Two Trilogies:On Stewart Parker and Tom Murphy

This chapter discusses the relations between Irish cinema and the other arts- chiefly, literature, theatre, painting, and photography. It provides a critical overview of the main scholarly approaches to those forms of adaptation and citation that have tended to dominate Irish film production. It argues that factors such as the historic marginalization of non-literary modernist art in Ireland, a deep cultural resistance to intellectual and politically-engaged filmmaking, and a commercially-driven attachment to formulaic narrative structures, are among the reasons why Ireland has generally failed to produce a distinctive and successful cinema. The chapter concludes by discussing some films that have resisted this trend by offering their audiences a more creative approach to -- or poetics of -- adaptation that has more in common with the visual -- rather than literary -- arts in Ireland.

Ultrasensitive non-resonant detection of ultrasound with plasmonic metamaterials

Optical sensors for ultrasound detection provide high sensitivity and bandwidth, essential for photoacoustic imaging in clinical diagnostics and biomedical research. Implementing plasmonic metamaterials in a non-resonant regime facilitates sub-nanosecond, highly sensitive detectors while eliminating cumbersome optical alignment necessary for resonant sensors.

Banished to the Barn - John Doherty and 'Bonnie Kate'

John Doherty (1900-1980) was one of the most influential Irish musicians of the twentieth century. His music has had a lasting impact on Irish traditional music making around the globe. This paper traces the development of his setting of the canonical reel 'Bonnie Kate'. Using transcription historical investigation Doherty's style is examined in comparison to his contemporaries.

MiR-433 induces cellular senescence rendering ovarian cancer cells less likely to undergo chemotherapy-induced apoptosis

Annually, ovarian cancer (OC) affects 240,000 women worldwide and is the most lethal gynaecological malignancy. Such mortality is predominantly associated with the development of an intrinsic and acquired resistance to chemotherapy, the lack of targeted therapies and the lack of biomarkers predicting therapeutic response.

Our clinical data demonstrates that increased miR-433 expression in primary high grade serous OC (HGSOCs) is significantly associated with poor PFS (n=46, p=0.024). Interestingly, the IHC analysis of two miR-433 targets: MAD2 [Furlong et al., 2012 PMID:22069160] and HDAC6 shows that low IHC levels of both proteins is also significantly associated with worse outcome (p=0.002 and 0.002 respectively; n=43). Additionally, the analysis of miR 433 in the publicly available TCGA dataset corroborates that high miR-433 is significantly correlated with worse OS for patients presenting with OC (n=558 and p=0.027). In vitro, in a panel of OC cell lines, higher miR-433 and lower MAD2 and HDAC6 levels were associated with resistance to paclitaxel.

To further investigate the role of miR-433 in the cellular response to chemotherapy, we generated an OC cell line stably expressing miR-433, or miR-control. MTT viability assays and Western Blot analyses established that miR-433 cells were more resistant to paclitaxel treatment (50nM) compared to miR-controls. Importantly, we have shown for the first time that miR 433 induced senescence, exemplified by a flattened morphology and down-regulation of phosphorylated Retinoblastoma (p-Rb), a molecular marker of senescence. Surprisingly, miR 433 induced senescence was independent from two well recognised senescent drivers: namely p53/p21 and p16. To explore this further we performed an in silico analysis of seven microRNA platforms which indicated that miR 433 potentially targets Cyclin-dependent kinase CDK6, which promotes sustained phosphorylation of Rb and thus cell cycle progression. In vitro, the overexpression of pre-miR-433 resulted in diminished CDK6 expression demonstrating a novel interaction between miR-433 and CDK6.

In conclusion, this study demonstrates that high miR-433 expression predicts poor outcome in OC patients by putatively rendering OC cells resistant to paclitaxel treatment through the induction of cellular senescence identifying this microRNA as a potential marker of chemoresponse.