The psychology of immersion and development of a quantitative measure of immersive response in games

This study sets out to investigate the psychology of immersion and the immersive response of individuals in relation to video and computer games. Initially, an exhaustive review of literature is presented, including research into games, player demographics, personality and identity. Play in traditional psychology is also reviewed, as well as previous research into immersion and attempts to define and measure this construct. An online qualitative study was carried out (N=38), and data was analysed using content analysis. A definition of immersion emerged, as well as a classification of two separate types of immersion, namely, vicarious immersion and visceral immersion. A survey study (N=217) verified the discrete nature of these categories and rejected the null hypothesis that there was no difference between individuals' interpretations of vicarious and visceral immersion. The primary aim of this research was to create a quantitative instrument which measures the immersive response as experienced by the player in a single game session. The IMX Questionnaire was developed using data from the initial qualitative study and quantitative survey. Exploratory Factor Analysis was carried out on data from 300 participants for the IMX Version 1, and Confirmatory Factor Analysis was conducted on data from 380 participants on the IMX Version 2. IMX Version 3 was developed from the results of these analyses. This questionnaire was found to have high internal consistency reliability and validity.

Analysis of expression quantitative trait loci in D. melanogaster

Expression Quantitative Trait Loci (eQTL) analysis allows for the identification of genetic variation associated with variation in gene expression. It is often unclear however, which of the associated variants are causal, and by what mechanism. Integrating functional genomic data with eQTL data can provide insight into the impact of natural variation in the population, and the nature of the transcriptional machinery itself. In this thesis, I integrate functional genomic data with eQTL data derived from both 5’ CAGE and 3’ TagXseq expression assays, in developing embryos. I first use both datasets to analyse the transcription landscape in embryonic D., melanogaster, and then carry out an analysis of sequence motifs associated with transcription factor binding sites, promoters, and 3’ polyadenylation sites. Finally, I integrate functional genomic data, including these novel sequence motifs, to shed light on the mechanisms of gene expression variation in D.,melanogaster. I am able to demonstrate that some variants effecting gene regulation in Drosophila are found within haplotypes which buffer their effects.

Micronutrient intakes and the role of nutritional supplements in the diets of Irish adults and pre-school children

To investigate micronutrient intakes and the role of nutritional supplements in the diets of Irish adults aged 18-64 years and pre-school children aged 1-4 years. Analysis is based on data from the National Adult Nutrition Survey (NANS) (n=1274) and the National Pre-School Nutrition Survey (NPNS) (n=500). Food and beverage intakes and nutritional supplement use were recorded using 4-day food records. Nutrients were estimated using WISP© which is based on McCance and Widdowson’s The Composition of Foods, 6thEd and the Irish Food Composition Database. “Meats”, “milk/yoghurt”, “breads”, “fruit/fruit juices” and “breakfast cereals” made important contributions to the intakes of a number of micronutrients. Micronutrient intakes were generally adequate, with the exception of iron (in adult females and 1 year olds) and vitamin D (in all population groups). For iron, zinc, copper and vitamin B6, up to 2% of adults had intakes that exceeded the upper limit (UL). Small proportions of children had intakes of zinc (11%), copper (2%), retinol (4%) and folic acid (5%) exceeding the UL. Nutritional supplements (predominantly multivitamin and/or mineral preparations) were consumed by 28% of adults and 20% of pre-school children. Among users, supplements were effective in reducing the % with inadequate intakes for vitamins A and D (both population groups) and iron (adult females only). Supplement users had a lower prevalence of inadequate intakes for vitamin A and iron compared to non-users. In adults only, users had a lower prevalence of inadequate intakes for magnesium, calcium and zinc, and displayed better compliance with dietary recommendations and lifestyle characteristics compared with non-users. There is poor compliance among women of childbearing age for the recommendation to take a supplement containing 400µg/day of folic acid. These findings are important for the development of nutrition policies and future recommendations for adults and pre-school children in Ireland and the EU.

Catalyst, additive and substrate effects in intramolecular aromatic additions of alpha-diazoketones

This thesis is focused on transition metal catalysed reaction of α-diazoketones leading to aromatic addition to form azulenones, with particular emphasis on enantiocontrol through use of chiral copper catalysts. The first chapter provides an overview of the influence of variation of the substituent at the diazo carbon on the outcome of subsequent reaction pathways, focusing in particular on C-H insertion, cyclopropanation, aromatic addition and ylide formation drawing together for the first time input from a range of primary reports. Chapter two describes the synthesis of a range of novel α-diazoketones. Rhodium and copper catalysed cyclisation of these to form a range of azulenones is described. Variation of the transition metal catalyst was undertaken using both copper and rhodium based systems and ligand variation, including the design and synthesis of a novel bisoxazoline ligand. The influence of additives, especially NaBARF, on the enantiocontrol was explored in detail and displayed an interesting impact which was sensitive to substituent effects. Further exploration demonstrated that it is the sodium cation which is critical in the additive effects. For the first time, enantiocontrol in the aromatic addition of terminal diazoketones was demonstrated indicating enantiofacial control in the aromatic addition is feasible in the absence of a bridgehead substituent. Determination of the enantiopurity in these compounds was particularly challenging due to the lability of the products. A substantial portion of the work was focused on determining the stereochemical outcome of the aromatic addition processes, both the absolute stereochemistry and extent of enantiopurity. Formation of PTAD adducts was beneficial in this regard. The third chapter contains the full experimental details and spectral characterisation of all novel compounds synthesised in this project, while details of chiral stationary phase HPLC and 1H NMR analysis are included in the appendix.

Cystic fibrosis gene repair: correction of ΔF508 using ZFN and CRISPR/Cas9 guide RNA gene editing tools

Cystic Fibrosis (CF) is an autosomal recessive monogenic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene with the ΔF508 mutation accounting for approximately 70% of all CF cases worldwide. This thesis investigates whether existing zinc finger nucleases designed in this lab and CRISPR/gRNAs designed in this thesis can mediate efficient homology-directed repair (HDR) with appropriate donor repair plasmids to correct CF-causing mutations in a CF cell line. Firstly, the most common mutation, ΔF508, was corrected using a pair of existing ZFNs, which cleave in intron 9, and the donor repair plasmid pITR-donor-XC, which contains the correct CTT sequence and two unique restriction sites. HDR was initially determined to be <1% but further analysis by next generation sequencing (NGS) revealed HDR occurred at a level of 2%. This relatively low level of repair was determined to be a consequence of distance from the cut site to the mutation and so rather than designing a new pair of ZFNs, the position of the existing intron 9 ZFNs was exploited and attempts made to correct >80% of CF-causing mutations. The ZFN cut site was used as the site for HDR of a mini-gene construct comprising exons 10-24 from CFTR cDNA (with appropriate splice acceptor and poly A sites) to allow production of full length corrected CFTR mRNA. Finally, the ability to cleave closer to the mutation and mediate repair of CFTR using the latest gene editing tool CRISPR/Cas9 was explored. Two CRISPR gRNAs were tested; CRISPR ex10 was shown to cleave at an efficiency of 15% and CRISPR in9 cleaved at 3%. Both CRISPR gRNAs mediated HDR with appropriate donor plasmids at a rate of ~1% as determined by NGS. This is the first evidence of CRISPR induced HDR in CF cell lines.