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.

Sustainable housing: family experiences with supply chain ethics

Climate change, resource depletion and increasing urbanization are converging global issues that are challenging the way we design, construct and operate buildings. The housing sector is a significant contributor to these global issues through consumption of limited resources, waste generation and disposal (solid, liquid and atmospheric waste) and negative human health impacts (Senick 2006). Although the design and construction of ‘sustainable housing’ would appear to be an obvious and technically feasible solution, there remains multi-faceted issues affecting the delivery of sustainable housing (Holloway and Bunker 2006). Two fundamental issues - what makes a house sustainable, and to what extent regulation should be used to deliver sustainability - have been, and continue to be, debated at multiple levels in society. Despite personal, professional and political views on these issues, three key characteristics of the whole housing supply chain require fundamental change if we are to successfully address sustainability challenges (Birkeland 2008). These include: fragmentation; established methods, practices and processes, and the relationships between players. A more in-depth understanding of the role of ethics (values, beliefs and standards) and potential ethical conflicts within the supply chain will assist in better defining the nature of the fundamental changes required...

Lean supply chain performance evaluation method

Increasing global competitiveness worldwide has forced manufacturing organizations to produce high-quality products more quickly and at a competitive cost which demand of continuous improvements techniques. In this paper, we propose a fuzzy based performance evaluation method for lean supply chain. To understand the overall performance of cost competitive supply chain, we investigate the alignment of market strategy and position of the supply chain. Competitive strategies can be achieved by using a different weight calculation for different supply chain situations. By identifying optimal performance metrics and applying performance evaluation methods, managers can predict the overall supply chain performance under lean strategy.

Demand for, and Supply of, the Services of Primary Producer Representative Bodies in Queensland

In Queensland, at least 93 bodies exist to represent the interests of, and provide other services for, their farmer members, and their industries. The bodies vary greatly in focus, roles and activities, priorities, resources, size, and affiliations with other bodies. Results from a survey of 68 producer representative bodies (PRBs), and other data and information are used to examine the demand for, and supply of, farmer representational and other services in Queensland. The main results were: 1. member demand for services varies considerably between PRBs and is influenced by numerous factors; 2. members and non-members of one PRB vary significantly in the importance attached to some services; 3. the types of activities undertaken by PRBs varies between those for emerging and established industries; and 4. PRBs with paid staff/officers undertake more activities than others. The paper concludes that PRBs must continue to evolve and adapt their operations and structures to take account of changes in member and industry needs, external environments, cost pressures, resource availability, and sources of funding/assistance.

Effects of oxygen on zonal marker expression in human articular chondrocytes

Articular cartilage is organized in depth zones with phenotypically distinct subpopulations of chondrocytes that are exposed to different oxygen tensions. Despite growing evidence of the critical role for oxygen in chondrogenesis, little is known about its effect on chondrocytes from different zones. This study evaluates zonal marker expression of human articular chondrocytes from different zones under various oxygen tensions. Chondrocytes isolated from full-thickness, superficial, and middle/deep cartilage from knee replacement surgeries were expanded and redifferentiated under hypoxic (5% O 2) or normoxic (20% O 2) conditions. Differentiation under hypoxia increased expression of hypoxia-inducible factors 1alpha and 2alpha and accumulation of extracellular matrix, particularly in middle/deep chondrocytes, and favored re-expression of proteoglycan 4 by superficial chondrocytes compared with middle/deep cells. Zone-dependent expression of clusterin varied with culture duration. These results demonstrate that zonal chondrocytes retain important phenotypic differences during in vitro cultivation, and that these characteristics can be improved by altering the oxygen environment. However, transcript levels for pleiotrophin, cartilage intermediate layer protein, and collagen type X were similar between zones, challenging their reliability as zonal markers for tissue-engineered cartilage from osteoarthritis patients. Key factors including oxygen tension and cell source should be considered to prescribe zone-specific properties to tissue-engineered cartilage. © 2012, Mary Ann Liebert, Inc.

Corporate social and environmental responsibility in relation to the agricultural sector and the food supply chain : a Case Study of Waitrose

Waitrose has a strong commitment to organic farming but also uses products from 'conventional' farms. At the production stage, Waitrose own-label products are fully traceable, GM-free and all suppliers undergo a detailed assessment programme based on current best practice. Crop suppliers to Waitrose operate an authenticity programme to certify that each assignment is GM-free and produce is screened for pesticide residues. Waitrose sources conventional crops grown from 'Integrated Crop Management Systems' (ICMS) using best horticultural practices. The 'Assured Product' scheme regulates all UK produce to ICMS standards and these audits are being extended worldwide. Business is withdrawn from suppliers who fail the audit. In relation to this, Waitrose has increased its Fairtrade range as in its view 'Buying these products provides direct additional benefit to workers in the developing countries where they are produced and assists marginal producers by giving them access to markets they would not otherwise have'. Currently, Waitrose is developing its own sustainable timber assessment criteria. For livestock, protocols are in place to ensure that animals are reared under the 'most natural conditions possible' and free range produce is offered where animals have access to open space although some produce is not from free-range animals. Waitrose also use a 'Hazards Analysis Critical Points' system to identify food safety hazards that occur at any stage from production to point of sale and to ensure that full measures are in place to control them. In addition, mechanisms have been implemented to reduce fuel use and hence reduce CO2 emissions in the transport of products and staff, and to increase the energy use efficiency of refrigeration systems which account for approximately 60% of Waitrose energy use.

