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  • 1
    Online Resource
    Online Resource
    DOCK2 is involved in the host genetics and biology of severe COVID-19
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 609, No. 7928 ( 2022-09-22), p. 754-760
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 609, No. 7928 ( 2022-09-22), p. 754-760
    Abstract: Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge 1–5 . 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.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-05163-5
    RVK:
    TA 1000
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    UA 1000
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    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 2
    Online Resource
    Online Resource
    Preparation and Properties of Bi 2 SiO 5 /Si Structures
    IOP Publishing ; 2000
    In:  Japanese Journal of Applied Physics Vol. 39, No. 9S ( 2000-09-01), p. 5512-
    Details
    In: Japanese Journal of Applied Physics, IOP Publishing, Vol. 39, No. 9S ( 2000-09-01), p. 5512-
    Abstract: Bismuth silicate (Bi 2 SiO 5 ) films, expected as the intermediate buffer layer between the bismuth layer-structured ferroelectrics (BLSF) and silicon substrate, were prepared on (100)-oriented silicon wafers by rf magnetron sputtering. The c -axis-oriented Bi 2 SiO 5 films with smooth surface morphology were obtained at the substrate temperature of 400°C. The leakage current density is on the order of 10 -10 A·cm -2 , under the applied electric field of less than 350 kV·cm -1 . From capacitance–voltage characteristics measurement results, it is worth noting that hysteresis is hardly observed. The interface trap density at the midgap is estimated to be approximately 6 ×10 12 cm -2 ·eV -1 . The numerical evaluation results indicate that the metal-ferroelectric-insulator-semiconductor (MFIS) capacitor can be reversed at a low applied voltage. This suggests that Bi 4 Ti 3 O 12 /Bi 2 SiO 5 /Si structures are suitable for application for ferroelectric memory devices.
    Type of Medium: Online Resource
    ISSN: 0021-4922 , 1347-4065
    URL: Article
    DOI: 10.1143/JJAP.39.5512
    RVK:
    UA 4210.1
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    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2000
    detail.hit.zdb_id: 218223-3
    detail.hit.zdb_id: 797294-5
    detail.hit.zdb_id: 2006801-3
    detail.hit.zdb_id: 797295-7
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  • 3
    Online Resource
    Online Resource
    Precise Stress Control of Ta Absorber using Low Stress Alumina Etching Mask for X-Ray Mask Fabrication
    IOP Publishing ; 1996
    In:  Japanese Journal of Applied Physics Vol. 35, No. 12S ( 1996-12-01), p. 6463-
    Details
    In: Japanese Journal of Applied Physics, IOP Publishing, Vol. 35, No. 12S ( 1996-12-01), p. 6463-
    Abstract: In the stress control of an X-ray mask absorber, the repeatability of control and stability are important. We found that the change in the stress in a Ta film resulting from annealing depends on the oxygen concentration in the film; the magnitude of the stress change is determined by the annealing temperature and time. Using this characteristic of Ta film, we have successfully controlled the stress in the Ta absorber to less than 5 MPa with good repeatability. In our mask fabrication process, Al 2 O 3 film was used as an etching mask. We found that the Al 2 O 3 film prevented the Ta absorber stress from changing in high-temperature atmospheres because the Al 2 O 3 film prevented oxygen diffusion into the Ta film. Utilizing Al 2 O 3 films, we succeeded in preventing changes in Ta absorber stress in the thermal processes after Ta stress control, such as frame bonding and resist baking. Consequently, we were able to precisely control the Ta absorber stress in X-ray masks with good repeatability and stability in a realistic X-ray mask fabrication process.
    Type of Medium: Online Resource
    ISSN: 0021-4922 , 1347-4065
    URL: Article
    DOI: 10.1143/JJAP.35.6463
    RVK:
    UA 4210.1
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    UA 4210.2
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    UA 4210
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 1996
    detail.hit.zdb_id: 218223-3
    detail.hit.zdb_id: 797294-5
    detail.hit.zdb_id: 2006801-3
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  • 4
    Online Resource
    Online Resource
    Properties of Bi 4 Ti 3 O 12 Thin Films Grown at Low Temperatures
    IOP Publishing ; 1997
    In:  Japanese Journal of Applied Physics Vol. 36, No. 9S ( 1997-09-01), p. 5885-
    Details
    In: Japanese Journal of Applied Physics, IOP Publishing, Vol. 36, No. 9S ( 1997-09-01), p. 5885-
    Abstract: Bismuth titanate (Bi 4 Ti 3 O 12 ) thin films have been deposited on a (100) silicon substrate with a buffer layer, using a rf planer magnetron sputtering technique. The buffer layer was formed by the heat treatment of an amorphous layer at 550°C, and exhibits a pyrochlore phase with a smooth surface. The amorphous layer consists of Bi, Ti and O atoms, which are the elements of the ferroelectric Bi 4 Ti 3 O 12 thin film. Ferroelectric Bi 4 Ti 3 O 12 thin films were deposited on the buffer layer at a low substrate temperature of 500°C. The Bi 4 Ti 3 O 12 thin films have a dense and small grain structure. A D – E hysteresis characteristic has been observed at room temperature. The apparent remanent polarization and the apparent coercive field of this film at the measurement frequency of 50 Hz were estimated to be 2.4 µC/cm 2 and 2.3 kV/cm, respectively.
    Type of Medium: Online Resource
    ISSN: 0021-4922 , 1347-4065
    URL: Article
    DOI: 10.1143/JJAP.36.5885
    RVK:
    UA 4210.1
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    UA 4210.2
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    UA 4210
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 1997
    detail.hit.zdb_id: 218223-3
    detail.hit.zdb_id: 797294-5
    detail.hit.zdb_id: 2006801-3
    detail.hit.zdb_id: 797295-7
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  • 5
    Online Resource
    Online Resource
    Preparation and Characterization of Ferroelectric Bi 4 Ti 3 O 12 Thin Films Grown on (100)-Oriented Silicon Wafers
    IOP Publishing ; 1996
    In:  Japanese Journal of Applied Physics Vol. 35, No. 9S ( 1996-09-01), p. 4984-
    Details
    In: Japanese Journal of Applied Physics, IOP Publishing, Vol. 35, No. 9S ( 1996-09-01), p. 4984-
    Abstract: Ferroelectric bismuth titanate (Bi 4 Ti 3 O 12 ) thin films were prepared directly on (100) silicon substrate by rf planar magnetron sputtering using a Bi 2 TiO 5 ceramic target. Highly c -axis-oriented films were obtained at a high deposition rate of about 17 nm/min. The deposited thin films, consisting of plate-like grains about 2 µm in diameter, were grown uniformly parallel to the substrate surface. The remanent polarization ( P r ) and the coercive field ( E c ) of this film at 50 Hz were estimated to be 0.8 µC/cm 2 and 20 kV/cm, respectively.
    Type of Medium: Online Resource
    ISSN: 0021-4922 , 1347-4065
    URL: Article
    DOI: 10.1143/JJAP.35.4984
    RVK:
    UA 4210.1
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    UA 4210.2
    RVK:
    UA 4210
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 1996
    detail.hit.zdb_id: 218223-3
    detail.hit.zdb_id: 797294-5
    detail.hit.zdb_id: 2006801-3
    detail.hit.zdb_id: 797295-7
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  • 6
    Online Resource
    Online Resource
    Preparation of Bi 4 Ti 3 O 12 /Bi 2 SiO 5 /Si Structures Derived by Metal Organic Decomposition Technique
    IOP Publishing ; 2001
    In:  Japanese Journal of Applied Physics Vol. 40, No. 9S ( 2001-09-01), p. 5559-
    Details
    In: Japanese Journal of Applied Physics, IOP Publishing, Vol. 40, No. 9S ( 2001-09-01), p. 5559-
    Abstract: Bismuth titanate (Bi 4 Ti 3 O 12 ) thin films were fabricated on a bismuth silicate (Bi 2 SiO 5 )-coated silicon substrate by the metal-organic decomposition (MOD) method. It was confirmed that the resultant films were single-phase Bi 4 Ti 3 O 12 thin films with c -axis-dominant orientation. However, the fabricated films have a high leakage current density of approximately 10 4 A·cm -2 . It is considered that this is mainly caused by the surface roughness due to the growth of plate-like grains. The growth of the Bi 4 Ti 3 O 12 thin films using the MOD method is influenced by the substrate. Therefore, it is regarded that the addition of Bi 2 SiO 5 thin film improves the crystallinity of Bi 4 Ti 3 O 12 thin films.
