<p>This thesis concerns the development and validation of high performance liquid chromatography (HPLC) methods aimed for two industrially important areas: (i) analysis of biotechnological synthesis and (ii) determination of adsorption isotherm parameters. There is today a lack of detailed recommendations for analytical procedures in the field of biotechnological production of drugs. Therefore, guidelines were given for analytical development and validation in this field; the production of 9α-hydroxyprogesterone was used as model. In addition, a rapid method using HPLC coupled with diode-array-detection (DAD) and mass spectrometry (MS), was developed for the preliminary identification and quantification of the product. In addition, requirements and recommendations were developed for the selection of the internal standard and for its inclusion in the process liquid. By using this approach the precision and accuracy of the quantitative method were considerably improved. </p><p>Preparative chromatography is a powerful separation method for the purification of pure compounds from more or less complex sample mixtures. One such mixture can be the process liquid from a fermentation, another example can be a racemic mixture of compounds whose enantiomeric constituents must be isolated. Computer-assisted modeling can be used to optimize preparative chromatography. However, competitive adsorption isotherm parameters are required as input data for the computer simulations. In this thesis, a new injection technique, based on a firm theoretical basis, was developed for the peak perturbation (PP) method allowing the determination of binary competitive adsorption isotherm parameters from a broad concentration range. With the new method the determination of adsorption isotherm parameters from a quaternary mixture could be done for the first time. The profiles simulated with these parameters showed excellent agreement with the corresponding experimental profiles, validating the accuracy of the adsorption isotherm parameters derived by the new method.</p>

This thesis concerns the development and validation of high performance liquid chromatography (HPLC) methods aimed for two industrially important areas: (i) analysis of biotechnological synthesis and (ii) determination of adsorption isotherm parameters. There is today a lack of detailed recommendations for analytical procedures in the field of biotechnological production of drugs. Therefore, guidelines were given for analytical development and validation in this field; the production of 9α-hydroxyprogesterone was used as model. In addition, a rapid method using HPLC coupled with diode-array-detection (DAD) and mass spectrometry (MS), was developed for the preliminary identification and quantification of the product. In addition, requirements and recommendations were developed for the selection of the internal standard and for its inclusion in the process liquid. By using this approach the precision and accuracy of the quantitative method were considerably improved. Preparative chromatography is a powerful separation method for the purification of pure compounds from more or less complex sample mixtures. One such mixture can be the process liquid from a fermentation, another example can be a racemic mixture of compounds whose enantiomeric constituents must be isolated. Computer-assisted modeling can be used to optimize preparative chromatography. However, competitive adsorption isotherm parameters are required as input data for the computer simulations. In this thesis, a new injection technique, based on a firm theoretical basis, was developed for the peak perturbation (PP) method allowing the determination of binary competitive adsorption isotherm parameters from a broad concentration range. With the new method the determination of adsorption isotherm parameters from a quaternary mixture could be done for the first time. The profiles simulated with these parameters showed excellent agreement with the corresponding experimental profiles, validating the accuracy of the adsorption isotherm parameters derived by the new method.

