere with reduced ODSs as well as efforts to understand the evolution of stratospheric ozone in the presence of increasing greenhouse gases are key current research topics. These require a critical examination of the ozone changes with an accurate knowledge of the spatial (geographical and vertical) and temporal ozone response. For such an examination, it is vital that the quality of the measurements used be as high as possible and measurement uncertainties well quantified. In preparation for the 2014 United Nations Environment Programme (UNEP)/World Meteorological Organization (WMO) Scientific Assessment of Ozone Depletion, the SPARC/IO3C/IGACO-O3/NDACC (SI2N) Initiative was designed to study and document changes in the global ozone profile distribution. This requires assessing long-term ozone profile data sets in regards to measurement stability and uncertainty characteristics. The ultimate goal is to establish suitability for estimating long-term ozone trends to contribute to ozone recovery studies. Some of the data sets have been improved as part of this initiative with updated versions now available. This summary presents an overview of stratospheric ozone profile measurement data sets (ground and satellite based) available for ozone recovery studies. Here we document measurement techniques, spatial and temporal coverage, vertical resolution, native units and measurement uncertainties. In addition, the latest data versions are briefly described (including data version updates as well as detailing multiple retrievals when available for a given satellite instrument). Archive location information for each data set is also given.
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| 10. |
- Storck, Sonja, et al.
(författare)
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Lifetime measurement of the 26 0 g.s. At SAMURAI
- 2020
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1643:1
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Konferensbidrag (refereegranskat)abstract
- The ground state of the neutron unbound nucleus O is speculated to have a lifetime in the pico-second regime. In order to determine the decay lifetime of the O ground state with high sensitivity and precision, a new method has been applied. The experiment was performed in December 2016 at the Superconducting Analyzer for MUlti-particle from Radio Isotope Beams (SAMURAI) at the Radioactive Isotope Beam Factory (RIBF) at RIKEN. A F beam was produced in the fragment separator BigRIPS and impinged on a W/Pt target stack where O was produced. According to the lifetime, the decay of O happens either in or outside the target. Thus, the velocity difference between the decay neutrons and the fragment O delivers a characteristic spectrum from which the lifetime can be extracted.
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