Theory has been used to complement experiment in the development of both drugs and delivery systems. Theoretical methods are capable of identifying the molecular basis of drug formulation inadequacies and systematic theoretical studies may suggest fruitful avenues for material modification. This thesis highlights the utility of computer-based theoretical calculations for guiding the design of drug formulations and enhancing material-drug compatibility and stability. Specifically, the present work explores the applications of semi-empirical methods and atomistic molecular dynamics (MD) simulations to enhance the performance of nano-emulsions and polymer micelle formulations for the delivery of hydrophobic drugs. This work includes three separate studies preceded by an introductory summary of available theoretical techniques. The first study evaluates the accuracy and reliability of semi-empirical methods and MD simulations as means to select suitable excipients to formulate the anti-cancer drug docetaxel in an emulsion. Here, simulations accurately predict the rank order of drug solubility in various excipients, suggesting that simulation is useful for library enrichment. In the second study, a drug conjugation approach is used to further improve the stability and solubility of docetaxel in a triglyceride-based nano-emulsion. Here, optimal conjugates are identified with computer-based theoretical calculations and conjugates with formulation-compatible moieties are synthesized. As predicted, the conjugates exhibit enhanced solubility and loading efficiency in a nano-emulsion. The goal of the third study is to rationally design a stable unimolecular star copolymer that, as a unimer, does not disassemble upon the dilution that accompanies intravenous injection. Here, MD simulation is used to systematically investigate the solution properties of differently composed star copolymers. Overall, star copolymers with a hydrophobic PCL core ≤ 2 kDa and hydrophilic PEG blocks approaching 14.6 kDa per arm are predicted to form unimolecular micelles that remain unimeric at high concentrations. The studies presented in this thesis demonstrate that theoretical approaches are useful for fast pre-screening of drug formulation materials and for the development of delivery systems and drug derivatives.

Dans cette thèse nous étudions le phénomène d'effondrement de différents modèles d'homopolymères. Nous étudions une marche aléatoire partiellement dirigée en dimension 1+1, auto-évitante et en auto-interaction, connue sous l'acronyme anglais IPDSAW. Il est établi que le modèle IPDSAW a une transition de phase d'effondrement en un paramètre critique $\beta_c$. Pour étudier la fonction de partition de ce modèle, nous développons une nouvelle méthode qui nous permet d'en déduire une formule variationnelle pour son énergie libre. Cette formule variationnelle peut être utilisée pour prouver l'existence de la transition d'effondrement et pour identifier simplement le point critique. Nous donnons une asymptotique précise de l'énergie libre au voisinage du point critique. Ensuite, nous établissons plusieurs propriétés trajectorielles de notre marche aléatoire à l'intérieur de la phase effondrée ($\beta>\beta_c$). Finalement, nous étudions le modèle IPDSAW soumis à une force extérieure. Nous montrons comment détecter la présence d'un phénomène de ré-entrance sans toutefois résoudre intégralement le modèle.

Theory has been used to complement experiment in the development of both drugs and delivery systems. Theoretical methods are capable of identifying the molecular basis of drug formulation inadequacies and systematic theoretical studies may suggest fruitful avenues for material modification. This thesis highlights the utility of computer-based theoretical calculations for guiding the design of drug formulations and enhancing material-drug compatibility and stability. Specifically, the present work explores the applications of semi-empirical methods and atomistic molecular dynamics (MD) simulations to enhance the performance of nano-emulsions and polymer micelle formulations for the delivery of hydrophobic drugs. This work includes three separate studies preceded by an introductory summary of available theoretical techniques. The first study evaluates the accuracy and reliability of semi-empirical methods and MD simulations as means to select suitable excipients to formulate the anti-cancer drug docetaxel in an emulsion. Here, simulations accurately predict the rank order of drug solubility in various excipients, suggesting that simulation is useful for library enrichment. In the second study, a drug conjugation approach is used to further improve the stability and solubility of docetaxel in a triglyceride-based nano-emulsion. Here, optimal conjugates are identified with computer-based theoretical calculations and conjugates with formulation-compatible moieties are synthesized. As predicted, the conjugates exhibit enhanced solubility and loading efficiency in a nano-emulsion. The goal of the third study is to rationally design a stable unimolecular star copolymer that, as a unimer, does not disassemble upon the dilution that accompanies intravenous injection. Here, MD simulation is used to systematically investigate the solution properties of differently composed star copolymers. Overall, star copolymers with a hydrophobic PCL core ≤ 2 kDa and hydrophilic PEG blocks approaching 14.6 kDa per arm are predicted to form unimolecular micelles that remain unimeric at high concentrations. The studies presented in this thesis demonstrate that theoretical approaches are useful for fast pre-screening of drug formulation materials and for the development of delivery systems and drug derivatives.

