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- 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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- Wang, QBS, et al.
(author)
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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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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Journal article (peer-reviewed)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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- Abdellaoui, G., et al.
(author)
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Meteor studies in the framework of the JEM-EUSO program
- 2017
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In: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 143, s. 245-255
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Journal article (peer-reviewed)abstract
- We summarize the state of the art of a program of UV observations from space of meteor phenomena, a secondary objective of the JEM-EUSO international collaboration. Our preliminary analysis indicates that JEM-EUSO, taking advantage of its large FOV and good sensitivity, should be able to detect meteors down to absolute magnitude close to 7. This means that JEM-EUSO should be able to record a statistically significant flux of meteors, including both sporadic ones, and events produced by different meteor streams. Being unaffected by adverse weather conditions, JEM-EUSO can also be a very important facility for the detection of bright meteors and fireballs, as these events can be detected even in conditions of very high sky background. In the case of bright events, moreover, exhibiting some persistence of the meteor train, preliminary simulations show that it should be possible to exploit the motion of the ISS itself and derive at least a rough 3D reconstruction of the meteor trajectory. Moreover, the observing strategy developed to detect meteors may also be applied to the detection of nuclearites, exotic particles whose existence has been suggested by some theoretical investigations. Nuclearites are expected to move at higher velocities than meteoroids, and to exhibit a wider range of possible trajectories, including particles moving upward after crossing the Earth. Some pilot studies, including the approved Mini-EUSO mission, a precursor of JEM-EUSO, are currently operational or in preparation. We are doing simulations to assess the performance of Mini-EUSO for meteor studies, while a few meteor events have been already detected using the ground-based facility EUSO-TA.
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18. |
- Abdellaoui, G., et al.
(author)
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First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere
- 2018
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In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13
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Journal article (peer-reviewed)abstract
- EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
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- Sakatani, N., et al.
(author)
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Anomalously porous boulders on (162173) Ryugu as primordial materials from its parent body
- 2021
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In: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:8, s. 766-774
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Journal article (peer-reviewed)abstract
- Planetesimals—the initial stage of the planetary formation process—are considered to be initially very porous aggregates of dusts1,2, and subsequent thermal and compaction processes reduce their porosity3. The Hayabusa2 spacecraft found that boulders on the surface of asteroid (162173) Ryugu have an average porosity of 30–50% (refs. 4,5,6), higher than meteorites but lower than cometary nuclei7, which are considered to be remnants of the original planetesimals8. Here, using high-resolution thermal and optical imaging of Ryugu’s surface, we discovered, on the floor of fresh small craters (<20 m in diameter), boulders with reflectance (~0.015) lower than the Ryugu average6 and porosity >70%, which is as high as in cometary bodies. The artificial crater formed by Hayabusa2’s impact experiment9 is similar to these craters in size but does not have such high-porosity boulders. Thus, we argue that the observed high porosity is intrinsic and not created by subsequent impact comminution and/or cracking. We propose that these boulders are the least processed material on Ryugu and represent remnants of porous planetesimals that did not undergo a high degree of heating and compaction3. Our multi-instrumental analysis suggests that fragments of the highly porous boulders are mixed within the surface regolith globally, implying that they might be captured within collected samples by touch-down operations10,11.
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21. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Bakker, D. C. E., et al.
(author)
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An update to the surface ocean CO2 atlas (SOCAT version 2)
- 2014
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In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 6:1, s. 69-90
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Journal article (peer-reviewed)abstract
- The Surface Ocean CO2 Atlas (SOCAT), an activity of the international marine carbon research community, provides access to synthesis and gridded fCO2 (fugacity of carbon dioxide) products for the surface oceans. Version 2 of SOCAT is an update of the previous release (version 1) with more data (increased from 6.3 million to 10.1 million surface water fCO 2 values) and extended data coverage (from 1968-2007 to 1968-2011). The quality control criteria, while identical in both versions, have been applied more strictly in version 2 than in version 1. The SOCAT website (http://www.socat.info/) has links to quality control comments, metadata, individual data set files, and synthesis and gridded data products. Interactive online tools allow visitors to explore the richness of the data. Applications of SOCAT include process studies, quantification of the ocean carbon sink and its spatial, seasonal, year-to-year and longerterm variation, as well as initialisation or validation of ocean carbon models and coupled climate-carbon models. © Author(s) 2014. CC Attribution 3.0 License.
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- Doornenbal, P., et al.
(author)
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RISING: Gamma‐ray Spectroscopy with Radioactive Beams at GSI
- 2007
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In: AIP Conference Proceedings. - : AIP. - 0094-243X. - 9780735413283 ; 891, s. 99-107
-
Conference paper (peer-reviewed)abstract
- The Rare Isotope Spectroscopic INvestigation at GSI (RISING) project is a major pan‐European collaboration. Its physics aims are the studies of exotic nuclear matter with abnormal proton‐to‐neutron ratios compared with naturally occurring isotopes. RISING combines the FRagment Separator (FRS) which allows relativistic energies and projectile fragmentation reactions with EUROBALL Ge Cluster detectors for γ spectroscopic research. The RISING setup can be used in two different configurations. Either the nuclei of interest are investigated after being stopped or the heavy ions hit a secondary target at relativistic energies and the thereby occurring excitations are studied. For the latter case, MINIBALL Ge detectors and the HECTOR array are used in addition. Example achievements of the Fast Beam setup are presented and compared to various shell model calculations, while for the Stopped Beam setup initial results are shown.
