Cell migration and proliferation on homogeneous and non-homogeneous domains : modelling on the scale of individuals and populations

Cell migration is a behaviour critical to many key biological effects, including wound healing, cancerous cell invasion and morphogenesis, the development of an organism from an embryo. However, given that each of these situations is distinctly different and cells are extremely complicated biological objects, interest lies in more basic experiments which seek to remove conflating factors and present a less complex environment within which cell migration can be experimentally examined. These include in vitro studies like the scratch assay or circle migration assay, and ex vivo studies like the colonisation of the hindgut by neural crest cells. The reduced complexity of these experiments also makes them much more enticing as problems to mathematically model, like done here. The primary goal of the mathematical models used in this thesis is to shed light on which cellular behaviours work to generate the travelling waves of invasion observed in these experiments, and to explore how variations in these behaviours can potentially predict differences in this invasive pattern which are experimentally observed when cell types or chemical environment are changed. Relevant literature has already identified the difficulty of distinguishing between these behaviours when using traditional mathematical biology techniques operating on a macroscopic scale, and so here a sophisticated individual-cell-level model, an extension of the Cellular Potts Model (CPM), is been constructed and used to model a scratch assay experiment. This model includes a novel mechanism for dealing with cell proliferations that allowed for the differing properties of quiescent and proliferative cells to be implemented into their behaviour. This model is considered both for its predictive power and used to make comparisons with the travelling waves which result in more traditional macroscopic simulations. These comparisons demonstrate a surprising amount of agreement between the two modelling frameworks, and suggest further novel modifications to the CPM that would allow it to better model cell migration. Considerations of the model’s behaviour are used to argue that the dominant effect governing cell migration (random motility or signal-driven taxis) likely depends on the sort of invasion demonstrated by cells, as easily seen by microscopic photography. Additionally, a scratch assay simulated on a non-homogeneous domain consisting of a ’fast’ and ’slow’ region is also used to further differentiate between these different potential cell motility behaviours. A heterogeneous domain is a novel situation which has not been considered mathematically in this context, nor has it been constructed experimentally to the best of the candidate’s knowledge. Thus this problem serves as a thought experiment used to test the conclusions arising from the simulations on homogeneous domains, and to suggest what might be observed should this non-homogeneous assay situation be experimentally realised. Non-intuitive cell invasion patterns are predicted for diffusely-invading cells which respond to a cell-consumed signal or nutrient, contrasted with rather expected behaviour in the case of random-motility-driven invasion. The potential experimental observation of these behaviours is demonstrated by the individual-cell-level model used in this thesis, which does agree with the PDE model in predicting these unexpected invasion patterns. In the interest of examining such a case of a non-homogeneous domain experimentally, some brief suggestion is made as to how this could be achieved.

Fractional models for the migration of biological cells in complex spatial domains

Travelling wave phenomena are observed in many biological applications. Mathematical theory of standard reaction-diffusion problems shows that simple partial differential equations exhibit travelling wave solutions with constant wavespeed and such models are used to describe, for example, waves of chemical concentrations, electrical signals, cell migration, waves of epidemics and population dynamics. However, as in the study of cell motion in complex spatial geometries, experimental data are often not consistent with constant wavespeed. Non-local spatial models have successfully been used to model anomalous diffusion and spatial heterogeneity in different physical contexts. In this paper, we develop a fractional model based on the Fisher-Kolmogoroff equation and analyse it for its wavespeed properties, attempting to relate the numerical results obtained from our simulations to experimental data describing enteric neural crest-derived cells migrating along the intact gut of mouse embryos. The model proposed essentially combines fractional and standard diffusion in different regions of the spatial domain and qualitatively reproduces the behaviour of neural crest-derived cells observed in the caecum and the hindgut of mouse embryos during in vivo experiments.

