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Sökning: WFRF:(Kojima T)

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1.
  • 2017
  • swepub:Mat__t
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2.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • Namkoong, H, et al. (författare)
  • DOCK2 is involved in the host genetics and biology of severe COVID-19
  • 2022
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
  • 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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  • Wang, QBS, et al. (författare)
  • The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
  • 2022
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
  • 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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  • Forrest, ARR, et al. (författare)
  • A promoter-level mammalian expression atlas
  • 2014
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 507:7493, s. 462-
  • Tidskriftsartikel (refereegranskat)
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  • Noguchi, S, et al. (författare)
  • FANTOM5 CAGE profiles of human and mouse samples
  • 2017
  • Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
  • Tidskriftsartikel (refereegranskat)abstract
    • In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
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  • Carninci, P, et al. (författare)
  • The transcriptional landscape of the mammalian genome
  • 2005
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
  • Tidskriftsartikel (refereegranskat)abstract
    • This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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  • Miyoshi, Y., et al. (författare)
  • The energization and radiation in geospace (ERG) project
  • 2012
  • Ingår i: Dynamics of The Earth's Radiation Belts and Inner Magnetosphere. - : American Geophysical Union (AGU). - 9780875904894 ; , s. 103-116
  • Konferensbidrag (refereegranskat)abstract
    • The Energization and Radiation in Geospace (ERG) project for solar cycle 24 will explore how relativistic electrons in the radiation belts are generated during space storms. This geospace exploration project consists of three research teams: the ERG satellite observation team, the ground-based network observation team, and the integrated data analysis/simulation team. Satellite observation will provide in situ measurements of features such as the plasma distribution function, electric and magnetic fields, and plasma waves, whereas remote sensing by ground-based observations using, for example, HF radars, magnetometers, optical instruments, and radio wave receivers will provide the global state of the geospace. Various kinds of data will be integrated and compared with numerical simulations for quantitative understanding. Such a synergetic approach is essential for comprehensive understanding of relativistic electron generation/loss processes through crossenergy and cross-regional coupling in which different plasma populations and regions are dynamically coupled with each other. In addition, the ERG satellite will utilize a new and innovative measurement technique for wave-particle interactions that can directly measure the energy exchange process between particles and plasma waves. In this paper, we briefly review some of the profound problems regarding relativistic electron accelerations and losses that will be solved by the ERG project, and we provide an overview of the project.
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13.
  • Müller, T D, et al. (författare)
  • Ghrelin.
  • 2015
  • Ingår i: Molecular metabolism. - : Elsevier BV. - 2212-8778. ; 4:6, s. 437-60
  • Tidskriftsartikel (refereegranskat)abstract
    • The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.
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  • Ramilowski, JA, et al. (författare)
  • Functional annotation of human long noncoding RNAs via molecular phenotyping
  • 2020
  • Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 30:7, s. 1060-1072
  • Tidskriftsartikel (refereegranskat)abstract
    • Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.
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  • Hattori, T, et al. (författare)
  • Administration of umbilical cord blood cells transiently decreased hypoxic-ischemic brain injury in neonatal rats
  • 2015
  • Ingår i: Developmental neuroscience. - : S. Karger AG. - 1421-9859 .- 0378-5866. ; 37:2, s. 95-104
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to investigate whether the administration of mononuclear cells derived from human umbilical cord blood cells (UCBCs) could ameliorate hypoxic-ischemic brain injury in a neonatal rat model. The left carotid arteries of 7-day-old rats were ligated, and the rats were then exposed to 8% oxygen for 60 min. Mononuclear cells derived from UCBCs using the Ficoll-Hypaque technique were injected intraperitoneally 6 h after the insult (1.0 × 10<sup>7</sup> cells). Twenty-four hours after the insult, the number of cells positive for the oxidative stress markers 4-hydroxy-2-nonenal and nitrotyrosine, in the dentate gyrus of the hippocampus in the UCBC-treated group, decreased by 36 and 42%, respectively, compared with those in the control group. In addition, the number of cells positive for the apoptosis markers active caspase-3 and apoptosis-inducing factor decreased by 53 and 58%, respectively. The number of activated microglia (ED1-positive cells) was 51% lower in the UCBC group compared with the control group. In a gait analysis performed 2 weeks after the insult, there were no significant differences among the sham-operated, control and UCBC groups. An active avoidance test using a shuttle box the following week also revealed no significant differences among the groups. Neither the volumes of the hippocampi, corpus callosum and cortices nor the numbers of neurons in the hippocampus were different between the UCBC and control groups. In summary, a single intraperitoneal injection of UCBC-derived mononuclear cells 6 h after an ischemic insult was associated with a transient reduction in numbers of apoptosis and oxidative stress marker-positive cells, but it did not induce long-term morphological or functional protection. Repeated administration or a combination treatment may be required to achieve sustained protection.
