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Using Rayleigh-Mie scattered light and polarised multidimensional fluorescence emission in combination for protein quantification in a model clarified bioreactor harvest
No full textBackground
Accurate monitoring and control of bioprocesses require the measurement of critical parameters, such as product and interfering protein concentrations, particularly in the bioreactor harvest prior to during downstream purification. One promising approach is to combine polarised multidimensional fluorescence measurements of intrinsic emission with light scattering measurements. This offers a non-invasive and sensitive method for protein quantification that can be implemented using either polarised Excitation Emission Matrix (pEEM) or Total Synchronous Fluorescence (pTSFS) measurement modes which can deal with matrix interferences from the complex cell culture media which is also fluorescent.
Results
Polarised Synchronous Light Scattering (pSyLS), pTSFS, and pEEM measurements on a sample set of 45 unique samples with varying protein (Immunoglobulin G and Bovine Serum Albumin) and media (yeastolate) concentrations (the model for a clarified, multi-protein bioreactor harvest) were made. Spectral data were evaluated using Principal Component Analysis (PCA) and Partial Least Squares (PLS) regression used for quantifying IgG and total protein content. Best results were achieved with parallel polarised (||) measurements for both total protein content with prediction errors of 11 %, 14 %, and 14 % using TSFS||, EEM||, and SyLS|| measurements respectively, and IgG content, with prediction errors of 10 % for both TSFS|| and EEM||. Quantification was best when the Rayleigh-Mie scattered light signal was included. The primary limitations were a combination of low sample numbers (n = 45) along with a relatively low target analyte range (max 1.8 gL–1), with reference method accuracy being a secondary consideration.
Significance & novelty
Demonstrated for the first time that pSyLS can be used for protein quantification in a complex clarified bioreactor harvest model. This is also the first comparison between polarised TSFS, SyLS, and EEM measurements for estimating total protein and IgG content in a complex interfering matrix. For pEEM measurements the significant result is that for samples with a constrained particle size distribution, including Rayleigh-Mie scatter signal in the model enables better protein quantification. This shows the strong potential of pSyLS, pTSFS, and pEEM measurements for real time bioprocess monitoring of protein content.This publication emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grant number (14/IA/2282, Advanced Analytics for Biological Therapeutic Manufacture, to AGR). We also thank Horiba (Piscataway, NJ, USA) for the loan of the Aqualog system used. The authors declare no financial or commercial conflict of interest
Structural assessment and machine learning-based fatigue prediction of wind turbine blades
No full textThis thesis investigates the structural behaviour and fatigue performance of composite wind turbine blades by integrating full-scale mechanical testing with machine learning (ML) techniques. As wind energy systems grow in importance for delivering sustainable and cost-effective power, accurate prediction blade performance remains a technical challenge due to complex loading, material variability, and environmental effects.
The primary objective of this research is to develop a hybrid experimental-ML framework to improve fatigue life prediction and reduce reliance on time-consuming full-scale testing. To achieve this, two full-scale blades - a 13-metre glass fibre-reinforced epoxy blade and a 4.5-metre blade made from woven Twintex - were subjected to static, dynamic, and fatigue testing in accordance with IEC TS 61400-23. Key mechanical parameters such as tip deflection, strain, natural frequencies, and stiffness were experimentally obtained and validated against finite element models developed in ABAQUS.
Complementing the physical tests, a suite of supervised ML models - Random Forest (RF), Gradient Boosting (GB), Bagging, Decision Trees (DT), XGBoost, and Gene Expression Programming (GEP) – were trained using experimental and literature-based fatigue data. Input features included fibre volume fraction, maximum/minimum stress, frequency, R-value, and laminate thickness.
The best performing models (RF and Bagging) achieved mean R² values above 0.91 during 10-fold cross-validation, while Grading Boostinghad the lowest average MAE (0.73 log cycles), indicating high absolute accuracy in fatigue life prediction. Feature importance analysis and SHAP (SHapley Additive exPlanations) values revealed that loading frequency is the most influential factor in fatigue progression, followed by stress levels and thickness, aligning with physical fatigue mechanisms. The use of explainable AI techniques enabled the interpretation of model behaviour and enhanced model transparency for practical deployment. A user-friendly Graphical User Interface (GUI) was also developed using Python’s Tkinter framework, allowing non-programmers to predict fatigue life and mechanical performance based on defined inputs. This GUI acts as a bridge between data science models and engineering applications, promoting user accessibility and supporting real-time decision-making in blade design, testing, and maintenance.
