‘Bhíodh muid ag damhsa go maidin’ : dance, music, and community in Árainn

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The Superiority Complex of the English Gentry and the Lifting of the Jewish Other in Two versions of George Eliot’s Daniel Deronda

This study examines two central themes in Daniel Deronda, both the 1876 novel by George Eliot and the 2002 BBC film adaptation based on the novel. The two themes are interconnected and are defined as the superiority complex of the English gentry and the lifting of the Jewish subordinate Other. The dual statement which this study reads in the narrative is firstly: a critique of imperial attitudes of arrogance and prejudice amongst the English gentry, and particularly the English gentleman, which results in a dis-enthroning of the English gentleman as an iconic ideal; and secondly, a dignifying treatment of Jewish characters and Jewishness which lifts the Jews as a group from the position of marginalized subordinate Other which they held in 19th century European society. This study asserts that the public reception of the adaptation was more positive than the initial reception of Eliot's novel and examines whether or not the more positive reaction is the result of some mitigating change in the treatment of these two themes. The findings are that the controversial statement has not been softened in the adaptation, but slightly accentuated. The concluding discussion suggests that the statement of the narrative is less offensive today because of a widening of audience and a significant change in prevalent social and ideological attitudes in the early 21st century. The study adopts a postcolonial theoretical approach to the material.fi=Opinnäytetyö kokotekstinä PDF-muodossa.|en=Thesis fulltext in PDF format.|sv=Lärdomsprov tillgängligt som fulltext i PDF-format

“Listening for landfall”: how silence and fear marginalized the music of the Aran Islands

The Aran Islands off the west coast of Ireland are a palimpsest bearing layers of representations in a myriad of forms including literature, film, television, radio, photography, and art, representations created by islanders and visitors. In the resulting Aran canon, which is dominated by visiting authors instead of local authors, the music of the Aran Islands – which is classified here as Irish traditional or folk music – has, however, been marginalised. This is surprising because both Irish traditional music and Aran itself are often cast independently of each other as entities that depict Irishness, entities that are, in fact, for many observers, exemplars of that identity. This article questions how the visitor’s experience of listening in Aran, which differs radically from that of locals, has contributed to the marginalisation of local music in the wider discourse and practice of Irish traditional music and Irish culture. It focuses on two of the forces at work in the marginalisation of the music of Aran. They are an appetite for silence and the silencing of music. Referencing the work of John Millington Synge, Kuno Meyer, Fr. Eoghan Ó Gramhnaigh and Andrew McNeillie, and that of the local poet Máirtín Ó Direáin, it considers the motives and fears that led visitors and islanders to treat the music of Aran as they did. This article is ultimately about how the act of listening to the world around us has a fundamental impact on how we represent islands and their cultures. Acknowledging the strong association between music and place that permeates the discourse of Irish traditional music and how, through the uniquely visceral experience of listening, that association has come to be so pervasive, it questions how and why, through the choices we make when we are listening, we perform notions of authenticity, musicality, and identity.Les Îles d’Aran, sur la côte ouest de l’Irlande sont un palimpseste à travers lequel on distingue de multiples niveaux de représentation sous une myriade de formes dont la littérature, le cinéma, la télévision, la radio, la photographie et les arts plastiques, représentations crées autant par les habitants que les visiteurs. Dans le canon artistique qui en résulte, et qui est dominé plutôt par les auteurs visiteurs que les auteurs résidents, la musique des Îles d’Aran – qui est qualifiée ici de musique traditionnelle ou populaire – a été marginalisée. Ceci est surprenant dans la mesure où les musiques traditionnelles irlandaise et de l’Île d'Aran elle-même sont souvent considérées en tant qu’entités indépendantes, alors que l’une comme l’autre caractérisent l’Irlande pour beaucoup d’observateurs. Cet article interroge en quoi l’expérience d’écoute par les visiteurs des Îles d’Aran, qui est radicalement distincte de celle des habitants, a contribué à marginaliser la musique locale dans la considération et la pratique plus large de la musique traditionnelle et la culture irlandaise. Il se concentre sur les deux forces à l’œuvre dans la marginalisation de la musique d’Aran: l’appétit pour le silence et la mise en sourdine de la musique. En s'appuyant sur les travaux de John Millington Synge, Kuno Meyer, Fr. Eoghan Ó Gramhnaigh et Andrew McNeillie, et sur ceux du poète local Máirtín Ó Direáin, cet article considère les motifs et les peurs qui ont conduit les visiteurs et les insulaires à traiter la musique d’Aran comme ils l’ont fait. Cet article observe, en essence, comment l’acte d’écouter le monde qui nous entoure a une influence fondamentale sur la façon dont nous représentons les iles et leurs cultures. En reconnaissant l’association forte entre la musique et le lieu, qui imprègne le discours sur la musique traditionnelle irlandaise, et comment, à travers l’expérience viscérale de l’écoute, cette association est devenue aussi prévalente; cet article interroge comment et pourquoi à travers les choix que nous faisons quand nous écoutons, nous mettons en forme des notions d’authenticité, de musicalité et d’identité

