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Assessment and optimization of co-digestion of grass silage and animal slurry
No full textPasture-based beef systems can provide cattle slurry and grass silage for anaerobic digestion (AD). However, there are still considerable gaps in the full-scale anaerobic co-digestion of these feedstocks, particularly the capacity to predict AD performance under a range of grass silage and cattle slurry characteristics, and how AD can be integrated into livestock farming. The objectives of this PhD research included: (1) application of the Anaerobic Digestion Model No. 1 (ADM1) to simulate the full-scale co-digestion of grass silage and cattle slurry, and determination of the most influential parameters; (2) assessment of the performance of simplified ADM1 and two machine learning algorithms in simulating biogas and methane production from a full-scale AD plant co-digesting different agricultural feedstocks; and (3) assessment of the integration of AD into a livestock farming system in terms of feedstock provision, greenhouse gas emissions (GHG), digestate management and economic viability. Results indicated that a simplified version of the ADM1 was able to accurately depict the biogas and methane production as well as general trends of pH and ammonium nitrogen from a full-scale AD plant co-digesting grass silage and cattle slurry. Results from substrate composition variability indicated that the variations in crude carbohydrates, proteins and lipids concentrations did not significantly affect biogas and methane yields across the data sets analyzed. In contrast, carbohydrate degradability emerged as the most significant parameter in explaining the variability in biogas and methane production. For a full-scale AD plant co-digesting various agricultural feedstocks, a simplified ADM1 model (ADM1-R3) and two machine learning (ML) algorithms, random forest (RF) and long short-term memory (LSTM), demonstrated high accuracy in simulating biogas and methane production. Unlike ADM1, which required detailed feedstock characterization, the ML algorithms achieved comparable performance using only fresh feedstock quantities and volatile solids (VS) as inputs. LSTM exhibited the highest computational demand, with simulation times 141 times longer than ADM1-R3 and 11 times higher than RF. Among the tested input variables, maize silage (fresh quantity and volatile solids) was identified as the most influential feature in the ML models.Teagasc Walsh Scholars Programm
Examining caffeine consumption in Ireland and its association with cognitive performance
No full textBackground: Caffeine is one of the most widely consumed psychostimulants worldwide and is increasingly being added to a variety of consumable and external- use products including beverages, medications, workout supplements, and cosmetics. The health benefits, cognitive enhancing effects, and neuroprotective effects of caffeine have long been studied with recent reviews indicating a strong neuroprotective link between regular caffeine consumption and improved cognition and lower dementia risk. Additional clinical research is needed to support the link whilst accounting for confounding variables between individuals. It is estimated that there has been an increase in caffeine consumption in the Irish population, but no research study confirmed this to date.
Aim: To survey caffeine consumption habits in Irish adults and investigate its association with cognitive lapses. Additionally, to gather data on potential confounding variables related to dementia risk, aiding future longitudinal research examining the neuroprotective effects of caffeine on dementia risk and Alzheimer's disease.
Method: A survey was developed based on an internet search of tools assessing caffeine intake. The Cognitive Failures Questionnaire (CFQ), a self-report measure of everyday cognitive lapses, was included as a cognitive screening measure. A total of 968 adults living in Ireland participated in the study, with 586 completing the survey in full. Responses were collected via Qualtrics. Pearson’s correlation analysis was used to examine the association between CFQ scores and caffeine intake. Results: The mean daily caffeine intake was 361.29mg (SD=312.02) and the mean CFQ score was 40.5 (SD=16.9). A very weak but statistically significant positive correlation was detected between CFQ scores and daily caffeine intake (N=600, r=0.09, p=0.03). A similarly weak but non-significant positive correlation was observed between coffee intake specifically and CFQ scores (N=485, r=0.09, p=0.051).
Conclusion: Coffee was the most popular caffeinated beverage consumed amongst Irish adults in this sample. This was the first study to examine caffeine intake habits across various products consumed by adults in Ireland. Likely due to the large sample size, a statistically significant but negligible correlation was found between CFQ scores and daily caffeine intake. Future epidemiological studies investigating the link between caffeine and cognition should collect extensive longitudinal data on cognitive performance using a comprehensive battery of cognitive assessments, along with neuroimaging data and information on genetic variability. This is especially important within subgroups of dementia patients and healthy controls to draw robust conclusions about the neuroprotective effects of caffeine. Future analyses should also focus on examining the individual effects of confounding variables, such as age, gender, lifestyle factors, and comorbidities, to better understand their influence on the relationship between caffeine intake and cognitive performance
The optimization of thermodynamic and rate constant rules to describe the oxidation of large alkane fuels
No full textIn this study, a consistent set of rate constant rules have been developed to describe the pyrolysis and oxidation of large alkanes. Initially, the rate rules were developed based on 2,2,3-, 2,3,4-, and 2,2,4-trimethylpentane, chosen for their complex molecular structures. These rate rules were then applied to construct a combustion mechanism for n-decane. However, due to the limited structural variety (only three branched octanes) used in the rate rule development, further refinements are necessary to improve the predictive accuracy for n-decane. To develop more transferable and broadly applicable rate rules, a greater diversity of fuels is needed for the optimization process. The present work includes various pentane, hexane, heptane isomers, iso-octane, and large n-alkanes (C8–C12). However, due to the large number of fuels, an automated optimization methodology was developed to enhance efficiency. This automated approach was tested on the three pentane isomers and further refined through experimental investigations of first-stage ignition behaviour measured in rapid compression machine (RCM) experiments. To address the “global optimized” challenge of optimization for a large set of rate rules, a two-stage optimization strategy was implemented: (a) optimizing alkanes with only primary, secondary, and quaternary carbon atoms, followed by (b) optimizing those containing tertiary carbon atoms. The optimization was carried out using experimental ignition delay time data measured in shock tubes and in RCMs, and species concentration versus time/temperarture data measured in jet-stirred reactors, together with advanced computational techniques such as PCA-SUE and Optima++. The final optimized rate rules were successfully applied to establish combustion chemistry models for and n-undecane and 2-methyl decane. Experimental validation demonstrated accurate predictions of ignition delay times and species concentration profiles, confirming the effectiveness of the rate rules developed. This work provides a systematic approach for refining alkane combustion mechanisms and contributes to an improved understanding of large-alkane oxidation chemistry
Development of a biomaterial releasing immunomodulatory extracellular vesicles for enhanced corneal repair
No full textIntroduction:
The cornea is the dome-shaped, transparent, outermost layer of the eye, playing a crucial role in both vision and protection of intraocular structures. Corneal diseases represent a leading cause of blindness worldwide. Despite advances in available therapies, effective treatment options for severe corneal injuries remain an unmet clinical need. Mesenchymal stromal cells (MSCs) have emerged as promising candidates for corneal repair due to their anti-inflammatory, immunomodulatory, and regenerative properties. However, the clinical application of MSCs is challenged by issues such as optimal dosage and delivery, potential immunogenicity and tumorigenicity, as well as donor variability and dependency. Extracellular vesicles (EVs) are nanoscale particles secreted by virtually all cell types, including MSCs (MSC-EVs). Acting as mediators of intercellular communication, EVs deliver functional cargo, such as proteins, lipids, and nucleic acids (including miRNAs), to recipient cells, thereby recapitulating many of the therapeutic effects of their parent cells. MSC-EVs have demonstrated immunomodulatory and regenerative effects in corneal tissue, while potentially overcoming several limitations associated with cell-based therapies. Pre-conditioning or ‘licensing’ of MSCs with cytokines such as IFN-γ and TGF-β1, either individually or in combination, can enhance their immunomodulatory capacity and, consequently, the therapeutic efficacy of their EVs in tissue regeneration. Nonetheless, the systemic administration of MSC-EVs is limited by rapid clearance and off-target accumulation in organs such as the liver and lungs. Local ocular delivery, particularly via topical eye drops, also faces significant challenges, including rapid clearance and limited retention on the ocular surface due to tear turnover and blinking. Alternative delivery systems have been explored, among which fluid gels, such as gellan gum fluid gels, have shown promise for ocular application. Gellan gum fluid gels exhibit unique rheological properties, enabling easy application to the ocular surface, prolonged retention, controlled release of therapeutic agents like MSC-EVs, and gradual removal through natural blinking. In this work, we suggest cytokine-licensed MSC-EVs as a novel therapeutic for ocular diseases, which can be delivered to the ocular surface in a controlled manner employing innovative phase-transition gellan gum fluid gel system.