For many centuries, the study of the Sun has been an important testbed for understanding stars that are further away. One of the first astronomical observations Galileo Galilei made in 1612 with the newly invented telescope concerned the sunspots, and in 1814, Joseph von Fraunhofer employed his new spectroscope to discover the absorption lines in the solar spectrum that are now named after him. Even though more refined and new modes of observation are now available than in the days of Galileo and Fraunhofer, the study of the Sun is still high on the agenda of contemporary science, due to three guiding interests. The first is connected to the ages-old human striving to understand the structure of the larger world surrounding us. Modern telescopes, some of them even based outside the Earth’s atmosphere in space, have succeeded in observing astronomical objects that are billions of light- years away. However, for practical reasons precision data that are important for understanding stars can still only be gained from the Sun. In a sense, the observations of far-away astronomical objects thus call for a more precise study of the closeby, of the Sun, for their interpretation. The second interest stems from the human desire to understand the essence of the world, in particular the elementary particles of which it consists. Large accelerators have been constructed to produce and collide these particles. However, man-made machines can never be as luminous as the Sun when it comes to producing particles. Solar neutrinos have thus served not only as an astronomical tool to understand the Sun’s inner workings, but their behavior on the way from the Sun to the Earth is also being studied with the aim to understand their nature and interactions. The third interest is strictly connected to life on Earth. A multitude of research has shown that even relatively slight changes in the Earth’s climate may strongly affect the living conditions in a number of densely populated areas, mainly near the ocean shore and in arid regions. Thus, great effort is expended on the study of greenhouse gases in the Earth’s atmosphere. Also the Sun, via the solar irradiance and via the effects of the so-called solar wind of magnetic particles on the Earth’s atmosphere, may affect the climate. There is no proof linking solar effects to short-term changes in the Earth’s climate. However, such effects cannot be excluded, either, making it necessary to study the Sun. The experiments summarized in the present work contribute to the present-day study of our Sun by repeating, in the laboratory, some of the nuclear processes that take place in the core of the Sun. They aim to improve the precision of the nuclear cross section data that lay the foundation of the model of the nuclear reactions generating energy and producing neutrinos in the Sun. In order to reach this goal, low-energy nuclear physics experiments are performed. Wherever possible, the data are taken in a low-background, underground environment. There is only one underground accelerator facility in the world, the Laboratory Underground for Nuclear Astro- physics (LUNA) 0.4 MV accelerator in the Gran Sasso laboratory in Italy. Much of the research described here is based on experiments at LUNA. Background and feasibility studies shown here lay the base for future, higher-energy underground accelerators. Finally, it is shown that such a device can even be placed in a shallow-underground facility such as the Dresden Felsenkeller without great loss of sensitivity.

In this thesis, we study the unit root tests which includes the ADF, PP and KPSS tests, the long memory tests such as the R/S and GPH tests, and the applications of these methods in high frequency financial data analysis. The software SPLUS was adopted to analyze data and correction of the SPLUS program in unit tests are also proposed. To apply these two test methods in high frequency data, we quoted the library, HFlibrary designed by Yan and Zivot in 2003 for preliminary data analysis and propose a new library HFanalysis, which can be used in correcting high frequency data (excluding N.A. value, sorting transactions and retrieve a certain time of transactions), obtaining equi-distanced time intervals and testing for unit root and long memory properties. In additions, we apply this proposed library to simulate the power of traditional unit root methods such as the ADF test and long memory test method such as the R/S and to perform an empirical study. Finally, we explore the power of the ADF for testing data simulated from a threshold unit root model and simulate the percentiles of the null distribution of the following threshold unit root tests: WALD, LM, LR and W£f.

