Chapter 1 provides an overview on the chemistry of pyridines and aminopyridines, their biological activities and their synthesis using Bohlmann-Rahtz, Hantzsch and Chichibabin methodology. It discusses the application of modern alternative reaction platforms, such as microwave-assisted synthesis and flow chemistry, of relevance to the synthesis and reactions of pyridine derivatrives. Chapter 2 discusses Lewis acid catalysis in the Bohlmann-Rahtz pyridine synthesis and describes new one-pot, two- and three-component methodologies that have been developed for the synthesis of natural products containing the pyridine motif. These methods have been compared and contrasted and applied to the use of tetranuclear coordination clusters as Lewis acid mixed metal catalysts for Bohlmann-Rahtz cyclodehydration and pyridine synthesis. Chapter 3 discusses the use of the Bohlman–Rahtz pyridine synthesis for the preparation of a range of fused heterocycles containing the pyridine moiety in high yield, including 1,3,7-trimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione, 1,3-dimethyl-7-phenylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione, 1,7-dimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)dione and 1-methyl-7-phenylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione. Chapter 4 describes new substrate scope for the Bohlmann-Rahtz pyridine synthesis by incorporating an amino group at the 2-position of the products. The synthesis of a range of 2,3,6-trisubstituted and 2,3,4,6-tetrasubstituted pyridines was accomplished with total regiocontrol using this new method under microwave-assisted conditions. Chapter 5 describes a new microwave-assisted method for the synthesis of poly-deuterated pyridines. The microwave mediated deuteration of aminopyridine derivatives both with and without the presence of DCl has been studied. The regioselectivity and yields for these processes were compared. Following discovery of a new method for single cycle H/D exchange at multiple positions, high yield and high levels of deuterium incorporation have been found for a range of substrates.

This study in the doctrine of God, with special reference to the thought of John Macquarrie and Charles Hartshorne, addresses the issue of the relational problematic and suggests a potential resolution. The 'Relational Problematic' focusses on the notion of aseity and the doctrine of the Trinity. It concerns the ontological conundrum posed by, on the one hand, the insistence that the external relations God has are of no ontological consequence to him, together with, on the other hand, the witness of the Christian tradition that suggests such relations are not, in fact, inconsequential for the being of God. The task of constructing a resolution begins with the ontology of the early Heidegger which is implicitly relational. Thus 'relational ontology' furnishes a hermeneutical key whereby a 'Relational Theology' may be developed. This development involves, first, the analysis of John Macquarrie's existential- ontological theism, which concludes that to speak of God in the language of 'Being' is to speak of the relational being of God. Second, and alongside this, is placed the analysis and discussion of the neoclassical theism of Charles Hartshorne: the pluriform language of Becoming by which God is conceived in process thought has at its base the perception of the essential relatedness of God. But both Macquarrie and Hartshorne have as a common problem the question of the "entitative status" of God. The solution is suggested by way of conceiving God as "Relational Entity" . The 'Being' and the 'Becoming' of God are manifest in ad extra relatedness: such relationality forms the fundamental ontological motif in the conception of God. This relational perspective frames the resolution to the relational problematic. Aseity is reinterpreted in the light of the relational context of God: God is existentially prior, but not relationally self-sufficient. Trinity is interpreted in terms of relational identity: the necessary ad extra relatedness of God is manifest in three particular patterns of relating. 'God' is thus ontologically conceived as singular relational entity manifesting threefold relational identity.

The present study critically evaluates the alleged close floristic links between Chaco and Caatingas vegetation in South America. A reassessment of the phytogeography of these areas has been made by (a) comparing species lists in virtually all of the available literature, and (b) plotting dot-map distributions of relevant taxa based on the author's own herbarium studies and recent monographs. The environmental factors, geology and geomorphology, climate and soils of both areas were also analyzed to assess their degree of internal coherence. The prevailing concept of the Chaco itself proved to be a broad geographical entity rather than a well-defined geobotanic unit in vegetational terms, and a redefinition of the Chaco sensu stricto and a new map of the province has been proposed. Several forest communities have been excluded from the Chaco s.s. since their floristic composition clearly link them to other neighbouring provinces. Although the Caatingas province vegetation is not so well known, the area appears to be a consistent natural region, and a new vegetation type has been briefly described. Detailed floristic lists of the main woody and succulent species of the Chaco s.s., the Caatingas and the Subandean Piedmont Forests are presented, which provide the basis for a subsequent phytosociological analyses (classical and numerical approaches) of these vegetation units vis-a-vis the rest of the seasonal forests and woodlands of South America. The results suggest that the alleged affinities Chaco-Caatingas are very feeble indeed, particularly when they are compared to the actual links between the Caatingas and other seasonal communities in the continent: the Guajira province in N Colombia and Venezuela, the dry forests of W Ecuador, and very particularly the Subandean Piedmont Forests in NW Argentina and SW Bolivia. Some basic patterns of distribution of the floristic elements of seasonal forests in South America have been identified and found to form coherent trends in a series of accurate dot maps: a) Chaco endemics; b) Caatingas endemics; c) Neotropical seasonal forests pattern, including c.1- Residual Pleistocenic Seasonal Formations Arc (or 'Pleistocenic Arc'), extending from the Caatingas through some Planalto forests and calcium-rich localities in the Cerrados, SW Mato Grosso do Sul and the Santiago and Chiquitos Sierras, to the Parana-Paraguay river system and the Subandean Piedmont Forests; c.2- Tropical and Subtropical Seasonal Forests in South America; and c.3- Amphitropical Seasonal Forests pattern. The zoological evidence regarded until present as further proof of the Chaco-Caatingas links is also analysed and mapped, and the results are sharply coincidental with those found for plant distribution. An attempt has also been made to interpret the origin of the Caatingas flora; a hypothetical framework of probable ancient connections across South America between present-day seasonal woody communities is postulated, which have been interpreted here as migratory routes during the wet-dry climatic fluctuations of the late Pleistocene (18-12 ka BP). It is therefore concluded that the floristic links between the Chaco and the Caatingas are very weak and negligible when compared to other relationships, such as those between Chaco-Monte or Caatingas-Subandean Piedmont Forests. It is proposed that the Caatingas should be removed from the Chaquenian Dominium and placed in the Amazonian Dominium, with which they show much stronger affinities.

