Travelling waves for a velocity–jump model of cell migration and proliferation

Cell invasion, characterised by moving fronts of cells, is an essential aspect of development, repair and disease. Typically, mathematical models of cell invasion are based on the Fisher–Kolmogorov equation. These traditional parabolic models can not be used to represent experimental measurements of individual cell velocities within the invading population since they imply that information propagates with infinite speed. To overcome this limitation we study combined cell motility and proliferation based on a velocity–jump process where information propagates with finite speed. The model treats the total population of cells as two interacting subpopulations: a subpopulation of left–moving cells, $L(x,t)$, and a subpopulation of right–moving cells, $R(x,t)$. This leads to a system of hyperbolic partial differential equations that includes a turning rate, $\Lambda \ge 0$, describing the rate at which individuals in the population change direction of movement. We present exact travelling wave solutions of the system of partial differential equations for the special case where $\Lambda = 0$ and in the limit that $\Lambda \to \infty$. For intermediate turning rates, $0 < \Lambda < \infty$, we analyse the travelling waves using the phase plane and we demonstrate a transition from smooth monotone travelling waves to smooth nonmonotone travelling waves as $\Lambda$ decreases through a critical value $\Lambda_{crit}$. We conclude by providing a qualitative comparison between the travelling wave solutions of our model and experimental observations of cell invasion. This comparison indicates that the small $\Lambda$ limit produces results that are consistent with experimental observations.

Video-based road commentary training improves hazard perception of young drivers in a dual task

This study used a video-based hazard perception dual task to compare the hazard perception skills of young drivers with middle aged, more experienced drivers and to determine if these skills can be improved with video-based road commentary training. The primary task required the participants to detect and verbally identify immediate hazard on video-based traffic scenarios while concurrently performing a secondary tracking task, simulating the steering of real driving. The results showed that the young drivers perceived fewer immediate hazards (mean = 75.2%, n = 24, 19 females) than the more experienced drivers (mean = 87.5%, n = 8, all females), and had longer hazard perception times, but performed better in the secondary tracking task. After the road commentary training, the mean percentage of hazards detected and identified by the young drivers improved to the level of the experienced drivers and was significantly higher than that of an age and driving experience matched control group. The results will be discussed in the context of psychological theories of hazard perception and in relation to road commentary as an evidence-based training intervention that seems to improve many aspects of unsafe driving behaviour in young drivers.

Sensitivity of edge detection methods for quantifying cell migration assays

Quantitative imaging methods to analyze cell migration assays are not standardized. Here we present a suite of two–dimensional barrier assays describing the collective spreading of an initially–confined population of 3T3 fibroblast cells. To quantify the motility rate we apply two different automatic image detection methods to locate the position of the leading edge of the spreading population after 24, 48 and 72 hours. These results are compared with a manual edge detection method where we systematically vary the detection threshold. Our results indicate that the observed spreading rates are very sensitive to the choice of image analysis tools and we show that a standard measure of cell migration can vary by as much as 25% for the same experimental images depending on the details of the image analysis tools. Our results imply that it is very difficult, if not impossible, to meaningfully compare previously published measures of cell migration since previous results have been obtained using different image analysis techniques and the details of these techniques are not always reported. Using a mathematical model, we provide a physical interpretation of our edge detection results. The physical interpretation is important since edge detection algorithms alone do not specify any physical measure, or physical definition, of the leading edge of the spreading population. Our modeling indicates that variations in the image threshold parameter correspond to a consistent variation in the local cell density. This means that varying the threshold parameter is equivalent to varying the location of the leading edge in the range of approximately 1–5% of the maximum cell density.

The effect of exercise repetition on the frequency characteristics of motor output force : Implications for Achilles tendinopathy rehabilitation

Objectives: To investigate the frequency characteristics of the ground reaction force (GRF) recorded throughout the eccentric Achilles tendon rehabilitation programme described by Alfredson. Design: Controlled laboratory study, longitudinal. Methods: Nine healthy adult males performed six sets (15 repetitions per set) of eccentric ankle exercise. Ground reaction force was recorded throughout the exercise protocol. For each exercise repetition the frequency power spectrum of the resultant ground reaction force was calculated and normalised to total power. The magnitude of peak relative power within the 8-12 Hz bandwidth and the frequency at which this peak occurred was determined. Results: The magnitude of peak relative power within the 8-12 Hz bandwidth increased with each successive exercise set and following the 4th set (60 repetitions) of exercise the frequency at which peak relative power occurred shifted from 9 to 10 Hz. Conclusions: The increase in magnitude and frequency of ground reaction force vibrations with an increasing number of exercise repetitions is likely connected to changes in muscle activation with fatigue and tendon conditioning. This research illustrates the potential for the number of exercise repetitions performed to influence the tendons' mechanical environment, with implications for tendon remodelling and the clinical efficacy of eccentric rehabilitation programmes for Achilles tendinopathy.

How much is enough? The effect of exercise repetition on the force frequency characteristics of eccentric exercise used for tendinopathy rehabilitation

Introduction: Eccentric exercise (EE) is a commonly used treatment for Achilles tendinopathy. While vibrations in the 8–12 Hz frequency range generated during eccentric muscle actions have been put forward as a potential mechanism for the beneficial effect of EE, optimal loading parameters required to expedite recovery are currently unknown. Alfredson's original protocol employed 90 repetitions of eccentric loading, however abbreviated protocols consisting of fewer repetitions (typically 45) have been developed, albeit with less beneficial effect. Given that 8–12 Hz vibrations generated during isometric muscle actions have been previously shown to increase with fatigue, this research evaluated the effect of exercise repetition on motor output vibrations generated during EE by investigating the frequency characteristics of ground reaction force (GRF) recorded throughout the 90 repetitions of Alfredson's protocol. Methods: Nine healthy adult males performed six sets (15 repetitions per set) of eccentric ankle exercise. GRF was recorded at a frequency of 1000 Hz throughout the exercise protocol. The frequency power spectrum of the resultant GRF was calculated and normalized to total power. Relative spectral power was summed over 1 Hz widows within the frequency rage 7.5–11.5 Hz. The effect of each additional exercise set (15 repetitions) on the relative power within each widow was investigated using a general linear modelling approach. Results: The magnitude of peak relative power within the 7.5–11.5 Hz bandwidth increased across the six exercise sets from 0.03 in exercise set one to 0.12 in exercise set six (P < 0.05). Following the 4th set of exercise the frequency at which peak relative power occurred shifted from 9 to 10 Hz. Discussion: This study has demonstrated that successive repetitions of eccentric loading over six exercise sets results in an increase in the amplitude of motor output vibrations in the 7.5–11.5 Hz bandwidth, with an increase in the frequency of these vibrations occurring after the 4th set (60th repetition). These findings are consistent with findings from previous studies of muscle fatigue. Assuming that the magnitude and frequency of these vibrations represent important stimuli for tendon remodelling as hypothesized within the literature, the findings of this study question the role of abbreviated EE protocols and raise the question; can EE protocols for tendinopathy be optimized by performing eccentric loading to fatigue?

Achilles tendinopathy modulates force frequency characteristics of eccentric exercise

Introduction Previous research has demonstrated that ground reaction force (GRF) recorded during eccentric ankle exercise is characterised by greater power in the 8-12Hz bandwidth when compared to that recorded during concentric ankle exercise. Subsequently, it was suggested that vibrations in this bandwidth may underpin the beneficial effect of eccentric loading in tendon repair. However, this observation has been made only in individuals without Achilles tendinopathy. This research compared the force frequency characteristics of eccentric and concentric exercises in individuals with and without Achilles tendinopathy., Methods Eleven male adults with unilateral mid-portion Achilles tendinopathy and nine control male adults without tendinopathy participated in the research. Kinematics and GRF were recorded while the participants performed a common eccentric rehabilitation exercise protocol and a concentric equivalent. Ankle joint kinematics and the frequency power spectrum of the resultant GRF were calculated. Results Eccentric exercise was characterised by a significantly greater proportion of spectral power between 4.5 and 11.5Hz when compared to concentric exercise. There were no significant differences between limbs in the force frequency characteristics of concentric exercise. Eccentric exercise, in contrast, was defined by a shift in the power spectrum of the symptomatic limb, resulting in a second spectral peak at 9Hz, rather than 10Hz in the control limb. Conclusions Compared to healthy tendon, Achilles tendinopathy was characterised by lower frequency vibrations during eccentric rehabilitation exercises. This finding may be associated with changes in neuromuscular activation and tendon stiffness which have been shown to occur with tendinopathy and provides a possible rationale for the previous observation of a different biochemical response to eccentric exercise in healthy and injured Achilles tendons., (C)2012The American College of Sports Medicine

Integrating agency and resource dependence theory : firm profitability, industry regulation, and board task performance

Boards of directors are key governancemechanisms in organizations and fulfill twomain tasks:monitoringmanagers and firm performance, and providing advice and access to resources. In spite of a wealth of researchmuch remains unknown about how boards attend to the two tasks. This study investigates whether organizational (firm profitability) and environmental factors (industry regulation) affect board task performance. The data combine CEOs' responses to a questionnaire, and archival data from a sample of large Italian firms. Findings show that past firm performance is negatively associatedwith board monitoring and advice tasks; greater industry regulation enhances perceived board task performance; board monitoring and advice tasks tend to reinforce each other, despite their theoretical and practical distinction.

The NLP task at INEX 2004

The INEX workshop is concerned with evaluating the effectiveness of XML retrieval systems. In 2004 a natural language query task was added to the INEX Ad hoc track. Standard INEX Ad hoc topic titles are specified in NEXI -- a simplified and restricted subset of XPath, with a similar feel, and yet with a distinct IR flavour and interpretation. The syntax of NEXI is rigid and it imposes some limitations on the kind of information need that it can faithfully capture. At INEX 2004 the NLP question to be answered was simple -- is it practical to use a natural language query that is the equivalent of the formal NEXI title? The results of this experiment are reported and some information on the future direction of the NLP task is presented.

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.