京都大学 / 0048 / 新制・課程博士 / 博士(生命科学) / 甲第21223号 / 生博第392号 / 新制||生||52(附属図書館) / 京都大学大学院生命科学研究科統合生命科学専攻 / (主査)教授 上村 匡, 教授 根岸 学, 教授 松崎 文雄 / 学位規則第4条第1項該当 / Doctor of Philosophy in Life Sciences / Kyoto University / DFAM

To determine whether prolonged supersensitization of dopamine D-1 receptors could be produced during ontogeny, rats were treated daily, from birth, for 33 consecutive days with the D-1 receptor agonist, SKF 38393 HC1 (3.0 mg/kg per day i.p.). These rats were additionally treated at 3 days after birth with the neurotoxin, 6-hydroxydopamine HBr (6-OHDA; 200 μg, i.c.v., half in each lateral ventricle) or its vehicle. At 6 to 7 weeks from birth a challenge dose of SKF 38393 HCl (3.0 mg/kg i.p.) increased stereotypy scores for a number of behaviors in 6-OHDA-lesioned rats that were treated repeatedly during ontogeny with SKF 38393. These accentuated behaviors included licking, grooming, taffy pulling, jumping, paw treading and locomotion. Although the findings demonstrate an increased sensitivity of D-1 receptors to an agonist, there was no change in the Bmax or Kd for D-1 receptors in the striatum. In rats that were treated during postnatal development with SKF 38393, but not lesioned with 6-OHDA, SKF 38393-induced stereotyped behaviors were not substantially different from control. The neonatally primed rat model may be useful for probing mechanisms of receptor supersensitivity.

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A variety of soybean oils (SOs) were developed with improved functional properties. Some of the modified SOs contain altered fatty acid (FA) composition by selective breeding methods. Currently, low α- linolenic acid soybean oil (LLSO) and low α- linolenic acid and mid oleic acid soybean oil (LLMOSO) are available FA modified SOs in the market. The consumption of FA modified SOs has been increased because the United States Food and Drug Administration required listing trans fat content in food products sold in U.S. as an effort to reduce possible health risks caused by trans fat beginning 2006. However, the effects of these FA modified SOs on human chronic diseases including breast cancer (BC) have not been studied. BC has become the most frequently diagnosed cancer and is the second leading cause of cancer death among American women. The type of dietary fat, FA composition, and n-6/n-3 ratio are known to influence BC development. Therefore, it is possible that the changed FA composition and n-6/n-3 ratio in the FA modified SOs may affect BC progression, and its critical health concern needs to be investigated. Increased human epithelial growth factor receptor 2 (Her-2/neu) and fatty acid synthase (FAS) are associated with BC progression. In fact, FAS activity and expression are affected by dietary FA composition and FA metabolism. Hypothesis of this research is that LLSO and LLMOSO may affect Her-2/neu and FAS expressing human BC (SK-Br3) cell growth in vitro and in vivo. To test our hypothesis, we investigated the potential adverse or beneficial effects of LLSO and LLMOSO in comparison with conventional SO and lard on human BC cells and then examined the possible mechanisms of action by evaluating the expression level of genes markers involved in growth factor mediated signal transduction pathway, specifically Her-2/neu PI 3-kinase (phophoinositide 3- kinase)-FAS signal transduction pathway. In vitro study demonstrated that all the tested oils at 0-2 μl/ml level have cytotoxic effects. LLMOSO had less cytotoxic effects on the growth of SK-Br3 cells compared to SO. However, there was no difference in SK-Br3 cell growth between LLSO and SO. The apoptotic protein markers (mutant p53 and caspase-3) analysis revealed that the cell growth inhibition by oil treatments was cytotoxic by triggering apoptosis. Western blot analysis demonstrated that LLSO- and LLMOSO- induced changes on cell growth involve Her-2/neu and FAS signaling transduction pathway and sterol regulatory element binding protein-1 (SREBP-1), mitogen activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI 3-kinase) are possible down-stream effectors of Her-2/neu signaling pathway. We also evaluated the dietary effects of LLSO (20% fat of total calorie), SO (20%), and lard (20%) on the growth of SK-Br3 tumors implanted in athymic mice. Changes in tumor surface area, body weight, and food intake were monitored during the 6 months feeding study. After termination, tumor net weight, Her-2/neu and FAS mRNA expression in tumors, FAS protein expression in liver, lipid composition in diets, abdominal fat, and serum, as well as plasma total cholesterol and triglyceride levels were analyzed. In vivo study showed that there were no statistical differences in tumor size and tumor net weight among SO, LLSO, and lard groups. No differences in FAS mRNA and protein expression levels between the LLSO and SO groups were observed. Tumors from the lard group expressed higher Her-2/neu and FAS mRNA than those from the LLSO and SO group. The lipid analysis demonstrated that LLSO was not significantly distinct from SO in trans fat concentration after metabolism. Serum cholesterol and triglyceride levels were unchanged in LLSO fed compared to SO fed mice. In summary, LLSO which contained modification in αLA concentration showed similar effects on SK-Br3 as SO in both in vitro and in vivo. However, LLMOSO which contained more drastic modifications on FA composition exhibited less cytotoxicity compared to SO in vitro. / Master of Science