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  • Kitamura, N., et al. (författare)
  • Direct observations of energy transfer from resonant electrons to whistler-mode waves in magnetosheath of Earth
  • 2022
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Excitation of whistler-mode waves by cyclotron instability is considered as the likely generation process of the waves. Here, the authors show direct observational evidence for locally ongoing secular energy transfer from the resonant electrons to the whistler-mode waves in Earth's magnetosheath. Electromagnetic whistler-mode waves in space plasmas play critical roles in collisionless energy transfer between the electrons and the electromagnetic field. Although resonant interactions have been considered as the likely generation process of the waves, observational identification has been extremely difficult due to the short time scale of resonant electron dynamics. Here we show strong nongyrotropy, which rotate with the wave, of cyclotron resonant electrons as direct evidence for the locally ongoing secular energy transfer from the resonant electrons to the whistler-mode waves using ultra-high temporal resolution data obtained by NASA's Magnetospheric Multiscale (MMS) mission in the magnetosheath. The nongyrotropic electrons carry a resonant current, which is the energy source of the wave as predicted by the nonlinear wave growth theory. This result proves the nonlinear wave growth theory, and furthermore demonstrates that the degree of nongyrotropy, which cannot be predicted even by that nonlinear theory, can be studied by observations.
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27.
  • Kojima, T, et al. (författare)
  • The Effects of High Molecular Weight Hyaluronic Acid Eye Drop Application in Environmental Dry Eye Stress Model Mice
  • 2020
  • Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 21:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Hyaluronic acid (HA) ophthalmic solution is widely used in dry eye treatment worldwide. However, there are no reports comparing the dry eye treatment effects of high molecular weight HA with low molecular weight HA. Sixty eight-week-old C57BL/6 mice were assigned to the following 6 groups and exposed to environmental dry eye stress (EDES) that mimics office work environment: (1) 0.1% low molecular weight HA (LMWHA) eye drops, (2) 0.3% LMWHA eye drops, (3) 3% diquafosol sodium (DQ) eye drops, (4) 0.15% high molecular weight HA (HMWHA) eye drops, (5) no treatment with exposure to EDES (EDES+/Treatment−), and (6) no treatment without exposure to EDES (EDES−/Treatment−). After EDES, the HMWHA group had significantly longer break-up time (BUT) than the 0.1%, 0.3% LMWHA groups and the DQ group. After EDES, the HMWHA group had significantly lower lissamine green staining scores than the LMWHA and DQ groups. Subepithelial presumed dendritic cell density in the HMWHA group was significantly lower than the EDES+/Treatment− group. After EDES exposure, Conjunctival Muc5AC mRNA expression in the HMWHA group was significantly higher than the 0.1 and 0.3% LMWHA groups. Ophthalmic HMWHA solution may have a better dry eye treatment effect than LMWHA or DQ solution, owing to its anti-inflammatory effect.
