アリル特異的抗HLA抗体を用いた治療モデルの開発

学位の種別:課程博士University of Tokyo(東京大学

A safeguard system for induced pluripotent stem cell-derived rejuvenated T cell therapy

The discovery of induced pluripotent stem cells (iPSCs) has created promising new avenues for therapies in regenerative medicine. However, the tumorigenic potential of undifferentiated iPSCs is a major safety concern for clinical translation. To address this issue, we demonstrated the efficacy of suicide gene therapy by introducing inducible caspase-9 (iC9) into iPSCs. Activation of iC9 with a specific chemical inducer of dimerization (CID) initiates a caspase cascade that eliminates iPSCs and tumors originated from iPSCs. We introduced this iC9/CID safeguard system into a previously reported iPSC-derived, rejuvenated cytotoxic T lymphocyte (rejCTL) therapy model and confirmed that we can generate rejCTLs from iPSCs expressing high levels of iC9 without disturbing antigen-specific killing activity. iC9-expressing rejCTLs exert antitumor effects in vivo. The system efficiently and safely induces apoptosis in these rejCTLs. These results unite to suggest that the iC9/CID safeguard system is a promising tool for future iPSC-mediated approaches to clinical therapy

Characterizing Volatiles and Organics on Asteroid (162173) Ryugu

Outline: Overview of Hayabusa2 mission and its target asteroid Ryugu; Spectroscopic laboratory measurements under asteroid-like conditions of carbonaceous chondrites; Recent ground-based observations of carbonaceous asteroids relevant to Ryugu; Implications of meteorite spectroscopic measurements & asteroid observations for Hayabusa2s observations of Ryugu

Four‐dimensional‐STEM analysis of the phyllosilicate‐rich matrix of Ryugu samples

Ryugu asteroid grains brought back to the Earth by the Hayabusa2 space mission are pristine samples containing hydrated minerals and organic compounds. Here, we investigate the mineralogy of their phyllosilicate-rich matrix with four-dimensional scanning transmission electron microscopy (4D-STEM). We have identified and mapped the mineral phases at the nanometer scale (serpentine, smectite, pyrrhotite), observed the presence of Ni-bearing pyrrhotite, and identified the serpentine polymorph as lizardite, in agreement with the reported aqueous alteration history of Ryugu. Furthermore, we have mapped the d-spacings of smectite and observed a broad distribution of values, ranging from 1 to 2 nm, with an average d-spacing of 1.24 nm, indicating significant heterogeneity within the sample. Such d-spacing variability could be the result of either the presence of organic matter trapped in the interlayers or the influence of various geochemical conditions at the submicrometer scale, suggestive of a range of organic compounds and/or changes in smectite crystal chemistry

Influx of nitrogen-rich material from the outer Solar System indicated by iron nitride in Ryugu samples

Large amounts of nitrogen compounds, such as ammonium salts, may be stored in icy bodies and comets, but the transport of these nitrogen-bearing solids into the near-Earth region is not well understood. Here, we report the discovery of iron nitride on magnetite grains from the surface of the near-Earth C-type carbonaceous asteroid Ryugu, suggesting inorganic nitrogen fixation. Micrometeoroid impacts and solar wind irradiation may have caused the selective loss of volatile species from major iron-bearing minerals to form the metallic iron. Iron nitride is a product of nitridation of the iron metal by impacts of micrometeoroids that have higher nitrogen contents than the CI chondrites. The impactors are probably primitive materials with origins in the nitrogen-rich reservoirs in the outer Solar System. Our observation implies that the amount of nitrogen available for planetary formation and prebiotic reactions in the inner Solar System is greater than previously recognized

A dehydrated space-weathered skin cloaking the hydrated interior of Ryugu

Without a protective atmosphere, space-exposed surfaces of airless Solar System bodies gradually experience an alteration in composition, structure and optical properties through a collective process called space weathering. The return of samples from near-Earth asteroid (162173) Ryugu by Hayabusa2 provides the first opportunity for laboratory study of space-weathering signatures on the most abundant type of inner solar system body: a C-type asteroid, composed of materials largely unchanged since the formation of the Solar System. Weathered Ryugu grains show areas of surface amorphization and partial melting of phyllosilicates, in which reduction from Fe3+ to Fe2+ and dehydration developed. Space weathering probably contributed to dehydration by dehydroxylation of Ryugu surface phyllosilicates that had already lost interlayer water molecules and to weakening of the 2.7 µm hydroxyl (–OH) band in reflectance spectra. For C-type asteroids in general, this indicates that a weak 2.7 µm band can signify space-weathering-induced surface dehydration, rather than bulk volatile loss

Experts and novices use the same factors--but differently--to evaluate pearl quality.

Well-trained experts in pearl grading have been thought to evaluate pearls according to their glossiness, interference color, and shape. However, the characteristics of their evaluations are not fully understood. Using pearl grading experiments, we investigate the consistency of novice (i.e., without knowledge of pearl grading) and expert participants' pearl grading skill and then compare the novices' grading with that of experts; furthermore, we discuss the relationship between grading, interference color, and glossiness. We found that novices' grading was significantly less concordant with experts average grading than was experts' grading; more than half of novices graded pearls the opposite of how experts graded those same pearls. However, while experts graded pearls more consistently than novices did, novices' consistency was relatively high. We also found differences between the groups in regression analyses that used interference color and glossiness as explanatory variables and were conducted for each trial. Although the regression coefficient was significant in 60% of novices' trials, there were fewer significant trials for the experts (20%). This indicates that novices can also make use of these two factors, but that their usage is simpler than that of the experts. These results suggest that experts and novices share some values about pearls but that the evaluation method is elaborated for experts