Η παρούσα διατριβή είχε ως σκοπό τη μελέτη της επίδρασης της επαναμορφοποίησης στις μηχανικές κυρίως ιδιότητες δυο πολύ κοινών πολυμερών, του πολυαιθυλενίου και του πολυπροπυλενίου. Τα πολυμερή αυτά, χρησιμοποιούνται σε πολλές εφαρμογές και για αυτό το λόγο ο όγκος των απορριμμάτων τους αποτελεί ένα σοβαρό περιβαλλοντικό πρόβλημα. Παρόλο που αποτελούν υλικά εύκολα ανακυκλώσιμα, πολύ μικρό ποσοστό από τα απορρίμματα τους ανακτώνται. Περιβαλλοντικοί αλλά και οικονομικοί λόγοι οδήγησαν στην ιδέα να κατασκευαστούν κάποια προϊόντα χαμηλών απαιτήσεων, τα οποία μέχρι τώρα κατασκευάζονται από καθαρά πολυμερή, από πλήρως ανακτημένη πρώτη ύλη. Η δυσκολία στην εφαρμογή των ανακτημένων υλικών έγκειται στο ότι αυτά περιέχουν διάφορα πρόσθετα, καταπονούνται αρκετά από την έκθεση τους σε περιβαλλοντικούς παράγοντες όσο διάστημα χρησιμοποιούνται ή βρίσκονται στους χώρους ενταφιασμού και οι πολλαπλές επαναμορφοποιήσεις τους είναι πιθανόν να προκαλέσουν υποβάθμιση του υλικού. Για αυτό το λόγο, μελετήθηκαν επαναμορφοποιημένα δείγματα από πολυαιθυλένιο και πολυπροπυλένιο άγνωστης προϊστορίας και καταπόνησης σε σύγκριση με τα αντίστοιχα καθαρά υλικά, προκειμένου να γίνει σύγκριση των ιδιοτήτων τους και κατ’ επέκταση μια εκτίμηση της επίδρασης του βαθμού επαναμορφοποίησης στη μηχανική τους συμπεριφορά. Παράλληλα, όλα τα δείγματα, επαναμορφοποιημένα και μη, μελετήθηκαν φασματοσκοπικά, ώστε να διαπιστωθεί αν η διαδικασία ανάκτησης έχει προκαλέσει μεταβολές στη χημική δομή των υλικών αυτών. Από τις τεχνικές χαρακτηρισμού που χρησιμοποιήθηκαν (φασματοσκοπία υπερύθρου και Raman, DSC και TGA) διαπιστώθηκε ότι δεν έχει επέλθει αλλαγή στη χημική δομή των ανακυκλωμένων υλικών. Όσον αφορά τις διαφοροποιήσεις που εκείνα παρουσίασαν σε σχέση με τα αντίστοιχα καθαρά υλικά, αποδίδονται στην παρουσία προσθέτων, χρωστικών ουσιών κυρίως, που τα ανακτημένα υλικά περιείχαν. Η μηχανική συμπεριφορά των επαναμορφοποιημένων, ιδιαίτερα στην περίπτωση του πολυαιθυλενίου ήταν παρόμοια με αυτή των καθαρών δειγμάτων και τα αποτελέσματα συγκρίσιμα. Αντίθετα, στην περίπτωση του πολυπροπυλενίου η διαδικασία ανάκτησης είχε υποβαθμίσει πολύ το υλικό με αποτέλεσμα να εμφανίζει πολύ κατώτερες μηχανικές ιδιότητες. Όλα τα επαναμορφοποιημένα υλικά είχαν υποστεί ως ένα βαθμό περιβαλλοντική γήρανση καθώς ήταν εκτεθειμένα για αρκετό χρονικό διάστημα σε περιβαλλοντικές συνθήκες. Η επίδραση της έκθεσης όμως δεν ήταν δυνατόν να αξιολογηθεί, αφού δε ήταν γνωστό το ακριβές χρονικό διάστημα καθώς και οι συνθήκες θερμοκρασίας, υγρασίας κ.λπ. Για αυτό το λόγο, τόσο τα ανακτημένα όσο και τα καθαρά δείγματα, υπέστησαν τεχνητή επιταχυνόμενη περιβαλλοντική γήρανση, προκειμένου να μελετηθεί η επίδρασή της στις ιδιότητες των υλικών. Αυτό που παρατηρήθηκε και σε αυτές τις δοκιμές ήταν ότι, ανάλογα με τον βαθμό επαναμορφοποίησης στα μη γηρασμένα υλικά, η τεχνητή γήρανση επηρέασε κατά κύριο λόγο τις αντοχές των υλικών σε κάθε μηχανική καταπόνηση και δευτερευόντως τις φυσικές ιδιότητες τους. Σε γενικές γραμμές, διαπιστώθηκε ότι τα επαναμορφοποιημένα δείγματα HDPE δεν παρουσιάζουν μεταβολές ως προς τη χημική δομή τους, ενώ δίνουν συγκρίσιμα αποτελέσματα στις μηχανικές δοκιμές τόσο στο μέτρο ελαστικότητας όσο και στην αντοχή. Μετά τη γήρανση, η αντοχή τους μειώνεται σημαντικά παρόλα αυτά, η συνολική τους μηχανική απόκριση κρίνεται ικανοποιητική. Αντίθετα τα επαναμορφοποιημένα δείγματα ΡΡ, εμφάνισαν ακόμα και πριν την τεχνητή γήρανση, αισθητά χαμηλότερες μηχανικές ιδιότητες (χαμηλότερο μέτρο ελαστικότητας και αντοχή σε σχέση με τα παρθένα υλικά), παρόλο που δεν παρουσίασαν καμία αλλαγή στη χημική τους δομή. / Reforming effect on thermoplastics mechanical properties was the subject of this thesis. More specifically, samples of polyethylene and polypropylene were chosen to be tested, as they are widely used in many applications and consequently there is a large amount of municipal waste of this kind. Even though, these polymers are easily recyclable compared to other polymers, only 2% of this kind of municipal