Le follicule pileux est un micro-organe spécifique des mammifères responsable de la formation des poils. Au cours de la vie postnatale, le follicule pileux subit des phases récurrentes de croissance (anagène), régression (catagène) et repos (télogène). Les mécanismes cellulaires et moléculaires qui régulent le cycle pilaire rappellent certains des évènements qui ont lieu durant la morphogénèse. Bien qu’il y ait eu des avancées significatives dans la connaissance de la biologie du follicule pileux ; les mécanismes qui régulent le passage de la phase anagène à la phase catagène restent mystérieux. Fgf5, un membre de la famille des facteurs de croissance des fibroblastes, a été identifié comme un régulateur clé de la transition anagène-catagène. Les souris qui ne produisent pas de protéine Fgf5 active présentent un phénotype angora (go/go) caractérisé par une phase anagène plus longue et de longs poils. Cependant, les follicules pileux n’ayant pas Fgf5, entrent quand même dans la phase catagène, ce qui suggère que d’autres mécanismes contribuent au control du cycle pilaire. Des précédents résultats obtenus dans notre laboratoire ont établis une relation très proche entre le déclenchement de la phase catagène et le diamètre du poil. En utilisant le follicule de vibrisse comme modèle, nous avons confirmé ces résultats en démontrant, par in hybridation in situ, que l’expression du gène Fgf5 s’active dans les cellules de la gaine épithéliale externe localisées dans la région supra-bulbaire, progressivement l’expression de Fgf5 s’étend jusqu’à l’extrémité inférieur de la gaine épithéliale externe et s’éteint quelques jours avant le début de la phase catagène, de nouveau dans les cellules de la gaine épithéliale externe localisées dans la partie supra-bulbaire. Nous avons également démontré que le nombre de couche cellulaires dans la région du cortex du poil, augmente progressivement au cours du temps jusqu’à atteindre exactement le même nombre de couche, quelques jours avant la fin de la phase de croissance, chez la souris sauvage et la souris Fgf5LacZ/LacZ. Ces résultats confirment notre hypothèse établissant que Fgf5 ne déclenche pas de façon direct la phase catagène. Ensuite, nous avons démontré pour la première fois que les cellules progénitrices du cortex peuvent se diviser symétriquement. Ces divisions symétriques très rares se traduisent, quelques jours après, en la formation d’une nouvelle couche cellulaire dans le cortex du poil. Ces résultats appuient notre hypothèse qu’une boucle de régulation complexe impliquant, la gaine épithéliale externe, la papille dermique (qui exprime Fgfr1, le récepteur de Fgf5), la matrice et la région supra-bulbaire ; est indispensable au control du cycle pilaire. Nous avons ensuite démontré par qRT-PCR et des marquages immunologiques que plusieurs canaux mécano-sensitifs sont exprimés de façon spécifique dans ces régions d’intérêts. De plus, plusieurs gènes importants pour la signalisation, sont également exprimés dans ces régions. Tout cela mis ensemble nos résultats soutiennent l’hypothèse provocatrice que la croissance progressive de la largeur du poil induit une pression mécanique qui entraine l’activation de canaux mécano-sensitifs, qui vont à leur tour activer des voies de signalisation pour finalement contrôler l’expression de Fgf5 dans la région supra-bulbaire et ainsi contrôler le cycle pilaire. / The hair follicle is a skin micro-organ specific to mammals and responsible for the formation of the hair. During postnatal life, the hair follicle undergoes recurrent phases of growth (anagen), regression (catagen) and rest (telogen) termed the hair cycle. The cellular and molecular mechanisms that regulate the hair cycle recapitulate some of the events occurring during morphogenesis. Despite significant advances in the understanding of biology of the hair follicle, the mechanisms regulating the switch from anagen to catagen remain mysterious. Fgf5, a member of the fibroblast growth factor family, has been proposed as a key regulator of the transition between anagen and catagen. Mice that do not produce active Fgf5 have an angora (go/go) phenotype characterized by an extended anagen phase and long hairs. Nevertheless, Fgf5 null hair follicles still enter catagen, suggesting that other mechanisms contribute to the control of the hair cycle. Previous work in the laboratory using Fgf5Lacz/LacZ null mice has unraveled a close connection between the onset of catagen and the diameter of the hair. Using the whisker follicle as a model system, we have confirmed these results and demonstrated by in situ hybridization that the expression of the Fgf5 gene is switched-on in the supra-bulbar region of the outer root sheath, progressively extends towards the lower extremity of the outer root sheath and is switched-off in the supra-bulbar region of the outer root sheath several days before the onset of catagen. We have also demonstrated that the number of cell layers in the hair cortex progressively increases with time to reach the exact same number a few days before the end of anagen in both wild-type and Fgf5 null follicles confirming our working hypothesis that Fgf5 does not directly trigger catagen. Next, we have demonstrated for the first time that the basal cortex-forming cells could divide symmetrically. These rare symmetrical divisions result in the formation of additional cell layers in the cortex. These results support our working hypothesis that a complex regulatory loop involving the outer sheath, the dermal papilla (that express Fgfr1, the Fgf5 receptor), the cortical matrix and the supra bulbar region is critical in controlling whisker growth. We have then demonstrated by q-RTPCR and immunostaining that several mechanosensitive channels are specifically expressed in the regions of interest. Moreover, several genes important for signaling are also expressed in these regions. Altogether, our results support the provocative hypothesis that the progressive increase in the width of the hair induces a mechanical pressure that leads to the activation of mechanosensitive channels, which in turn activate specific signaling pathways and ultimately result in the control of the expression of the Fgf5 gene in the supra-bulbar region of the outer root sheath and then in the control of the hair cycle.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20408号 / 工博第4345号 / 新制||工||1673(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 赤木 和夫, 教授 古賀 毅, 教授 辻井 敬亘 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