This thesis is an investigation into the image of the emperor Heraclius as depicted by the ancient sources who cover his reign (610-641 A. D.). In order to establish the relevant criteria for the portrayal of an emperor it was first necessary to provide the reader with a synopsis of writings on the role of the emperor from the time of Eusebius onwards. The reign of Heraclius was then treated in roughly chronological fashion, there follow four chapters concerning the sources' description of his military exploits, his coup, and the warfare with the Avars and the Persians, including the siege of Constantinople. Here the discussion concerns the personal role of Heraclius in events and his culpability for their outcome. Heraclius' triumph in these wars led him to seek a compromise with the Monophysite Church that was defeated by opposition from the Chalcedonian Church in the recently liberated provinces. His failure to achieve any lasting settlement is then discussed as a reason for the success of the Arab invasions that followed. Heraclius' reputation as a reformer, amongst ancient and modern authors alike, is then considered with special reference to the controversy surrounding the introduction of the themes. The last chapter is a review of the interrelationship of all the sources that describe Heraclius' reign, in an attempt to define their various influences.

This thesis deals with theologies of the Resurrection in the twentieth century. We have chosen for study seven major theologians whose work reflects significant achievement in this area. We begin with a look at 'dialectical' theologians Karl Barth and Rudolf Bultmann and deal with their debate on the nature and meaning of the Resurrection. Because of their importance to theology they are dealt with extensively. From there we move on to the contemporary theologians of 'hope, ' Jürgen Moltmann and Wolfhart Pannenberg, before completing our research with a chapter on the Catholic theologians Karl Rahner, Edward Schillebeeckx, and Hans Küng. It was our purpose initially (and we hope we have been consistent throughout) to give a well-rounded purview, and thus a fairer criticism, of each theology. Yet into the research it seemed obvious that a consistent major concern of each theologian centered on how one comes to faith in such a unique event. It was certainly at the core of the Barth-Bultmann debate and remains crucial. Thus it may be stated that the concerns which receive the primacy in this work are those discussions in our theologies which deal with the nature of the Resurrection, its status as an event of history, and its ability to be proved and thus believed as other events of history are proved and believed. We ultimately conclude that the most satisfactory entry into faith in the Resurrection is through a juxtaposing of the work of Wolfhart Pannenberg and Hans Küng. The focus of the paper is changed in the second half of the Conclusion as we suggest what course studies on the Resurrection might take in the future. Here we find the perspective of Jewish New Testament theologian Pinchas Lapide to be most provocative and speculate on the possibilities that the Resurrection might hold for Jewish-Christian relations.

