京都大学 / 新制・課程博士 / 博士(医学) / 甲第24505号 / 医博第4947号 / 新制||医||1064(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 渡邉 大, 教授 林 康紀, 教授 井上 治久 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Infrastructure in the form of payment systems is a necessity to allow for payments to reach from payer to payee, but it is also subject to product differentiation between banks. In the euro countries, a domestic-integration zone termed SEPA that consolidates payment systems into a singular system has been regulated, providing market efficiencies for customers and companies. However, in Sweden, banks use unstandardized file communication that is costly for stakeholders to interface against, and is becoming increasingly difficult to oversee. With the introduction of novel payment solutions (e.g. mobile payments), there is also an increase in competitors that access the infrastructure. A rising customer demand for faster, global and integrated payments has been identified. This increased fragmentation of the market requires large investments for banks and reduces customer mobility, which motivates the need for consolidation of payment flows. The purpose of this thesis is to identify the roles of stakeholders in the clearing and settlement mechanism, and to identify the drivers and inhibitors that affect business decisions to change the systems in place. These results are categorized according to co-opetition theory. Furthermore, the thesis brings forward the global industry standard for financial messaging ISO 20022 to the business context, and discusses its implications in the Swedish market from an interoperability point of view. The study has been conducted using mixed methods with a qualitative approach. It includes: Analysis of documents and materials, non-participative observation, interviews with 9 industry experts and an in-depth case study of real-time payments in Sweden (Betalningar i Realtid). Results show that actors’ perceptions of one another are ambiguous, but cooperation is well-established and reaps many positive effects for firms. Co-opetition activities in banks are inclined to drive change, while competitive moves are likely to leave the system unchanged. Co-opetition is only possible under certain pre-agreed rules such as differentiation by implementing flexible payment solutions. The main implication for migration to an improved, standardized payment flow is connected to the governance of infrastructure. It is suggested that if agreements between stakeholders are not reached in due time then SEPA-like regulation put forward by higher instances is a likely outcome.

The 15q13.3 microdeletion is a common genetic disorder associated with multiple neurodevelopmental disorders including autism spectrum disorder, epilepsy, and schizophrenia. Patients have diverse clinical presentations, often prompting genetic assays that identify the CNV in the clinic. This late-stage screening leaves a considerable gap in our understanding of the prenatal and prediagnostic developmental impairments in these individuals, providing a barrier to understanding the disease pathobiology. We provide the first investigation into embryonic brain development of individuals with the 15q13.3 microdeletion by generating multiple 3D neural organoid models from the largest clinical cohort in reported literature. We incorporated unguided and guided forebrain organoid models into our multi-transcriptomic phenotyping pipeline to uncover changes in cell type emergence and disruptions to circuit development, all of which had underlying changes to cell adhesion pathways. Specifically, we identified accelerated growth trajectories in 15q13.3del unguided neural organoids and used single cell RNA sequencing to identify changes in radial glia dynamics that affect neurogenesis. We measured changes in the pseudotemporal trajectory of matured unguided neural organoids, and later identified disruptions in synaptic signaling modules amongst the primary constituents to neural circuitry, excitatory and inhibitory neurons. We leveraged dorsal and ventral forebrain organoid models to better assess circuit dynamics, as they faithfully produce the excitatory and inhibitory neurons in the pallium and subpallium, respectively. We then used the entire 15q13.3del cohort and performed bulk RNA sequencing on each tissue type at two timepoints and discovered convergence on transcriptional dysregulation and disruptions to human-specific zinc finger proteins localized to chromosome 19. We also identified cell type-specific vulnerabilities to DNA damage and cell migration amongst the dorsal and ventral organoids, respectively, which was consistent with the excitatory and inhibitory neural subpopulations amongst the unguided neural organoids scRNA Seq, respectively. We then examined neuron migration in a 3D assembloid model by sparsely labeling dorsal-ventral forebrain organoids from multiple genotype-lineage combinations. Light sheet microscopy identified deficits in inhibitory neuron migration and morphology, but not migration distance, suggesting a complex disruption to cortical circuitry. This novel combination of cell type characterization, pathway identification, and circuitry phenotyping provides a novel perspective of how the 15q13.3 deletions impair prenatal development and can be applied to other NDD models to leverage understanding of early disease pathogenesis. / Dissertation / Doctor of Science (PhD) / The development of the human brain is a highly complex and tightly regulated process that requires the participation of multiple cell types throughout development. Disturbances to the emergence, differentiation, or placement of these cell types can cause disruptions and local miswiring of neural circuits, which is often associated with neurodevelopmental disorders (NDDs). The 15q13.3 microdeletion syndrome is a highly complex condition associated with multiple NDDs and has seldom been studied in a human context. To address this, we used stem cells derived from a 15q13.3 microdeletion syndrome cohort and their typically developing familial controls to generate unguided (“whole brain”) and region-specific organoids to investigate early fetal development across time. We used the largest 15q13.3 microdeletion cohort in reported literature to identify shared disruptions in early developmental milestones such as neurogenesis, neural migration, and neural patterning. We identified expansion of specific cell populations, including progenitors that later give rise to mature neurons. Abnormalities persisted in more mature cell populations, including the inhibitory neurons responsible for establishing critical microcircuitry in the human cortex. By generating guided organoids that enrich for excitatory and inhibitory neural populations, we were able to merge the models to form assembloids, where we captured early migratory and morphological deficits in inhibitory neuron populations, which is supported by the multi-transcriptomics experiments performed in both organoid models. This study provides a framework for examining fetal development in a neurodevelopmental disorder context. By using the 15q13.3 microdeletion background, we found novel disruptions in cell type emergence and circuit formation previously unreported in mouse or 2D neuron models, highlighting the utility of the phenotyping platform for disease modeling.

