Lattice-free models of cell invasion : discrete simulations and travelling waves

Invasion waves of cells play an important role in development, disease and repair. Standard discrete models of such processes typically involve simulating cell motility, cell proliferation and cell-to-cell crowding effects in a lattice-based framework. The continuum-limit description is often given by a reaction–diffusion equation that is related to the Fisher–Kolmogorov equation. One of the limitations of a standard lattice-based approach is that real cells move and proliferate in continuous space and are not restricted to a predefined lattice structure. We present a lattice-free model of cell motility and proliferation, with cell-to-cell crowding effects, and we use the model to replicate invasion wave-type behaviour. The continuum-limit description of the discrete model is a reaction–diffusion equation with a proliferation term that is different from lattice-based models. Comparing lattice based and lattice-free simulations indicates that both models lead to invasion fronts that are similar at the leading edge, where the cell density is low. Conversely, the two models make different predictions in the high density region of the domain, well behind the leading edge. We analyse the continuum-limit description of the lattice based and lattice-free models to show that both give rise to invasion wave type solutions that move with the same speed but have very different shapes. We explore the significance of these differences by calibrating the parameters in the standard Fisher–Kolmogorov equation using data from the lattice-free model. We conclude that estimating parameters using this kind of standard procedure can produce misleading results.

In vitro models for investigating keratinocyte responses to ultraviolet B radiation

This thesis describes the use of 2- and 3-dimensional cell-based models for studying how skin cells respond to ultraviolet radiation. These methods were used to investigate skin damage and repair after exposure to radiation in the context of skin cancer development. Interactions between different skin cell types were demonstrated as being significant in protecting against ultraviolet radiation-induced skin damage. This has important implications in understanding how skin cancers occur, as well as in the development of new strategies to prevent and treat them.

Improving business process models using observed behavior

Process-aware information systems (PAISs) can be configured using a reference process model, which is typically obtained via expert interviews. Over time, however, contextual factors and system requirements may cause the operational process to start deviating from this reference model. While a reference model should ideally be updated to remain aligned with such changes, this is a costly and often neglected activity. We present a new process mining technique that automatically improves the reference model on the basis of the observed behavior as recorded in the event logs of a PAIS. We discuss how to balance the four basic quality dimensions for process mining (fitness, precision, simplicity and generalization) and a new dimension, namely the structural similarity between the reference model and the discovered model. We demonstrate the applicability of this technique using a real-life scenario from a Dutch municipality.

Universal active and reactive power control of electronically interfaced distributed generation sources in virtual power plants operating in gridconnected and islanding modes

The control paradigms of the distributed generation (DG) sources in the smart grid are realised by either utilising virtual power plant (VPP) or by employing MicroGrid structures. Both VPP and MicroGrid are presented with the problem of control of power flow between their comprising DG sources. This study depicts this issue for VPP and proposes a novel and improved universal active and reactive power flow controllers for three-phase pulse width modulated voltage source inverters (PWM-VSI) operating in the VPP environment. The proposed controller takes into account all cases of R-X relationship, thus allowing it to function in systems operating at high, medium (MV) and low-voltage (LV) levels. Also proposed control scheme for the first time in an inverter control takes into account the capacitance of the transmission line which is an important factor to accurately represent medium length transmission lines. This allows the proposed control scheme to be applied in VPP structures, where DG sources can operate at MV LV levels over a short/medium length transmission line. The authors also conducted small signal stability analysis of the proposed controller and compared it against the small signal study of the existing controllers.

A retrospective cohort investigation of active range of motion within one week of open reduction and internal fixation of distal radius fractures

Distal radius fractures stabilized by open reduction internal fixation (ORIF) have become increasingly common. There is currently no consensus on the optimal time to commence range of motion (ROM) exercises post-ORIF. A retrospective cohort review was conducted over a five-year period to compare wrist and forearm range of motion outcomes and number of therapy sessions between patients who commenced active ROM exercises within the first seven days and from day eight onward following ORIF of distal radius fractures. One hundred and twenty-one patient cases were identified. Clinical data, active ROM at initial and discharge therapy assessments, fracture type, surgical approaches, and number of therapy sessions attended were recorded. One hundred and seven (88.4%) cases had complete datasets. The early active ROM group (n = 37) commenced ROM a mean (SD) of 4.27 (1.8) days post-ORIF. The comparator group (n = 70) commenced ROM exercises 24.3 (13.6) days post-ORIF. No significant differences were identified between groups in ROM at initial or discharge assessments, or therapy sessions attended. The results from this study indicate that patients who commenced active ROM exercises an average of 24 days after surgery achieved comparable ROM outcomes with similar number of therapy sessions to those who commenced ROM exercises within the first week.

