University of Galway Research Repository
Open access to publications, including peer-reviewed articles, conference papers, working papers, reports, and other scholarly communications by University of Galway researchers.
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Publication Market uncertainties and too-big-to-fail perception: Evidence from Chinese P2P registration requirements(Elsevier, 2024-08-01)The enforcement of peer-to-peer (P2P) registration requirements in mid-2018 triggered a P2P market meltdown, highlighting the inherent challenge faced by Chinese market participants in distinguishing between genuine and fraudulent fintech firms. The difference-in-difference results suggest that the too-big-to-fail (TBTF) perception can effectively halve investor outflows and borrower outflows during periods of uncertainty. Dynamic analysis further validates the parallel- trend assumption and underscores the persistent influence of TBTF perception. Moreover, the empirical findings suggest that, in the face of a market downturn, fintech market participants become unresponsive to all other certification mechanisms, including venture capital participa- tion, custodian banks, and third-party guarantees.Publication A modelling and computational study of biofilm dynamics: Exploring the role of initial attachment and horizontal gene transfer(University of Galway, 2024-12-03)Biofilms are ubiquitous in nature and one of the most successful lifestyles on earth. This success is largely due to the high level of interactions within biofilms, leading to the specialisation of subpopulations and subsequent heterogeneity. Biofilms have gathered research attention because of their potential use in engineering, but also because of the need to control their formation in man-made systems. However, due to their complexity and heterogeneity, biofilm systems can be cumbersome to analyse. In this context, model biofilm systems, whether they are experimental or mathematical, offer a reduction of the system to a more observable one through simplifying assumptions and hence allow easier analysis. This thesis aims to propose innovative biofilm models, focusing on diverse key aspects of biofilm ecosystems. More specifically, this dissertation is divided between an original experimental model system, proposed to investigate cross-kingdom interactions in anaerobic communities during biofilm formation and four novel mathematical models, introduced to describe the main regulatory effects of trace metals on microbial biofilms. To this aim, novel mathematical functions are introduced to describe key phenomena linked to trace metals in biofilms dynamics: bacterial attachment (and subsequent biofilm initiation) and horizontal gene transfer, one of the drivers of genotypic diversity and antibiotic resistance. The experimental model system is an undefined, engineered model system mimicking growth conditions in an Upflow Anaerobic Sludge Blanket reactor. It was studied with a sampling campaign during the first five days of the biofilm establishment, followed by biofilm characterisation with fluorescence microscopy and DNA sequencing at different time points. To complement DNA sequencing, a network-based analysis was carried out to investigate correlations between fungal and bacterial populations in different samples. This exploratory study into an unknown biofilm type brought to light the importance of the interactions between the bacterial microbiome and its fungal counterpart. The mathematical models in this thesis are continuum models, formulated as systems of non-linear partial differential equations. Non-linear hyperbolic PDEs govern the advective transport and growth of the solid-phase species forming the biofilm, while parabolic quasi-linear PDEs model the diffusion-reaction of soluble substrates and bacteriophages. The first model presented focuses on the influence of ionic strength on bacterial attachment and subsequent biofilm formation, and is formulated as a 1D free boundary problem. This model focuses on drinking water distribution systems biofilms and their invasion by pathogenic bacteria Legionella pneumophila, with a focus on the necrotrophic metabolism of the latter, which gives it the ability to persist in biofilms. The second model is formulated as a free-boundary problem describing the impact of conjugation on plasmid spread in biofilm communities. More specifically, conjugation is modelled as a mass-action kinetics process subsequent to gene expression, modelled as a nonlocal term to account for recipient-sensing. The existence and uniqueness of the solutions are proved using the method of characteristics and the fixed point theorem. The third model is formulated as a multidimensional problem, and proposes a modelling framework to natural transformation in biofilms, modelled as a frequency-dependent process. It investigates the comparative influence of conjugation and transformation on the spread of antibiotic resistance and biofilm compartmentalisation due to differences in metabolisms and sensitivities to toxic stressors. Finally, the last model describes the interaction between bacteriophages and biofilm communities and includes generalised transduction. This model is the first biofilm model that includes the three main horizontal gene transfer mechanisms: conjugation, transformation and transduction. All models are integrated numerically through the implementation of original code in MatLab and Comsol Multiphysics. Numerical simulations allow investigating the behaviour of the models, which are able to describe and predict key phenomena of biofilm dynamics. The results of the experimental section demonstrate