Biomedical optics is a rapidly expanding field of research focusing on the development of methods to detect, diagnose, and treat disease using light. While there are a myriad of optical systems that have been developed for biological tissue imaging, optical diagnostics, and optical therapeutics, all of these methods suffer severely limited penetration depths due to attenuation of light by tissue constituent chromophores, including cells, water, blood, and protein structures. Tissue optical clearing is a recent area of study within biomedical optics and photonics, where chemical agents have been used to alter tissue optical properties, reducing optical absorption and scattering and enabling light delivery to and collection from deeper tissue regions. However, there are concerns as to the safety and efficacy of these chemical clearing agents in vivo, especially in the skin, where the projective barrier function of the stratum corneum must be removed. Mechanical optical clearing is a recently developed technology which utilizes mechanical loading to reversibly modify light transport through soft tissues, and much of the work published on this technique has focused on applications in skin tissue. This clearing technique enables deeper light delivery into soft tissues but does not require use of exogenous chemicals, nor does it compromise the skin barrier function. While this clearing effect is thought to be resultant from interstitial water and blood transport, the underlying mechanism has not been concretely identified nor characterized. The hypothesis of this body of work was that interstitial transport of tissue chromophores (e.g. water and blood) causes intrinsic optical property changes, reduces tissue optical absorption and scattering, and improves light delivery in diagnostic applications. To test this hypothesis, we first developed a mathematical framework to simulate mechanical optical clearing, using both mechanical finite element models and optical Monte Carlo simulations. By directly simulating interstitial water transport in response to loading, data from mechanical simulations was combined with optical Monte Carlo simulations, which enabled prediction of light transmission measurements made during mechanical indentation experiments. We also investigated changes in optical properties during mechanical indentation using diffuse reflectance spectroscopy. These studies used controlled flat indentation by a fiberoptic probe to dynamically measure intrinsic optical properties as they changed over time. Finally, we apply mechanical optical clearing principles to functional near-infrared spectroscopy for neuroimaging. By building a prototypical mechanical optical clearing device for measuring cerebral hemodynamics, we demonstrated that mechanical optical clearing devices modify measured cerebral hemodynamic signals in human subjects, improving signal quality. / Ph. D.

