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    Mathematical modelling of the bovine estrus cycle and an investigation into silent heat and twinning /

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    Development of novel polymeric delivery systems for the controlled release of therapeutic agents to prevent the spread of Zoonotic diseases

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    The agricultural revolution and related activities have led to new connections between humans and farm animals, which are expected to expand due to the global trade of livestock and growth in the demand for animal protein for human consumption. Ireland is a globally recognised trading nation, providing high-quality meat, milk, and dairy products. In order to remain viable and grow over time, the Irish agricultural sector will need to focus on animal health to maximise productivity, mainly because parasitic infections represent a major production-limiting issue with the possibility of transmission within animal populations and from animal to human populations. Repidose® Ready Pulse bolus is the only orally administered anthelmintic intraruminal delivery device for grazing cattle in Ireland. Therefore, the aim of this research was to develop novel controlled-release solid dispersion formulations for the safe and efficient delivery of benzimidazole anthelmintics to cattle, achieved through processing the active ingredient with biodegradable polymers via hot-melt processing technologies. To accomplish this goal, five specific objectives were defined (i) to improve the poor water solubility of fenbendazole using a biocompatible, biodegradable, and hydrophilic polymer; (ii) to identify and analyse other polymers compatible with fenbendazole; (iii) to design and manufacture fenbendazole extended-release extruded formulations; (iv) to design and mould solid dispersion formulations for the extended-release of fenbendazole; and (v) to upgrade the solid dosage form with oxfendazole as is present in the commercial Repidose® bolus. The results achieved during this research revealed that (i) solid dispersions of fenbendazole and PEO are physically and chemically compatible, with higher percentages of PEO processed at lower screw speed being more effective in enhancing the drug dissolution properties; (ii) Kolliphor® P 407, PCL, and PLA are compatible with fenbendazole and have potential for further application in the development of solid dosage forms; (iii) melt-extruded matrices showed that the drug release rate from a PEO/PCL blend can be tailored by altering the ratio of PEO and PCL; (iv) moulded tablets of amorphous solid dispersions improved the dissolution properties of fenbendazole, with the PEO/PCL blend-based matrices showing an extended-release profile; and (v) hot-melt extrusion coupled with micro-injection moulding produced extended-release amorphous solid dispersion of oxfendazole, which is a novel pharmaceutical strategy with the potential to improve upon the Repidose® bolus. This research project successfully demonstrated the application of a semi-continuous manufacturing process for the production of plasticised solid dispersion tablets of oxfendazole as a potentially viable alternative to the current tablet formulation present in the Repidose® bolus, thus this technology could be viable on the market to provide effective parasite control.ye

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    Critical studies on the novel development and implementation of vaporized hydrogen peroxide (VH202) for terminal sterilization of medical devices encompassing use of flow cytometry for the real-time commensurate monitoring of microbial inactivation

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    Aims and Rationale: Sterilization microbiology relies on determining the linearity of microbial survivor curves for calculating decimal reduction times (D-values) that is used to inform sterility assurance levels (SAL), critical to efficacious sterilization of medical device for patient care application. Medical devices play an important role in the provision of healthcare, with a global market estimated at 432bnandexpectedtosurpass432bn and expected to surpass 650bn by 2028. Terminal sterilization of medical devices is currently provided by established methods including Gamma, E-beam and X-ray radiation with Ethylene Oxide gas sterilization continuing to be the method of choice due to wide ranging material compatibility. Given the hazards associated with EO gas, alternative methods are actively being pursued by the global medical device industry. Furthermore, there is an increasing opportunity to develop sustainable sterilization microbiology processes necessary to meet emerging needs including evolution of device features containing heat sensitive polymers, inclusion of sensor technology and biologics. This constitutes the first, and timely study to (i) establish and alternative method using vaporized hydrogen peroxide (VH2O2) at an industrial sterilization scale and (ii) report on the linearity of microbial inactivation plots for treated Geobacillus stearothermophilus and Bacillus atrophaeus spores to demonstrate the appropriateness of process validation as a means of confidently determining SAL.ye

    Novel investigations into the genomic architecture affecting the muscle growth and development of Irish beef and dairy cattle

