An improved model of tumour-immune system interactions

The immune system plays an important role in defending the body against tumours and other threats. Currently, mechanisms involved in immune system interactions with tumour cells are not fully understood. Here we develop a mathematical tool that can be used in aiding to address this shortfall in understanding. This paper de- scribes a hybrid cellular automata model of the interaction between a growing tumour and cells of the innate and specific immune system including the effects of chemokines that builds on previous models of tumour-immune system interactions. In particular, the model is focused on the response of immune cells to tumour cells and how the dynamics of the tumour cells change due to the immune system of the host. We present results and predictions of in silico experiments including simulations of Kaplan-Meier survival-like curves.

The persistence of phase-separation in LiFePO4 with two-dimensional Li+ transport : the Cahn-Hilliard-reaction equation and the role of defects

We examine the solution of the two-dimensional Cahn-Hilliard-reaction (CHR) equation in the xy plane as a model of Li+ intercalation into LiFePO4 material. We validate our numerical solution against the solution of the depth-averaged equation, which has been used to model intercalation in the limit of highly orthotropic diffusivity and gradient penalty tensors. We then examine the phase-change behaviour in the full CHR system as these parameters become more isotropic, and find that as the Li+ diffusivity is increased in the x direction, phase separation persists at high currents, even in small crystals with averaged coherency strain included. The resulting voltage curves decrease monotonically, which has previously been considered a hallmark of crystals that fill homogeneously.

Closed system isolation and scalable expansion of human placental mesenchymal stem cells

Mesenchymal stem cells (MSC) are emerging as a leading cellular therapy for a number of diseases. However, for such treatments to become available as a routine therapeutic option, efficient and cost-effective means for industrial manufacture of MSC are required. At present, clinical grade MSC are manufactured through a process of manual cell culture in specialized cGMP facilities. This process is open, extremely labor intensive, costly, and impractical for anything more than a small number of patients. While it has been shown that MSC can be cultivated in stirred bioreactor systems using microcarriers, providing a route to process scale-up, the degree of numerical expansion achieved has generally been limited. Furthermore, little attention has been given to the issue of primary cell isolation from complex tissues such as placenta. In this article we describe the initial development of a closed process for bulk isolation of MSC from human placenta, and subsequent cultivation on microcarriers in scalable single-use bioreactor systems. Based on our initial data, we estimate that a single placenta may be sufficient to produce over 7,000 doses of therapeutic MSC using a large-scale process.

Planning for transit system reliability using productive performance and risk assessment

Urban transit system performance may be quantified and assessed using transit capacity and productive capacity for planning, design and operational management. Bunker (4) defines important productive performance measures of an individual transit service and transit line. Transit work (p-km) captures transit task performed over distance. Transit productiveness (p-km/h) captures transit work performed over time. This paper applies productive performance with risk assessment to quantify transit system reliability. Theory is developed to monetize transit segment reliability risk on the basis of demonstration Annual Reliability Event rates by transit facility type, segment productiveness, and unit-event severity. A comparative example of peak hour performance of a transit sub-system containing bus-on-street, busway, and rail components in Brisbane, Australia demonstrates through practical application the importance of valuing reliability. Comparison reveals the highest risk segments to be long, highly productive on street bus segments followed by busway (BRT) segments and then rail segments. A transit reliability risk reduction treatment example demonstrates that benefits can be significant and should be incorporated into project evaluation in addition to those of regular travel time savings, reduced emissions and safety improvements. Reliability can be used to identify high risk components of the transit system and draw comparisons between modes both in planning and operations settings, and value improvement scenarios in a project evaluation setting. The methodology can also be applied to inform daily transit system operational management.

Planning for transit system reliability using productive performance and risk assessment

Urban transit system performance may be quantified and assessed using transit capacity and productive capacity for planning, design and operational management. Bunker (4) defines important productive performance measures of an individual transit service and transit line. Transit work (p-km) captures transit task performed over distance. Transit productiveness (p-km/h) captures transit work performed over time. This paper applies productive performance with risk assessment to quantify transit system reliability. Theory is developed to monetize transit segment reliability risk on the basis of demonstration Annual Reliability Event rates by transit facility type, segment productiveness, and unit-event severity. A comparative example of peak hour performance of a transit sub-system containing bus-on-street, busway, and rail components in Brisbane, Australia demonstrates through practical application the importance of valuing reliability. Comparison reveals the highest risk segments to be long, highly productive on street bus segments followed by busway (BRT) segments and then rail segments. A transit reliability risk reduction treatment example demonstrates that benefits can be significant and should be incorporated into project evaluation in addition to those of regular travel time savings, reduced emissions and safety improvements. Reliability can be used to identify high risk components of the transit system and draw comparisons between modes both in planning and operations settings, and value improvement scenarios in a project evaluation setting. The methodology can also be applied to inform daily transit system operational management.

