内視鏡的非治癒切除となった大腸T1 癌治療後の予後 1)大腸T1 癌に対する先行したESD は追加外科手術後の予後に影響を与えない 2)LST T1 癌治療後の長期予後

内容の要旨, 審査の要旨広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

Klotho mice: a novel wound model of aged skin.

BackgroundAs the elderly population continues to expand, it becomes increasingly important to develop treatments to improve wound healing in the elderly. One problem limiting the research is the lack of appropriate animal models for wound healing in elderly patients. We hypothesized that the Klotho mouse of premature aging is a suitable animal model to shed light on many of the biological processes involved in aging skin.MethodsKlotho mice (kl/kl), Klotho-heterozygous mice (kl/+), and wild-type mice (+/+) were wounded, and the area of the wound was measured every 3 days until the wound was healed. To compare the klotho phenotype with wild-type mice, wounds were also harvested at 4 and 7 days after wounding. For histological examination, paraffin-embedded sections were stained with hematoxylin and eosin and Masson trichrome. Collagen expression in the wound was also studied by analyzing messenger RNA using real-time polymerase chain reaction.ResultsKlotho mice showed a significantly slower rate of wound closure compared with Klotho-heterozygous mice and wild-type mice. Histology showed substantial less healing and collagen deposition in the wounds of the Klotho mice. The expression of collagen messenger RNA in Klotho mice was also less than that in heterozygous and wild-type mice. The Klotho mice exhibited significant phenotypic similarities with aged skin, such as atrophy and delayed wound healing.ConclusionThese preliminary data suggest that the Klotho mouse may be a model to further investigate wound healing in the elderly

Near-Infrared Spectroscopy of the Cool Brown Dwarf, SDSS 1624+00

Using the Subaru Telescope, we have obtained multiple near-infrared spectra of the cool brown dwarf, SDSS 1624+00, in search of spectral variability in an 80 minute time span. We have found the suspected variability of water vapor absorption throughout the observations, which requires confirmation by a longer time baseline. After coadding the spectra, we have obtained a high-quality spectrum covering 1.05 to 1.8 um. Three kinds of spectral indicators, the water vapor bands, methane band, and KI lines in J band, suggest that SDSS 1624+00 is warmer and dustier than Gl 229B.Comment: 6 figures, to appear in PAS

Induction of Autophagy by Amino Acid Starvation in Fish Cells

Autophagy is well established as a starvation-induced process in yeast and mammalian cells and tissues. To elucidate the cellular mechanisms induced by starvation in fish, we characterized the induction of autophagy in cultured zebrafish cells under starvation conditions. As an autophagic marker protein, the microtubule-associated protein 1-light chain 3B protein (MAP1-LC3B) was cloned from the fish cells, and its expression and localization were characterized. In zebrafish embryonic (ZE) cells, posttranslational modifications produced two distinct forms of MAP1-LC3B, i.e., a cytosolic form and a membrane-bound form (types I and II, respectively). Immunofluorescence microscopy revealed fluorescently labeled autophagosomes in cells stably transfected with a green fluorescent protein (GFP)–MAP1-LC3B fusion protein and showed that this protein accumulated in punctate dots in a time-dependent manner in response to amino acid starvation. Starvation also induced the degradation of long-lived proteins. Treatment with 3-methyladenine and wortmannin, two class-III inhibitors of phosphoinositide 3-kinase (PI3K), repressed autophagy under starvation conditions, indicating that the PI3K class-III pathway regulates starvation-induced autophagy in fish

Development of a Novel Output Value for Quantitative Assessment in Methylated DNA Immunoprecipitation-CpG Island Microarray Analysis

In DNA methylation microarray analysis, quantitative assessment of intermediate methylation levels in samples with various global methylation levels is still difficult. Here, specifically for methylated DNA immunoprecipitation-CpG island (CGI) microarray analysis, we developed a new output value. The signal log ratio reflected the global methylation levels, but had only moderate linear correlation (r = 0.72) with the fraction of DNA molecules immunoprecipitated. By multiplying the signal log ratio using a coefficient obtained from the probability value that took account of signals in neighbouring probes, its linearity was markedly improved (r = 0.94). The new output value, Me value, reflected the global methylation level, had a strong correlation also with the fraction of methylated CpG sites obtained by bisulphite sequencing (r = 0.88), and had an accuracy of 71.8 and 83.8% in detecting completely methylated and unmethylated CGIs. Analysis of gastric cancer cell lines using the Me value showed that methylation of CGIs in promoters and gene bodies was associated with low and high, respectively, gene expression. The degree of demethylation of promoter CGIs after 5-aza-2'-deoxycytidine treatment had no association with that of induction of gene expression. The Me value was considered to be useful for analysis of intermediate methylation levels of CGIs