the adequacy of model systems for investigating biofilm formation. The mathematical models can reproduce crucial elements of biofilm ecology, namely initial bacterial attachment and the main aspects of plasmid spread, such as horizontal gene transfer, the impact of selective pressure on vertical gene transfer or bacteriophage activity.Publication Auranofin loaded silk fibroin nanoparticles for colorectal cancer treatment(Springer, 2024-10-09)Colorectal cancer (CRC) is the second most common cause of cancer related deaths worldwide and the prevalence in young people especially is increasing annually. In the search for innovative approaches to treat the disease, drug delivery systems (DDS) are promising owing to their unique properties, which allow improved therapeutic results with lower drug concentrations, overcoming drug resistance and at the same time potentially reducing side effects. Silk fibroin is a biopolymer that can be processed to obtain biocompatible and biodegradable nanoparticles that can be efficiently loaded by surface adsorption with small-molecule therapeutics and allow their transport and sustained release by modulating their pharmacokinetics. Auranofin (AF) has recently been repurposed for its strong anticancer activity and is currently in clinical trials. Its mechanism of action is through the inhibition of thioredoxin reductase enzymes, which play an essential role in several intracellular processes and are overexpressed in some tumours. Taking into account that AF has a low solubility in water, we propose silk fibroin nanoparticles (SFN) as AF carrier in order to improve its bioavailability, increasing cellular absorption and preventing its degradation or avoiding some resistance mechanisms. Here we report the preparation and characterization of a new formulation of AF-loaded silk fibroin nanoparticles (SFN-AF), its functionalization with FITC for the analysis of cellular uptake, as well as its cytotoxic activity against cell lines of human colorectal cancer (HT29 and HCT116) in both 2D and 3D cell cultures. 3D spheroid models provide a 3D environment which mimics the 3D aspects of CRC observed in vivo and represents an effective 3D environment to screen therapeutics for the treatment of CRC. The loaded nanoparticles showed a spherical morphology with a hydrodynamic diameter of ~ 160 nm and good stability in aqueous solution due to their negative surface charges. FESEM-EDX analysis revealed a homogeneous distribution of Au clusters with high electron density on the surface of the nanoparticles. SFN-AF incubated in phosphate buffer at 37 °C released 77% of the loaded AF over 10 days, showing an initial burst and then sustained release. Flow cytometry analysis showed that FITC-SFN-AF was efficiently internalized by both cell lines, which was confirmed by confocal microscopy imaging. SFN enhanced the cytotoxicity of AF in 2D cultures in both CRC lines. Promising results were also obtained in 3D culture paving the way for future application of this strategy as a therapy for CRC.Publication The return of the tortured ghost in Harkaitz Cano’s novel Twist (2011)(Liverpool University Press, 2024-11-04)This article investigates the issue of political torture and forced disappearances within the context of the Basque political conflict as represented in the novel Twist by Harkaitz Cano. Although all violence is traumatic, the violence implicit in the systematic infliction of pain and humiliation on the state’s political ‘enemies’ by members of its security forces and, in some cases, their enforced disappearance translates into a traumatic memory that afflicts not only the victims, but the society represented by that state. Unresolved traumatic memory installs itself in the collective consciousness and generates ghosts that haunt the living and the future generations. One way they may be exorcised is by the cultural transmission of the events that caused the trauma through literary fiction.Publication A pagan philosopher in salvation history: Placing the Seneca-Paul correspondence in its fourth-century context(University of Galway, 2024-12-03)The Seneca-Paul correspondence comprises fourteen short letters exchanged between the Roman pagan philosopher Seneca and the apostle Paul in the years immediately preceding the two men’s violent deaths in Rome at the hands of the same emperor. Though the authorship of the correspondence has been debated since the early-sixteenth century, there remain few points on which scholars agree. However, it is generally accepted on the basis of the linguistic evidence that the letters were not authored by Paul and Seneca but by a Christian writer in the second half of the fourth century, with a firm terminus ante quem of 392. This dissertation seeks to answer the question: what can the Seneca-Paul correspondence’s hypothesised late-fourth-century date of composition tell us about the nature of this enigmatic work, which is partly imaginative, partly historiographical and partly apocryphal? In particular, it interrogates what the late-fourth-century context in which the correspondence was written can tell us about the issues it raises, the historical assumptions it makes, the themes it foregrounds, and why it draws a connection between Paul and Seneca in the first place. It also seeks to answer the question: how does the Seneca-Paul correspondence compare to other fourth-century Christian texts which take equally seriously the significance of the overlap between Paul’s Roman mission and the calamitous events of Nero’s later reign, particularly those texts composed in the second half of the fourth century?
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