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Representation(s) of the Garden in Poetry by Women in Ireland, From the Mid-Twentieth Century to the Present
No full textIn Ireland, women poets in Ireland have been marginalized for centuries from main literary circles, a lack of visibility which has had an impact on the construction and (self-)identification of contemporary women poets. This thesis is particularly interested in the recovery of works by women poets from the mid-twentieth century – a generation that was almost erased from literary history – and puts their creative input in discussion with contemporary women poets’ work in order to establish patterns of transmission that had not been acknowledged until today. These connections, this thesis argues, are particularly strong when women poets (re-)write and (re-)appropriate the space of the garden. Defying conventional representations of the garden, women poets in Ireland have, between the mid-twentieth century and today, redefined the trope according to their own terms, which sometimes materializes – or is conceptualized - in sometimes unexpected manners. It is the possibility for women poets to make the garden their “own” that has allowed them turn the space into one of safe and free expression. There, and through their practice of a philosophy and ethics of the garden – a hortosophy – women poets have been able to address socio-political debates of their times and revise their roles and status as women. As this thesis demonstrates, these women poets’ gardens are a space of expression but also a space of connection, both with other women (poets) – from and beyond Ireland – but also with their environment, which enables them to work towards the reconciliation of the two poles of the concept of the “woman-poet”, in a sustainable manner. In this thesis, I am bringing together ecofeminism and affect theories with the help of poststructuralist concepts that helped me coin and theorise the concept of hortosophy that is, as this thesis shows, the thread that connects all the women poets that I am looking at here
Gender, Sovereignty, and the Changing Nation: Irish Feminist Mythmaking, 1963-2022
No full textIn pre-Christian mythology, Mother Ireland or “the sovereignty goddess” endowed a prospective king with power over the land through a consummation, imagined either as a sexual or allegorical encounter. This thesis identifies the ways in which Irish women’s writing over the last seven decades queers and critiques the sovereignty ritual central to that mythology at flashpoints of socio-political change related to society’s Other. More specifically, I argue that Iris Murdoch’s The Unicorn (1963), Emma Donoghue’s Hood (1995), Anne Enright’s The Green Road (2015), and select rap songs by Denise Chaila (2020-2022) disinter the sovereignty goddess in a previously undocumented strand of feminist neo-mythmaking that queers the tradition’s sovereignty ritual for the allegorical assimilation of LGBTQIA+ characters, migrants, and queer migrants into Ireland’s cultural imaginary. Deploying Bracha Ettinger’s psychoanalytic feminism, Julia Kristeva’s work on “abjection”, and Mikhail Bakhtin’s narratological studies, I contend that these texts are matrixial borderspaces that exploit the goddess figure’s primordial association with the cycle of pre-birth, birth, death, and re-birth in an attempt to deconstruct phallogocentric allegory and produce new, intersectional foundation myths. However, these texts are not utopian, nor do they imagine facile progress narratives of the Irish state. Some hierarchies of privilege remain intact by their conclusions, exposing the obstinate, pervasive, and sometimes surreptitious mechanisms of heteropatriarchy, capitalism, and white supremacy. Alongside traditional theoretical frameworks, I develop a novel cultural analytics approach to mapping. Charting the chronotopes in Murdoch, Donoghue, and Enright’s novels, I illustrate how these narratologies are imbued with mythopoeic storytelling, down to their configurations of individual time-space units and how, despite being published over a fifty-year period, these novels construct comparable mythic landscapes in which their queer sovereignty rituals can occur
Queering Urban Ecologies: Reading the Forms and Aesthetics of Ecological Materialisms in Indigenous Queer Ecopoetics
No full textThis PhD project examines the representations of urban ecological materialisms (water, energy, and food-systems) in contemporary US Indigenous and queer, or “Indigiqueer”, ecopoetics, in order to register cultural attitudes towards urban ecological systems, and theorise the ways that queer cultural production has been shaped by them. This research takes place at the intersection of queer studies and environmental humanities, and contributes to the burgeoning field of queer ecology by introducing to it the first full-length study of urban Indigiqueer ecopoetics as both an aesthetic and formal mode for critiquing urban environmental mismanagement.