This paper proposes a large Bayesian Vector Autoregressive (BVAR) model with common stochastic volatility to forecast global equity indices. Using a dataset consisting of monthly data on global stock indices the BVAR model inherently incorporates co-movements in the stock markets. The time-varying specification of the covariance structure moreover accounts for sudden shifts in the level of volatility. In an out-of-sample forecasting application we show that the BVAR model with stochastic volatility significantly outperforms the random walk both in terms of root mean squared errors as well as Bayesian log predictive scores. The BVAR model without stochastic volatility, on the other hand, underperforms relative to the random walk. In a portfolio allocation exercise we moreover show that it is possible to use the forecasts obtained from our BVAR model with common stochastic volatility to set up simple investment strategies. Our results indicate that these simple investment schemes outperform a naive buy-and-hold strategy. (authors' abstract) / Series: Department of Economics Working Paper Series

- The thesis is focused on Swedish foreign policy during the period 1660 - 1675, the early years of Charles XI's reign. Although Sweden is considered as an empire practically all over the 17th century, from the economic point of view it was a weak country. Sweden was totally depending on financial help from its allies, especially during periods of peace, as it was the case between 1660 and 1675. This fact belongs to the main aspects influencing the Swedish foreign policy at this time. Main part of the thesis is dedicated to relations between Sweden and other European states. The most significant were the relations with France and Denmark, since France was the ally which provided Sweden the needed finance. The role of Denmark was also essential because of its geographical position as neighbouring country to Sweden. The thesis indeed discusses relations to some other states that played an important role as well - England, the Netherlands, Brandenburg, other German states, Poland and Russia. The aim of the thesis is not just to analyse the Swedish foreign policy, but even to answer questions if there was any alternative or if the way this policy was conducted was the only possible one and also, if such policy can be considered as success or failure. These questions are answered at the final part of...

Es wird die Theorie der generischen pro-$p$ Hecke-Algebren und ihrer Bernstein-Abbildungen entwickelt. Für eine Unterklasse diese Algebren, der \textit{affinen} pro-$p$ Hecke-Algebren wird ein Struktursatz bewiesen, nachdem diese Algebren unter anderem stets noethersch sind, wenn es der Koeffizientenring ist. Hilfsmittel ist dabei der Nachweis der Bernsteinrelationen, der in abstrakter Weise geführt wird und so die bestehende Theorie verallgemeinert. Ferner wird der top. Raum der Orientierungen einer Coxetergruppe eingeführt und im Falle der erweiterten modularen Gruppe $\operatorname{PGL}_2(\mathds{Z})$ untersucht, und ausgenutzt um Kenntnisse über die Struktur der zugehörigen Hecke-Algebra als Modul über einer gewissen Unteralgebra, welche zur Spitze im Unendlichen zugeordnet ist, zu erlangen. Schließlich wird die Frage des Zerfallens des Normalisators eines maximalen zerfallenden Torus innerhalb einer zerfallenden reduktiven Gruppe als Erweiterung der Weylgruppe durch die Gruppe der rationalen Punkte des Torus untersucht, und mittels zuvor erreichter Ergebnisse auf eine kohomologische Frage zurückgeführt. Zur Teilbeantwortung dieser werden dann die Kohomologiegruppen bis zur Dimension drei der Kocharaktergitter der fasteinfachen halbeinfachen Wurzeldaten einschließlich des Rangs 8 berechnet. Mittels der Theorie der $\mathbf{FI}$-Moduln wird daraus die Berechnung der Kohomologie der mod-2-Reduktion der Kowurzelgitter für den Typ $A$ in allen Rängen bewiesen. / The theory of generic pro-$p$ Hecke algebras and their Bernstein maps is developed. For a certain subclass, the \textit{affine} pro-$p$ Hecke algebras, we are able to prove a structure theorem that in particular shows that the latter algebras are always noetherian if the ring of coefficients is. The crucial technical tool are the Bernstein relations, which are proven in an abstract way that generalizes the known cases. Moreover, the topological space of orientations is introduced and studied in the case of the extended modular group $\operatorname{PGL}_2(\mathds{Z})$, and used to determine the structure of its Hecke algebra as a module over a certain subalgebra, attached to the cusp at infinity. Finally, the question of the splitness of the normalizer of a maximal split torus inside a split reductive groups as an extension of the Weyl group by the group of rational points is studied. Using results obtained previously, this questioned is then reduced to a cohomological one. A partial answer to this question is obtained via computer calculations of the cohomology groups of the cocharacter lattices of all almost-simple semisimple root data of rank up to $8$. Using the theory of $\mathbf{FI}$-modules, these computations are used to determine the cohomology of the mod 2 reduction of the coroot lattices for type $A$ and all ranks.