In our experience of teaching Calculus to engineering undergraduates we have had to grapple with many different problems. A major hurdle has been students’ inability to appreciate the importance of the theory. In their view the theoretical part of mathematics is separate from the computing part. In general, students also believe that they can pass their exams even though they do not have a real understanding of the theory behind the problems they are required to solve. In an effort to surmount these difficulties we tried to find ways to make students better understand the theoretical part of Calculus. This paper describes our experience of teaching Calculus. It reports on the continuation of our previous research.

This study presents a new approach for nonlinear multi-scale constitutive models using artificial neural networks (ANNs). Three ANN classes are proposed to characterize the nonlinear multi-axial stress-strain behavior of metallic, polymeric, and fiber reinforced polymeric (FRP) materials, respectively. Load-displacement responses from nanoindentation of metallic and polymeric materials are used to train new generation of dimensionless ANN models with different micro-structural properties as additional variables to the load-deflection. The proposed ANN models are effective in inverse-problems set to back-calculate in-situ material parameters from given overall nanoindentation test data with/without time-dependent material behavior. Towards that goal, nanoindentation tests have been performed for silicon (Si) substrate with/without a copper (Cu) film. Nanoindentation creep test data, available in the literature for Polycarbonate substrate, are used in these inverse problems. The predicted properties from the ANN models can also be used to calibrate classical constitutive parameters. The third class of ANN models is used to generate the effective multi-axial stress-strain behavior of FRP composites under plane-stress conditions. The training data are obtained from coupon tests performed in this study using off-axis tension/compression and pure shear tests for pultruded FRP E-glass/polyester composite systems. It is shown that the trained nonlinear ANN model can be directly coupled with finite-element (FE) formulation as a material model at the Gaussian integration points of each layered-shell element. This FE-ANN modeling approach is applied to simulate an FRP plate with an open-hole and compared with experimental results. Micromechanical nonlinear ANN models with damage formulation are also formulated and trained using simulated FE modeling of the periodic microstructure. These new multi-scale ANN constitutive models are effective and can be extended by including more material variables to capture complex material behavior, such as softening due to micro-structural damage or failure.

In this work, the mathematical implications of merging two different turbulence modeling approaches are addressed by deriving the exact hybrid RANS/LES Navier-Stokes equations. These equations are derived by introducing an additive-filter, which linearly combines the RANS and LES operators with a blending function. The equations derived predict additional hybrid terms, which represent the interactions between RANS and LES formulations. Theoretically, the prediction of the hybrid terms demonstrates that the hybridization of the two approaches cannot be accomplished only by the turbulence model equations, as it is claimed in current hybrid RANS/LES models. The importance of the exact hybrid RANS/LES equations is demonstrated by conducting numerical calculations on a turbulent flat-plate boundary layer. Results indicate that the hybrid terms help to maintain an equilibrated model transition when the hybrid formulation switches from RANS to LES. Results also indicate, that when the hybrid terms are not included, the accuracy of the calculations strongly relies on the blending function implemented in the additive-filter. On the other hand, if the exact equations are resolved, results are only weakly affected by the characteristics of the blending function. Unfortunately, for practical applications the hybrid terms cannot be exactly computed. Consequently, a reconstruction procedure is proposed to approximate these terms. Results show, that the model proposed is able to mimic the exact hybrid terms, enhancing the accuracy of current hybrid RANS/LES approaches. In a second effort, the Two Level Simulation (TLS) approach is proposed as a near-wall model for LES. Here, TLS is first extended to compressible flows by deriving the small-scale equations required by the model. The full compressible TLS formulation and the hybrid TLS/LES approach is validated simulating the flow over a flat-plate turbulent boundary layer. Overall, results are found in reasonable agreement with experimental data and LES calculations.

