1. |
- Namkoong, H, et al.
(author)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Journal article (peer-reviewed)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. |
- Abe, K., et al.
(author)
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Neutron tagging following atmospheric neutrino events in a water Cherenkov detector
- 2022
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In: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 17:10
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Journal article (peer-reviewed)abstract
- We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218 +/- 9 mu s.
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3. |
- Abe, K., et al.
(author)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Reports (peer-reviewed)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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4. |
- Ryu, Y. -H., et al.
(author)
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OGLE-2016-BLG-1190Lb : The First Spitzer Bulge Planet Lies Near the Planet/Brown-dwarf Boundary
- 2018
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 155:1
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Journal article (peer-reviewed)abstract
- We report the discovery of OGLE-2016-BLG-1190Lb, which is likely to be the first Spitzer microlensing planet in the Galactic bulge/ bar, an assignation that can be confirmed by two epochs of high-resolution imaging of the combined source-lens baseline object. The planet's mass, M-p = 13.4 +/- 0.9 M-J, places it right at the deuteriumburning limit, i. e., the conventional boundary between planets and brown dwarfs. Its existence raises the question of whether such objects are really planets (formed within the disks of their hosts) or failed stars (lowmass objects formed by gas fragmentation). This question may ultimately be addressed by comparing disk and bulge/bar planets, which is a goal of the Spitzer microlens program. The host is a G dwarf, M-host = 0.89. +/- 0.07 M-circle dot, and the planet has a semimajor axis a similar to 2.0 au. We use Kepler K2 Campaign 9 microlensing data to break the lens-mass degeneracy that generically impacts parallax solutions from Earth-Spitzer observations alone, which is the first successful application of this approach. The microlensing data, derived primarily from near-continuous, ultradense survey observations from OGLE, MOA, and three KMTNet telescopes, contain more orbital information than for any previous microlensing planet, but not quite enough to accurately specify the full orbit. However, these data do permit the first rigorous test of microlensing orbital-motion measurements, which are typically derived from data taken over < 1% of an orbital period.
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6. |
- Sumi, T., et al.
(author)
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The first Neptune analog or super-earth with a Neptune-like orbit : MOA-2013-BLG-605LB
- 2016
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In: Astrophysical Journal. - 0004-637X. ; 825:2
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Journal article (peer-reviewed)abstract
- We present the discovery of the first Neptune analog exoplanet or super-Earth with a Neptune-like orbit, MOA-2013-BLG-605Lb. This planet has a mass similar to that of Neptune or a super-Earth and it orbits at 9 ∼ 14 times the expected position of the snow line, a snow, which is similar to Neptune's separation of 11 a snow from the Sun. The planet/host-star mass ratio is q = (3.6 ± 0.7) × 10-4 and the projected separation normalized by the Einstein radius is s = 2.39 ± 0.05. There are three degenerate physical solutions and two of these are due to a new type of degeneracy in the microlensing parallax parameters, which we designate "the wide degeneracy." The three models have (i) a Neptune-mass planet with a mass of Mp = 21-7 +6M⊕ orbiting a low-mass M-dwarf with a mass of Mh = 0.19-0.06 +0.05M⊙, (ii) a mini-Neptune with Mp = 7.9-1.2 +1.8M⊕ orbiting a brown dwarf host with Mh = 0.068-0.011 +0.019M⊙, and (iii) a super-Earth with Mp = 3.2-0.3 +0.5MM⊕ orbiting a low-mass brown dwarf host with Mh = 0.025-0.0004 +0.005M⊙, which is slightly favored. The 3D planet-host separations are 4.6-1.2 +4.7au, 2.1-0.2 +1.0au, and 0.94-0.02 +0.67au, which are 8.9-1.4 +10.5, 12-1 +7, or 14-1 +11 times larger than a snow for these models, respectively. Keck adaptive optics observations confirm that the lens is faint. This discovery suggests that low-mass planets with Neptune-like orbits are common. Therefore processes similar to the one that formed Neptune in our own solar system or cold super-Earths may be common in other solar systems.
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10. |
- Blondel, A., et al.