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    Muscle growth and development in livestock is an important indicator of carcass yield and performance. Investigating the complex polygenic nature of carcass traits may yield additional knowledge and important insights into the role of genomic variation in muscle growth and development. This thesis describes the approaches undertaken to dissect the genomic variation and biological processes governing bovine muscle growth and development. Chapter two describes the estimation of the frequency and effects of genomic polymorphisms in Myostatin (MSTN) on milk, fertility and carcass performance in a population of dairy cows. The role of MSTN in muscle growth and development is long established however the aim here was to estimate both the beneficial and possible antagonistic effects on production traits of economic importance in the dairy industry. Similarly, the role μ-calpain (CAPN1) and Calpastatin (CAST) in post-mortem tenderisation is widely reported and in chapter three, the frequency and effects of genomic polymorphisms in CAPN1 and CAST on fertility and carcass performance were estimated in a population of beef cows. Chapter four describes the approaches taken to identify genomic polymorphisms with novel functional roles in bovine muscle growth and development and the disentanglement of their impact on gene function while also estimating the frequency of same polymorphisms in a large population of Irish cattle. Finally, the objective of chapter five was to identify novel associations between regions of the bovine genome with carcass performance using a GWAS in a population of beef cattle. Additionally, a functional genomics dataset in the form of gene expression data was integrated with GWAS results and subsequent gene ontology and pathway analysis contributed to an improved and enhanced understanding of the genomic variation underlying carcass performance. The project identified a number of gene polymorphisms, genomic regions and biological pathways significantly associated with carcass performance.ye

    Novel studies into the improvement of cattle fertility using multiple technologies that converges bioinformatics with machine learning.

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    This study aimed to evaluate the presence of a panel of 18 candidate lethal recessives in the Irish dairy, and beef cattle populations. Establishing the presence and frequency of such recessive alleles will assist the scientific, and animal breeding communities. The frequency of variants in Irish Holstein – Friesian dairy cattle are included in the dairy chapter. Furthermore, the beef cattle chapter assesses six different breeds Aberdeen Angus, Belgian Blue, Charolais, Hereford, Limousin and Simmental. Animal breeders have established that the optimal breeding goal is a more balanced and informed breeding approach; thus, the lethal recessives in the various population were assessed for any associated effects on 16 production traits in both the dairy and beef cattle prior to any breeding decisions made on-farm, for example culling, which may reduce the overall genetic diversity, increasing inbreeding depression and ultimately reducing population viability. A comparative genomics approach followed the above candidate lethal recessive association studies. This chapter identified variants in essential genes, using alternative mammalian species studies as supporting evidence. Variants were identified and prepared for genotyping approximately 350 K cattle, the results were analysed for potential candidates associated with embryo loss. Furthermore, variants within a 500 kb range of the candidates were selected and submitted to identify segregating variants that were possibly unknown to industry. Genetics and high throughput data are one aspect of improving cattle fertility. It is clear that in addition to genomic programmes, predictive technologies will be used in making forecasts in the agricultural sector, particularly machine learning and AI models. Such predictive technologies may ultimately incorporate genomic and environmental data into selection programmes; however, interdisciplinary studies are currently at the point of combining technologies. ReproDoc assesses cattle pregnancy status using mobile ultrasound technology and has amassed a database of animal-related details. This chapter prepared a private commercial database for predictive models to determine when individual cows are optimal for insemination. Customers would be the first to benefit from the success of such a technology, as the requirement for semen, and insemination attempts would decrease, and the need for herd replacements would be optimised, ultimately reducing the demand for replacements. Such information could provide farmers reassurance in allowing a cow to remain on the farm until the next breeding cycle, thus improving welfare and reducing wastage.ye

    Estimation of the frequency and effects of casual mutations on fertility and production traits in Irish dairy cattle

