Mathematical modelling of tumour-induced angiogenesis

The growth of solid tumours beyond a critical size is dependent upon angiogenesis, the formation of new blood vessels from an existing vasculature. Tumours may remain dormant at microscopic sizes for some years before switching to a mode in which growth of a supportive vasculature is initiated. The new blood vessels supply nutrients, oxygen, and access to routes by which tumour cells may travel to other sites within the host (metastasize). In recent decades an abundance of biological research has focused on tumour-induced angiogenesis in the hope that treatments targeted at the vasculature may result in a stabilisation or regression of the disease: a tantalizing prospect. The complex and fascinating process of angiogenesis has also attracted the interest of researchers in the field of mathematical biology, a discipline that is, for mathematics, relatively new. The challenge in mathematical biology is to produce a model that captures the essential elements and critical dependencies of a biological system. Such a model may ultimately be used as a predictive tool. In this thesis we examine a number of aspects of tumour-induced angiogenesis, focusing on growth of the neovasculature external to the tumour. Firstly we present a one-dimensional continuum model of tumour-induced angiogenesis in which elements of the immune system or other tumour-cytotoxins are delivered via the newly formed vessels. This model, based on observations from experiments by Judah Folkman et al., is able to show regression of the tumour for some parameter regimes. The modelling highlights a number of interesting aspects of the process that may be characterised further in the laboratory. The next model we present examines the initiation positions of blood vessel sprouts on an existing vessel, in a two-dimensional domain. This model hypothesises that a simple feedback inhibition mechanism may be used to describe the spacing of these sprouts with the inhibitor being produced by breakdown of the existing vessel's basement membrane. Finally, we have developed a stochastic model of blood vessel growth and anastomosis in three dimensions. The model has been implemented in C++, includes an openGL interface, and uses a novel algorithm for calculating proximity of the line segments representing a growing vessel. This choice of programming language and graphics interface allows for near-simultaneous calculation and visualisation of blood vessel networks using a contemporary personal computer. In addition the visualised results may be transformed interactively, and drop-down menus facilitate changes in the parameter values. Visualisation of results is of vital importance in the communication of mathematical information to a wide audience, and we aim to incorporate this philosophy in the thesis. As biological research further uncovers the intriguing processes involved in tumourinduced angiogenesis, we conclude with a comment from mathematical biologist Jim Murray, Mathematical biology is : : : the most exciting modern application of mathematics.

Virtual worlds as a model-view approach to the communication of business processes models

The improvement and optimization of business processes is one of the top priorities in an organization. Although process analysis methods are mature today, business analysts and stakeholders are still hampered by communication issues. That is, analysts cannot effectively obtain accurate business requirements from stakeholders, and stakeholders are often confused about analytic results offered by analysts. We argue that using a virtual world to model a business process can benefit communication activities. We believe that virtual worlds can be used as an efficient model-view approach, increasing the cognition of business requirements and analytic results, as well as the possibility of business plan validation. A healthcare case study is provided as an approach instance, illustrating how intuitive such an approach can be. As an exploration paper, we believe that this promising research can encourage people to investigate more research topics in the interdisciplinary area of information system, visualization and multi-user virtual worlds.

The use of dashboards in performance management : evidence from sales managers

The purpose of this paper is to identify and empirically examine the key features, purposes, uses, and benefits of performance dashboards. We find that only about a quarter of the sales managers surveyed1 in Finland used a dashboard, which was lower than previously reported. Dashboards were used for four distinct purposes: (i) monitoring, (ii) problem solving, (iii) rationalizing, and (iv) communication and consistency. There was a high correlation between the different uses of dashboards and user productivity indicating that dashboards were perceived as effective tools in performance management, not just for monitoring one‟s own performance but for other purposes including communication. The quality of the data in dashboards did not seem to be a concern (except for completeness) but it was a critical driver regarding its use. This is the first empirical study on performance dashboards in terms of adoption rates, key features, and benefits. The study highlights the research potential and benefits of dashboards, which could be valuable for future researchers and practitioners.