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  • Blomberg, Lars G., et al. (författare)
  • MEFISTO - An electric field instrument for BepiColombo/MMO
  • 2006
  • Ingår i: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 38:4, s. 672-679
  • Tidskriftsartikel (refereegranskat)abstract
    • MEFISTO, together with the companion instrument WPT, are planning the first-ever in situ measurements of the electric field in the magnetosphere of planet Mercury. The instruments have been selected by JAXA for inclusion in the BepiColombo/MMO payload, as part of the Plasma Wave Investigation coordinated by Kyoto University. The magnetosphere of Mercury was discovered by Mariner 10 in 1974 and will be studied further by Messenger starting in 2011. However, neither spacecraft did or will measure the electric field. Electric fields are crucial in the dynamics of a magnetosphere and for the energy and plasma transport between different regions within the magnetosphere as well as between the magnetosphere and the surrounding regions. The MEFISTO instrument will be capable of measuring electric fields from DC to 3 MHz, and will thus also allow diagnostics of waves at all frequencies of relevance to the Hermean magnetosphere. MEFISTO is a double-probe electric field instrument. The double-probe technique has strong heritage and is well proven on missions such as Viking, Polar, and Cluster. For BepiColombo, a newly developed deployment mechanism is planned which reduces the mass by a factor of about 5 compared to conventional mechanisms for 15 in long booms. We describe the basic characteristics of the instrument and briefly discuss the new developments made to tailor the instrument to flight in Mercury orbit.
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  • Fustin, JM, et al. (författare)
  • Methylation deficiency disrupts biological rhythms from bacteria to humans
  • 2020
  • Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 211-
  • Tidskriftsartikel (refereegranskat)abstract
    • The methyl cycle is a universal metabolic pathway providing methyl groups for the methylation of nuclei acids and proteins, regulating all aspects of cellular physiology. We have previously shown that methyl cycle inhibition in mammals strongly affects circadian rhythms. Since the methyl cycle and circadian clocks have evolved early during evolution and operate in organisms across the tree of life, we sought to determine whether the link between the two is also conserved. Here, we show that methyl cycle inhibition affects biological rhythms in species ranging from unicellular algae to humans, separated by more than 1 billion years of evolution. In contrast, the cyanobacterial clock is resistant to methyl cycle inhibition, although we demonstrate that methylations themselves regulate circadian rhythms in this organism. Mammalian cells with a rewired bacteria-like methyl cycle are protected, like cyanobacteria, from methyl cycle inhibition, providing interesting new possibilities for the treatment of methylation deficiencies.
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  • Grapotte, M, et al. (författare)
  • Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3297-
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
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  • Green, Richard E., et al. (författare)
  • Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1335-
  • Tidskriftsartikel (refereegranskat)abstract
    • To provide context for the diversification of archosaurs-the group that includes crocodilians, dinosaurs, and birds-we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.
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  • Hirscher, Michael, et al. (författare)
  • Materials for hydrogen-based energy storage - past, recent progress and future outlook
  • 2020
  • Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 827
  • Tidskriftsartikel (refereegranskat)abstract
    • Globally, the accelerating use of renewable energy sources, enabled by increased efficiencies and reduced costs, and driven by the need to mitigate the effects of climate change, has significantly increased research in the areas of renewable energy production, storage, distribution and end-use. Central to this discussion is the use of hydrogen, as a clean, efficient energy vector for energy storage. This review, by experts of Task 32, Hydrogen-based Energy Storage of the International Energy Agency, Hydrogen TCP, reports on the development over the last 6 years of hydrogen storage materials, methods and techniques, including electrochemical and thermal storage systems. An overview is given on the background to the various methods, the current state of development and the future prospects. The following areas are covered; porous materials, liquid hydrogen carriers, complex hydrides, intermetallic hydrides, electrochemical storage of energy, thermal energy storage, hydrogen energy systems and an outlook is presented for future prospects and research on hydrogen-based energy storage.
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41.
  • Kojima, K., et al. (författare)
  • Nonlinearity-Tolerant Four-Dimensional 2A8PSK Family for 5-7 Bits/Symbol Spectral Efficiency
  • 2017
  • Ingår i: Journal of Lightwave Technology. - : Institute of Electrical and Electronics Engineers (IEEE). - 0733-8724 .- 1558-2213. ; 35:8, s. 1383-1391
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe in detail the recently proposed four-dimensional modulation format family based on 2-ary amplitude 8-ary phase-shift keying (2A8PSK), supporting spectral efficiencies of 5, 6, and 7 bits/symbol. These formats nicely fill the spectral efficiency gap between the dual-polarization (DP) quadrature PSK (QPSK) and DP 16-ary quadrature-amplitude modulation (16QAM), with excellent linear and nonlinear performance. Since these modulation formats just use different parity bit expressions in the same constellation, similar digital signal processing can be seamlessly used for different spectral efficiency. A series of nonlinear transmission simulation results shows that this modulation format family outperforms the conventional modulation formats at the corresponding spectral efficiency. We also investigate the adaptive equalizer for these modulation formats.
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  • Milillo, A., et al. (författare)
  • Investigating Mercury's Environment with the Two-Spacecraft BepiColombo Mission
  • 2020
  • Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 216:5
  • Forskningsöversikt (refereegranskat)abstract
    • The ESA-JAXA BepiColombo mission will provide simultaneous measurements from two spacecraft, offering an unprecedented opportunity to investigate magnetospheric and exospheric dynamics at Mercury as well as their interactions with the solar wind, radiation, and interplanetary dust. Many scientific instruments onboard the two spacecraft will be completely, or partially devoted to study the near-space environment of Mercury as well as the complex processes that govern it. Many issues remain unsolved even after the MESSENGER mission that ended in 2015. The specific orbits of the two spacecraft, MPO and Mio, and the comprehensive scientific payload allow a wider range of scientific questions to be addressed than those that could be achieved by the individual instruments acting alone, or by previous missions. These joint observations are of key importance because many phenomena in Mercury's environment are highly temporally and spatially variable. Examples of possible coordinated observations are described in this article, analysing the required geometrical conditions, pointing, resolutions and operation timing of different BepiColombo instruments sensors.
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48.
  • Tran, C. -T, et al. (författare)
  • A study on transient heat transfer of the EU-ABWR external core catcher using the Phase-change Effective Convectivity Model
  • 2015
  • Ingår i: International Topical Meeting on Nuclear Reactor Thermal Hydraulics 2015, NURETH 2015. - : American Nuclear Society. - 9781510811843 ; , s. 6821-6834
  • Konferensbidrag (refereegranskat)abstract
    • In advanced designs of Nuclear Power Plants (NPPs), for mitigation of severe accident consequences, on the one hand, the In-Vessel Retention (IVR) concept has been implemented. On the other hand in other new NPP designs (Generation HI and III+) with large power reactors, the External Core Catcher (ECC) has been widely adopted. Assessment of ECC design robustness is largely based on analysis of heat transfer of a melt pool formed in the ECC. Transient heat transfer analysis of an ECC is challenging due to (i) uncertainty in the in-vessel accident progression and subsequent vessel failure modes; (ii) long transient, (iii) high Rayleigh number and complex flows involving phase change of the melt pool formed in an ECC. The present paper is concerned with analysis of transient melt pool heat transfer in the ECC of new Advanced Boiling Water Reactor (ABWR) designed by Toshiba Corporation (Japan). According to the ABWR severe accident management strategy, the ECC is initially dry. In order to prevent steam explosion flooding is initiated after termination of melt relocation from the vessel. The ECC full of melt is cooled from the top directly by water and from the bottom through the ECC walls. In order to assess sustainability of the ECC, heat transfer simulation of a stratified melt pool formed in the ECC is carried out. The problem addressed in this work is heat flux distribution at ECC boundaries when cooling is applied (i) from the bottom, (ii) from the top and from the bottom. To perform melt pool heat transfer simulation, we employ Phase-change Effective Convectivity Model (PECM) which was originally developed as a computationally efficient, sufficiently accurate, 2D/3D accident analysis tools for simulation of transient melt pool heat transfer in the reactor lower plenum. Thermal loads from the melt pool to ECC boundaries are determined for selected ex-vessel accident scenarios. Performance of the ECC, efficiency of severe accident management (SAM) measures and procedures are evaluated based on results of PECM simulation and severe accident analysis.
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