X-Ray Spectrum of a Peculiar Supernova Remnant G359.1-0.5

We present the Suzaku results of a supernova remnant (SNR), G359.1-0.5 in the direction of the Galactic center region. From the SNR, we find prominent K-shell lines of highly ionized Si and S ions, together with unusual structures at 2.5-3.0 and 3.1-3.6 keV. No canonical SNR plasma model, in either ionization equilibrium or under-ionization, can explain the structures. The energies and shapes of the structures are similar to those of the radiative transitions of free electrons to the K-shell of He-like Si and S ions (radiative recombination continuum: RRC). The presence of the strong RRC structures indicates that the plasma is in over-ionization. In fact, the observed spectrum is well fitted with an over-ionized plasma model. The best-fit electron temperature of 0.29 keV is far smaller than the ionization temperature of 0.77 keV, which means that G359.1-0.5 is in extreme condition of over-ionization. We report some cautions on the physical parameters, and comment possible origins for the over-ionized plasma.Comment: 7 pages, 5 figures, accepted for publication in PAS

New Insights into SNR Evolution Revealed by the Discovery of Recombining Plasmas

We report the discovery of recombining plasmas in three supernova remnants (SNRs) with the Suzaku X-ray astronomy satellite. During SNR's evolution, the expanding supernova ejecta and the ambient matter are compressed and heated by the reverse and forward shocks to form an X-ray emitting hot plasma. Since ionization proceeds slowly compared to shock heating, most young or middle-aged SNRs have ionizing (underionized) plasmas. Owing to high sensitivity of Suzaku, however, we have detected radiative recombination continua (RRCs) from the SNRs IC 443, W49B, and G359.1-0.5. The presence of the strong RRC is the definitive evidence that the plasma is recombining (overionized). As a possible origin of the overionization, an interaction between the ejecta and dense circumstellar matter is proposed; the highly ionized gas was made at the initial phase of the SNR evolution in dense regions, and subsequent rapid adiabatic expansion caused sudden cooling of the electrons. The analysis on the full X-ray band spectrum of IC 443, which is newly presented in this paper, provides a consistent picture with this scenario. We also comment on the implications from the fact that all the SNRs having recombining plasmas are correlated with the mixed-morphology class.Comment: Published by Advances in Space Researc

Culture and Egocentric Perceptions of Fairness in Conflict and Negotiation

In this article, the authors advanced a cultural view of judgment biases in conflict and negotiation. The authors predicted that disputants’ self-serving biases of fairness would be more prevalent in individualistic cultures, such as the United States, in which the self is served by focusing on one’s positive attributes to “stand out” and be better than others, yet would be attenuated in collectivistic cultures, such as Japan, where the self is served by focusing on one’s negative characteristics to “blend in” (S. J. Heine, D. R. Lehman, H. R. Markus, & S. Kitayama, 1999). Four studies that used different methodologies (free recall, scenarios, and a laboratory experiment) supported this notion. Implications for the science and practice of negotiation are discussed

Expansion Velocity of Ejecta in Tycho's Supernova Remnant Measured by Doppler Broadened X-ray Line Emission

We show that the expansion of ejecta in Tycho's supernova remnant (SNR) is consistent with a spherically symmetric shell, based on Suzaku measurements of the Doppler broadened X-ray emission lines. All the strong K_alpha line emission show broader widths at the center than at the rim, while the centroid energies are constant across the remnant (except for Ca). This is the pattern expected for Doppler broadening due to expansion of the SNR ejecta in a spherical shell. To determine the expansion velocities of the ejecta, we applied a model for each emission line feature having two Gaussian components separately representing red- and blue-shifted gas, and inferred the Doppler velocity difference between these two components directly from the fitted centroid energy difference. Taking into account the effect of projecting a three-dimensional shell to the plane of the detector, we derived average spherical expansion velocities independently for the K_alpha emission of Si, S, Ar, and Fe, and K_beta of Si. We found that the expansion velocities of Si, S, and Ar ejecta of 4700+/-100 km/s are distinctly higher than that obtained from Fe K_alpha emission, 4000+/-300 km/s, which is consistent with segregation of the Fe in the inner ejecta. Combining the observed ejecta velocities with the ejecta proper-motion measurements by Chandra, we derived a distance to the Tycho's SNR of 4+/-1 kpc.Comment: Accepted to Apj, 25 pages, 7 figures, 5 table

Mice deficient in the Shmt2 gene have mitochondrial respiration defects and are embryonic lethal

Accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for human aging and age-associated mitochondrial respiration defects. However, our previous findings suggested an alternative hypothesis of human aging—that epigenetic changes but not mutations regulate age-associated mitochondrial respiration defects, and that epigenetic downregulation of nuclear-coded genes responsible for mitochondrial translation [e.g., glycine C-acetyltransferase (GCAT), serine hydroxymethyltransferase 2 (SHMT2)] is related to age-associated respiration defects. To examine our hypothesis, here we generated mice deficient in Gcat or Shmt2 and investigated whether they have respiration defects and premature aging phenotypes. Gcat-deficient mice showed no macroscopic abnormalities including premature aging phenotypes for up to 9 months after birth. In contrast, Shmt2-deficient mice showed embryonic lethality after 13.5 days post coitum (dpc), and fibroblasts obtained from 12.5-dpc Shmt2-deficient embryos had respiration defects and retardation of cell growth. Because Shmt2 substantially controls production of N-formylmethionine-tRNA (fMet-tRNA) in mitochondria, its suppression would reduce mitochondrial translation, resulting in expression of the respiration defects in fibroblasts from Shmt2-deficient embryos. These findings support our hypothesis that age-associated respiration defects in fibroblasts of elderly humans are caused not by mtDNA mutations but by epigenetic regulation of nuclear genes including SHMT2

Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC

Introduction: Programmed cell death-1 (PD-1) inhibitors effectively treat NSCLC and prolong survival. Robust biomarkers for predicting clinical benefits of good response and long survival with anti-PD-1 therapy have yet to be identified; therefore, predictive biomarkers are needed to select patients with benefits. Methods: We conducted a prospective study to explore whether serum antibody against NY-ESO-1 and/or XAGE1 cancer-testis antigens predicted primarily good clinical response and secondarily long survival with anti-PD-1 therapy for NSCLC. The serum antibody was detected by enzyme-linked immunosorbent assay, and tumor immune microenvironment and mutation burden were analyzed by immunohistochemistry and next-generation sequencing. Results: In the discovery cohort (n = 13), six antibody-positive NSCLC cases responded to anti-PD-1 therapy (two complete and four partial responses), whereas seven antibody-negative NSCLC cases did not. Antibody positivity was associated with good response and survival, regardless of tumor programmed death ligand 1 (PD-L1) expression, mutation burden, and CD8+ T-cell infiltration. In the validation cohort (n = 75), 17 antibody-positive NSCLC cases responded well to anti-PD-1 therapy as compared with 58 negative NSCLC cases (objective response rate 65% versus 19%, p = 0.0006) and showed significantly prolonged progression-free survival and overall survival. Antibody titers highly correlated with tumor reduction rates. In the multivariate analysis, response biomarkers were tumor programmed death ligand 1 expression and antibody positivity, and only antibody positivity was a significantly better predictive biomarker of progression-free survival (hazard ratio = 0.4, p = 0.01) and overall survival (hazard ratio = 0.2, p = 0.004). Conclusions: Our results suggest that NY-ESO-1 and/or XAGE1 serum antibodies are useful biomarkers for predicting clinical benefits in anti-PD-1 therapy for NSCLC and probably for other cancers

Long-term eradication of extranodal natural killer/T-cell lymphoma, nasal type, by induced pluripotent stem cell-derived Epstein-Barr virus-specific rejuvenated T cells in vivo

Functionally rejuvenated induced pluripotent stem cell (iPSC)-derived antigen-specific cytotoxic T lymphocytes (CTL) are expected to be a potent immunotherapy for tumors. When L-asparaginase-containing standard chemotherapy fails in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), no effective salvage therapy exists. The clinical course then is miserable. We demonstrate prolonged and robust eradication of ENKL in vivo by Epstein-Barr virus-specific iPSC-derived antigen-specific CTL, with iPSC-derived antigen-specific CTL persisting as central memory T cells in the mouse spleen for at least six months. The anti-tumor response is so strong that any concomitant effect of the programmed cell death 1 (PD-1) blockade is unclear. These results suggest that long-term persistent Epstein-Barr virus-specific iPSC-derived antigen-specific CTL contribute to a continuous anti-tumor effect and offer an effective salvage therapy for relapsed and refractory ENKL

04 『良友』画報と上海の文学研究

2017年度共同研究グループ経過報

Severe esophagitis directly induced by accumulation of crizotinib-residue at the esophageal mucosa proven with polarizing microscope examination

Crizotinib demonstrates dramatic effects for the patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase gene (ALK) fusion or c-ros oncogene 1 (ROS-1) fusion-positive lung cancer, with some characteristic toxicities. Although several studies reported that serious esophagitis was induced by crizotinib, the detailed mechanisms and ways to ameliorate the esophagitis have not been clarified. In this report, we report two cases with lung cancer who had been treated with crizotinib and developed severe esophagitis. Polarizing microscope examination clearly revealed that the accumulation of crizotinib-residue in the esophageal biopsy samples at the second anatomical narrowing of the esophagus in both cases. Since it seemed that the accumulation of crizotinib-residue in the esophageal mucosa directly caused the esophageal inflammation, we recommended taking crizotinib with a large amount of water (more than 200 ml) and to stay sitting upright for 30 minutes after intake. After that, the esophagitis gradually improved and the patients could continue taking crizotinib without dose reduction or withdrawal. Our experiences suggest that this crizotinib-induced esophagitis could be easily prevented by proper administration of crizotinib