Inhibition of iron-catalysed hydroxyl radical formation by inositol polyphosphates: a possible physiological function for myo-inositol hexakisphosphate

1. The ability of myo-inositol polyphosphates to inhibit iron-catalysed hydroxyl radical formation was studied in a hypoxanthine/xanthine oxidase system [Graf, Empson and Eaton (1987) J. Biol. Chem. 262, 11647-11650]. Fe3+ present in the assay reagents supported some radical formation, and a standard assay, with 5 microM Fe3+ added, was used to investigate the specificity of compounds which could inhibit radical generation. 2. InsP6 (phytic acid) was able to inhibit radical formation in this assay completely. In this respect it was similar to the effects of the high affinity Fe3+ chelator Desferral, and dissimilar to the effects of EDTA which, even at high concentrations, still allowed detectable radical formation to take place. 3. The six isomers of InsP5 were purified from an alkaline hydrolysate of InsP6 (four of them as two enantiomeric mixtures) and they were compared with InsP6 in this assay. Ins(1,2,3,4,6)P5 and D/L-Ins(1,2,3,4,5)P5 were similar to InsP6 in that they caused a complete inhibition of iron-catalysed radical formation at > 30 microM. Ins(1,3,4,5,6)P5 and D/L-Ins(1,2,4,5,6)P5, however, were markedly less potent than InsP6, and did not inhibit radical formation completely; even when Ins(1,3,4,5,6)P5 was added up to 600 microM, significant radical formation was still detected. Thus InsP5s lacking 2 or 1/3 phosphates are in this respect qualitatively different from InsP6 and the other InsP5s. 4. scyllo-Inositol hexakisphosphate was also tested, and although it caused a greater inhibition than Ins(1,3,4,5,6)P5, it too still allowed detectable free radical formation even at 600 microM. 5. We conclude that the 1,2,3 (equatorial-axial-equatorial) phosphate grouping in InsP6 has a conformation that uniquely provides a specific interaction with iron to inhibit totally its ability to catalyse hydroxyl radical formation; we suggest that a physiological function of InsP6 might be to act as a 'safe' binding site for iron during its transport through the cytosol or cellular organelles

Measuring the influence of similarity on category-specific effects

There is evidence for both advantages and disadvantages in normal recognition of living over nonliving things. This paradox has been attributed to high levels of perceptual similarity within living categories having a different effect on performance in different contexts. However, since living things are intrinsically more similar to each other, previous studies could not determine whether the various category effects were due to perceptual similarity, or to other characteristics of living things. We used novel animal and vehicle stimuli that were matched for similarity to measure the influence of perceptual similarity in different contexts. We found that displaying highly similar objects in blocked sets reduced their perceived similarity, eliminating the detrimental effect on naming performance. Experiment 1 demonstrated a disadvantage for highly similar objects in name learning and name verification using mixed groups of similar and dissimilar animals and vehicles. Experiment 2 demonstrated no disadvantage for the same highly similar objects when they were blocked, e.g., similar animals presented alone. Thus, perceptual similarity, rather than other characteristics particular to living things, is affected by context, and could create apparent category effects under certain testing conditions.

Meta-analytic model comparisons of surface- and deep-level relational diversity effects on social integration and individual effectiveness