Thesis (MScConEcol (Conservation Ecology and Entomology))--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Invasive alien plants (IAPs) reduce streamflow and threaten the biodiversity of South Africa’s Cape Floristic Region. Up-to-date information on invasive vegetation is required for land management agencies to formulate policies and make appropriate resource management decisions. Invasion maps are typically not updated often enough because of the time and expenses required to do so. As a result, invasion maps for South Africa are limited to coarse resolution data or isolated small scale studies. Invasive alien plants change the landscape by destabilizing catchments and thereby increasing soil erosion, altering fire regimes and hydrology, as well as changing the physical and chemical composition of the soil. Information on IAPs is needed at a landscape scale. Remote sensing is a powerful tool that can be used to characterise landscapes in a biologically meaningful manner. The Normalised Difference Vegetation Index (NDVI) was used to create an up-to-date invasion map of the Agulhas Plain, lying at the heart of the species rich Cape Floristic Region. This information was combined with actual evapotranspiration data from the Surface Energy Balance Algorithm for Land (SEBAL) study done by Water Watch and the Council for Scientific and Industrial Research. The results showed that invasive vegetation uses more water than natural fynbos vegetation and that the greatest amount of water would be made available by clearing the invaded deep sands on the Agulhas Plain. These deep sand areas conflict with the priority areas of the Working for Water programme. This IAP eradication programme targets sparsely invaded upland areas for long-term sustainability. The recommendation of this study is to clear invaded wetland and riparian areas as these zones yield the greatest hydrological benefit per hectare and meet the priorities of Working for Water. Overall, 36 million cubic meters of water would be made available by clearing the Agulhas Plain. It can be concluded that there is a significant hydrological benefit to clearing invasive alien vegetation on the Agulhas Plain. / AFRIKAANSE OPSOMMING: Indringerplante (IP) verminder stroomvloei en bedreig die biodiversiteit van Suid-Afrika se Kaapse Floristiese Streek. Die nuutste inligting oor uitheemse plantegroei is nodig vir grondbestuuragentskappe om beleide te formuleer vir die neem van toepaslike hulpbronbestuur besluite. As gevolg van die tyd en uitgawes wat nodig is om indringingskaarte op te dateer, word dit gewoonlik nie dikwels genoeg gedoen nie. Dus is indringingskaarte vir Suid-Afrika beperk tot growwe resolusie data of geïsoleerde kleinskaal studies. Indringerplante verander die landskap deur opvangsgebiede te destabiliseer en sodoende te lei tot gronderosie, verandering van vuurregimes en hidrologie, sowel as die verandering in die fisiese en chemiese samestelling van die grond. Inligting oor IP is nodig op 'n landskapskaal. Afstandswaarneming is 'n kragtige tegniek wat gebruik kan word om landskappe op 'n biologies betekenisvolle manier te karakteriseer. Die Normalised Difference plantegroei-indeks (NDVI) is gebruik om 'n opgedateerde indringingskaart van die Agulhas-vlakte, wat in die hart van die spesiesryke Kaapse Floristiese Streek lê, te skep. Hierdie inligting is gekombineer met die werklike evapotranspirasie data vanaf die Surface Energy Balance Algorithm for Land (SEBAL) studie gedoen deur Water Watch en die Raad vir Wetenskaplike en Nywerheidnavorsing. Die resultate het getoon dat uitheemse plantegroei meer water gebruik as natuurlike fynbosplantegroei en dat die grootste hoeveelheid van hierdie water beskikbaar gestel sal word deur IP op diepsand op die Agulhas-vlakte skoonte maak. Hierdie diepsand areas is in konflik met die prioriteitsgebiede van die Werk vir Water-program. Hierdie IP uitroeiingsprogram fokus op yl ingedringde berggebiede vir langtermyn volhoubaarheid. Die aanbeveling van hierdie studie is om duidelik ingedringde vleilande en oewergebiede skoon te maak, siende dat hierdie sones die hoogste opbrengs en die grootste hidrologiese voordeel per hektaar bied, en voldoen aan die prioriteite van Werk vir Water. In totaal sou 36 miljoen kubieke meter water beskikbaar gestel word deur die skoonmaak van die Agulhas-vlakte. Dus kan dit afgelei word dat die verwydering van hidrologiese indringerplante op die Agulhas-vlakte 'n beduidende voordeel sal inhou.

區塊鏈技術藉著比特幣而發揚光大，經過將近十年的考驗，區塊鏈被視為足 以改變全球經濟模式的火紅科技，各種應用的想法如雨後春筍般出現，本文趁勢 提出台灣股票結算交割的區塊鏈應用。本文從最原始的區塊鏈系統——比特幣介 紹起，深入討論區塊鏈運作的機制，包括共識的形成與交易的驗證方式。比特幣 的區塊鏈系統中的某些設定對於股票結算交割來說是缺陷，本文提出改良的方式， 包括許可制的區塊鏈、引入特殊功能節點及採用實名制等，試圖讓區塊鏈技術能 夠完美的應用於結算交割系統。最後分析應用區塊鏈之後所能夠達到的經濟與社 會效益。 / After nearly ten-year challenge, blockchain was known because of Bitcoin, and regarded as the most famous technology that could change the way how the whole world works. Lots of application ideas appear at this moment, this paper tries to follow the trend and discuss about the Taiwan stock clearing and settlement system. Begin with the original blockchain system, Bitcoin, reveal how actually blockchain works including the formation of consensus and the way of transactions verification. There are some defects when implementing the application by using Bitcoin system directly. This thesis proposes the way to improve the blockchain system which includes permission blockchain system, special functional nodes and implementation of real name blockchain system, and try to make modified blockchian system applicable to clearing and settlement system. Last but not least, this thesis analyzes the benefit of economy and society when the application is employed.