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29. |
- 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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- Rademacher, G., et al.
(author)
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10.66 Peta-Bit/s Transmission over a 38-Core-Three-Mode Fiber
- 2020
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In: 2020 Optical Fiber Communications Conference and Exhibition, OFC 2020 - Proceedings. - : Institute of Electrical and Electronics Engineers Inc..
-
Conference paper (peer-reviewed)abstract
- We demonstrate transmission of 368-WDM-38-core-3-mode × 24.5-GBaud 64- and 256-QAM signals over 13 km. Record data-rate and spectral-efficiency of 1158.7 b/s/Hz were enabled by a low DMD 38-core-3-mode fiber with high uniformity amongst cores.
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32. |
- Spinoglio, L., et al.
(author)
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- 2017
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In: Publications Astronomical Society of Australia. - : Cambridge University Press (CUP). - 1323-3580 .- 1448-6083. ; 34
-
Journal article (peer-reviewed)abstract
- IR spectroscopy in the range 12-230 mu m with the SPace IR telescope for Cosmology and Astrophysics (SPICA) will reveal the physical processes governing the formation and evolution of galaxies and black holes through cosmic time, bridging the gap between the James Webb Space Telescope and the upcoming Extremely Large Telescopes at shorter wavelengths and the Atacama Large Millimeter Array at longer wavelengths. The SPICA, with its 2.5-m telescope actively cooled to below 8 K, will obtain the first spectroscopic determination, in the mid-IR rest-frame, of both the star-formation rate and black hole accretion rate histories of galaxies, reaching lookback times of 12 Gyr, for large statistically significant samples. Densities, temperatures, radiation fields, and gas-phase metallicities will be measured in dust-obscured galaxies and active galactic nuclei, sampling a large range in mass and luminosity, from faint local dwarf galaxies to luminous quasars in the distant Universe. Active galactic nuclei and starburst feedback and feeding mechanisms in distant galaxies will be uncovered through detailed measurements of molecular and atomic line profiles. The SPICA's large-area deep spectrophotometric surveys will provide mid-IR spectra and continuum fluxes for unbiased samples of tens of thousands of galaxies, out to redshifts of z similar to 6.
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- Roelfsema, P. R., et al.
(author)
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SPICA-A Large Cryogenic Infrared Space Telescope : Unveiling the Obscured Universe
- 2018
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In: Publications Astronomical Society of Australia. - : Cambridge University Press (CUP). - 1323-3580 .- 1448-6083. ; 35
-
Journal article (peer-reviewed)abstract
- Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity. SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope. cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions. SPICA instruments offer spectral resolving power ranging from R similar to 50 through 11 000 in the 17-230 mu m domain and R similar to 28.000 spectroscopy between 12 and 18 mu m.SPICA will provide efficient 30-37 mu m broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 mu m. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of similar to 5 x 10(-20) W m (-2) (5 sigma/1 h)-over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
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39. |
- Frank, TD, et al.
(author)
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Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017
- 2019
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In: The lancet. HIV. - 2352-3018. ; 6:12, s. E831-E859
-
Journal article (peer-reviewed)
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40. |
- Hirai, T., et al.
(author)
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Performance and erosion of a tungsten brush limiter exposed at the TEXTOR tokamak
- 2003
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In: Journal of Nuclear Materials. - 0022-3115 .- 1873-4820. ; 313, s. 67-71
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Journal article (peer-reviewed)abstract
- To examine the performance of a castellated structure under plasma loading, a hemispherical solid tungsten brush limiter was exposed to the plasma in the TEXTOR-94 tokamak. Due to the thermally isolated column of W segments, IR camera showed a non-uniform temperature distribution. The maximum incident power density was calculated to be about 35-40 MW/m(2). Concerning impurity generation, the structure did not show any particular effects. During plasma exposure, only some minor cracks developed in one of the columns, however, the crack propagation was interrupted by a groove. It can be concluded that the W brush limiter had comparable performance and superior mechanical behaviour compared to a solid W limiter. To study erosion and long-range transport of W atoms, a graphite limiter was exposed simultaneously with the brush limiter. As a result, the deposited W atoms via long-range transportation were estimated to be 10(15) cm(-2) shot(-1) at 46.5 cm from the plasma centre of TEXTOR.
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- Fukuzawa, H., et al.