Methods:
MSC-EVs were isolated from both naïve and cytokine-licensed (IFN-γ and TGF-β1) MSC-conditioned media using size exclusion chromatography (SEC). The isolated EVs were characterized for size distribution by nanoparticle tracking analysis (NTA), morphology by transmission electron microscopy (TEM), surface and intraluminal markers by flow cytometry and western blotting, and miRNA cargo profiling. The immunomodulatory effects of MSC-EVs were assessed using macrophage and T cell functional assays. Additionally, the tissue repair potential of MSC-EVs was evaluated in human corneal epithelial (HCEpi) and human corneal keratocyte (HCK) cell cultures, as well as in ex-vivo human and bovine corneal injury models. To elucidate the mechanisms underlying MSC-EV-mediated wound healing, mRNA sequencing was performed on HCEpi cells treated with MSC-EVs during the active phase of wound repair, enabling the identification of key miRNA-mRNA regulatory interactions. Gellan gum fluid gels (FGs) were synthesized and optimized based on their rheological properties under small and large deformations. MSC-EVs were incorporated into FGs, and their distribution and release kinetics were evaluated using confocal microscopy and spectrophotometry. The bioactivity of released MSC-EVs was assessed by their uptake into HCEpi and HCK cells, in-vitro wound healing assays, and an ex-vivo bovine corneal alkali burn model. The therapeutic efficacy of FG-delivered MSC-EVs was further investigated in a pre-clinical limbal stem cell deficiency (LSCD) model, with outcomes measured in terms of corneal vascularization and wound healing.
Results:
Cytokine-licensed MSC-EVs exhibited a uniform size distribution of approximately 100 ± 20 nm and a characteristic lipid-bilayer, spherical morphology. These vesicles expressed canonical tetraspanin surface markers (CD9, CD63, CD81) and the intraluminal marker TSG101. MSC-EVs accelerated corneal wound healing in-vitro (HCEpi and HCK cells) and in ex-vivo human and bovine corneal injury models. Cytokine licensing altered the miRNA profile of MSC-EVs, and integrative mRNA-miRNA analysis revealed novel regulatory interactions implicated in corneal repair. Functionally, MSC-EVs derived from cytokine-licensed MSCs exhibited enhanced immunomodulatory activity, significantly suppressing pro-inflammatory macrophage activation, promoting an anti-inflammatory phenotype, and reducing the secretion of cytokines such as TNF-α and IL-1β. Moreover, cytokine-licensed MSC-EVs more effectively inhibited allogeneic T cell proliferation and increased regulatory T cell induction compared to naïve MSC-EVs. Gellan gum fluid gels demonstrated phase transition and shear-thinning properties ideal for ocular drug delivery. FGs enabled controlled release of MSC-EVs, with approximately 18% of the loaded vesicles released after 6 hours. Released MSC-EVs retained their bioactivity, as evidenced by successful cellular uptake and promotion of wound healing in-vitro and in the ex-vivo bovine corneal model. In the pre-clinical LSCD model, FG-functionalized MSC-EVs significantly enhanced corneal wound healing, although no significant effect on corneal neovascularization was observed.
Conclusion:
Cytokine licensing enhances the immunomodulatory and regenerative properties of MSC-EVs. These licensed MSC-EVs promote ocular surface repair across in-vitro, ex-vivo, and pre-clinical models, supporting their potential as therapeutic agents for corneal injuries. Gellan gum fluid gels provide an effective platform for the controlled delivery and sustained release of MSC-EVs, preserving their biological activity and offering a promising approach for ocular drug delivery. Collectively, the findings of this thesis suggest that cytokine-licensed MSC-EVs delivered via gellan gum fluid gels represent a novel and promising therapeutic strategy for ocular injuries, necessitating further optimization and preclinical investigation
Vulnerability as a technology of EU migration management in the Aegean: From humanitarian exceptions to border violence
No full textThis thesis conceptualises vulnerability as a technology of migration management in order to reveal the relationship between international law, and the production and normalisation of border violence. It sheds light on an exclusionary logic of humanitarian exceptionalism that structures racialised migrants’ access to territory and protection in international and European law. On land and at sea, access to protection for the world’s ‘unwanted’ migrants, whose right to cross national borders is unrecognised, and who lack the necessary passport and financial means to travel freely, is, in practice, increasingly contingent on the logic of humanitarian exceptionalism. In the context of the EU border and migration management policies in Greece, this logic plays out in the way that two parallel concepts of vulnerability determine access to asylum: increasingly, we see that in order to gain admission, asylum seekers must be recognised as ‘vulnerable’ on land or ‘in distress’ at sea. Both function as criteria for protection and have been employed through migration management policies in a way that is, in practice, limiting the core right to seek and enjoy asylum at the external borders of the EU. By demonstrating the role of vulnerability as a technology of migration management, this thesis advances an understanding of the relationship between the paradigm of European migration management, the erosion of the right to seek asylum and the increasing forms of violence, both ‘slow’ and ‘spectacular,’ against irregularised migrants at external borders of the EU
Crystal growth and morphology control of needle-shaped organic crystals
No full textUnderstanding the growth of needle-shaped molecular crystals and the factors that influence the needle morphology is not only a fundamental research question but is also important in the design of industrial crystallization processes. Needle-like crystals have poor flow properties, are difficult to filter and to dry and – in the case of pharmaceuticals – difficult to formulate. While the morphology can often be controlled by changing the solvent, some compounds are persistent needle-formers that grow from all solvents as highly anisotropic crystals. In this highlight article we discuss the structural properties that lead to (persistent) needle growth. We also review strategies to modify the morphology such as the use of tailor-made additives, polymeric growth modifiers and cocrystallization.This publication has 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 12/RC/2275
Deconstruction of farm machine-related safety interventions: a systematic review and narrative synthesis
No full textIntroduction
Agricultural workplaces have a high number of incidents and fatalities, with the majority occurring from machinery use. Farmers’ behaviour plays a critical role in maintaining safety, as improper or unsafe practices often lead to injuries and fatalities. This review categorises interventions targeting farm machine safety, examining both the behaviour change techniques (BCTs) used and their reported outcomes to understand how the techniques influence safety practices and outcomes on farms.
Methods
The systematic review is reported in accordance with the Preferred reporting items for systematic reviews and meta-analysis guidelines. Seven electronic databases were searched for relevant studies published before June 2024, and the quality of included studies was assessed using Cochrane risk of bias assessment tools. Analysis of intervention behavioural components was guided by the behaviour change wheel framework and BCT taxonomy (v1). The findings were synthesised using a narrative review.
Results
Nine studies were included and a total of 21 BCTs were identified. The most frequently coded BCTs were 4.1 (instruction on how to perform the behaviour), 10.8 (incentive [outcome]), and 16.3 (vicarious consequences) (each n = 6). Reported outcomes included reductions in injury rates, improved adoption of safety devices, implementation of safety measures, and positive shifts in safety norms and perceptions. However, due to variations in intervention design and reporting, assessing the direct impact of specific BCTs on these outcomes proved challenging.
Discussion
The use of BCT taxonomy provided a common language for describing intervention components and enabled the standardisation of intervention content analysis. While patterns were observed regarding the commonly used BCTs, their implementation and outcomes, the heterogeneity and limited details provided by studies limited our ability to discern their effectiveness. Providing (i) greater transparency in reporting active intervention components and (ii) clearer connections between components and specific outcomes, will enable enhanced comparisons of future studies, and facilitate a greater understanding of how to support safe machine-related behaviours on farms.The study was funded by the Department of Agriculture, Food and the Marine, Government of Ireland Research Stimulus Programme (#17S269).peer-reviewe
Optimizing mesenchymal stromal cell-facilitated ex vivo expansion of human regulatory T cells
No full textRegulatory T cells (Treg) are essential for suppressing immune overactivity. Clinical trials have confirmed the safety and potential efficacy of ex vivo-expanded Treg for immune-mediated diseases, yet challenges remain in achieving consistent Treg yield, purity, and cytokine profiles. This thesis project aimed to evaluate the potential to enhance culture expansion of primary human total Treg (CD4+/CD25+/CD127lo) and Treg subpopulations through coculture with human umbilical cord-derived mesenchymal stromal cells (hUC-MSC).
In 14-21 day anti-CD3/anti-CD28-, interleukin-2- and rapamycin-containing cultures, FACS-purified total human Treg underwent 4-fold greater expansion following hUC-MSC coculture. The suppressive function of hUC-MSC-expanded Treg on effector T cell proliferation was maintained and correlated with increased expression of HLA-DR, CD39, and ICOS. Enhanced yields were also noted in hUC-MSC-facilitated ex vivo expansion of FACS-purified Treg subpopulations [CD45RA+ (naïve), CD45RA-HLA-DR+ and CD45RA-HLA-DR- (non-naive)]. Notably, the magnitude of expansion was substantially greater in non-naïve Treg than in naïve Treg. In non-naïve Treg, hUC-MSC coculture also led to increased percentages of FoxP3⁺ and Helios⁺ cells. Additionally, coculture with hUC-MSC upregulated HLA-DR expression across all Treg subtypes, while preserving their suppressive potency and maintaining IL-10 and IFN-y production (ELISA). Using intracellular flow cytometry, IFN-y-producing cells were found to be FoxP3+/- but predominantly Helios⁻ and present in ex vivo-expanded CD45RA⁻CD39⁻ Treg subsets. PMA/ionomycin stimulation followed by magnetic depletion effectively reduced these IFN-y-producing cells. Although stimulation led to substantial FoxP3 loss, coculture with hUC-MSC mitigated this effect. Additionally, freshly isolated CD39⁺ Treg displayed stable CD39 and FoxP3 expression during expansion, showed increased yield with hUC-MSC coculture, and were notably more frequent in blood of patients with diabetic kidney disease than in healthy volunteers.
Collectively, these findings demonstrate that coculture with clinical-grade hUC-MSC significantly enhances ex vivo yield and phenotypic stability of total Treg and Treg subpopulations while preserving their suppressive potency. The findings have potential to facilitate identification, functional characterization and manufacturing of Treg subpopulations with distinct therapeutic benefits.This research and PhD thesis were supported by a China Scholarship Council PhD fellowship (Grant number 202106370032) and a Science Foundation Ireland Research Centres grant (CÚRAM, grant number 13/RC/2073_P2)
How Francis Douce (1757–1834) annotated the early French printed volumes in his collection
No full textAs an antiquarian at the beginning of the age of professional scholarship, Francis Douce (1737–1834) has enjoyed a mixed reputation, exemplified by Meg Twycross’s account of his influence on beliefs regarding the origins of the Towneley Plays. Widely-read and embedded in a network of like-minded enthusiasts, Douce does not appear to have recorded his insights for publication, but he nevertheless participated in what might be considered scholarly exchange. This article will pay attention to the annotations that Douce made in the margins of – and on sheets tipped into – French-language books published before 1600. It will look at what sort of features attracted Douce’s attention (primarily bibliographical, but also some relating to the content of the books he was reading). It will consider where Douce was getting his information about the works he collected and will note instances where Douce revisited and revised his opinions, evaluating the extent to which he was up-to-date with contemporary advances. Where Douce expresses his own opinion, this article will examine whether this opinion has been supported by later scholars. In short, what do the annotations tell us about the state of scholarship in the first decades of the nineteenth century?peer-reviewe
The tumour glyco-code: Sialylation as a mediator of stromal cell immunosuppression in the tumour microenvironment
No full textThe tumour microenvironment (TME) comprises a complex interplay of tumour cells, nonmalignant cells (including endothelial, immune, and stromal cells), and secreted factors within the extracellular matrix (ECM). Immunosuppression within the TME significantly hinders the efficacy of cancer immunotherapies. Stromal-rich TMEs, characterised by an abundance of mesenchymal stromal cells (MSCs) and cancer-associated fibroblasts (CAFs), are particularly immunosuppressive and associated with poor responses to conventional and immune-based therapies. Glycans, carbohydrate structures on cell surfaces, are dynamically regulated during tumourigenesis and mediate crucial cell–cell communications through receptor–ligand interactions. Sialylation, the addition of sialic acids to glycans, forms sialoglycans that can engage inhibitory Siglec receptors expressed on immune cells and promote immunosuppressive signalling. Emerging evidence implicates aberrant sialylation in the TME as a key driver of immunosuppression. More recently, sialylation of stromal cells in the TME has been shown to suppress anti-tumor immunity. This review explores the role of sialylation within stromal-rich, immunosuppressive TMEs, focusing on how specific sialic acid/Siglec interactions dictate innate and adaptive immune responses. We discuss the potential of targeting glycoimmune checkpoints to overcome stromal-mediated resistance and enhance anti-tumour immunity.This work was funded by the Research Ireland Starting Investigator Grant and Frontiers for the Future Programme Award to Dr Aideen Ryan (19/FFP/6446 and 15/SIRG/3456) and an HRB-HRCI Irish Cancer Society Award to Prof Michael O'Dwyer and Dr Aideen Ryan (HRCI-HRB-2024-018).peer-reviewe