Designing molecularly imprinted polymers for the analysis of the components of complex matrices

Molecular imprinting technology is a field of analytical chemistry of ever-increasing importance, offenng an effective and economic means of producing molecule-specific synthetic materials, with potential application in separation, sensing and catalytic technologies. This thesis descnbes a detailed investigation of the method and examines how it may be incorporated into a typical analytical application (solid phase extraction of the active ingredient in a pharmaceutical preparation), and investigates some of the practical considerations of such an approach - choice of appropriate functional monomer, the possibility of swelling effects affecting recognition properties of the polymers, and the use of pH control to adjust selectivity when recognition is based on ionic interactons. The performance of the MIPs presented in the second chapter is then used as a platform for probing more fundamental aspects of MIP behaviour. Properties of pre-polymerisaton mixtures which have consequences for final MIP recognition behaviour are examined in detail in Chapters three and four, with NMR spectroscopy (coupled with subsequent HPLC evaluation of the MIP recognition capabilities) playing an important role. The impact of more subtle effects, such as n-n stacking and phase partition, is of particular note Chapter five shows how spectroscopic data, as acquired in Chapter 4, can be used to refine simulated models of pre-polymerisaton complexes, which may be of significant benefit in predicting MIP properties and ultimately in creating a step-by-step protocol for designing efficient MIPs

Rearrangement and trapping of organozinc carbenoids.

This thesis is divided into six chapters. Chapter one presents a review on metallocarbenoid chemistry and is divided into three parts. The first part gives a general survey of the influence of substituents on the reactivity and stability of free carbenes. The second part describes the reactions of transition metal carbenoids, particularly in relation to the oxidation state of the metal and the stoichiometry of carbenoid generation. The final part discusses the reactions of zinc carbenoids and the means of their formation. Chapter two is prefaced by a review on the generation and reactivity of organozinc carbenoids within the group, coupled with a mechanistic study of their formation. Studies on the hydrogen migration in open chain and more rigid cyclic ketone derived zinc carbenoids are presented. The organozinc carbenoids were shown to exhibit greater overall selectivity for the more thermodynamically favoured alkene isomer. Finally, the one-step conversion of aldehydes to terminal alkenes is presented. This conversion is shown to be accelerated by the addition of Lewis acids, particularly zinc chloride. Chapter three describes the direct one-pot conversion of acetals and ketals to organozinc carbenoids. It was found that carbenoids could be prepared efficiently from ketals containing the 1,3-dioxane, 1,3-dioxolane or dimethoxy moiety. However, for the acetal derivatives, only the dimethoxy and 1,3-dioxolane acetals could be readily reduced to the carbenoid. In chapter four, the carbenoids derived from aromatic aldehydes were shown to cyclopropanate olefins, and a brief study some of the steric and electronic effects of the alkene component is presented. The derived dimethoxy and 1,3-dioxolane acetals were also shown to cyclopropanate some simple olefins, with the syn:anti ratio dependant on the amount of added zinc chloride. Chapter five concludes the results and discussion, and gives a perspective to further work. Chapter six provides a formal description of the experimental results and procedures

A Comparison of Alcohol Abusers who have and have not Experienced Blackouts

This study examined the proposition that the experience of alcoholic blackouts is related to other indices of cerebral involvement in the alcoholic process. In particular it was suggested that those who experience alcoholic blackouts would also show signs of the effects of alcoholic damage in the form of lower scores on cognitive functions vulnerable to the effects of long-term alcohol abuse. While some evidence was found linking the experience of blackout to severity of the alcohol problem no relationship was found between cognitive functioning and the experience of blackout. The possibility that different mechanisms may underlie the various cognitive sequelae of alcohol abuse is raised

Residue analyses and exposure assessment of the Irish population to nitrofuran metabolites from different food commodities in 2009–2010

peer-reviewedAn exposure assessment to nitrofuran residues was performed for three human populations (adults, teenagers and children), based on residue analyses of foods of animal origin (liver, honey, eggs and aquaculture) covering the 2-year period 2009– 2010. The occurrence of nitrofuran metabolites in food on the Irish market was determined for the selected period using the data from Ireland’s National Food Residue Database (NFRD) and from results obtained from the analysis of retail samples (aquaculture and honey). Laboratory analyses of residues were performed by methods validated in accordance with Commission Decision 2002/657/EC regarding performance of the analytical method and interpretation of results. Semicarbazide (SEM) was the contaminant most frequently identified and its content ranged from 0.09 to 1.27 μg kg−1. SEM is currently used as a marker of nitrofuran abuse, but it may also occur from other sources. The presence of nitrofuran metabolite 3-amino-2-oxazolidinone (AOZ) was detected in two aquaculture samples (prawns) at 1.63 and 1.14 μg kg−1, but such a low number of positive cases did not present sufficient data for a full AOZ exposure assessment. Therefore, the evaluation of exposure was focused on SEM-containing food groups only. Exposure assessments were completed using a probabilistic approach that generated 10 iterations. The results of both the upper- and lower-bound exposure assessments demonstrate that SEM exposure for Irish adults, teenagers and children from selected food commodities are well below EFSA-estimated safe levels.This research was funded by the Food for Health Research Initiative (FHRI) administered by the Irish Department of Agriculture, Food and the Marine and the Health Research Board (Contract 07FHRIAFRC5

A comparison of pilot-scale supersonic direct steam injection to conventional steam infusion and tubular heating systems for the heat treatment of protein-enriched skim milk-based beverages

peer-reviewedDirect supersonic steam injection, direct steam infusion, and indirect tubular heating were each applied to protein-enriched skim milk-based beverages with 4, 6 and 8% (w/w) total protein, and the effect of final heat temperature on the physical properties of these beverages was investigated. Supersonic steam injection resulted in significantly lower levels of denaturation of β-lactoglobulin (34.5%), compared to both infusion (76.3%) and tubular (97.1%) heating technologies. Viscosity, particle size and accelerated physical stability of formulations did not differ significantly between the heating technologies, while noticeable colour differences due to heat treatment (mainly attributed to increasing b* value) were observed, particularly for tubular heating. Overall, the extent of protein denaturation in high-protein dairy products was significantly influenced by the particular heating technology applied. The application of supersonic steam injection technology, with rapid heating and high shear characteristics, may enable differenciated product characteristics for ready-to-drink ambient-delivery high-protein dairy beverages. Industrial relevance: The design and application of novel direct supersonic steam injection technology was comprehensively studied and found to provide significant benefits over direct steam infusion and indirect tubular heating technologies for skim milk-based protein beverages. This type of injection heating system resulted in heat-treated formulations with lower levels of denatured whey proteins, compared to tubular and infusion heating, offering an alternative opportunity to the industry in terms of producing shelf-stable dairy protein beverages

Mapping research across the undergraduate curriculum in UCC

UCC identifies itself as a research-led University and has stated the ambition to strengthen the integration of research, teaching and learning by maximising opportunities for students to participate in research programmes throughout their undergraduate studies. The number of undergraduate programmes with student-involved research from first year onwards is an important measure of this ambition. A curriculum analytics project was enacted by CIRTL staff and Academic Systems Administration to gather evidence of research-oriented and research-based teaching in undergraduate programmes offered to students via the CAO system in 2015/2016. The review showed that 55% of undergraduate programmes make explicit mention of research and inquiry in their programme learning outcomes. Analysis of module learning outcomes further showed that 45% of the reviewed programmes provide students with exposure to research-based or research-oriented teaching across the duration of their programme. The project provides an important baseline of existing research in the undergraduate curriculum, it uncovers exemplar activities across a range of subject areas and disciplines, and extends the vocabulary around research and inquiry to include discipline-specific approaches and understandings. Future work will include gathering feedback from staff and qualitative research with students to correct any inaccuracies in the data with a view to refining the search query and running a regular, more automated analysis