High-voltage modular power supply using parallel and series configurations of flyback converter for pulsed power applications

To cover wide range of pulsed power applications, this paper proposes a modularity concept to improve the performance and flexibility of the pulsed power supply. The proposed scheme utilizes the advantage of parallel and series configurations of flyback modules in obtaining high-voltage levels with fast rise time (dv/dt). Prototypes were implemented using 600-V insulated-gate bipolar transistor (IGBT) switches to generate up to 4-kV output pulses with 1-kHz repetition rate for experimentation. To assess the proposed modular approach for higher number of the modules, prototypes were implemented using 1700-V IGBTs switches, based on ten-series modules, and tested up to 20 kV. Conducted experimental results verified the effectiveness of the proposed method

Building and construction industries supply chain project (domestic) : report for Commonwealth Department of Industry, Science and Resources

The Commonwealth Department of Industry, Science and Resources is identifying best practice case study examples of supply chain management within the building and construction industry to illustrate the concepts, innovations and initiatives that are at work. The projects provide individual enterprises with examples of how to improve their performance, and the competitiveness of the industry as a whole.

Preparation, characterisation and in vivo osteogenesis of mesoporous bioactive glasses

Bone defects, especially large bone defects, remain a major challenge in orthopaedic surgery. Autologous bone transplantation is considered the most effective treatment, but insufficient donor tissue, coupled with concerns about donor site morbidity, has hindered this approach in large-scale applications. Alternative approaches include implanting biomaterials such as bioactive glass (BG), which has been widely used for bone defect healing, due to having generally good biocompatibility, and can be gradually biodegraded during the process of new bone formation. Mesoporous bioactive glass (MBG) is a newly developed bioactive glass which has been proven to have enhanced in-vitro bioactivity; however the in-vivo osteogenesis has not been studied. A critical problem in using the bone tissue engineering approach to restore large bone defects is that the nutrient supply and cell viability at the centre of the scaffold is severely hampered since the diffusion distance of nutrients and oxygen for cell survival is limited to 150-200µm. Cobalt ions has been shown to mimic hypoxia, which plays a pivotal role in coupling angiogenesis with osteogenesis in-vivo by activating hypoxia inducing factor-1α (HIF-1α) transcription factor, subsequently initiating the expression of genes associated with tissue regeneration. Therefore, one aim of this study is to investigate the in-vivo osteogenesis of MBG by comparison with BG and β-TCP, which are widely used clinically. The other aim is to explore hypoxia-mimicking biomaterials by incorporating Cobalt into MBG and β-TCP. MBG and β-TCP incorporated with 5% cobalt (5Co-MBG and 5CCP) have also been studied in-vivo to determine whether the hypoxic effect has a beneficial effect on the bone formation. The composition and microstructure of synthesised materials (BG, MBG, 5Co-MBG, 5CCP) were characterised, along with the mesopore properties of the MBG materials. Dissolution and cytotoxicity of the Co-containing materials were also investigated. Femoral samples with defects harvested at 4 and 8 weeks were scanned using micro-CT followed by processing for histology (H&E staining) to determine bone formation. Histology of MBG showed a slower rate of bone formation at 4 weeks than BG, however at 8 weeks it could be clearly seen that MBG had more bone formation. The in-vivo results show that the osteogenesis of MBG reciprocates the enhanced performance shown in-vitro compared to BG. Dissolution study showed that Co ions can be efficiently released from MBG and β-TCP in a controllable way. Low amounts of Co incorporated into the MBG and β-TCP showed no significant cytotoxicity and the Co-MBG powders maintained a mesopore structure although not as highly ordered as pure MBG. Preliminary study has shown that Co incorporated samples showed little to no bone formation, instead incurring high lymphocyte activity. Further studies need to be done on Co incorporated materials to determine the cause for high lymphocyte activity in-vivo, which appear to hinder bone formation. In conclusion, this study demonstrated the osteogenic activity of MBG and provided some valuable information of tissue reaction to Co-incorporated MBG and TCP materials.