While diversity might give an organization a competitive advantage, individuals have a tendency to prefer homogenous group settings. Prior research suggests that group members who are dissimilar (vs. similar) to their peers in terms of a given diversity attribute (e.g. demographics, attitudes, values or traits) feel less attached to their work group, experience less satisfying and more conflicted relationships with their colleagues, and consequently are less effective. However, prior empirical findings tend to be weak and inconsistent, and it remains unclear when, how and to what extent such differences affect group members’ social integration (i.e. attachment with their work group, satisfaction and conflicted relationships with their peers) and effectiveness. To address these issues the current study conducted a meta-analysis and integrated the empirical results of 129 studies. For demographic diversity attributes (such as gender, ethnicity, race, nationality, age, functional background, and tenure) the findings support the idea that demographic dissimilarity undermines individual member performance via lower levels of social integration. These negative effects were more pronounced in pseudo teams – i.e. work groups in which group members pursue individual goals, work on individual tasks, and are rewarded for their individual performance. These negative effects were however non-existent in real teams - i.e. work groups in which groups members pursue group goals, work on interdependent tasks, and are rewarded (at least partially) based on their work group’s performance. In contrast, for underlying psychological diversity attributes (such as attitudes, personality, and values), the relationship between dissimilarity and social integration was more negative in real teams than in pseudo teams, which in return translated into even lower individual performance. At the same time however, differences in underlying psychological attributes had an even stronger positive effect on dissimilar group member’s individual performance, when the negative effects of social integration were controlled for. This implies that managers should implement real work groups to overcome the negative effects of group member’s demographic dissimilarity. To harness the positive effects of group members’ dissimilarity on underlying psychological attributes, they need to make sure that dissimilar group members become socially integrated.

Fabrication and applications of fibre Bragg gratings

The consequences of fabricating Bragg gratings in various fibres, with or without hydrogen loading, and with varying laser power levels are explored. Three new techniques for fabricating chirped gratings are presented. Beams with dissimilar wavefront curvatures are interfered to give chirped gratings. With the same aim techniques of writing gratings on tapered fibres and on deformed fibres are also covered. With these techniques, a wide variety of gratings has been fabricated from the 'superbroad' (with bandwidths of up to 180 nm), small to medium bandwidth gratings with linear chirp profiles and quadratic chirped gratings. It is demonstrated that chirped grating can be concatenated to form all-fibre Fabry-Perot and Moiré resonators. These are further concatenated with chirped gratings to produce filters with narrow passbands and very broad stopbands. A number of other applications are also addressed. The use of chirped fibre gratings for dispersion compensation and femtosecond chirped pulse amplification is demonstrated. Chirped gratings are used as dispersive elements in modelocked fibre lasers producing ultrashort pulses. A chirped fibre grating Fabry-Perot transmission filter is used in a continuous wave laser that exhibits eleven simultaneously lasing wavelengths. Finally, the use of grating-coupler devices as variable reflectivity mirrors for laser optimisation and gain clamping is considered.

The effect of interocular phase difference on perceived contrast

Binocular vision is traditionally treated as two processes: the fusion of similar images, and the interocular suppression of dissimilar images (e.g. binocular rivalry). Recent work has demonstrated that interocular suppression is phase-insensitive, whereas binocular summation occurs only when stimuli are in phase. But how do these processes affect our perception of binocular contrast? We measured perceived contrast using a matching paradigm for a wide range of interocular phase offsets (0–180°) and matching contrasts (2–32%). Our results revealed a complex interaction between contrast and interocular phase. At low contrasts, perceived contrast reduced monotonically with increasing phase offset, by up to a factor of 1.6. At higher contrasts the pattern was non-monotonic: perceived contrast was veridical for in-phase and antiphase conditions, and monocular presentation, but increased a little at intermediate phase angles. These findings challenge a recent model in which contrast perception is phase-invariant. The results were predicted by a binocular contrast gain control model. The model involves monocular gain controls with interocular suppression from positive and negative phase channels, followed by summation across eyes and then across space. Importantly, this model—applied to conditions with vertical disparity—has only a single (zero) disparity channel and embodies both fusion and suppression processes within a single framework.