In Chapter One, I read the poetry of Kumeyaay poet, Tommy Pico, to theorise how his representations of food, hunger, waste, and food-related illnesses precipitate the importance of food culture in forming a sense of community, belonging, and kinship for urban Indigiqueer people. Throughout this chapter, I also read Pico’s metaphorization of food-systems and use of sarcasm to critique the colonial logics underpinning neoliberal trends in urban governance. Chapter Two reads the experimental ecopoetics of Mescalero and Lipan Apache poet Julian T. Brolaski in gowanus atropolis (2011) to register the ways that urban waterfronts have historically facilitated queer political programming and cultural production. By reading the ways that Brolaski utilises queer kinship metaphors, synecdoche, and translinguistics, I analyse how Brolaski writes contaminated and ensnarled relationships between Indigiqueerness and non-human life within and along the toxified Gowanus Canal in Brooklyn, New York. Lastly, in Chapter Three, I move beyond a study of Indigiqueer cultural production in New York City, to explore representations of petrosexuality in proximity to sites of extractivism in Diné poet Jake Skeets’ Eyes Bottle Dark with A Mouthful of Flowers (2019). In this chapter, I read for how the colonialist-capitalist legacy of resource extraction and energy poverty in Gallup, New Mexico, is represented within his Indigiqueer ecopoetics, before conceptualising how Skeets uses motifs of glitter and water to imagine forms of rehabilitation with the land and sexuality.
This project develops a critical understanding of the ways that Indigiqueer ecopoetics interrogates urban ecological infrastructures and forms of environmental mismanagement and their role in whitewashing and invisibilising Indigenous and queer cultures in urban spaces. This project registers how the formal and aesthetic conventions of these emergent poetic forms write necessary ways of unpacking the legacies of colonialism and industrialisation in New York City and Gallup, New Mexico, and insist on recognising and facilitating the lives of intersectional marginalised communities in the development of urban futures
Personifications of abstract ideas and elite identity in the late antique Eastern Mediterranean
No full textPersonifications are a frequent motif in the visual culture of the late antique Eastern Mediterranean, especially in urban centres such as Antioch. Following a case study approach and focusing on personifications of abstract ideas this thesis presents an in-depth analysis of some popular figures such as Ktisis (‘Foundation’), Ananeosis (‘Renewal’), Charis (‘Grace’), Tryphe (‘Luxury’), Apolausis (‘Enjoyment’) or Megalopsychia (‘Greatness of soul’), depicted not only in floor mosaics but also in book illumination and jewellery. Many personifications are not only late antique innovations without earlier precedents, but they often appear in combination with others and can only be identified through an accompanying Greek name label since they lack iconographical consistency and can share attributes. The iconographical and spatial analysis of each figure supplemented by a detailed discussion of the respective concepts in literature and epigraphy helps understand their meanings and functions and emphasizes the connections between these concepts in the late antique imagination. While the personifications refer specifically to elite self-representation and expressions of elite identity, they do not allude to general notions of paideia (‘education’), as discussed in previous scholarship, but each personification communicates a distinct element of this identity in a concise, efficient and customisable manner. While the name labels provide the overarching reference to the personified concepts, the iconographic variation and spatial context of each depiction add further nuance. However, due to the multivalent nature of these complex ideas many depictions remain purposefully ambivalent and can allude to the whole spectrum of nuances of each concept leaving their interpretation to the viewer. The personifications found on the floors and jewellery of the late antique elites illuminate first-hand the characteristics they wished to advertise in a single or a few chosen personifications. Thus, they reflect the attitudes of late antique elites, their desire to present themselves as megalopsychoi and ktistai and thus as members of an exclusive privileged minority and to unapologetically celebrate their luxurious way of life
Investigating the Intracellular Distribution of Cell-Derived Nanoparticle Complexes, Their Effects on Mitochondrial Dynamics and Mitochondria-ER Contact Sites
