The role of the IL-1 type 1 receptor in the life, death and differentiation of adult hippocampal neural precursor cells

Neurogenesis occurs in two distinct regions of the adult brain; the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the subventricular zone (SVZ) lining the lateral ventricles. It is now well-known that adult hippocampal neurogenesis can be modulated by a number of intrinsic and extrinsic factors e.g. local signalling molecules, exercise, environmental enrichment and learning. Moreover, levels of adult hippocampal neurogenesis decrease with age, at least in rodents, and alterations in hippocampal neurogenesis have been reported in animal models and human studies of neuropsychiatric and neurodegenerative conditions. Neuroinflammation is a common pathological feature of these conditions and is also a potent modulator of adult hippocampal neurogenesis. Recently, the orphan nuclear receptor TLX has been identified as an important regulator of adult hippocampal neurogenesis as its expression is necessary to maintain the neural precursor cell (NPC) pool in the adult DG. Likewise, exposure of animals to voluntary exercise has been consistently demonstrated to promote adult hippocampal neurogenesis. Lentivirus (LV)- mediated gene transfer is a useful tool to elucidate gene function and to explore potential therapeutic candidates across an array of conditions as it facilitates sustained gene expression in both dividing and post-mitotic cell populations. Both intrinsic and extrinsic factors are important regulators of adult hippocampal neurogenesis. Examining how these factors are affected by an inflammatory stimulus, and the subsequent effects on adult hippocampal neurogenesis provides important information for the development of novel treatment strategies for neuropsychiatric and neurodegenerative conditions in which adult hippocampal neurogenesis is impaired. The aims of the series of experiments presented in this thesis were to examine the effect of the pro-inflammatory cytokine interleukin-1β (IL-1β) on adult hippocampal NPCs both in vitro and in vivo. In vitro, we have shown that IL-1β reduces proliferation of adult hippocampal NPCs in a dose and time-dependent manner. In addition, we have demonstrated that TLX expression is reduced by IL-1β. Blockade of IL-1β signalling prevented both the IL-1β-induced reduction in cell proliferation and TLX expression. In vivo, we examined the effect of short term and long term exposure to LV-IL-1β in sedentary mice and in mice exposed to voluntary running. We demonstrated that impaired hippocampal neurogenesis is only evident after long term exposure to IL-1β. In mice exposed to voluntary running, hippocampal neurogenesis is significantly increased following short-term but not long-term exposure to running. Moreover, short-term running effectively prevents any IL-1β-induced effects on hippocampal neurogenesis; however, no such effects are seen following long-term exposure to running.

Aesthetic campaigns and counter-campaigns. Jorge Luis Borges and a century of the Argentine detective story (1877-1977)

This cultural history of Argentine crime fiction involves a comprehensive analysis of the literary and critical traditions within the genre, paying particular attention to the series of ‘aesthetic campaigns’ waged by Jorge Luis Borges and others during the period between 1933 and 1977. The methodological approach described in the introductory chapter builds upon the critical insight that in Argentina, generic discourse has consistently been the domain, not only of literary critics in the traditional mould, but also of prominent writers of fiction and specialists from other disciplines, effectively transcending the traditional tripartite ‘division of labour’ between writers, critics and readers. Chapter One charts the early development of crime fiction, and contextualises the evolution of the classical and hardboiled variants that were to provide a durable conceptual framework for discourse in the Argentine context. Chapter Two examines a number of pioneering early works by Argentine authors, before analysing Borges’ multi-faceted aesthetic campaign on behalf of the ‘classical’ detective story. Chapter Three examines a transitional period for the Argentine crime genre, book-ended by the three Vea y Lea magazine-sponsored detective story competitions that acted as a vital stimulus to innovation among Argentine writers. It includes a substantial treatment of the work of Rodolfo Walsh, documenting his transition from crime writer and anthologist to pioneer of the non-fiction novel and investigative journalism traditions. Chapter Four examines the period in which the novela negra came to achieve dominance in Argentina, in particular the aesthetic counter-campaigns conducted by Ricardo Piglia and others on behalf of the hard-boiled variant. The study concludes with a detailed analysis of Pablo Leonardo’s La mala guita (1976), which is considered as a paradigmatic example of crime fiction in Argentina in this period. The final chapter presents conclusions and a summary of the dissertation, and recommendations for further research.