La protéine de stress p8 fut découverte et caractérisée dans notre laboratoire. Cette protéine est surexprimée dans l'adénocarcinome pancréatique et possède un rôle dans la progression tumorale. Pendant ce travail de thèse, nous nous sommes focalisé sur le rôle de p8 dans les phases initiales de la tumorigénèse pancréatique et sur ses mécanismes d'action, impliqués dans la progression tumorale. Nous avons montré que p8 joue un rôle essentiel dans l'apparition des lésions PanINs suite à l'activation de l'oncogène Kras. Au niveau cellulaire, nous avons montré que la protéine p8 protège les cellules tumorales pancréatiques contre le stress de la privation en nutriments via la régulation de l'expression de RelB et IER3. La voie p8, RelB et IER3 est impliquée dans l'inhibition de l'apoptose suite au stress. De plus, nous avons observé que ces trois protéines sont co-exprimées dans les adénocarcinomes humains et leur expression corrèle avec l'évolution de la maladie. Dans un second lieu, nous avons démontré le rôle essentiel de la protéine p8 dans la résistance des cellules tumorales pancréatiques à l'hypoxie et à la privation en glucose. Nous avons identifié la voie p8/Aurora KinaseA, qui en réponse au stress métabolique, réduit l'apparition des dommages à l'ADN en contrôlant l'expression des gènes liés au cycle cellulaire et à la réparation de l'ADN. De plus, nos recherches ont montré que p8 protège les cellules tumorales du stress métabolique en inhibant la mort cellulaire dépendante de l'autophagie. Nous espérons que nos résultats aideront à mieux cibler les cellules tumorales pancréatiques et leur caractère résistant au stress micro-environnemental extrême. / The stress protein p8 was discovered and characterized in our laboratory. Over expressed in pancreatic adenocarcinoma, p8 is involved in tumor progression. During my PhD studies, we focused on the role of p8 in pancreatic cancer development and on its mechanisms of action. First, we demonstrated that p8 is essential for PanIN development following Kras oncogene activation. At the cellular level, we found that p8 protects pancreatic cancer cells upon nutrient starvation stress through the regulation of RelB and IER3 expression. p8, RelB and IER3-dependent cascade inhibits apoptosis after the starvation stress. Furthermore, we showed that these tree proteins are co expressed in human pancreatic adenocarcinoma. One the other hand, our study showed that p8 is involved in pancreatic cancer cells resistance to hypoxia and glucose starvation. We identified a p8/Aurora KinaseA pathway which, in response to such metabolic stress, reduces DNA damage by regulating cell cycle and DNA repair genes expression. Moreover, our studies demonstrated that p8/AURKA path protects cancer cells against metabolic stress by inhibiting autophagy-associated cell death. We expect that our data will help to get new therapeutics against pancreatic cancer.

Die Pathophysiologie der akuten Pankreatitis ist durch eine immunologische Dysregulation gekennzeichnet, deren genaue Mechanismen unvollständig verstanden sind. Zur Untersuchung des Einflusses des Stressproteins p8 wurde die akute experimentelle Pankreatitis in einer p8-defizienten Mauslinie induziert und das Immunsystem phänotypisiert. Auf die Entwicklung des Immun- und Organsystems hat eine p8-Deletion keinen Einfluss, jedoch ist die Immunseneszenz verbunden mit einer Splenomegalie, Milzsiderose und extramedullärer Hämatopoese. Die akute Pankreatitis verläuft bei Fehlen von p8 wesentlich schwerer, begleitet von einem stärkeren Verlust an CD4+ T-Zellen in Blut und Milz. In der Phase der Rekonvaleszenz kommt es unter p8-Defizienz zu einem gehäuften Auftreten lymphozytärer Apoptosen in der Milz, begleitet von einer schweren Mikroarchitekturstörung und Verlust von Lymphfollikeln. Es kann erstmals eine antiapoptotische Wirkung von p8 auf aktivierte Milzlymphozyten während der postinflammatorischen Immunrekonstitution postuliert werden, wobei die involvierten Signalwege weiter untersucht werden müssen.

“The existing work is easy to summarise; despite the ever present nature of furniture in people's lives, and its obvious position in a social context as a reflection of taste, wealth and progress, the study in Scotland of the trade which made it, and the furniture itself, has until recently been sadly neglected.” -- From the Preface. “This thesis is intended to hang flesh on the bones of Francis Bamford's ‘Dictionary of Edinburgh Wrights', rather than to be a counterpart to Pat Kirkham's study of the London trade¹². Whereas in Glasgow 'no rich vein of documentation has revealed the existence of a dominant city manufacturer comparable with Trotter of Edinburgh, whose furniture and business activities can be traced back into the eighteenth century¹³', in Edinburgh rich veins do exist. They have been used not only to illuminate the careers of individuals but also to explore the great range of services which these individuals offered. The editorial of the 1992 volume of ‘Regional Furniture' states that 'some work on Norwich, Chester, Doncaster, Lancaster and Glasgow is in print, but coverage is patchy'. That Edinburgh had such a clearly vibrant trade will hopefully be of encouragement to historians of all major British cities, even those that did not benefit from the privileges of a capital city, or bask in the reflected glow of the Enlightenment.” – From the Introduction.

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Die Pathophysiologie der akuten Pankreatitis ist durch eine immunologische Dysregulation gekennzeichnet, deren genaue Mechanismen unvollständig verstanden sind. Zur Untersuchung des Einflusses des Stressproteins p8 wurde die akute experimentelle Pankreatitis in einer p8-defizienten Mauslinie induziert und das Immunsystem phänotypisiert. Auf die Entwicklung des Immun- und Organsystems hat eine p8-Deletion keinen Einfluss, jedoch ist die Immunseneszenz verbunden mit einer Splenomegalie, Milzsiderose und extramedullärer Hämatopoese. Die akute Pankreatitis verläuft bei Fehlen von p8 wesentlich schwerer, begleitet von einem stärkeren Verlust an CD4+ T-Zellen in Blut und Milz. In der Phase der Rekonvaleszenz kommt es unter p8-Defizienz zu einem gehäuften Auftreten lymphozytärer Apoptosen in der Milz, begleitet von einer schweren Mikroarchitekturstörung und Verlust von Lymphfollikeln. Es kann erstmals eine antiapoptotische Wirkung von p8 auf aktivierte Milzlymphozyten während der postinflammatorischen Immunrekonstitution postuliert werden, wobei die involvierten Signalwege weiter untersucht werden müssen.