Studies on equine milk and comparative studies on equine and bovine milk systems

The composition of equine milk differs considerably from that of the milk of the principal dairying species, i.e., the cow, buffalo, goat and sheep. Because equine milk resembles human milk in many respects and is claimed to have special therapeutic properties, it is becoming increasingly popular in Western Europe, where it is produced on large farms in several countries. Equine milk is considered to be highly digestible, rich in essential nutrients and to possess an optimum whey protein:casein ratio, making it very suitable as a substitute for bovine milk in paediatric dietetics. There is some scientific basis for the special nutritional and health-giving properties of equine milk but this study provides a comprehensive analysis of the composition and physico-chemical properties of equine milk which is required to fully exploit its potential in human nutrition. Quantification and distribution of the nitrogenous components and principal salts of equine milk are reported. The effects of the high concentration of ionic calcium, large casein micelles (~ 260 nm), low protein, lack of a sulphydryl group in equine β-lactoglobulin and a very low level of κ-casein on the physico-chemical properties of equine milk are reported. This thesis provides an insight into the stability of equine casein micelles to heat, ethanol, high pressure, rennet or acid. Differences in rennet- and acid-induced coagulation between equine and bovine milk are attributed not only to the low casein content of equine milk but also to differences in the mechanism by which the respective micelles are stabilized. It has been reported that β-casein plays a role in the stabilization of equine casein micelles and proteomic techniques support this view. In this study, equine κ-casein appeared to be resistant to hydrolysis by calf chymosin but equine β-casein was readily hydrolysed. Resolution of equine milk proteins by urea-PAGE showed the multi-phosphorylated isoforms of equine αs- and β-caseins and capillary zone electrophoresis showed 3 to 7 phosphorylated residues in equine β-casein. In vitro digestion of equine β-casein by pepsin and Corolase PP™ did not produce casomorphins BCM-5 or BCM-7, believed to be harmful to human health. Electron microscopy provided very clear, detailed images of equine casein micelles in their native state and when renneted or acidified. Equine milk formed flocs rather then a gel when renneted or acidified which is supported by dynamic oscillatory analysis. The results presented in this thesis will assist in the development of new products from equine milk for human consumption which will retain some of its unique compositional and health-giving properties.

Axial symmetry and transverse trace-free tensors in numerical relativity

Transverse trace-free (TT) tensors play an important role in the initial conditions of numerical relativity, containing two of the component freedoms. Expressing a TT tensor entirely, by the choice of two scalar potentials, is not a trivial task however. Assuming the added condition of axial symmetry, expressions are given in both spherical and cylindrical coordinates, for TT tensors in flat space. A coordinate relation is then calculated between the scalar potentials of each coordinate system. This is extended to a non-flat space, though only one potential is found. The remaining equations are reduced to form a second order partial differential equation in two of the tensor components. With the axially symmetric flat space tensors, the choice of potentials giving Bowen-York conformal curvatures, are derived. A restriction is found for the potentials which ensure an axially symmetric TT tensor, which is regular at the origin, and conditions on the potentials, which give an axially symmetric TT tensor with a spherically symmetric scalar product, are also derived. A comparison is made of the extrinsic curvatures of the exact Kerr solution and numerical Bowen-York solution for axially symmetric black hole space-times. The Brill wave, believed to act as the difference between the Kerr and Bowen-York space-times, is also studied, with an approximate numerical solution found for a mass-factor, under different amplitudes of the metric.

