Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(エネルギー科学) / 甲第19093号 / エネ博第317号 / 新制||エネ||64 / 32044 / 京都大学大学院エネルギー科学研究科エネルギー変換科学専攻 / (主査)教授 木村 晃彦, 教授 星出 敏彦, 教授 今谷 勝次 / 学位規則第4条第1項該当

In many previous physiological and psychoacoustic studies, Schroeder-phase masking (using Schroeder harmonic complexes to mask other sounds) has proven useful in understanding different aspects of cochlear function, particularly the phase curvature of the cochlea and cochlear nonlinearity. The common method of measuring Schroeder-phase masking functions uses a very time consuming three-alternative forced choice (3AFC) process, which limits its research and clinical usefulness. This thesis describes a fast method for measuring Schroeder-phase masking functions that we developed to address this problem. By adapting the Békésy tracking technique, we demonstrate how the measurement time can be reliably shortened by almost 80% in comparison to the commonly-used method. Using the fast method, we have demonstrated that the difference in masking effectiveness produced by different phases of Schroeder maskers (known as the ‘phase effect’) is reduced in conditions where cochlear non-linearity is expected to be reduced (i.e. at low intensity levels and in sensorineural hearing loss subjects) – findings which are consistent with previous studies. The possible involvement of other mechanisms in producing the Schroeder phase effect (particularly the medial olivocochlear (MOC) reflex) is discussed. Given the shorter testing time and higher resolution data it can give, the fast method can be a useful tool in estimating cochlear phase curvature. The reduction in testing time in particular may significantly aid the investigation of different aspects of cochlear function which might have been limited by the long testing time given by the commonly-used method.

Störungen der Schluckfunktion werden im Alter zunehmend diagnostiziert und beeinträchtigen die Lebensqualität der betroffenen Patienten sehr. Ein abnormes Schluckmuster bei Kindern und Jugendlichen kann eine pathologische Wirkung auf die Entwicklung der Zahnstellung haben. In dieser Studie wurde bei einem gesunden Probandenkollektiv von 52 Teilnehmern (40 w; 12 m) im Alter von 20 - 45 (MW: 25.48; SD:4.68) Jahren die orale Phase des Schluckaktes untersucht. Für diese Zwecke, wurde ein intraorales Mundstück angewendet (Silencos®, Bredent, Senden, Deutschland), das aufgrund der Einbringung einer Silikonschlaufe die intraorale Bolusapplikation und Druckmessung erlaubte. Extraoral wurde das Mundstück einerseits an einer mit Flüssigkeit gefüllten Spritze zur Bolusapplikation und andererseits an ein digitales Manometer (GDUSB 1000®, Greisinger electronics, Regenstauf Deutschland) angeschlossen. Das genutzte Messgerät besaß die Fähigkeit, mit einer Frequenz von 1kHz Messungen in einem Bereich von 2000 bis -1000 mbar durchzuführen. Zum Schutz der Probanden und zur Sicherung der Messung wurde am Schlauchsystem ein Bakterienfilter und ein Wasserabscheider angebracht. Mit dieser Versuchsanordnung wurden drei Schluckmodalitäten untersucht. Jede Modalität beinhaltete 10 Schluckvorgänge. Die erste Untersuchung bezog sich auf die aktive Einnahme eines Bolus aus Wasser. Die Probanden führten Saugimpulse aus, indem sie Flüssigkeit aus einer Spritze zogen und diese anschließend schluckten. Die zweite und dritte Untersuchung basierte auf der passiven Gabe eines Bolus, der in einem Volumen von 2 ml appliziert wurde. In diesem Versuch wurde jeweils ein 2-ml-Bolus aus Wasser und aus Gel verabreicht. Bei den erhobenen Daten konnten hauptsächlich negative Druckamplituden beobachtet werden. Dabei wurde ein Mittelwert von -290 mbar bei der aktiven Bolus-Einnahme, -31 mbar während der passiven Gabe eines Bolus aus Wasser und -37 mbar bei der passiven Gabe eines Bolus aus Gel gemessen. Auch die Dauer der Schluckereignisse wurde gemessen. Hierbei ergab sich ein Mittelwert von 5.1 s bei der aktiven Bolus-Einnahme, 1.8 s bei der passiven Gabe eines Bolus aus Wasser und 1.5 s bei der passiven Gabe eines Bolus aus Gel. In Abhängigkeit von der Art der Bolusapplikation und der Boluskonsistenz konnten signifikante Differenzen zwischen den erhobenen Druckamplituden und Druckverläufen beobachtet werden. Die aktive Einnahme eines Bolus zeigte höhere negative Druckverläufe sowie eine längere Dauer als bei der passiven Gabe eines Bolus. Auch signifikante Unterschiede zwischen den Konsistenzen konnten beobachtet werden: die Gabe eines Bolus aus Gel wies polyphasische Kurven auf. Im Vergleich dazu zeigten sich vorwiegend monophasische Kurven beim Schlucken von Wasser. Der vorgeschlagene Schlucktest zeigte eine einfache Anwendbarkeit und konnte bei allen Probanden problemlos durchgeführt werden. Der technische Aufwand war gering und die Untersuchung brachte keine Nebenwirkungen für die Probanden mit sich. Anhand dieses Tests wurden Datensätze zur Schluckfunktion erzeugt, welche qualitativ und quantitativ ausgewertet wurden und als Normwert für zukünftige Untersuchungen dienen. Die Interpretation der erhobenen Daten anhand des biofunktionellen Modells ermöglicht eine methodische Erfassung der Schluckphysiologie. Eine klinische Anwendung bietet sich als diagnostischer Test sowie auch in der Übungstherapie an. Die durchgeführten Untersuchungen konnten die funktionelle Ähnlichkeit der Funktionen Saugen und Schlucken belegen und zeigten, dass das vom biofunktionellen Modell ausgewiesene Kompartiment 2 offensichtlich zum Transport von Flüssigkeiten einen Saugmechanismus und nicht einen Propulsionsmechanismus durch Verdrängen des Bolus bevorzugt.

