University of Galway Theses (Research Masters Theses)

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  • Publication
    Synthesis and characterisation of new metal-organic frameworks as carriers of antibacterial agents
    (NUI Galway, 2024-04-18) Kelly, Aileen; Papatriantafyllopoulou, Constantina; Thomas, Olivier
    Metal Organic Frameworks are highly porous, crystalline materials that have been used for a multitude of applications, with drug delivery and sensing at the forefront. These frameworks are extremely versatile and can be applied to multimodal applications, allowing for combined therapies and treatments to be developed. In this project, multimodal MOFs and mixed metal MOFs capable of antibacterial significance and a novel organic linker with the capability to form a theranostic MOF for luminescence and drug delivery was synthesised. Multi Drug Resistant Tuberculosis (MDR TB) is a disease that has become a threat to global health, killing 1.6 million people yearly thus being the second leading cause of human death via infectious disease. First and second line therapies are beginning to lose their efficacy as more drug resistant strains are on the rise. Additionally, the drugs that are currently on the market to treat MDR TB entail solubility issues, side effects and undergo rapid metabolism. To overcome the API issues alongside preventing the development of drug resistance, the multimodal MOFs, [Zn2(AZA)], [Mg2(AZA)] and [Co2(AZA)], were synthesised. These MOFs combined a prodrug organic linker azodisalicylic acid (AZA) as the organic component of the MOF, the antimicrobial metals Zn2+, Mg2+, Co2+ & Cu2+ and the APIs isoniazid, rifampicin, and ciprofloxacin. The MOFs successfully encapsulated isoniazid and ciprofloxacin and antibacterial assays were performed. A mixed metal MOF, [Zn2Cu2AZA], using the AZA prodrug linker and the metals Zn2+ and Cu2+ was synthesised. These metals were chosen in the hopes of achieving a controlled release of drug, while also combining the synergistic antimicrobial properties of each metal. These MOFs are currently undergoing MIC antibacterial studies to determine their efficacy. A stilbene-based ligand, cyanostilbene dicarboxylic acid, was synthesised with the potential of synthesising a MOF capable of both chemotherapeutic delivery and bioimaging. Alongside this, a second stilbene linker stilbene tricarboxylic acid was synthesised with the aim to produce a highly porous MOF capable of high drug loading and luminescence.
  • Publication
    Application of Ulva biomass for bioremediation of wastewater
    (NUI Galway, 2024-04-18) Nelly, Alisha; Sulpice, Ronan
    The remarkable growth rate and environmental adaptability of Ulva species have attracted considerable interest for their potential applications in aquaculture and bioremediation. Ulva's capacity to absorb nutrients from various wastewaters, including those originating from the dairy industry, positions it as a promising solution for addressing soluble contaminants. To identify Ulva strains with enhanced tolerance to low salinity to support applications with typical terrestrial wastewater streams, a series of laboratory and pilot scale experiments were performed. These experiments involved the co-cultivation of multiple strains from three distinct Ulva species(Ulva lacinulata, Ulva gigantea and Ulva compressa) under different conditions, encompassing varying salinity levels (17.5 PPT and 35 PPT salinity) and diverse wastewater sources. Waters tested included Final Effluent (FEF) water (treated water ready for release downstream), reverse osmosis reject (RO) water (by-product of reverse osmosis process containing concentrated impurities (high nitrate levels) which of often used for treatment of fats), river water (water from River Deel running parallel to factory), balance water (raw sewage which has undergone pH alteration and fat removal) and filtered balance water (balance water filtered to reduce turbidity). The findings from these experiments revealed that filtered balance water supported superior growth rates compared to unfiltered balance water. The co-cultivation studies highlights the strain-specific nature of Ulva's tolerance to low salinity, with certain strains exhibiting higher growth and survival rates under specific conditions. The investigation unveiled fluctuations in the characteristics of FEF water as growth media over a seven-day period. The presence of precipitate (identified as aragonite, a crystal form of CaCO3) on Ulva biomass cultivated in FEF and ASW (Artificial Seawater) dilution was associated with diminished growth and nutrient uptake, emphasizing the intricate relationship between environmental factors and Ulva's growth dynamics. Additionally, the study demonstrated that while FEF water alone did not sustain Ulva growth, the supplementation of F/2 nutrients to FEF water resulted in enhanced growth rates compared to F/2 + ASW alone, which also facilitated a prolonged selection process, allowing for the coexistence of multiple Ulva species. The final aspect of the project focused on the outdoor cultivation trials of the best performing Ulva species (Ulva lacinulata), coupled with detailed biochemical analyses, to elucidate the impact of growth conditions on biomass quality. The results indicated that a density of 2 g/L was excessive for outdoor Ulva cultivation, leading to self-shading and reduced growth rates. Reducing the density to 1 g/L resulted in improved growth performance, suggesting its suitability for outdoor cultivation under optimal conditions. The addition of river water failed to mitigate the formation of precipitate on Ulva biomass when combined with FEF or RO water. Metabolite analysis revealed variations in ash and ulvan content in Ulva cultivated in RO + FEF + river water. Ulva grown in river water exhibits higher ulvan and lower protein content, consistent with the low nitrate levels in river water. Although river water alone did not support Ulva growth due to its low nitrate content, continuous water flow was identified as a potential factor that could enhance Ulva cultivation in such conditions. To conclude, this project shows that wastewater type, time of collection, salinity and strain of Ulva all play important roles in the use of Ulva for bioremediation. Indicating the potential of Ulva spp. in bioremediation of dairy factory effluent. Moreover, conducting additional trials has potential to develop a reliable treatment protocol, capable of not only remedying polluted waters but also generating valuable compounds for diverse downstream applications.
