Speech and narrative: characterisation techniques in the "Aeneid"

The thesis provides a comprehensive analysis of the characterisation of two of the major figures in the Aeneid, Aeneas and Turnus. Particular attention is paid to their direct speeches, all of which are examined and, where relevant, compared to Homeric models and parallels. To this purpose considerable use is made of the indices in Knauer's Die Aeneis und Homer. A more general comparison is made between the dramatic (direct speech) role of Aeneas and those of Homer's Achilles (Iliad) and Odysseus (Odyssey). An appraisal is made (from the viewpoint of depiction of character) of the relationship between the direct and indirect speeches in the Aeneid. Reasons are given to suggest that it is not mere chance, or for the sake of variety, that certain speeches of Aeneas and Turnus are expressed in oratio obliqua. In addition, the narrative portrayal of Aeneas and Turnus is considered in apposition to that of the speeches. A distinction is drawn between Vergil's direct method of characterisation (direct speeches) and his indirect methods (narrative/oratio obliqua). Inevitably, the analysis involves major consideration of the Roman values which pervade the work. All speeches, thoughts and actions of Aeneas and Turnus are assessed in terms of pietas, impietas, furor, virtus, ratio, clementia, humanitas (etc.). It is shown that individual concepts (such as pietas and impietas) are reflected in Vergil's direct and indirect methods of characterisation. The workings of fate and their relevance to the pietas concept are discussed throughout.

TRIB2 in normal and malignant hematopoiesis - a transcription factor network

Hematopoiesis is the tightly controlled and complex process in which the entire blood system is formed and maintained by a rare pool of hematopoietic stem cells (HSCs), and its dysregulation results in the formation of leukaemia. TRIB2, a member of the Tribbles family of serine/threonine pseudokinases, has been implicated in a variety of cancers and is a potent murine oncogene that induces acute myeloid leukaemia (AML) in vivo via modulation of the essential myeloid transcription factor CCAAT-enhancer binding protein α (C/EBPα). C/EBPα, which is crucial for myeloid cell differentiation, is commonly dysregulated in a variety of cancers, including AML. Two isoforms of C/EBPα exist - the full-length p42 isoform, and the truncated oncogenic p30 isoform. TRIB2 has been shown to selectively degrade the p42 isoform of C/EBPα and induce p30 expression in AML. In this study, overexpression of the p30 isoform in a bone marrow transplant (BMT) leads to perturbation of myelopoiesis, and in the presence of physiological levels of p42, this oncogene exhibited weak transformative ability. It was also shown by BMT that despite their degradative relationship, expression of C/EBPα was essential for TRIB2 mediated leukaemia. A conditional mouse model was used to demonstrate that oncogenic p30 cooperates with TRIB2 to reduce disease latency, only in the presence of p42. At the molecular level, a ubiquitination assay was used to show that TRIB2 degrades p42 by K48-mediated proteasomal ubiquitination and was unable to ubiquitinate p30. Mutation of a critical lysine residue in the C-terminus of C/EBPα abrogated TRIB2 mediated C/EBPα ubiquitination suggesting that this site, which is frequently mutated in AML, is the site at which TRIB2 mediates its degradative effects. The TRIB2-C/EBPα axis was effectively targeted by proteasome inhibition. AML is a very difficult disease to target therapeutically due to the extensive array of chromosomal translocations and genetic aberrations that contribute to the disease. The cell from which a specific leukaemia arises, or leukaemia initiating cell (LIC), can affect the phenotype and chemotherapeutic response of the resultant disease. The LIC has been elucidated for some common oncogenes but it is unknown for TRIB2. The data presented in this thesis investigate the ability of the oncogene TRIB2 to transform hematopoietic stem and progenitor cells in vitro and in vivo. TRIB2 overexpression conferred in vitro serially replating ability to all stem and progenitor cells studied. Upon transplantation, only TRIB2 overexpressing HSCs and granulocyte/macrophage progenitors (GMPs) resulted in the generation of leukaemia in vivo. TRIB2 induced a mature myeloid leukaemia from the GMP, and a mixed lineage leukaemia from the HSC. As such the role of TRIB2 in steady state hematopoiesis was also explored using a Trib2-/- mouse and it was determined that loss of Trib2 had no effect on lineage distribution in the hematopoietic compartment under steady-state conditions. The process of hematopoiesis is controlled by a host of lineage restricted transcription factors. Recently members of the Nuclear Factor 1 family of transcription factors (NFIA, NFIB, NFIC and NFIX) have been implicated in hematopoiesis. Little is known about the role of NFIX in lineage determination. Here we describe a novel role for NFIX in lineage fate determination. In human and murine datasets the expression of Nfix was shown to decrease as cells differentiated along the lymphoid pathway. NFIX overexpression resulted in enhanced myelopoiesis in vivo and in vitro and a block in B cell development at the pre-pro-B cell stage. Loss of NFIX resulted in disruption of myeloid and lymphoid differentiation in vivo. These effects on stem and progenitor cell fate correlated with changes in the expression levels of key transcription factors involved in hematopoietic differentiation including a 15-fold increase in Cebpa expression in Nfix overexpressing cells. The data presented support a role for NFIX as an important transcription factor influencing hematopoietic lineage specification. The identification of NFIX as a novel transcription factor influencing lineage determination will lead to further study of its role in hematopoiesis, and contribute to a better understanding of the process of differentiation. Elucidating the relationship between TRIB2 and C/EBPα not only impacts on our understanding of the pathophysiology of AML but is also relevant in other cancer types including lung and liver cancer. Thus in summary, the data presented in this thesis provide important insights into key areas which will facilitate the development of future therapeutic approaches in cancer treatment.

Solidarity, the network and the history of workers' self-management from the Gdańsk Agreement to shock therapy

This PhD thesis is an empirical research project in the field of modern Polish history. The thesis focuses on Solidarity, the Network and the idea of workers’ self-management. In addition, the thesis is based on an in-depth analysis of Solidarity archival material. The Solidarity trade union was born in August 1980 after talks between the communist government and strike leaders at the Gdansk Lenin Shipyards. In 1981 a group called the Network rose up, due to cooperation between Poland’s great industrial factory plants. The Network grew out of Solidarity; it was made up of Solidarity activists, and the group acted as an economic partner to the union. The Network was the base of a grass-roots, nationwide workers’ self-management movement. Solidarity and the self-management movement were crushed by the imposition of Martial Law in December 1981. Solidarity revived itself immediately, and the union created an underground society. The Network also revived in the underground, and it continued to promote self-management activity where this was possible. When Solidarity regained its legal status in April 1989, workers’ self-management no longer had the same importance in the union. Solidarity’s new politico-economic strategy focused on free markets, foreign investment and privatization. This research project ends in July 1990, when the new Solidarity-backed government enacted a privatization law. The government decided to transform the property ownership structure through a centralized privatization process, which was a blow for supporters of workers’ self-management. This PhD thesis provides new insight into the evolution of the Solidarity union from 1980-1990 by analyzing the fate of workers’ self-management. This project also examines the role of the Network throughout the 1980s. There is analysis of the important link between workers’ self-management and the core ideas of Solidarity. In addition, the link between political and economic reform is an important theme in this research project. The Network was aware that authentic workers’ self-management required reforms to the authoritarian political system. Workers’ self-management competed against other politico-economic ideas during the 1980s in Poland. The outcome of this competition between different reform concepts has shaped modern-day Polish politics, economics and society.