Before the 2008 financial crisis, most research in financial mathematics focused on the risk management and the pricing of options without considering effects of counterparties’ default, illiquidity problems, systemic risk and the role of the repurchase agreement (Repo). During the 2008 financial crisis, a frozen Repo market led to a shutdown of short sales in the stock market. Cyclical interdependencies among financial corporations caused that a default of one firm seriously affected other firms and even the whole financial network. In this dissertation, we will consider financial markets which are shaped by financial crisis. This will be done from two distinct perspectives, an investor’s and a regulator’s. From an investor’s perspective, recently models were proposed to compute the total valuation adjustment (XVA) of derivatives without considering a potential crisis in the market. In our research, we include a possible crisis by apply an alternating renewal process to describe a switching between a normal financial status and a financial crisis status. We develop a framework for pricing the XVA of a European claim in this state-dependent framework. We represent the price as a solution to a backward stochastic differential equation and prove the existence and uniqueness of the solution. To study financial networks from a regulator’s perspective, one popular method is the fixed point based approach by L. Eisenberg and T. Noe. However, in practice, there is no accurate record of the interbank liabilities and thus one has to estimate them to use Eisenberg - Noe type models. In our research, we conduct a sensitivity analysis of the Eisenberg - Noe framework, and quantify the effect of the estimation errors to the clearing payments. We show that the effect of the missing specification of interbank connection to clearing payments can be described via directional derivatives that can be represented as solutions of fixed point equations. We also compute the probability of observing clearing payment deviations of a certain magnitude.

A presente tese de doutoramento é composta de três ensaios independentes (ainda que complementares) sobre a História do Pensamento Econômico, mais especificamente, da Macroeconomia. O primeiro ensaio - \"Uma Breve História sobre a Abordagem de Desequilíbrio na Macroeconomia\" - é uma versão revista e ampliada do artigo apresentado no XXXVIII Encontro Nacional de Economia da ANPEC em 2010 (Uma Breve História sobre a Abordagem de Desequilíbrio na Economia). Nossa argumentação vai de encontro às interpretações de Romer (1989) e Mankiw (2005) sobre a compreensão histórica daquele episódio, como também a hipótese levantada por Backhouse & Boianovsky (2005) sobre o fracasso da Macroeconomia do Desequilíbrio. O segundo ensaio se chama \"Uma Análise Histórica (e Retórica) do Discurso Doutrinário de Robert E. Lucas Jr.\". Se no primeiro ensaio argumentamos que parte do \"fracasso\" da Abordagem de Desequilíbrio deveu-se ao surgimento de um método entendido como superior pela maior parte dos economistas (o método de Lucas), neste investigamos o conteúdo daqueles artigos em que Lucas busca convencer os leitores da superioridade do seu método não a partir da comparação dos resultados obtidos por seu modelo em comparação a uma estrutura alternativa, mas sim com uma retórica polemista, fazendo uso de uma série de estratagemas retóricos. Nossa intenção é checar a validade de algumas de suas teses históricas e teóricas, bem como fazer um escrutínio dos expedientes retóricos utilizados pelo autor. O terceiro ensaio - \"Tese da Ancestralidade, Reinvenção da Tradição ou Superação Positiva? Uma Investigação sobre a \"Macroeconomia\" anterior a Keynes e as Causas do Sucesso da Teoria Geral\" - é derivada do segundo ensaio. Partimos da contraposição de hipóteses históricas de dois grandes autores da Macroeconomia sobre o estado da teoria \"macroeconômica\" anterior a Keynes, e as causas do sucesso da Teoria Geral. De um lado, Robert Lucas trata a Macroeconomia fundada por Keynes como um desvio na tradição equilibrista das análises de flutuação, cujo sucesso foi um \'feliz acidente histórico\', provocado principalmente por fatores alheios as vontades e até as simpatias de Keynes. De outro, Olivier Blanchard argumenta que o que havia antes de Keynes era uma grande diversidade de métodos e ausência de um aparato hegemônico, e o sucesso de Keynes deveu-se exclusivamente aos avanços teóricos e metodológicos apresentados naquela obra. / This PhD thesis contains three independent (although complementary) essays on the History of Economic Thought, more specifically on Macroeconomics History. The first essay - A Brief History of the Disequilibrium Approach in Macroeconomics - is a revised and expanded version of paper presented at the XXXVIII Meeting of ANPEC. Our argumentation challenges Romer (1989) and Mankiw (2005) interpretations about that episode. We also disagree (at some level) with Backhouse & Boianovsky (2005) hypothesis