A Franco-British comparison of patterns of working hours in large-scale grocery retailing, with specific reference to part-time work

In this thesis patterns of working hours in large-scale grocery retailing in Britain and France are compared. The research is carried out using cross-national comparative methodology, and the analysis is based on information derived from secondary sources and empirical research in large-scale grocery retailing involving employers and trade unions at industry level and case studies at outlet level. The thesis begins by comparing national patterns of working hours in Britain and France over the post-war period. Subsequently, a detailed comparison of working hours in large-scale grocery retailing in Britain and France is carried out through the analysis of secondary sources and empirical data. Emphasis is placed on analyzing part-time working hours. They are contrasted and compared at national level and explained in terms of supply and demand factors. The relationships between the structuring of, and satisfaction with, working hours and factors determining women's integration in the workforce in Britain and France are investigated. Part-time hours are then compared and contrasted in large-scale grocery retailing in the context of the analysis of working hours. The relationship between the structuring of working hours and satisfaction with them is examined in both countries through research with women part-timers in case study outlets. The cross-national comparative methodology is used to examine whether dissimilar national contexts in Britain and France have led to different patterns of working hours in large-scale grocery retailing. The principal conclusion is that significant differences are found in the length, organization and flexibility of working hours and that these differences can be attributed to dissimilar socio-economic, political, and cultural contexts in the two countries.

Development of plasmid dna formulations for application as microspheric dna vaccines

The advent of DNA vaccines has heralded a new technology allowing the design and elicitation of immune responses more adequate for a wider range of pathogens. The formulation of these vaccines into the desired dosage forms extends their capability in terms of stability, routes of administration and efficacy. This thesis describes an investigation into the fabrication of plasmid DNA, the active principle of DNA vaccines, into microspheres, based on the tenet of an increased cellular uptake of microparticulate matter by phagocytic cells. The formulation of plasmid DNA into microspheres using two methods, is presented. Formulation of microspheric plasmid DNA using the double emulsion solvent evaporation method and a spray-drying method was explored. The former approach involves formation of a double emulsion, by homogenisation. This method produced microspheres of uniform size and smooth morphology, but had a detrimental effect on the formulated DNA. The spray-drying method resulted in microspheres with an improved preservation of DNA stability. The use of polyethylenimine (PEI) and stearylamine (SA) as agents in the microspheric formulation of plasmid DNA is a novel approach to DNA vaccine design. Using these molecules as model positively-charged agents, their influence on the characteristics of the microspheric formulations was investigated. PEI improved the entrapment efficiency of the plasmid DNA in microspheres, and has minimal effect on either the surface charge, morphology or size distribution of the formulations. Stearylamine effected an increase in the entrapment efficiency and stability of the plasmid DNA and its effect on the micropshere morphology was dependent on the method of preparation. The differences in the effects of the two molecules on microsphere formulations may be attributable to their dissimilar physico-chemical properties. PEI is water-soluble and highly-branched, while SA is hydrophobic and amphipathic. The positive charge of both molecules is imparted by amine functional groups. Preliminary data on the in vivo application of formulated DNA vaccine, using hepatitis B plasmid, showed superior humoral responses to the formulated antigen, compared with free (unformulated) antigen.

Synchronization processes in nonlinear systems and their relation to cortical oscillatory dynamics

This thesis was focused on theoretical models of synchronization to cortical dynamics as measured by magnetoencephalography (MEG). Dynamical systems theory was used in both identifying relevant variables for brain coordination and also in devising methods for their quantification. We presented a method for studying interactions of linear and chaotic neuronal sources using MEG beamforming techniques. We showed that such sources can be accurately reconstructed in terms of their location, temporal dynamics and possible interactions. Synchronization in low-dimensional nonlinear systems was studied to explore specific correlates of functional integration and segregation. In the case of interacting dissimilar systems, relevant coordination phenomena involved generalized and phase synchronization, which were often intermittent. Spatially-extended systems were then studied. For locally-coupled dissimilar systems, as in the case of cortical columns, clustering behaviour occurred. Synchronized clusters emerged at different frequencies and their boundaries were marked through oscillation death. The macroscopic mean field revealed sharp spectral peaks at the frequencies of the clusters and broader spectral drops at their boundaries. These results question existing models of Event Related Synchronization and Desynchronization. We re-examined the concept of the steady-state evoked response following an AM stimulus. We showed that very little variability in the AM following response could be accounted by system noise. We presented a methodology for detecting local and global nonlinear interactions from MEG data in order to account for residual variability. We found crosshemispheric nonlinear interactions of ongoing cortical rhythms concurrent with the stimulus and interactions of these rhythms with the following AM responses. Finally, we hypothesized that holistic spatial stimuli would be accompanied by the emergence of clusters in primary visual cortex resulting in frequency-specific MEG oscillations. Indeed, we found different frequency distributions in induced gamma oscillations for different spatial stimuli, which was suggestive of temporal coding of these spatial stimuli. Further, we addressed the bursting character of these oscillations, which was suggestive of intermittent nonlinear dynamics. However, we did not observe the characteristic-3/2 power-law scaling in the distribution of interburst intervals. Further, this distribution was only seldom significantly different to the one obtained in surrogate data, where nonlinear structure was destroyed. In conclusion, the work presented in this thesis suggests that advances in dynamical systems theory in conjunction with developments in magnetoencephalography may facilitate a mapping between levels of description int he brain. this may potentially represent a major advancement in neuroscience.