FLT3-driven redox signalling in acute myeloid leukaemia

Acute myeloid leukaemia refers to cancer of the blood and bone marrow characterised by the rapid expansion of immature blasts of the myeloid lineage. The aberrant proliferation of these blasts interferes with normal haematopoiesis, resulting in symptoms such as anaemia, poor coagulation and infections. The molecular mechanisms underpinning acute myeloid leukaemia are multi-faceted and complex, with a range of diverse genetic and cytogenetic abnormalities giving rise to the acute myeloid leukaemia phenotype. Amongst the most common causative factors are mutations of the FLT3 gene, which codes for a growth factor receptor tyrosine kinase required by developing haematopoietic cells. Disruptions to this gene can result in constitutively active FLT3, driving the de-regulated proliferation of undifferentiated precursor blasts. FLT3-targeted drugs provide the opportunity to inhibit this oncogenic receptor, but over time can give rise to resistance within the blast population. The identification of targetable components of the FLT3 signalling pathway may allow for combination therapies to be used to impede the emergence of resistance. However, the intracellular signal transduction pathway of FLT3 is relatively obscure. The objective of this study is to further elucidate this pathway, with particular focus on the redox signalling element which is thought to be involved. Signalling via reactive oxygen species is becoming increasingly recognised as a crucial aspect of physiological and pathological processes within the cell. The first part of this study examined the effects of NADPH oxidase-derived reactive oxygen species on the tyrosine phosphorylation levels of acute myeloid leukaemia cell lines. Using two-dimensional phosphotyrosine immunoblotting, a range of proteins were identified as undergoing tyrosine phosphorylation in response to NADPH oxidase activity. Ezrin, a cytoskeletal regulatory protein and substrate of Src kinase, was selected for further study. The next part of this study established that NADPH oxidase is subject to regulation by FLT3. Both wild type and oncogenic FLT3 signalling were shown to affect the expression of a key NADPH oxidase subunit, p22phox, and FLT3 was also demonstrated to drive intracellular reactive oxygen species production. The NADPH oxidase target protein, Ezrin, undergoes phosphorylation on two tyrosine residues downstream of FLT3 signalling, an effect which was shown to be p22phox-dependent and which was attributed to the redox regulation of Src. The cytoskeletal associations of Ezrin and its established role in metastasis prompted the investigation of the effects of FLT3 and NADPH oxidase activity on the migration of acute myeloid leukaemia cell lines. It was found that inhibition of either FLT3 or NADPH oxidase negatively impacted on the motility of acute myeloid leukaemia cells. The final part of this study focused on the relationship between FLT3 signalling and phosphatase activity. It was determined, using phosphatase expression profiling and real-time PCR, that several phosphatases are subject to regulation at the levels of transcription and post-translational modification downstream of oncogenic FLT3 activity. In summary, this study demonstrates that FLT3 signal transduction utilises a NADPH oxidase-dependent redox element, which affects Src kinase, and modulates leukaemic cell migration through Ezrin. Furthermore, the expression and activity of several phosphatases is tightly linked to FLT3 signalling. This work reveals novel components of the FLT3 signalling cascade and indicates a range of potential therapeutic targets.

A programmer's environment for music analysis

A model for representing music scores in a form suitable for general processing by a music-analyst-programmer is proposed and implemented. Typical input to the model consists of one or more pieces of music which are encoded in a file-based score representation. File-based representations are in a form unsuited for general processing, as they do not provide a suitable level of abstraction for a programmer-analyst. Instead, a representation is created giving a programmer's view of the score. This frees the analyst-programmer from implementation details, that otherwise would form a substantial barrier to progress. The score representation uses an object-oriented approach to create a natural and robust software environment for the musicologist. The system is used to explore ways in which it could benefit musicologists. Methodologies for analysing music corpora are presented in a series of analytic examples which illustrate some of the potential of this model. Proving hypotheses or performing analysis on corpora involves the construction of algorithms. Some unique aspects of using this score model for corpus-based musicology are: - Algorithms impose a discipline which arises from the necessity for formalism. - Automatic analysis enables musicologists to complete tasks that otherwise would be infeasible because of limitations of their energy, attentiveness, accuracy and time.