(author)
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The SuperFGD Prototype charged particle beam tests
- 2020
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In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 15:12
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Journal article (peer-reviewed)abstract
- A novel scintillator detector, the SuperFGD, has been selected as the main neutrino target for an upgrade of the T2K experiment ND280 near detector. The detector design will allow nearly 47r coverage for neutrino interactions at the near detector and will provide lower energy thresholds, significantly reducing systematic errors for the experiment. The SuperFGD is made of optically-isolated scintillator cubes of size 10 x 10 x 10 mm(3), providing the required spatial and energy resolution to reduce systematic uncertainties for future T2K runs. The SuperFGD for T2K will have close to two million cubes in a 1920 x 560 x 1840 mm(3) volume. A prototype made of 24 x 8 x 48 cubes was tested at a charged particle beamline at the CERN PS facility. The SuperFGD Prototype was instrumented with readout electronics similar to the future implementation for T2K. Results on electronics and detector response are reported in this paper, along with a discussion of the 3D reconstruction capabilities of this type of detector. Several physics analyses with the prototype data are also discussed, including a study of stopping protons.
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11. |
- Gould, A., et al.
(author)
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MOA-2010-BLG-523:" Failed Planet"= RS CVn Star
- 2013
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In: Astrophysical Journal. - 0004-637X. ; 763:2
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Journal article (peer-reviewed)abstract
- The Galactic bulge source MOA-2010-BLG-523S exhibited short-term deviations from a standard microlensing light curve near the peak of an A(max) similar to 265 high-magnification microlensing event. The deviations originally seemed consistent with expectations for a planetary companion to the principal lens. We combine long-term photometric monitoring with a previously published high-resolution spectrum taken near peak to demonstrate that this is an RS CVn variable, so that planetary microlensing is not required to explain the light-curve deviations. This is the first spectroscopically confirmed RS CVn star discovered in the Galactic bulge.
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14. |
- Matsubara, K., et al.
(author)
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No Interstitial Telomeres on Autosomes but Remarkable Amplification of Telomeric Repeats on the W Sex Chromosome in the Sand Lizard (Lacerta agilis)
- 2015
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In: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 106:6, s. 753-757
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Journal article (peer-reviewed)abstract
- Telomeres are repeat ( TTAGGG) (n) sequences that form terminal ends of chromosomes and have several functions, such as protecting the coding DNA from erosion at mitosis. Due to chromosomal rearrangements through evolutionary history ( e.g., inversions and fusions), telomeric sequences are also found between the centromere and the terminal ends ( i.e., at interstitial telomeric sites, ITSs). ITS telomere sequences have been implicated in heritable disease caused by genomic instability of ITS polymorphic variants, both with respect to copy number and sequence. In the sand lizard ( Lacerta agilis), we have shown that telomere length is predictive of lifetime fitness in females but not males. To assess whether this sex specific fitness effect could be traced to ITSs differences, we mapped ( TTAGGG) n sequences using fluorescence in situ hybridization in fibroblast cells cultured from 4 specimens of known sex. No ITSs could be found on autosomes in either sex. However, females have heterogametic sex chromosomes in sand lizards ( ZW, 2n = 38) and the female W chromosome showed degeneration and remarkable ( TTAGGG) n amplification, which was absent in the Z chromosomes. This work warrants further research on sex chromosome content, in particular of the degenerate W chromosome, and links to female fitness in sand lizards.
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15. |
- Molina, F., et al.
(author)
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Tz=-1 → 0 β-Decays of 54Ni, 50Fe, 46Cr, and 42Ti and Comparison With Mirror (3He,t) Measurements
- 2015
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:1
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Journal article (peer-reviewed)abstract
- We have studied the β decay of the Tz=−1, f7/2 shell nuclei Ni54, Fe50, Cr46, and Ti42 produced in fragmentation reactions. The proton separation energies in the daughter Tz=0 nuclei are relatively large (≈4–5 MeV) so studies of the γ rays are essential. The experiments were performed at GSI as part of the Stopped-beam campaign with the RISING setup consisting of 15 Euroball Cluster Ge detectors. From the newly obtained high precision β-decay half-lives, excitation energies, and β branching ratios, we were able to extract Fermi and Gamow-Teller transition strengths in these β decays. With these improved results it was possible to compare in detail the Gamow-Teller (GT) transition strengths observed in beta decay including a sensitivity limit with the strengths of the Tz=+1 to Tz=0 transitions derived from high resolution (3He,t) reactions on the mirror target nuclei at RCNP, Osaka. The accumulated B(GT) strength obtained from both experiments looks very similar although the charge exchange reaction provides information on a broader energy range. Using the “merged analysis” one can obtain a full picture of the B(GT) over the full Qβ range. Looking at the individual transitions some differences are observed, especially for the weak transitions. Their possible origins are discussed.
