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Sökning: WFRF:(Kohno Takashi)

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1.
  • Kubo, Minoru, et al. (författare)
  • Nanosecond pump-probe device for time-resolved serial femtosecond crystallography developed at SACLA
  • 2017
  • Ingår i: Journal of Synchrotron Radiation. - : INT UNION CRYSTALLOGRAPHY. - 0909-0495 .- 1600-5775. ; 24, s. 1086-1091
  • Tidskriftsartikel (refereegranskat)abstract
    • X-ray free-electron lasers (XFELs) have opened new opportunities for timeresolved X-ray crystallography. Here a nanosecond optical-pump XFEL-probe device developed for time-resolved serial femtosecond crystallography (TRSFX) studies of photo-induced reactions in proteins at the SPring-8 Angstrom Compact free-electron LAser (SACLA) is reported. The optical-fiber-based system is a good choice for a quick setup in a limited beam time and allows pump illumination from two directions to achieve high excitation efficiency of protein microcrystals. Two types of injectors are used: one for extruding highly viscous samples such as lipidic cubic phase (LCP) and the other for pulsed liquid droplets. Under standard sample flow conditions from the viscous-sample injector, delay times from nanoseconds to tens of milliseconds are accessible, typical time scales required to study large protein conformational changes. A first demonstration of a TR-SFX experiment on bacteriorhodopsin in bicelle using a setup with a droplet-type injector is also presented.
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2.
  • Bakx, Tom J. L. C., et al. (författare)
  • ALMA uncovers the [C II] emission and warm dust continuum in a z=8.31 Lyman break galaxy
  • 2020
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 493:3, s. 4294-4307
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the detection of the [C II] 157.7 mu m emission from the Lyman break galaxy (LBG) MACS0416_Y1 at z = 8.3113, by using the Atacama Large Millimeter/submillimeter Array (ALMA). The luminosity ratio of [O III] 88 mu m (from previous campaigns) to [CII] is 9.3 +/- 2.6, indicative of hard interstellar radiation fields and/or a low covering fraction of photodissociation regions. The emission of [C II] is cospatial to the 850 mu m dust emission (90 mu m rest frame, from previous campaigns), however the peak [C II] emission does not agree with the peak [O III] emission, suggesting that the lines originate from different conditions in the interstellar medium. We fail to detect continuum emission at 1.5 mm (160 mu m rest frame) down to 18 mu Jy (3 sigma). This non-detection places a strong limits on the dust spectrum, considering the 137 +/- 26 mu Jy continuum emission at 850 mu m. This suggests an unusually warm dust component (T > 80 K, 90 per cent confidence limit), and/or a steep dust-emissivity index (beta(dust) > 2), compared to galaxy-wide dust emission found at lower redshifts (typically T similar to 30-50 K, beta(dust) similar to 1-2). If such temperatures are common, thiswould reduce the required dust mass and relax the dust production problem at the highest redshifts. We therefore warn against the use of only single-wavelength information to derive physical properties, recommend a more thorough examination of dust temperatures in the early Universe, and stress the need for instrumentation that probes the peak of warm dust in the Epoch of Reionization.
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3.
  • George, Julie, et al. (författare)
  • Comprehensive genomic profiles of small cell lung cancer
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
  • Tidskriftsartikel (refereegranskat)abstract
    • We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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4.
  • Hashimoto, Takuya, et al. (författare)
  • Big Three Dragons: A z=7.15 Lyman-break galaxy detected in [Oiii] 88 mu m, [Cii] 158 mu m, and dust continuum with ALMA
  • 2019
  • Ingår i: Publication of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 2053-051X .- 0004-6264. ; 71:4
  • Tidskriftsartikel (refereegranskat)abstract
    • We present new ALMA observations and physical properties of a Lyman break galaxy at z = 7.15. Our target, B14-65666, has a bright ultra-violet (UV) absolute magnitude, M-UV approximate to -22.4, and has been spectroscopically identified in Ly alpha with a small rest-frame equivalent width of approximate to 4 angstrom. A previous Hubble Space TElescope (HST) image has shown that the target is composed of two spatially separated clumps in the rest-frame UV. With ALMA, we have newly detected spatially resolved [Oiii] 88 mu m, [Cii] 158 mu m, and their underlying dust continuum emission. In the whole system of B14-65666, the [Oiii] and [Cii] lines have consistent redshifts of 7.1520 +/- 0.0003, and the [Oiii] luminosity, (34.4 +/- 4.1)x 10(8)L(circle dot), is about three times higher than the [Cii] luminosity, (11.0 +/- 1.4) x 10(8)L(circle dot). With our two continuum flux densities, the dust temperature is constrained to be T-d approximate to 50-60K under the assumption of a dust emissivity index of beta(d) = 2.0-1.5, leading to a large total infrared luminosity of L-TIR approximate to 1 x 10(12)L(circle dot). Owing to our high spatial resolution data, we show that the [Oiii] and [Cii] emission can be spatially decomposed into two clumps associated with the two rest-frame UV clumps whose spectra are kinematically separated by approximate to 200kms(-1). We also find these two clumps have comparable UV, infrared, [Oiii], and [Cii] luminosities. Based on these results, we argue that B14-65666 is a starburst galaxy induced by a major merger. The merger interpretation is also supported by the large specific star formation rate (defined as the star formation rate per unit stellar mass), sSFR Gyr(-1), inferred from our SED fitting. Probably, a strong UV radiation field caused by intense star formation contributes to its high dust temperature and the [Oiii]-to-[Cii] luminosity ratio.