A study of the oxygen electrochemistry of ruthenium and iridium

This thesis is concerned with an investigation of the anodic behaviour of ruthenium and iridium in aqueous solution and particularly of oxygen evolution on these metals. The latter process is of major interest in the large-scale production of hydrogen gas by the electrolysis of water. The presence of low levels of ruthenium trichloride ca. 10-4 mol dm-3 in acid solution give a considerable increase in the rate of oxygen evolution from platinum and gold, but not graphite, anodes. The mechanism of this catalytic effect was investigated using potential step and a.c. impedance technique. Earlier suggestions that the effect is due to catalysis by metal ions in solution were proved to be incorrect and it was shown that ruthenium species were incorporated into the surface oxide film. Changes in the oxidation state of these ruthenium species is probably responsible for the lowering of the oxygen overvoltage. Both the theoretical and practical aspects of the reaction were complicated by the fact that at constant potential the rates of both the catalysed and the uncatalysed oxygen evolution processes exhibit an appreciable, continuous decrease with either time or degree of oxidation of the substrate. The anodic behaviour of iridium in the oxide layer region has been investigated using conventional electrochemical techniques such as cyclic voltammetry. Applying a triangular voltage sweep at 10 Hz, 0.01 to 1.50V increases the amount of electric charge which the surface can store in the oxide region. This activation effect and the mechanism of charge storage is discussed in terms of both an expanded lattice theory for oxide growth on noble metals and a more recent theory of irreversible oxide formation with subsequent stoichiometry changes. The lack of hysteresis between the anodic and cathodic peaks at ca. 0.9 V suggests that the process involved here is proton migration in a relatively thick surface layer, i.e. that the reaction involved is some type of oxide-hydroxide transition. Lack of chloride ion inhibition in the anodic region also supports the irreversible oxide formation theory; however, to account for the hydrogen region of the potential sweep a compromise theory involving partial reduction of the outer regions of iridium oxide film is proposed. The loss of charge storage capacity when the activated iridium surface is anodized for a short time above ca. 1.60 V is attributed to loss by corrosion of the outer active layer from the metal surface. The behaviour of iridium at higher anodic potentials in acid solution was investigated. Current-time curves at constant potential and Tafel plots suggested that a change in the mechanism of the oxygen evolution reaction occurs at ca. 1.8 V. Above this potential, corrosion of the metal occurred, giving rise to an absorbance in the visible spectrum of the electrolyte (λ max = 455 nm). It is suggested that the species involved was Ir(O2)2+. A similar investigation in the case of alkaline electrolyte gave no evidence for a change in mechanism at 1.8 V and corrosion of the iridium was not observed. Oxygen evolution overpotentials were much lower for iridium than for platinum in both acidic and alkaline solutions.

序破急 Jo-Ha-Kyu: enticement - crux - consolidation. From study to learning: Process drama projects in the Japanese English language university classroom

This dissertation investigates how social issues can be explored through process drama projects in the Japanese university English as a Foreign Language classroom context. The trajectory of this dissertation moves along a traditional Noh three part macro-continuum, called Jo-Ha-Kyu, interpreted as enticement, crux and consolidation. Within these three parts, there are six further divisions. Part I consists of three sections: Section I, the introduction, sets the backdrop for the entire dissertation, that of Japan, and aims to draw the reader into its culturally unique and specific world. This section outlines the rationale for placing the ethnographer at the centre of the research, and presents Japan through the eyes of the writer. Section II outlines relevant Japanese cultural norms, mores and values, the English educational landscape of Japan and an overview of theatre in Japan and its possible influences on the Japanese university student today. Section III provides three literature reviews: second language acquisition, drama in education to process drama, and Content Language Integrated Learning. In Part 2, Sections IV and V respectively consist of the research methodology and the action research at the core of this dissertation. Section IV describes the case of Kwansei Gakuin University, then explains the design of the process drama curricula. Section V details the three-process drama projects based around the three social issues at the centre of this dissertation. There is also a description of an extra project that of the guest lecturer project. The ultimate goals of all four projects were to change motivation through English in a CLIL context, to develop linguistic spontaneity and to deepen emotional engagement with the themes. Part 3 serves to reflect upon the viability of using process drama in the Japanese university curriculum, and to critically self-reflect on the project as a whole.