waste gets recycled in Greece nowadays. Economical and environmental reasons, researchers led to the idea of constructing products out of completely recycled materials. Recycling process faces many difficulties; the most important of these is the addition of pigments (additives) such as colors, coupling agents etc, which make polymer recycling heavier or even impossible in some cases. Moreover, these materials degrade signifantly because of their exposure to the environment while they are used in exterior application or get thrown in landfills after use. As the collection of completely recycled materials was quite impossible, virgin and reformed of known and unknown history samples of polyethylene and polypropylene, are examined, as for their chemical structure and mechanical properties, in order to get compared and finally reach a conclusion if reformed materials are appropriate for getting used in some applications. Through Raman and Infrared Spectroscopy, it was observed no change in reformed materials’ chemical structure before and after reforming process. Also, their thermal behavior appeared many similarities between virgin materials and reformed ones. However, these similarities did not appear in mechanical tests. Even though, reformed HDPE of known and unknown history showed comparable and very close properties with these of virgin, it is observed a lack of stability in their mechanical behavior, especially in case of reformed unknown history polyethylene. In the case of polypropylene, the reformed samples were always inferior to the virgin ones, in all tests, probably to its degradation during reforming process. In order to determine accurately, the weathering effect on samples behaviour, they were imposed to artificial ageing in oven, in controlled temperature, humidity etc. As in non aged samples, reforming ratio plays significant role in samples’ physical properties, which appear dominantly changed after ageing. As it was expected, mechanical behavior has changed after ageing, too. However, there were no significant reduce in moduli of elasticity in tensile, compression and flexural tests, a dramatic reduce in strength in every mechanical test was observed between samples before and after ageing.

The draft for a Common Consolidated Corporate Tax Base Directive in the European Union includes the suggestion for an apportionment formula which allocates taxable group profits to group member corporations. These allocated profits shall then be taxed in the respective Member States. The draft directive delegates the right to define one factor of the apportionment formula, the term "Employee" to the Member States, who are therefore free to choose a narrow or a broad definition, the latter including also atypical employment schemes. Using a game-theoretic approach the paper shows that the individually rational strategy of any Member State to define "Employee" broadly so as to maximize the volume of the apportionment factor and thus maximize the allocated share of taxable income is only the best solution when tax rate differences and differences in the volume of atypical employment schemes are disregarded. If such differentials and the corporate groups' reactions to different Member States' definitions are included in modelling the game's pay-offs a narrow definition of "Employee" yields the highest individual pay-offs to the Member States involved. This change of dominant strategies is triggered by the corporate group's shifting of the employment factor from high-tax to low-tax Member States. Our paper differs from previous research on the economic effects of the CCCTB apportionment formula as it is the first paper identifying and analysing the employment factor and its distorting effects. The paper discusses possible tax minimizing strategies for corporate groups by shifting workforce and develops a model to quantify these potential relocations. Furthermore the paper presents advice to policy makers in their "Employee" definition decision and shows how Member States could use this definition to both minimize outward factor shifting and maximize inward factor shifting.(authors' abstract) / Series: WU International Taxation Research Paper Series