The thesis contributes significantly to the field by offering a validated, scalable, and interpretable approach to structural performance prediction, reducing the dependency on full-scale testing and enabling faster design iterations. It aligns closely with the goals of structural health monitoring (SHM), predictive maintenance, and digital twin strategies for wind energy systems. The hybrid framework developed here serves not only to improve current design and assessment methodologies but also sets a foundation for future research into physics-informed ML, real-time SHM integration, and model generalisation to a broader class of composite structures. The framework demonstrates the potential of combining experimental mechanics with explainable AI to accelerate innovation in sustainable energy technologies
Facing the polycrisis: human-environmental security for planet earth
No full textThis chapter reflects on the urgency of a holistic vision for human-environmental security for the future of the planet. It begins by setting out how a widening of the UN concept of ‘human security’ can aid us in devising effective governmental strategies in facing the overlapping human and environmental crises of the Anthropocene. In particular, it points to how ‘human security’ objectives can be allied with ‘human rights’ concerns in the envisioning and operation of responsible government policy in the safeguarding of planet Earth. It then showcases an illustrative example from the Caribbean of what is possible when such a security vision is legally enacted, resourced and systematically administered. The focus then turns to ‘migration’, its contextual understanding, and the necessary holistic strategies of response that factor in the historical and contemporary human and environmental dimensions that lead to ‘crises’. Finally, the chapter concludes by offering constructive ways in which we can enable solidarity and responsible governance in tackling the overarching human-environmental polycrisis the world faces. It sets out core mechanisms of governance that can be mobilized in a more responsible regulation of the economic modalities of late modern capitalism, and the curtailment of its destructive ecological and social effects
Advancing cardiovascular disease prevention in asymptomatic carotid artery disease: integrative approaches through dietary interventions, multidisciplinary programs, and adherence strategies
No full textBackground
Cardiovascular disease (CVD) is the leading global cause of mortality, responsible for 17.9 million deaths annually, with significant economic burdens. Modifiable risk factors, such as poor diet, physical inactivity, and low adherence to preventive strategies, contribute to its high prevalence. High-risk populations, such as those with asymptomatic carotid artery disease (ACAD), face limited effectiveness in current prevention approaches due to insufficient integration of multidisciplinary care and adherence strategies.
Objectives
This thesis aimed to advance CVD prevention by:
1. Systematically evaluating the DASH diet’s impact on cardiovascular events and risk factors.
2. Investigating outcomes of a novel multidisciplinary risk management program (IP-CARD) for ACAD patients.
3. Assessing the effectiveness of telephone reminders in improving adherence in cardiovascular clinical trials.
Methods
Three interconnected studies were conducted:
1. A Cochrane systematic review of randomized controlled trials (RCTs) assessed the DASH diet’s effects on cardiovascular outcomes and risk factors.
2. A single-center RCT evaluated the IP-CARD program’s impact on non-fatal cardiovascular events, carotid stenosis progression, and quality of life in ACAD patients.
3. A Study Within a Trial (SWAT) explored the role of telephone reminders in enhancing adherence during a cardiovascular prevention trial.
Results
1. DASH Diet Review: The systematic review included five RCTs and demonstrated significant reductions in blood pressure and cholesterol profiles. However, evidence on its effects on myocardial infarction, stroke, or mortality was inconclusive due to limited sample sizes and follow-up durations.
2. IP-CARD Program: The RCT showed a significant reduction in non-fatal cardiovascular events and carotid stenosis progression. Intervention participants achieved better control of blood pressure, LDL cholesterol, and physical activity, alongside significant quality-of-life improvements.
3. SWAT on Adherence: Telephone reminders significantly improved adherence rates and engagement with trial protocols, with potential reductions in dropout rates and improved adherence scores.
Conclusions
This thesis highlights the potential of integrative approaches combining dietary interventions, multidisciplinary programs, and adherence strategies to reduce CVD risk in high-risk populations. While the DASH diet effectively reduces cardiovascular risk factors, further large-scale, long-term trials are needed to confirm its impact on major events like myocardial infarction and stroke. The IP-CARD program demonstrates the value of structured multidisciplinary interventions in managing ACAD, while adherence strategies, such as telephone reminders, optimize trial engagement and outcomes.
