The Letter Collections of Anselm of Canterbury

Anselm of Canterbury (1033–1109) was a prolific letter writer. The modern edition of his letter collection comprises more than 600 folio-size pages in print and includes 472 letters, the vast majority of which were sent by him. Our knowledge of Anselm’s letters is derived from collections of his letters, for none of his correspondence survives in its original form of individual letters. There was no one canonical version of the collection, and the extant manuscripts generally differ substantially: the largest medieval manuscript witnesses include over 400 letters, while the smallest contain only a few. We know 38 manuscript witnesses, but no authorial manuscript survives. Certain references in Anselm’s letters reveal, however, that he collected his correspondence on at least two occasions while he was still abbot of Bec, and this study proposes that a third collection was possibly made under his supervision in Christ Church. The third collection also covered Anselm’s Canterbury period. Whether the third collection was authorial or posthumous is unclear. Certain contextual evidence and references in letters would suggest that the collection was authorial. If so, the collection was probably a register book, which was started in c. 1101 at the earliest. There is no positive proof that any of the three surviving minor collections may be authorial. Each of these collections was circulating at a very early stage, however, some probably in Anselm’s lifetime. Moreover, the minor collections seem to have been put together from smaller source units, which possibly originated at Bec. The contents of these units suggest very early and possibly authorial origins: the letters are mainly from Anselm’s years as prior of Bec. The critical edition by F. S. Schmitt represents the current phase in the textual tradition of Anselm’s letter collection. This study demonstrates that the value of the edition is weakened in particular by the way in which Schmitt selected manuscripts for collation, doubtless influenced by the fact that he had not established the structure of the tradition properly. Ultimately it is impossible to undertake systematic research on the letter collection on the basis of Schmitt’s edition.

Oncolytic Adenoviruses for Gynecologic Cancer

Gene therapy is a promising novel approach for treating cancers resistant to or escaping currently available modalities. Treatment approaches are based on taking advantage of molecular differences between normal and tumor cells. Various strategies are currently in clinical development with adenoviruses as the most popular vehicle. Recent developments include improving targeting strategies for gene delivery to tumor cells with tumor specific promoters or infectivity enhancement. A rapidly developing field is as well replication competent agents, which allow improved tumor penetration and local amplification of the anti-tumor effect. Adenoviral cancer gene therapy approaches lack cross-resistance with other treatment options and therefore synergistic effects are possible. This study focused on development of adenoviral vectors suitable for treatment of various gynecologic cancer types, describing the development of the field from non-replicating adenoviral vectors to multiple-modified conditional replicating viruses. Transcriptional targeting of gynecologic cancer cells by the use of the promoter of vascular endothelial growth factor receptor type 1 (flt-1) was evaluated. Flt-1 is not expressed in the liver and thus an ideal promoter for transcriptional targeting of adenoviruses. Our studies implied that the flt-1 promoter is active in teratocarcinomas.and therefore a good candidate for development of oncolytic adenoviruses for treatment of this often problematic disease with then poor outcome. A tropism modified conditionally replicating adenovirus (CRAd), Ad5-Δ24RGD, was studied in gynecologic cancers. Ad5-Δ24RGD is an adenovirus selectively replication competent in cells defective in the p16/Rb pathway, including many or most tumor cells. The fiber of Ad5-Δ24RGD contains an integrin binding arginine-glycine-aspartic acid motif (RGD-4C), allowing coxackie-adenovirus receptor independent infection of cancer cells. This approach is attractive because expression levels of CAR are highly variable and often low on primary gynecological cancer cells. Oncolysis could be shown for a wide variety of ovarian and cervical cancer cell lines as well as primary ovarian cancer cell spheroids, a novel system developed for in vitro analysis of CRAds on primary tumor substrates. Biodistribution was evaluated and preclinical safety data was obtained by demonstrating lack of replication in human peripheral blood mononuclear cells. The efficicacy of Ad5-Δ24RGD was shown in different orthotopic murine models including a highly aggressive intraperitoneal model of disseminated ovarian cancer cells, where Ad5-Δ24RGD resulted in complete eradication of intraperitoneal disease in half of the mice. To further improve the selectivity and specificity of CRAds, triple-targeted oncolytic adenoviruses were cloned, featuring the cyclo-oxygenase-2 (cox-2) promoter, E1A transcomplementation and serotype chimerism. Those viruses were evaluated on ovarian cancer cells for specificity and oncolytic potency with regard to two different cox2 versions and three different variants of E1A (wild type, delta24 and delta2delta24). Ad5/3cox2Ld24 emerged as the best combination due to enhanced selectivity without potency lost in vitro or in an aggressive intraperitoneal orthotopic ovarian tumor model. In summary, the preclinical therapeutic efficacy of the CRAds tested in this study, taken together with promising biodistribution and safety data, suggest that these CRAds are interesting candidates for translation into clinical trials for gynecologic cancer.

Valistus suomalaisessa kirjakulttuurissa 1700-luvulla

The dissertation discusses the history of the book and the Enlightenment in Finland by studying the reception and diffusion of eighteenth-century books and by approaching the discourse on the Enlightenment in Finnish source material. The methods used relate to historian Robert Darnton s studies on eighteenth-century print culture and his analyses of the relations between print culture and society. The study is based on diverse eighteenth-century sources: books, pamphlets and dissertations, bibliographies, book auction protocols, parliamentary documents, estate inventory deeds, newspapers, letters, lectures, memoirs and commonplace books. By the end of the eighteenth century, book production had increased and secular literature had begun to challenge the dominance of religious literature. The books of the Enlightenment belonged to the new literature that found its way into Finnish book collections previously dominated by religious literature. Enlightenment literature is not a set selection of books but rather diverse works from different genres. Thus the study introduces a variety of printed material, from philosophical tracts and textbooks to novels and pornography. In the case of books of the Enlightenment, the works of French Voltaire and German Christian Wolff were among the most widely read and circulated books in Finland. First and foremost, the Enlightenment was an era of intellectual debate. These debates carried strong criticism of the prevailing systems of thought. Enlightenment ideas challenged the Lutheran society of Sweden and especially its sense of conformity. Contemporaries saw many of the books of the Enlightenment as vessels of new ideas and criticism. Furthermore, this kind of print material was interpreted as being dangerous for uneducated readers. Belonging to a certain estate and social class had a major impact on individuals reading habits and their acquisition of books. One specific social group stands out in the Finnish source material: the officers at the Sveaborg naval fortress possessed and distributed Enlightenment books more than the members of any other social class. Other essential social groups were scholars, the nobility and the clergy, who took part in debates concerning the ideas and benefits of the Enlightenment. In the Finnish debates at the time, the concept of Enlightenment involved three primary notions. Firstly, it referred to the French philosophers, les philosophes, and to their works as well as to the social changes that took place during the French revolution. It also carried the idea of philosophical light or the light of reason, in a sense similar to Immanuel Kant s writings. Most importantly, it referred to a belief in progress and to a trust in true knowledge that would supercede ignorance and fanaticism. Hence, it is impossible to speak about the Enlightenment era in the Swedish realm without such concepts as reason, benefit or progress. These concepts likewise marked the books of the Enlightenment in eighteenth-century Finland.