This thesis is an experimental study of shear effect of a two-degree-of-freedom cylinder in fluid flow in terms of different mass ratio. This study is done using an elastic cylinder of high natural frequency, and the free stream velocity is 0.2m/s to 1.5m/s. The results show that as mass ratio increases, the motion of cylinder becomes more stable and small, and the frequency response of cylinder self-excited is bigger than vortex-shedding response when spring constant is bigger enough. Thus it is not easy to observe the vortex-shedding frequency variation with respect to various velocities by dint of cylinder vibration. When it come to the shear effect, the effect of shear flow could decreases the drag force, and increases the lift force. Orbits of cylinder vibration is not symmetric; the displacement is more significant on low velocity side.

Breast cancer is the most common cancer in Taiwanese women and the invasive ductal carcinoma (IDC) is the most common type. Increasing evidence shows that cancer stem cells (CSCs) have been implicated in tumorigenesis, tumor progression, and drug-resistance. In addition, four reprogramming factors (Octamer-binding Protein 4 (Oct4), Sex-determining Region Y (SRY)-related Box 2 (Sox2), Nanog and Lin28) employed to induce induced pluripotent stem (iPS) cells are associated with CSCs formation. The purpose of this study was to investigate the relationship of the protein expression levels of the reprogramming factors (Oct4, Sox2, Nanog and Lin28) with the tumorigenesis, clinicopathologic outcomes and prognosis of breast IDC patients. Immunohistochemistry (IHC) assay of tissue microarrays, made by 309 IDC and 20 breast fibrosis paraffin embedded samples, were used to examine the protein expression levels of Oct4, Sox2, Nanog and Lin28 in normal mammary ductal tissues, tumor adjacent normal mammary ductal tissues, ductal carcinoma in situ (DCIS), IDC and recurrence tissues. Our IHC results showed that Sox2 and Lin28 were expressed in half of breast IDC patients¡¦ tumor tissue (49.6% and 49.7%, respectively), but Oct4 and Nanog are less expressed (13.5% and 24.7%, respectively). The protein expression levels of the four proteins were positively correlated with each other. In addition, the expression levels of the four proteins were upregulated in tumor adjacent normal tissue as compared to breast fibrosis pateints¡¦ normal mammary ductal tissue. To compare the expression levels of the four proteins in different tissues; such as tumor adjacent normal, DCIS, IDC and recurrence tissues, the expression levels of the four protiens gradually decreased when tumor developed and progressed. However, their expression levels were comparable between IDC and recurrence tissues. Additionally, the high expression levels of four proteins were high in two good clinicopathological characteristics and a biomarker of breast cancer; such as nuclear Sox2 and Lin28 in those with pathology stage I; nucleus expression of the four proteins in those with well and moderate cell differentiation; and Sox2 in those with positive estrogen receptor. However, the four proteins¡¦ expression levels were not correlated with IDC patients¡¦ survival. In conclusion, the reprogramming factors: Oct4, Sox2, Nanog and Lin28 may play an important role in tumorigenesis of breast IDC, but their impacts on tumor progression were quite small.

Dans cette thèse, nous analysons les différents aspects des externalités de connaissance et la façon dont les citations de brevet peuvent être utilisées comme un indicateur de ces flux. La première partie de cette thèse examine la littérature traditionnelle sur les externalités de connaissance, et cela d'un point de vue à la fois qualitatif et quantitatif (la forme quantitative est réalisée grâce à une méta-analyse). Nous insistons sur les conséquences résultant de l'utilisation de différents canaux de mesure de ces externalités, précisément nous nous attardons sur les hypothèses sous-jacentes et sur leurs implications en termes d'estimations empiriques. Ce point est important car ces canaux sont la principale source d'hétérogénéité des résultats empiriques. Dans la seconde partie, nous explorons des données de brevets et de citations de brevet encore peu étudiées (ces données sont extraites de la base de données Patstat pour les offices de brevets du G5, de l'OEB et de l'OMPI). Cette analyse est à nouveau réalisée à la fois en termes qualitatifs et quantitatifs. La troisième partie, dans un premier temps, examine de façon empirique les caractéristiques des flux de connaissance entre et au sein des inventeurs des pays du G5 et cela pour 13 secteurs industriels. Dans un deuxième temps, cette partie propose et valide la création d'un indicateur de stocks de connaissance qui prend en compte les externalités de connaissance internationales. Cet indicateur se révèle particulièrement utile puisque les indicateurs traditionnels ne sont pas toujours disponibles (comme les indicateurs basés sur les dépenses de R&D). Enfin, l'indicateur précédemment créé sera appliqué à une étude de cas consacrée à l'analyse des déterminants de l'innovation pour les technologies énergétiques efficientes. / In this dissertation, we analyze the different aspects of knowledge spillovers with special emphasis on the use of patent citations as an indicator of knowledge flows. The first part of the thesis reviews the traditional knowledge spillovers literature both with a qualitative and a quantitative view (the quantitative form is done through a meta-analysis). A particular focus is placed on the consequences of using the different channels reflecting different weighted functions, i.e. about the underlying assumptions and the implications in terms of estimates. This point is important since these channels are the main source of heterogeneity in the analysis of knowledge spillovers. In the second part, we shed some light on patent and patent citation data that have not been much studied (taken from the Patstat database for the G5 patent offices plus the EPO and the WIPO). Once again this analysis is conducted both in qualitative and quantitative terms. The third part, in a first time, investigates empirically the diffusion pattern of knowledge between and within the G5 inventors for 13 manufacturing sectors. In a second time, it proposes and validates the creation of an input-based indicator of knowledge that takes into account international knowledge spillovers. This indicator can be very helpful since traditional indicators are not always available (such as R&D indicators). Finally, the previously created indicator will be applied in a case study dedicated to analyze the determinants of innovation for energy efficient technologies.

In the past decade there has been a significant increase in focus on the effect upper body vibration (UBV) has on the recovery of skeletal muscle after exercise-induced muscle damage. Recovery can be defined and investigated using a wide variety of methods. This study used three different measurements to track muscle recovery over 7 days following an exercise muscle damage protocol and applied vibration to a mathematical model. A visual analog scale (VAS) was used to measure muscle pain, a strain gauge was used to obtain maximum voluntary isometric contraction (MVIC) strength measurements, and shear wave elastography (SWE) represented muscle stiffness over the 7-day experiment. Thirty-three participants were divided into three groups. The first was a control group (C) that experienced no exercise and no therapy. The no vibration group (NV) performed the damage an exercise protocol but received no therapy. The vibration group (V) performed the same exercise protocol but also received vibration therapy. The exercise protocol consisted of 100 dumbbell curls at starting at 50% of their MVIC with one minute of rest after each set of ten. The data provided convincing evidence (27.2%, p < 0.0001) that group NV was not back to its normal stiffness after 7 days unlike group V, which was shown not to be any different from its baseline at the end of the week (9.15%, p = 0.137). Three vibration factors (����1, ����2, ����3) were added to a skeletal muscle regeneration model (SK) to simulate how vibration affects muscle regeneration. The three factors were determined by analyzing previous research to understand how vibration affects cells in the regeneration process. Adding these into SK decreased the time to recovery from about 13 days to about 7 days. Recovery was defined by reaching 10% of the original number of myofibers within the damaged muscle.

京都大学 / 0048 / 新制・論文博士 / 博士(工学) / 乙第13173号 / 論工博第4164号 / 新制||工||1699(附属図書館) / (主査)教授 寶 馨, 教授 渦岡 良介, 准教授 佐山 敬洋 / 学位規則第4条第2項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

O Direito Tributário não tem como finalidade única a arrecadação de receitas para custear os gastos estatais. Embora esta seja a sua finalidade principal, a verdade é que ela coexiste com outras funções, como a finalidade de distribuição de riqueza e de intervenção na ordem econômica e social. Nesse contexto, o objetivo desta dissertação é aprofundar o estudo sobre a utilização instrumental das normas tributárias, determinando quais seriam os critérios de controle para a utilização dessas normas cuja função precípua é a promoção de determinada finalidade social, política ou econômica, e não a mera arrecadação de recursos. Para isso, inicia-se o trabalho com a delimitação do regime jurídico atinente a estas normas, analisando a legitimidade da função indutora na tributação diante da Constituição de 1988 e verificando quais são as limitações próprias da tributação e os princípios da ordem econômica a elas aplicáveis. Em seguida, passa-se a demonstrar que a função extrafiscal precisa ser controlada através da verificação da validade da finalidade buscada com relação às restrições impostas aos direitos envolvidos, especialmente no que tange ao princípio da igualdade e a aplicação da capacidade contributiva. Além disso, evidencia-se que a função extrafiscal não pode ser definida apenas pela sua causa, mas também pelos seus efeitos no mercado, uma vez que a indução de comportamentos faz parte de sua própria natureza. Após isso, identifica-se a necessidade de controle sobre a utilização das normas tributárias indutoras, apresentando os critérios para tanto: o princípio da igualdade, a aplicação da capacidade contributiva, o controle de eficácia, o exame de proporcionalidade, a complementaridade, a subsidiariedade, a economicidade e o cumprimento da finalidade. Por fim, estes critérios são aplicados em exemplos de normas tributárias indutoras no sistema tributário brasileiro, a fim de contribuir para o desenvolvimento do debate jurídico acerca da extrafiscalidade. / The Tax Law does not have the sole purpose of raising revenue to fund state spending. Although this is its main purpose, the truth is that it coexists with other functions such as the purpose of distribution of wealth and intervention in economic and social order. In this context, the aim of this dissertation is to deepen the study of the instrumental use of tax rules, determining the criteria to control the use of tax rules whose primary function is the promotion of a specific social purpose, political or economic, not mere fundraising. For this, the work begins with the definition of the separate legal status to these rules, analyzing the legitimacy of the regulatory function in taxation in the 1988 Constitution and checking what are the limitations of taxation and the principles of Economic Order applicable to them. Then it goes to show that the extrafiscal function needs to be monitored by checking the validity of the order sought in relation to restrictions on rights involved, especially with regard to the principle of equality and the implementation of ability to pay. Furthermore, it is evident that the extrafiscal function cannot be defined only by their cause, but also for their effects on the market, since the induction of behavior is part of their nature. After that, we identify the need for control over the use of Tax rules to induce the taxpayers behavior, presenting the criteria for that: the principle of equality, the implementation of ability to pay principle, effectiveness control, proportionality test and complementarity, subsidiarity, economy and fulfillment of purpose. Finally, these criteria are applied to examples of Tax rules to induce the taxpayers behavior in the Brazilian tax system in order to contribute to the development of the legal debate over extrafiscality.

