The growing neutropenic patient population provides an ideal target for opportunistic fungal infections. Several effective antifungal drugs are toxic at high doses and contraindicated for long-term treatment. Recombinant human granulocyte colony stimulating factor (rhG-CSF) has been shown to increase neutrophilic numbers and functions, thus providing enhanced host defense. Improved efficacy by using rhG-CSF in conjunction with various antifungal agents was the primary focus of these studies. Use of rhG-CSF in a murine model of vaginal candidiasis did not reduce vaginal colony counts, or improve vaginal histophathology scores. Administration of rhG-CSF in a murine model of pulmonary aspergillosis improved survival, clinical signs, and gross pathology and histophathology scores of the lungs, and increased weight gain. The rhG-CSF was not shown to be an effective therapeutic treatment in this model of vaginal candidiasis. The rhG-CSF was, however, an effective prophylactic treatment in this model of pulmonary aspergillosis.

Les bactéries se répandent aux interfaces en formant des colonies, qui peuvent être considérées comme des suspensions denses actives. L'objet de cette thèse est le développement et l'analyse de modèles simples pour élucider le rôle des phénomènes physico-chimiques et passifs - tels que l'osmose, la tension de surface et le mouillage - dans l'expansion des colonies bactériennes aux interfaces solide/air. Les modèles sont basés sur une description hydrodynamique des couches minces de suspensions liquides, qui est complété par des processus bioactifs.Dans un premier temps, nous nous sommes intéressés à l'expansion osmotique des biofilms. Dans ce mécanisme, la bactérie sécrète une matrice polymérique qui agit comme un osmolyte et entraîne un afflux d'eau, riche en nutriments, du substrat humide vers le biofilm. Nous avons constaté que la mouillabilité du substrat est une des déterminantes principales de la vitesse d'expansion du biofilm. En-dessous d'une mouillabilité critique l'expansion s'interrompt, bien que la colonie soit biologiquement active. Cependant, une légère réduction de la tension de surface et une amélioration de la mouillabilité qui en résulte suffisent à induire un étalement continu. Les bactéries peuvent activement contrôler la tension de surface par la production de bio-surfactants.Dans un deuxième temps, nous avons étudié l'expansion de colonies bactériennes aidée par des molécules biologiques tensioactives auto-produites. Dans ce mécanisme, des flux de Marangoni résultant d'une concentration non uniforme de molécules tensioactives aux bords de la colonie peuvent favoriser l'expansion coopérative et provoquer une instabilité de la forme axi-symétrique des colonies bactériennes. Notre modèle nous a permis de reproduire quatre modes de développement différentes, à savoir l'étalement arrêté et continu des colonies circulaires, l'étalement des colonies avec des bords légèrement modulées et la formation de doigts prononcés.Dans la dernière partie, nous avons fait un premier pas vers l'incorporation de la motilité actif des bactéries dans notre modèle et présentons donc un modèle phénoménologique pour un film mince active. / Bacteria colonise interfaces by the formation of dense aggregates. In this thesis, we develop and analyse simple models to clarify the role of passive physico-chemical forces and processes - such as osmosis, surface tension effects and wettability - in the spreading of bacterial colonies at solid-air interfaces. The models are based on a hydrodynamic description for thin films of liquid suspensions that is supplemented by bioactive processes.We first focus on the osmotic spreading mechanism of bacterial colonies that relies on the generation of osmotic pressure gradients. The bacteria secrete a polymeric matrix which acts as an osmolyte and triggers the influx of nutrient-rich water from the moist substrate into the colony. We find that wettability crucially affects the spreading dynamics. At low wettability, the lateral expansion of the colony is arrested, albeit the colony is biologically active. However, a small reduction of the surface tension and the resulting improvement of the wettability suffices to induce continuous spreading. This can, e.g., result from the production of bio-surfactants by the bacteria.Next, we study passive liquid films covered by insoluble surfactants before developing a model for the surfactant-driven spreading of bacterial colonies. In this spreading mechanism, Marangoni fluxes arising due to a non-uniform surfactant concentration at the edges of the colony drive cooperative spreading and may cause an instability of the circular colony shape. We find that variations in wettability and surfactant production suffice to reproduce four different types of colony growth, namely, arrested and continuous spreading of circular colonies, slightly modulated front lines and the formation of pronounced fingers.In the final part, we take a first step towards the incorporation of active collective bacterial motion in the employed thin-film framework and present a phenomenologically derived model for active polar films.

Measuring hormonal changes is vital for understanding how the social and physical environment influences behaviour, reproduction and survival. Various methods of hormone measurement exist, potentially explaining variation in results across studies; methods should be cross validated to ensure they correlate. I directly compare faecal and plasma hormone measurements (Chapter 2), and use the most suitable endocrine measure to test the Darling hypothesis (Chapter 3) - that breeding is hastened and synchronized in larger colonies due to increased social stimulation (mediated by the endocrine system). Blood and faecal samples were simultaneously collected from individual Adelie penguins (Pygoscelis adeliae) for comparison, and assayed for testosterone and corticosterone (or their metabolites). Sex differences and variability within each measure, and correlation of values across measures were compared. For both hormones, plasma samples showed greater variation than faecal samples. Males had higher corticosterone levels than females, but the difference was only significant in faecal samples. Plasma testosterone, but not faecal testosterone, was significantly higher in males than females. Correlation between sample types was poor overall, and weaker in females than in males; perhaps because measures from plasma represent hormones that are both free and bound to globulins, whereas measures from faeces represent only the free portion. Faecal samples also represent a cumulative measure of hormones over time, as opposed to a plasma 'snapshot' concentration. Faecal sampling appears more suitable for assessing baseline hormone levels. In the second study I examined, over two seasons, whether the timing of breeding varied with colony size; larger colonies present occupants with higher levels of social stimulation and are predicted to show earlier, more synchronous breeding. Baseline faecal hormone levels throughout the breeding season, and survival, were measured to investigate possible proximate and ultimate mechanisms for the results. The influence of environmental variability was examined, by relating the timing of breeding, survival, and endocrine changes to sea ice conditions. Colony size did not influence the timing or synchrony of breeding, survival, or hormone levels within years; perhaps because colonies in an Adelie rookery are not independent from the 'social environment' of adjacent colonies. Across years, synchrony in the smaller rookery was higher than in the larger rookery. The scale of these comparisons may exceed the applicability of the Darling hypothesis. Therefore, no support was found for the Darling hypothesis, at the colony or rookery level, in this species. Higher corticosterone metabolite and lower sex hormone levels in the first season correlated to later breeding and lower survival compared to the second season. This is likely due to the persistence of extensive sea ice conditions late into the first season. Researchers should take care in selecting the most appropriate method of hormone measurement for their question. Future studies testing the Darling hypothesis must carefully select their definition of a colony (i.e. a truly isolated social unit) and the scale at which the hypothesis is tested. Combining endocrine measurements with behavioural, survival, and environmental information allows for a more comprehensive interpretation of animal ecology.

Combinatorial optimisation problems (COPs) pervade human society: scheduling, design, layout, distribution, timetabling, resource allocation and project management all feature problems where the solution is some combination of elements, the overall value of which needs to be either maximised or minimised (i.e., optimised), typically subject to a number of constraints. Thus, techniques to efficiently solve such problems are an important area of research. A popular group of optimisation algorithms are the metaheuristics, approaches that specify how to search the space of solutions in a problem independent way so that high quality solutions are likely to result in a reasonable amount of computational time. Although metaheuristic algorithms are specified in a problem independent manner, they must be tailored to suit each particular problem to which they are applied. This thesis investigates a number of aspects of the application of the relatively new Ant Colony Optimisation (ACO) metaheuristic to different COPs.The standard ACO metaheuristic is a constructive algorithm loosely based on the foraging behaviour of ant colonies, which are able to find the shortest path to a food source by indirect communication through pheromones. ACO’s artificial pheromone represents a model of the solution components that its artificial ants use to construct solutions. Developing an appropriate pheromone representation is a key aspect of the application of ACO to a problem. An examination of existing ACO applications and the constructive approach more generally reveals how the metaheuristic can be applied more systematically across a range of COPs. The two main issues addressed in this thesis are biases inherent in the constructive process and the systematic selection of pheromone representations.The systematisation of ACO should lead to more consistently high performance of the algorithm across different problems. Additionally, it supports the creation of a generalised ACO system, capable of adapting itself to suit many different combinatorial problems without the need for manual intervention.

A Large Scale Robot Colony (LSRC) is a complex artifact comprising of a significant population of both mobile and static robots. LSRC research is in its literary infancy and it is therefore necessary to rely upon external fields for the appropriate framework, Multi Agent Systems (MAS) and Large Scale Systems (LSS). At the intersection of MAS, LSS and LSRC exist near identical issues, problems and solutions. If attention is paid to coherence then solution portability is possible. The issue of Self-Reliability is poorly addressed by the MAS research field. Disparity between the real world and simulation is another area of concern. Despite these deficiencies, MAS and LSS are perceived as the most appropriate frameworks. MAS research focuses on three prime areas, cognitive science, management and interaction. LSRC is focused on Self-Sustainability, Self-Management and Self-Organization. While LSS research was not primarily intended for populations of mobile robots, it does address key issues of LSRC, such as effective sustainability and management. Implementation of LSRC that is based upon the optimal solution for any one or two of the three aspects will be inferior to a coherent solution based upon all three. LSRC’s are complex organizations with significant populations of both static and mobile robots. The increase in population size and the requirement to address the issue of Self-Reliance give rise to new issues. It is no longer sufficient to speak only in terms of robot intelligence, architecture, interaction or team behaviour, even though these are still valid topics. Issues such as population sustainability and management have greater significance within LSRC. As the size of a robot populations increases, minor uneconomical decisions and actions inhibit the performance of the population. Interaction must be made economical within the context of the LSRC. Sustainability of the population becomes significant as it enables stable performance and extended operational lifespan. Management becomes significant as a mechanism to direct the population so as to achieve near optimal performance. The Self-Sustainability, Self-Management and Self-Organization of LSRC are vastly more complex than in team robotics. Performance of the overall population becomes more significant than individual or team achievement. This thesis is a presentation of the Cooperative Autonomous Robot Colony (CARC) architecture. The CARC architecture is novel in that it offers a coherent baseline solution to the issue of mobile robot Self-Reliance. This research uses decomposition as a mechanism to reduce problem complexity. Self-Reliance is decomposed into Self-Sustainability, Self-Management, and Self-Organization. A solution to the issue of Self-Reliance will comprise of conflicting sub-solutions. A product of this research is a set of guidelines that manages the conflict of sub-solutions and maintains a coherent solution. In addressing the issue of Self-Reliance, it became apparent that Economies of Scale, played an important role. The effects of Economies of Scale directed the research towards LSRC’s. LSRC’s demonstrated improved efficiency and greater capability to achieve the requirements of Self-Reliance. LSRC’s implemented with the CARC architecture would extend human capability, enabling large scale operations to be performed in an economical manner, within real world and real time environments, including those of a remote and hostile nature. The theory and architecture are supported using published literature, experiments, observations and mathematical projections. Contributions of this work are focused upon the three pillars of Self-Reliance addressed by CARC: Self-Sustainability, Self-Management and Self-Organization. The chapter on Self-Sustainability explains and justifies the relevance of this issue, what it is, why it is important and how it can be achieved. Self-Sustainability enables robots to continue to operate beyond disabling events by addressing failure and routine maintenance. Mathematical projections are used to compare populations of non-sustained and sustained robots. Computer modeling experiments are used to demonstrate the feasibility of Self-Sustainability, including extended operational life, the maintenance of optimal work flow and graceful physical degradation (GPD). A detailed explanation is presented of Sustainability Functions, Colony Sites, Static Robot Roles, Static Robot Failure Options, and Polymorphism. The chapter on Self-Management explores LSS research as a mechanism to exert influence over a LSRC. An experimental reactive management strategy is demonstrated. This strategy while limited does indicate promising potential directions for future research including the Man in the Loop (MITL) strategy highly desired by NASA JPL for off world command and control of a significant robot colony (Huntsberger, et. al., 2000). Experiments on Communication evaluate both Broadcast Conveyance (BC) and Message Passing Conveyance (MPC). These experiments demonstrate the potential of Message Passing as a low cost system for LSRC communication. Analysis of Metrics indicates that a Performance Based Feedback Method (PBFM) and a Task Achievement Method (TAM) are both necessary and sufficient to monitor a LSRC. The chapter on Self-Organization describes a number of experiments, algorithms and protocols on Reasoning Robotics, a minor variant of Reactive Robotics. Reasoning Robotics utilizes an Event Driven Architecture (EDA) rather than a Stimulus Driven Architecture (SDA) common to Reactive Robotics. Enhanced robot performance is demonstrated by a combination of EDA and environmental modification enabling stigmergy. These experiments cover Intersection Navigation with contingency for Multilane Intersections, a Radio Packet Controller (RPC) algorithm, Active and Passive Beacons including a communication protocol, mobile robot navigation using Migration Decision Functions (MDF’s), including MDF positional errors. The central issue addressed by this thesis is the production of Self-Reliance guidelines for LSRC’s. Self-Reliance is perceived as a critical issue in advancing the useful and productive applications for LSRC’s. LSRC’s are complex with many issues in related fields of MAS and LSS. Decomposition of Self-Reliance into Self-Sustainability, Self-Management and Self-Organization were used to aid in problem understanding. It was found that Self-Sustainability extends the operational life of individual robots and the LSRC. Self-Management enables the exertion of human influence over the LSRC, such that the ratio of humans to robots is reduced but not eliminated. Self-Organization achieves and enhances performance through a routine and reliable LSRC environment. The product of this research was the novel CARC architecture, which consists of a set of Self-Reliance guidelines and algorithms. The Self-Reliance guidelines manage conflict between optimal solutions and provide a framework for LSRC design. This research was supported by literature, experiments, observations and mathematical projections.

This thesis seeks to examine the nineteenth-century art collections and architectural style of the original buildings at the University of Sydney in order to demonstrate ways in which visual material may be employed to shape public perception of an institution. I shall argue that the architectural style of the original university buildings was specifically chosen with particular aims which extended beyond the mere establishment of a tertiary institution for the colony. I will also argue that the style shaped the character of the institution, contributed to the maintenance of law and order in the colony, linked the colony more firmly than hitherto to the mother country and provided social benefits for the founders of the institution. The instant history and character thus imposed upon the institution was reinforced by the assembly of a portrait collection in emulation of other collections of portraits at leading institutions of the colony and the mother country, including the Oxbridge universities. Once the building proclaimed that the institution was comparable with the great universities of the world, the subjects of the portraits at the university could be placed in the class of founders of a great historical institution, thus at the same time enhancing the reputation of the institution and the individuals. The construction of an indentity through visual images was extended by the benefactions of Sir Charles Nicholson, the principal donor of works of art to the university in the nineteenth century. I argue that his intentions in relation to his collections were didactic but were also concerned with the entrenchment of the imperial hegemony over the colony, and again with the enhancement of his personal repuatation. This analysis shows how, by a complex of personal ambition and aspiration for the colony, the style of the buildings and the art collections formed were used to establish the colony as civilized and the new university as a bastion of English tradition.

This study explores the early history of Sydney's Rocks area at two levels. First, it provides a much-needed history of the city's earliest, oldest-surviving and best-known precinct, one which allows an investigation of popular beliefs about the Rocks' convict origins, and which challenges and qualifies its reputation for lowlife, vice and squalor. Second, by examining fundamental aspects of everyday life - townscape, community and commonality, family life and work, human interaction and rites of passage - this study throws new light on the origins of Sydney from the perspective of the convict and ex-convict majority. Despite longstanding historical interest in Sydney's beginnings, the cultural identity, values, habits, beliefs of the convicts and ex-convicts remained largely hidden. The examination of such aspects reveals another Sydney altogether from that presented by governors, artists and mapmakers. Instead of an orderly oupost of empire, a gaol-town, or a 'gulag', the Sydney the Rocks represents was built and occupied largely according to the tastes, priorities and inclination of the people, with relatively little official regulation or interference. While the Rocks appeared 'disorderly' in the eyes of the elite, it nevertheless functioned according to cultural rules, those of the lower orders - the artisans, shopkeepers, publicans, labouring people, the majority of whom were convicts and ex-convicts.

Includes nine pages of amendments. / Bibliography: leaves 140-211. / 211, [200] leaves, [12] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Aims to determine the reason for the lack of ability of many myeloid leukaemic cell populations to stimulate allogeneic lymphocytes in mixed leucocyte culture (MLC), with a view to manipulating the immunogenicity of these cells for therapeutic purposes. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1995

Copies of author's previously published articles inserted. / Includes bibliographical references. / vi, 135, [109] leaves, [23] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Studies the structure-function properties of the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF) in order to generate molecules with novel biological properties. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1995

The rapid emergence of bacterial resistance to antibiotics has necessitated the development of alternative treatment strategies. Antimicrobial peptides (AMPs) are important immune system components that kill microbes rapidly and have broad activity-spectra, making them promising leads for new pharmaceuticals. Although the need for novel antimicrobials is great, we also need a better understanding of the mechanisms underlying resistance development to enable design of more efficient drugs and reduce the rate of resistance development. The focus of this thesis has been to examine development of bacterial resistance to AMPs and the resulting effects on bacterial physiology. The major model organism used was Salmonella enterica variant Typhimurium LT2. In Paper I, we observed that bacteria resistant to PR-39 appeared at a high rate, and that the underlying sbmA resistance mutations were low cost or even cost-free. Such mutants are more likely to rapidly appear in a population and, most importantly, will not disappear easily once the selective pressure is removed. In paper II, we isolated protamine-resistant hem- and cydC-mutants that had reduced growth rates and were cross-resistant to several other antimicrobials. These mutants were small colony variants (SCVs), a phenotype often associated with persistent infections. One SCV with a hemC-mutation reverted to faster growth when evolved in the absence of protamine. In paper III, the mechanism behind this fitness compensation was determined, and was found to occur through hemC gene amplification and subsequent point mutations. The study provides a novel mechanism for reversion of the SCV-phenotype and further evidence that gene amplification is a common adaptive mechanism in bacteria. In Paper IV, the antibacterial properties of cyclotides, cyclic mini-proteins from plants, were evaluated. Cycloviolacin O2 from violets was found to be bactericidal against Gram-negative bacteria. Cyclotides are very stable molecules and may be potential starting points for development of peptide antibiotics.