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5.
  • Inoue, Akio K., et al. (författare)
  • Detection of an oxygen emission line from a high-redshift galaxy in the reionization epoch
  • 2016
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 352:6293, s. 1559-1562
  • Tidskriftsartikel (refereegranskat)abstract
    • The physical properties and elemental abundances of the interstellar medium in galaxies during cosmic reionization are important for understanding the role of galaxies in this process. We report the Atacama Large Millimeter/submillimeter Array detection of an oxygen emission line at a wavelength of 88 micrometers from a galaxy at an epoch about 700 million years after the Big Bang. The oxygen abundance of this galaxy is estimated at about one-tenth that of the Sun. The nondetection of far-infrared continuum emission indicates a deficiency of interstellar dust in the galaxy. A carbon emission line at a wavelength of 158 micrometers is also not detected, implying an unusually small amount of neutral gas. These properties might allow ionizing photons to escape into the intergalactic medium.
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6.
  • Izumi, Takuma, et al. (författare)
  • ALMA OBSERVATIONS OF THE SUBMILLIMETER DENSE MOLECULAR GAS TRACERS IN THE LUMINOUS TYPE-1 ACTIVE NUCLEUS OF NGC 7469
  • 2015
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 811:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 1 observations of the central kiloparsec region of the luminous type. 1 Seyfert galaxy NGC 7469 with unprecedented high resolution (0.'' 5x0.'' 4 = 165 x 132 pc) at submillimeter wavelengths. Utilizing the wide. bandwidth of ALMA, we simultaneously obtained HCN(4-3), HCO+(4-3), CS(7-6), and partially CO(3-2) line maps, as well as the 860 mu m continuum. The region consists of the central similar to 1 '' component and the surrounding starburst ring with a radius of similar to 1.'' 5-2.'' 5. Several structures connect these components. Except for CO(3-2), these dense gas tracers are significantly concentrated toward the central similar to 1 '', suggesting their suitability to probe the nuclear regions of galaxies. Their spatial distribution resembles well those of centimeter and mid-infrared continuum emissions, but it is anticorrelated with the optical one, indicating the existence of dust-obscured star formation. The integrated intensity ratios of HCN(4-3)/HCO+(4-3) and HCN(4-3)/CS(7-6) are higher at the active galactic nucleus (AGN) position than at the starburst ring, which is consistent with our previous findings (submillimeter-HCN enhancement). However, the HCN(4-3)/HCO+(4-3) ratio at the AGN position of NGC 7469 (1.11 +/- 0.06) is almost half of the corresponding value of the low-luminosity type. 1 Seyfert galaxy NGC 1097 (2.0 +/- 0.2), despite the more than two orders of magnitude higher X-ray luminosity of NGC 7469. But the ratio is comparable to that of the close vicinity of the AGN of NGC 1068 (similar to 1.5). Based on these results, we speculate that some heating mechanisms other than X-ray (e.g., mechanical heating due to an AGN jet) can contribute significantly for shaping the chemical composition in NGC 1097.
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7.
  • Sampson, Joshua N., et al. (författare)
  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
  • 2015
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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8.
  • Tamura, Yoichi, et al. (författare)
  • Detection of the Far-infrared [O III] and Dust Emission in a Galaxy at Redshift 8.312 : Early Metal Enrichment in the Heart of the Reionization Era
  • 2019
  • Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 874:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the Atacama Large Millimeter/submillimeter Array detection of the [O III] 88 mu m line and rest-frame 90 mu m dust continuum emission in a Y-dropout Lyman break galaxy (LBG), MACS0416_Y1 lying behind the Frontier Field cluster MACS J0416.1-2403. This [O III] detection confirms the LBG with a spectroscopic redshift of z = 8.3118 +/- 0.0003, making this object one of the farthest galaxies ever identified spectroscopically. The observed 850 mu m flux density of 137 +/- 26 mu Jy corresponds to a de-lensed total infrared (IR) luminosity of L-IR = (1.7 +/- 0.3) x 10(11) L-circle dot if assuming a dust temperature of T-dust = 50 K and an emissivity index of beta = 1.5, yielding a large dust mass of 4 x 10(6) M-circle dot. The ultraviolet-to-far-IR spectral energy distribution modeling where the [O III] emissivity model is incorporated suggests the presence of a young (tau(age) approximate to 4 Myr), star-forming (SFR approximate to 60 M-circle dot yr(-1)), moderately metal-polluted (Z approximate to 0.2 Z(circle dot)) stellar component with a mass of M-star = 3 x 10(8) M-circle dot. An analytic dust mass evolution model with a single episode of star formation does not reproduce the metallicity and dust mass in tau(age) approximate to 4 Myr, suggesting a pre-existing evolved stellar component with M-star similar to 3 x 10(9) M-circle dot and tau(age) similar to 0.3 Gyr as the origin of the dust mass.
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9.
  • Wang, Zhaoming, et al. (författare)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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  • Resultat 1-9 av 9

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