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16. |
- Srikulnath, K., et al.
(author)
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Identification of the linkage group of the Z sex chromosomes of the sand lizard (Lacerta agilis, Lacertidae) and elucidation of karyotype evolution in lacertid lizards
- 2014
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In: Chromosoma. - : Springer Science and Business Media LLC. - 0009-5915 .- 1432-0886. ; 123:6, s. 563-575
-
Journal article (peer-reviewed)abstract
- The sand lizard (Lacerta agilis, Lacertidae) has a chromosome number of 2n = 38, with 17 pairs of acrocentric chromosomes, one pair of microchromosomes, a large acrocentric Z chromosome, and a micro-W chromosome. To investigate the process of karyotype evolution in L. agilis, we performed chromosome banding and fluorescent in situ hybridization for gene mapping and constructed a cytogenetic map with 86 functional genes. Chromosome banding revealed that the Z chromosome is the fifth largest chromosome. The cytogenetic map revealed homology of the L. agilis Z chromosome with chicken chromosomes 6 and 9. Comparison of the L. agilis cytogenetic map with those of four Toxicofera species with many microchromosomes (Elaphe quadrivirgata, Varanus salvator macromaculatus, Leiolepis reevesii rubritaeniata, and Anolis carolinensis) showed highly conserved linkage homology of L. agilis chromosomes (LAG) 1, 2, 3, 4, 5(Z), 7, 8, 9, and 10 with macrochromosomes and/or macrochromosome segments of the four Toxicofera species. Most of the genes located on the microchromosomes of Toxicofera were localized to LAG6, small acrocentric chromosomes (LAG11-18), and a microchromosome (LAG19) in L. agilis. These results suggest that the L. agilis karyotype resulted from frequent fusions of microchromosomes, which occurred in the ancestral karyotype of Toxicofera and led to the disappearance of microchromosomes and the appearance of many small macrochromosomes.
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17. |
- Fizazi, Karim, et al.
(author)
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Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer
- 2017
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In: New England Journal of Medicine. - 0028-4793. ; 377:4, s. 352-360
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Journal article (peer-reviewed)abstract
- BACKGROUND: Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer.METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival.RESULTS: After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P<0.001). The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group (hazard ratio for disease progression or death, 0.47; 95% CI, 0.39 to 0.55; P<0.001). Significantly better outcomes in all secondary end points were observed in the abiraterone group, including the time until pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, and prostate-specific antigen progression (P<0.001 for all comparisons), along with next symptomatic skeletal events (P=0.009). These findings led to the unanimous recommendation by the independent data and safety monitoring committee that the trial be unblinded and crossover be allowed for patients in the placebo group to receive abiraterone. Rates of grade 3 hypertension and hypokalemia were higher in the abiraterone group.CONCLUSIONS: The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic progression-free survival in men with newly diagnosed, metastatic, castration-sensitive prostate cancer. (Funded by Janssen Research and Development; LATITUDE ClinicalTrials.gov number, NCT01715285 .).
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19. |
- Hirao, Yuki, et al.
(author)
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OGLE-2017-BLG-0406 : Spitzer Microlens Parallax Reveals Saturn-mass Planet Orbiting M-dwarf Host in the Inner Galactic Disk
- 2020
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:2
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Journal article (peer-reviewed)abstract
- We report the discovery and analysis of the planetary microlensing event OGLE-2017-BLG-0406, which was observed both from the ground and by the Spitzer satellite in a solar orbit. At high magnification, the anomaly in the light curve was densely observed by ground-based-survey and follow-up groups, and it was found to be explained by a planetary lens with a planet/host mass ratio of q = 7.0 x 10(-4) from the light-curve modeling. The ground-only and Spitzer-only data each provide very strong one-dimensional (1D) constraints on the 2D microlens parallax vector pi(E). When combined, these yield a precise measurement of pi(E) and of the masses of the host M-host = 0.56 +/- 0.07 M-circle dot and planet M-planet = 0.41 +/- 0.05 M-Jup. The system lies at a distance D-L = 5.2 +/- 0.5 kpc from the Sun toward the Galactic bulge, and the host is more likely to be a disk population star according to the kinematics of the lens. The projected separation of the planet from the host is a(perpendicular to) = 3.5 +/- 0.3 au (i.e., just over twice the snow line). The Galactic-disk kinematics are established in part from a precise measurement of the source proper motion based on OGLE-IV data. By contrast, the Gaia proper-motion measurement of the source suffers from a catastrophic 10 sigma error.