  • Publication
    A 3-D radiative transfer analysis of AGB winds
    (NUI Galway, 2024-04-16) Clarke, Seán Vivian; Redman, Matthew P.
    The chemical enrichment of the interstellar medium is driven by stars of low to intermediate masses shedding their external layers through powerful stellar winds. Eventually, after many years in this phase, the core of the star ionises these expelled layers and becomes a planetary nebula, where the shape and morpology of the surrounding gas was imprinted during the previous mass loss phase of its life. In this project, two aims are established. The first, to test two 3-D radiative transfer codes, MOLLIE and LIME, which were written for cold molecular clouds in their ability to model the conditions present in stellar winds of these asymptotic giant branch stars. The second is then using a code to model observational data of such a star. Two models were constructed for this work in accordance with the two aims established. The first model is a representation of the conditions present within the circumstellar envelope of an asymptotic giant branch star while the second is a model of the star IK Tauri, using literature and the code itself to constrain the parameters for accurately modelling the out flow. Both models use carbon monoxide as the rotational molecule due to its proliferation throughout stars and that it closely follows hydrogen lines while also being much visible than hydrogen itself. From the analysis of the test model, we determined MOLLIE unfit for the purpose of this work, so further modelling was carried out by LIME alone. With LIME we obtained accurate fits to the IK Tauri data for each rotational line, isotopolgue, and resolution studied. This ver ifies that the relatively simple model could produce line profiles supported by observational data while being less complex in comparison to 1-D radiative transfer models for similar results.
  • Publication
    In vitro model development for pulsed-field ablation treatment of atrial fibrillation
    (NUI Galway, 2024-04-15) Baena Montes, Jara Maria; Quinlan, Leo
    Atrial fibrillation is the most common type of cardiac arrhythmias in humans, mostly based on hyperexcitation of specific areas in the atrium that results in dyssynchronous atrial contraction, leading to severe consequences such as heart failure and stroke. Among the current treatment options, catheter-based ablation is used to isolate and destroy the abnormal tissue in the heart that promotes atrial fibrillation and has shown to be a good alternative to anti-arrhythmic pharmacological treatment. However, due to the large number of parameters involved, the selection and optimization of a good in vitro model is essential before translating the treatment to clinical trials. To this aim, this project focuses on the development of three in vitro culture models to be used as ablation testing platforms and the information that they can provide, indicating their potential as models in different stages of the treatment testing. The models presented are connected so that the results of the simpler model will influence the parameter decision of more complex models, reducing the parameter range while increasing the physiological resemblance to the real cardiac tissue. This study concludes by highlighting the potential of irreversible electroporation as a treatment for atrial fibrillation and the valuable information that can be obtained from these models.
  • Publication
    Analysing bovine sperm cells using flow cytometry
    (NUI Galway, 2024-04-10) Waters, Irene; Spillane, Charles; Brychkova, Galina; O’Meara, Ciara
    The accurate assessment of bull fertility is extremely important to the beef and dairy industry. In recent years, flow cytometry has become the dominant approach in sperm evaluation and is increasingly being used for quality assessment and for research in veterinary science. The aim of this research was to show how flow cytometry can be used to assess the quality of semen used in artificial insemination. The review focuses on the methodologies, currently used for bovine sperm concentration assessment and the advantage of flow cytometry has over other methods used for the semen concentration assessment. The research article investigates the technological differences between AccuCell Vs Flow Cytometry to determine semen concentration. It also accesses the reproducibility of results depending on the personnel’s techniques. Based on the analysis of sample diluents’ effect on the results generated with the flow cytometer and estimation of debris’ presence effect in samples, the optimal parameters of ejaculates to determine semen concentration using the flow cytometer are presented. Finally, the sustainability assessment of novel flow cytometry methodology for the semen concentration analysis of an ejaculate demonstrated that flow cytometry is a more sustainable method to use to determine the concentration of an ejaculate.
  • Publication
    Boundary behaviour in the Irish Bronze Age: A study of social and ritual practices in the mid-late Bronze Age
    (NUI Galway, 2024-04-08) Byrne, Marcus; Jones, Carleton
    The purpose of this thesis is to gain an insight into how boundaries were understood and utilised in the social and ritual lives of Bronze Age people. Boundaries are known in many forms, from visible physical linear earthworks in the landscape, to socially prescribed ways of interacting with people, places and things. Boundaries are situated at the limits of human interaction, and it is through actions performed at boundary locations that we can gain insight into how Bronze Age people considered abstract concepts involving social identity, death and territorial regulation. The theoretical attributes for boundary behaviour was explored and various forms of boundaries were outlined at the beginning of the thesis and several theoretical approaches to boundaries, borders and thresholds were explored. Furthermore, I set out to examine boundary behaviour through the lens of settlement, artefact deposition and mortuary practices to determine whether an integrated approach could help comprehend social and ritual behaviours at boundary locations on both a local and landscape scale. Settlement patterns were investigated to establish whether different levels of settlement operated at, or influenced, local and regional territorial boundaries. Roundhouses, lakeside settlements and hillforts were mapped and analysed to determine which were most influential as boundary indicators. Likewise, the location and composition of metal deposition was explored to comprehend ritual aspects to boundary marking by deposition. The data was integrated into a model of settlement patterns to determine boundary behaviour at the landscape scale, especially in relation to hillforts. The third element comprised mortuary ritual, assessing how various ways of treating human remains and the location they were interred disclose how boundaries were utilised to express identity, ancestry and possibly territorial control. This is a desk-based thesis which incorporated a GIS element for spatial analysis of currently available data. This data was integrated into a map and scrutinised for evidence boundary behaviour through settlement distribution, location of artefact and hoard deposition and mortuary practice though the placement of barrows and ring-ditches. The results of this an analysis supported the original research question in determining boundary behaviour on a local and landscape scale and combined divergent approaches to boundary behaviour in the Bronze Age.