Children and young people using public space : models of rights, optimism and wellbeing

This presentation discusses topics and issues that connect closely with the Conference Themes and themes in the ARACY Report Card. For example, developing models of public space that are safe, welcoming and relevant to children and young people will impact on their overall wellbeing and may help to prevent many of the tensions occurring in Australia and elsewhere around the world. This area is the subject of ongoing international debate, research and policy formation, relevant to concerns in the ARACY Report Card about children and young people’s health and safety, participation, behaviours and risks and peer and family relationships.

Sampling stored-product insect pests : a comparison of four statistical sampling models for probability of pest detection

Background: Developing sampling strategies to target biological pests such as insects in stored grain is inherently difficult owing to species biology and behavioural characteristics. The design of robust sampling programmes should be based on an underlying statistical distribution that is sufficiently flexible to capture variations in the spatial distribution of the target species. Results: Comparisons are made of the accuracy of four probability-of-detection sampling models - the negative binomial model,1 the Poisson model,1 the double logarithmic model2 and the compound model3 - for detection of insects over a broad range of insect densities. Although the double log and negative binomial models performed well under specific conditions, it is shown that, of the four models examined, the compound model performed the best over a broad range of insect spatial distributions and densities. In particular, this model predicted well the number of samples required when insect density was high and clumped within experimental storages. Conclusions: This paper reinforces the need for effective sampling programs designed to detect insects over a broad range of spatial distributions. The compound model is robust over a broad range of insect densities and leads to substantial improvement in detection probabilities within highly variable systems such as grain storage.

A systematic review of mathematical models of mosquito-borne pathogen transmission: 1970-2010

Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.

Accurate pattern prediction of very closely spaced mismatched antennas using measured active element patterns

A method for prediction of the radiation pattern of N strongly coupled antennas with mismatched sources is presented. The method facilitates fast and accurate design of compact arrays. The prediction is based on the measured N-port S parameters of the coupled antennas and the N active element patterns measured in a 50 ω environment. By introducing equivalent power sources, the radiation pattern with excitation by sources with arbitrary impedances and various decoupling and matching networks (DMN) can be accurately predicted without the need for additional measurements. Two experiments were carried out for verification: pattern prediction for parasitic antennas with different loads and for antennas with DMN. The difference between measured and predicted patterns was within 1 to 2 dB.

Scene invariant multi camera crowd counting

Automated crowd counting has become an active field of computer vision research in recent years. Existing approaches are scene-specific, as they are designed to operate in the single camera viewpoint that was used to train the system. Real world camera networks often span multiple viewpoints within a facility, including many regions of overlap. This paper proposes a novel scene invariant crowd counting algorithm that is designed to operate across multiple cameras. The approach uses camera calibration to normalise features between viewpoints and to compensate for regions of overlap. This compensation is performed by constructing an 'overlap map' which provides a measure of how much an object at one location is visible within other viewpoints. An investigation into the suitability of various feature types and regression models for scene invariant crowd counting is also conducted. The features investigated include object size, shape, edges and keypoints. The regression models evaluated include neural networks, K-nearest neighbours, linear and Gaussian process regresion. Our experiments demonstrate that accurate crowd counting was achieved across seven benchmark datasets, with optimal performance observed when all features were used and when Gaussian process regression was used. The combination of scene invariance and multi camera crowd counting is evaluated by training the system on footage obtained from the QUT camera network and testing it on three cameras from the PETS 2009 database. Highly accurate crowd counting was observed with a mean relative error of less than 10%. Our approach enables a pre-trained system to be deployed on a new environment without any additional training, bringing the field one step closer toward a 'plug and play' system.