Overview of the NTCIR-10 cross-lingual link discovery task

This paper presents an overview of NTCIR-10 Cross-lingual Link Discovery (CrossLink-2) task. For the task, we continued using the evaluation framework developed for the NTCIR-9 CrossLink-1 task. Overall, recommended links were evaluated at two levels (file-to-file and anchor-to-file); and system performance was evaluated with metrics: LMAP, R-Prec and P@N.

NTCIR-10 crosslink-2 task : a link mining strategy

At NTCIR-10 we participated in the cross-lingual link discovery (CrossLink-2) task. In this paper we describe our systems for discovering cross-lingual links between the Chinese, Japanese, and Korean (CJK) Wikipedia and the English Wikipedia. The evaluation results show that our implementation of the cross-lingual linking method achieved promising results.

Implementation and removal of an affirmative-action quota : the impact on task assignment and workers’ skill acquisition

Both the United States and Canada have federal legislation that attempts to address employment inequities across specific target groups. The US has a long tradition of affirmative action, dating back to President Kennedy’s 1961 Executive Order; Canada enacted its Employment Equity Act in 1986. Employment Equity/Affirmative Action policy has attracted significant controversy, with high profile court cases and the repeal of state/provincial legislation. Coate and Loury (1993) examine the theoretical impact of introducing affirmative action. Unfortunately the theoretical impact of affirmative action is ambiguous. The current paper employs a laboratory experiment to shed empirical light on this theoretical ambiguity.

Retrieval of health advice on the web: AEHRC at ShARe/CLEF eHealth Evaluation Lab Task 3

This paper details the participation of the Australian e- Health Research Centre (AEHRC) in the ShARe/CLEF 2013 eHealth Evaluation Lab { Task 3. This task aims to evaluate the use of information retrieval (IR) systems to aid consumers (e.g. patients and their relatives) in seeking health advice on the Web. Our submissions to the ShARe/CLEF challenge are based on language models generated from the web corpus provided by the organisers. Our baseline system is a standard Dirichlet smoothed language model. We enhance the baseline by identifying and correcting spelling mistakes in queries, as well as expanding acronyms using AEHRC's Medtex medical text analysis platform. We then consider the readability and the authoritativeness of web pages to further enhance the quality of the document ranking. Measures of readability are integrated in the language models used for retrieval via prior probabilities. Prior probabilities are also used to encode authoritativeness information derived from a list of top-100 consumer health websites. Empirical results show that correcting spelling mistakes and expanding acronyms found in queries signi cantly improves the e ectiveness of the language model baseline. Readability priors seem to increase retrieval e ectiveness for graded relevance at early ranks (nDCG@5, but not precision), but no improvements are found at later ranks and when considering binary relevance. The authoritativeness prior does not appear to provide retrieval gains over the baseline: this is likely to be because of the small overlap between websites in the corpus and those in the top-100 consumer-health websites we acquired.

Identify disorders in health records using Conditional Random Fields and Metamap: AEHRC at ShARe/CLEF 2013 eHealth Evaluation Lab Task 1

The Australian e-Health Research Centre (AEHRC) recently participated in the ShARe/CLEF eHealth Evaluation Lab Task 1. The goal of this task is to individuate mentions of disorders in free-text electronic health records and map disorders to SNOMED CT concepts in the UMLS metathesaurus. This paper details our participation to this ShARe/CLEF task. Our approaches are based on using the clinical natural language processing tool Metamap and Conditional Random Fields (CRF) to individuate mentions of disorders and then to map those to SNOMED CT concepts. Empirical results obtained on the 2013 ShARe/CLEF task highlight that our instance of Metamap (after ltering irrelevant semantic types), although achieving a high level of precision, is only able to identify a small amount of disorders (about 21% to 28%) from free-text health records. On the other hand, the addition of the CRF models allows for a much higher recall (57% to 79%) of disorders from free-text, without sensible detriment in precision. When evaluating the accuracy of the mapping of disorders to SNOMED CT concepts in the UMLS, we observe that the mapping obtained by our ltered instance of Metamap delivers state-of-the-art e ectiveness if only spans individuated by our system are considered (`relaxed' accuracy).

The impact of interface modality on police officers' visual behaviour when using an in-vehicle system

Background Standard operating procedures state that police officers should not drive while interacting with their mobile data terminal (MDT) which provides in-vehicle information essential to police work. Such interactions do however occur in practice and represent a potential source of driver distraction. The MDT comprises visual output with manual input via touch screen and keyboard. This study investigated the potential for alternative input and output methods to mitigate driver distraction with specific focus on eye movements. Method Nineteen experienced drivers of police vehicles (one female) from the NSW Police Force completed four simulated urban drives. Three drives included a concurrent secondary task: imitation licence plate search using an emulated MDT. Three different interface methods were examined: Visual-Manual, Visual-Voice, and Audio-Voice (“Visual” and “Audio” = output modality; “Manual” and “Voice” = input modality). During each drive, eye movements were recorded using FaceLAB™ (Seeing Machines Ltd, Canberra, ACT). Gaze direction and glances on the MDT were assessed. Results The Visual-Voice and Visual-Manual interfaces resulted in a significantly greater number of glances towards the MDT than Audio-Voice or Baseline. The Visual-Manual and Visual-Voice interfaces resulted in significantly more glances to the display than Audio-Voice or Baseline. For longer duration glances (>2s and 1-2s) the Visual-Manual interface resulted in significantly more fixations than Baseline or Audio-Voice. The short duration glances (<1s) were significantly greater for both Visual-Voice and Visual-Manual compared with Baseline and Audio-Voice. There were no significant differences between Baseline and Audio-Voice. Conclusion An Audio-Voice interface has the greatest potential to decrease visual distraction to police drivers. However, it is acknowledged that an audio output may have limitations for information presentation compared with visual output. The Visual-Voice interface offers an environment where the capacity to present information is sustained, whilst distraction to the driver is reduced (compared to Visual-Manual) by enabling adaptation of fixation behaviour.

Introduction : the anthropology of migration

This introduction to the volume places the study of migration within the wider processes of social change and the complex actions of class, gender and ethnicity that are integrated into the experience of displacement. It argues that the articles in this volume contribute important new ethnographic and theoretical analyses to our knowledge and understanding of the constraints and the opportunities provided by cultural diversity in several societies by elaborating upon recent advances made in conceptualisations of migrancy. It places particular emphasis on developing phenomenological approaches to migration studies which incorporate the lived experience of migrants into any analysis. It also suggests that redressing the neglect of this area of study in Australia has the possibility of generating informed interruptions into the current political shift towards divisive public debates on immigration and cultural pluralism.

Generate : Youth Culture and Migration Heritage in Western Sydney

Executive Summary This report is the first in-depth exploration of identity and popular culture among Middle Eastern and Asian youth. It documents preliminary research findings on the contribution of Middle Eastern and Asian youth to Sydney’s cultural life and migration heritage. While young people from these communities, the largest migrant communities in NSW, are often negatively portrayed, this research has focused on their social practices of cultural invention, opening up new and creative means of mobilising cultural difference. These young people’s cultural negotiations between migrant family background and the wider society require real engagement with difference and provide rich resources for invigorating the multicultural fabric of the nation. Their repertoire of cultural skills and their involvement in different cultural worlds are often viewed as evidence of not ‘belonging’ to the mainstream or dominant culture. However, the results of our research reveal that the ‘in-betweenness’ of these young people often enables them to move easily between different social and cultural groupings, embracing cultural diversity as inherent and integral to their everyday experience, that is, ‘normal’ to urban life. In this report, we document the changing nature of friendship networks and family relations, the particular meanings and uses of different languages and expressions, and the patterns of consumption of Middle Eastern and Asian youth. In these everyday activities these young people contribute to a changing migration heritage and are redefining what it means to be Australian.