A new any-point biasing scheme for Mach-Zehnder interferometer modulators which considers the complex phase is proposed. The Mach-Zehnder arm loss imbalance (imaginary part of the phase bias) is found by slightly perturbing the real and imaginary parts of the phase in each arm with low frequency pilot tones and monitoring and manipulating the spectral content at the output. This technique can be used to extend the possible extinction ratio, reduce the phase error, and better quantify the system chirp but also has some performance degradations which are also quantified and discussed. Simulation results indicate that the maximum extinction ratio of a typical modulator can be extended to ≳ 40 dB and maintained in the presence of ambient complex phase drift in the arms. Practical challenges for implementing this method with a silicon Mach-Zehnder modulator are discussed, but the analysis is general to other material platforms.

A new any-point biasing scheme for Mach-Zehnder interferometer modulators which considers the complex phase is proposed. The Mach-Zehnder arm loss imbalance (imaginary part of the phase bias) is found by slightly perturbing the real and imaginary parts of the phase in each arm with low frequency pilot tones and monitoring and manipulating the spectral content at the output. This technique can be used to extend the possible extinction ratio, reduce the phase error, and better quantify the system chirp but also has some performance degradations which are also quantified and discussed. Simulation results indicate that the maximum extinction ratio of a typical modulator can be extended to ≳ 40 dB and maintained in the presence of ambient complex phase drift in the arms. Practical challenges for implementing this method with a silicon Mach-Zehnder modulator are discussed, but the analysis is general to other material platforms.