(author)
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Deep Inner-Shell Multiphoton Ionization by Intense X-Ray Free-Electron Laser Pulses
- 2013
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In: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 110:17
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Journal article (peer-reviewed)abstract
- We have investigated multiphoton multiple ionization dynamics of xenon atoms using a new x-ray free-electron laser facility, SPring-8 Angstrom Compact free electron LAser (SACLA) in Japan, and identified that Xen+ with n up to 26 is produced at a photon energy of 5.5 keV. The observed high charge states (n >= 24) are produced via five-photon absorption, evidencing the occurrence of multiphoton absorption involving deep inner shells. A newly developed theoretical model, which shows good agreement with the experiment, elucidates the complex pathways of sequential electronic decay cascades accessible in heavy atoms. The present study of heavy-atom ionization dynamics in high-intensity hard-x-ray pulses makes a step forward towards molecular structure determination with x-ray free-electron lasers. DOI: 10.1103/PhysRevLett.110.173005
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47. |
- Hirai, T., et al.
(author)
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Testing of tungsten and tantalum limiters at the TEXTOR tokamak : Material performance and deuterium retention
- 2003
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In: Physica Scripta. - 0031-8949 .- 1402-4896. ; T103, s. 59-62
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Journal article (peer-reviewed)abstract
- Tungsten and tantaium were examined in the TEXTOR tokamak as test limiters in order to compare their performance under plasma operation and to recognise fuel recycling on endothermic (W) and exothermic (Ta) hydrogen absorbers. Differences have been noticed in the distribution and microstructure of co-deposits. in the fuel inventory in the bulk of metals and, in the deuterium release mechanism (ratio of molecules to atoms). As a result of poor thermal conductivity. the surface temperature of Ta during the power deposition was higher than that of W and it increased shot-by-shot because of the degradation of thermal properties due to surface modification. Results on thermal response, fuel recycling and inventory show that. as a candidate material for plasma facing components. tungsten is superior to tantalum.
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48. |
- Motomura, K., et al.
(author)
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Sequential multiphoton multiple ionization of atomic argon and xenon irradiated by X-ray free-electron laser pulses from SACLA
- 2013
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In: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 46:16
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Journal article (peer-reviewed)abstract
- We have investigated multiphoton multiple ionization of argon and xenon atoms at 5 keV using a new x-ray free electron laser (XFEL) facility, the SPring-8 Angstrom Compact free electron LAser (SACLA) in Japan. The experimental results are compared with the new theoretical results presented here. The absolute fluence of the XFEL pulse has been determined with the help of the calculations utilizing two-photon processes in the argon atom. The high charge states up to +22 observed for Xe in comparison with the calculations point to the occurrence of sequential L-shell multiphoton absorption and of resonance-enabled x-ray multiple ionization.
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49. |
- Ohya, K., et al.
(author)
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Modeling of erosion and deposition patterns on C-W and W-Ta twin limiters exposed to the TEXTOR edge plasmas
- 2004
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In: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 329-33, s. 732-736
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Journal article (peer-reviewed)abstract
- The erosion and deposition patterns on tungsten and tantalum test limiters exposed to the TEXTOR deuterium plasma containing a small amount of C impurity are simulated with the modified EDDY code. At the very top of the W and Ta limiters, there occurs neither erosion nor deposition, but the erosion proceeds slowly along the surface. When approaching the edge, the surface is covered by a thick C layer, which shows a very sharp boundary similar to the observation in surface measurements. In the erosion zone, the re-deposited carbon forms a W (Ta)-C mixed layer with small C concentration. Assumptions for chemical erosion yields of similar to0.01 for W and
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50. |
- Yao, T. D., et al.
(author)
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The imbalance of the Asian water tower
- 2022
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In: Nature Reviews Earth & Environment. - : Springer Science and Business Media LLC. - 2662-138X.
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Journal article (peer-reviewed)abstract
- The Hindu Kush-Karakoram-Himalayan system, named the Third Pole because it is the largest global store of frozen water after the polar regions, provides a reliable water supply to almost 2 billion people. Marked atmospheric warming has changed the balance of this so-called Asian water tower and altered water resources in downstream countries. In this Review, we synthesize observational evidence and model projections that describe an imbalance in the Asian water tower caused by accelerated transformation of ice and snow into liquid water. This phase change is associated with a south-north disparity due to the spatio-temporal interaction between the westerlies and the Indian monsoon. A corresponding spatial imbalance is exhibited by alterations in freshwater resources in endorheic or exorheic basins. Global warming is expected to amplify this imbalance, alleviating water scarcity in the Yellow and Yangtze River basins and increasing scarcity in the Indus and Amu Darya River basins. However, the future of the Asian water tower remains highly uncertain. Accurate predictions of future water supply require the establishment of comprehensive monitoring stations in data-scarce regions and the development of advanced coupled atmosphere-cryosphere-hydrology models. Such models are needed to inform the development of actionable policies for sustainable water resource management. Atmospheric warming has imbalanced the Hindu Kush-Karakoram-Himalayan system (the Asian water tower (AWT)). Yao et al. review observed changes in atmospheric water and freshwater AWT constituents, focusing on their future consequences for freshwater resources and vulnerable societies across downstream basins.
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