Antecedents and consequences of the social categorization of expatriates in India

Multinational organizations have dramatically increased their operations in Asian countries in recent years. The success of expatriate assignments has therefore become increasingly important for multinationals. Social and cultural psychologists have proposed that host country nationals' (HCN) attitudes toward expatriates are key antecedents of interpersonally supportive behavior related to assignment success. We developed and tested a model of HCN social categorization and helping of expatriates based on the social–psychological theory. Results indicated that perceived values similarity and collectivism are negatively related to social categorization of expatriates, and that social categorization is negatively related to the provision of role information and social support by HCNs. Results are discussed in terms of their implications for theory and for organizations sending expatriates to culturally dissimilar host countries.

Increased diversity of libraries from libraries: chemoinformatic analysis of bis-diazacyclic libraries

Combinatorial libraries continue to play a key role in drug discovery. To increase structural diversity, several experimental methods have been developed. However, limited efforts have been performed so far to quantify the diversity of the broadly used diversity-oriented synthetic (DOS) libraries. Herein we report a comprehensive characterization of 15 bis-diazacyclic combinatorial libraries obtained through libraries from libraries, which is a DOS approach. Using MACCS keys, radial and different pharmacophoric fingerprints as well as six molecular properties, it was demonstrated the increased structural and property diversity of the libraries from libraries over the individual libraries. Comparison of the libraries to existing drugs, NCI Diversity and the Molecular Libraries Small Molecule Repository revealed the structural uniqueness of the combinatorial libraries (mean similarity < 0.5 for any fingerprint representation). In particular, bis-cyclic thiourea libraries were the most structurally dissimilar to drugs retaining drug-like character in property space. This study represents the first comprehensive quantification of the diversity of libraries from libraries providing a solid quantitative approach to compare and contrast the diversity of DOS libraries with existing drugs or any other compound collection.

Relational diversity, social integration and individual effectiveness: a social self-regulation perspective