Aims Protein Phosphatase Inhibitor 1 (I-1) functions as an amplifier of the β-adrenergic cascade in cardiomyocytes. Once activated via PKA, I-1 specifically blocks PP-1-mediated dephosphorylation of phospholamban and the ryanodine receptor-1. In heart failure I-1 activity as well as its expression is significantly reduced. It is still unclear whether this adaptation is protective or detrimental. This work aims at examining the impact of I-1 depletion on the course of pressure-induced heart failure, more precisely on acute and long-term mortality, on cardiac morphology and function and on expression levels of hypertrophy markers. Results may help evaluating the benefit of putative I-1 inhibiting substances in the therapy of heart failure. Methods and Results 25 I-1KO and 28 WT mice (C57Bl/6J, age- and sex-matched) underwent transverse aortic constriction (TAC). Cardiac function was assessed via transthoracic echocardiography prior to the intervention and weekly afterwards. Additionally, mice were exposed to β-adrenergic stimulation by injection of dobutamine once prior to TAC and two times afterwards, each controlled by echocardiography. For male mice acute survival was significantly increased in WT compared to I-1KO, whereas the mortality of surviving animals did not differ during the investigation period. For female mice no difference was seen in acute mortality after TAC, but during heart failure progression I-1KO revealed a significantly better survival. Prior to TAC contractility in I-1KO after application of dobutamine was significantly lower than in WT. This effect was mainly induced by female mice. Overall female mice of both WT and I-1KO showed smaller increases in heart rate (HR) and stroke volume (SV) when stimulated. In contrast, following TAC neither line- nor sex-dependent differences were found according to β-adrenergic stimulation. The comparison of hypertrophy markers in control groups revealed clearly decreased levels for I-1KO compared to WT. Conclusion In pressure-induced heart failure, I-1 knockout alters cardiac contractility and modulates mortality in a phase- and sex-dependent way. The depletion is detrimental for male mice in the acute phase of cardiac stress, whereas it is protective for female mice during heart failure progression. The increased mortality in the acute phase might result from the loss of I-1 as an amplifier of β-adrenergic signaling as this leads to a restriction of contractile adaptation. The increased survival in heart failure progression might be caused by a reduced transmission of pathologically increased sympathetic activity on the SR due to the depletion of I-1. Additionally, hypertrophy marker analyses point to differences in expression levels even under non-pathological conditions. / Ziel Der Proteinphosphatase-Inhibitor I-1 wirkt als ein Verstärker der β-adrenergen Kaskade in Kardiomyozyten. Nach PKA-abhängiger Phosphorylierung hemmt er spezifisch die Dephosphorylierung von PLB und RYR-2 durch die Proteinphosphatase-1. Im Rahmen einer Herzinsuffizienz sind sowohl Aktivität als auch Expression von I-1 deutlich reduziert. Hierbei ist unklar, ob dies eine protektive oder eine schädliche Adaption der β-adrenergen Kaskade darstellt. Diese Arbeit untersucht den Einfluss einer Depletion des I-1 (I-1KO) im Rahmen der druckinduzierten Herzinsuffizienz auf die akute bzw. auf die langfristige Mortalität, auf die kardiale Morphologie und Funktion sowie auf die Expression typischer Hypertrophiemarker. Hieraus sollen Erkenntnisse über den Nutzen der Verwendung putativ I-1 inhibierender Substanzen in der Behandlung der Herzinsuffizienz gewonnen werden. Methoden und Resultate 25 I-1KO- sowie 28 WT-Mäuse (C57Bl/6J, age and sex matched) erhielten eine Transverse Aortic Constriction (TAC). Die kardiale Funktion wurde einmalig vor der Intervention sowie danach wöchentlich mittels TTE untersucht. Zusätzlich wurden die Tiere einmalig vor TAC und zweimalig danach unter echokardiographischer Kontrolle mittels Dobutamin β-adrenerg stimuliert. Für die männlichen Tiere zeigte sich in den ersten Tagen nach TAC eine signifikant erhöhte Überlebensrate des WT gegenüber I-1KO. Die Mortalität der überlebenden männlichen Tiere unterschied sich hingegen nicht über den Versuchszeitraum. Für die weiblichen Tiere bestand kein Unterschied in der akuten Sterblichkeit nach TAC, während sich im Verlauf eine signifikant bessere Überlebensrate der weiblichen I-1KO gegenüber WT zeigte. Vor TAC wurde eine signifikant herabgesetzte Kontraktilität (FAS) des I-1KO unter Dobutamin festgestellt, der im Wesentlichen durch die weiblichen Tiere bewirkt wird. Insgesamt zeigten die weiblichen Tiere beider Linien unter β-adrenerger Stimulation eine geringere Zunahme von Herzfrequenz (HR) und Schlagvolumen (SV). Hingegen waren nach TAC keine linien- oder geschlechtsabhängigen Unterschiede unter Dobutamingabe feststellbar. Ein Vergleich der Hypertrophiemarker in der Kontrollgruppe zeigte für I-1KO ein deutlich vermindertes Niveau der Marker gegenüber WT. Ergebnis Der I-1-Knockout verändert die kardiale Kontraktilität und wirkt sowohl in phasen- als auch in geschlechtsabhängiger Weise auf die Mortalität infolge druckinduzierter Herzinsuffizienz. Er ist nachteilig für männliche Tiere in der akuten Phase kardialer Belastung, während er für weibliche Tiere im weiteren Verlauf protektive Wirkung entfaltet. Eine erhöhte Mortalität in der akuten Phase kann durch den Ausfall der Verstärkerfunktion des I-1 erklärt werden, da hiermit eine Einschränkung der akut notwendigen kontraktilen Adaptionsfähigkeit einhergeht. Ein Überlebensvorteil bei chronischer kardialer Belastung könnte darauf zurückzuführen sein, dass die pathologisch erhöhte sympathische Aktivierung der β-adrenergen Kaskade infolge der I-1-Depletion eine geringere Auswirkung auf die Zielstrukturen des aktivierten I-1 am Sarkoplasmatischen Retikulum hat. Darüber hinaus lassen die Analysen der Hypertrophiemarker eine veränderte Genexpression zwischen I-1KO und WT auch unter nicht-pathologischen Bedingungen vermuten.

Worldwide income taxation in the country of residence is a legal dogma of international taxation. We question this dogma from the perspective of relations between developed and developing countries from a legal and economic perspective, and make a modern and fair proposal for tax treaties. We will show under which conditions a developing and a developed country will voluntarily sign a tax treaty where information is exchanged truthfully and whether they should share revenues. Moreover, we will demonstrate how the conclusion of a tax treaty can assist in the implementation of a tax audit system. / Series: WU International Taxation Research Paper Series

To what degree developing countries gain from signing double tax treaties is being hotly debated. In this paper, we analyze the Austrian tax treaty policy. Combining legal and economic perspectives, we find that developing countries are likely to expect both positive and negative impacts from signing a double tax treaty (DTT) with Austria. On the one hand, the results of our econometric analysis suggest that middle-income countries that sign a DTT with Austria may expect an increased number of foreign direct investment projects from Austrian companies. On the other hand, the signatory states may suffer from limited withholding taxation rights established in the DTTs for the source country, which could lead to reduced tax revenues in the developing countries. (authors' abstract) / Series: WU International Taxation Research Paper Series

京都大学 / 新制・課程博士 / 博士(理学) / 甲第22999号 / 理博第4676号 / 新制||理||1671(附属図書館) / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査) 長野 邦浩, 教授 中家 剛, 准教授 吉岡 興一 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM