付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム / 京都大学 / 新制・課程博士 / 博士(医学) / 甲第23789号 / 医博第4835号 / 新制||医||1057(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邊 直樹, 教授 松田 道行, 教授 寺田 智祐 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

[pt] A natureza física do amortecimento nos solos e sua formulação matemática têm sido objeto de intensa pesquisa ao longo do último meio século. Estes vários ensaios para explicar os mecanismos de perda de energia durante os episódios de vibração surgem da importância do amortecimento no problema de propagação de ondas para fins de engenharia. O objetivo deste estudo é propor uma maneira alternativa de analisar o fenômeno do amortecimento em solos, considerando o problema de vibração como um problema matemático poromecânico acoplado onde deslocamentos relativos e velocidades entre as duas fases que compõem o material geológico, fluido e sólido, gera forças de interação nas interfaces e pode desempenhar um papel importante na perda de energia vibracional dos solos. Presume-se que o problema seja resolvido na escala de poros, concentrando-se nas condições cinéticas e dinâmicas na interface entre o esqueleto sólido e o fluido de saturação. Variáveis adimensionais que misturam propriedades fluidas e sólidas permitem o acoplamento do problema, resultando no surgimento de uma massa aparente, coeficientes de amortecimento e rigidez que serão introduzidos posteriormente nas equações de movimento. A equação proposta de amortecimento será então justaposta a testes de laboratório e uma comparação com os modelos mais importantes da literatura será feita usando o software DEEPSOIL para análise de propagação de ondas para verificar sua validade. / [en] The physical nature of damping in soils and its mathematical formulation attempts have been the subject of intensive researches along the last half century. These several trials to explain the mechanisms of energy loss during vibration episodes arise from the importance of damping in the wave propagation problem for engineering purposes. The aim of this study is to propose an alternative way to analyze the damping phenomenon in soils by looking at the vibration problem as a coupled poromechanical mathematical problem where relative displacements and velocities in between the two phases that compose the geological material, fluid and solid, generates interaction forces at the interfaces and can play an important role in the vibrational energy loss of soils. The problem is assumed to be solved at the pore scale, focusing on the kinetic and dynamic conditions at the interface in between the solid skeleton and the saturating fluid. Dimensionless variables that mixes fluid and solid properties allows the coupling of the problem, resulting on the rising of an apparent mass, damping and stiffness coefficients that will be introduced later in the equations of motion. The proposed equation of damping will thus be juxtaposed to laboratory tests data and a comparison with the most important models in the literature will be done further using the software DEEPSOIL for wave propagation analysis to check its validity.

Breast cancer is the second leading cause of death in United States. Using 2D-HPLE, a novel separation technology, G-protein coupled receptor-associated sorting protein 1(GASP-1) was identified in sera of patients with early stage cancer, while it could not be detected in sera from healthy individuals. This was the first indication that GASP-1 was positively correlated with breast cancer. However, the function of GASP-1 in breast cancer was unknown. In this study, I verified the 2D-HPLE results by quantifying the expression level of GASP-1 in sera and tissue specimens of cancer patients using specific antibodies against GASP-1. A GASP-1 specific ELISA was developed and used to quantify GASP-1 levels in cancer patient sera. Immunohistochemistry was performed to verify and localize GASP-1 expression in tumor. I also characterized the tumorigenic potential of GASP-1 andidentified the signaling pathways mediated by GASP-1 in breast cancer cells in vitro.GASP-1 expression levelsin MDA-MB-231 cells were modified by transfecting cells with anti-GASP-1 shRNA and over-expression plasmids. Stable cell lines were prepared and their tumorigenic potential was evaluated using cell proliferation, migration, and colony formation assays. These cells were analyzed for markers used to identify epithelial to mesenchymal transition (EMT) using RT-PCR and western blot. They were also analyzed for NFkappaB activity, src phosphorylation, and GPR30 expression. The results showed that GASP-1 was over-expressed in sera and tissue specimens of breast cancer patients and other cancer types including brain, lung, liver and pancreatic cancer and that it correlated with early stage disease. GASP-1 positively regulated migration, and is required for cell proliferation and colony formation. GASP-1 is also necessary for the expression of EMT marker slug, increases NFkappaB activity and GPR30 expression level, while decreases the inhibitory phospho-src Tyr 530. I conclude that GASP-1 is a nearly marker for multiple cancer types. GASP-1 promotes tumorigenesis in breast cancer, possibly through multiple cancer related signaling pathways. These findings may contribute to our understanding of the mechanism of breast cancer tumorigenesis and identify new biomarkers that can be used for diagnosis and therapy of cancer. / Biology

no / The interface tribo-layer (ITL) in an automotive brake friction pair is a layer of material created from transfer films, wear particles, and surface transformations between the rotor and stator. Its presence in a brake friction interface has been proven, e.g. by the existence of a temperature ‘jump’ across the friction interface. In this paper two static transient heat transfer models which force one dimensional heat flow, have been used to investigate the ITL behaviour and obtain an equivalent thermal conductance value. The ITL equivalent thermal conductance value is important as it reduces computational requirements and software restrictions encountered in the physical model of the ITL. This approach is developed into a more realistic two-dimensional coupled temperature-displacement model using commercial FEA software (ABAQUS). A newly developed relationship that utilises the contact pressure, real contact area, and the ITL equivalent thermal conductance, has been used to estimate the effective thermal conductance at the friction interface. Subsequently the effective thermal conductance relationship is combined with the 2-D coupled temperaturedisplacement model. The combination of this relationship with the 2D FE model provides a new method of heat partition prediction in brake friction pairs. Heat partition at a brake friction interface is confirmed to be neither uniform nor constant with time. / IMechE / The full text will not be made available in Bradford Scholars due to the publisher's copyright policies.

We clear up two issues regarding the eigenvalue problem for the Manakov system; these problems relate directly to the existence of the soliton [sic] effect in fiber optic cables. The first issue is a bound on the eigenvalues of the Manakov system: if the parameter ξ is an eigenvalue, then it must lie in a certain region in the complex plane. The second issue has to do with a chirped Manakov system. We show that if a system is chirped too much, the soliton effect disappears. While this has been known for some time experimentally, there has not yet been a theoretical result along these lines for the Manakov system. / Ph. D.

Three-dimensional gravity-capillary steady waves on water of finite-depth, which are uniformly translating in a horizontal propagation direction and periodic in a transverse direction, are considered. The exact Euler equations are formulated as a spatial dynamic system in which the variable used for the propagating direction is the time-like variable. The existence of the solutions of the system is determined by two non-dimensional constants: the Bond number b and λ (the inverse of the square of the Froude number). The property of Sobolev spaces and the spectral analysis show that the spectrum of the linear part consists of isolated eigenvalues of finite algebraic multiplicity and the number of purely imaginary eigenvalues are finite. The distribution of eigenvalues is described by b and λ. Assume that C₁ is the curve in (b,λ)-plane on which the first two eigenvalues for three-dimensional waves collide at the imaginary axis, and that the intersection point of the curve C₁ with the line λ=1 is (b₀,1) where b₀>0. Two cases (b₀,1) and (b,λ) â C₁ where 0< b< b₀ are investigated. A center-manifold reduction technique and a normal form analysis are applied to show that for each case the dynamical system can be reduced to a system of ordinary differential equations with finite dimensions. The dominant system for the case (b₀,1) is coupled Schrödinger-KdV equations while it is a Schrödinger equation for another case (b,λ) â C₁. Then, from the existence of the homoclinic orbit connecting to the two-dimensional periodic solution (called generalized solitary wave) for the dominant system, it is obtained that such generalized solitary wave solution persists for the original system by using the perturbation method and adjusting some appropriate constants. / Ph. D.

Wildfire activity has increased in recent years in the United States, endangering both environment and society. Appropriate management of this phenomenon is only achievable with a thorough understanding of the critical factors influencing wildfire activity in each region. In three essays, I use statistical and mathematical models to examine wildfires and propose solutions to mitigate their impact on society. In the first essay, I focused on building a systematic framework for modeling wildfire as a coupled human-natural system. I employ system dynamics modeling, which was previously applied in various fields, including healthcare, sustainability, and disaster mitigation. I show how, in the absence of exogenous factors such as temperature or lightning, the human perception of fire danger may establish a feedback loop that can yield significant trends such as fluctuation or even fluctuation with rising amplitude when linked with the natural system. This conclusion is counter-intuitive, given that the human contribution to wildfire is typically described in the literature using constant or semi-constant variables. Additionally, I analyzed the impact of three important fire protection measures on reducing burning rates (prescribed burning, enhancing immediate suppression accomplishment, and regulating the rate of WUI growth). The research concludes that appropriately integrating several policies can result in a synergistic effect that is greater than the sum of the effects of the individual policies. The second essay calibrates the model built in the first essay and examines wildfire trends across the contiguous United States. The simulation results closely match the real data, and the model serves as a foundation for data-driven policy research. To be more precise, I fit the model to each state separately and then compare the model's goodness of fit. Following that, I examine the influence of various policies and scenarios on wildfire behavior. In the scenario, I examine the effect of maintaining constant temperatures and precipitation levels relative to the average values for these variables over the last century. For the policy analysis, I examine the influence of three policies on each state (prescribed burning, increasing immediate suppression achievement, and regulating the rate of WUI development). Here, I provide state-specific suggestions about the primary factors that contribute to wildfires and the most effective policies for each state. In the third essay, I have implemented the Oregon wildfire history dataset and integrated it with two other aerial datasets, including meteorological data gathered by weather stations located around the state and counties. Then, using hierarchical modeling on over 10,000 wildfire ignitions, I developed a classification system for determining if a given fire has the potential to grow major or not. However, utilizing a huge dataset and a variety of resources presents several obstacles, such as the presence of missing data. I imputed the missing numbers using a sophisticated mathematical approach called "Predictive Mean Matching". / Doctor of Philosophy / Wildfire activity has increased in recent decades in the United States, which put many people in danger. Climate change, the Settlement of people in the Wildland Urban Interface, and an increase in vegetation density each play a role in this increase. In this dissertation, we discuss the wildfire in the United States in three essays. In the first essay, we develop a mathematical model to show how humans and nature affect wildfire activity in any area. We then test different major wildfire management policies on the hypothetical situation to compare the outcome of these policies together. In the second essay, we use the model developed in the essay (with some minor changes) to model the wildfire activity in 11 states of the U.S. which has the most wildfire activity in recent years. First, we show that our model can replicate the wildfire activity in each state. Second, we test the effect of wildfire mitigation policies on each state. This essay proposes state-specific policy recommendations based on the main reasons for the increase in wildfire activity in each state. Finally, in the third essay, we develop a statistical model to predict the existence of large wildfires in the next month in Oregon counties. We use climate, land, and fire history data to develop a warning system. Policymakers can use this system to move the fire suppression resources to counties with a high probability of experiencing large wildfires over the next month. Finally, all essays aim to enhance our understanding of the reasons for the increase in wildfire activity in recent years and suggest finding the appropriate way to deal with this change to reduce the effect of wildfire on human life.