Considering weather in simulation traffic

The impact of weather on traffic and its behavior is not well studied in literature primarily due to lack of integrated traffic and weather data. Weather can significant effect the traffic and traffic management measures developed for fine weather might not be optimal for adverse weather. Simulation is an efficient tool for analyzing traffic management measures even before their actual implementation. Therefore, in order to develop and test traffic management measures for adverse weather condition we need to first analyze the effect of weather on fundamental traffic parameters and thereafter, calibrate the simulation model parameters in order to simulate the traffic under adverse weather conditions. In this paper we first, analyses the impact of weather on motorway traffic flow and drivers’ behaviour with traffic data from Swiss motorways and weather data from MeteoSuisse. Thereafter, we develop methodology to calibrate a microscopic simulation model with the aim to utilize the simulation model for simulating traffic under adverse weather conditions. Here, study is performed using AIMSUN, a microscopic traffic simulator.

Critical time scales for advection–diffusion–reaction processes

The concept of local accumulation time (LAT) was introduced by Berezhkovskii and coworkers in 2010–2011 to give a finite measure of the time required for the transient solution of a reaction–diffusion equation to approach the steady–state solution (Biophys J. 99, L59 (2010); Phys Rev E. 83, 051906 (2011)). Such a measure is referred to as a critical time. Here, we show that LAT is, in fact, identical to the concept of mean action time (MAT) that was first introduced by McNabb in 1991 (IMA J Appl Math. 47, 193 (1991)). Although McNabb’s initial argument was motivated by considering the mean particle lifetime (MPLT) for a linear death process, he applied the ideas to study diffusion. We extend the work of these authors by deriving expressions for the MAT for a general one–dimensional linear advection–diffusion–reaction problem. Using a combination of continuum and discrete approaches, we show that MAT and MPLT are equivalent for certain uniform–to-uniform transitions; these results provide a practical interpretation for MAT, by directly linking the stochastic microscopic processes to a meaningful macroscopic timescale. We find that for more general transitions, the equivalence between MAT and MPLT does not hold. Unlike other critical time definitions, we show that it is possible to evaluate the MAT without solving the underlying partial differential equation (pde). This makes MAT a simple and attractive quantity for practical situations. Finally, our work explores the accuracy of certain approximations derived using the MAT, showing that useful approximations for nonlinear kinetic processes can be obtained, again without treating the governing pde directly.

Windows

In this video, words emerge out of an abstract, ‘digital’, animated horizon line. The words are accompanied by a female voice-over who narrates a seductive relaxation and visualization activity. This work examines the nature of consciousness and identity in a contemporary context. It mixes the languages of meditation, new age philosophy and pop-psychology. Drawing on Zygmunt Bauman’s theoretical work on “liquid modernity”, this work questions how and where we find space for contemplation and reflection in a contemporary context increasingly defined by temporary social bonds and consumer choices.

Driver response time of queuing vehicles at urban signalized intersections

Driver response (reaction) time (tr) of the second queuing vehicle is generally longer than other vehicles at signalized intersections. Though this phenomenon was revealed in 1972, the above factor is still ignored in conventional departure models. This paper highlights the need for quantitative measurements and analysis of queuing vehicle performance in spontaneous discharge pattern because it can improve microsimulation. Video recording from major cities in Australia plus twenty two sets of vehicle trajectories extracted from the Next Generation Simulation (NGSIM) Peachtree Street Dataset have been analyzed to better understand queuing vehicle performance in the discharge process. Findings from this research will alleviate driver response time and also can be used for the calibration of the microscopic traffic simulation model.

A behavioural car-following model that captures traffic oscillations

This paper presents a behavioral car-following model based on empirical trajectory data that is able to reproduce the spontaneous formation and ensuing propagation of stop-and-go waves in congested traffic. By analyzing individual drivers’ car-following behavior throughout oscillation cycles it is found that this behavior is consistent across drivers and can be captured by a simple model. The statistical analysis of the model’s parameters reveals that there is a strong correlation between driver behavior before and during the oscillation, and that this correlation should not be ignored if one is interested in microscopic output. If macroscopic outputs are of interest, simulation results indicate that an existing model with fewer parameters can be used instead. This is shown for traffic oscillations caused by rubbernecking as observed in the US 101 NGSIM dataset. The same experiment is used to establish the relationship between rubbernecking behavior and the period of oscillations.

