The ways in which new public management ideas impact upon the administrative culture of 'street-level' bureaucrats and professionals working within Irish social policy

The conventional meaning of culture is ‘widely shared and strongly held values’ of a particular group or society (Bradley and Parker, 2006: 89). Culture is not a rigid concept; it can be influenced or altered by new ideas or forces. This research examines the ways in which one set of ideas in particular, that is, those associated with New Public Management, have impacted upon the administrative culture of 'street-level' bureaucrats and professionals within Irish social policy. Lipsky (1980: 3) defined 'street-level' bureaucrats as ‘public service workers who interact directly with citizens in the course of their jobs, and who have substantial discretion in the execution of their work’. Utilising the Competing Values Framework (CVF) in the analysis of eighty three semi-structured interviews with 'street-level' bureaucrats and professionals, an evaluation is made as to the impact of NPM ideas on both visible and invisible aspects of administrative culture. Overall, the influence of NPM is confined to superficial aspects of administrative culture such as; increased flexibility in working hours and to some degree job contracts; increased time commitment; and a customer service focus. However, the extent of these changes varies depending on policy sector and occupational group. Aspects of consensual and hierarchical cultures remain firmly in place. These coincide with features of developmental and market cultures. Contrary to the view that members of hierarchical and consensual culture would pose resistance to change, this research clearly illustrates that a very large appetite for change exists in the attitudes of 'street-level' bureaucrats and professionals within Irish social policy, with many of them suggesting changes that correspond to NPM ideas. This study demonstrates the relevance of employing the CVF model as it is clear that administrative culture is very much a dynamic system of competing and co-existing cultures.

Total synthesis of furospongolide and related furanolipid analogues as potential anti-tumour agents

This thesis details the design, development and execution of innovative methodology in the total synthesis of the terpene-derived marine natural product, furospongolide. It also outlines the synthetic routes used to prepare a novel range of furanolipids derivatives and subsequent evaluation of their potential as antitumour agents. The first chapter is a review of the literature describing efforts undertaken towards the synthesis of biologically active furanosesterterpenoid marine natural products. A brief discussion on the sources and biological activity exhibited by furan natural products is also provided. In addition, a concise account of the role of hypoxia in cancer, and the increasing interest in HIF-1 inhibition as a target for chemotherapeutics is examined. The second chapter discusses the concise synthesis of the marine HIF-1 inhibitor furospongolide, which was achieved in five linear steps from (E,E)-farnesyl acetate. The synthetic strategy features a selective oxidation reaction, a Schlosser sp3-sp3 cross-coupling, a Wittig cross-coupling and an elaborate one-pot selective reduction, lactonisation and isomerization reaction to install the butenolide ring. The structure-activity relationship of furospongolide was also investigated. This involved the design and synthesis of a library of structurally modified analogues sharing the same C1-C13 subunit. This was achieved by exploiting the brevity and high level of convergence of our synthetic route together with the readily amenable structure of our target molecule. Exploiting the Schlosser cross-coupling allowed for replacement of furan with other heterocycles in the preparation of various furanolipid and thiophenolipid derivatives. The employment of reductive amination and Wittig chemistry further added to our novel library of structural derivatives. The third chapter discusses the results obtained from the NCI from biological evaluation From a collection of 28 novel compounds evaluated against the NCI-60 cancer cell array, six drug candidates were successfully selected for further biological evaluation on the basis of antitumour activity. COMPARE analysis revealed a strong correlation between some of our design analogues and the blockbuster anticancer agent tamoxifen, further supporting the potential of furanolipids in the treatment of breast cancer. The fourth chapter, details the full experimental procedures, including spectroscopic and analytical data for all the compounds prepared during this research.

Impurity profiling and synthesis of precursors to the hallucinogenic amphetamine DOB