By asking “What’s the problem?” this thesis addresses the crucial relationship between how strategic decision-makers formulate organizational problems and how the relevant actors attempt to solve these problems. This thesis holds that the creation of strategy can be conceived of as a decision-making process in which the strategists find, formulate and attempt to solve problems by choosing a set of means to reduce the perceived gap between the current state and the desired state of the organization. The thesis particularly explores and postulates what is refered to as the means-end fallacy in which end-problems are treated as means-problems. In effect the decision-makers take the ends of the organization for granted and only ask “How can we fix it?” instead of critically examining the purpose of the organization by asking “What should we fix and why?” The purpose of this thesis is twofold. First, it is to explore the dysfunctional consequences of the means-end fallacy in organizational decision-making and creation of strategy. Secondly, it is to illuminate the implications of applying the problem-formulation perspective in the creation of organizational strategies. To achieve these purposes the problem-formulation phenomenon is explored in five appended papers. Paper I discusses the paradox of profitability and responsibility and the means-end fallacy in the context of strategic theory and practice. Papers II, III and IV explore the relationship between how a problem is formulated and how different actors attempt to solve it. This is done with a comprehensive case study of the substance-abuse problem and the different organizational strategies that are implemented to resolve it. Paper V offers a concrete discussion of how inappropriate formulations of organizational problems undermine the intended ends, particularly with regard to the paradox of profitability and responsibility. This thesis argues that the strategic decision-makers need both to be more problem-oriented; that they should balance the different dimensions of the problem; and, thus, that they should recognize that decision-making is an art of balance. Moreover, it suggests that the problem-formulation perspective can contribute with an insight into the black box of strategy creation, and that this can be achieved by looking back or rewinding from the organization’s strategy to the initial formulation of the organization’s problems. As a mirror image it suggests that strategic decision-makers can avoid the means-end fallacy by forwarding from an appropriate formulation of the problem to a balanced strategy.

Informed economic decisions are made on the basis of accounting data. It is therefore crucial to have rigorous and scientific approaches for measuring, modelling and forecasting accounting numbers. Dr Falta's research was motivated by two observations. Firstly, in accounting practice, decision-making often relies on subjective quantifications and forecasts of business activities and, thus, does not account for uncertainty in a rational way. Secondly, there are some academic foundations for statistical approaches to accounting, yet none has been developed carefully enough for results to penetrate and to contribute to practitioners' needs. Dr Falta applied components of mathematics, statistics, econometrics, finance and computing to aspects of accounting and auditing. He developed an enhanced framework for scientific measurement of business process costing and recording accounting transaction data. This has enabled a better understanding of risk in accounting-based decision-making. His research is being incorporated in projects with the Royal Australian Navy and SunWater.

Rural and remote areas of Australia remain the last bastion of health disadvantage in a developed nation with an enviable health score-card. During the last ten years, rural and remote health has emerged as a significant issue in the media and the political arena. This thesis examines print media, policy documents and interviews from selected informants to ascertain how they represent medical practitioners and health services in rural and remote areas of Australia, why they do so, and the consequences of such positions. In many of these representations, rural and remote medical practitioners are aligned with national and cultural mythologies, while health services are characterised as dysfunctional and at crisis point. Ostensibly, the representations and identity formulations are aimed at redressing the health inequities in remote rural and Australia. They define and elaborate debates and contestations about needs and claims and how they should be addressed; a process that is crucial in the development of professional identity and power (Fraser; 1989). The research involves an analysis and critical reading of the entwined discourses of culture, power, and the politics of need. Following Wodak and others (1999), these dynamics are explored by examining documents that are part of the discursive constitution of the field. In particular, the research examines how prevailing cultural concepts are used to configure the Australian rural and remote medical practitioner in ways that reflect and advance socio-cultural hegemony. The conceptual tools used to explore these dynamics are drawn from critical and post-structural theory, and draw upon the work of Nancy Fraser (1989; 1997) and Ruth Wodak (1999). Both theorists developed approaches that enable investigation into the effects of language use in order to understand how the cultural framing of particular work can influence power relations in a professional field. The research follows a cultural studies approach, focussing on texts as objects of research and acknowledging the importance of discourse in the development of cultural meaning (Nightingale, 1993). The methodological approach employs Critical Discourse Analysis, specifically the Discourse Historical Method (Wodak, 1999). It is used to explore the linguistic hallmarks of social and cultural processes and structures, and to identify the ways in which political control and dominance are advanced through language-based strategies. An analytical tool developed by Ruth Wodak, Rudolf de Cillia, Martin Reisigl and Karin Leibhart (1999) was adapted and used to identify nationalistic identity formulations and related linguistic manoeuvres in the texts. The dissertation argues that the textual linguistic manoeuvres and identity formulations produce and privilege a particular identity for rural and remote medical practitioners, and that cultural myth is used to popularise, shore up and advance the goals of rural doctors during a period of crisis and change. Important in this process is the differentiation of rural and remote medicine from other disciplines in order to define and advance its political needs and claims (Fraser, 1989). This activity has unexpected legacies for the rural and remote health sector. In developing a strong identity for rural doctors, discursive rules have been established by the discipline regarding roles, personal and professional characteristics, and practice style; rules which hold confounding factors for the sustainability of remote and rural medical practice and health care generally. These factors include: the professional fragmentation of the discipline of primary medical care into general practice and rural medicine; and identity formulations that do not accommodate an ageing workforce characterised by cultural diversity, decreasing engagement in full time work, and a higher proportion of women participants. Both of these factors have repercussions for the recruitment and retention of rural and remote health professionals and the maintenance of a sustainable health workforce. The dissertation argues that the formulated identities of rural and remote medical practitioners in the texts maintain and reproduce relationships of cultural, political and social power. They have also influenced the ways in which rural and remote health services have been developed and funded. They selectively represent and value particular roles and approaches to health care. In doing so, they misrepresent the breadth and complexities of rural and remote health issues, and reinforce a reputational economy built on differential professional and cultural respect, and political and economic advantage. This disadvantages the community, professions and interest groups of lower value and esteem, and other groups whose voices are often not heard. Thus, regardless of their altruistic motivations, the politics of identity and differentiation employed in the formulated identities in the texts are based on an approach that undermines the redistributive goals of justice and equity (Fraser 1997), and works primarily to develop and advantage the discipline of rural medicine.