SeqSLAM : visual route-based navigation for sunny summer days and stormy winter nights

Learning and then recognizing a route, whether travelled during the day or at night, in clear or inclement weather, and in summer or winter is a challenging task for state of the art algorithms in computer vision and robotics. In this paper, we present a new approach to visual navigation under changing conditions dubbed SeqSLAM. Instead of calculating the single location most likely given a current image, our approach calculates the best candidate matching location within every local navigation sequence. Localization is then achieved by recognizing coherent sequences of these “local best matches”. This approach removes the need for global matching performance by the vision front-end - instead it must only pick the best match within any short sequence of images. The approach is applicable over environment changes that render traditional feature-based techniques ineffective. Using two car-mounted camera datasets we demonstrate the effectiveness of the algorithm and compare it to one of the most successful feature-based SLAM algorithms, FAB-MAP. The perceptual change in the datasets is extreme; repeated traverses through environments during the day and then in the middle of the night, at times separated by months or years and in opposite seasons, and in clear weather and extremely heavy rain. While the feature-based method fails, the sequence-based algorithm is able to match trajectory segments at 100% precision with recall rates of up to 60%.

Capping computation time and storage requirements for appearance-based localization with CAT-SLAM

Appearance-based localization is increasingly used for loop closure detection in metric SLAM systems. Since it relies only upon the appearance-based similarity between images from two locations, it can perform loop closure regardless of accumulated metric error. However, the computation time and memory requirements of current appearance-based methods scale linearly not only with the size of the environment but also with the operation time of the platform. These properties impose severe restrictions on longterm autonomy for mobile robots, as loop closure performance will inevitably degrade with increased operation time. We present a set of improvements to the appearance-based SLAM algorithm CAT-SLAM to constrain computation scaling and memory usage with minimal degradation in performance over time. The appearance-based comparison stage is accelerated by exploiting properties of the particle observation update, and nodes in the continuous trajectory map are removed according to minimal information loss criteria. We demonstrate constant time and space loop closure detection in a large urban environment with recall performance exceeding FAB-MAP by a factor of 3 at 100% precision, and investigate the minimum computational and memory requirements for maintaining mapping performance.

Developing key concepts in physics : Is it more effective to teach using scientific visualizations?

A quantitative, quasi-experimental study of the effectiveness of computer-based scientific visualizations for concept learning on the part of Year 11 physics students (n=80) was conducted in six Queensland high school classrooms. Students’ gender and academic ability were also considered as factors in relation to the effectiveness of teaching with visualizations. Learning with visualizations was found to be equally effective as learning without them for all students, with no statistically significant difference in outcomes being observed for the group as a whole or on the academic ability dimension. Male students were found to learn significantly better with visualizations than without, while no such effect was observed for female students. This may give rise to some concern for the equity issues raised by introducing visualizations. Given that other research shows that students enjoy learning with visualizations and that their engagement with learning is enhanced, the finding that the learning outcomes are the same as for teaching without visualizations supports teachers’ use of visualizations.

A safety adapted car following model for traffic safety studies

Traffic safety studies demand more than what current micro-simulation models can provide as they presume that all drivers exhibit safe behaviors. All the microscopic traffic simulation models include a car following model. This paper highlights the limitations of the Gipps car following model ability to emulate driver behavior for safety study purposes. A safety adapted car following model based on the Gipps car following model is proposed to simulate unsafe vehicle movements, with safety indicators below critical thresholds. The modifications are based on the observations of driver behavior in real data and also psychophysical notions. NGSIM vehicle trajectory data is used to evaluate the new model and short following headways and Time To Collision are employed to assess critical safety events within traffic flow. Risky events are extracted from available NGSIM data to evaluate the modified model against them. The results from simulation tests illustrate that the proposed model can predict the safety metrics better than the generic Gipps model. The outcome of this paper can potentially facilitate assessing and predicting traffic safety using microscopic simulation.

Neural network-based detection of virtual environment anomalies

The increasingly widespread use of large-scale 3D virtual environments has translated into an increasing effort required from designers, developers and testers. While considerable research has been conducted into assisting the design of virtual world content and mechanics, to date, only limited contributions have been made regarding the automatic testing of the underpinning graphics software and hardware. In the work presented in this paper, two novel neural network-based approaches are presented to predict the correct visualization of 3D content. Multilayer perceptrons and self-organizing maps are trained to learn the normal geometric and color appearance of objects from validated frames and then used to detect novel or anomalous renderings in new images. Our approach is general, for the appearance of the object is learned rather than explicitly represented. Experiments were conducted on a game engine to determine the applicability and effectiveness of our algorithms. The results show that the neural network technology can be effectively used to address the problem of automatic and reliable visual testing of 3D virtual environments.