Structure of l-rhamnose isomerase in complex with l-rhamnopyranose demonstrates the sugar-ring opening mechanism and the role of a substrate sub-binding site

Abstractl-Rhamnose isomerase (l-RhI) catalyzes the reversible isomerization of l-rhamnose to l-rhamnulose. Previously determined X-ray structures of l-RhI showed a hydride-shift mechanism for the isomerization of substrates in a linear form, but the mechanism for opening of the sugar-ring is still unclear. To elucidate this mechanism, we determined X-ray structures of a mutant l-RhI in complex with l-rhamnopyranose and d-allopyranose. Results suggest that a catalytic water molecule, which acts as an acid/base catalyst in the isomerization reaction, is likely to be involved in pyranose-ring opening, and that a newly found substrate sub-binding site in the vicinity of the catalytic site may recognize different anomers of substrates

Spatial-photonic Boltzmann machines: low-rank combinatorial optimization and statistical learning by spatial light modulation

The spatial-photonic Ising machine (SPIM) [D. Pierangeli et al., Phys. Rev. Lett. 122, 213902 (2019)] is a promising optical architecture utilizing spatial light modulation for solving large-scale combinatorial optimization problems efficiently. However, the SPIM can accommodate Ising problems with only rank-one interaction matrices, which limits its applicability to various real-world problems. In this Letter, we propose a new computing model for the SPIM that can accommodate any Ising problem without changing its optical implementation. The proposed model is particularly efficient for Ising problems with low-rank interaction matrices, such as knapsack problems. Moreover, the model acquires learning ability and can thus be termed a spatial-photonic Boltzmann machine (SPBM). We demonstrate that learning, classification, and sampling of the MNIST handwritten digit images are achieved efficiently using SPBMs with low-rank interactions. Thus, the proposed SPBM model exhibits higher practical applicability to various problems of combinatorial optimization and statistical learning, without losing the scalability inherent in the SPIM architecture.Comment: 7 pages, 5 figures (with a 3-page supplemental

A Study on the Relationship between Social Movement of Life Time Sports and School Physical Education in Japan (II) : From the View Point of the Curriculum Development Study

先報(1991)では, 『生涯スポーツ』概念の形成課程を吟味することと, その概念の実質的イメージについて検討した。そして, それらの作業に基づいて, 生涯スポーツ概念と学校体育の機能との関係を問題にした。議論の結果, 生涯スポーツや生涯体育の概念が活発に議論されて, 学校の機能・役割との関係も議論された割合には, 生涯スポーツの実態もイメージも余り明確でなく, 従って両者の関係も曖昧モコとしていることが明らかになった。そして, 生涯スポーツ運動に連動する形で, 中等教育学校で〈習熟度別授業〉や〈選択制履修授業(以下「選択制」と略す)〉を積極的に位置づけようとする働きが, 理論的にも実質的にも相当不可解なものと理解された。 さらに, こうした実態もイメージも不明確な状況でありながら, それでいて体育の教科内容や教科課程にかかわる問題意識は一般にさほど高くない。少なくとも, 日本体育学会や日本教科教育学会でみる限り, こうした学校内外の体育・スポーツの将来構想にかかわる問題意識をもつテーマは, 一部シンポジウム等を除けば最近の5年間ほとんど設定されていない事実も認められる。 そこで, 生涯スポーツに関連させようとする学校体育の趨勢, 即ち代表的には選択制の導入等は今日的に, かつ将来的にはいかなる意味をもち, 学校教育にどのような影響をおよぼすかについて, 改めて予測的に検討したい。その際, スポーツや運動は, 〈国民的教養〉あるいは〈国民的権利〉とさえ把握されようとしてきた思想や社会的運動そして歴史・伝統に, 学校体育が現実にどうかかわっていけるのかという視点を軸としたい。The purposes of this study were to make clear the problems of the curriculum study, and to search the possibility of an optional physical education system through discussing the idea of life time sports in Japan. As the result of the examination what are judged from the social sports situations and the characters of Japanese school system, it is considered that this system does not contain the conditions of a generalization or a diffusion, though this optional physical education system is an important and an urgent problems. The main results are follows; 1) From viewpoint of curriculum research and development in physical education, the discussion of the fearture that contain the abolition of physical education in school, are need in the private affairs of sports and game. 2) The optional physical education system in secondary education will be done by halves near fearture, because of a lack of considerations about the real school conditions. And the result of failre in optional system may cause the discussoin of unnecessary of physical education in high school. 3) From view of the fact, discussed in 2), it is predicted that a school physical education is confused, at least the base or value of the physical education in school is fundamentally discussed, and we must protect ourselves by new theories that will be re-integrated in near fearture. 4) The tentative plan, it is accepted to the sociaty, is to open the school sports facilities and instructors for the outside of school,and to full up the present school physical education class for the inside of school. It can be started to coexist the public sports activities and private one's by functioning the tentative plan