This dissertation describes the advantages and feasibility of newly synthesized near-infrared (NIR) bis-heptamethine cyanine (BHmC) dyes for non-covalent labeling schemes. The NIR BHmCs were synthesized for biomolecule assay. The advantages of NIR BHmCs for biomolecule labeling and the instrumental advantages of the near-infrared region are also demonstrated. Chapter 1 introduces the theory and applications of dye chemistry. For bioanalysis, this chapter presents covalent and non-covalent labeling. The covalent labeling depends on the functionality of amino acids and the non-covalent labeling relies on the binding site of a protein. Due to the complicated binding process in non-covalent labeling, this chapter also discusses the binding equilibria in spectroscopic and chromatographic analyses. Chapter 2 and 3 evaluate the novel BHmCs for non-covalent labeling with human serum albumin (HSA) and report the influence of micro-environment on BHmCs. The interesting character of BHmCs in aqueous solutions is that the dyes exhibit non- or low-fluorescence compared to their monomer counterpart, RK780. It is due to their H-type closed clam-shell form in the solutions. The addition of HSA or organic solvents opens up the clam-shell form and enhances fluorescence. The binding equilibria are also examed. Chapter 4 provides a brief introduction that summaries the use of capillary electrophoresis (CE), and offers a detailed instrumentation that discusses the importance and advantage of a detector in NIR region for CE separation. Chapter 5 focuses on the use of NIR cyanine dyes with capillary electrcophoresis with near-infrared laser induce fluorescence (CE-NIR-LIF) detection. The NIR dyes with different functional groups show that RK780 is a suitable NIR dye for HSA labeling. The use of BHmCs with CE-NIR-LIF reduces signal noises that are commonly caused by the interaction between NIR cyanine dyes and negatively charged capillary wall. In addition, bovine carbonic anhydrase II (BCA II) is applied to study the influence of hydrophobicity on non-covalent labeling. Finally, chapter 6 presents the conformational dependency of BHmCs on the mobility in capillary and evaluates the further possibility of BHmCs for small molecule detection. Acridine orange (AO) is used as a sample and it breaks up the aggregate and enhances fluorescence. The inserted AO into BHmC changes the mobility in capillary, owing to the conformational changes by AO.

The widespread pollution of mercury motivates research into its atmospheric chemistry and transport. Gaseous elemental mercury (Hg(0)) dominates mercury emission to the atmosphere, but the rate of its oxidation to mercury compound (Hg(II)) plays a significant role in controlling where and when mercury deposits to ecosystems. Atomic bromine is regarded as the main oxidant for Hg(0) oxidation, known to initiate the oxidation via a two-step process in the atmosphere – formation of BrHg (R1) and subsequent reactions of BrHg with abundant free radicals Y, i.e., NO2, HOO, etc. (R2), where the reaction of BrHg +Y could also lead to the reduction of Hg(I) to Hg(0) (R3). A different oxidation pathway of BrHg + O3 (R4) is currently regarded as the dominant Hg(II) oxidation pathway in the atmosphere. Hg + Br + M → BrHg + M (R1) BrHg + Y + M → BrHgY + M (R2) BrHg + Y → BrY +Hg (R3) BrHg + O3 → BrHgO + O2 (R4) While the rate constants of R1 have been experimentally measured a decade ago, this research focuses on the experimental kinetic studies on the reaction of R2-R4 to better assist the efforts to predict how emission reductions impact the spatial distribution of mercury entry into ecosystems. The kinetic studies of BrHg redox chemistry are conducted by utilizing laser photolysis-laser induced fluorescence-cavity ringdown spectroscopy (LP-LIF-CRDS) systems, where BrHg radicals are generated via laser photolysis and monitored in the reaction via LIF and CRDS measurements. We report mainly on our experimental kinetic studies of the redox reactions of BrHg with relatively abundant trace gases such as NO2, NO, O3, O2, and VOCs, especially on the temperature and pressure dependence of the reaction rate constants using our LP-LIF system. We present the development and the characterization of a novel LP-CRDS system, which is a powerful tool to study reactions during which fluorescence quenching interferes with LIF measurement, and to study the spectroscopy of Hg(I) and Hg(II) compounds.