Modeling the co-precipitation of silica and calcium oxalate in sugar solutions

Solution chemistry plays a significant role in the rate and type of foulant formed on heated industrial surfaces. This paper describes the effect of sucrose, silica (SiO2), Ca2+ and Mg2+ ions, and trans-aconitic acid on the kinetics and solubility of SiO2 and calcium oxalate monohydrate (COM) in mixed salt solutions containing sucrose and refines models previously proposed. The developed SiO2 models show that sucrose and SiO2 concentrations are the main parameters that determine apparent order (n) and apparent rate of reaction (k) and SiO2 solubility over a 24 h period. The calcium oxalate solubility model shows that while increasing [Mg2+] increases COM solubility, the reverse is so with increasing sucrose concentrations. The role of solution species on COM crystal habit is discussed and the appearance of the uncommon (001) face is explained.

Designing innovative business models: Five emerging meta-models

Business models to date have remained the creation of management, however, it is the belief of the authors that designers should be critically approaching, challenging and creating new business models as part of their practice. This belief portrays a new era where business model constructs become the new design brief of the future and fuel design and innovation to work together at the strategic level of an organisation. Innovation can no longer rely on technology and R&D alone but must incorporate business models. Business model innovation has become a strong type of competitive advantage. As firms choose not to compete only on price, but through the delivery of a unique value proposition in order to engage with customers and to differentiate a company within a competitive market. The purpose of this paper is to explore and investigate business model design through various product and/or service deliveries, and identify common drivers that are catalysts for business model innovation. Fifty companies spanning a diverse range of criteria were chosen, to evaluate and compare commonalities and differences in the design of their business models. The analysis of these business cases uncovered commonalities of the key strategic drivers behind these innovative business models. Five Meta Models were derived from this content analysis: Customer Led, Cost Driven, Resource Led, Partnership Led and Price Led. These five key foci provide a designer with a focus from which quick prototypes of new business models are created. Implications from this research suggest there is no ‘one right’ model, but rather through experimentation, the generation of many unique and diverse concepts can result in greater possibilities for future innovation and sustained competitive advantage.