This study investigated an oxidation-reduction reaction involving a mixture of minerals, glass, and aluminum that exhibited thermite-type reaction behavior. Thermite reactions are a class of Self-propagating High-temperature Synthesis (SHS) reactions. Chemical reactions between raw minerals and a reducing agent, which exhibit thermite-type reaction behavior, are termed geothermite reactions by the author. Geothermite reactions have the potential for use in In-Situ Resource Utilization (ISRU) applications on the Earth, the Moon, Mars, and beyond. A geothermite reaction was shown to occur between two particle size distributions of lunar regolith simulant. Regolith simulant is a naturally occurring mixture of minerals and glass mined from a volcanic ash deposit. The chemical composition of the simulant is similar to actual lunar regolith found on the Moon. The product of the reaction was a ceramic-composite material. The effect of reactant stoichiometry, regolith simulant particle size, and reaction environment on phase formation, microstructure, and compressive strength of the reaction product was investigated. Reaction environments used in this study included a standard atmosphere and a vacuum environment of 0.600 Torr. In addition, the energy required to initiate each reaction using various reaction parameters was measured. X-ray diffraction (XRD) analysis of reaction products synthesized in a standard atmosphere and in vacuum typically indicated the presence of the chemical species: silicon, corundum (α -Al₂O₃), spinel (MgAl₂O₄), and grossite (CaAl₄O₇). Many additional chemical species were present; their occurrence depended on reaction parameters used during synthesis. Diffraction peaks were observed for phases of aluminum nitride within all reaction products formed in a standard atmosphere. Scanning Electron Microscopy (SEM) showed the presence of whisker networks throughout the microstructure for all reactions conducted in a standard atmosphere. Energy Dispersive Spectroscopy (EDS) indicated the presence of aluminum and nitrogen within many of the whiskers. It was hypothesized that many of the whisker networks were composed of phases of aluminum nitride. No whisker networks were observed in the vacuum synthesized reaction products. Maximum mean compressive strengths were found to be ~ 18 MPa and occurred in the coarse particle size distribution of simulant using the smallest quantity of aluminum. Reactant mixtures using a coarse particle size distribution of regolith simulant were found to require substantially more energy to initiate the reaction than the simulant with the fine particle size distribution. / Master of Science

No description available.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第19038号 / 農博第2116号 / 新制||農||1031(附属図書館) / 学位論文||H27||N4920(農学部図書室) / 31989 / 京都大学大学院農学研究科森林科学専攻 / (主査)教授 木村 恒久, 教授 西尾 嘉之, 教授 髙野 俊幸 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

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Ratten verwenden Schnurrhaare (Vibrissen) zur Berührungswahrnehmung, und die Leitungsbahn von den Vibrissen zum primären somatosensorischen Areal (Barrel Cortex, BC) ist gut untersucht. Ratten zeigen auch vielfältiges Sozialverhalten, u.a. Berührung von Artgenossen mit ihren Vibrissen. Es ist jedoch unbekannt, wie diese sozialen Berührungssignale im Gehirn repräsentiert sind. Deshalb hatte die vorliegende Studie zum Ziel, die neuronale Repräsentation von sozialen Berührungen im BC zu untersuchen und mit anderer somatosensorischer Stimulation zu vergleichen. Mit extrazellulären Einzelzellableitungen in sich frei bewegenden Ratten habe ich gezeigt, dass die Aktivität eines Großteils von Neuronen im BC durch soziale Berührungen moduliert wird. Antworten waren meist erregend und Feuerraten während sozialer Interaktionen unterschieden sich zwischen kortikalen Schichten. Ratten bevorzugten Interaktionen mit Artgenossen gegenüber unbelebten Stimuli. Auch die Berührungsstrategien unterschieden sich, dabei wurden Objekte mit regelmäßigeren Bewegungen abgetastet, und die Vibrissen weiter vorgestreckt. Neuronale Antworten unterschieden sich ebenso, mit leicht aber konsistent schwächeren Antworten auf Objekte. Interessanterweise habe ich geschlechtsspezifische Unterschiede in neuronalen Antworten beobachtet. Der ausgeprägteste war die stärkere Modulation regulär-feuernder (RF) Zellen in Männchen während sozialer Berührungen. Dieser Unterschied konnte nicht mit sozialem Berührungsverhalten erklärt werden, was eventuell auf eine neurale Grundlage dieser Differenz hindeutet. Zudem feuerten RF-Zellen von Weibchen deutlich seltener, wenn das Weibchen im Östrus war. Zusammenfassend ist dies die erste Studie, die soziale Signale in einem primären sensorischen Areal bei sich frei bewegenden Tieren auf zellulärer Ebene untersuchte. Sie legt nahe, dass die Repräsentationen sensorischer Hirnrinde weniger stimulusabhängig und stärker top-down-moduliert sein könnten, als zuvor angenommen. / Rats use their stiff facial hairs (whiskers) for somatosensation, and the pathway from the whiskers to the primary somatosensory cortex (barrel cortex, BC) is well known. Rats also show diverse social behaviors, including touch of conspecifics with their whiskers. The representation of these social touch signals in the brain is however unknown. Thus, the present study aimed at characterizing the neuronal representation of social touch signals in BC and comparing them with non-social somatosensory stimulation. Using extracellular single-cell recordings in freely-moving rats, I could show that the activity of a large fraction of BC neurons is modulated by social touch. Responses were typically excitatory and the pattern of firing rates during interactions differed between cortical layers. Rats preferred interactions with alive conspecifics over inanimate stimuli. Whisking strategies also differed in that inanimate stimuli were whisked at with more regular movements from more protracted set angles. Neuronal responses were also different, such that objects elicited slightly but consistently weaker responses than alive rats. Interestingly, I observed sex-specific differences in neuronal responses. Prominently, there was stronger modulation by social touch in regular-spikers (RS) recorded from males. This could not be explained by behavioral measures, possibly indicating a neural origin of this difference. Further, RS from females fired much more weakly when females were in estrus. In summary, this is the first study that investigated social signals in a primary sensory area of freely-moving animals at the cellular level. It suggests that representations in sensory cortices might be less stimulus-driven and more top-down modulated than previously thought.

No description available.

<p>The superior high-temperature elastic-plastic properties coupled with greater damage tolerance when compared with monolithic ceramics make ceramic matrix composites, CMCs, promising candidates for challenging applications such as engine components, rocket nozzles, cutting tools and nuclear energy reactor core components. Anelastic recovery is the time-dependent back strain observed upon the load removal following creep. In whisker-reinforced CMCs this can be a factor limiting operating conditions. Plastic strain misfit between two phases is thought to be the main driver in terms of the interactions within a percolating network. However, the network deformation mechanisms are still unclear and a previous neutron diffraction study showed an unexpected decrease of peak width after creep contradicting the theoretical predictions.</p> <p>In this contribution, the finite element method (FEM) is applied to a representative volume element (RVE) with proper boundary conditions in order to simulate the creep deformation and hot pressing processes. Three geometries have been generated and studied: a 3D randomly-oriented short-fiber unit cell without fiber to fiber contact, generated by a random sequential adsorption algorithm; 3D regularly aligned single fiber unit cells; and 2D regularly aligned percolating unit cells. Deformation mechanism has been studied from an energy point of view and compared with a modified analytical model. Then a virtual diffraction model has been developed providing a framework to transfer information between the FEM simulations (strain fields) and the diffraction pattern in terms of the peak width (full width at half maximum: <strong><em>FWHM</em></strong>) and peak position as a measure of stress distribution and mean stress state respectively. Furthermore, the coupling effects of external stress, deformation mode, and thermal stress on the diffraction patterns have been studied.</p> <p>The critical importance of a percolating whisker network for the anelastic recovery is demonstrated based on the 3D multi-whisker random unit cell. Whisker bending is shown to be the dominant mechanism over contact effects during the creep deformation of a composite containing a well aligned percolating whisker network based on the 2D unit cell model. Good qualitative agreement was found between our FEM simulations and the analytical model of Wilkinson and Pompe with regards to the maximum recoverable strain and the characteristic relaxation time. The analytical model captures all the critical factors characterizing the strain recovery, e.g., the effect of creep pre-exponent constant, whisker Young’s modulus and aspect ratio. Furthermore, it is found that the deformation from an initial stress-free state inevitably introduces peak broadening of whiskers inside the matrix. Several factors determine the peak-width and -shift, i.e., creep strain, applied stress, aspect ratio and geometry. However, thermal stress from the cooling stages following creep and hot pressing processes shelters this broadening effect and complicates the trends. Wide-ranging peak-width changes from narrowing to broadening are predicted depending on the geometry and applied stress. The peak position is shifted to a lower angle due to this thermal effect. This clearly explains the contradicting phenomena motivating this work and leads to that recommendation that a diffraction source with high angular resolution is needed to detect the subtle change of peak profile during creep.</p> / Doctor of Philosophy (PhD)

No description available.