多能性幹細胞を用いたヒト分節時計の再現

京都大学0048新制・課程博士博士(医科学)甲第22699号医科博第114号新制||医科||8(附属図書館)京都大学大学院医学研究科医科学専攻(主査)教授 影山 龍一郎, 教授 妻木 範行, 教授 長船 健二学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

A Probability-based Evolutionary Algorithm with Mutations to Learn Bayesian Networks

Bayesian networks are regarded as one of the essential tools to analyze causal relationship between events from data. To learn the structure of highly-reliable Bayesian networks from data as quickly as possible is one of the important problems that several studies have been tried to achieve. In recent years, probability-based evolutionary algorithms have been proposed as a new efficient approach to learn Bayesian networks. In this paper, we target on one of the probability-based evolutionary algorithms called PBIL (Probability-Based Incremental Learning), and propose a new mutation operator. Through performance evaluation, we found that the proposed mutation operator has a good performance in learning Bayesian networks

Yokomichi : Une collection du Paléolithique supérieur du Japon abordée selon un œil technologique français

Since the 1970’s, the study of lithic prehistoric collections in France has improved through a profound modernisation. André Leroi-Gourhan, first interested in traditional and ethnological techniques, decided to consider all remains and traces left by a human group within a prehistoric site as evidence of its activity, thus opening the “palethnological perspective”. He also promoted the principle of “chaîne opératoire” (that is, to consider the successive actions and gestures engaged in the transformation of diverse raw materials) a notion which had been formerly introduced by Marcel Mauss. But, it is the experimentalists of stone knapping, François Bordes and Jacques Tixier, who made it possible to enrich this notion with its concrete applications. Above all, Tixier, armed with his clear practical understanding of knapped pieces and his pedagogic skills, enriched and stabilized the lithic terminology, and systematized the “technological reading” of lithics, in other words, the reading of the direction and order of the different scars (negatives of previous removals) visible upon the surface of a flake, a core, or a shaped tool, thus allowing one to mentally reconstruct the fabrication of a tool or the reduction of a core. He also introduced the capital distinction between the “method of knapping” (the arrangement and succession of the removals to reach the goal of the chaîne opératoire, i.e., a type or a class of blanks or tools), and the “knapping techniques” (that is, the practical mode of detachment, e.g., direct percussion with a hard stone or a wooden billet, pressure with an antler or copper point, etc.). On this basis, in 1980, Tixier together with a few close colleagues from France and Belgium introduced the concepts of economy of raw materials, debitage, and tools, all three concepts being corollaries of the concept of management rules. The notion of intention - which articulates the blank production modalities and the morphology of the blanks obtained and that of the final tools - also appears, which is the basis of the postulate according to which the knapping modalities (effective decisions and actions) are coherent with the morphology of the expected or priority products. It is this postulate, parallel to that of “design theory” taken up by Brian Hayden, which founded, through the consideration of all the lithic remains, the French approach in lithic technology:  to perceive - to understand - the intentions of lithic production within a site or collection before classifying and measuring. This principle is then applied to the small (324 pieces, including 30 to 40 tools) lithic collection from the site of Yokomichi (Yamagata Dept., Northeastern Honshu), with blade production but without (i.e., anterior to) bladelet or microblade production; thus datable to approximately 18,000 BP C14 non-calibrated, from regional chronostratigraphical comparisons). At first it appears that two different blade productions co-exist: one of light and straight blades with a small platform remnant detached from slender cores, and the other of larger blades with a thick platform remnant detached from wider cores. Among the retouched tools, it is the few “Sugikubo knives” (straight and pointed backed points) whose blanks correspond to the priority intention of the slender core reduction, a few other tools being retouched on “second choice” blanks (irregular, too thick, etc.). Such a Sugibuko knife, in a similar collection, shows a fracture with a ventral elongated tongue [“languette” in French] that strongly indicates that this type of tools is actually, at least in part, a projectile point. Various observations then suggest that the priority intention of the wide core reduction was to obtain one or a few large pointed blades, which are very difficult to achieve, while its many second choice products and by-products (being too short, having cortex, etc.) could have been used as unretouched knives or resharpened as “Kamiyama burins” (these are indeed blades or flakes modified by a “pseudo” upper plane burin blow from an inverse truncation, very similar to Kostienki knives). A further experiment shows that both blade productions were made by direct percussion with a soft stone, but in different ways: by tangential percussion for the light blades with a small platform, and by direct percussion inside the striking platform for the stronger blades with a thick platform.Depuis les années 1970, l’étude des collections lithiques préhistoriques a vécu en France une profonde modernisation. André Leroi-Gourhan, d’abord intéressé par les techniques traditionnelles, prit pour objectif d’appréhender les activités techniques menées dans un site par un groupe préhistorique, dans une perspective ainsi dénommée « palethnologique ». Il a aussi promu la notion de chaîne opératoire introduite auparavant par Marcel Mauss. Mais ce sont les expérimentateurs de la taille des roches dures, F. Bordes et J. Tixier, qui vont permettre d’enrichir cette notion de ses applications concrètes. J. Tixier, surtout, stabilise la terminologie de la pierre taillée, et systématise la « lecture technologique » qui permet de reconstituer mentalement le déroulement du façonnage d’un outil ou du débitage d’un nucléus. Il introduit aussi une distinction fondamentale entre « méthode » (la démarche -l’agencement des enlèvements successifs-  suivie pour atteindre le but de la chaîne opératoire : un type ou une classe de produits) et « technique(s) » (qui réfère aux modalités pratiques d’exécution des enlèvements). Sur cette base, dès 1980, Tixier et collègues introduisent les notions d’économie des matières premières, du débitage et de l’outillage, corollaires de la notion de règles de gestion. La notion d’intention -entre débitage, supports et (certains) outils- apparaît également, fondant le postulat selon lequel les modalités de la taille sont cohérentes avec la morphologie des produits recherchés. C’est ce postulat que suit la démarche française en technologie lithique : percevoir -comprendre- les intentions de la production lithique, avant de classer et de mesurer. Cette démarche est ensuite appliquée à la collection lithique de Yokomichi (Dept de Yamagata, NE de Honshu), à débitage laminaire mais antérieure à la production de lamelles, ainsi datable d’environ 18 000 BP. On perçoit d’abord qu’y coexistent deux débitages laminaires : l’un de lames légères et rectilignes à petit talon, tirées de nucléus étroits, et l’autre de fortes lames à talons épais débitées de nucléus plus larges. Parmi les outils retouchés, ce sont les quelques « couteaux de Sugikubo » (des pointes à dos élancées de profil rectiligne) dont les supports correspondent à l’intention première du débitage étroit, quelques autres outils étant réalisés sur des supports de second choix. Un tel couteau de Sugikubo, dans une collection similaire, présente une fracture à longue languette inverse qui suggère fortement qu’il s’agit en fait, au moins pour partie, de pointes de projectile. Le débitage large, lui, avait pour intention première l’obtention de grandes lames pointues, très difficiles à réaliser, tandis que ses nombreux produits de second choix et d’aménagement restent bruts (utilisables comme couteaux) ou se retrouvent dans les « burins de Kamiyama » (en fait, de très probables couteaux ravivés comme les couteaux de Kostienki). Une expérimentation montre que les deux débitages sont réalisés par percussion directe à la pierre tendre, mais selon des modalités distinctes : par percussion tangentielle pour les lames légères à petit talon, par percussion en retrait pour les lames plus fortes à gros talon

Central Mandibular Reconstruction by Semiopen Wedge Osteotomy Double-barrel Fibula Flap for a Slim Aesthetic Appearance

Mandibular reconstruction involving the central segment after malignant tumor resection requires the achievement of both functional and aesthetic quality. Three-dimensional reproduction based on the concept of a double arc composed of a marginal arc and an occlusal arc is important. Most reports of fibula flaps applied three-segmented closed wedge fibula osteotomy (bilateral and central segments); however, the aesthetic outcome sometimes became too stout for female patients because of the large central segment. We performed four-segmented fibula osteotomy for a 78-year-old woman using a semiopen wedge technique characterized by a half-open wedge and half-closed wedge. This procedure obtained a slim mandibular contour and made double-barrel reconstruction easier to apply. We used titanium plates that were prebent according to the shape of a three-dimensional model constructed from CT data. Small bone cortex fragments made from a surplus fibula segment were inserted in a half-opened area. The build-up preparation for central mandibular reconstruction was all performed at the lower leg area before cutting the peroneal pedicle. This prefabricated double-barrel fibula free flap was transferred to the mandibular defect with arterial and venous anastomosis to the right superior thyroid artery, right external jugular vein, and right common facial vein. Although the patient was nearly 80 years of age, the bone segments, including free cortex tips, were fused with smooth remodeling. Semiopen wedge osteotomy can be a key to reproducing an aesthetically slim feminine chin with a functional height of mandibular bone maintained for stability of the dental prosthesis

