An investigation of thin amorphous carbon-based sputtered coatings for MEMS and micro-engineering applications

The work presented in this thesis describes an investigation into the production and properties of thin amorphous C films, with and without Cr doping, as a low wear / friction coating applicable to MEMS and other micro- and nano-engineering applications. Firstly, an assessment was made of the available testing techniques. Secondly, the optimised test methods were applied to a series of sputtered films of thickness 10 - 2000 nm in order to: (i) investigate the effect of thickness on the properties of coatingslcoating process (ii) investigate fundamental tribology at the nano-scale and (iii) provide a starting point for nanotribological coating optimisation at ultra low thickness. The use of XPS was investigated for the determination of Sp3/Sp2 carbon bonding. Under C 1s peak analysis, significant errors were identified and this was attributed to the absence of sufficient instrument resolution to guide the component peak structure (even with a high resolution instrument). A simple peak width analysis and correlation work with C KLL D value confirmed the errors. The use of XPS for Sp3/Sp2 was therefore limited to initial tentative estimations. Nanoindentation was shown to provide consistent hardness and reduced modulus results with depth (to < 7nm) when replicate data was suitably statistically processed. No significant pile-up or cracking of the films was identified under nanoindentation. Nanowear experimentation by multiple nanoscratching provided some useful information, however the conditions of test were very different to those expect for MEMS and micro- / nano-engineering systems. A novel 'sample oscillated nanoindentation' system was developed for testing nanowear under more relevant conditions. The films were produced in an industrial production coating line. In order to maximise the available information and to take account of uncontrolled process variation a statistical design of experiment procedure was used to investigate the effect of four key process control parameters. Cr doping was the most significant control parameter at all thicknesses tested and produced a softening effect and thus increased nanowear. Substrate bias voltage was also a significant parameter and produced hardening and a wear reducing effect at all thicknesses tested. The use of a Cr adhesion layer produced beneficial results at 150 nm thickness, but was ineffective at 50 nm. Argon flow to the coating chamber produced a complex effect. All effects reduced significantly with reducing film thickness. Classic fretting wear was produced at low amplitude under nanowear testing. Reciprocating sliding was produced at higher amplitude which generated three body abrasive wear and this was generally consistent with the Archard model. Specific wear rates were very low (typically 10-16 - 10-18 m3N-1m-1). Wear rates reduced exponentially with reduced film thickness and below (approx.) 20 nm, thickness was identified as the most important control of wear.

Forecasting and risk analysis applied to management planning and control

The aim of this research was to improve the quantitative support to project planning and control principally through the use of more accurate forecasting for which new techniques were developed. This study arose from the observation that in most cases construction project forecasts were based on a methodology (c.1980) which relied on the DHSS cumulative cubic cost model and network based risk analysis (PERT). The former of these, in particular, imposes severe limitations which this study overcomes. Three areas of study were identified, namely growth curve forecasting, risk analysis and the interface of these quantitative techniques with project management. These fields have been used as a basis for the research programme. In order to give a sound basis for the research, industrial support was sought. This resulted in both the acquisition of cost profiles for a large number of projects and the opportunity to validate practical implementation. The outcome of this research project was deemed successful both in theory and practice. The new forecasting theory was shown to give major reductions in projection errors. The integration of the new predictive and risk analysis technologies with management principles, allowed the development of a viable software management aid which fills an acknowledged gap in current technology.

Interaction of peptides, peptidomimetics and other drug candidates with the DI/tripeptide transport system in intestinal epithelial cells, using the in vitro caco-2 cell culture system

An uptake system was developed using Caco-2 cell monolayers and the dipeptide, glycyl-[3H]L-proline, as a probe compound. Glycyl-[3H]L-proline uptake was via the di-/tripeptide transport system (DTS) and, exhibited concentration-, pH- and temperature-dependency. Dipeptides inhibited uptake of the probe, and the design of the system allowed competitors to be ranked against one another with respect to affinity for the transporter. The structural features required to ensure or increase interaction with the DTS were defined by studying the effect of a series of glycyl-L-proline and angiotensin-converting enzyme (ACE)-inhibitor (SQ-29852) analogues on the uptake of the probe. The SQ-29852 structure was divided into six domains (A-F) and competitors were grouped into series depending on structural variations within specific regions. Domain A was found to prefer a hydrophobic function, such as a phenyl group, and was intolerant to positive charges and H+ -acceptors and donors. SQ-29852 analogues were more tolerant of substitutions in the C domain, compared to glycyl-L-proline analogues, suggesting that interactions along the length of the SQ-29852 molecule may override the effects of substitutions in the C domain. SQ-29852 analogues showed a preference for a positive function, such as an amine group in this region, but dipeptide structures favoured an uncharged substitution. Lipophilic substituents in domain D increased affinity of SQ-29852 analogues with the DTS. A similar effect was observed for ACE-NEP inhibitor analogues. Domain E, corresponding to the carboxyl group was found to be tolerant of esterification for SQ-29852 analogues but not for dipeptides. Structural features which may increase interaction for one series of compounds, may not have the same effect for another series, indicating that the presence of multiple recognition sites on a molecule may override the deleterious effect of anyone change. Modifying current, poorly absorbed peptidomimetic structures to fit the proposed hypothetical model may improve oral bioavailability by increasing affinity for the DTS. The stereochemical preference of the transporter was explored using four series of compounds (SQ-29852, lysylproline, alanylproline and alanylalanine enantiomers). The L, L stereochemistry was the preferred conformation for all four series, agreeing with previous studies. However, D, D enantiomers were shown in some cases to be substrates for the DTS, although exhibiting a lower affinity than their L, L counterparts. All the ACE-inhibitors and β-lactam antibiotics investigated, produced a degree of inhibition of the probe, and thus show some affinity for the DTS. This contrasts with previous reports that found several ACE inhibitors to be absorbed via a passive process, thus suggesting that compounds are capable of binding to the transporter site and inhibiting the probe without being translocated into the cell. This was also shown to be the case for oligodeoxynucleotide conjugated to a lipophilic group (vitamin E), and highlights the possibility that other orally administered drug candidates may exert non-specific effects on the DTS and possibly have a nutritional impact. Molecular modelling of selected ACE-NEP inhibitors revealed that the three carbonyl functions can be oriented in a similar direction, and this conformation was found to exist in a local energy-minimised state, indicating that the carbonyls may possibly be involved in hydrogen-bond formation with the binding site of the DTS.