Investigating the function of PINK1 in cancer development and pathogenesis

PTEN‐induced kinase 1 (PINK1) was identified initially in cancer cells as a gene up‐regulated by overexpression of the central tumour suppressor, PTEN. Loss‐of‐function mutations in PINK1 were discovered subsequently to cause autosomal recessive Parkinsonʹs disease (ARPD). Despite much research focusing on the proposed mechanism(s) through which loss of PINKI function causes neurodegeneration, few studies have focused on a direct role for this serine/threonine kinase in cancer biology. The focus of this thesis was to examine a direct role for PINK1 function in tumourigenesis. Initial studies showed that loss of PINK1 reduces tumour‐associated phenotypes including cell growth, colony formation and invasiveness, in several cell types in vitro, indicating a pro‐tumourigenic role for PINK1 in cancer. Furthermore, results revealed for the first time that PINK1 deletion, examined in mouse embryonic fibroblasts (MEFS) from PINK1 knock‐out animals, causes cell cycle defects, whereby cells arrest at in cytokinesis, giving rise to a highly significant increase in the number of multinucleated cells. This results in several key changes in the expression profile of cell cycle associated protein. In addition, PINK1‐deficient MEFs were found to resist cell cycle exit, with a proportion of cells remaining in proliferative phases upon removal of serum. The ability of cells to progress through mitosis conferred by PINK1 expression was independent of its kinase activity, while the cell cycle exit following serum withdrawal was kinase dependent. Investigations into the mechanism through which loss of PINK1 function gives rise to cell cycle defects revealed that dynamin related protein 1 (Drp1)‐mediated mitochondrial fission is enhanced in PINK1‐ deficient MEFs, and that increased expression of Drp1 on mitochondria and activation of Drp1 is highly significant in PINK1‐deficient multinucleated cells. Deregulated and increased levels and activation of mitochondrial fission via Drp1 was shown to be a major feature of cell cycle defects caused by PINK1 deletion, both during progression through G2/M and cell cycle exit following serum removal. Altered PINK1 localisation was also observed during progression of mitosis, and upon serum deprivation. Thus, PINK1 dissociated from the mitochondria during the mitotic phases and localised to mitochondria upon serum withdrawal. During serum withdrawal deletion of PINK1 disabled the ability of MEFs to increase mitochondrial membrane potential (ΔΨm), and increase autophagy. This was co‐incident with increased mitochondrial fission, and increased localisation of Drp1 to mitochondria following serum deprivation. Together, this indicates an inability of PINK1‐negative cells to respond protectively to this stress‐induced state, primarily via impaired mitochondrial function. In contrast, PINK1 overexpression was found to protect cells from DNA damage following treatment with oxidants. In addition, deletion of PINK1 blocked the ability of cells to re‐enter the cell cycle in response to insulin‐like growth factor‐1 (IGF‐1), a major cancer promoting agonistwhich acts primarily via PI3‐kinase/Akt activation. Furthermore, PINK1 mRNA expression was significantly increased following serum deprivation of MCF‐7 cells, and this was rendered more significant upon additional inhibition of PI3‐kinase. Conversely, IGF‐1 activation of PI3‐kinase/Akt causes a time‐dependent and significant reduction of PINK1 mRNA expression that was PI3‐kinase dependent. Together these results indicate that PINK1 expression is necessary for IGF‐1 signalling and is regulated reciprocally in the absence and presence of IGF‐1, via PI3‐kinase/Akt, a signalling system which has major tumour‐promoting capacity in cancer cell biology. The results of this thesis indicate PINK1 is a candidate tumour-promoting gene which has a significant function in the regulation of the cell cycle, and growth factor responses, at key cell cycle checkpoints, namely, during progression through G2/M and during exit of the cell cycle following removal of serum. Furthermore, the results reveal that the regulation of mitochondrial fission and Drp1 function is mechanistically important in the regulation of cell cycle control by PINK1. As deregulation of the cell cycle is linked to both tumourigenesis and neurodegeneration, the findings of this thesis are of importance not just for understanding cancer biology, but also in the context of PINK1‐associated neurodegeneration.

Inquiring into perspective transformation in university education

My Portfolio of Exploration tackles the difficult question as to whether adult mental development can be accelerated and if so how. Rooted in constructive-developmental ideas, adult mental development is explained as an evolutionary unfolding of human capability. Going beyond this I look at the possibility of advancing development as transformational growth in adulthood in the belief that a broader perspective leads to increased effectiveness in professional life. Initially I explored my own meaning making, to make sense of my experiences, knowledge, relationships and my own motivations. This exploration has provided me with a ‘developmental bridge’ between my current way of knowing and a new more enlightened way. I have come to view my way of making meaning in the world as an evolving and progressive sequence of emotional and cognitive development. Through the formation of new stretching experiences, increased self - awareness and reflection my previous perspective has been overtaken by a more complex form of being aware of myself, others and the world. I refer to this process of growth as transformation. As part of my own transformational work I have conducted an inquiry into transformational growth and learning in the early academic life of university undergraduates. The result shows how accelerated adult mental development can be achieved in an academic environment ably preparing students for the workplace. This new model of education is part of a truly unique and exciting model signalling ground-breaking change for the undergraduate experience. The overhaul of a traditional BA degree in Economics into a world-class transformational programme is discussed through-out my Portfolio. Central to my broadening awareness is the challenge and nurturing required to awaken the student’s ‘internal authority’ . This involves stimulating students to take ownership for their own thinking, steering them away from the passivity and complacency of thinking through the minds of others. In doing so, the ultimate aim of renewing the BA is to narrow the developmental ‘mismatch’ which exists for m any college students between them and the world of work, by encouraging and inviting them to take on the challenge of thinking independently. Mindfulness, awareness, and personal authority are treated with reverence throughout the exploration as I consider them core parts of the students engaging with development. Engagement is construed as an active and open-minded process of awareness involving planning and reviewing one’s own goals and performance, engaging in constructive feedback, reflection and new action. I conclude with a view that the journey of adult mental development is relentless and that undergraduate education represents a crucial beginning. The value and relevance of transformational education rooted in developmental principles provides a significant opportunity in advancing development and perspectives at the start of adult life.

A social history of sport in Cork, Tipperary and Waterford, c. 1880-1930

This thesis seeks to explore the development of sport in Munster in the late nineteenth and early twentieth centuries by comparing developments in three counties: Cork, Tipperary and Waterford. In particular this thesis considers the development of rugby and soccer in comparative perspective across these three counties, asking what local factors impacted on their uneven development in the region and considering the extent to which the traditional model of diffusion applies to the reception of these sports in the three counties. By giving consideration to these two particular non-indigenous sports, the thesis will, through answering that question, explore ideas of cultural reception, national identity and class as expressed at local level. These themes will be explored by placing the comparative analysis of these two sports into a wider context of sporting development regionally and nationally in the period, in particular the emerging commercialisation of sport, and also the diverse sporting culture of which these two sports were a part. Utilising a wide range of archival sources from local, national and sporting newspapers, to club records, official publications and ephemera this thesis builds a picture of sport in Munster that is deeply rooted in the community, and that forms an important facet of the social world of Cork, Tipperary and Waterford from 1880-1930.

College adjustment, depressive symptoms and peer support among undergraduate university students

Background: College adjustment is a developmental milestone that can be stressful and may lead to mental health problems such as depression. Support during this adjustment period is seen as essential, however it is unknown if informal peer support from fellow students has any impact on either college adjustment or depressive symptoms. Aim: To identify levels of social and personal college adjustment, depressive symptoms and peer support among students, and to examine the relationship between the variables. Design: A quantitative correlational design was used Instruments: Data were collected using two subscales of the Student Adaptation to College Questionnaire; the Centre for Epidemiology Depressive Symptoms Scale and a subscale of the Peer Support Evaluation Inventory. Sample: The sample consisted of 417, first (n=188), second (n=134) and fourth (n=94) year nursing and midwifery students from one University in Ireland. Findings: The findings indicated that 20% of participants were poorly personally adjusted and 9% poorly socially adjusted. Furthermore, 34% of participants experienced significant depressive symptoms. Most students had good levels of peer support. Statistically significant relationships were found between all key variables, the strongest of which were between personal adjustment and depressive symptoms and social adjustment and depressive symptoms. Differences in adjustment and depressive symptom scores were found based on year of study, with second year students experiencing more depressive symptoms and having poorer personal adjustment scores. Participants who had poor relationships with their father’s experienced greater depressive symptoms and had more difficulties personally and socially adjusting to college. The alcohol consumption of participants had a statistically significant correlation with college adjustment, depressive symptoms and peer support, with higher consumption having a positive impact on the variables.