The distinctive architecture of the stratum corneum with its unique nature of an interstitial lipoidal environment plays the major role in regulating the barrier function of the skin. The major problem with the transdermal delivery of 5-fluorouracil or idoxuridine is the permeation of sufficient amounts to the deeper layers of the skin and into the systemic circulation. In an attempt to enhance the transdermal permeability of 5-fluorouracil and idoxuridine, the aim of this study was to evaluate two lamellar gel phase systems (Physiogel dermaquadrille® and Physiogel NT®) and Emzaloids® as transdermal delivery vehicles for the two actives. Lamellar gel phase systems (LGPS) and Emzaloids® are both novel drug delivery systems. The epidermis of female abdominal skin was used in vertically mounted Franz diffusion cell experiments. An average amount of 250 mg of the 1% m/m LGPS was applied to cover the entire diffusion area of 1,075 cm2 of the skin, which contained 2,5 mg of the active. Samples of the actives in Emzaloids® were prepared and applied in the same way. The control solutions of the actives in water were prepared so that 1 ml of the applied solution contained the same amount of drug that was applied to the experimental cells. The entire receptor phase of the cells was removed at 2,4,6, 8, 10, 12 and 24 hours and was replaced with fresh 37°C receptor phase. The amount of active in the receptor phase was determined by HPLC analysis. Graphs of the cumulative amount of the active that permeated the skin over the 24 hour period were drawn and the slope of the graphs represented the flux in µg/ml/h. The average flux values of six experimental cells and six control cells were compared. Entrapment of the actives in the Emzaloid® vesicles was confirmed with the use of confocal laser scanning microscopy. Results for the LGPS indicate an enhancement ratio in the order of 4,2 for 5-fluorouracil and 1,7 for idoxuridine when compared to the control cells. There were no viscosity changes in the LGPS samples containing 1% m/m of the active when compared with the blank LGPS samples, suggesting that no change in the internal structure of the LGPS occurred after the addition of the actives to it. There were also no significant changes in the pH of the samples. Entrapment of the actives in the Emzaloid® vesicles occurred readily. The Emzaloid® vehicle showed a lower rate of release for idoxuridine than the LGPS did during the VanKel dissolution experiments. This suggests that higher flux values would be obtained with the LGPS for idoxuridine than with the Emzaloid® formulation, since more drug was available for permeation through the skin. This was, however, not the case. The Emzaloid® formulation showed much higher flux values, showing that even with a smaller amount of active available to permeate the skin higher flux values were obtained. Enhancement ratios of 20,33 and 3,50 were achieved with the Emzaloid® formulation for 5-fluorouracil and idoxuridine respectively. The internal LGPS structure which mimics the skins lipid components remained unchanged after the addition of the actives. Greater success might be achieved with the LGPS for different model drugs, since the drugs' physicochemical properties play an important part in its permeation through the skin. The Emzaloid® formulation, which is closely related to liposomes and transfersomes, showed great potential for commercially marketable formulations for the drugs tested but further research on the formulation has to be done. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

Degassing and in situ formation of a mobile gas phase takes place when an aqueous phase equilibrated with a gas at a pressure higher than the subsurface pressure is injected in water-saturated porous media. This process, which has been termed supersaturated water injection (SWI), is a novel and hitherto unexplored means of introducing a gas phase into the subsurface. Herein is a first macroscopic account of the SWI process on the basis of continuum scale simulations and column experiments with CO2 as the dissolved gas. A published empirical mass transfer correlation (Nambi and Powers, Water Resour Res, 2003) is found to adequately describe the non-equilibrium transfer of CO2 between the aqueous and gas phases. Remarkably, the dynamics of gas-water two-phase flow, observed in a series of SWI experiments in homogeneous columns packed with silica sand or glass beads, are accurately predicted by traditional two-phase flow theory which allows the corresponding gas phase relative permeability to be determined. A key consequence of the finding, that the displacement of the aqueous phase by gas is compact at the macroscopic scale, is consistent with pore scale simulations of repeated mobilization, fragmentation and coalescence of large gas clusters (i.e., large ganglion dynamics) driven entirely by mass transfer. The significance of this finding for the efficient delivery of a gas phase below the water table in relation to the alternative process of in-situ air sparging and the potential advantages of SWI are discussed. SWI has been shown to mobilize a previously immobile oil phase in the subsurface of 3-phase systems (oil, water and gas). A macroscopic account of the SWI process is given on the basis of continuum-scale simulations and column experiments using CO2 as the dissolved gas and kerosene as the trapped oil phase. Experimental observations show that the presence of oil ganglia in the subsurface alters gas phase mobility from 2-phase predictions. A corresponding 3-phase gas relative permeability function is determined, whereas a published 3-phase relative permeability correlation (Stone, Journal of Cana Petro Tech, 1973) is found to be inadequate for describing oil phase flow during SWI. A function to predict oil phase relative permeability is developed for use during SWI at high aqueous phase saturations with a disconnected oil phase and quasi-disconnected gas phase. Remarkably, the dynamics of gas-water-oil 3-phase flow, observed in a series of SWI experiments in homogeneous columns packed with silica sand or glass beads, are accurately predicted by traditional continuum-scale flow theory. The developed relative permeability function is compared to Stone’s Method and shown to approximate it in all regions while accurately describing oil flow during SWI. A published validation of Stone’s Method (Fayers and Matthews, Soc of Petro Eng Journal, 1984) is cited to validate this approximation of Stone’s Method.