影響海外可轉換公司債的因素有許多，包括股價、國內利率、國外利率、匯率，若將時間變數也加入計算，其變動因子高達5階，這種「高維度」的問題已非有限差分法或樹狀方法能處理；且海外可轉債常附有平均式條款、回顧式條款等「路徑相依」性質的選擇權，更是格狀結構數值法(Lattice)難以處理的問題。若使用蒙地卡羅模擬，雖然可以處理高維度及路徑相依的問題，但遇到美式契約時，則會有無法判斷轉換時點的問題，更遑論還必須處理的重設條款或界限型契約。 本論文研究海外可轉換公司債的評價，特點是可以處理其契約中各種可能的複雜條款，本文所使用的最小平方蒙地卡羅模擬，由Longstaff and Schwartz [2000]提出，對於美式契約、路徑相依及高維度問題皆可處理。本文並以Hull and White利率三元樹配適公司債利率符合市場利率期間結構。此外本研究加入海外可轉換公司債評價中最重要的信用風險因素，過去可轉債文獻理論價格大都高於實際市價，這是由於忽略了公司的信用風險溢酬，本文所使用的信用風險模型是由Lando [1998]所提出，特點是不以信用等級作為考量，探討公司特性與所屬產業，並考慮總體因素對違約機率的影響，從市場價格中估計違約密度參數，進而求得信用價差。 本研究對仁寶電腦在2002年所發的ECB做實證研究，比較LSM理論價格與實際市價之誤差，及對Takahashi[2001]所提出之歐式模型做比較，發現本文提出模型之評價結果相當不錯，誤差僅有0.83%；此外並對建華金控2002所發之ECB，探討各種複雜新奇條款對ECB價格的影響，發現市場上嚴重低估了重設條款所提高的價值，而實際市價卻十分接近僅含賣回條款的理論價格。

I hjärnan finns neuron och gliaceller. Förut trodde man att neuroner var dem enda som hade en viktig funktion i hjärnan men på senare tid har upptäckt att gliaceller har en större betydande roll än man tidigare trott. Gliaceller är ett samlingsnamn som innefattar bland annat microglia celler, oligodendrocyter och astrocyter. Östrogen är ett steroidhormon som har många viktiga funktioner i kroppen som bland annat reproduktionen, immunförsvaret, skelettet och endokrina system. Östrogen binder till östrogenreceptorer och de finns 3 stycken olika som kallas för östrogenreceptor alfa (α), östrogenreceptor beta (β) och G-proteinkopplade östrogenreceptor (GRP30). Alla dessa östrogenreceptorer har man funnit i hjärnan. Syftet med detta projektarbete är att ge en djupare förståelse om östrogens signalering i hjärnans gliaceller och om östrogens signalering kan ge någon relevant funktion till framtida farmakologiska behandlingar.  Systematisk litteraturstudie gjordes och sökningar på databasen PubMed. Begränsade antalet träffar med sökord, inklusionskriterier och exklusionskriterier. Artiklar granskades sedan via ett urvalssystem och relevanta artiklar användes för att besvara syfte och frågeställningar.  Östrogensignaleringen på gliaceller har många olika effekter. En signalering på östrogenreceptor β på oligodendrocyter leder till mognad, differentiering, bättre överlevd och att remyeliniseringen aktiverades. Medan en östrogens signalering på microglia cellens östrogenreceptorer α, β och GRP30 leder dämpning av inflammation och förbättrad kognitiv funktion. Östrogensignaleringen på astrocyter ger flera olika effekter såsom metabolismen av glukos, progesteron syntesen, glutamattransportören GLT-1, tillväxtfaktorn TGF-α, upptaget av glutamat samt ökad proteinproduktion av AMPA-receptor. Den nya kunskapen om östrogens signalering på hjärnans gliaceller kan leda till framtida farmakologiska behandlingar vid hjärnskada och ischemisk stroke. Östrogenet har visat på neuronskyddande effekter via signalering på gliaceller. Svagheten är att de endast är djurstudier som ligger till grund för kunskapen om östrogens signalering på gliaceller. I framtiden skulle det behövas styrkas med studier gjorda på människa. En styrka är att djurstudierna ger en fingervisning om östrogen signaleringen eftersom hjärnans uppbyggnad är likvärdig.