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22. |
- Komaguchi, K, et al.
(author)
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An ESR and ENDOR study of irradiated 6Li-formate
- 2007
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In: Spectrochimica Acta Part A - Molecular and Biomolecular Spectroscopy. - : Elsevier BV. - 1386-1425 .- 1873-3557. ; 66:3, s. 754-760
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Journal article (peer-reviewed)abstract
- Lithium formate (6LiOOCH·H2O), 95% 6Li enrichment, combined with an exchange of crystallization water with D2O was investigated. The ESR spectrum of the radiation induced free radicals stable at room temperature consists of a singlet with a narrow line width, 0.92 mT. 6Li has smaller magnetic moment and nuclear spin, which resulted in the narrower line width accompanied with an increase in peak amplitude. In comparison with lithium formate with natural isotopic composition, 6Li (7.5%, I = 1) and 7Li (92.5%, I = 3/2), the sensitivity was increased by a factor of two. With optimised spectrometer settings 6Li formate had seven times higher sensitivity compared to alanine. Therefore this material is proposed as a dosimeter material in a dose range down to 0.1 Gy. The g and the 13C-hyperfine (hf) tensors of the CO2- radical anion, major paramagnetic products, were evaluated to be g = (2.0037, 1.9975, 2.0017), and A(13C) = (465.5, 447.5, 581.3) MHz for polycrystalline samples at room temperature. Furthermore, the 1H-hf and 6Li-hf tensors observed for the surroundings of CO2- by ENDOR technique were in fairly good agreement with DFT calculations. The CO2- radicals are found to be so stable that the formate is applicable to the ESR dosimetry, because of fully relaxing in a fully relaxed geometrical structure of the CO2- component and remaining tight binding with the surroundings after the H atom detachment from HCO2-. © 2006 Elsevier B.V. All rights reserved.
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23. |
- Matsubara, Nami, et al.
(author)
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Neutron powder diffraction study of NaMn2O4 and Li0.92Mn2O4 : Insights on spin-charge-orbital ordering
- 2020
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In: Physical Review Research. - : American Physical Society (APS). - 2643-1564. ; 2:4
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Journal article (peer-reviewed)abstract
- High-pressure synthesized quasi-one-dimensional NaMn2O4 and Li0.92Mn2O4 are both antiferromagnetic insulators. Here their atomic and magnetic structures are investigated using neutron powder diffraction. The present crystal structural analyses of NaMn2O4 reveal that a Mn3+/Mn4+ charge-ordering state exists even at low temperature (down to 1.5 K). It is evident that one of the Mn sites shows a strongly distorted Mn3+ octahedron due to the Jahn-Teller effect. Above TN=35 K, a two-dimensional short-range correlation is observed, as indicated by asymmetric diffuse scattering. Below TN, two antiferromagnetic transitions are observed: (i) a commensurate long-range Mn3+ spin ordering below TN1=35 K and (ii) an incommensurate Mn4+ spin ordering below TN2=11 K. Surprisingly, the two antiferromagnetic orders are found to be independent of each other. The commensurate magnetic structure (kC=0.5,0.5,0.5) follows the magnetic anisotropy of the local easy axes of Mn3+, while the incommensurate Mn4+ one shows a spin-density-wave or a cycloidal order with kIC=(0,0,0.216). For Li0.92Mn2O4, on the other hand, the absence of a long-range spin-ordered state is confirmed down to 1.5 K.
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24. |
- Takeuchi, Fumihiko, et al.
(author)
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Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- 2018
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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