Sustainable, safe, smart—three key elements of Singapore’s evolving transport policies

Sustainability, safety and smartness are three key elements of a modern transportation system. This study illustrates various policy directions and initiatives of Singapore to address how its transportation system is progressing in light of these three components. Sustainability targets economical efficiency, environmental justice and social equity by including policies for integrating land use and transport planning, ensuring adequate transport supply measures, managing travel demand efficiently, and incorporating environment-friendly strategies. Safety initiatives of its transportation system aim to minimize injuries and incidents of all users including motorists, public transport commuters, pedestrians, and bicyclists. Smartness incorporates qualities like real time sensing, fast processing and decision making, and automated action-taking into its control, monitoring, information management and revenue collection systems. Various policy implications and technology applications along these three directions reveal that smart technologies facilitate implementation of policies promoting sustainability and safety. The Singapore experience could serve as a good reference for other cities in promoting a transportation system that is sustainable, safe and smart.

Insulin and the insulin-like growth factor system : a novel theory for hyperinsulinemic laminitis pathogenesis

Research into hyperinsulinemic laminitis has progressed significantly in recent years with the use of the prolonged-euglycemic, hyperinsulinemic clamp (p-EHC). Previous investigations of laminitis pathophysiology have focused on digital vascular dysfunction, inflammation, altered glucose metabolism within the lamellae, and lamellar basement membrane breakdown by metalloproteinases. The etiopathogenesis of laminitis occurring in association with hyperinsulinemia is yet to be fully characterized, but it may not involve these mechanisms. Insulin stimulates cellular proliferation and can also affect other body systems, such as the insulin-like growth factor (IGF) system. Insulin-like growth factor-1 (IGF-1) is structurally homologous to insulin and, like insulin, binds with strong affinity to a specific tyrosine kinase receptor on the cell surface to produce its effects, which include promoting cell proliferation. Receptors for IGF-1 (IGF-1R) are present in the lamellar epidermis. An alternative theory for the pathogenesis of hyperinsulinemic laminitis is that uncontrolled cell proliferation, mediated through both the insulin receptor (InsR) and IGF-1R, leads to lengthening, weakening, and failure of the lamellae. An analysis of the proliferative activity of lamellar epidermal cells during the developmental and acute phases of hyperinsulinemic laminitis, and lamellar gene expression of the InsR and IGF-1R was undertaken.

Towards proximity-based passenger sensing on public transport buses

While substantial research on intelligent transportation systems has focused on the development of novel wireless communication technologies and protocols, relatively little work has sought to fully exploit proximity-based wireless technologies that passengers actually carry with them today. This paper presents the real-world deployment of a system that exploits public transit bus passengers’ Bluetooth-capable devices to capture and reconstruct micro- and macro-passenger behavior. We present supporting evidence that approximately 12% of passengers already carry Bluetooth-enabled devices and that the data collected on these passengers captures with almost 80 % accuracy the daily fluctuation of actual passengers flows. The paper makes three contributions in terms of understanding passenger behavior: We verify that the length of passenger trips is exponentially bounded, the frequency of passenger trips follows a power law distribution, and the microstructure of the network of passenger movements is polycentric.

A reliable real-time transport protocol for networked control systems over wireless networks

Deploying wireless networks in networked control systems (NCSs) has become more and more popular during the last few years. As a typical type of real-time control systems, an NCS is sensitive to long and nondeterministic time delay and packet losses. However, the nature of the wireless channel has the potential to degrade the performance of NCS networks in many aspects, particularly in time delay and packet losses. Transport layer protocols could play an important role in providing both reliable and fast transmission service to fulfill NCS’s real-time transmission requirements. Unfortunately, none of the existing transport protocols, including the Transport Control Protocol (TCP) and the User Datagram Protocol (UDP), was designed for real-time control applications. Moreover, periodic data and sporadic data are two types of real-time data traffic with different priorities in an NCS. Due to the lack of support for prioritized transmission service, the real-time performance for periodic and sporadic data in an NCS network is often degraded significantly, particularly under congested network conditions. To address these problems, a new transport layer protocol called Reliable Real-Time Transport Protocol (RRTTP) is proposed in this thesis. As a UDP-based protocol, RRTTP inherits UDP’s simplicity and fast transmission features. To improve the reliability, a retransmission and an acknowledgement mechanism are designed in RRTTP to compensate for packet losses. They are able to avoid unnecessary retransmission of the out-of-date packets in NCSs, and collisions are unlikely to happen, and small transmission delay can be achieved. Moreover, a prioritized transmission mechanism is also designed in RRTTP to improve the real-time performance of NCS networks under congested traffic conditions. Furthermore, the proposed RRTTP is implemented in the Network Simulator 2 for comprehensive simulations. The simulation results demonstrate that RRTTP outperforms TCP and UDP in terms of real-time transmissions in an NCS over wireless networks.

Mathematical modelling of tumour growth and interaction with host tissue and the immune system

In this thesis, three mathematical models describing the growth of solid tumour incorporating the host tissue and the immune system response are developed and investigated. The initial model describes the dynamics of the growing tumour and immune response before being extended in the second model by introducing a time-varying dendritic cell-based treatment strategy. Finally, in the third model, we present a mathematical model of a growing tumour using a hybrid cellular automata. These models can provide information to pre-experimental work to assist in designing more effective and efficient laboratory experiments related to tumour growth and interactions with the immune system and immunotherapy.

The biology of the glutamatergic system and potential role in migraine

Migraine is a common genetically linked neurovascular disorder. Approximately ~12% of the Caucasian population are affected including 18% of adult women and 6% of adult men (1, 2). A notable female bias is observed in migraine prevalence studies with females affected ~3 times more than males and is credited to differences in hormone levels arising from reproductive achievements. Migraine is extremely debilitating with wide-ranging socioeconomic impact significantly affecting people's health and quality of life. A number of neurotransmitter systems have been implicated in migraine, the most studied include the serotonergic and dopaminergic systems. Extensive genetic research has been carried out to identify genetic variants that may alter the activity of a number of genes involved in synthesis and transport of neurotransmitters of these systems. The biology of the Glutamatergic system in migraine is the least studied however there is mounting evidence that its constituents could contribute to migraine. The discovery of antagonists that selectively block glutamate receptors has enabled studies on the physiologic role of glutamate, on one hand, and opened new perspectives pertaining to the potential therapeutic applications of glutamate receptor antagonists in diverse neurologic diseases. In this brief review, we discuss the biology of the Glutamatergic system in migraine outlining recent findings that support a role for altered Glutamatergic neurotransmission from biochemical and genetic studies in the manifestation of migraine and the implications of this on migraine treatment.

Migrating to a sustainable energy system : distributed generation and storage, fuel cells and hypercars

This paper examines a number of issues in sustainable energy generation and distribution, and explores avenues that are available for integration of our society’s energy supplies. In particular, the paper presents a way in which transport vehicle energy supplies could be integrated with distributed generation schemes to achieve synergistic and beneficial outcomes. The worldwide energy system contains fundamental problems that result directly from the use of unsustainable fuels and a lack of energy system integration. There is a need to adopt an integrated, sustainable energy system for our society. The adoption of distributed generation could result in beneficial restructuring of the energy trade, and a change in the role of energy providers. Inherent benefits in distributed generation schemes would directly combat barriers to installation of renewable generation facilities, which might prove distributed renewable energy sources to be more feasible. The presence of fuel cells, batteries, power electronic inverters and intelligent controls in vehicles of the future provides many opportunities for the integration of vehicle energy supplies into a distributed generation scheme. In such a system, vehicles could play a major role in power generation and storage.

Migrating to a sustainable energy system : distributed generation and storage, fuel cells and hypercars

This paper examines a number of issues in sustainable energy generation and distribution, and explores avenues that are available for integration of our society’s energy supplies. In particular, the paper presents a way in which transport vehicle energy supplies could be integrated with distributed generation schemes to achieve synergistic and beneficial outcomes. The worldwide energy system contains fundamental problems that result directly from the use of unsustainable fuels and a lack of energy system integration. There is a need to adopt an integrated, sustainable energy system for our society. The adoption of distributed generation could result in beneficial restructuring of the energy trade, and a change in the role of energy providers. Inherent benefits in distributed generation schemes would directly combat barriers to installation of renewable generation facilities, which might prove distributed renewable energy sources to be more feasible. The presence of fuel cells, batteries, power electronic inverters and intelligent controls in vehicles of the future provides many opportunities for the integration of vehicle energy supplies into a distributed generation scheme. In such a system, vehicles could play a major role in power generation and storage.

Mathematical modelling of soft callus formation in early murine bone repair

Fracture healing is a complicated coupling of many processes. Yet despite the apparent complexity, fracture repair is usually effective. There is, however, no comprehensive mathematical model addressing the multiple interactions of cells, cytokines and oxygen that includes extra-cellular matrix production and that results in the formation of the early stage soft callus. This thesis develops a one dimensional continuum transport model in the context of early fracture healing. Although fracture healing is a complex interplay of many local factors, critical components are identified and used to construct an hypothesis about regulation of the evolution of early callus formation. Multiple cell lines, cellular differentiation, oxygen levels and cytokine concentrations are examined as factors affecting this model of early bone repair. The model presumes diffusive and chemotactic cell migration mechanisms. It is proposed that the initial signalling regime and oxygen availability arising as consequences of bone fracture, are sufficient to determine the quantity and quality of early soft callus formation. Readily available software and purpose written algorithms have been used to obtain numerical solutions representative of various initial conditions. These numerical distributions of cellular populations reflect available histology obtained from murine osteotomies. The behaviour of the numerical system in response to differing initial conditions can be described by alternative in vivo healing pathways. An experimental basis, as illustrated in murine fracture histology, has been utilised to validate the mathematical model outcomes. The model developed in this thesis has potential for future extension, to incorporate processes leading to woven bone deposition, while maintaining the characteristics that regulate early callus formation.