Plasmonic nanostructures can enhance light-matter interactions in the subwavelength domain, which is useful for photodetection, light emission, optical biosensing, and spectroscopy. However, conventional plasmonic devices are optimized to operate in a single wavelength band, which is not efficient for wavelength-multiplexed operations and quantum optical applications involving multi-photon nonlinear processes at multiple wavelength bands. Overcoming the limitations of single-resonant plasmonics requires development of plasmonic devices that can enhance the optical interactions at the same locations but at different resonance wavelengths. This dissertation comprehensively studies the theory, design, and applications of such devices, called "multiresonant plasmonic systems with spatial mode overlap". We start by a literature review to elucidate the importance of this topic as well as its current and potential applications. Then, we briefly discuss the fundamentals of plasmonic resonances and mode hybridization to thoroughly explore, classify, and compare the different architectures of the multiresonant plasmonic systems with spatial mode overlap. Also, we establish the black-box coupled mode theory to quantify the coupling of optical modes and analyze the complicated dynamics of optical interactions in multiresonant plasmonic systems. Next, we introduce the nanolaminate plasmonic crystals (NPCs), wafer-scale metamaterials structures that support many (>10) highly-excitable plasmonic modes with spatial overlap across the visible and near-infrared optical bands. The enabling factors behind the NPC's superior performance as multiresonant systems are also theoretically and experimentally investigated. After that, we experimentally demonstrate the NPCs application in simultaneous second harmonic generation and anti-Stokes photoluminescence (ASPL) with controllable nonlinear emission properties. By designing specific non-linear optical experiments and developing advanced ASPL models, this work addresses some important but previously unresolved questions on the ASPL mechanism as well. Finally, we conclude the dissertation by discussing the potential applications of out-of-plane plasmonic systems with spatial mode overlap in wavelength-multiplexed devices and presenting some preliminary results. / Doctor of Philosophy / Emergence of electronic devices such as cellphones and computers has revolutionized our lifestyles over the past century. By manipulating the flow/storage of electrons at the nanometer scale, electronic components can be very compact, but their speed and energy performance is ultimately limited due to ohmic losses and finite velocity of the electrons. In parallel, photonic devices and circuits have been proposed that by molding the flow of light can overcome the mentioned limitations but are not as integrable as their electronic counterparts. Plasmonics is an emerging research field that combines electronics and photonics using nanostructures that can couple the light waves to the free electrons in metals. By confining the light at deep subwavelength scales, plasmonic devices can highly enhance the light-matter interactions, with applications in ultrafast optical communications, energy-harvesting, optical sensing, and biodetection. Conventionally, plasmonic devices are optimized to operate with a single light color, which limits their performance in wavelength-multiplexed operations and ultrafast non-linear optics. For such applications, it is far more efficient to use the more advanced "multiresonant plasmonic systems with spatial mode overlap" that can enhance the optical interactions at the same locations but for multiple light colors. This dissertation comprehensively studies these systems in terms of the fundamental concepts, design ideas, and applications. Our work advances the plasmonic field from both science and technology perspectives. In particular, we explore and classify the strategies of building multiresonant plasmonic systems with spatial mode overlap for the first time. Also, we establish the black-box coupled mode theory, a novel framework for analysis and design of complicated plasmonic structures with optimized performance. Furthermore, we introduce the "nanolaminate plasmonic crystals" (NPCs), large area and cost-effective devices that can enhance the optical processes for both visible and near-infrared lights. Finally, we demonstrate NPCs ability in simultaneous frequency-doubling and broadband emission of light and come up with advanced theoretical models that can explain the light generation and color conversion in plasmonic devices.

Tesis por compendio / [ES] La simulación de transitorios forma parte del proceso de licenciamiento de una central nuclear. Esto implica que los códigos, así como los modelos utilizados deben estar verificados y validados. Normalmente, esta simulación se realiza con códigos termohidráulicos de planta que tienen una definición de la cinética del reactor muy simplificada con cinética puntual o unidimensional. Una mejora importante en la simulación de transitorios base de diseño se basa en la utilización de códigos acoplados termohidráulico-neutrónicos, que permiten obtener resultados sobre la evolución de la potencia del reactor en tres dimensiones. Los códigos neutrónicos 3D necesitan parámetros de la cinética y secciones eficaces también en 3D ajustados al punto del ciclo que se quiere simular y que abarquen las condiciones que se alcancen durante el transitorio. Por otro lado, para poder verificar tanto los códigos como los modelos es necesario llevar a cabo una serie de simulaciones de diferentes transitorios. De esta manera, se comprueba cómo funciona el código acoplado en diferentes condiciones de operación y simulación. Esta tesis contribuye al conocimiento del uso de códigos termohidráulico-neutrónicos acoplados en la simulación de transitorios base de diseño (Design Basis Accidents -DBAs). Los códigos mejorados y verificados son los códigos termohidráulicos RELAP5, TRAC-BF1 y TRACE y el código neutrónico PARCS. Los parámetros neutrónicos necesarios en PARCS se han obtenido aplicando una metodología que simplifica el modelo del núcleo. Esta metodología, ya desarrollada e implementada, denominada SIMTAB, se ha mejorado, tanto en las posibilidades de aplicación de la misma como en la optimización y actualización de la programación del código fuente. Los transitorios analizados con los códigos RELAP5/PARCS acoplados son: transitorio por expulsión de barra de control y transitorio de inyección de boro en un reactor PWR. Con los códigos TRAC-BF1/PARCS acoplados se ha analizado el transitorio por disparo de turbina en la C. N. Peach Bottom. Para llevar a cabo las simulaciones con TRAC-BF1/PARCS se ha implementado el acoplamiento de ambos códigos, puesto que originalmente el código TRAC-BF1 no estaba preparado para ello. El análisis de inestabilidades en reactores BWR se ha realizado con RELAP5/PARCS en dos reactores BWR: C. N. Peach Bottom y C. N. Ringhals 1. Para ello se ha desarrollado una metodología de análisis que abarca desde la definición del modelo termohidráulico y del modelo neutrónico hasta el análisis de las señales simuladas obtenidas con PARCS. La metodología también incluye la aplicación de diferentes perturbaciones basadas en los modos Lambda y en el análisis de las señales reales de planta. Se ha llevado a cabo un estudio del modelo para el cálculo de la concentración de Boro en los códigos termohidráulicos y se ha mejorado este modelo en el código TRAC-BF1, incorporando un nuevo método de resolución en el código fuente. El modelo para el cálculo del calor de desintegración también se ha revisado y mejorado en los códigos TRAC-BF1 y PARCS. En ambos casos se ha implementado el modelo ANS 2005. El análisis de sensibilidad e incertidumbre está ligado a los resultados de los códigos de mejor estimación como los mejorados en esta tesis. Este análisis se ha realizado sobre los transitorios de expulsión de barra en un reactor PWR y el transitorio de caída de barra en un reactor BWR con RELAP5/PARCS. Los resultados de estos trabajos aportan una metodología de aplicación para la simulación correcta de transitorios con códigos acoplados. Además, ha servido para detectar y subsanar deficiencias en los códigos, y de esta manera disponer de unos códigos de mejor estimación preparados para el análisis de transitorios base de diseño. / [CA] La simulació de transitoris forma part del procés de llicenciament d'una central nuclear. Això implica que els codis, així com els models utilitzats han d'estar verificats i validats. Normalment, aquesta simulació es realitza amb codis termohidràulics de planta que tenen una definició de la cinètica del reactor molt simplificada amb cinètica puntual o unidimensional. Una millora important en la simulació de transitoris base de disseny es basa en la utilització de codis acoblats termohidràulic-neutrònics, que permeten obtindre resultats sobre l'evolució de la potència del reactor en tres dimensions. Els codis neutrònics 3D necessiten paràmetres de la cinètica i seccions eficaces també en 3D ajustats al punt del cicle que es vol simular i que abasten les condicions que s'aconseguisquen durant el transitori. D'altra banda, per a poder verificar tant els codis com els models és necessari dur a terme una sèrie de simulacions de diferents transitoris. D'aquesta manera, es comprova com funciona el codi acoblat en diferents condicions d'operació i simulació. Aquesta tesi contribueix al coneixement de l'ús de codis termohidràulic-neutrònics acoblats en la simulació de transitoris base de disseny. Els codis millorats i verificats són els codis termohidràulics RELAP5, TRAC-BF1 i TRACE i el codi neutrònic PARCS. Els paràmetres neutrònics necessaris en PARCS s'han obtingut aplicant una metodologia que simplifica el model del nucli. Aquesta metodologia, ja desenvolupada i implementada, denominada SIMTAB, s'ha millorat, tant en les possibilitats d'aplicació de la mateixa com en l'optimització i actualització de la programació del codi font. Els transitoris analitzats amb els codis RELAP5/PARCS acoblats són: transitori per expulsió de barra de control i transitori d'injecció de bor en un reactor PWR. Amb els codis TRAC-BF1/PARCS acoblats s'ha analitzat el transitori per disparament de turbina en la C. N. Peach Bottom. Per a dur a terme les simulacions amb TRAC-BF1/PARCS s'ha implementat l'acoblament de tots dos codis, ja que originalment el codi TRAC-BF1 no estava preparat per a això. L'anàlisi d'inestabilitats