| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- 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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| 5. |
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| 6. |
- 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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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Pirozhkov, A. S., et al.
(author)
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Diagnostic of laser contrast using target reflectivity
- 2009
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 94:24
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Journal article (peer-reviewed)abstract
- Using three different laser systems, we demonstrate a convenient and simple plasma based diagnostic of the contrast of high-power short-pulse lasers. The technique is based on measuring the specular reflectivity from a solid target. The reflectivity remains high even at relativistic intensities above 10(19) W/cm(2) in the case of a high-contrast prepulse-free laser. On the contrary, the specular reflectivity drops with increasing intensities in the case of systems with insufficient contrast due to beam breakup and increased absorption caused by preplasma.
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| 11. |
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| 12. |
- Kou, I, et al.
(author)
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A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 11575-
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Journal article (peer-reviewed)abstract
- Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 × 10−20; odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.
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| 13. |
- Noh, Y., et al.
(author)
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Development of an Airway Management Training System that Embeds an Array of Sensors on a Conventional Mannequin
- 2007
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In: Intelligent Robots and Systems, 2007. IROS 2007. IEEE/RSJ International Conference on. - 9781424409129 - 9781424409129 ; , s. 1296-1301
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Conference paper (peer-reviewed)abstract
- Airway management is provided by emergency medical technicians or anesthetists in order to save unconscious patients who are unable to breathe. Even though it is a basic technique, many accidents may occur when the procedure is not provided followed. In order to avoid any risks to patients, emergency medical technicians are required to practice airway management using training devices such as mannequins; which are designed to accurately reproduce the human anatomy. However, such training devices do not provide any quantitative information about the learning progress of trainees (passive training). For that purpose, we have proposed the development of a airway management training system which is designed to embed array of sensors so that quantitative information of trainees' performance can be acquired. In this paper, we are presenting the Waseda-KyotoKagaku airway No. 1 (WKA-1). The WKA-1 consists of three different kinds of array of sensors which are embedded into a conventional mannequin. In order to embed the array of sensors, we have simplified the design of some of the simulated organs (upper airway, oral cavity, tongue and teeth) of the mannequin. A set of evaluation parameters were proposed based on the information collected through the sensors. A set of experiments were proposed to experimentally verify the effectiveness of the proposed evaluation parameters to quantitatively detect differences among different levels of skills (anesthetists and unskilled persons).
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| 14. |
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| 15. |
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| 16. |
- Ogura, Y, et al.
(author)
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An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4730-
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Journal article (peer-reviewed)abstract
- Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10−18 (odds ratio = 1.19, 95% confidence interval = 1.14–1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.
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| 17. |
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| 18. |
- Kodaira, S., et al.
(author)
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On the use of CR-39 PNTD with AFM analysis in measuring proton-induced target fragmentation particles
- 2015
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In: Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 349, s. 163-168
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Journal article (peer-reviewed)abstract
- In addition to energy loss by ionization process, protons of energy >similar to 50 MeV, such as those used in proton radiotherapy, can undergo nuclear interactions with nuclei of Z > 1, resulting in the production, of short range (<20 gm), high-LET (linear energy transfer) target fragment particles. One of the few methods to detect these short-range particles is by means of CR-39 plastic nuclear track detector (PNTD) analyzed with an atomic force microscope (AFM). However, due to the LET-dependent angular sensitivity of CR-39 PNTD, multiple detectors exposed at a range of incident angles to the primary proton beam, must be analyzed in order to accurately determine the LET spectrum, absorbed dose and dose equivalent. The LET spectrum of 160 MeV proton-induced secondary particles was experimentally measured with CR-39 PNTDs, which were exposed at six different incident angles to take into account the intrinsic sensitivity of the critical angle for track registration. The irradiated detectors were chemically processed to remove a 1 gm thick volume of CR-39 PNTD. The measured LET range of short range tracks was from 15 key/mu m up to 1.5 MeV/mu m. The absorbed dose contribution (D-s/D-p) from secondary particles to primary proton dose was similar to 1%, while the dose equivalent contribution (H-s/D-p) was found to be similar to 20%. Analysis of CR-39 PNTD by AFM yielded similar to 60% higher value for absorbed dose compared to standard optical microscopy analysis.
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| 19. |
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| 20. |
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