Development of germanium/silicon integration for near infrared detection

Silicon (Si) is the base material for electronic technologies and is emerging as a very attractive platform for photonic integrated circuits (PICs). PICs allow optical systems to be made more compact with higher performance than discrete optical components. Applications for PICs are in the area of fibre-optic communication, biomedical devices, photovoltaics and imaging. Germanium (Ge), due to its suitable bandgap for telecommunications and its compatibility with Si technology is preferred over III-V compounds as an integrated on-chip detector at near infrared wavelengths. There are two main approaches for Ge/Si integration: through epitaxial growth and through direct wafer bonding. The lattice mismatch of ~4.2% between Ge and Si is the main problem of the former technique which leads to a high density of dislocations while the bond strength and conductivity of the interface are the main challenges of the latter. Both result in trap states which are expected to play a critical role. Understanding the physics of the interface is a key contribution of this thesis. This thesis investigates Ge/Si diodes using these two methods. The effects of interface traps on the static and dynamic performance of Ge/Si avalanche photodetectors have been modelled for the first time. The thesis outlines the original process development and characterization of mesa diodes which were fabricated by transferring a ~700 nm thick layer of p-type Ge onto n-type Si using direct wafer bonding and layer exfoliation. The effects of low temperature annealing on the device performance and on the conductivity of the interface have been investigated. It is shown that the diode ideality factor and the series resistance of the device are reduced after annealing. The carrier transport mechanism is shown to be dominated by generation–recombination before annealing and by direct tunnelling in forward bias and band-to-band tunnelling in reverse bias after annealing. The thesis presents a novel technique to realise photodetectors where one of the substrates is thinned by chemical mechanical polishing (CMP) after bonding the Si-Ge wafers. Based on this technique, Ge/Si detectors with remarkably high responsivities, in excess of 3.5 A/W at 1.55 μm at −2 V, under surface normal illumination have been measured. By performing electrical and optical measurements at various temperatures, the carrier transport through the hetero-interface is analysed by monitoring the Ge band bending from which a detailed band structure of the Ge/Si interface is proposed for the first time. The above unity responsivity of the detectors was explained by light induced potential barrier lowering at the interface. To our knowledge this is the first report of light-gated responsivity for vertically illuminated Ge/Si photodiodes. The wafer bonding approach followed by layer exfoliation or by CMP is a low temperature wafer scale process. In principle, the technique could be extended to other materials such as Ge on GaAs, or Ge on SOI. The unique results reported here are compatible with surface normal illumination and are capable of being integrated with CMOS electronics and readout units in the form of 2D arrays of detectors. One potential future application is a low-cost Si process-compatible near infrared camera.

Resonant power conversion topologies for inductive charging of electrical vehicle batteries

This thesis is concerned with inductive charging of electric vehicle batteries. Rectified power form the 50/60 Hz utility feeds a dc-ac converter which delivers high-frequency ac power to the electric vehicle inductive coupling inlet. The inlet configuration has been defined by the Society of Automotive Engineers in Recommended Practice J-1773. This thesis studies converter topologies related to the series resonant converter. When coupled to the vehicle inlet, the frequency-controlled series-resonant converter results in a capacitively-filtered series-parallel LCLC (SP-LCLC) resonant converter topology with zero voltage switching and many other desirable features. A novel time-domain transformation analysis, termed Modal Analysis, is developed, using a state variable transformation, to analyze and characterize this multi-resonant fourth-orderconverter. Next, Fundamental Mode Approximation (FMA) Analysis, based on a voltage-source model of the load, and its novel extension, Rectifier-Compensated FMA (RCFMA) Analysis, are developed and applied to the SP-LCLC converter. The RCFMA Analysis is a simpler and more intuitive analysis than the Modal Analysis, and provides a relatively accurate closed-form solution for the converter behavior. Phase control of the SP-LCLC converter is investigated as a control option. FMA and RCFMA Analyses are used for detailed characterization. The analyses identify areas of operation, which are also validated experimentally, where it is advantageous to phase control the converter. A novel hybrid control scheme is proposed which integrates frequency and phase control and achieves reduced operating frequency range and improved partial-load efficiency. The phase-controlled SP-LCLC converter can also be configured with a parallel load and is an excellent option for the application. The resulting topology implements soft-switching over the entire load range and has high full-load and partial-load efficiencies. RCFMA Analysis is used to analyze and characterize the new converter topology, and good correlation is shown with experimental results. Finally, a novel single-stage power-factor-corrected ac-dc converter is introduced, which uses the current-source characteristic of the SP-LCLC topology to provide power factor correction over a wide output power range from zero to full load. This converter exhibits all the advantageous characteristics of its dc-dc counterpart, with a reduced parts count and cost. Simulation and experimental results verify the operation of the new converter.