An analytical tool that quantifies cellular morphology changes from three-dimensional fluorescence images

The most common software analysis tools available for measuring fluorescence images are for two-dimensional (2D) data that rely on manual settings for inclusion and exclusion of data points, and computer-aided pattern recognition to support the interpretation and findings of the analysis. It has become increasingly important to be able to measure fluorescence images constructed from three-dimensional (3D) datasets in order to be able to capture the complexity of cellular dynamics and understand the basis of cellular plasticity within biological systems. Sophisticated microscopy instruments have permitted the visualization of 3D fluorescence images through the acquisition of multispectral fluorescence images and powerful analytical software that reconstructs the images from confocal stacks that then provide a 3D representation of the collected 2D images. Advanced design-based stereology methods have progressed from the approximation and assumptions of the original model-based stereology(1) even in complex tissue sections(2). Despite these scientific advances in microscopy, a need remains for an automated analytic method that fully exploits the intrinsic 3D data to allow for the analysis and quantification of the complex changes in cell morphology, protein localization and receptor trafficking. Current techniques available to quantify fluorescence images include Meta-Morph (Molecular Devices, Sunnyvale, CA) and Image J (NIH) which provide manual analysis. Imaris (Andor Technology, Belfast, Northern Ireland) software provides the feature MeasurementPro, which allows the manual creation of measurement points that can be placed in a volume image or drawn on a series of 2D slices to create a 3D object. This method is useful for single-click point measurements to measure a line distance between two objects or to create a polygon that encloses a region of interest, but it is difficult to apply to complex cellular network structures. Filament Tracer (Andor) allows automatic detection of the 3D neuronal filament-like however, this module has been developed to measure defined structures such as neurons, which are comprised of dendrites, axons and spines (tree-like structure). This module has been ingeniously utilized to make morphological measurements to non-neuronal cells(3), however, the output data provide information of an extended cellular network by using a software that depends on a defined cell shape rather than being an amorphous-shaped cellular model. To overcome the issue of analyzing amorphous-shaped cells and making the software more suitable to a biological application, Imaris developed Imaris Cell. This was a scientific project with the Eidgenössische Technische Hochschule, which has been developed to calculate the relationship between cells and organelles. While the software enables the detection of biological constraints, by forcing one nucleus per cell and using cell membranes to segment cells, it cannot be utilized to analyze fluorescence data that are not continuous because ideally it builds cell surface without void spaces. To our knowledge, at present no user-modifiable automated approach that provides morphometric information from 3D fluorescence images has been developed that achieves cellular spatial information of an undefined shape (Figure 1). We have developed an analytical platform using the Imaris core software module and Imaris XT interfaced to MATLAB (Mat Works, Inc.). These tools allow the 3D measurement of cells without a pre-defined shape and with inconsistent fluorescence network components. Furthermore, this method will allow researchers who have extended expertise in biological systems, but not familiarity to computer applications, to perform quantification of morphological changes in cell dynamics.

Evaluation of the GHR car following model for traffic safety studies

Traffic safety studies mandate more than what existing micro-simulation models can offer as they postulate that every driver exhibits a safe behaviour. All the microscopic traffic simulation models are consisting of a car-following model and the Gazis–Herman–Rothery (GHR) car-following model is a widely used model. This paper highlights the limitations of the GHR car-following model capability to model longitudinal driving behaviour for safety study purposes. This study reviews and compares different version of the GHR model. To empower the GHR model on precise metrics reproduction a new set of car-following model parameters is offered to simulate unsafe vehicle conflicts. NGSIM vehicle trajectory data is used to evaluate the new model and short following headways and Time to Collision are employed to assess critical safety events within traffic flow. Risky events are extracted from available NGSIM data to evaluate the modified model against the generic versions of the GHR model. The results from simulation tests illustrate that the proposed model does predict the safety metrics better than the generic GHR model. Additionally it can potentially facilitate assessing and predicting traffic facilities’ safety using microscopic simulation. The new model can predict Near-miss rear-end crashes.