  • Publication
    Developing a three dimensional (3D) in vitro model of adrenocortical carcinoma (ACC)
    (NUI Galway, 2024-04-05) Ribes Martinez, Eduardo; Dennedy, Conall; Pandit, Abhay
    Adrenocortical carcinoma (ACC) is a rare orphan disease and a rare cancer which carries a poor prognosis. The only licensed pharmacological treatment is mitotane, an insecticide. Typically, 2D cell culture models have been used to study ACC and represent the best available disease models for mechanistic insight of disease and therapeutics. However, these models have limited representation of disease in humans. Moreover, the rare nature of disease translates to a lack of human tissue specimens for research and culture, again limiting the investigation of disease mechanism in the context of ACC. As such all-cell lines and animal models are limited in their representation of human disease and hence multiple models are usually necessary to design investigative approaches to disease which help thoroughly understand and study the biology and propagation of this cancer. In the current thesis of work, we developed and characterize a spheroid model for primary tumour cell line, H295R and a metastatic cell line, MUC-1, showing a steroidogenic enzymatic cell profile. Additionally, we develop a collagen scaffold 3D model of H295R and MUC-1 that attempts to mimic the complexity of the extracellular matrix (ECM) supporting cell viability, metabolic activity, steroids production. Despite the lack of experimental replicates, altogether represents a preliminary data for a model to study ACC which retains its phenotype and steroidogenic properties.
  • Publication
    Intraguild impact of the invasive Noble false widow spider Steatoda nobilis (Thorell, 1875) in Ireland
    (NUI Galway, 2024-04-04) Collier, Brandon L.; Dugon, Michel M.
    With rapid urbanisation during the Anthropocene, several generalist spider species have adapted to synanthropic microhabitats and have established large populations outside of their native ranges. On the island of Ireland, the establishment and distribution of the Noble false widow spider Steatoda nobilis (Araneae: Theridiidae) (Thorell, 1875) within the last 20 years has spurred questions relating to its effect on native spider populations, the likelihood of other Theridiid spider establishing on the island, such as the medically significant black widows of the genus Latrodectus, and the likelihood of S. nobilis to establish in highly endemic insular habitats. Through an extensive field survey of six urban centres, we seek to establish population demographics for Steatoda nobilis and other synanthropic spiders in Ireland for the first time. We survey fence/railing microhabitats for spider density and diversity over the course of 11 months to draw comparisons with other variables such as prey availability and climate. In total, 20 identifiable spider species were observed occupying fence/railing microhabitats in urban centres around the island. Results indicate that S. nobilis and the missing sector orb weaver Zygiella x-notata (Clerck, 1757) typically make up more than 80% of the spider abundance within favourable microhabitats in Ireland regardless of the location surveyed; this includes two new counties where S. nobilis was previously not recorded but is now well established (Co. Mayo and Co. Sligo). The results also indicate that the diversity of synanthropic spiders is significantly affected by prey availability but not by daily weather conditions nor the removal of spiders through non-pesticidal means. Additionally, a comprehensive literature review of previous Latrodectus introductions to Ireland was conducted to determine the likelihood of establishment on the island. In addition to three published records, three additional records of Latrodectus importation, including the first record of L. hesperus in Ireland, were compiled and analysed. The global fruit trade was identified as a primary vector for black widows entering Ireland. Analysis of the case history indicates that it is unlikely that any member of the genus Latrodectus will be able to establish large populations on the island without relying on specific human-made structures (i.e., hot-houses). Overall, the data indicates that Steatoda nobilis’ rapid dispersal, large populations in urban microhabitats, and ability to outcompete native species in a lab setting meet the criteria to be considered an invasive species in Ireland. More synanthropic diversity surveys and comparative studies will be needed to understand the traits that make S. nobilis an effective alien species on a global scale, and to prevent it from invading areas of high endemism.
  • Publication
    Exploring advanced methodologies for the generation of synthetic data
    (NUI Galway, 2024-03-21) Duignan, Samuel; Schukat, Michael; Corcoran, Peter
    In the field of computer vision and machine learning the need for high-quality diverse data sets are crucial. However, acquiring such data sets with detailed ground truth can be challenging. This problem led to the increased attention towards synthetic data generation as a cost-effective and scalable solution. This research introduces a novel pipeline to generate synthetic data sets, lever aging both open-source and commercially available software. This approach democ ratizes synthetic data creation which often restricted to large organizations with extensive resources. The pipeline employs an innovative use of OpenPose, a tool for estimating facial landmarks, to fit an animatable mesh to each 3D scan. By refining and filtering OpenPose predictions, the accuracy of mesh fitting is significantly improved, leading to the generation of more diverse synthetic data. Further, we use a custom rendering pipeline built on Blender, an open-source 3D creation suite, to simulate intricate lighting scenarios improving the realism of the synthetic data. The data set is rich with variations in expressions, lighting, eye gaze, and head pose orientations that mirrors the complexities of real-world situations. Alongside synthetic facial images our pipeline generates a wealth of metadata such as bounding boxes, expression/action values as well as eye gaze and head pose values. This accurately labeled metadata serves as a rich source of ground truth data, extending the utility of our data set to various computer vision and image analysis tasks.
