The battle of the stages : the conflict between the theatre and the institutions of government and religion in England 1660-1890

Between 1660 and 1880 a number of Royal Patents were granted and Acts of ParI iament passed whose purpose and effect, it has generally been acknowledged, was to restrict the spread and availability of English theatre, in particular that within the two cities of the metropolis, and to limit its potential as a forum of debate for the examination of ideas or the promotion of political dissent. During the same period, although not necessarily at the same time, theatre came under fire from religious groups of many different denominations. This condemnation and the measures taken by this special interest group in society to combat the influence of the stage has also been held to have had a restrictive effect on the institution of theatre. This research has been primarily based on an examination and analysis oflegislation, parliamentary debates, religious tracts, papers and letters in Lambeth Palace Library, letters in the Manuscript Department of the British Library, theatre texts, the writings of contemporary theatre critics, articles in contemporary newspapers and journals specialising in theatrical topics, specialist reports and magazines published by various religious denominations, contemporary pamphlets, diaries, biographies, theatre ephemera and current critical writing in specialist magazines and books devoted to theatrical and religious topics. After discussing the reasons for setting the parameters of 1660 and the late 1880s for this research, the thesis considers the importance of the institution of theatre in the particular period studied and its relationship to the whole panorama of the history of theatre. After detailing a number of questions regarding the purpose of theatre and the effect it has and has had on society, this research examines the objects, effects and motivation behind the main statutes that were enacted to deal with the phenomenon of theatre between 1660 and 1880. In particular the genesis and context of The Restoration Patents, the Licensing Act (1737), the Disorderly Houses Act (1751), the Theatrical Representations Act (1788), the failed Sadler's Wells Bill (1788), and Interludes Bill (1788), and the Theatres Act (1843) have been examined, the aims of each debated and the effects of each of the legislative measures on theatre as a whole is explored. The opposition that came from religious forces within the country during the period under study is also examined and analysed. The complaints from Church and Chapel were various: blasphemy, indolence, vice, perversion (particularly of the young), consorting with unwholesome company and drawing people away from God were all cited as sins of the stage. The underlying causes ofthe censure of important religious figures as well as that which came from different denominations is examined. The various measures put into operation to combat the dangers perceived to be coming from theatre are explored and their efficiency debated. Finally the study examines the nature of the theatrical experience and how this has been affected by the legislation and condemnation of the religious interest in the country. A principal conclusion is that theatre in England was not repressed or rendered impotent by any of the legislation nor was it by the tactical opposition of the religious faction in society. Indeed theatre gained strength and potency by finding ways to circumvent the opposition it encountered. So successful was it in overcoming the ploys of the legislature and religious interests and so instrumental was theatre as a focus for life in England during the period under study that both of the forces of opposition eventually had to adopt theatre as an ally in the implementation of their own political agenda

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The battle of the stages The conflict between the theatre and the institutions of government and religion in England 1660-1890

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Asymmetric Electrostatic and Hydrophobic–Hydrophilic Interaction Forces between Mica Surfaces and Silicone Polymer Thin Films

We have synthesized model hydrophobic silicone thin films on gold surfaces by a two-step covalent grafting procedure. An amino-functionalized gold surface reacts with monoepoxy-terminated polydimethylsiloxane (PDMS) via a click reaction, resulting in a covalently attached nanoscale thin film of PDMS, and the click chemistry synthesis route provides great selectivity, reproducibility, and stability in the resulting model hydrophobic silicone thin films. The asymmetric interaction forces between the PDMS thin films and mica surfaces were measured with the surface forces apparatus in aqueous sodium chloride solutions. At an acidic pH of 3, attractive interactions are measured, resulting in instabilities during both approach (jump-in) and separation (jump-out from adhesive contact). Quantitative analysis of the results indicates that the Derjaguin-Landau-Verwey-Overbeek theory alone, i.e., the combination of electrostatic repulsion and van der Waals attraction, cannot fully describe the measured forces and that the additional measured adhesion is likely due to hydrophobic interactions. The surface interactions are highly pH-dependent, and a basic pH of 10 results in fully repulsive interactions at all distances, due to repulsive electrostatic and steric-hydration interactions, indicating that the PDMS is negatively charged at high pH. We describe an interaction potential with a parameter, known as the Hydra parameter, that can account for the extra attraction (low pH) due to hydrophobicity as well as the extra repulsion (high pH) due to hydrophilic (steric-hydration) interactions. The interaction potential is general and provides a quantitative measure of interfacial hydrophobicity/hydrophilicity for any set of interacting surfaces in aqueous solution