Relational demographers and dissimilarity researchers contend that group members who are dissimilar (vs. similar) to their peers in terms of a given diversity attribute (e.g. demographics, attitudes, values or traits) feel less attached to their work group, experience less satisfying and more conflicted relationships with their colleagues, and consequently are less effective. However, qualitative reviews suggest empirical findings tend to be weak and inconsistent (Chattopadhyay, Tluchowska and George, 2004; Riordan, 2000; Tsui and Gutek, 1999), and that it remains unclear when, how and to what extent such differences (i.e. relational diversity) affect group members social integration (i.e. attachment with their work group, satisfaction and conflicted relationships with their peers) and effectiveness (Riordan, 2000). This absence of meta-analytically derived effect size estimates and the lack of an integrative theoretical framework leave practitioners with inconclusive advice regarding whether the effects elicited by relational diversity are practically relevant, and if so how these should be managed. The current research develops an integrative theoretical framework, which it tests by using meta-analysis techniques and adding two further empirical studies to the literature. The first study reports a meta-analytic integration of the results of 129 tests of the relationship between relational diversity with social integration and individual effectiveness. Using meta-analytic and structural equation modelling techniques, it shows different effects of surface- and deep-level relational diversity on social integration Specifically, low levels of interdependence accentuated the negative effects of surface-level relational diversity on social integration, while high levels of interdependence accentuated the negative effects of deep-level relational diversity on social integration. The second study builds on a social self-regulation framework (Abrams, 1994) and suggests that under high levels of interdependence relational diversity is not one but two things: visibility and separation. Using ethnicity as a prominent example it was proposed that separation has a negative effect on group members effectiveness leading for those high in visibility and low in separation to overall positive additive effects, while to overall negative additive effects for those low in visibility and high in separation. These propositions were sustained in a sample of 621 business students working in 135 ethnically diverse work groups in a business simulation course over a period of 24 weeks. The third study suggests visibility has a positive effect on group members self-monitoring, while separation has a negative effect. The study proposed that high levels of visibility and low levels of separation lead to overall positive additive effects on self-monitoring but overall negative additive effects for those low in visibility and high in separation. Results from four waves of data on 261 business students working in 69 ethnically diverse work groups in a business simulation course held over a period of 24 weeks support these propositions.

Active vibration control at machinery feet

The unmitigated transmission of undesirable vibration can result in problems by way of causing human discomfort, machinery and equipment failure, and affecting the quality of a manufacturing process. When identifiable transmission paths are discernible, vibrations from the source can be isolated from the rest of the system and this prevents or minimises the problems. The approach proposed here for vibration isolation is active force cancellation at points close to the vibration source. It uses force feedback for multiple-input and multiple-output control at the mounting locations. This is particularly attractive for rigid mounting of machine on relative flexible base where machine alignment and motions are to be restricted. The force transfer function matrix is used as a disturbance rejection performance specification for the design of MIMO controllers. For machine soft-mounted via flexible isolators, a model for this matrix has been derived. Under certain conditions, a simple multiplicative uncertainty model is obtained that shows the amount of perturbation a flexible base has on the machine-isolator-rigid base transmissibility matrix. Such a model is very suitable for use with robust control design paradigm. A different model is derived for the machine on hard-mounts without the flexible isolators. With this model, the level of force transmitted from a machine to a final mounting structure using the measurements for the machine running on another mounting structure can be determined. The two mounting structures have dissimilar dynamic characteristics. Experiments have verified the usefulness of the expression. The model compares well with other methods in the literature. The disadvantage lies with the large amount of data that has to be collected. Active force cancellation is demonstrated on an experimental rig using an AC industrial motor hard-mounted onto a relative flexible structure. The force transfer function matrix, determined from measurements, is used to design H and Static Output Feedback controllers. Both types of controllers are stable and robust to modelling errors within the identified frequency range. They reduce the RMS of transmitted force by between 30?80% at all mounting locations for machine running at 1340 rpm. At the rated speed of 1440 rpm only the static gain controller is able to provide 30?55% reduction at all locations. The H controllers on the other hand could only give a small reduction at one mount location. This is due in part to the deficient of the model used in the design. Higher frequency dynamics has been ignored in the model. This can be resolved by the use of a higher order model that can result in a high order controller. A low order static gain controller, with some tuning, performs better. But it lacks the analytical framework for analysis and design.