<p>The surface of cell membranes can display a high degree of lateral heterogeneity. This non-uniform distribution of constituents is characterized by mobile nanodomain clusters called rafts. Enriched by saturated phospholipids, cholesterol and proteins, rafts are considered to be vital for several important cellular functions such as signalling and trafficking, morphological transformations associated with exocytosis and endocytosis and even as sites for the replication of viruses. Understanding the evolving distribution of these domains can provide significant insight into the regulation of cell function. Giant vesicles are simple prototypes of cell membranes. Microdomains on vesicles can be considered as simple analogues of rafts on cell membranes and offer a means to study various features of cellular processes in isolation. </p><p>In this work, we employ a continuum approach to model the evolution of microdomains on the surface of Giant Unilamellar Vesicles (GUVs). The interplay of species transport on the vesicle surface and the mechanics of vesicle shape change is captured using a chemo-mechanical model. Specifically, the approach focuses on the regime of vesicle dynamics where shape change occurs on a much faster time scale in comparison to species transport, as has been observed in several experimental studies on GUVs. In this study, shape changes are assumed to be instantaneous, while species transport, which is modeled by phase separation and domain coarsening, follows a natural time scale described by the Cahn--Hilliard dynamics.</p><p>The curvature energy of the vesicle membrane is defined by the classical Canham--Helfrich--Evans model. Dependence of flexural rigidity and spontaneous curvature on the lipid species is built into the energy functional. The chemical energy is characterized by a Cahn--Hilliard type density function that intrinsically captures the line energy of interfaces between two phases. Both curvature and chemical contributions to the vesicle energetics are consistently non-dimensionalized.</p><p>The coupled model is cast in a diffuse-interface form using the phase-field framework. The phase-field form of the governing equations describing shape equilibrium and species transport are both fourth-order and nonlinear. The system of equations is discretized using the finite element method with a uniform cubic-spline basis that satisfies global higher-order continuity. For shape equilibrium, geometric constraints of constant internal volume and constant surface area of the vesicle are imposed weakly using the penalty approach. A time-stepping scheme based on the unconditionally gradient-stable convexity-splitting technique is employed for explicit time integration of nonlocal integrals arising from the geometric constraints.</p><p>Numerical examples of axisymmetric stationary shapes of uniform vesicles are presented. Further, two- and three-dimensional numerical examples of domain formation and growth coupled to vesicle shape changes are discussed. Simulations qualitatively depicting curvature-dependent domain sorting and shape changes to minimize line tension are presented. The effect of capturing the difference in time scales is also brought out in a few numerical simulations that predict a starkly different pathway to equilibrium.</p> / Dissertation

L'étude des propriétés de diffusion moléculaire d'un dopant dans une phase lamellaire orientée nous permet de mettre en évidence les caractéristiques de diffusion dans un milieux fortement anisotrope. En particulier, la variation continue de la dilution du système montre l'existence de deux régimes : un régime dilué où les molécules diffusent comme dans un solvant et un nouveau régime, très confiné, dans lequel les molécules diffusent comme des dopants membranaires. Le développement d'un modèle prenant en compte la fluidité des membranes nous permet d'interpréter ces résultats dans la majorité des cas et révèle l'importance de l'anisotropie des diffuseurs. Dans la seconde partie, nous nous intéressons à l'étude du mécanisme microscopique mis en jeu dans la transition smectique - cholestérique dans les cristaux liquides lyotropes. En utilisant un système déjà connu au laboratoire (DMPC/C12E5/H2O), nous validons expérimentalement le scénario de transition par débouclage de boucles de dislocations proposé théoriquement depuis plusieurs années. Nous proposons ainsi un système expérimental de choix pour l'étude de ce genre de transition, prédites dans différents domaines de la physique de la matière condensée. La visualisation directe des défauts, la mise en évidence de leur structure en boucle, l'observation de leur différentes organisations nous permet également de proposer l'existence de nouvelles phases dans le domaine des cristaux liquides lyotropes (smectique biaxe et phase TGB).