Es sei A_2 der toroidal kompaktifizierte Modulraum prinzipal polarisierter komplexer abelscher Flächen, und M_k(Sp_4(Z)) das Geradenbündel Siegel'scher Modulformen von Gewicht k auf A_2, versehen mit der Petersson-Metrik. Betrachtet man A_2 als komplexe Faser einer arithmetischen Varietät über Spec(Z), und M_k(Sp_4(Z)) als das von einem Geradenbündel auf dieser arithmetischen Varietät induzierte Geradenbündel, so kann man die Frage nach dem arithmetischen Grad dieses Geradenbündels stellen. Wir stellen nachfolgend den Grad als Ausdruck in speziellen Werten der logarithmischen Ableitung der Riemann'schen Zeta-Funktion dar. Der arithmetische Grad setzt sich aus einem Beitrag vom Schnitt über den endlichen Fasern und einem Integral von Green'schen Formen über die komplexe Faser zusammen. Die Berechnung des von der komplexen Faser A_2 induzierten Anteils am arithmetischen Grad erfolgt durch eine spezifische Wahl von Schnitten von M_k(Sp_4(Z)), deren Eigenschaften bekannt oder durch ihre Darstellung als Polynome in Theta-Funktionen ableitbar sind. Mittels eines induktiven Arguments werden wir das Integral über das Stern-Produkt der zugehörigen Green'schen Formen auf eine Summe von Integralen über spezielle Zykel zurückführen, die beim sukzessiven Schneiden der zu den Schnitten gehörigen Divisoren auftauchen. Bei diesem Prozess entstehen Randterme in Form von Integralen um den toroidalen Rand. Wir werden zeigen, dass diese verschwinden, indem wir Minkowski-Theorie anwenden und eine bestimmte Wahl der Teilung der Eins treffen, die in der arithmetischen Schnitttheorie für logarithmisch singuläre Metriken auftaucht. Die Integrale über die speziellen Zykel berechnen wir durch Zurückführen auf ein Resultat von Kudla sowie auf eine modulare Version der Jensen-Formel. / Let A_2 be the toroidally compactified moduli stack of principally polarized complex abelian surfaces, and let M_k(Sp_4(Z)) be the line bundle of Siegel modular forms of weight k on A_2, equipped with the Petersson metric. Viewing A_2 as the complex fibre of an arithmetic variety over Spec(Z), and M_k(Sp_4(Z)) as the complex line bundle induced by a line bundle on this arithmetic variety, we can ask for the arithmetic degree of this line bundle. We will state a formula for the arithmetic degree in terms of special values of the logarithmic derivative of the Riemann zeta-function. The arithmetic degree consists of a contribution from intersection over Spec(Z), and from an integral of Green forms over the complex fibre. The computation of the summand of the arithmetic degree coming from the complex fibre A_2 will be approached by making a specific choice of sections of M_k(Sp_4(Z)), whose behaviour is well-known or can be worked out by their representation via theta-functions. With an induction argument, we will trace back the integral over the star-product of the corresponding Green forms to a sum of integrals over particular cycles on A_2 coming from the successive intersection of the divisors of these sections, as well as some boundary terms in the form of integrals around the toroidal boundary. We will prove that the boundary terms vanish, using Minkowski theory and a specific choice of the partition of unity that appears in arithmetic intersection theory for logarithmically singular metrics. The integrals over the special cycles will be traced back to results of Kudla and an application of a modular version of Jensen's formula.

Diese Arbeit befasst sich mit Untersuchung der Hölder Calmness, eines Stabilitätskonzeptes das man als Verallgemeinerung des Begriffs der Calmness erhält. Ausgehend von Charakterisierungen dieser Eigenschaft für Niveaumengen von Funktionen, werden, unter der Voraussetzung der Hölder Calmness, Prozeduren zur Bestimmung von Elementen dieser Mengen analysiert. Ebenso werden hinreichende Bedingungen für Hölder Calmness studiert. Da Hölder Calmness (nichtleerer) Lösungsmengen endlicher Ungleichungssysteme mittels (lokaler) Fehlerabschätzungen beschrieben werden kann, werden auch Erweiterungen der lokalen zu globalen Ergebnissen diskutiert. Als Anwendung betrachten wir speziell den Fall von Niveaumengen von Polynomen bzw. allgemeine Lösungsmengen polynomialer Gleichungen und Ungleichungen. Eine konkrete Frage, die wir beantworten wollen, ist die nach dem Zusammenhang zwischen dem größten Grad der beteiligten Polynome sowie dem Typ, d.h. dem auftretenden Exponenten, der Hölder Calmness des entsprechenden Systems. / This thesis is concerned with an analysis of Hölder calmness, a stability property derived from the concept of calmness. On the basis of its characterization for (sub)level sets, we will cogitate about procedures to determine points in such sets under a Hölder calmness assumption. Also sufficient conditions for Hölder calmness of (sub)level sets and of inequality systems will be given and examined. Further, since Hölder calmness of (nonempty) solution sets of finite inequality systems may be described in terms of (local) error bounds, we will as well amplify the local propositions to global ones. As an application we investigate the case of (sub)level sets of polynomials and of general solution sets of polynomial equations and inequalities. A concrete question we want to answer here is, in which way the maximal degree of the involved polynomials is connected to the exponent of Hölder calmness or of the error bound for the system in question.

Mein Ziel ist eine Begründung der Physik aus der Operationalisierung ihrer Grundmaße. Wir beginnen mit der klassischen und relativistischen Kinematik. Dann greifen wir einen programmatischen Entwurf von Heinrich Hertz auf und gelangen über die Quantifizierung von Energie und Impuls zu den Bewegungsgleichungen und dem Wirkungsfunktional. Den Abschluß bildet eine relativistische Revision der Energie, Impuls und Massenvorstellung. Das Ziel ist nicht primär, den mathematischen Aufbau der Mechanik zu ändern oder zu verbessern, sondern ein tieferes physikalisches Verständnis der Mechanik zu erlangen, so wie Einstein mit seinen Gedankenexperimenten zur relativistischen Kinematik. Ausgehend von anerkannten Messhandlungen und Naturprinzipien wird der mathematische Formalismus erst erzeugt und somit neu beleuchtet. Die Arbeit steht damit im selben Kontext wie die aktuellen Bemühungen zur "Fundierung der Quantenmechanik", nur eben mit Bezug auf die Interpretation der klassischen und relativistischen Kalküle. / My objective is a foundation of physics from the operationalization of its basic observables. We begin with classical and relativistic kinematics. Seizing on a programmatic proposal by Heinrich Hertz we arrive via quantification of energy-momentum at the equations of motion and the action functional. Finally we present a relativistic revision of energy, momentum and inertial mass. The goal is not primarily to change or improve the mathematical structure of mechanics, but to gain a deeper physical understanding of mechanics like Einstein with his gendanken experiments on relativistic kinematics. Starting from undisputed measurement operations and natural principles the mathematical formalism is only created and thus shown in a new light. This work is in the same context as current efforts to the "foundation of quantum mechanics", just with respect to the interpretation of the classical and relativistic calculuses.