Optical and biomechanical factors, associated with near work and myopia

Near work may play an important role in the development of myopia in the younger population. The prevalence of myopia has also been found to be higher in occupations that involve substantial near work tasks, for example in microscopists and textile workers. When nearwork is performed, it typically involves accommodation, convergence and downward gaze. A number of previous studies have examined the effects of accommodation and convergence on changes in the optics and biometrics of the eye in primary gaze. However, little is known about the influence of accommodation on the eye in downward gaze. This thesis is primarily concerned with investigating the changes in the eye during near work in downward gaze under natural viewing conditions. To measure wavefront aberrations in downward gaze under natural viewing conditions, we modified a commercial Shack-Hartmann wavefront sensor by adding a relay lens system to allow on-axis ocular aberration measurements in primary gaze and downward gaze, with binocular fixation. Measurements with the modified wavefront sensor in primary and downward gaze were validated against a conventional aberrometer using both a model eye and in 9 human subjects. We then conducted an experiment to investigate changes in ocular aberrations associated with accommodation in downward gaze over 10 mins in groups of both myopes (n = 14) and emmetropes (n =12) using the modified Shack-Hartmann wavefront sensor. During the distance accommodation task, small but significant changes in refractive power (myopic shift) and higher order aberrations were observed in downward gaze compared to primary gaze. Accommodation caused greater changes in higher order aberrations (in particular coma and spherical aberration) in downward gaze than primary gaze, and there was evidence that the changes in certain aberrations with accommodation over time were different in downward gaze compared to primary gaze. There were no obvious systematic differences in higher order aberrations between refractive error groups during accommodation or downward gaze for fixed pupils. However, myopes exhibited a significantly greater change in higher order aberrations (in particular spherical aberration) than emmetropes for natural pupils after 10 mins of a near task (5 D accommodation) in downward gaze. These findings indicated that ocular aberrations change from primary to downward gaze, particularly with accommodation. To understand the mechanism underlying these changes in greater detail, we then extended this work to examine the characteristics of the corneal optics, internal optics, anterior biometrics and axial length of the eye during a near task, in downward gaze, over 10 mins. Twenty young adult subjects (10 emmetropes and 10 myopes) participated in this study. To measure corneal topography and ocular biometrics in downward gaze, a rotating Scheimpflug camera and an optical biometer were inclined on a custom built, height and tilt adjustable table. We found that both corneal optics and internal optics change with downward gaze, resulting in a myopic shift (~0.10 D) in the spherical power of the eye. The changes in corneal optics appear to be due to eyelid pressure on the anterior surface of the cornea, whereas the changes in the internal optics (an increase in axial length and a decrease in anterior chamber depth) may be associated with movement of the crystalline lens, under the action of gravity, and the influence of altered biomechanical forces from the extraocular muscles on the globe with downward gaze. Changes in axial length with accommodation were significantly greater in downward gaze than primary gaze (p < 0.05), indicating an increased effect of the mechanical forces from the ciliary muscle and extraocular muscles. A subsequent study was conducted to investigate the changes in anterior biometrics, axial length and choroidal thickness in nine cardinal gaze directions under the actions of the extraocular muscles. Ocular biometry measurements were obtained from 30 young adults (10 emmetropes, 10 low myopes and 10 moderate myopes) through a rotating prism with 15° deviation, along the foveal axis, using a non-contact optical biometer in each of nine different cardinal directions of gaze, over 5 mins. There was a significant influence of gaze angle and time on axial length (both p < 0.001), with the greatest axial elongation (+18 ± 8 μm) occurring with infero-nasal gaze (p < 0.001) and a slight decrease in axial length in superior gaze (−12 ± 17 μm) compared with primary gaze (p < 0.001). There was a significant correlation between refractive error (spherical equivalent refraction) and the mean change in axial length in the infero-nasal gaze direction (Pearson's R2 = 0.71, p < 0.001). To further investigate the relative effect of gravity and extraocular muscle force on the axial length, we measured axial length in 15° and 25° downward gaze with the biometer inclined on a tilting table that allowed gaze shifts to occur with either full head turn but no eye turn (reflects the effect of gravity), or full eye turn with no head turn (reflects the effect of extraocular muscle forces). We observed a significant axial elongation in 15° and 25° downward gaze in the full eye turn condition. However, axial length did not change significantly in downward gaze over 5 mins (p > 0.05) in the full head turn condition. The elongation of the axial length in downward gaze appears to be due to the influence of the extraocular muscles, since the effect was not present when head turn was used instead of eye turn. The findings of these experiments collectively show the dynamic characteristics of the optics and biometrics of the eye in downward gaze during a near task, over time. These were small but significant differences between myopic and emmetropic eyes in both the optical and biomechanical changes associated with shifts of gaze direction. These differences between myopes and emmetropes could arise as a consequence of excessive eye growth associated with myopia. However the potentially additive effects of repeated or long lasting near work activities employing infero-nasal gaze could also act to promote elongation of the eye due to optical and/or biomechanical stimuli.

Performance of a cognitive, but not visual, secondary task interacts with alcohol-induced balance impairment in novice and experienced motorcycle riders

The appropriateness of applying drink driving legislation to motorcycle riding has been questioned as there may be fundamental differences in the effects of alcohol on driving and motorcycling. It has been suggested that alcohol may redirect riders’ focus from higher-order cognitive skills such as cornering, judgement and hazard perception, to more physical skills such as maintaining balance. To test this hypothesis, the effects of low doses of alcohol on balance ability were investigated in a laboratory setting. The static balance of twenty experienced and twenty novice riders was measured while they performed either no secondary task, a visual (search) task, or a cognitive (arithmetic) task following the administration of alcohol (0%, 0.02%, and 0.05% BAC). Subjective ratings of intoxication and balance impairment increased in a dose-dependent manner in both novice and experienced motorcycle riders, while a BAC of 0.05%, but not 0.02%, was associated with impairments in static balance ability. This balance impairment was exacerbated when riders performed a cognitive, but not a visual, secondary task. Likewise, 0.05% BAC was associated with impairments in novice and experienced riders’ performance of a cognitive, but not a visual, secondary task, suggesting that interactive processes underlie balance and cognitive task performance. There were no observed differences between novice vs. experienced riders on static balance and secondary task performance, either alone or in combination. Implications for road safety and future ‘drink riding’ policy considerations are discussed.

Incorporating spatial correlations into multispecies mean-field models

In biology, we frequently observe different species existing within the same environment. For example, there are many cell types in a tumour, or different animal species may occupy a given habitat. In modelling interactions between such species, we often make use of the mean field approximation, whereby spatial correlations between the locations of individuals are neglected. Whilst this approximation holds in certain situations, this is not always the case, and care must be taken to ensure the mean field approximation is only used in appropriate settings. In circumstances where the mean field approximation is unsuitable we need to include information on the spatial distributions of individuals, which is not a simple task. In this paper we provide a method that overcomes many of the failures of the mean field approximation for an on-lattice volume-excluding birth-death-movement process with multiple species. We explicitly take into account spatial information on the distribution of individuals by including partial differential equation descriptions of lattice site occupancy correlations. We demonstrate how to derive these equations for the multi-species case, and show results specific to a two-species problem. We compare averaged discrete results to both the mean field approximation and our improved method which incorporates spatial correlations. We note that the mean field approximation fails dramatically in some cases, predicting very different behaviour from that seen upon averaging multiple realisations of the discrete system. In contrast, our improved method provides excellent agreement with the averaged discrete behaviour in all cases, thus providing a more reliable modelling framework. Furthermore, our method is tractable as the resulting partial differential equations can be solved efficiently using standard numerical techniques.