Le cancer est considéré comme l’une des principales causes de morbidité et de mortalité et, en Espagne, représente à lui seul 25% du taux de mortalité globale. Lorsqu’une personne et sa famille font l’expérience de traverser la phase avancée du cancer, celles-ci vivent un grand choc émotionnel où les souffrances physique, psychique et spirituelle peuvent être présentes. L’information donnée par les professionnels de la santé aux membres de la famille, incluant la personne atteinte, en ce qui concerne le diagnostic et le pronostic du cancer est maintenant plus fréquente dans le contexte méditerranéen. Il n'est pas clair, toutefois, comment cette nouvelle approche est vécue par les familles. C’est pourquoi, le but de cette recherche qualitative de type phénoménologique est d’explorer la signification de l’expérience de familles dont l’un des membres est atteint d’un cancer terminal, alors que tous connaissent le pronostic de la maladie. Les résultats obtenus reposent sur l’analyse en profondeur d’entrevues réalisées auprès de quatre couples. L’analyse des données, à l’aide de la méthode phénoménologique de Giorgi (1997), fait émerger deux thèmes centraux caractérisant la signification de cette expérience de la phase palliative de cancer, alors que l’information sur le mauvais pronostic est connue tant par la personne atteinte que sa famille. Le premier thème central est celui de vivre intensément la perte de la vie rêvée et comporte le vécu suite au choc du pronostic fatal, le fait de vivre constamment des sentiments et des émotions liés à différentes pertes telles que la tristesse, la frustration, l’inquiétude et l’incertitude, et l’espoir de ne pas souffrir. Le deuxième thème central qui ressort est le développement de stratégies par les couples participants afin de rendre leur vie plus supportable. Ces stratégies sont les suivantes : accueillir l’information et le soutien professionnel, retrouver une certaine normalité dans la vie quotidienne, profiter de la vie, recevoir l’aide de la famille et des amis, maintenir une communication cognitive et instrumentale ouverte, se protéger au niveau émotionnel et envisager l’avenir sans la personne aimée. Tous ces éléments, dans le contexte individuel de vie de chaque famille transforment chacun de ces vécus en une expérience unique qui doit être comprise et respectée comme telle par tous les professionnels de la santé impliqués. Les connaissances développées par cette recherche permettront aux infirmières de mieux comprendre l’expérience de la phase palliative du cancer pour des couples dont le diagnostic et le pronostic fatal sont connus par tous, ceci afin d’améliorer leur qualité des soins. Afin de poursuivre le développement du savoir infirmier, il est recommandé de poursuivre des études afin d’explorer plus en profondeur la communication au sein des couples. / Nowadays cancer constitutes one of the most prevalent morbilty and mortality causes, representing 25% of the total mortality rate in the Spanish context. When patients and their families live through the palliative phase of cancer, they experience a great emotional shock where physical, psychological and spiritual suffering may come at play. Having health professionals inform all family members including the patient about cancer diagnosis and related prognosis is a more and more common situation encountered within Mediterranean contexts. Nevertheless, it is not yet clear how this new approach to information disclosure is experienced by family members. Thus, the goal of this phenomenological research study was to explore and further understand the meaning these families assign to the experience of living through the terminal phase of cancer of a loved one, while being all informed about the related prognosis. The findings of this study rely on in-depth interviews with four couples (patient and spouse). The data analysis, developed upon the guidance provided by Giorgi’s (1997) phenomenological method, presents two central themes that characterize the meaning of the experience of the palliative phase of cancer, when information on the poor prognosis is known both by the patient and his/her family. The first theme concerns the fact of intensively living the loss of a dreamed-of life. This first theme is mainly develop around the lived experience regarding the shock associated with the fatal prognosis, the constant feelings and emotions such as sadness, frustration, worry and uncertainty, and related to different losses, as well as the hope for an absence of suffering. The second main theme is related to the strategies developed by these couples as they face the situation and try to make their lives as manageable as possible: to gather health professionals’ information and support, to search for a certain “normality” in their everyday life, to enjoy life, to get help from relatives and friends, to keep an open cognitive and instrumental communication dynamics, to emotionally protect themselves and to imagine and construct a future time where the loved one will no longer be present. All these elements of each family’s individual contexts transform their lived experiences into unique experiences that must be understood and respected as such by all health professionals involved. Knowledge developed by this research study will allow nurses to better understand the experience of the palliative phase of cancer for couples sharing the information on diagnosis and prognosis, aiming at improving their quality of care. Several suggestions, related the development of sounder nursing knowledge, evolve from these results in regards to the need to develop later studies that would further explore communication in the context of couple dynamics.