No full textNanomedicine has revolutionised disease treatment and prevention, offering promises for safer and more effective targeted drug delivery. Despite its potential, clinical translation of nanomedicine is often met with disappointment owing to many reasons, including high manufacturing cost, subpar efficacy, and complex regulatory requirements. In terms of understanding their efficacy, endocytosis has been one of the primary focuses in the field. Revealing how nanoparticles are taken up by cells helps to guide the design of nanomedicine with better targeting ability. Evidence on nanoparticle exocytosis on the other hand is relatively underwhelming, as very few studies follow through with their subsequent fates once they have exerted their therapeutic effects in the cells. Here, we describe a cell-derived nanoparticle complex (bionanosome, BNS), excreted by cells after internalising corona nanoparticle. Although biogenesis of BNS remains largely unelucidated, previous studies in our group have uncovered some of their properties unique from their original counterpart, corona. The surface of BNS is decorated with a combination of ribonucleoprotein granules and RNAs, of which we proposed they encode biological information. Our work here aimed to investigate the hypothesis that BNS acts as a delivery machinery for cell-to-cell communication. To achieve this, multiple confocal fluorescence imaging pipelines have been developed, combining with techniques including metabolic assays and flow cytometry. We demonstrated that BNS proteins can separate from their nanoparticle cores and follow a distinct trafficking pathway from their cores. We also illustrated that BNS proteins can evade lysosomal degradation, suggesting effective delivery. Studies on mitochondrial dynamics and mitochondria-ER contact sites have together shown that BNS helps to limit stress response and promote repairing effects in receiving cells. Although it has been reported elsewhere that exocytosis of nanoparticles can help reduce toxicity in the original cell population, to the best of our knowledge, we are the first to reveal their stress mitigating effects in cells on the receiving end of those exocytosed nanoparticles. Our work has shed some light on how cells communicate with each other as a population upon nanoparticle challenges. Such knowledge would serve to supplement the huge body of work in understanding and improving efficacy of nanomedicine
An investigation into Extracellular Vesicles content and function within the Multiple Myeloma tumour microenvironment
No full textMultiple myeloma (MM) is an incurable blood cancer that results from the monoclonal expansion of plasma cells in the bone marrow (BM). The progression of MM requires complex interactions between the cells and the bone marrow microenvironment (BME). These interactions are facilitated by extracellular vesicles (EVs) that transfer proteins and RNA between cells as a form of communication. The following study analysed the effects of MM EVs on monocyte cell function and tumour niche formation using an in vitro co-culture model to mimic the BME. In addition, a comprehensive multi-omic ex vivo analysis of MM patient-derived EVs isolated from BM and peripheral blood (PB) was performed. Overall, this research is critical for an improved understanding of MM EV function in the pathogenesis of MM as well as the identification of new therapeutic targets and disease biomarkers.
A novel in vitro co-culture model was established to study MM-EV uptake and function on immature monocyte cells and revealed differential effects that are dependent on the EV cell line of origin. Notably, H929 EVs were taken up by THP1 cells with greater efficiency than U266 and MM1s EVs. Furthermore, H929 EV uptake by THP1 cells correlated with a significant increase in the secretion of pro-inflammatory mediators IL-6 and MMP9 into the TME, which was only marginally detected following U266 EVs uptake and not detected following the uptake of MM1s EVs. Moreover, the conditioned media collected from THP1 cells following the uptake of H929 EVs enhanced the migration and proliferation of myeloma cells suggesting the formation of a metastatic niche. Proteomic analysis of MM-EVs derived from the three cell lines revealed significant differences in their protein cargo that could be correlated with phenotypic alterations within the BME. Specifically, pathway analysis highlighted potential pathophysiological mechanisms associated with pro-metastatic MM EVs, including multiple components of the spliceosome and its regulators that were highly enriched in H929 EVs compared to U266 and MM1s EVs.