Isolation, characterization, and functional assessment of novel smooth muscle like stem progenitors

Vascular smooth muscle cells (VSMC) are one of the key players in the pathogenesis of cardiovascular diseases. The origin of neointimal VSMC has thus become a prime focus of research. VSMC originate from multiple progenitors cell types. In embryo the well-defined sources of VSMC include; neural crest cells, proepicardial cells and EPC. In adults, though progenitor cells from bone marrow (BM), circulation and tissues giving rise to SMC have been identified, no progress has been made in terms of isolating highly proliferative clonal population of adult stem cells with potential to differentiate into SMC. Smooth muscle like stem progenitor cells (SMSPC) were isolated from cardiopulmonary bypass filters of adult patients undergoing CABG. Rat SMSPC have previously been isolated by our group from the bone marrow of Fischer rats and also from the peripheral blood of monocrotaline induced pulmonary hypertension (MCT-PHTN) animal model. Characterization of novel SMSPC exhibited stem cell characteristics and machinery for differentiation into SMC. The expression of Isl-1 on SMSPC provided unique molecular identity to these circulating stem progenitor cells. The functional potential of SMSPC was determined by monitoring adoptive transfer of GFP+ SMSPC in rodent models of vascular injury; carotid injury and MCT-PHTN. The participation of SMSPC in vascular pathology was confirmed by quantifying the peripheral blood, and engrafted levels of SMSPC using RT-PCR. In terms of translating into clinical practice, SMSPC could be a good tool for detecting the atherosclerotic plaque burden. The current study demonstrates the existence of novel adult stem progenitor cells in circulation, with the potential role in vascular pathology.

Cesarean section and rate of subsequent stillbirth, miscarriage and ectopic pregnancy: a Danish register-based cohort study

Background: With cesarean section rates increasing worldwide, clarity regarding negative effects is essential. This study aimed to investigate the rate of subsequent stillbirth, miscarriage, and ectopic pregnancy following primary cesarean section, controlling for confounding by indication. Methods and Findings: We performed a population-based cohort study using Danish national registry data linking various registers. The cohort included primiparous women with a live birth between January 1, 1982, and December 31, 2010 (n = 832,996), with follow-up until the next event (stillbirth, miscarriage, or ectopic pregnancy) or censoring by live birth, death, emigration, or study end. Cox regression models for all types of cesarean sections, sub-group analyses by type of cesarean, and competing risks analyses for the causes of stillbirth were performed. An increased rate of stillbirth (hazard ratio [HR] 1.14, 95% CI 1.01, 1.28) was found in women with primary cesarean section compared to spontaneous vaginal delivery, giving a theoretical absolute risk increase (ARI) of 0.03% for stillbirth, and a number needed to harm (NNH) of 3,333 women. Analyses by type of cesarean section showed similarly increased rates for emergency (HR 1.15, 95% CI 1.01, 1.31) and elective cesarean (HR 1.11, 95% CI 0.91, 1.35), although not statistically significant in the latter case. An increased rate of ectopic pregnancy was found among women with primary cesarean overall (HR 1.09, 95% CI 1.04, 1.15) and by type (emergency cesarean, HR 1.09, 95% CI 1.03, 1.15, and elective cesarean, HR 1.12, 95% CI 1.03, 1.21), yielding an ARI of 0.1% and a NNH of 1,000 women for ectopic pregnancy. No increased rate of miscarriage was found among women with primary cesarean, with maternally requested cesarean section associated with a decreased rate of miscarriage (HR 0.72, 95% CI 0.60, 0.85). Limitations include incomplete data on maternal body mass index, maternal smoking, fertility treatment, causes of stillbirth, and maternally requested cesarean section, as well as lack of data on antepartum/intrapartum stillbirth and gestational age for stillbirth and miscarriage. Conclusions: This study found that cesarean section is associated with a small increased rate of subsequent stillbirth and ectopic pregnancy. Underlying medical conditions, however, and confounding by indication for the primary cesarean delivery account for at least part of this increased rate. These findings will assist women and health-care providers to reach more informed decisions regarding mode of delivery.