Sulphur-isotopic composition of the deep-sea mussel Bathymodiolus marisindicus from currently active hydrothermal vents in the Indian Ocean

Sulphur-isotopic composition of soft tissues from bathymodiolus marisindicus collected from hydrothermal vents in the indian ocean was reported. the [delta]34s values of the soft tissues (+3[similar]+5‰ vs cañyon diablo troilite) were nearly identical to those from the associated hydrothermal fluid and chimney sulphides (+5 to +8‰), but were significantly different from that of the common seawater sulphate (+21‰), which suggested that the endosymbiotic bacteria used sulphide in the fluid as an energy source. transmission electron microscopic observation of the endosymbionts also suggested that the symbiont is a thioautotroph. bathymodiolus species, which depend on either sulphide or methane oxidation, or both, have a worldwide distribution. bathymodiolus marisindicus from the indian ocean has a close relationship with congeners in the pacific ocean as evidenced by form of symbiosis. biogeography and migration of the genus bathymodiolus based on the relevant data are briefly discussed.</p

Difference in NaCl tolerance of membrane-bound 5′-nucleotidases purified from deep-sea and brackish water Shewanella species

Shewanella species are widely distributed in sea, brackish, and fresh water areas, growing psychrophilically or mesophilically, and piezophilically or piezo-sensitively. Here, membrane-bound 5′-nucleotidases (NTases) from deep-sea Shewanella violacea and brackish water Shewanella amazonensis were examined from the aspect of NaCl tolerance in order to gain an insight into protein stability against salt. Both NTases were single polypeptides with molecular masses of ~59 kDa, as determined on mass spectroscopy. They similarly required 10 mM MgCl2 for their activities, and they exhibited the same pH dependency and substrate specificity for 5′-nucleotides. However, S. violacea 5′-nucleotidase (SVNTase) was active enough in the presence of 2.5 M NaCl, whereas S. amazonensis 5′-nucleotidase (SANTase) exhibited significantly reduced activity with the same concentration of the salt. Although SVNTase and SANTase exhibited high sequence identity (69.7%), differences in the ratio of acidic to basic amino acid residues and the number of potential salt bridges maybe being responsible for the difference in the protein stability against salt. 5′-Nucleotidases from these Shewanella species will provide useful information regarding NaCl tolerance, which may be fundamental for understanding bacterial adaptation to growth environments.This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan [No. 26240045], a grant from the Japan Society for the Promotion of Science [No. 25-1446], and The Salt Science Research Foundation [No. 1655]

Human cultured epidermis accelerates wound healing regardless of its viability in a diabetic mouse model

Allogeneic cultured epidermis (allo-CE) is a cultured keratinocyte sheet manufactured from donor cells and promotes wound healing when used in deep dermal burns, donor sites, and chronic ulcers and serves as a wound dressing. Allo-CE is usually cryopreserved to be ready to use. However, the cryopreservation procedure will damage the cell viability, and the influence of Allo-CE, according to its viability or wound healing process, has not been evaluated sufficiently. In this study, we aimed to prove the influence of keratinocyte viability contained in allo-CEs on wound healing. We prepared CEs with Green’s method using keratinocytes obtained from a polydactyly patient and then prepared four kinds of CEs with different cell viabilities [fresh, cryopreserved, frozen, and FT (freeze and thaw)]. The cell viabilities of fresh, cryopreserved, frozen, and FT CEs were 95.7%, 59.9%, 16.7%, and 0.0%, respectively. The four CEs had homogeneous characteristics, except for small gaps found in the FT sheet by transmission electron microscopy observation. The four CEs were applied on the full-thickness skin defect of diabetic mice (BKS.Cg-Dock 7m +/+ Leprdb/Jcl), and the wound area and neoepithelium length were evaluated on days 4, 7, and 14. As a result, FT CEs without viable cells similarly promoted epithelialization on days 4 and 7 (p<0.05) and accelerated wound closure on day 7 (p<0.01) as fresh CEs compared with the control group. In conclusion, the promoting effect of allo-CE on wound healing does not depend on cell viability. Lyophilized CEs may be a suitable wound dressing with a long storage period at room temperature

Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro

Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required