about the so-called \"failure\" of Non-Market-Clearing Approach. The second essay - A Historical (and Rhetorical) Analysis of Robert E. Lucas Junior\'s Doctrinaire Speech - is still a work in progress. If the first essay we argue that part of the \"failure\" of Disequilibrium Approach was due to the emergence of a method perceived as superior by most economists (lucasian method), here we investigate the content of those articles where Lucas seeks to persuade its readers of the superiority of his method not from the scrutiny of the results obtained by a specific model in comparison to an alternative structure, but mainly through a polemicist rhetoric. Our intention is to check the validity of some of its historical and theoretical arguments, and make a scrutiny of rhetorical expedients used by the author. The third essay - Ancestry Thesis, Reinvention of a Tradition or Cumulative Progress? A Research on \"Macroeconomics\" before Keynes and some Speculation about the causes of General Theory\'s Success\" - is derived from the second paper. We start from the juxtaposition of historical hypotheses of two great authors about the state\'s theory of \"macroeconomic\" before Keynes, and the causes of the success of the General Theory. On one hand, Robert Lucas argues that Macroeconomics as developed by Keynes was a deviation in the tradition of equilibrist fluctuation analysis, whose success was a fortunate historical accident. On the other, Olivier Blanchard argues that what was before Keynes was a great diversity of methods and the absence of a hegemonic apparatus, and the success of Keynes was due exclusively to theoretical and methodological advances made in that work.

Alternative renewable energy sources such as solar, wind, and bio energy have brought uncertainties into the power flow of electric power systems. Purely deterministic tools and models are suitable to guarantee the safe operation of these systems. A necessity arises to develop and use methods that deal with uncertainties in the analysis. Several methodologies have been proposed to assess the transient stability of power systems considering uncertainties. However, most of these techniques are based on the execution of successive simulations, requiring a high computational effort. Hence, they are limited to off-line applications in small systems. In view of the foregoing, this work proposes the development of two methodologies to assess – in real time – the transient stability of power systems with parametric and operational uncertainties. The first one is an extension of PEBS, which is a direct method for stability assessment. This method, called robust PEBS, employs an interval energy function of the power system to determine a robust estimate critical clearing time. The second one is the use of optimization methods to find a robust estimate critical clearing time. Notably, we employ the Simulated Annealing and Differential Evolution algorithms. Besides developing methods to estimate the critical clearing time, this work also contributes to the analysis of power systems with uncertainties by introducing a technique to reduce the analysis effort. To be specific, a methodology is proposed to identify the most influential parameters for the transient analysis assessment based on a sensitivity analysis of the generator angles with respect to the system parameters. / A utilização crescente de fontes alternativas intermitentes de energia como eólica e solar tem trazido incertezas em relação ao nível de geração e ao fluxo de potência em Sistemas Elétricos de Potência (SEP). Assim, a utilização de modelagem e ferramentas puramente determinísticas na análise de estabilidade não são mais suficientes para garantir a operação segura destes sistemas. Torna-se necessário, então, o desenvolvimento e utilização de métodos que incluam essas incertezas nas análises. Diversas metodologias foram propostas para avaliar a estabilidade transitória de Sistemas Elétricos de Potência considerando incertezas. Porém, grande parte destas técnicas é baseada em execuções de inúmeras simulações e, portanto, exige grande esforços computacionais e são limitadas a aplicações off-line e em sistemas elétricos de pequeno porte. Face ao exposto, propõe-se o desenvolvimento de uma metodologia rápida para a avaliação de estabilidade transitória de SEPs em tempo real considerando incertezas paramétricas. Esta metodologia deverá ser capaz de fornecer rapidamente um resultado robusto sobre a estabilidade. Para tal pretende-se estender a aplicação do método direto PEBS para a análise de estabilidade de sistemas elétricos com incertezas. Além disso, neste trabalho, aplicam-se métodos de otimização para se encontrar o tempo crítico de abertura sem o uso de uma simulação de Monte Carlo e determinam-se os parâmetros que mais influenciam para o estudo de estabilidade transitória utilizando uma análise de sensibilidade dos ângulos dos geradores em relação aos parâmetros do sistema elétrico de potência.