en reactors BWR s'ha realitzat amb RELAP5/PARCS en dos reactors BWR: C. N. Peach Bottom i C. N. Ringhals 1. Per a això s'ha desenvolupat una metodologia d'anàlisi que abasta des de la definició del model termohidràulic i del model neutrònic fins a l'anàlisi dels senyals simulats. La metodologia també inclou l'aplicació de diferents pertorbacions basades en els modes Lambda i en l'anàlisi dels senyals reals de planta. S'ha dut a terme un estudi del model per al càlcul de la concentració de Bor en els codis termohidràulics i s'ha millorat aquest model en el codi TRAC-BF1, incorporant un nou mètode de resolució en el codi font. El model per al càlcul de la calor de desintegració també s'ha revisat i millorat en els codis TRAC-BF1 i PARCS. En tots dos casos s'ha implementat el model ANS 2005. L'anàlisi de sensibilitat i incertesa està lligat als resultats dels codis de millor estimació com els millorats en aquesta tesi. Aquesta anàlisi s'ha realitzat sobre els transitoris d'expulsió de barra en un reactor PWR i el transitori de caiguda de barra en un reactor BWR amb RELAP5/PARCS. Els resultats d'aquests treballs aporten una metodologia d'aplicació per a la simulació correcta de transitoris amb codis acoblats. A més, ha servit per a detectar i esmenar deficiències en els codis, i d'aquesta manera disposar d'uns codis de millor estimació preparats per a l'anàlisi de transitoris base de disseny. / [EN] The simulation of transients is part of the licensing process of a nuclear power plant. This implies that the codes as well as the models used must be verified and validated. Normally, this simulation is performed with thermalhydraulic plant codes that have a very simplified definition of reactor kinetics with point or one-dimensional kinetics. An important improvement in the simulation of design-basis transients rely on the use of thermohydraulic-neutronic coupled codes, which allow to obtain results of the evolution of the reactor power in three dimensions. The 3D neutron codes need parameters of the kinetics and cross-sections also in 3D adjusted to the point of the cycle to be simulated that must cover the conditions reached during the transient. On the other hand, to be able to verify both the codes and the models it is necessary to carry out a series of simulations of different transients. In this way, it is checked how the coupled code works in different operating and simulation conditions. This thesis contributes to increase the knowledge of the use of thermalhydraulic-neutronic coupled codes in the simulation of design basis accidents (DBAs). The improved and verified codes are the thermalhydraulic codes RELAP5, TRAC-BF1 and TRACE and the neutronic code PARCS. The necessary neutronic parameters in PARCS have been obtained by applying a methodology that simplifies the core model. This methodology, already developed and implemented, called SIMTAB, has been improved in this thesis in its application possibilities and also in the optimization and updating of the source code. The transients analyzed with RELAP5/PARCS coupled code are: control rod ejection transient and boron injection transient in a PWR reactor. With TRAC-BF1/PARCS coupled code, the transient analyzed is the turbine trip transient in Peach Bottom NPP. To carry out the simulations with TRAC-BF1/PARCS, the coupling of both codes has been implemented before, since originally the TRAC-BF1 code was not prepared for it. The analysis of instabilities in BWR reactors has been carried out with RELAP5/PARCS in two BWR reactors: Peach Bottom NPP and Ringhals 1 NPP. A methodology has been developed which cover from the definition of the thermalhydraulic model and the neutron model to the simulated signal analysis. The methodology also includes the application of different disturbances based on Lambda modes and the analysis of real plant signals. A study of the model for the calculation of the Boron concentration in thermalhydraulic codes has been carried out. This model has been improved in the TRAC-BF1 code, incorporating a new resolution method in the source code. The model for the calculation of the decay heat has also been revised and improved in TRAC-BF1 and PARCS codes. In both cases, the ANS 2005 model has been implemented. The sensitivity and uncertainty analysis is linked to the results of the best estimate codes such as those improved in this thesis. This analysis has been carried out on the control rod ejection transients in a PWR reactor and the control rod drop transient in a BWR reactor with RELAP5/PARCS. The results of these works provide an application methodology for the correct simulation of transients with coupled codes. In addition, it has been used to detect and correct deficiencies in the codes, and therefore, to have better estimate codes prepared for the analysis of design-basis transients. / Barrachina Celda, TM. (2020). Aportaciones y Mejoras en los Códigos Termohidráulicos y Neutrónicos de Estimación Óptima RELAP5, TRAC-BF1, TRACE Y PARCS [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/158745 / Compendio

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