Implications
This research offers actionable insights for clinical practice, public health policy, and future research. It supports the integration of evidence-based dietary, lifestyle, and adherence interventions into clinical guidelines. Structured prevention programs for ACAD patients and high-risk populations, combined with robust adherence strategies, can significantly reduce the global burden of CVD while improving patient quality of life. These findings emphasize the need for funding and policy support to implement and sustain these programs on a broader scale
Unstable ontologies: The self-conscious fantastic of Lord Dunsany
No full textThis doctoral dissertation examines the narrative configuration of the impossible domain as manifestations of the fantastic in selected prose writings by Edward Plunkett, Lord Dunsany (1878-1957). This examination elucidates that there is a consistent presence of ontological tension, implicit or explicit, which disrupts the internal coherence coding the text as mimetic or as fantasy, thereby interrogating the instability of both domains (the possible and the impossible). The analysis conducted in this thesis demonstrates that the configuration of Dunsany’s fiction forces the reader to assess the discourses challenged by diegetic tension, thereby highlighting the erosion of truth and reality, the dissolution of nature, the construction of the other, and the non-human in modernity. This critical reappraisal disputes previous interpretations of Dunsany’s work that posit the manifestations of the impossible in his texts as fantasy, stable within its self-standing ontology; or alternatively, as the product of uncomplicated orientalism or escapism. Instead, this thesis demonstrates that Dunsany’s work exhibits a fluctuation in ontological dominance from text to text, regardless of genre, yet maintains a consistent, self-conscious ontological instability that situates it firmly within the field of the fantastic. Extended scholarly analyses of his work through the lens of its narrative configuration, leveraging theories of the fantastic and metafiction, have not been explored in a sustained critical manner heretofore. This research contributes to the fields of the fantastic and metafiction, offering a revised theorization of the fantastic. The fantastic, as posited here, is not a restrictive model based on epistemological instability or specific configurations reliant on dominance of the domain of the possible, but a mode of narration based on an ontological tension or problematization—it is an intrinsically self-conscious narrative mode in that it appeals to the reader to consider the notions of possibility, impossibility, the limits of language and the concept of the “real” itself. My approach critically repositions Dunsany more firmly within the modern Irish literary canon, challenging the frequent reception of his work as an isolated phenomenon. I also advance the conceptualization of the fantastic as a narrative mode within the field of Irish Studies, the significance of which necessitates further theoretical concretization, investigating it as transgressive and destabilizing to established discourses and paradigms of reality and possibility
Topological state switches in hard-magnetic meta-structures
No full textWe propose a metamaterial design principle that enables the remote switching of topological states. Dynamic breaking of space-inversion symmetry is achieved through the intricate design of magnetic spring structures within the metamaterial building blocks, whose stiffness can be remotely altered using an external magnetic field. We develop a mathematical model to predict the magnetic field-induced deformation and tangential stiffness of the spring structure with hard- magnetic constituent phase. Building on the predictive model, we explore the necessary conditions – including the magnetization distribution and the direction of the actuating magnetic field – that enable magnetically tunable stiffness. To demonstrate the functionality of topological state switching, we apply the proposed magnetic spring to the topological metamaterial design where a tunable stiffness landscape is essential for reversible topological phase transition. Our mathematical modeling indicates that we can remotely modulate both the dispersion properties and the topological invariants (including Zak phase and winding number) of the underlying bands in the proposed metamaterial system. Finally, we show that this tunable capability extends to controlling topologically protected edge and interface states within the finite-sized metamaterial lattice. Our design strategy for the switching of topological state paves the way for the realization of smart and intelligent metamaterials featuring tunable and active wave dynamics. It also highlights the potential of magneto-mechanical coupling in the design of advanced functional materials.QZ thanks the support of the European Union's (EU) Horizon Europe research and innovation funding program through the Marie Skłodowska-Curie Actions (Grant No. 101106301), as well as the support of the College of Science and Engineering at University of Galway through the Sustainable Development Goals (SDG) Research Support Fund. SR thanks for the support of the European Research Council (ERC) through Grant No. 852281-MAGIC.peer-reviewe
Business creation model: Development of an applied business model for novice enterprises
No full textEconomies worldwide depend on successful businesses to create value, employment, and prosperity. Entrepreneurship has been linked to the creation of wealth, increases in productivity, and improvements in the overall quality of life. In Ireland however, 99.8% of businesses are small to medium in size (i.e., employing fewer than 250 individuals), and their management skills lag behind those of other high-income European countries.