Comprehensive multi-omic protein and miRNA analysis of plasma EVs isolated from the BM and PB of patients at various stages of the disease, from the pre-malignant MGUS to various stages of MM including active disease, remission and relapse was performed by mass spectrometry and RNA sequencing, respectively. Bioinformatic analysis of the data revealed significant dysregulation in MM EV protein and miRNA content compared to EVs from control and MGUS BM and PB EVs. The MM BM and PB EVs exhibit enrichment for several pro-tumourigenic proteins and miRNAs previously associated with MM or MM EVs, supporting their involvement in disease development and potential as diagnostic biomarkers. Furthermore, the unique enrichment of proteins and miRNAs could be correlated with the disease stage, highlighting their potential for disease monitoring. Finally, findings from the protein and miRNA analysis informed the development of MM PB EV protein and miRNA biomarker signatures with diagnostic and predictive power, and potential for clinical application as a non-invasive liquid biopsy. Overall, the results from this study contribute to our understanding of the role of EVs in MM cell communication and disease progression and provide novel EV biomarker signatures for MM diagnosis and monitoring
Development of a Green Biorefinery Whole Cell Biosensor Array
No full textThis research aimed to develop an array of Escherichia coli whole cell biosensors, to be used to detect key performance indicator analytes at-line within biological leachates produced from grass-silage fed green biorefineries. Each biosensor presented within this thesis has been developed to specifically detect a single analyte with the exclusion of all other analytes present in a grass silage fed green biorefinery pressed juice solution by removing catabolic pathways of interfering analytes from a previously developed acetic acid biosensor. The application of this process has resulted in the green biorefinery exclusion strain JSK0115, which does not have a biosensor response for any carbohydrates present in grass silage leachate except for amino acids. This response was around the 1 mV s-1 when supplied with 10% grass silage leachate, which was deemed small enough for the purpose of this study. Attempts were made to develop a biosensor that can detect butyric acid using a precursor of the exclusion strain. This biosensor also had a response for other volatile fatty acid and a poor longevity, more research was needed to develop a butyric acid specific biosensor. However, a biosensor was developed that could be used to detect volatile fatty acids with a chain length of six or higher. This biosensor had a response of around 2 mV s-1 for 72 hours when supplied with hexanoic acid. The exclusion strain was also used to develop two stereospecific lactic acid biosensors, which had a biosensor response around 8.5 mV s-1 and 5.5 mV s-1 for 20 hours when supplied with D- or L-lactic acid, respectively. These biosensors were used to qualify the D- or L-lactic acid content in grass silage leachate. More research is needed to be able to quantify the D- or L-lactic acid in grass silage leachate with these biosensors. This is due to differences between the concentration determined with the biosensor compared to the concentration determined with an enzymatic kit. The method applied to construct the D- and L-lactic acid biosensor can easily be applied to develop an analyte specific biosensor for most key analytes of a grass silage fed green biorefinery
Understanding the Fatigue Behaviour in Additively Manufactured Ti-6Al-4V Alloy: A Comprehensive Study and Predictive Modelling Approach
No full textMetal additive manufacturing (AM) has emerged as an important technology in sectors such biomedical and aerospace engineering, employing materials such as titanium (Ti) alloys, particularly Ti-6Al-4V, known for their strength and biocompatibility. However, predicting fatigue failure in additively manufactured components is complex as they possess process-induced potential defects, and their microstructures vary significantly due to changes in process parameters. This thesis aims to develop a fatigue prediction model for AM Ti-6Al-4V by determining the individual roles of microstructure and defects and linking mechanical properties with fatigue behaviour.
Ti-6Al-4V alloy was produced using two different, common, metal AM processes involving powder-bed-fusion (PBF) namely electron beam powder-bed-fusion (EB-PBF) and laser powder-bed-fusion (L-PBF). The material was post processed to yield six distinctly different conditions of AM Ti-6Al-4V alloy. The material created by the different conditions were characterised and tested using a variety of methods to gain further understanding of the relationship between various material properties and fatigue. Significant differences in the fatigue limit were observed in the examined conditions ranging from 50 – 575 MPa. It was found that heat-treatment (HT) caused a slight increase in fatigue limit due to the increase in β-phase content and α-lamellae (α-lath) thickness. The application of hot isostatic pressing (HIP) caused a greater increase in fatigue limit also due to the increase in β-phase content and α-lath thickness but more importantly because of the removal of porosity. It was determined that microstructure has a measurable influence on the fatigue limit. However, the removal of porosity is identified as the leading cause for improvements in fatigue limit as evident by a 9-fold increase in the L-PBF produced Ti-6Al-4V fatigue limit upon HIP compared to only a 2-fold increase upon HT. Charpy impact energy was found to directly correlate with the fatigue limit, highlighting the fact that Charpy impact testing may be a useful tool for rapid fatigue limit prediction.
Fatigue crack growth studies on material produced from L-PBF and tested both as-built and heat-treated showed that HT led to increased crack growth resistance, particularly early-stage crack growth. The near threshold stress intensity factor range (ΔKth) was increased from 2.16 MPa m−1/2 → 4.96 MPa m−1/2 upon HT. The interaction of early-stage fatigue cracks with microstructure was analysed using electron backscattered diffraction kernel average misorientation (EBSD-KAM) and fracture surface examination, leading to the conclusion that increases in β-phase content and α-lath thickness caused increases early-stage crack growth resistance due to the mechanical mismatch of the α and β phases. The increases in distance between adjacent grain boundaries as well as roughness induced crack closure.
A fatigue fracture surface study was carried out on failed S-N fatigue samples of Ti-6Al-4V alloy produced using L-PBF and tested both as-built and post HT, to quantify the size, location, and shape of fatigue critical defects. The information from the study was used to create a system to identify critical defects in S-N specimens, where defects were filtered based on defect edge-distance (<50 µm) and maximum square root of the x-y-projected defect area (√A). Critical defects in S-N specimens were identified using x-ray µ-computed tomography (CT) scans and fatigue failure predictions were made by modelling crack growth emanating from critical defects. Predicted cycles to failure were compared to experimental cycles to failure at various stress levels for as-built and heat-treated L-PBF produced Ti-6Al-4V alloy. Good agreement between experimental and predicted fatigue S-N curves were obtained, where heat-treated curves yielding better predictions
Elucidating Platelet and Haemostatic Dysfunction in Myeloproliferative Neoplasms: The EMPRESS Study
No full textMyeloproliferative neoplasms (MPN) are chronic haematological malignancies characterised by clonal proliferation of haematopoietic precursors and elevated cell counts in the peripheral blood. Thrombosis, including both arterial and venous events, represents the leading cause of morbidity and mortality for affected patients. Risk of thrombosis is highest around the time of initial diagnosis, and current treatment paradigms focus on ameliorating hypercoagulability and preventing vascular complications. However, conventional cytoreductive and antiplatelet therapies do not fully mitigate these risks. Furthermore, the management of thrombosis is complicated by the fact that patients may present with a competing risk of haemorrhage, which is also mediated through MPN-related haemostatic dysfunction. Thrombocytosis is a hallmark of MPN, and emerging evidence suggests that platelets are phenotypically distinct in numerous disease states with critical roles in a myriad of biological processes including inflammation and malignancy. The precise contribution of the platelet proteome to pathologic sequalae (both from a vascular and disease pathobiology perspective) in MPN has yet to be fully elucidated but qualitative platelet abnormalities in MPN have been widely reported. The work described in this thesis was conducted with the aim of addressing the hypothesis that platelet proteomic analysis and plasma haemostatic Profiling would provide a snapshot into the haemostatic, thrombotic, and inflammatory derangements which drive the clinical complications experienced by patients. The data described in this thesis defines the untargeted proteomic profile of platelets from two large, independent MPN cohorts of PV and ET patients, including the first such characterisation from newly diagnosed, treatment-naïve patients. In keeping with the observation that thrombotic risk remains elevated in chronically treated patients, evidence of an altered platelet proteome, with a predominance of thromboinflammatory mediators, was demonstrated in these patients despite standard therapy. Additionally, the MPN platelet proteome was enriched for biologic pathways of relevance to MPN pathobiology (such as unfolded protein response and MTORC signalling). Moreover, the description of the platelet proteome among newly diagnosed treatment-naïve patients with ET and PV captured the unique pattern of protein expression during the period of highest clinical risk. These data highlighted the upregulation of proteins with prothrombotic and proinflammatory potential in MPN such as LGALS1, FcγRIIA, and MMP1, while paradoxically platelet proteins with important physiological haemostatic properties were found to be downregulated. Meanwhile, interrogation of the plasma haemostatic profile of newly diagnosed, treatment naïve patients revealed evidence of platelet and endothelial activation and reduced tissue factor-stimulated thrombin generation. While these data demonstrate evidence of haemostatic imbalance, an overall hypocoagulable phenotype in plasma was observed among patients with MPN. Interestingly, while conventional physiological coagulation pathway activity was suppressed in the MPN group, sensitivity to inhibitors of the contact pathway of coagulation activation was similar to controls. As the contact pathway is emerging as a major new target for novel anticoagulants, these in vitro data present the intriguing hypothesis that these novel agents may represent an attractive option for use in MPN. Overall, these observations reflect the clinical phenotype experienced by patients and broaden our understanding of the pathobiology driving MPN and its associated complications. Future work will focus on elucidating longitudinal changes in platelet proteomic patterns in response to MPN-directed therapy and further functional studies will aim to delineate the in vivo impact of these alterations in platelet and haemostatic pathway activity in patients with MPN.2025-11-12 JG: Author's signature removed from PD
Next Generation Laboratory Soft X-Ray Microscope for 3D Nanoimaging
No full textRecent advancements in microscopy techniques are continually pushing the boundaries of our understanding of cellular structures and functions. Soft X-ray microscopy in the water window region of the electromagnetic spectrum is a powerful technique for high-resolution 3D imaging of biological samples. The natural contrast between carbon structures and cellular water allows for high resolution imaging while preserving structural integrity through cryo-fixation. Traditionally performed at synchrotrons, the limited number of soft X-ray beamlines has hindered wider accessibility. Developing a laboratory based source would significantly broaden access, particularly benefiting biologists. This PhD research focuses on enhancing the soft X-ray intensity at the sample plane to empower laboratory-based microscopy. The goal is to enable the microscope to produce 3D tomography images that are of a comparable quality to those obtained at synchrotrons, all within a practical and acceptable timeframe. This has been achieved by (a) increasing the radiance of the microscope source by an order of magnitude and (b) enhancing the overall efficiency of the soft X-ray beamline to the sample by an order of magnitude, by demonstrating the performance of new optics. A high-power laser was initially acquired, complemented by the integration of advanced, higher-specification optics into the microscope. To further optimize performance, a second laser with a shorter pulse width was also tested. I, along with the team at SiriusXT, designed a series of experiments to measure the impact of these enhancements on the other components of the microscope. My research examined various source parameters, including laser repetition rate (750Hz-2kHz), pulse energy (14mJ-60mJ), and pulse-width (2.5ns-6ns). Additionally, I characterized improvements in soft X-ray optics. The insights gained from these investigations have already guided enhancements to the microscope’s capabilities, paving the way for advancements in soft X-ray microscopy research and providing biologists with high-performance tools for exploring cellular ultrastructure