DOB (4‐bromo‐2,5‐dimethoxyamphetamine) is a newly emerging hallucinogenic amphetamine that sparked serious health warnings in Ireland, following its first seizure back in 2003. Known more commonly as “snowball”, this drug is highly potent and may be used as a substitute to ecstasy (MDMA) and lysergic acid diethylamide (LSD). To date, the work carried out on the impurity profiling of DOB is limited in comparison to amphetamine, methamphetamine and MDMA. In this work, the impurity profile of 4‐bromo‐2,5‐dimethoxyphenyl‐2‐propanone (4‐Br‐2,5‐P2P) is explored. This ketone is a direct precursor to DOB. Its more versatile non‐bromo analogue, 2,5‐ dimethoxyphenyl‐2‐propanone (2,5‐P2P) is also examined, as in addition to DOB, it may be used in the synthesis of a range of several other hallucinogenic amphetamines. A number of different routes to both 2,5‐P2P and 4‐Br‐2,5‐P2P were investigated. For each of these routes, the impurities produced were carefully isolated. Following isolation, the impurities were fully characterised (by 1H‐NMR/13C‐NMR spectroscopy, IR, MS), in order to aid structure elucidation. Compounds not easily resolved by flash column chromatography were analysed by LC‐MS and/or independently synthesised for the purpose of attaining reference standards. Adaptation of the well‐known ‘phenylacetic acid route’ to synthesis of both 2,5‐P2P and 4‐Br‐2,5‐P2P, was found to provide low yields of the expected ketone products. Four impurities were isolated during the preparation of both ketones. The yield of one of these impurities (possessing a dibenzylketone core), was greatly influenced by the amount of acetic anhydride reagent used during the reaction. Having carried out the reaction with several different equivalents of acetic anhydride, it was found that formation of the ‘dibenzylketone’ could not be eliminated. This may increase its likelihood of being detected in the final drug product. The ‘Darzens route’, having very recently emerged as a synthetic route to amphetamine and MDMA precursors, was discovered to be a viable route for manufacture of 2,5‐P2P and 4‐Br‐2,5‐P2P. Despite execution of the reaction being more tedious, the route provides superior yields (≈50–60%) to those achieved using the ‘phenylacetic acid route’ (≈35–38%). Incorporation of a bromine atom (at the aromatic 4‐position) is required at some stage during synthesis of DOB. The bromination of many intermediates/starting materials was therefore also examined in detail. Bromination of the acid starting material 2,5‐dimethoxyphenylacetic acid (2,5‐PAA) was found to be clean and high yielding. This was in stark contrast to the bromination of the benzaldehyde starting material, the ketone precursor 2,5‐P2P and the dibenzylketone‐based impurity. Numerous brominated products were isolated from each of these reactions, many of which were novel compounds, and previously unreported as impurities in the literature. The unpredictable/nondescript nature of these brominations is likely to have a significant impact on the impurity profile of illicitly produced DOB.

Average-case analysis of power consumption in embedded systems

Power efficiency is one of the most important constraints in the design of embedded systems since such systems are generally driven by batteries with limited energy budget or restricted power supply. In every embedded system, there are one or more processor cores to run the software and interact with the other hardware components of the system. The power consumption of the processor core(s) has an important impact on the total power dissipated in the system. Hence, the processor power optimization is crucial in satisfying the power consumption constraints, and developing low-power embedded systems. A key aspect of research in processor power optimization and management is “power estimation”. Having a fast and accurate method for processor power estimation at design time helps the designer to explore a large space of design possibilities, to make the optimal choices for developing a power efficient processor. Likewise, understanding the processor power dissipation behaviour of a specific software/application is the key for choosing appropriate algorithms in order to write power efficient software. Simulation-based methods for measuring the processor power achieve very high accuracy, but are available only late in the design process, and are often quite slow. Therefore, the need has arisen for faster, higher-level power prediction methods that allow the system designer to explore many alternatives for developing powerefficient hardware and software. The aim of this thesis is to present fast and high-level power models for the prediction of processor power consumption. Power predictability in this work is achieved in two ways: first, using a design method to develop power predictable circuits; second, analysing the power of the functions in the code which repeat during execution, then building the power model based on average number of repetitions. In the first case, a design method called Asynchronous Charge Sharing Logic (ACSL) is used to implement the Arithmetic Logic Unit (ALU) for the 8051 microcontroller. The ACSL circuits are power predictable due to the independency of their power consumption to the input data. Based on this property, a fast prediction method is presented to estimate the power of ALU by analysing the software program, and extracting the number of ALU-related instructions. This method achieves less than 1% error in power estimation and more than 100 times speedup in comparison to conventional simulation-based methods. In the second case, an average-case processor energy model is developed for the Insertion sort algorithm based on the number of comparisons that take place in the execution of the algorithm. The average number of comparisons is calculated using a high level methodology called MOdular Quantitative Analysis (MOQA). The parameters of the energy model are measured for the LEON3 processor core, but the model is general and can be used for any processor. The model has been validated through the power measurement experiments, and offers high accuracy and orders of magnitude speedup over the simulation-based method.

The impact of storage conditions upon gentamicin coated antimicrobial implants

A systematic approach was developed to investigate the stability of gentamicin sulfate (GS) and GS/poly (lactic-co-glycolic acid) (PLGA) coatings on hydroxyapatite surfaces. The influence of environmental factors (light, humidity, oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry. GS coated rods were found to be stable across the range of environments assessed, with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition. In contrast, rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C, 75% relative humidity or exposure to light. The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect. Finally, liquid chromatography–mass spectrometry analysis revealed that known gentamines C1, C1a and C2 were the major degradants formed. Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities.