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. |
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3. |
- 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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4. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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5. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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6. |
- Ozawa, A., et al.
(författare)
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Charge-changing cross sections of 30Ne, 32,33Na with a proton target
- 2014
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 89, s. 044602-1-044602-5
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Tidskriftsartikel (refereegranskat)abstract
- The total charge-changing, charge pick-up, and partial charge-changing cross sections of very neutron-rich nuclei (30Ne, 32,33Na) with a proton target have been measured at ~240A MeV for the first time. We introduced the phenomenological correction factor in Glauber-model calculations for the total charge-changing cross sections with the proton target, and applied it to deduce the proton radii of these nuclei. For 30Ne and 32Na, the neutron skin thicknesses of the nuclei were deduced by comparing the proton radii with the matter radii deduced from the interaction cross-section measurements. A significant thick neutron-skin has been observed for the nuclei. We also found that the charge pick-up cross sections are much larger than those in the systematics of stable nuclei.
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7. |
- Fukuda, M., et al.
(författare)
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Reaction cross section studies at NIRS and RIBF
- 2010
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Ingår i: American Institute of Physics Conference Series. - American Institute of Physics : AIP. ; , s. 270-273
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Konferensbidrag (refereegranskat)abstract
- Reaction cross sections for stable nuclei at intermediate energies have been measured precisely and systematically. The data have been found to be reproduced nicely by the optical‐limit approximation of Glauber theory modified to include the nucleon multiple scattering effect and the Fermi‐motion effect. Applying this prescription, the nucleon density distribution of 17Ne has been studied. The surface structure of 8B and 11Be has been also studied using this prescription and hydrogen targets. Using the RIBF that has just started application to studies of exotic nuclei, neutron‐rich Ne isotopes around the Island of Inversion have been investigated through measurements of their interaction cross sections.
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8. |
- Takechi, M., et al.
(författare)
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Interaction cross sections for Ne isotopes towards the island of inversion and halo structures of 29Ne and 31Ne
- 2012
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Ingår i: Physics Letters B. - Elsevier : Elsevier BV. - 0370-2693 .- 1873-2445. ; 707:3-4, s. 357-361
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Tidskriftsartikel (refereegranskat)abstract
- Interaction cross sections (σI) for Ne isotopes from the stability line to the vicinity of the neutron dripline have been measured at around 240 MeV/nucleon using BigRIPS at RIBF, RIKEN. The σI for 27–32Ne in every case exceed the systematic mass-number dependence of σI for stable nuclei, which can be explained by considering the nuclear deformation. In particular the σI for 29Ne and 31Ne are significantly greater than those of their neighboring nuclides. These enhancements of σI for 29Ne and 31Ne cannot be explained by a single-particle model calculation under the assumption that the valence neutron of 29Ne (31Ne) occupies the 0d3/2 (0f7/2 ) orbital, as expected from the standard spherical shell ordering. The present data suggest an s dominant halo structure of 29Ne and s- or p-orbital halo in 31Ne.
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9. |
- Takechi, M., et al.
(författare)
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Measurements of nuclear radii for neutron-rich Ne isotopes 28-32Ne
- 2010
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Ingår i: Nuclear Physics A. - Elsevier : Elsevier BV. - 0375-9474 .- 1873-1554. ; 834:1-4, s. 412c-415c
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Tidskriftsartikel (refereegranskat)abstract
- Interaction cross sections (σI) for neutron-rich Ne isotopes, 28-32Ne on C target have been measured at 240A MeV using the RIBF at RIKEN. A large enhancement of σI beyond the systematics of stable nuclei have been observed for neutron-rich Ne isotopes, particularly for 31Ne. The possible halo structure for 29,31Ne which would be caused by the lowering of the pf-shell and nuclear deformation of Ne isotopes are discussed by the preliminary analysis.
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10. |
- Doornenbal, P., et al.
(författare)
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Spectroscopy of 32Ne and the "Island of Inversion"
- 2009
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Ingår i: Physical Review Letters. - American Physical Society. - 0031-9007 .- 1079-7114. ; 103:3, s. 032501-1-032501-4
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first spectroscopic study of the N = 22 nucleus 32Ne at the newly completed RIKEN Radioactive Ion Beam Factory. A single γ-ray line with an energy of 722(9) keV was observed in both inelastic scattering of a 226 MeV=u 32Ne beam on a carbon target and proton removal from 33Na at 245 MeV=u. This transition is assigned to the deexcitation of the first Jπ = 2+ state in 32Ne to the 0+ ground state. Interpreted through comparison with state-of-the-art shell-model calculations, the low excitation energy demonstrates that the ‘‘island of inversion’’ extends to at least N = 22 for the Ne isotopes.
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11. |
- Kuboki, T.a, et al.
(författare)
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Measurement of interaction cross-sections for neutron-rich Na isotopes
- 2011
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Ingår i: Acta Physica Polonica B. - : Jagellonian University. - 0587-4254 .- 1509-5770. ; 42:3-4, s. 765-768
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Tidskriftsartikel (refereegranskat)abstract
- The interaction cross-sections (σI) of neutron-rich Na isotopes, 23-35Na, on C target have been measured at 250A MeV using the RI beam factory (RIBF) at RIKEN. Mass dependence of σI for 27-35Na suggests monotonic growth of the skin thickness. The root-mean-square nuclear matter radii (rm) of 23-35Na were deduced from observed σI via a Glauber-type calculation. These rm are in a good agreement with the theoretical prediction by relativistic mean field model (RMF). rm of 33-35Na were determined for the first time.
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12. |
- Abazajian, Kevork, et al.
(författare)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
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Tidskriftsartikel (refereegranskat)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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13. |
- Ade, Peter, et al.
(författare)
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The Simons Observatory : science goals and forecasts
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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