Supply chain management systems benefits : the expectation-confirmation theory perspective

Organizations adopt a Supply Chain Management System (SCMS) expecting benefits to the organization and its functions. However, organizations are facing mounting challenges to realizing benefits through SCMS. Studies suggest a growing dissatisfaction among client organizations due to an increasing gap between expectations and realization of SCMS benefits. Further, reflecting the Enterprise System studies such as Seddon et al. (2010), SCMS benefits are also expected to flow to the organization throughout its lifecycle rather than being realized all at once. This research therefore proposes to derive a lifecycle-wide understanding of SCMS benefits and realization to derive a benefit expectation management framework to attain the full potential of an SCMS. The primary research question of this study is: How can client organizations better manage their benefit expectations of SCM systems? The specific research goals of the current study include: (1) to better understand the misalignment of received and expected benefits of SCM systems; (2) to identify the key factors influencing SCM system expectations and to develop a framework to manage SCMS benefits; (3) to explore how organizational satisfaction is influenced by the lack of SCMS benefit confirmation; and (4) to explore how to improve the realization of SCM system benefits. Expectation-Confirmation Theory (ECT) provides the theoretical underpinning for this study. ECT has been widely used in the consumer behavior literature to study customer satisfaction, post-purchase behavior and service marketing in general. Recently, ECT has been extended into Information Systems (IS) research focusing on individual user satisfaction and IS continuance. However, only a handful of studies have employed ECT to study organizational satisfaction on large-scale IS. The current study will enrich the research stream by extending ECT into organizational-level analysis and verifying the preliminary findings of relevant works by Staples et al. (2002), Nevo and Chan (2007) and Nevo and Wade (2007). Moreover, this study will go further trying to operationalize the constructs of ECT into the context of SCMS. The empirical findings of the study commence with a content analysis, through which 41 vendor reports and academic reports are analyzed yielding sixty expected benefits of SCMS. Then, the expected benefits are compared with the benefits realized at a case organization in the Fast Moving Consumer Goods industry sector that had implemented a SAP Supply Chain Management System seven years earlier. The study develops an SCMS Benefit Expectation Management (SCMS-BEM) Framework. The comparison of benefit expectations and confirmations highlights that, while certain benefits are realized earlier in the lifecycle, other benefits could take almost a decade to realize. Further analysis and discussion on how the developed SCMS-BEM Framework influences ECT when applied in SCMS was also conducted. It is recommended that when establishing their expectations of the SCMS, clients should remember that confirmation of these expectations will have a long lifecycle, as shown in the different time periods in the SCMS-BEM Framework. Moreover, the SCMS-BEM Framework will allow organizations to maintain high levels of satisfaction through careful mitigation and confirming expectations based on the lifecycle phase. In addition, the study reveals that different stakeholder groups have different expectations of the same SCMS. The perspective of multiple stakeholders has significant implications for the application of ECT in the SCMS context. When forming expectations of the SCMS, the collection of organizational benefits of SCMS should represent the perceptions of all stakeholder groups. The same mechanism should be employed in the measurements of received SCMS benefits. Moreover, for SCMS, there exists interdependence of the satisfaction among the various stakeholders. The satisfaction of decision-makers or the authorized staff is not only driven by their own expectation confirmation level, it is also influenced by the confirmation level of other stakeholders‘ expectations in the organization. Satisfaction from any one particular stakeholder group can not reflect the true satisfaction of the client organization. Furthermore, it is inferred from the SCMS-BEM Framework that organizations should place emphasis on the viewpoints of the operational and management staff when evaluating the benefits of SCMS in the short and middle term. At the same time, organizations should be placing more attention on the perspectives of strategic staff when evaluating the performance of the SCMS in the long term.

Modelling resilience in a water supply system : contrasting conditions of drought and flood

This paper presents an approach to modelling the resilience of a generic (potable) water supply system. The system is contextualized as a meta-system consisting of three subsystems to represent the natural catchment, the water treatment plant and the water distribution infrastructure for urban use. An abstract mathematical model of the meta-system is disaggregated progressively to form a cascade of equations forming a relational matrix of models. This allows the investigation of commonly implicit relationships between various operational components within the meta system, the in-depth understanding of specific system components and influential factors and the incorporation of explicit disturbances to explore system behaviour. Consequently, this will facilitate long-term decision making to achieve sustainable solutions for issues such as, meeting a growing demand or managing supply-side influences in the meta-system under diverse water availability regimes. This approach is based on the hypothesis that the means to achieve resilient supply of water may be better managed by modelling the effects of changes at specific levels that have a direct or in some cases indirect impact on higher-order outcomes. Additionally, the proposed strategy allows the definition of approaches to combine disparate data sets to synthesise previously missing or incomplete higher-order information, a scientifically robust means to define and carry out meta-analyses using knowledge from diverse yet relatable disciplines relevant to different levels of the system and for enhancing the understanding of dependencies and inter-dependencies of variable factors at various levels across the meta-system. The proposed concept introduces an approach for modelling a complex infrastructure system as a meta system which consists of a combination of bio-ecological, technical and socio-technical subsystems.