The Gentleman-Scholar at Home: Domesticity, Masculinity, and Civility in Dutch Seventeenth-Century Genre Painting

This dissertation examines the gentleman-scholar depicted at home in Dutch seventeenth-century genre paintings, focusing primarily on art created in the Northern Netherlands from the 1630s through the 1670s. The methodological approach is art historical but also pertains to history of architecture, history of dress, and gender studies. Employing the framework of the 'Ages of Man', this thesis investigates three related pictorial themes: the student, the scholar in his prime, and the aged scholar. Variations of male scholarly figures and the accoutrements of the study have a long history in Europe. Prototypical sources include religious history paintings of learned hermit-saints; artistic interest in the allegorical Saturnine persona; portraits of famous scholars; and the iconography of scholarly melancholy implied through vanitas allusions in portraiture and genre paintings. While the majority of Dutch genre paintings pertain to themes of women, male domestic routines form a small but important subset of this imagery and have not been studied. By the 1640s, this subject is readily identified by his setting, clothing, and actions. The ubiquity of scholarly attributes, such as books and globes, paired with the wearing of scholarly robes suggest the merits of intellectual curiosity and the privileges of studying as a pastime and designating a room as a study (studeerkamer). Distinct themes in genre also imply the challenges and rewards of scholarly activity pursued in concert with masculine civic and familial duty. Central to the development of this pictorial theme were: the innovative treatment of learned men by Rembrandt and his circle; the fijnschilder subjects of Dou; and the practice of amateur study by elite men, as suggested by the art of Vermeer. As this dissertation reveals, this convention did not grow to be consistent across the Northern Netherlands, nor was artistic interest limited to university towns. Rather, the larger relevance of scholars in Dutch society is evident in visual and literary sources. The domesticity of this figure in genre painting suggests that scholars mediated between an active and a contemplative life. Societal respect was garnered for scholars through their balance of familial and social duties with the honorable pastime of scholarly leisure.

ROLE OF STAT1 AND CXCL10 IN THE TUMOUR IMMUNE MICROENVIRONMENT OF HIGH-GRADE SEROUS OVARIAN CANCER

High-grade serous ovarian cancer (HGSC) is the most prevalent epithelial ovarian cancer characterized by late detection, metastasis and resistance to chemotherapy. Previous studies on the tumour immune microenvironment in HGSC identified STAT1 and CXCL10 as the most differentially expressed genes between treatment naïve chemotherapy resistant and sensitive tumours. Interferon-induced STAT1 is a transcription factor, which induces many genes including tumour suppressor genes and those involved in recruitment of immune cells to the tumour immune microenvironment (TME), including CXCL10. CXCL10 is a chemokine that recruits tumour infiltrating lymphocytes (TILs) and exhibits angiostatic function. The current study was performed to determine the effects of differential STAT1 and CXCL10 expression on HGSC disease progression and TME. STAT1 expression and intratumoural CD8+ T cells were evaluated as prognostic and predictive biomarkers via immunohistochemistry on 734 HGSC tumours accrued from the Terry Fox Research Institute-Canadian Ovarian Experimental Unified Resource. The combined effect of STAT1 expression and CD8+ TIL density was confirmed as prognostic and predictive companion biomarkers in the second independent biomarker validation study. Significant positive correlation between STAT1 expression and intratumoral CD8+ TIL density was observed. The effects of enforced CXCL10 expression on HGSC tumour growth, vasculature and immune tumour microenvironment were studied in the ID8 mouse ovarian cancer cell engraftment in immunocompetent C57BL/6 mice. Significant decrease in tumour progression in mice injected with ID8 CXCL10 overexpressing cells compared to mice injected with ID8 vector control cells was observed. Multiplexed cytokine analysis of ascites showed differential expression of IL-6, VEGF and CXCL9 between the two groups. Endothelial cell marker staining showed differences in tumour vasculature between the two groups. Immune transcriptomic profiling identified distinct expression profiles in genes associated with cytokines, chemokines, interferons, T cell function and apoptosis between the two groups. These findings provide evidence that STAT1 is an independent biomarker and in combination with CD8+ TIL density could be applied as novel immune-based biomarkers in HGSC. These results provide the basis for future studies aimed at understanding mechanisms underlying differential tumour STAT1 and CXCL10 expression and its role in pre-existing tumour immunologic diversity, thus potentially contributing to biomarker guided immune modulatory therapies.