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"Walsh, Ian R"
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THEATRICALITY IN VERSE: DONAGH MACDONAGH'S HAPPY AS LARRY AND THE LYRIC THEATRE
This article considers MacDonagh's Happy as Larry in terms of performance by examining its dramaturgical experimentation. It shows that a piece of Irish drama from the maligned mid-century period was part of a wider international movement away from realistic mimetic representation toward what Erika Fischer-Lichte has termed the \"retheatricalisation of theatre\" in the twentieth century.3 Here, theatre progresses from functioning as a model of reality (mimetic representation) toward functioning as a model of a theatrical reality. In such a theatre, reality is no longer presented to the spectator as fixed and objective but rather as a construct that he/she makes. Fischer-Lichte calls this \"process of construction\" triggered in the spectator \"theatricality\".4 In its use of these strategies Happy as Larry challenges the accepted notion that Irish drama at mid-century consisted exclusively of conventionalized parochial plays \"trapped in a realistic form\".5
Journal Article
Review: Jordan, Eamonn. The theatre and films of Conor McPherson: conspicuous communities. Methuen, 2019
Book Review of The Theatre and Films of Conor McPherson by Eamonn Jordan
Book Review
Book Review: The Theatre and Films of Conor McPherson: Conspicuous Communities by Eamonn Jordan. Methuen, 2019
Lesser-known works such as Come on Over and Rum and Vodka are included in the analysis here alongside the better-known This Lime Tree Bower, The Good Thief and Port Authority. In plays such as St. Nicholas and Shining City or in the film Eclipse and the television series Paula, McPherson offers the spectator a sense of the precariousness of existence when he first presents a conventional, safe reality only then to undermine this through a supernatural occurrence. The reader learns how Christmas as a dramatic event forces tensions in the works between the commercial and the communal, the material and the spiritual, abundance and scarcity while it also \"marks moments of transition, and a movement towards light and away from darkness, not by way of linearity per se, but more by way of circularity, seasonality and continuity\" (16). A significant strength of the book is Jordan's dedication to following and experiencing McPherson's work over three decades and offering the reader first-hand accounts of so many productions of the plays.
Book Review
Large-scale integration of artificial atoms in hybrid photonic circuits
A central challenge in developing quantum computers and long-range quantum networks is the distribution of entanglement across many individually controllable qubits
1
. Colour centres in diamond have emerged as leading solid-state ‘artificial atom’ qubits
2
,
3
because they enable on-demand remote entanglement
4
, coherent control of over ten ancillae qubits with minute-long coherence times
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and memory-enhanced quantum communication
6
. A critical next step is to integrate large numbers of artificial atoms with photonic architectures to enable large-scale quantum information processing systems. So far, these efforts have been stymied by qubit inhomogeneities, low device yield and complex device requirements. Here we introduce a process for the high-yield heterogeneous integration of ‘quantum microchiplets’—diamond waveguide arrays containing highly coherent colour centres—on a photonic integrated circuit (PIC). We use this process to realize a 128-channel, defect-free array of germanium-vacancy and silicon-vacancy colour centres in an aluminium nitride PIC. Photoluminescence spectroscopy reveals long-term, stable and narrow average optical linewidths of 54 megahertz (146 megahertz) for germanium-vacancy (silicon-vacancy) emitters, close to the lifetime-limited linewidth of 32 megahertz (93 megahertz). We show that inhomogeneities of individual colour centre optical transitions can be compensated in situ by integrated tuning over 50 gigahertz without linewidth degradation. The ability to assemble large numbers of nearly indistinguishable and tunable artificial atoms into phase-stable PICs marks a key step towards multiplexed quantum repeaters
7
,
8
and general-purpose quantum processors
9
–
12
.
An approach for integrating a large number of solid-state qubits on a photonic integrated circuit is used to construct a 128-channel artificial atom chip containing diamond quantum emitters.
Journal Article
Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis
Liver disease in the UK stands out as the one glaring exception to the vast improvements made during the past 30 years in health and life expectancy for chronic disorders such as stroke, heart disease, and many cancers. Mortality rates have increased 400% since 1970, and in people younger than 65 years have risen by almost five-times.
Journal Article
Nasal Colonisation by Staphylococcus aureus Depends upon Clumping Factor B Binding to the Squamous Epithelial Cell Envelope Protein Loricrin
Staphylococcus aureus asymptomatically colonises the anterior nares, but the host and bacterial factors that facilitate colonisation remain incompletely understood. The S. aureus surface protein ClfB has been shown to mediate adherence to squamous epithelial cells in vitro and to promote nasal colonisation in both mice and humans. Here, we demonstrate that the squamous epithelial cell envelope protein loricrin represents the major target ligand for ClfB during S. aureus nasal colonisation. In vitro adherence assays indicated that bacteria expressing ClfB bound loricrin most likely by the \"dock, lock and latch\" mechanism. Using surface plasmon resonance we showed that ClfB bound cytokeratin 10 (K10), a structural protein of squamous epithelial cells, and loricrin with similar affinities that were in the low µM range. Loricrin is composed of three separate regions comprising GS-rich omega loops. Each loop was expressed separately and found to bind ClfB, However region 2 bound with highest affinity. To investigate if the specific interaction between ClfB and loricrin was sufficient to facilitate S. aureus nasal colonisation, we compared the ability of ClfB⁺S. aureus to colonise the nares of wild-type and loricrin-deficient (Lor⁻/⁻) mice. In the absence of loricrin, S. aureus nasal colonisation was significantly impaired. Furthermore a ClfB⁻ mutant colonised wild-type mice less efficiently than the parental ClfB⁺ strain whereas a similar lower level of colonisation was observed with both the parental strain and the ClfB⁻ mutant in the Lor⁻/⁻ mice. The ability of ClfB to support nasal colonisation by binding loricrin in vivo was confirmed by the ability of Lactococcus lactis expressing ClfB to be retained in the nares of WT mice but not in the Lor⁻/⁻ mice. By combining in vitro biochemical analysis with animal model studies we have identified the squamous epithelial cell envelope protein loricrin as the target ligand for ClfB during nasal colonisation by S. aureus.
Journal Article
Single-cell spatial immune landscapes of primary and metastatic brain tumours
Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell–cell relationships within the tumour microenvironment
1
,
2
, yet many single-cell studies lack spatial context and rely on dissociated tissues
3
. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.
Imaging mass cytometry of human brain tumours provides spatial information that, combined with existing transcriptomic data, reveals the existence of a cellular neighbourhood containing a rare macrophage population associated with prolonged survival.
Journal Article
Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression
Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.
Journal Article