  • Publication
    The impact of cognitive dysfunction on the occupational performance of cancer survivors post chemotherapy
    (NUI Galway, 2024-03-13) Mulhern, Jason; Shiel, Agnes
    Background: Cancer rates are increasing globally. Survivorship is also rising due to advancements in early detection and treatment. Chemotherapy is a common anti-cancer treatment with adverse effects reported due to its cytotoxic nature. Of these, one is cognitive dysfunction. Cancer survivors report the behavioural repercussions of this sequela in relation to occupational performance. Objectives: This study aims to examine cognitive dysfunction post-chemotherapy and its’ effect on the occupational performance of cancer survivors. Methods: The cognitive function of ten (non-central nervous system) cancer survivors post chemotherapy was compared with eight non-cancer controls, matched for age, sex and education. The influence of cognitive dysfunction on the occupational performance of cancer survivors was examined. Cognitive dysfunction was assessed using ecologically valid neuropsychological tests with good psychometric properties. Occupational performance was measured using the COPM (Law et al., 2014) and participant-reported scales. Results: Cancer survivors demonstrated significantly poorer performance on the Visual Elevator-Timing (Robertson et al., 1994) than non-cancer controls (t(16)=2.43, p=0.03). All other group differences were non-significant (p>0.05). The Digit Span-Sequencing (Lezak et al., 2012) directly predicted occupational performance (β=0.95, p=0.03). In addition, combinations between the Digit Span-Sequencing (Lezak et al., 2012) or Modified Six Elements (Wilson et al., 1996a) and confounding factors significantly predicted variance in occupational satisfaction, IADL performance and ability to participate in social roles and activities. Conclusions: The results demonstrated that cancer survivors experience occupational performance issues related to cognitive dysfunction post-chemotherapy. Cognitive abilities which rely on an executive control element seem most affected. The impact appears greatest on higher-level tasks such as IADLs, work, driving and reading. These findings provide evidence that occupational therapists should consider the cognitive needs of cancer survivors post-chemotherapy as standard practice.
  • Publication
    Large-scale production of engineered Extracellular Vesicles (EVs) in a serum-free continuous culture bioreactor
    (NUI Galway, 2024-02-26) Bruce, Kelsey; Dwyer, Róisín
    Extracellular vesicles (EVs) are nanoparticles produced by cells that facilitate intercellular communication through cargo transfer. When isolated from a biocompatible cell source, EVs can deliver therapeutic interventions directly to tumor sites. The study of EVs is limited by suitable approaches for scale up of production in reproducible, serum free conditions. This work addresses the need for large scale, dynamic serum free production of EVs.Triple negative breast cancer cells (MDA-MB-231) were transduced with lentivirus containing the sodium iodide symporter (NIS). PCR was used at multiple timepoints to confirm stable mRNA expression, with protein expression confirmed via immunocytochemistry. 1 x 109 cells were inoculated into a hollow fiber bioreactor and glucose consumption monitored daily. When stable 3D culture was established, the transition to serum free conditions was made. Glucose levels were used as an indicator of cell health, media requirements, and harvesting frequency. Cells were extracted at 5 time points, and 16 harvests of EV rich cell conditioned media (CCM) were performed. EVs were isolated from CCM via size exclusion chromatography (SEC) and analysed via nanoparticle tracking analysis and microBCA assay. Expression of NIS mRNA was confirmed in transduced cells (log102.6 fold increase), with protein localization to the cell membrane observed. Cells in the bioreactor consumed 367 mg of glucose within 24 hours, which decreased to an average of 240 mg/24 h over the next 6 days. By day 12, cells were established in the bioreactor and tolerated the transition to serum free culture well, indicated by increasing glucose consumption. Cells sampled from the 3D bioreactor retained original morphology and proliferative ability in 2D. Over the total 46 day culture period, cells retained elevated expression of NIS. EVs isolated via SEC were <200 nm in size and early SEC fractions contained 1.76 x 109 - 8.90 x 1010 EVs. Protein in these fractions did not exceed 16 μg/mL while later fractions contained up to 593 μg/mL. The total yield over the culture period was 4.30 x 1012 EVs. Both the yield and purity of EVs isolated via SEC from cells cultured in 3D dynamic serum free conditions were significantly improved compared to those isolated via ultracentrifugation from cells in 2D. This scalable approach to reproducible, serum free EV production will support advancement of this exciting field towards clinical translation.
  • Publication
    Gradient-index lenses: Symplectic ray tracing and optical testing
    (NUI Galway, 2024-02-22) McKeon, Ben; Goncharov, Alexander
    The chief objective of this thesis is to provide an introduction to symplectic numerical methods and how they may be applied to optical problems, particularly for tracing rays within gradientindex (GRIN) optics. Specifically, we investigate how symplectic methods compare in terms of accuracy with well-established numerical integration techniques such as Euler’s method and the fourth-order Runge-Kutta method (RK4). As a near-term application, symplectic methods are used to render a test image which requires nonlinear ray tracing. The accuracy of implicit numerical methods is also considered, in addition to the derivation of algebraic iteration schemes for lenses with separable index profiles thereby removing the need for root solvers when using implicit methods. Finally, the pyramid wavefront sensor, a component commonly employed in adaptive optics systems, is considered as a means of measuring aberrations present within GRIN elements and is proposed as a tool to undertake the characterisation and optical testing of same.
  • Publication
    Development and performance of a serological enzyme-linked immunosorbent assay (ELISA) for ruminant liver fluke disease
    (NUI Galway, 2024-02-02) López Corrales, Jesús; Dalton, John Pius
    Fasciola hepatica, also known as the liver fluke, is the causative agent of fasciolosis. It is classified by the World Health Organisation as a neglected tropical disease, affecting both humans and livestock globally. Moreover, infections caused by this parasite cause multimillion economic losses to the livestock industry. In order to minimise the effects of F. hepatica infections by applying the appropriate management and control interventions, it is essential to include the use of a reliable diagnostic method that is also effective in determining infections as early as possible with high sensitivity and specificity. Among the available methods, we show that serum-ELISA based on the detection of antibodies against cathepsin L1 peptidase has a high efficacy detecting infections at every developmental stage of the flukes in their definitive hosts. However, discovering new antigens is essential to provide more options for the development of liver fluke diagnostics and vaccines, allowing us to use one or more antigens to differentiate infected from vaccinated animals (DIVA). In this work, we evaluated the performance of an array of molecules produced by F. hepatica as antigens for indirect ELISA tests in comparison with recombinant cathepsin L1 (rFhCL1). Four antigens, namely rFhGAPDH, rFhGPI, rFhEnolase and rFhFBPA, were recombinantly produced during this study and assessed in ELISA, along with several more recombinant antigens (rFhHDM, rFhLAP, rFhPrx, rFhSOD1, rFhSOD3, rFhTrx, rFhCL2, rFhStf1 and rFhKT1), to analyse IgG responses in sera samples of sheep and cattle that were both experimentally and naturally infected. None of the studied antigens performed better than rFhCL1 because of their lower immunogenicity. In addition, some of them showed high background levels due to antibody cross-reactivity. In the case of E. coli produced antigens, this was possibly caused by E. coli infections in the animals or natural antibodies targeting E. coli proteins. In the case of P. pastoris produced antigens, the cross-reactivity possibly resulted from glycans present in the recombinant proteins. These sugar residues may be recognised by host antibodies produced after being fed with yeast-rich supplemented food. Finally, we studied a potential method to determine liver fluke infection stages, namely by calculating the ratio anti-rFhCL1/anti-rFhCB3 immune responses, with promising results. Future investigation including a larger number of samples and complementary parasitological data will be key to further prove its applicability.
  • Publication
    Enhancing blood circulation time and performance of nano-drug delivery systems using nanoparticles and hydrogels
    (NUI Galway, 2024-01-26) Kruk, Jakub; Erxleben, Andrea
    Mesoporous silica nanoparticles (MSNs) and hydrogels are some of the most sought-after methods of nano-drug delivery systems. Properties such as high biocompatibility, selectivity and loading capacity are among the many reasons as to the myriad of research performed using them as nano-drug delivery systems in addition to the increasing demand for more effective and safer treatments of cancer and cardiovascular disease. The aim of this project is to enhance blood circulation to improve the delivery of nano-drug systems, with the desired result being the development of more effective, ergonomic, and safer anti-cancer drugs replacing cisplatin as the standard chemotherapy treatment, with great emphasis on the carriers of the drugs; mesoporous silica nanoparticles (MSNs) and hydrogels. The MSNs, although synthesized, successfully aminofunctionalised and separated from their template (CTAB), and coated with gelatin, were only partially crosslinked with aldehyde groups, meaning that reliable pH-responsive surface linkers for targeting tumour cells were incomplete. Hydrogels were later synthesised as alternative drug delivery systems for anti cancer drugs: chitosan was initially used as the primary polymer and β-glycerophosphate as the crosslinking agent, but were generally irreversible: once solidified at physiological temperature (37 °C), they did not reliquefy. They released drugs at quicker rates than allowed for sustained release. Pluronic F-127-based hydrogels were reversible, solidifying at physiological temperature and reliquefying at room temperature, but had a relatively short shelf life, as they decomposed in the presence of water after 3 days at physiological temperature.
  • Publication
    Mechanistic and kinetic study on the anomerisation reaction and application in pharmaceutical research
    (NUI Galway, 2024-01-08) Holland, Trish; Murphy, Paul V.
    It is becoming increasingly apparent that carbohydrate-based pharmaceutically active compounds (PACs) play a key role in pharmaceutical advancement. Many new carbohydrate-based PACs have recently been developed with a plethora of functions ranging from antiviral and anticancer effects to drug delivery systems. With this increased interest in carbohydrate-based pharmaceutical research, gaps in the knowledge of carbohydrate chemistry have become apparent, with many challenges still being faced by carbohydrate chemists, including the stereoselective synthesis of anomers. The synthesis of glycosidic links is an essential aspect in the development of carbohydrate-based PACs. A possible route to the selective synthesis of carbohydrate anomers is the anomerisation reaction that is generally preformed using a Lewis acid catalyst. The aim of this thesis was to synthesise the new galacturonic acid derivative 2,3,4-tri-O-acetyl β-D-galactopyranosiduronic acid, methyl ester using the Koenigs-Knorr glycosylation reaction and investigate the kinetics of the anomerisation of this compound. The rate constant for this compound was calculated to be 5x10-5 at RT. This result led to an interest in the varying kinetic rate constants of different uronic acid derivatives. Therefore, further study of the kinetics of the anomerisation reaction of previously synthesised compounds was undertaken, specifically the change in rate constants of the reaction when varying the temperature, uronic acid derivative and catalyst concentration was investigated. The three uronic acid derivatives investigated were 2,3,4-Tri-O-acetyl-β-D galactopyranosiduronic acid, methyl ester ,Butyl 2-O-(4-phenylbenzoyl)-3,4-di O-benzoyl-α-D-glucopyranosiduronic acid methyl ester, Butyl 2-O-(4-bromolbenzoyl)-3,4-di-O-benzoyl-α-D-glucopyranosiduronic acid methyl ester and Butyl 2-O-(4-methylbenzoyl)-3,4-di-O-benzoyl-α-D glucopyranosiduronic acid, methyl ester By varying the temperature at which the anomerisation reaction takes place, the activation energy could be calculated from a set of experimentally determined rate constants and were found to be 17.71, 60.43 and 30.94 KJ/Mol respectively. This showed that EDG groups on the C2 substituent tended to increase the activation energy of the anomerisation reaction for compounds (5) and (6). Compound (7) activation energy was Due to probable experimental error, the rate constant calculated for compound (7) at 45°C was disregarded. Therefore the activation energy calculated may not be as accurate and more investigation is needed to evaluate trends in the effect of EDG and EWG groups on activation energy. Catalyst concentration studies were carried out and it was found that increasing the concertation above a 1:1 ratio had little to no effect on the reaction rate, indicating that the rate determining step of this reaction only requires one SnCl4 molecule.
  • Publication
    An online tool for guiding bus fleet decarbonisation through green hydrogen and electrification
    (NUI Galway, 2023-12-18) Cummins, Tadgh; Monaghan, Rory
    The transition to zero emission bus (ZEB) fleets is accelerating, and bus fleet operators are faced with no choice but to plan their decarbonisation approach now. Two prevalent ZEB options are battery electric buses (BEBs) and fuel cell electric buses (FCEBs) fuelled by green hydrogen. Hydrogen is labelled as green when it is produced by electrolysis powered by renewable electricity. It can often be unclear which combinations of BEBs and FCEBs are most suitable in terms of cost, emission reduction, and capability to maintain regular operation of the bus fleet. Additionally, as governments implement incentives to make public transport more appealing than using a car, fleet sizes and number of routes will grow, increasing the demand for ZEBs. This work develops the Enabling Support Tool (EST), an easy-to-use Microsoft Excel-based model that can assess the trade-offs between BEBs and FCEBs in terms of their technical performance, required infrastructure, cost, and emissions reduction potential. The novel aspects of this work are as follows. Firstly, the EST model was transferred to an online webpage featuring an interactive graphical user interface allowing stakeholders to interact with the model directly. Additionally, the model features a novel input process that minimises data collection and preparation time while requiring less training to use than previous models of similar purpose. This work is also novel in that it quantifies the effect of road gradient and passenger weight on the specific fuel consumption of BEBs and FCEBs using a regression analysis method. This model enables users to quickly explore the feasibility of different combinations of BEBs and FCEBs and thus guide cost-effective full fleet decarbonisation. Using the EST model, decarbonisation case studies were performed on existing bus fleets in Galway, Ireland and Saarland, Germany. The case studies envision the transition of the entire bus fleet from conventional diesel-fueled buses to ZEBs. The aim of the case studies was to determine the optimal combination of BEBs and FCEBs in a mixed fleet and to compare the total cost of ownership and emissions reduction achieved when switching to a mixed fleet, a BEB-only fleet, and an FCEB-only fleet. The main results of the case studies are as follows. For the Galway city fleet consisting of 31 double-deck buses, 15 additional buses would be required to maintain fleet operations if transitioning to an all-electric bus fleet due to the relatively short range of double-deck BEBs. This increases the total cost of ownership (TCO) by 0.21 €/km, leading an overall TCO of 1.37 €/km. A fleet comprising of FCEBs only would not require any additional buses but would be much more expensive due to the high cost of FCEBs and hydrogen. For a hydrogen price range of 2 €/kg – 12 €/kg, the calculated TCO is 1.06 €/km – 1.62 €/km. At a hydrogen price of 7 €/kg, the mixed fleet of BEBs for shorter routes and FCEBs for longer routes has the lowest predicted TCO out of the ZEB fleets, at 1.10 €/km. For Saarland, results show that BEB fleets are currently more economically attractive than FCEBs in the region due to a lower price of electricity and higher average range of single-deck BEBs which are used in the area. Sensitivity analysis of the key outputs of the EST shows that the parameters with the largest impact are fuel and electricity prices, bus price, and hydrogen infrastructure costs. Using prediction trends for the evolution of these parameters over time, scenarios were developed to investigate the changing roles of BEBs and FCEBs in bus fleets from 2023 to 2030. In the 2030 scenario featuring pessimistic cost reduction trends, ICEB technology remains the most cost effective. In the scenario featuring optimistic trends, the FCEB fleet is the most cost effective with a TCO of 0.84 €/km.
  • Publication
    Application of flow cytometry and membrane inlet mass spectrometry as tools to assess dimethyl sulfide produced in emiliania huxleyi (CHC108) cultures
    (NUI Galway, 2023-12-04) Wink, Adelaide; Croot, Peter
    Dimethyl sulphide (DMS) is a key component in the global sulphur cycle with emphasized significance in areas away from anthropogenic sources. Phytoplankton produce DMS when under stress as a defence mechanism from abiotic and biotic influences such as high wind stress and grazing. E. huxleyi was used as the phytoplankton of choice because of the cosmopolitan nature of the species along with the more robust nature of the coccolith. DMS has a high diffusion rate in the atmosphere so immediately monitoring the levels in the water column has proven difficult especially when looking at continuous input flux. In this study, membrane inlet mass spectrometry was used to monitor DMS flux over varying periods of time along with a possible variation of DMS under Mass 47 which excludes one of the methyl groups under different stressors. This continuous observation allowed for the observation in minute changes over longer periods of time rather than using the snapshot method which looks at chemical concentrations at singular points in time. This novel technique can give insights to the response times of the phytoplankton to the changing environment in real time. The added stressors to the water column did result in an increase of DMS but the lag time to the addition and the visible increase in DMS did not follow the expected trend. Of the parameters tested here, the most likely to initiate DMS production is heavy metal loading and water column acidification.
  • Publication
    Reading between the 'likes': Intertextuality and meaning in neo-Assyrian expressions of similarity, metaphorical identity, and analogy
    (NUI Galway, 2023-10-09) Mc Dermott, Luke; Clarke, Michael
    Figurative language is, in essence, the act of synthesising disparate concepts into one communicative image. Rather than merely a poetic technique, this process is fundamental in general understanding and expression of abstract or new ideas. Moreover, metaphorical and non-literal statements echo and signal the cultural network of meaning to which they contribute in a way that literal statements do not. In this sense, metaphorical language is semantically open where the literal is closed. Simile is even more inherently self-exegetical. The expression of X in terms of Y on the basis of implicit or explicit similar characteristics is itself a process of interpretation by comparison. Simile is also a more literal type of formulation than straight metaphor. That is, simile ‘has a job to do, and it does it: it proposes a comparison between two entities, in one particular respect, or at most in a few respects, as it is explicit in its comparative goal.’1 Language which highlights a conceptual proximity between expressed referents functions as a key for the reader. It accentuates the characteristics of the expressed X which are deemed prominent and relevant by their commonality with those of the compared Y. The style of expressing concepts in terms of one another, implicitly acknowledging their thematic or characteristic overlaps, is a technique that has been central throughout the Mesopotamian textual tradition. It does not just appear as a preserve of artistic or poetic writing, but is ubiquitous. As will be seen, this pattern based expression is structurally integrated into such societal and ritual events as divination political accords, and substitute rituals.2 Using the framework of template expressions of conceptual proximity laid out in the table below (Fig.1), this dissertation will analyse the metaphorical and analogical language that pervades its case study, The Underworld Vision of an Assyrian Prince (henceforth UWV). This philological process produces a deep engagement with the text. During this slow reading, the sense will emerge that the ways of expressing conceptual proximity and communicating ideas through their nexus of cultural associations and intertextual correlates was also of intellectual interest to UWV’s author. It will be argued here that the author sets up and explores the relationships between ideas by means of intricate figurative language, wordplay, intertextuality, and even meta-textuality, where the scribal narrative voice itself explicitly engages with the “moral” of the tale as it tells it. This dissertation will follow the threads of intertextuality which can often be discerned within the incorporation of figurative language throughout the narrative. The gradation of intertextual resonances along a spectrum which ranges from echoes of a shared cultural context to deliberate and authorially fixed allusion is discussed below (Fig.2). An overview of some of the contextual considerations that this study requires will be given below, such as the developments in the field of cognitive metaphor and the work that has thus far been done to bring this scholarship into the study of Mesopotamian writing. The following chapter will look at the central role and esteem that the culture of textuality enjoyed in the organisation of Mesopotamian society. It will show how important metaphorical language and the conceptualisation of ideas in terms of a comparandum were in central procedures of state and society. For example, it discusses how the protasis-apodosis relationship in divination was often an a priori association rooted in cultural or paronomastic affinities rather than any a posteriori observation of empirical causality. Moreover, Section 2.2 examines metaphorical language that manifested in the reification of a political accord.3 This will serve to underline the importance that metaphorical language and thought had in a culture whose modes of communication were so intertwined with literacy and textuality. The rest of this dissertation will be dedicated to a slow reading of the case study, The Underworld Vision of an Assyrian Prince. The emphasis of this reading will be on the figurative expressions of metaphorical predication and simile. Particular focus will be given to two passages, both coming on the reverse tablet. The first of these (r.2-10) is sequence of vivid descriptions, a catalogue of the various bodily compositions of the divine beings that the protagonist, Kummay, encounters on his journey through the underworld in a dream.4 It will be appraised in its own right, but also in juxtaposition with the bodily descriptions that are found in other texts, particularly in the teratological divinatory series Šumma izbu5 as well as the swapping of limbs between a spring lamb and the king of Arpad in a treaty between Aššur-nerari V and Mati’-ilu. 6 The other section (r.29-31) details the emotional maelstrom overcomes the prince upon waking from his infernal experience. His anguish is captured in a uniquely complex double simile which likens him first to a man hiding in the thicket from hunters, and then to a pig at the height of carnal excitement. Of course, other incorporations of analogy and metaphor in the narrative will also be discussed. For example, a simile (r.23) which describes the legacy of a royal corpse that the protagonist is shown in the underworld, which bears an intertextual relationship with the Letter of Gilgamesh.7 Considering the level of influence that was borne by Mesopotamian culture upon those of surrounding communities, increased understanding of the value associations of the former will shed further light upon its relationships with the latter. For example, understanding more keenly the semiotics of metaphorical expressions within a given cultural context aids efforts to trace a metaphor across cultures. This facilitates more comparative work to problematise and evaluate the transmission and translation of particular metaphor between textual communities. Throughout this dissertation, passages of text will generally draw on the translation work of other scholars, but also comment upon it; with deconstructions and suggestions of alternative interpretations offered where appropriate. In the instance of the primary case study, UWV, the translation of Livingstone8 will be most represented, though the interpretation of other scholars, such as Foster9 will also be incorporated. Where no notation is given, translation is my own. All of my own translation work, however, is based on the valuable transliteration from cuneiform of other scholars. Notation of the translation and edition used is given in each case throughout the dissertation.
  • Publication
    Exploring the perceived factors affecting participation in rugby for children with disabilities using the ‘F-words in child development’ framework: A mixed methods study
    (NUI Galway, 2023-10-09) Connolly, Cathal; Killeen, Hazel; Dempsey, Mairead
    Objective: The aim of this study was to explore the perceived facilitators and barriers to participation in rugby for children with disabilities from the perspective of three relevant stakeholders; parents of children with disabilities, rugby club personnel, and children with disabilities that play rugby. Methodology: This study adopted a mixed methods design using a concurrent triangulation approach. The ‘F-Words in Child Development’ framework was used to guide development of the data collection tools. Online questionnaires were distributed to parents and rugby club personnel nationwide. The questionnaires contained demographic questions, Likert scale ratings, and qualitative open-ended questions related to rugby participation. The parent questionnaire also contained the standardised Child and Adolescent Scale of Participation (CASP). Spearman rank order correlations were applied to rugby participation ratings and the CASP. Inductive thematic analysis was used for the qualitative responses from both questionnaires. Inductive thematic analysis was used to analyse the qualitative data from the questionnaires. Semi-structured interviews were held with three children with disabilities that play rugby. The data generated from these interviews was not included as it was deemed to be insufficient. Results: There were 39 parent questionnaire responses and 47 club personnel questionnaire responses. The parent questionnaire themes were ‘Striking the Right Balance’ and ‘Variety of Options to Match the Variety of Values’. The club personnel questionnaire themes were ‘Opportunities and Challenges of Inclusion’ and ‘Opportunities and Challenges of Development’.(iv) Discussion / Conclusion: This was the first study to examine the facilitators and barriers affecting participation for children with disabilities that play rugby. This study was also the first to apply the ‘F-Words for Child development’ framework to a community-based activity. The responses from the stakeholders demonstrated a range of factors affecting participation. Their responses highlighted important steps that need to be taken and issues that need to be addressed to ensure children with disabilities have positive participation opportunities and experiences throughout their childhood.
  • Publication
    Developing and implementing a l-openspim platform using in-air optics and measurement of tissue temperature changes
    (NUI Galway, 2023-10-07) Oluniran, Gideon; Colgan, Niall; Dockery, Peter
    Relative to other microscopy techniques, light sheet fluorescence microscopy is widely accepted due to its ability to provide optical sectioning, higher speed, larger field of view, lesser photobleaching, and physiological support for timelapse imaging. However, biologists interested in harnessing these benefits may not have access to commercial systems possibly due to limited funding. In cases where they do, the rapid development in research will ultimately render such platforms obsolete. Resulting in the need to consistently purchase new microscopes or upgrade modules off the shelf. At best, biologists will be forced to limit investigations to microscope capabilities. Do-it-yourself (DIY) versions exist and when combined with air objectives give greater flexibility. Biologists are therefore encouraged to learn the art of building their own microscope, starting off with platforms built off air optics, while gaining the skill required to consistently make changes when the need arises. openSPIM DIY versions arguably have the most detailed and published build instructions, but they are more tailored towards in-vivo imaging and samples that fit within the field of view. I further expand on this by documenting stepwise instructions and building a LopenSPIM platform using air objectives for in-vivo and in-vitro imaging. More practical insights into finer light sheet alignment, choice of image acquisition software, and efficient data acquisition and saving tips are documented. I show the ability of our SPIM platform to produce quality 3D images of a millimetre sized Varroa destructor, and to distinctly reveal cells of the optically transparent head of a Hydractinia symbiolongicarpus. Details needed to extend the microscope capacity to centimetre sized samples at a high isotropic raw image resolution are stated. This work primarily aims to aid biologists with limited technical experience, and I further describe a protocol for investigating thresholds on light sheet microscopes that limit laser induced heating effects and ensure tissue bio-fidelity. I show that 10 mW, 20 mW, 30 mW, 40 mW, 50 mW, and 60 mW of laser power corresponding to intensity values of 1182 mW/mm2 , 2363 mW/mm2 , 3545 mW/mm2 , 4726 mW/mm2 , 5908 mW/mm2 , and 7090 mW/mm2 should not be applied for more than 26 s, 10 s, 5 s, 4 s, 4 s, and 3 s to 1 mm2 of mammal tissue, respectively, to limit temperature rise to ~ <1 0C.