Watermarking biomedical time series data

This thesis addresses the problem of information hiding in low dimensional digital data focussing on issues of privacy and security in Electronic Patient Health Records (EPHRs). The thesis proposes a new security protocol based on data hiding techniques for EPHRs. This thesis contends that embedding of sensitive patient information inside the EPHR is the most appropriate solution currently available to resolve the issues of security in EPHRs. Watermarking techniques are applied to one-dimensional time series data such as the electroencephalogram (EEG) to show that they add a level of confidence (in terms of privacy and security) in an individual’s diverse bio-profile (the digital fingerprint of an individual’s medical history), ensure belief that the data being analysed does indeed belong to the correct person, and also that it is not being accessed by unauthorised personnel. Embedding information inside single channel biomedical time series data is more difficult than the standard application for images due to the reduced redundancy. A data hiding approach which has an in built capability to protect against illegal data snooping is developed. The capability of this secure method is enhanced by embedding not just a single message but multiple messages into an example one-dimensional EEG signal. Embedding multiple messages of similar characteristics, for example identities of clinicians accessing the medical record helps in creating a log of access while embedding multiple messages of dissimilar characteristics into an EPHR enhances confidence in the use of the EPHR. The novel method of embedding multiple messages of both similar and dissimilar characteristics into a single channel EEG demonstrated in this thesis shows how this embedding of data boosts the implementation and use of the EPHR securely.

The application of fibre Bragg grating networks as strain sensors and as phased array antenna true time delay elements

The fabrication of in-fibre Bragg gratings, and the application of arrays of such gratings as strain sensors and as true time delay elements for the control of phased array antennas is reported. Chirped period Bragg gratings were produced using the fibre deformation fabrication technique, with chirps of between 2.9nm and 17.3nm achieved. Arrays of 5mm and 2mm long uniform period Bragg gratings were fabricated using the inscription method, for use as true time delay elements,dissimilar wavefronts and their spectral characteristics recorded. The uniform period grating arrays were used to create minimum time delays of 9.09ps, 19.02ps and 31ps; making them suitable for controlling phased array antennas operating at RF frequencies of up to 3GHz, with 10° phase resolution. Four 4mm long chirped gratings were produced using the dissimilar wavefronts fabrication method, having chirps of 7nm, 12nm, 20nm and 30nm, and were used to create time delays of between 0.3ps and 59ps. Hence they are suitable for controlling phased array antennas at RF frequencies of up to 48GHz. The application of in fibre Bragg gratings as strain sensors within smart structure materials was investigated, with their sensitivity to applied strain and compression measured for both embedded and surface mounted uniform period and fibre Fabry-Perot filter gratings. A fibre Bragg grating sensor demultiplexing scheme based on a liquid crystal filled Fabry-Perot etalon tuneable transmission filter was proposed, successfully constructed and fully characterised. Three characteristics of the LCFP etalon were found to pose operational limitations to its application in a Bragg grating sensor system; most significantly, the resonance peak wavelength was highly (-2,77nm/°C) temperature dependent. Several methods for minimising this temperature sensitivity were investigated, but enjoyed only limited success. It was therefore concluded that this type (E7 filled) of LCFP etalon is unsuitable for use as a Bragg grating sensor demultiplexing element.

Leadership in American Evangelical churches:an explanatory theory

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT This study is about leadership in American Evangelical Churches, which as a sub-set of American Christianity, are growing, while American Christianity as a whole is in decline. As a result evangelicalism is quickly becoming the dominate iteration of American Christianity. It is anecdotal that well led churches grow while poorly led churches do not, yet no one has identified what leadership, in the evangelical church context, is. Researchers have investigated a number of aspects of church leadership (much of it without identifying whether or not the churches under investigation were evangelical or not) but no one has put forth a unified theory linking these aspects together. The purpose of this research is to address that gap and develop a theory that explains how evangelicals view leadership in their local churches. In this study of three churches, dissimilar in size and governance, a purely qualitative approach to data collection and analysis was employed. The study involved 60 interviews that sought points-of-view from top and mid-level leadership along with congregant followers. The study borrowed heavily from Glaser and Strauss (1967) Grounded Theory approach to data analysis. The results developed a theory which provides a unified explanation of how leadership actually works in the three evangelical churches. Several implications for practice are discussed as to the theory's usefulness as a method of leadership education and evaluation. An original discovery was found that an individual's incumbency within the organization was identified as a social power. Limitations to this research are the limitations generally imputed to purely qualitative research in that questions are raised about the theory's applicability to evangelical churches beyond the three studied. The suggestions for further research involve addressing those limitations