Reading Pitscottie's Cronicles: a case study on the history of literacy in Scotland, 1575-1814

This thesis addresses a range of research questions regarding literacy in early modern Scotland. Using the early modern manuscripts and printed editions of Robert Lindsay of Pitscottie’s late sixteenth-century 'Cronicles of Scotland' as a case study on literacy history, this thesis poses the complementary questions of how and why early modern Scottish reading communities were encountering Pitscottie’s 'Cronicles', and how features of the material page can be interpreted as indicators of contemporary literacy practices. The answers to these questions then provide the basis for the thesis to ask broader socio-cultural and theoretical questions regarding the overall literacy environment in Scotland between 1575 and 1814, and how theorists conceptualise the history of literacy. Positioned within the theoretical groundings of historical pragmatics and ‘new philology’ – and the related approach of pragmaphilology – this thesis returns to the earlier philological practice of close textual analysis, and engages with the theoretical concept of mouvance, in order to analyse how the changing ‘form’ of Pitscottie’s 'Cronicles', as it was reproduced in manuscript and print throughout the early modern period, indicates its changing ‘function’. More specifically, it suggests that the punctuation practices and paratextual features of individual witnesses of the text function to aid the highly-nuanced reading practices and purposes of the discrete reading communities for which they were produced. This thesis includes extensive descriptive material which presents previously unrecorded data regarding twenty manuscripts and printed witnesses of Pitscottie’s 'Cronicles', contributing to a gap in Scotland’s literary/historiographical canon. It then analyses this material using a transferable methodological framework which combines the quantitative analysis of micro-data with qualitative analysis of this data within its socio-cultural context, in order to conduct diachronic comparative analysis of copy-specific information. The principal findings of this thesis suggest that Pitscottie’s 'Cronicles' were being read for a combination of devotional and didactic purposes, and that multiple reading communities, employing highly nuanced reading practices, were encountering the text near-contemporaneously. This thesis further suggests that early modern literacy practices, and the specific reading communities which employ them, should be described as existing within a spectrum of available practices (i.e. more or less oral/aural or silent, and intensive or extensive in practice) rather than as dichotomous entities. As such, this thesis argues for the rejection of evolutionary theories of the history of literacy, suggesting that rather than being described antithetically, historical reading practices and purposes must be recognised as complex, coexisting socio-cultural practices, and the multiplicity of reading communities within a single society must be acknowledged and analysed as such, as opposed to being interpreted as universal entities.

A shadow replaced by realities: the theme of temple in relation to Christology, Pneumatology and Ecclesiology in John's Gospel

This dissertation seeks to examine the role of the temple in relation to Christology, Pneumatology, and Ecclesiology in John’s Gospel. The Jerusalem temple, which was believed to be the shadow of the true temple in the heavens, was destroyed in A.D. 70. John, writing his Gospel after its destruction, presented the person of Jesus as the new cultic center of Judaism, in whom the more transcendent reality of the heavenly temple was truly embodied. The eschatological Spirit would animate the new worship inaugurated in the messianic temple, so that the believers could worship the Father in spirit and in truth. The living water of the Spirit was expected to flow from the heavenly temple, which is the glorified Jesus, throughout the earth via the mission of the ecclesial community – a community now constituted as the sacred temple. In this way, the Fourth Gospel presents Israel’s temple and its cult replaced by new realities: the temple of Jesus’ body and the temple of the church. The former is incarnated as the temple, while the latter is transformed into the temple by the indwelling power of the Holy Spirit.

Development of radiotracers for nuclear imaging of poly(ADP-ribose) polymerase-1 and the translocator protein in glioblastoma.

Glioblastoma (GBM) is a highly aggressive and fatal brain cancer that is associated with a number of diagnostic, therapeutic, and treatment monitoring challenges. At the time of writing, inhibition of a protein called poly (ADP-ribose) polymerase-1 (PARP-1) in combination with chemotherapy was being investigated as a novel approach for the treatment of these tumours. However, human studies have encountered toxicity problems due to sub-optimal PARP-1 inhibitor and chemotherapeutic dosing regiments. Nuclear imaging of PARP-1 could help to address these issues and provide additional insight into potential PARP-1 inhibitor resistance mechanisms. Furthermore, nuclear imaging of the translocator protein (TSPO) could be used to improve GBM diagnosis, pre-surgical planning, and treatment monitoring as TSPO is overexpressed by GBM lesions in good contrast to surrounding brain tissue. To date, relatively few nuclear imaging radiotracers have been discovered for PARP-1. On the other hand, numerous tracers exist for TSPO many of which have been investigated in humans. However, these TSPO radiotracers suffer from either poor pharmacokinetic properties or high sensitivity to human TSPO polymorphism that can affect their binding to TSPO. Bearing in mind the above and the high attrition rates associated with advancement of radiotracers to the clinic, there is a need for novel radiotracers that can be used to image PARP-1 and TSPO. This thesis reports the pre-clinical discovery programme that led to the identification of two potent PARP-1 inhibitors, 4 and 17, that were successfully radiolabelled to generate the potential SPECT and PET imaging agents [123I]-4 and [18F]-17 respectively. Evaluation of these radiotracers in mice bearing subcutaneous human GBM xenografts using ex vivo biodistribution techniques revealed that the agents were retained in tumour tissue due to specific PARP-1 binding. This thesis also describes the pre-clinical in vivo evaluation of [18F]-AB5186, which is a novel radiotracer discovered previously within the research group with potential for PET imaging of TSPO. Using ex vivo autoradiography and PET imaging the agent was revealed to accumulate in intracranial human GBM tumour xenografts in good contrast to surrounding brain tissue, which was due to specific binding to TSPO. The in vivo data for all three radiolabelled compounds warrants further pre-clinical investigations with potential for clinical advancement in mind.