Big data-led cancer research, applications and insights

Insights distilled from integratingmultiple big-data or "omic" datasets have revealed functional hierarchies of molecular networks driving tumorigenesis and modifiers of treatment response. Identifying these novel key regulatory and dysregulated elements is now informing personalized medicine. Crucially, although there are many advantages to this approach, there are several key considerations to address. Here, we examine how this big data-led approach is impacting many diverse areas of cancer research, through review of the key presentations given at the Irish Association for Cancer Research Meeting and importantly how the results may be applied to positively affect patient outcomes

Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease

Cyclosporine A and IFNγ licencing enhances human mesenchymal stromal cell potency in a humanised mouse model of acute graft versus host disease

Immunosuppressive ability in human MSC donors has been shown to be variable and may be a limiting factor in MSC therapeutic efficacy in vivo. The importance of cytokine activation of mesenchymal stromal cells (MSCs) to facilitate their immunosuppressive function is well established. This study sought to further understand the interactions between MSCs and the commonly used calcineurin inhibitor cyclosporine A (CsA). The existing literature regarding approaches that use MSCs and cyclosporine are conflicting regarding the effect of CsA on MSC potency and function. Here, we clearly demonstrate that when added at the same time as MSCs, CsA negatively affects MSC suppression of T cell proliferation. However, licencing MSCs with IFNγ before addition of CsA protects MSCs from this negative effect. Notably, adding CsA to MSCs after IFNγ pre-stimulation enhances MSC production of IDO. Mechanistically, we identified that CsA reduces SOCS1 expression to facilitate enhanced IDO production in IFNγ pre-stimulated MSCs. Importantly, CsA exposure to IFNγ pre-stimulated MSC before administration, significantly enhanced the potency of MSCs in a human relevant humanised mouse model of acute Graft versus Host Disease. In summary, this study identified a novel licencing strategy to enhance MSC potency in vitro and in vivo

PINT: Pathways INtegration Tool

New pathway databases generally display pathways by retrieving information from a database dynamically. Some of them even provide their pathways in SBML or other exchangeable formats. Integrating these models is a challenging work, because these models were not built in the same way. Pathways integration Tool (PINT) may integrate the standard SBML files. Since these files may be obtained from different sources, any inconsistency in component names can be revised by using an annotation editor upon uploading a pathway model. This integration function greatly simplifies the building of a complex model from small models. To get new users started, about 190 curated public models of human pathways were collected by PINT. Relevant models can be selected and sent to the workbench by using a user-friendly query interface, which also accepts a gene list derived from high-throughput experiments. The models on the workbench, from either a public or a private source, can be integrated and painted. The painting function is useful for highlighting important genes or even their expression level on a merged pathway diagram, so that the biological significance can be revealed. This tool is freely available at http://csb2.ym.edu.tw/pint/

The anti-inflammatory compound candesartan cilexetil improves neurological outcomes in a mouse model of neonatal hypoxia

Recent studies suggest that mild hypoxia-induced neonatal seizures can trigger an acute neuroinflammatory response leading to long-lasting changes in brain excitability along with associated cognitive and behavioral deficits. The cellular elements and signaling pathways underlying neuroinflammation in this setting remain incompletely understood but could yield novel therapeutic targets. Here we show that brief global hypoxia-induced neonatal seizures in mice result in transient cytokine production, a selective expansion of microglia and long-lasting changes to the neuronal structure of pyramidal neurons in the hippocampus. Treatment of neonatal mice after hypoxia-seizures with the novel anti-inflammatory compound candesartan cilexetil suppressed acute seizure-damage and mitigated later-life aggravated seizure responses and hippocampus-dependent learning deficits. Together, these findings improve our understanding of the effects of neonatal seizures and identify potentially novel treatments to protect against short and long-lasting harmful effects