An investigation of the effects of antitumour and other drugs on cell morphology and the cytoskeleton of erythrocytes

Human arythrocytes were used as a model system for an investigation of the mechanism of action of the antiproliferative drug Adriamycin. Erythrocytes were induced to undergo a change in morphology by elevation of intracellular calcium. It was revealed that the widely used media employed for the study of morphological change were unsuitable; a new incubation medium was developed so that cells were metabolically replete. In this medium echinocytosis took place both in a calcium concentration- and time-dependent manner. Pretreatment of erythrocytes with Adriamycin (10 M for 10 mins) protected the erythrocytes against calcium-induced echinocytosis at calcium concentrations < 150M. SDS-PAGE analysis of the cytoskeletal proteins prepared from erythrocytes revealed the calcium-induced proteolysis of two main cytoskeletal proteins: band 2:1 and band 4:1. Only the rate of the proteolysis of band 2.1 correlated with the onset of echinocytosis. Adriamycin inhibited the breakdown of band 2.1 even when the cells formed echinocytes; this raises doubts concerning the importance of band 2.1 in the maintenance of discocyte morphology. Adriamycin only marginally inhibited the purified calcium-activated thio protease (calpain). Calcium-loading of human erythrocytes increased the phosphorylation of several major cytoskeletal proteins including pp120, band 3, band 4.1 and band 4.9. The pattern of increase resembled that induced by 12-0-tetradecanoyl-phorbol-13-acetate. Pre-treatment with Adriamycin prior to calcium loading caused a general lowering of basal phosphorylation. Adriamycin had no effect on the activity of the calcium-activated phospholipid-dependent protein kinase (protein kinase C). A hypothesis is put forward that the morphological transition of erythrocytes might be dependent upon the activity of a contractile system.

Spatial contrast sensitivity and external noise: applications to optical and neural modulation transfer functions

The thesis will show how to equalise the effect of quantal noise across spatial frequencies by keeping the retinal flux (If-2) constant. In addition, quantal noise is used to study the effect of grating area and spatial frequency on contrast sensitivity resulting in the extension of the new contrast detection model describing the human contrast detection system as a simple image processor. According to the model the human contrast detection system comprises low-pass filtering due to ocular optics, addition of light dependent noise at the event of quantal absorption, high-pass filtering due to the neural visual pathways, addition of internal neural noise, after which detection takes place by a local matched filter, whose sampling efficiency decreases as grating area is increased. Furthermore, this work will demonstrate how to extract both the optical and neural modulation transfer functions of the human eye. The neural transfer function is found to be proportional to spatial frequency up to the local cut-off frequency at eccentricities of 0 - 37 deg across the visual field. The optical transfer function of the human eye is proposed to be more affected by the Stiles-Crawford -effect than generally assumed in the literature. Similarly, this work questions the prevailing ideas about the factors limiting peripheral vision by showing that peripheral optical acts as a low-pass filter in normal viewing conditions, and therefore the effect of peripheral optics is worse than generally assumed.

The role of interpersonal functioning in the maintenance of eating psychopathology:a systematic review and testable model

This review aims to systematically evaluate the empirical literature relating to the interpersonal functioning of those with eating disorder psychopathology and presents a preliminary model to help the formulation of patients' problems. Following a thorough literature search, 35 papers were included in this systematic review. The vast majority of studies indicate a strong association between eating psychopathology and certain maladaptive personality traits. The origins of social anxiety and poor social support that have been described as maintaining eating disorders appear to differ according to diagnostic groups. Interpersonal difficulties in people with restrictive behaviors such as anorexia appear to be related to the avoidance of expressing feelings to others and to giving priority to other people's feeling over their own. While interpersonal difficulties in patients with bulimia nervosa appear to be more related to interpersonal distrust and negative interaction and conflict with others. These concepts are presented in a preliminary model of interpersonal functioning in the eating disorders. © 2012 Elsevier Ltd.

Environmental governance in a contested state:the influence of European Union and other external actors on energy sector regulation in Kosovo

This article examines environmental governance in Kosovo, with a particular focus on the energy sector. The article considers the degree to which the emerging model of environmental governance is characterised by hierarchical and non-hierarchical modes of coordination. We examine the roles of a number of domestic institutions and actors – ministries, agencies, and regulatory bodies– and the influence of external actors, including the EU, the US, and Serbia. The EU is building Kosovo’s own hierarchical governance capacity by strengthening domestic institutions, whilst the US focuses primarily on market liberalization, whilst simultaneously supporting EU efforts. Moreover, environmental policy change is not wholly or predominantly driven by domestic actors, which can partly be attributed to Kosovo’s limited domestic sovereignty. We conclude that the emerging model of environmental governance in Kosovo is characterized by a weak hierarchy, partly as a result of external actor involvement, which disincentivises the government from responding to domestic non-state actor pressure.