Whilst this underperformance is masked economically by the current excellent performance of the multinational sector, this systemic deficit poses clear risks to the continuing wealth and prosperity of the Irish economy and its society. Past attempts by Ireland’s enterprise development agencies (Enterprise Ireland and Local Enterprise Offices) to improve this underperformance have had mixed results. This research sets out to address this problem of underperformance for novice entrepreneurs. It focuses on the novice entrepreneur as the main actor in creating a business, and develops an entrepreneur-centric business creation model that empowers them to strategise, formulate, and implement prioritised business creation activities that build business capability and create value.
Employing a mixed-methods, exploratory sequential design, the study combines knowledge from academia and industry reports with insights from expert practitioners in entrepreneurship to ground the research in real-world experience. The research follows four phases, respectively: define goals, design the model, develop the model, and validate the model. Input and feedback were sequentially and iteratively gathered and analysed over several interviews and field tests to configure the emerging business creation model (BCM). Research participants included a group of 12 enterprise experts comprising academics, enterprise development officers, business mentors, experienced entrepreneurs, and 62 novice entrepreneurs (33 participating in pilot testing and iteration, and 29 performing validation tests on the finalised BCM).
The results indicate that the BCM largely attains its primary objective of facilitating the development of strategically capable novice entrepreneurs. This primary objective is supported by providing a holistic cognitive map of the enterprise domain with which to orient the user; by creating a usable model that is relevant to the user’s needs; by assembling an integrated toolbox (of standard tools, templates, and techniques) for sequenced application towards an end solution; by maintaining a focus on implementation; and by enabling the user to ‘right-size’ the model to a level that suits them.
This research makes novel contributions to addressing the serious problem of ongoing underperformance in the SME sector. It makes a practical contribution to the organisational and strategic capability of novice entrepreneurs and the field of applied BM research. It concludes by acknowledging its limitations, and by making recommendations for further study in this important area
A computational investigation to predict vessel and plaque injury risk due to catheter delivery in transcatheter aortic valve replacement surgery
No full textThis thesis aims to enhance the understanding of catheter tracking in transcatheter aortic valve replacement (TAVR) surgery. Stroke occurrence post-TAVR is a significant concern for TAVR patients. Injury to the arterial vessel or plaque tissue can result in embolus formation, which can lead to downstream complications such as stroke. However, it is unclear whether the cause of embolism formation during TAVR is due to the replacement valve or the catheter delivery system. Therefore, there is a need to quantify the stresses that arise during catheter delivery to understand the risks that catheter delivery systems may pose for emboli formation. In this thesis, computational methodologies are developed to investigate catheter tracking within idealised and patient-specific aorta arch anatomies. These finite element simulations are performed to analyse and predict the stresses experienced in arterial and plaque tissue during catheter delivery.
Chapter 3 developed computational models to simulate catheter tracking within an idealised aorta arch and predict the influence of catheter design on tracking forces and contact pressures. Frictional coefficients markedly impacted reaction forces during catheter tracking, highlighting the importance of hydrophobic-treated catheters during intervention with materials such as Teflon. Catheter tip stiffness did not affect reaction forces during tracking, but increased tip stiffness correlated with increased applied contact pressures. The models predicted corresponding increases in reaction forces when the arch lumen diameter and arch centreline curvature were narrowed. This chapter has emphasised the importance of many catheter design inputs and patient geometrical factors that can impact patient injury risk during catheter delivery.
Chapter 4 utilised the model developed in Chapter 3 to examine plaque tissue stresses during catheter delivery in TAVR. Finite element (FE) analysis was implemented to investigate further design inputs. Catheter tip length was positively correlated with reduced peak contact pressures. Next, the idealised aorta anatomy was further developed to include idealised plaque inclusions in the arch region and applied to investigate catheter tracking in an idealised calcified aorta anatomy. It was predicted that there was a risk of rupture for highly stiff calcified plaques during catheter tracking, regardless of location, compared to published plaque rupture stress thresholds. Plaques with reduced stiffness (less mature calcification) were shown to be susceptible to rupture if located at the aorta arch apex during catheter tracking. The results of this chapter could be applied to pre-TAVR planning by identifying highly calcified plaques and their location with respect to the arch apex to determine injury risk.