Visceral pain: role of the microbiome-gut-brain axis

A growing body of preclinical and clinical evidence supports a relationship between the complexity and diversity of the microorganisms that inhabit our gut (human gastrointestinal microbiome) and health status. These microbes can influence centrally regulated emotional behaviour through mechanisms including microbially derived bioactive molecules, mucosal immune and enteroendocrine cell activation, as well as vagal nerve stimulation. Changes to the microbial environment, as a consequence of illness, stress or injury can lead to a broad spectrum of local physiological and behavioural effects including a decrease in gut barrier integrity, altered gut motility, inflammatory mediator release, as well as nociceptive and distension receptor sensitization. Impacts at a central level include alterations in the hypothalamic-pituitary-adrenal axis, neuroinflammatory events and concomitant changes to neurotransmitter systems. Thus, both central and peripheral pathways associated with pain manifestation and perception are altered as a consequence of the microbiome-gut-brain axis imbalance. The dogmatic approach of antibiotic treatment in the latter century, for the treatment of many diseases and conditions, has undergone a radical change. We are 90% microbe, and pragmatism suggests that we manipulate this ecosystem for the treatment of various ailments, stress dysfunction and affective disorders, including the alleviation of visceral pain

Darned in 2013: inclusion of model organisms and linking with Wikipedia

DARNED (DAtabase of RNA EDiting, available at http://darned.ucc.ie) is a centralized repository of reference genome coordinates corresponding to RNA nucleotides having altered templated identities in the process of RNA editing. The data in DARNED are derived from published datasets of RNA editing events. RNA editing instances have been identified with various methods, such as bioinformatics screenings, deep sequencing and/or biochemical techniques. Here we report our current progress in the development and expansion of the DARNED. In addition to novel database features the DARNED update describes inclusion of Drosophila melanogaster and Mus musculus RNA editing events and the launch of a community-based annotation in the RNA WikiProject

Characterisation of cationic amphiphilic cyclodextrins for neuronal delivery of siRNA: effect of reversing primary and secondary face modifications

Significant research is focused on the development of non-viral vectors for delivery of siRNA to neurons and the central nervous system. Cyclodextrins (CDs) have shown great promise as efficient and low toxicity gene delivery vectors in various cell types. Here, we investigate two CDs for siRNA delivery in a neuronal cell model. These CDs were substituted on opposite faces (primary and secondary) with amphiphilic and cationic groups. Physical properties of CD.siRNA complexes, including size, charge and stability were measured. In vitro investigations were carried out in immortalised hypothalamic neurons. Neuronal cell uptake was measured by flow cytometry and cytotoxicity was assessed by MTT assay. Knockdown of a luciferase reporter gene was used as a measure of gene silencing efficiency. Both CDs interacted with siRNA, yielding nanosized cationic complexes which exhibited good stability on storage. A favourable toxicity profile was demonstrated for the CD.siRNA complexes. However, only one of the two CDs mediated high levels of neuronal uptake and efficient gene silencing, equivalent to those achieved with a commercial lipid-based vector. Despite the suitability of both CDs as siRNA delivery vectors in terms of their ability to complex siRNA and the properties of the complexes yielded, only one CD achieved good transfection efficiency. This was likely due to the differences in their chemical structures. The effective CD offers great potential as a novel non-toxic vector for neuronal siRNA delivery

Design, modelling and preliminary characterisation of microneedle-based electrodes for tissue electroporation in vivo

We analysed the use of microneedle-based electrodes to enhance electroporation of mouse testis with DNA vectors for production of transgenic mice. Different microneedle formats were developed and tested, and we ultimately used electrodes based on arrays of 500 μm tall microneedles. In a series of experiments involving injection of a DNA vector expressing Green Fluorescent Protein (GFP) and electroporation using microneedle electrodes and a commercially available voltage supply, we compared the performance of flat and microneedle electrodes by measuring GFP expression at various timepoints after electroporation. Our main finding, supported by both experimental and simulated data, is that needles significantly enhanced electroporation of testis