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    Fertility is a major driver for profitability and sustainability of livestock enterprises. Identifying and estimating the effects of known lethal recessive genetic mutations and genes of major effect on production traits in cattle populations provides additional information to the industry for potential incorporation into breeding programs. Such information may support breeders to make more informed decisions through the identification of carrier animals and the evaluation of potential strategic matings in cases where carrier animals may be of otherwise high genetic merit. This project aims to estimate the frequency and effects of a panel of DNA polymorphisms (n=18) in Irish Holstein Friesian cattle, some of which are validated as causative mutations responsible for lethal recessive disorders (CVM, BLAD, DUMPS and Brachyspina), and some of which have been observed to have major effects on production and functional traits in previous research studies (STAT1, STAT3, STAT5). Genotypes on 21,707 Holstein Friesian dairy cattle were obtained from the ICBF, as were phenotypic data on milk, fertility, carcass and health traits (n=16). Phenotypes, expressed as predicted transmitting abilities (PTAs) were prepared for inclusion in the analysis by removal of parental contributions through a deregression process. Haplotypes were predicted using PHASE for all SNPs with positions on the same chromosome. Subsequently, associations between each SNP/haplotype and PTA were analysed in ASReml using a weighted mixed animal model. Several associations between the genes of major effect and production and functional traits were evident and consistent with previous reports of such associations, for example SNPs within the DGAT and Casein genes were associated with milk composition traits as expected, however, they were also associated with fertility and carcass traits. SNPs within the STAT genes, of which there has not been extensive previous studies on in cattle populations, were associated with both production and functional traits in the population studied. Additionally, a candidate novel lethal recessive mutation in LFNG has been identified. The results from this project will be evaluated by our industry partners, the ICBF, responsible for national genomically assisted breeding programs in Irish cattl

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    How have artists’ perspectives on abstraction as a means of expressing the spiritual developed over time?

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    This dissertation examines how abstraction can reflect the spiritual, and how the development of artists’ perspectives on abstraction and spirituality can be traced in the writings and works of Wassily Kandinsky, Agnes Martin and Lee Ufan. My own creative practice moves fluidly between drawing, painting and printmaking. Formerly, my practice focused on conveying my experience of place. Drawn to the sense of mystery and spiritual resonance I encountered in the work of artists such as Lee Ufan and Agnes Martin, my practice has recently shifted towards abstraction. My current work explores abstract painting and drawing as a means of cultivating presence through an intuitive, open-ended engagement with my chosen media. My practice responds to the behaviour of my materials, where mark-making and gesture become conduits of both form and meaning. Rooted in a dissatisfaction with systems of control and subjugation – over the environment, its resources and its species – my practice proposes an alternative orientation: releasing the urge to dominate what lies outside the self, and instead cultivating inner attentiveness and discipline. My work reflects on the puzzle of how to be in the world as both an individual and a fragment of a greater whole, within a culture shaped by the illusion of separation. Through abstract compositions, I examine the interdependence of animate and inanimate forces, tracing how forms, materials and encounters continuously shape one another. This hybrid practice of painting and printmaking is a meditation on balance: between order and chance, freedom and restraint, rhythm and repetition, the individual and the collective. My work celebrates the physical act of painting and prioritises the body’s sensory intelligence over intellect. Attentive to the haptic and proprioceptive (the body’s sense of self-movement, force and position), my work seeks to make visible a lighter, more reciprocal way of being in the world. I began this project by researching the pioneering writings and works of Wassily Kandinsky. My interest in themes such as time, infinity and encounters, together with a desire to cultivate a grounded, meditative presence in my practice, led me to study the writings of Agnes Martin and Lee Ufan. Both artists explore abstraction to articulate the immaterial and the transcendent through a contemplative, process-based practice. While engaging with these works and writings, I have discovered thematic affinities with Martin and Ufan in particular. Their emphasis on attentiveness to process and unfolding encounters, rather than on predetermined outcomes or material results, resonates with my own practice. This perspective has allowed me to move away from the perceived safety of a representational anchor and predetermined outcome, toward a more experimental and open-ended approach that I feel offers more scope in examining the intangible themes developing in my work such as embodied presence and relationality. Chapter One of this dissertation investigates key themes in the writings of Wassily Kandinsky, Agnes Martin and Lee Ufan. Chapter Two focuses on the artists’ works, analysing how these paintings lend visual form to philosophical or spiritual perspectives. Chapter Three describes my own practice in relation to that of Martin and Ufan.n

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