Non-product related environmental process and production methods (NPR-PPMs): a view from international trade law and international environmental governance

The primary aim of this thesis is to analyse legal and governance issues in the use of Environmental NPR-PPMs, particularly those aiming to promote sustainable practices or to protect natural resources. NPR-PPMs have traditionally been thought of as being incompatible with the rules of the World Trade Organization (WTO). However, the issue remains untouched by WTO adjudicatory bodies. One can suggest that WTO adjudicatory bodies may want to leave this issue to the Members, but the analysis of the case law also seems to indicate that the question of legality of NPR-PPMs has not been brought ‘as such’ in dispute settlement. This thesis advances the argument that despite the fact that the legal status of NPR-PPMs remains unsettled, during the last decades adjudicatory bodies have been scrutinising environmental measures based on NPR-PPMs just as another expression of the regulatory autonomy of the Members. Though NPR-PPMs are regulatory choices associated with a wide range of environmental concerns, trade disputes giving rise to questions related to the legality of process-based measures have been mainly associated with the protection of marine wildlife (i.e., fishing techniques threatening or affecting animal species). This thesis argues that environmental objectives articulated as NPR-PPMs can indeed qualify as legitimate objectives both under the GATT and the TBT Agreement. However, an important challenge for the their compatibility with WTO law relate to aspects associated with arbitrary or unjustifiable discrimination. In the assessment of discrimination procedural issues play an important role. This thesis also elucidates other important dimensions to the issue from the perspective of global governance. One of the arguments advanced in this thesis is that a comprehensive analysis of environmental NPR-PPMs should consider not only their role in what is regarded as trade barriers (governmental and market-driven), but also their significance in global objectives such as the transition towards a green economy and sustainable patterns of consumption and production.

Narratives in early Irish law tracts

This thesis presents a study of the 112 narratives collected from the Corpus Iuris Hibernici. The selection of narratives is based on criteria informed by modern narratological theories. The significant presence of narratives in early Irish law tracts appears at odds with the normal conception of law texts as consisting solely of provisions, and therefore needs to be accounted for. Since no systematic study has been conducted of these legal narratives, this thesis serves as an introduction by giving firstly an index of narratives and secondly a categorisation of them in terms of distribution, dates and functions. It then carries out a general analysis of the relationship between legal narratives and early Irish literature, and a selected case study of the relationship between legal narratives and the legal institutions in the context of which the narratives are located. It has become clearer, with the progress of argument, that the use of narratives was an integral part of legal writing in medieval Ireland; and the narratives, though having many idiosyncratic features of themselves, are profoundly connected with the learned tradition at large. The legal narratives reveal the intellectual background and compositional concerns of medieval Irish jurists, and they formed a crucial part of the effort to accommodate law tracts into the dynamic tradition of senchas. Two appendices are included at the end: one consists of translations of 34 narratives from the index, and the other is a critical edition of one of the narratives discussed in detail, together with translations of some relevant passages.

Micro and nanostructured impedance sensors for biological and biomedical applications

This thesis work covered the fabrication and characterisation of impedance sensors for biological applications aiming in particular to the cytotoxicity monitoring of cultured cells exposed to different kind of chemical compounds and drugs and to the identification of different types of biological tissue (fat, muscles, nerves) using a sensor fabricated on the tip of a commercially available needle during peripheral nerve block procedures. Gold impedance electrodes have been successfully fabricated for impedance measurement on cells cultured on the electrode surface which was modified with the fabrication of gold nanopillars. These nanostructures have a height of 60nm or 100nm and they have highly ordered layout as they are fabricated through the e-beam technique. The fabrication of the threedimensional structures on the interdigitated electrodes was supposed to improve the sensitivity of the ECIS (electric cell-substrate impedance sensing) measurement while monitoring the cytotoxicity effects of two different drugs (Antrodia Camphorata extract and Nicotine) on three different cell lines (HeLa, A549 and BALBc 3T3) cultured on the impedance devices and change the morphology of the cells growing on the nanostructured electrodes. The fabrication of the nanostructures was achieved combining techniques like UV lithography, metal lift-off, evaporation and e-beam lithography techniques. The electrodes were packaged using a pressure sensitive, medical grade adhesive double-sided tape. The electrodes were then characterised with the aid of AFM and SEM imaging which confirmed the success of the fabrication processes showing the nanopillars fabricated with the right layout and dimensions figures. The introduction of nanopillars on the impedance electrodes, however, did not improve much the sensitivity of the assay with the exception of tests carried out with Nicotine. HeLa and A549 cells appeared to grow in a different way on the two surfaces, while no differences where noticed on the BALBc 3T3 cells. Impedance measurements obtained with the dead cells on the negative control electrodes or the test electrodes with the drugs can be compared to those done on the electrodes containing just media in the tested volume (as no cells are attached and cover the electrode surface). The impedance figures recorded using these electrodes were between 1.5kΩ and 2.5 kΩ, while the figures recorded on confluent cell layers range between 4kΩ and 5.5kΩ with peaks of almost 7 kΩ if there was more than one layer of cells growing on each other. There was then a very clear separation between the values of living cell compared to the dead ones which was almost 2.5 - 3kΩ. In this way it was very easy to determine whether the drugs affected the cells normal life cycle on not. However, little or no differences were noticed in the impedance analysis carried out on the two different kinds of electrodes using cultured cells. An increase of sensitivity was noticed only in a couple of experiments carried out on A549 cells growing on the nanostructured electrodes and exposed to different concentration of a solution containing Nicotine. More experiments to achieve a higher number of statistical evidences will be needed to prove these findings with an absolute confidence. The smart needle project aimed to reduce the limitations of the Electrical Nerve Stimulation (ENS) and the Ultra Sound Guided peripheral nerve block techniques giving the clinicians an additional tool for performing correctly the peripheral nerve block. Bioimpedance, as measured at the needle tip, provides additional information on needle tip location, thereby facilitating detection of intraneural needle placement. Using the needle as a precision instrument and guidance tool may provide additional information as to needle tip location and enhance safety in regional anaesthesia. In the time analysis, with the frequency fixed at 10kHz and the samples kept at 12°C, the approximate range for muscle bioimpedance was 203 – 616 Ω, the approximate bioimpedance range for fat was 5.02 - 17.8 kΩ and the approximate range for connective tissue was 790 Ω – 1.55 kΩ. While when the samples were heated at 37°C and measured again at 10kHz, the approximate bioimpedance range for muscle was 100-175Ω. The approximate bioimpedance range of fat was 627 Ω - 3.2 kΩ and the range for connective tissue was 221-540Ω. In the experiments done on the fresh slaughtered lamb carcass, replicating a scenario close to the real application, the impedance values recorded for fat were around 17 kΩ, for muscle and lean tissue around 1.3 kΩ while the nervous structures had an impedance value of 2.9 kΩ. With the data collected during this research, it was possible to conclude that measurements of bioimpedance at the needle tip location can give valuable information to the clinicians performing a peripheral nerve block procedure as the separation (in terms of impedance figures) was very marked between the different type of tissues. It is then feasible to use an impedance electrode fabricated on the needle tip to differentiate several tissues from the nerve tissue. Currently, several different methods are being studied to fabricate an impedance electrode on the surface of a commercially available needle used for the peripheral nerve block procedure.