Chapter 5 developed two patient-specific aorta and plaque anatomies for catheter tracking analysis. The patient anatomies were developed from pre-TAVR computed tomography (CT) scans of two patients with moderate and mild plaque burdens. Mimics (Materialise) imaging software was utilised to create 3D part meshes for analysis within the FE solver. Catheter tracking was simulated, applying the approach from the previous chapters within both anatomies with various plaque burdens and stiffnesses. The predicted stresses were compared to plaque rupture stress thresholds. It is reported that catheter tracking during TAVR produces a risk of plaque rupture in the intermediate stiffness plaques at a high burden only in Patient 1 but predicts no risk in Patient 2. Catheter tracking with highly stiff calcified nodules produces high peak stresses in the plaque tissue during catheter delivery. The results of this thesis provide evidence that there is a risk of plaque rupture due to catheter tracking in TAVR in high plaque burdens. These findings could inform physicians on treatment planning regarding the use of cerebral embolic protection devices during TAVR delivery
Investigation of pathogenic and toxigenic vibrio in Irish aquaculture
No full textIn recent years marine waters have warmed, causing more favourable environments for Vibrio species. With climate change, the distribution of Vibrio marine pathogens is expected to expand leading to an increase in pathogenic and toxigenic Vibrio throughout Europe posing a greater threat to human health and aquaculture. Vibrio vulnificus, V. parahaemolyticus and V. cholerae are causative agents of gastroenteritis in humans. Furthermore, opportunistic Vibrio species such as V. alginolyticus have been implicated in rising human and aquaculture infection. Reports on the presence of Vibrio species in Irish waters is sparse. V. parahaemolyticus is largely connected with seefood associated gastroenteristis.
Genomics revealed the presence of Type III Secretion System 2 (T3SS2) complexes and an array of pathogenic genes responsible for host colonisation and infections. This study uses a combination of culture, molecular and genomic methods to explore the occurrence, phylogeny and pathogenicity of the dominant Vibrio community. Shellfish, water and sediment samples were sourced from 5 prominent aquaculture sites located at the north and west of Ireland over a minimum of 12-month to provide a view on the naturally present and potentially pathogenic Vibrio. From this study, a diverse Vibrio community was identified at prominent coastal Irish aquaculture sites. The pathogen V parahaemolyticus along with a number of Vibrio species; Vibrio alginolyticus, Vibrio diabolicus, Vibrio jasicida, Vibrio metschnikovii and Vibrio proteolyticus were detected over the course of the study. The dominant Vibrio species detected from Irish oysters and mussels was V. diabolicus and opportunistic pathogen V. alginolyticus. Molecular and genomic analysis of Vibrio genomes identified the presence of potentially pathogenic V. parahaemolyticus and V. diabolicus isolates. The presence of V. diabolicus isolates containing the Type III Secretion System 2β (T3SS2β) with high homology to the virulent T3SS2β V. parahaemolyticus was observed through genomic comparison of whole genome sequenced isolates. Furthermore, potential for antimicrobial resistance and biosynthetic potential was uncovered using a genome mining approach.
Tetrodotoxin (TTX) is a potent neurotoxin demonstrating a wider distribution throughout European waters. The biosynthesis of TTX in Vibrio remains complex and unclear. This study set out to provide a comparative whole genome sequencing approach to investigate possible TTX producing Vibrio genes. This study provides a comprehensive review on the bacterial biosynthesis of tetrodotoxin with a focus on determining a molecular target. Immunological and UPLC-MS methods were explored to provide analysis on the toxigenic potential of Irish Vibrio and Shewanella with the aim of gaining insight into the TTX producing capabilities of Irish bacterial isolate
Mobilisation of the apartheid framework in Palestine: From grassroots organising and human rights advocacy to the pursuit of international accountability
No full textTracing its international law prohibition and mobilisation on the ground, this dissertation interrogates the origins, evolution, contributions, and critiques of the apartheid framework as mobilised by grassroots organisers and human rights organisations in the movement for freedom, justice, and equality in Palestine. Chapter 1 discusses apartheid and international law, highlighting the tools international law provides for the suppression and punishment of apartheid, arising as a result of the anti-apartheid and decolonisation struggles. Chapter 2 turns to the origins of the apartheid discourse in Palestine, rooting it in Palestinians’ articulations of their lived reality since the start of the Nakba (catastrophe) in 1948. Drawing on the findings of semi-structured interviews conducted during fieldwork in 2023, Chapters 3 and 4 trace the evolution of anti-apartheid mobilisation by grassroots organisers and human rights organisations on the ground in Palestine. What emerges is a rich discourse among practitioners and organisers on the nature of the Israeli regime and its root causes following over a century of Zionist settler colonialism as well as the limits of human rights work in this context. Chapter 4 also explores the opportunities and limitations of the apartheid framework and its potential for advancing international justice and accountability for the Palestinian people.This PhD project was funded by the Hardiman PhD Scholarship at the University of Galway (2020-2021) and the Irish Research Council Government of Ireland Postgraduate Scholarship (2021-2024)