| 1. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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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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| 2. |
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| 3. |
- Konishi, T, et al.
(författare)
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Electronic structure of the strongly hybridized ferromagnet CeFe2
- 2000
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Ingår i: PHYSICAL REVIEW B. - : AMERICAN PHYSICAL SOC. - 0163-1829. ; 62:21, s. 14304-14312
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Tidskriftsartikel (refereegranskat)abstract
- We report on results from high-energy spectroscopic measurements on CeFe2, a system of particular interest due to its anomalous ferromagnetism with an unusually low Curie temperature and small magnetization compared to the other rare-earth iron Laves phas
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| 4. |
- Konishi, T, et al.
(författare)
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Photoemission and inverse-photoemission study of ferromagnetic valence fluctuating system CeFe2
- 1998
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Ingår i: JOURNAL OF ELECTRON SPECTROSCOPY AND RELATED PHENOMENA. - : ELSEVIER SCIENCE BV. - 0368-2048. ; 88, s. 303-307
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Various electron-spectroscopic results including core-level X-ray photoemission, X-ray absorption, Ce 3d-4f and 4d-4f resonant photoemission, and inverse-photoemission spectroscopy on the valence fluctuating ferromagnet CeFe2 are presented and analyzed wi
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| 5. |
- Titarenko, Yu E., et al.
(författare)
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Measurement and simulation of the cross sections for nuclide production in Fe-56 and Cr-nat targets irradiated with 0.04- to 2.6-GeV protons
- 2011
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Ingår i: Physics of Atomic Nuclei. - 1063-7788 .- 1562-692X. ; 74:4, s. 523-536
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Tidskriftsartikel (refereegranskat)abstract
- The cross sections for nuclide production in thin Fe-56 and Cr-nat targets irradiated by 0.04-2.6-GeV protons are measured by direct gamma spectrometry using two gamma spectrometers with the resolutions of 1.8 and 1.7 keV for the Co-60 1332-keV gamma line. As a result, 649 yields of radioactive residual product nuclei have been obtained. The Al-27(p, x)Na-22 reaction has been used as a monitor reaction. The experimental data are compared with the MCNPX (BERTINI, ISABEL), CEM03.02, INCL4.2, INCL4.5, PHITS, and CASCADE07 calculations.
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| 6. |
- Titarenko, Yu E., et al.
(författare)
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Measurement and simulation of the cross sections for nuclide production in Nb-93 and Ni-nat targets irradiated with 0.04- to 2.6-GeV protons
- 2011
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Ingår i: Physics of Atomic Nuclei. - 1063-7788 .- 1562-692X. ; 74:4, s. 537-550
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Tidskriftsartikel (refereegranskat)abstract
- The cross sections for nuclide production in thin Nb-93 and Ni-nat targets irradiated by 0.04- to 2.6-GeV protons have been measured by direct gamma spectrometry using two gamma spectrometers with the resolutions of 1.8 and 1.7 keV in the Co-60 1332-keV gamma line. As a result, 1112 yields of radioactive residual nuclei have been obtained. The Al-27(p, x)Na-22 reaction has been used as a monitor reaction. The experimental data have been compared with the MCNPX (BERTINI, ISABEL), CEM03.02, INCL4.2, INCL4.5, PHITS, and CASCADE07 calculations.
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| 7. |
- Titarenko, Yu E., et al.
(författare)
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Measurement and simulation of the cross sections for nuclide production in W-nat and Ta-181 targets irradiated with 0.04- to 2.6-GeV protons
- 2011
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Ingår i: Physics of Atomic Nuclei. - 1063-7788 .- 1562-692X. ; 74:4, s. 551-572
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Tidskriftsartikel (refereegranskat)abstract
- The cross sections for nuclide production in thin (nat)Wand Ta-181 targets irradiated by 0.04-2.6-GeV protons have been measured by direct gamma spectrometry using two gamma spectrometers with the resolutions of 1.8 and 1.7 keV in the Co-60 1332-keV gamma line. As a result, 1895 yields of radioactive residual product nuclei have been obtained. The Al-27(p, x)Na-22 reaction has been used as a monitor reaction. The experimental data have been compared with the MCNPX (BERTINI, ISABEL), CEM03.02, INCL4.2, INCL4.5, PHITS, and CASCADE07 calculations.
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| 8. |
- Titarenko, Yu E., et al.
(författare)
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Measurement and simulation of the cross sections for the production of Gd-148 in thin W-nat and Ta-181 targets irradiated with 0.4- to 2.6-GeV protons
- 2011
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Ingår i: Physics of Atomic Nuclei. - 1063-7788 .- 1562-692X. ; 74:4, s. 573-579
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Tidskriftsartikel (refereegranskat)abstract
- The cross sections for the production of Gd-148 in W-nat and Ta-181 targets irradiated by 0.4-, 0.6-, 0.8-, 1.2-, 1.6-, and 2.6-GeV protons at the ITEP accelerator complex have been measured by direct alpha spectrometry without chemical separation. The experimental data have been compared with the data obtained at other laboratories and with the theoretical simulations of the yields on the basis of the BERTINI, ISABEL, CEM03.02, INCL4.2, INCL4.5, CASCADE07, and PHITS codes.
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| 9. |
- Titarenko, Yu. E., et al.
(författare)
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Verification of high-energy transport codes on the basis of activation data
- 2011
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 84:6, s. 064612-
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Tidskriftsartikel (refereegranskat)abstract
- Nuclide production cross sections measured at the Institute for Theoretical and Experimental Physics (ITEP) for the targets of (nat)Cr, (56)Fe, (nat)Ni, (93)Nb, (181)Ta, (nat)W, (nat)Pb, and (209)Bi irradiated by protons with energies from 40 to 2600 MeV were used to estimate the predictive accuracy of several popular high-energy transport codes. A general agreement of the ITEP data with the data obtained by other groups, including the numerous GSI data measured by the inverse kinematics method was found. Simulations of the measured data were performed with the MCNPX (BERTINI and ISABEL options), CEM03.02, INCL4.2 + ABLA, INCL4.5 + ABLA07, PHITS, and CASCADE.07 codes. Deviation factors between the calculated and experimental cross sections have been estimated for each target and for the whole energy range covered by our measurements. Two-dimensional diagrams of deviation factor values were produced for estimating the predictive power of every code for intermediate, not measured masses of nuclei targets and bombarding energies of protons. Further improvements of all tested here codes are recommended. In addition, new measurements at ITEP of nuclide yields from the (208)Pb target irradiated by 500-MeV protons are presented. A good agreement between these new data and the GSI measurements obtained by the inverse kinematics method was found.
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| 10. |
- Zaidi, Syed H., et al.
(författare)
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Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
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