The function and mechanisms of action of ghrelin and obestatin in ovarian cancer

In this study, we have demonstrated that the preproghrelin derived hormones, ghrelin and obestatin, may play a role in ovarian cancer. Ghrelin and obestatin stimulated an increase in cell migration in ovarian cancer cell lines and may play a role in cancer progression. Ovarian cancer is the leading cause of death among gynaecological cancers and is the sixth most common cause of cancer-related deaths in women in developed countries. As ovarian cancer is difficult to diagnose at a low tumour grade, two thirds of ovarian cancers are not diagnosed until the late stages of cancer development resulting in a poor prognosis for the patient. As a result, current treatment methods are limited and not ideal. There is an urgent need for improved diagnostic markers, as well better therapeutic approaches and adjunctive therapies for this disease. Ghrelin has a number of important physiological effects, including roles in appetite regulation and the stimulation of growth hormone release. It is also involved in regulating the immune, cardiovascular and reproductive systems and regulates sleep, memory and anxiety, and energy metabolism. Over the last decade, the ghrelin axis, (which includes the hormones ghrelin and obestatin and their receptors), has been implicated in the pathogenesis of many human diseases and it may t may also play an important role in the development of cancer. Ghrelin is a 28 amino acid peptide hormone that exists in two forms. Acyl ghrelin (usually referred to as ghrelin), has a unique n-octanoic acid post-translational modification (which is catalysed by ghrelin O-acyltransferase, GOAT), and desacyl ghrelin, which is a non-octanoylated form. Octanoylated ghrelin acts through the growth hormone secretagogue receptor type 1a (GHSR1a). GHSR1b, an alternatively spliced isoform of GHSR, is C-terminally truncated and does not bind ghrelin. Ghrelin has been implicated in the pathophysiology of a number of diseases Obestatin is a 23 amino acid, C-terminally amidated peptide which is derived from preproghrelin. Although GPR39 was originally thought to be the obestatin receptor this has been disproven, and its receptor remains unknown. Obestatin may have as diverse range of roles as ghrelin. Obestatin improves memory, inhibits thirst and anxiety, increases pancreatic juice secretion and has cardioprotective effects. Obestatin also has been shown to regulate cell proliferation, differentiation and apoptosis in some cell types. Prior to this study, little was known regarding the functions and mechanisms of action ghrelin and obestatin in ovarian cancer. In this study it was demonstrated that the full length ghrelin, GHSR1b and GOAT mRNA transcripts were expressed in all of the ovarian-derived cell lines examined (SKOV3, OV-MZ-6 and hOSE 17.1), however, these cell lines did not express GHSR1a. Ovarian cancer tissue of varying stages and normal ovarian tissue expressed the coding region for ghrelin, obestatin, and GOAT, but not GHSR1a, or GHSR1b. No correlations between cancer grade and the level of expression of these transcripts were observed. This study demonstrated for the first time that both ghrelin and obestatin increase cell migration in ovarian cancer cell lines. Treatment with ghrelin (for 72 hours) significantly increased cell migration in the SKOV3 and OV-MZ-6 ovarian cancer cell lines. Ghrelin (100 nM) stimulated cell migration in the SKOV3 (2.64 +/- 1.08 fold, p <0.05) and OV-MZ-6 (1.65 +/- 0.31 fold, p <0.05) ovarian cancer cell lines, but not in the representative normal cell line hOSE 17.1. This increase in migration was not accompanied by an increase in cell invasion through Matrigel. In contrast to other cancer types, ghrelin had no effect on proliferation. Ghrelin treatment (10nM) significantly decreased attachment of the SKOV3 ovarian cancer cell line to collagen IV (24.7 +/- 10.0 %, p <0.05), however, there were no changes in attachment to the other extracellular matrix molecules (ECM) tested (fibronectin, vitronectin and collagen I), and there were no changes in attachment to any of the ECM molecules in the OV-MZ-6 or hOSE 17.1 cell lines. It is, therefore, unclear if ghrelin plays a role in cell attachment in ovarian cancer. As ghrelin has previously been demonstrated to signal through the ERK1/2 pathway in cancer, we investigated ERK1/2 signalling in ovarian cancer cell lines. In the SKOV3 ovarian cancer cell line, a reduction in ERK1/2 phosphorylation (0.58 fold +/- 0.23, p <0.05) in response to 100 nM ghrelin treatment was observed, while no significant change in ERK1/2 signalling was seen in the OV-MZ-6 cell line with treatment. This suggests that this pathway is unlikely to be involved in mediating the increased migration seen in the ovarian cancer cell lines with ghrelin treatment. In this study ovarian cancer tissue of varying stages and normal ovarian tissue expressed the coding region for obestatin, however, no correlation between cancer grade and level of obestatin transcript expression was observed. In the ovarian-derived cell lines studied (SKOV3, OV-MZ-6 and hOSE 17.1) it was demonstrated that the full length preproghrelin mRNA transcripts were expressed in all cell lines, suggesting they have the ability to produce mature obestatin. This is the first study to demonstrate that obestatin stimulates cell migration and cell invasion. Obestatin induced a significant increase in migration in the SKOV3 ovarian cancer cell line with 10 nM (2.80 +/- 0.52 fold, p <0.05) and 100 nM treatments (3.12 +/- 0.68 fold, p <0.05) and in the OV-MZ-6 cancer cell line with 10 nM (2.04 +/- 0.10 fold, p <0.01) and 100 nM treatments (2.00 +/- 0.37 fold, p <0.05). Obestatin treatment did no affect cell migration in the hOSE 17.1normal ovarian epithelial cell line. Obestatin treatment (100 nM) also stimulated a significant increase in cell invasion in the OV-MZ-6 ovarian cancer cell line (1.45 fold +/- 0.13, p <0.05) and in the hOSE17.1 normal ovarian cell line cells (1.40 fold +/- 0.04 and 1.55 fold +/- 0.05 respectively, p <0.01) with 10 nM and 100 nM treatments. Obestatin treatment did not stimulate cell invasion in the SKOV3 ovarian cancer cell line. This lack of obestatin-stimulated invasion in the SKOV3 cell line may be a cell line specific result. In this study, obestatin did not stimulate cell proliferation in the ovarian cell lines and it has previously been shown to have no effect on cell proliferation in the BON-1 pancreatic neuroendocrine and GC rat somatotroph tumour cell lines. In contrast, obestatin has been shown to affect cell proliferation in gastric and thyroid cancer cell lines, and in some normal cell lines. Obestatin also had no effect on attachment of any of the cell lines to any of the ECM components tested (fibronectin, vitronectin, collagen I and collagen IV). The mechanism of action of obestatin was investigated further using a two dimensional-difference in gel electrophoresis (2D-DIGE) proteomic approach. After treatment with obestating (0, 10 and 100 nM), SKOV3 ovarian cancer and hOSE 17.1 normal ovarian cell lines were collected and 2D-DIGE analysis and mass spectrometry were performed to identify proteins that were differentially expressed in response to treatment. Twenty-six differentially expressed proteins were identified and analysed using Ingenuity Pathway Analysis (IPA). This linked 16 of these proteins in a network. The analysis suggested that the ERK1/2 MAPK pathway was a major mediator of obestatin action. ERK1/2 has previously been shown to be associated with obestatin-stimulated cell proliferation and with the anti-apoptotic effects of obestatin. Activation of the ERK1/2 signalling pathway by obestatin was, therefore, investigated in the SKOV3 and OV-MZ-6 ovarian cancer cell lines using anti-active antibodies and Western immunoblots. Obestatin treatment significantly decreased ERK1/2 phosphorylation at higher obestatin concentrations in both the SKOV3 (100 nM and 1000 nM) and OV-MZ-6 (1000 nM) cell lines compared to the untreated controls. Currently, very little is known about obestatin signalling in cancer. This thesis has demonstrated for the first time that the ghrelin axis may play a role in ovarian cancer migration. Ghrelin and obestatin increased cell migration in ovarian cancer cell lines, indicating that they may be a useful target for therapies that reduce ovarian cancer progression. Further studies investigating the role of the ghrelin axis using in vivo ovarian cancer metastasis models are warranted.

Exploring new and emerging models for nonlinear performative works

This dissertation seeks to define and classify potential forms of Nonlinear structure and explore the possibilities they afford for the creation of new musical works. It provides the first comprehensive framework for the discussion of Nonlinear structure in musical works and provides a detailed overview of the rise of nonlinearity in music during the 20th century. Nonlinear events are shown to emerge through significant parametrical discontinuity at the boundaries between regions of relatively strong internal cohesion. The dissertation situates Nonlinear structures in relation to linear structures and unstructured sonic phenomena and provides a means of evaluating Nonlinearity in a musical structure through the consideration of the degree to which the structure is integrated, contingent, compressible and determinate as a whole. It is proposed that Nonlinearity can be classified as a three dimensional space described by three continuums: the temporal continuum, encompassing sequential and multilinear forms of organization, the narrative continuum encompassing processual, game structure and developmental narrative forms and the referential continuum encompassing stylistic allusion, adaptation and quotation. The use of spectrograms of recorded musical works is proposed as a means of evaluating Nonlinearity in a musical work through the visual representation of parametrical divergence in pitch, duration, timbre and dynamic over time. Spectral and structural analysis of repertoire works is undertaken as part of an exploration of musical nonlinearity and the compositional and performative features that characterize it. The contribution of cultural, ideological, scientific and technological shifts to the emergence of Nonlinearity in music is discussed and a range of compositional factors that contributed to the emergence of musical Nonlinearity is examined. The evolution of notational innovations from the mobile score to the screen score is plotted and a novel framework for the discussion of these forms of musical transmission is proposed. A computer coordinated performative model is discussed, in which a computer synchronises screening of notational information, provides temporal coordination of the performers through click-tracks or similar methods and synchronises the audio processing and synthesized elements of the work. It is proposed that such a model constitutes a highly effective means of realizing complex Nonlinear structures. A creative folio comprising 29 original works that explore nonlinearity is presented, discussed and categorised utilising the proposed classifications. Spectrograms of these works are employed where appropriate to illustrate the instantiation of parametrically divergent substructures and examples of structural openness through multiple versioning.

Applications and equivalent models for coupled inductor parallel interleaved converters

Parallel interleaved converters are finding more applications everyday, for example they are frequently used for VRMs on PC main boards mainly to obtain better transient response. Parallel interleaved converters can have their inductances uncoupled, directly coupled or inversely coupled, all of which have different applications with associated advantages and disadvantages. Coupled systems offer more control over converter features, such as ripple currents, inductance volume and transient response. To be able to gain an intuitive understanding of which type of parallel interleaved converter, what amount of coupling, what number of levels and how much inductance should be used for different applications a simple equivalent model is needed. As all phases of an interleaved converter are supposed to be identical, the equivalent model is nothing more than a separate inductance which is common to all phases. Without utilising this simplification the design of a coupled system is quite daunting. Being able to design a coupled system involves solving and understanding the RMS currents of the input, individual phase (or cell) and output. A procedure using this equivalent model and a small amount of modulo arithmetic is detailed.