Young children’s peer interactions involve their use of interactional resources to organise, manage and participate in their social worlds. Investigation of children’s employment of interactional resources highlights how children participate in peer interaction and their social orders, providing insight into their active construction and management of their social worlds. Frequently, these interactions are described by adults as ‘play’. The term play is often used to describe children’s activities in early childhood education, and constructed in three main ways: as educative, as enjoyable, and as an activity of children. Play in educational settings is often constructed, and informed by, adult agendas such as learning and is often part of the educational routine. This study shows how children work with a different set of agendas to those routinely ascribed by adults, as they actively engage with local education orders, and use play for their own purposes as they construct their own social orders. By examining children’s peer interactions, and not describing these activities as play, the focus becomes the construction and organisation of their social worlds. In so doing, this study investigates some interactional resources that children draw upon to manage their social orders and organise their peer interactions. This study was conducted within an Australian, non-government elementary school. The participants were children in a preparatory year classroom (children aged 4 – 6 years). Over a one month period, children’s naturally occurring peer interactions within ‘free play’ were video-recorded. Selected video-recorded episodes were transcribed and analysed, using the approaches of ethnomethodology, conversation analysis and membership categorization analysis. These methodologies focus on everyday, naturalistic data, examining how participants orient to and produce social action. The focus is on the members’ perspectives, that of the children themselves, as they interact. Ethnomethodology, conversation analysis and membership categorization analysis allow for in-depth examination of talk and action, and are used in this study to provide a detailed account of the children’s interactional strategies. Analysis focused on features of children’s situated peer interaction, identifying three interactional resources upon which the children drew as they constructed, maintained, and transformed their social orders. The interactional resources included: justification; category work, in particular the category of mother; and the pretend formulation of place. The children used these interactional resources as a means of managing peer participation within interactions. First, the children used justification to provide reasons for their actions and to support their positions. Justifications built and reinforced individual children’s status, contributing to the social organisation of their peer group. Second, the children negotiated and oriented to categories within the pretend frame of ‘families’. The children’s talk and actions jointly-constructed the mother category as authoritative, enabling the child, within the category of mother, to effectively organise the interaction. Third, pretense was used by the children to negotiate and describe places, thus enabling them to effectively manage peer activity within these places. For a successful formulation of a place as something other than it actually was, the children had to work to produce shared understandings of the place. Examining instances of pretense demonstrated the highly collaborative nature of the children’s peer interactions. The study contributes to sociological understandings of childhood. By analysing situated episodes of children’s peer interaction, this study contributes empirical work to the sociology of childhood and insight into the interactional work of children organising their social worlds. It does this by closely analysing social interactions, as they unfold, among children. This study also makes a methodological contribution, using ethnomethodology, conversation analysis, and membership categorization analysis in conjunction to analyse children’s peer interactions in an early childhood setting. In so doing, the study provides alternative ways for educators to understand children’s interactions. For example, adult educational agendas, such as the educative value of play, can be applied to examine children’s family play, highlighting the learning opportunities provided through pretend role play, or indicating children’s understanding of adult roles. Alternatively, the children’s interaction could be subjected to fine-grained analysis to explicate how children construct shared understandings of the category of mother and use it to organise their interaction. Rather than examining the interaction to discern what children are learning, the interaction is examined with a focus on how children are accomplishing everyday social practices. Close analysis of children’s everyday peer interaction enables the complex interactional work of managing, and participating in, social order within an early childhood setting to be explicated. This offers educators insight into children’s social worlds, described not as play, but as the construction and negotiation of social order.