Electrical machine characterisation and analysis for renewable energy applications

There has been an increased use of the Doubly-Fed Induction Machine (DFIM) in ac drive applications in recent times, particularly in the field of renewable energy systems and other high power variable-speed drives. The DFIM is widely regarded as the optimal generation system for both onshore and offshore wind turbines and has also been considered in wave power applications. Wind power generation is the most mature renewable technology. However, wave energy has attracted a large interest recently as the potential for power extraction is very significant. Various wave energy converter (WEC) technologies currently exist with the oscillating water column (OWC) type converter being one of the most advanced. There are fundemental differences in the power profile of the pneumatic power supplied by the OWC WEC and that of a wind turbine and this causes significant challenges in the selection and rating of electrical generators for the OWC devises. The thesis initially aims to provide an accurate per-phase equivalent circuit model of the DFIM by investigating various characterisation testing procedures. Novel testing methodologies based on the series-coupling tests is employed and is found to provide a more accurate representation of the DFIM than the standard IEEE testing methods because the series-coupling tests provide a direct method of determining the equivalent-circuit resistances and inductances of the machine. A second novel method known as the extended short-circuit test is also presented and investigated as an alternative characterisation method. Experimental results on a 1.1 kW DFIM and a 30 kW DFIM utilising the various characterisation procedures are presented in the thesis. The various test methods are analysed and validated through comparison of model predictions and torque-versus-speed curves for each induction machine. Sensitivity analysis is also used as a means of quantifying the effect of experimental error on the results taken from each of the testing procedures and is used to determine the suitability of the test procedures for characterising each of the devices. The series-coupling differential test is demonstrated to be the optimum test. The research then focuses on the OWC WEC and the modelling of this device. A software model is implemented based on data obtained from a scaled prototype device situated at the Irish test site. Test data from the electrical system of the device is analysed and this data is used to develop a performance curve for the air turbine utilised in the WEC. This performance curve was applied in a software model to represent the turbine in the electro-mechanical system and the software results are validated by the measured electrical output data from the prototype test device. Finally, once both the DFIM and OWC WEC power take-off system have been modeled succesfully, an investigation of the application of the DFIM to the OWC WEC model is carried out to determine the electrical machine rating required for the pulsating power derived from OWC WEC device. Thermal analysis of a 30 kW induction machine is carried out using a first-order thermal model. The simulations quantify the limits of operation of the machine and enable thedevelopment of rating requirements for the electrical generation system of the OWC WEC. The thesis can be considered to have three sections. The first section of the thesis contains Chapters 2 and 3 and focuses on the accurate characterisation of the doubly-fed induction machine using various testing procedures. The second section, containing Chapter 4, concentrates on the modelling of the OWC WEC power-takeoff with particular focus on the Wells turbine. Validation of this model is carried out through comparision of simulations and experimental measurements. The third section of the thesis utilises the OWC WEC model from Chapter 4 with a 30 kW induction machine model to determine the optimum device rating for the specified machine. Simulations are carried out to perform thermal analysis of the machine to give a general insight into electrical machine rating for an OWC WEC device.

Na marbhnaí do Shéamas Óg Mac Coitir (1689-1720)

Go príomha, is tráchtas é seo a dhéanann staidéar ar ghné de litríocht iar-chlasaiceach na Gaeilge. Baineann sé go háirithe leis an sraith chaointe nó marbhnaí i bhfoirm véarsaíochta a cumadh do Shéamas Óg Mac Coitir (1689-1720), duine uasal Caitliceach ó Charraig Tuathail, Co. Chorcaí, nuair a ciontaíodh é in éigniú Elizabeth Squibb, bean de Chumann na gCarad; nuair a cuireadh pionós an bháis air; agus nuair a crochadh é i gCathair Chorcaí an 7 Bealtaine, 1720. Ó thaobh na staire de, scrúdaítear Clann Choitir mar shampla de theaghlach nár cheil a ndílseacht do chúis pholaitiúil na Stíobhartach agus a sheas an fód go cróga faoi mar a bhí a ngreim polaitiúil á dhaingniú ag an gCinsealacht Phrotastúnach ó dheireadh an 17ú haois amach. Tagraítear do sheicteachas na sochaí comhaimseartha agus don teannas idir an pobal Caitliceach agus an pobal Protastúnach ag an am. Déantar scagadh ar an véarsaíocht mar fhoinse luachmhar do dhearcadh míshásta an mhóraimh Chaitlicigh ar struchtúr polaitiúil chontae Chorcaí (agus na hÉireann) i dtosach an 18ú haois. Is feiniméan liteartha an dlús véarsaíochta seo a bhaineann go háirithe le traidisiún liteartha Chorcaí. Tá na dánta curtha in eagar agus aistriúchán go Béarla curtha ar fáil: is é seo croí an tráchtais. Tá an t-eagrán bunaithe ar scrúdú cuimsitheach ar thraidisiún na lsí; pléitear modheolaíocht na heagarthóireachta. Déantar iarracht ar na dánta a shuíomh sa traidisiún casta liteartha sa tráchtaireacht tosaigh; sa chuid eile den bhfearas scoláiriúil, scrúdaítear ceisteanna a bhaineann le cúrsaí teanga, foclóra, meadarachta agus stíle. Tá innéacsanna agus liosta foinsí le fáil i ndeireadh an tráchtais.