    Type of Medium: Online Resource
    ISSN: 0021-4922 , 1347-4065
    URL: Article
    DOI: 10.1143/JJAP.40.5559
    RVK:
    UA 4210.1
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    UA 4210
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2001
    detail.hit.zdb_id: 218223-3
    detail.hit.zdb_id: 797294-5
    detail.hit.zdb_id: 2006801-3
    detail.hit.zdb_id: 797295-7
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  • 7
    Online Resource
    Online Resource
    Physical Properties of Bi 4 Ti 3 O 12 Films Grown on Si(100) Wafers
    IOP Publishing ; 1995
    In:  Japanese Journal of Applied Physics Vol. 34, No. 9S ( 1995-09-01), p. 5116-
    Details
    In: Japanese Journal of Applied Physics, IOP Publishing, Vol. 34, No. 9S ( 1995-09-01), p. 5116-
    Abstract: Bismuth titanate (Bi 4 Ti 3 O 12 ) films were prepared on Si(100) wafers by rf planar magnetron sputtering using a target of Bi 2 TiO 5 ceramic. C -axis-oriented Bi 4 Ti 3 O 12 films were grown on Si(100) at a low substrate temperature of 550°C. However, these films did not exhibit ferroelectricity, and the dielectric constant ε r and dissipation factor tan δ were about 156 and 0.032, respectively. The dielectric constant was reduced with decreasing film thickness. This behavior was assuming supposing a low-dielectric-constant interface layer. These films showed the dielectric breakdown field of about 21 kV/cm.
    Type of Medium: Online Resource
    ISSN: 0021-4922 , 1347-4065
    URL: Article
    DOI: 10.1143/JJAP.34.5116
    RVK:
    UA 4210.1
    RVK:
    UA 4210.2
    RVK:
    UA 4210
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 1995
    detail.hit.zdb_id: 218223-3
    detail.hit.zdb_id: 797294-5
    detail.hit.zdb_id: 2006801-3
    detail.hit.zdb_id: 797295-7
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  • 8
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    Online Resource
    Effect of Grain Size on Bi 4 Ti 3 O 12 Thin Film Properties
    IOP Publishing ; 1998
    In:  Japanese Journal of Applied Physics Vol. 37, No. 9S ( 1998-09-01), p. 5166-
    Details
    In: Japanese Journal of Applied Physics, IOP Publishing, Vol. 37, No. 9S ( 1998-09-01), p. 5166-
    Abstract: Bismuth titanate (Bi 4 Ti 3 O 12 ) thin films with a c -axis orientation were prepared on (100) silicon wafers by rf magnetron sputtering. The average grain size and the c -axis lattice constant depend on the substrate temperature. The c -axis lattice constant was decreased with increasing grain size. The leakage current characteristics of the Bi 4 Ti 3 O 12 thin film consisting of small grains with a closely packed structure, are superior to those of others. The apparent remanent polarization and the apparent coercive field of the film with small grain sizes were estimated to be 2.4 µC·cm -2 and 2.3 kV·cm -1 , respectively. The refractive index dispersion characteristics for the film show that the large grains increase the distortion of the oxygen-octahedra. Consequently, this result indicates that the small grain size of Bi 4 Ti 3 O 12 thin films can improve the ferroelectric properties.
    Type of Medium: Online Resource
    ISSN: 0021-4922 , 1347-4065
    URL: Article
    DOI: 10.1143/JJAP.37.5166
    RVK:
    UA 4210.1
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    UA 4210.2
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    UA 4210
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 1998
    detail.hit.zdb_id: 218223-3
    detail.hit.zdb_id: 797294-5
    detail.hit.zdb_id: 2006801-3
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  • 9
    Online Resource
    Online Resource
    A second update on mapping the human genetic architecture of COVID-19
    Springer Science and Business Media LLC ; 2023
    In:  Nature Vol. 621, No. 7977 ( 2023-09-07), p. E7-E26
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 621, No. 7977 ( 2023-09-07), p. E7-E26
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-023-06355-3
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 10
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    Online Resource
    Mapping the human genetic architecture of COVID-19
    Springer Science and Business Media LLC ; 2021
    In:  Nature Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Abstract: The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-021-03767-x
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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