ERK-1/2 and p38 in the Regulation of Hypertrophic Changes of Normal Articular Cartilage Chondrocytes Induced by Osteoarthritic Subchondral Osteoblasts

Objective. Previous studies have shown the influence of subchondral bone osteoblasts (SBOs) on phenotypical changes of articular cartilage chondrocytes (ACCs) during the development of osteoarthritis (OA). The molecular mechanisms involved during this process remain elusive, in particular, the signal transduction pathways. The aim of this study was to investigate the in vitro effects of OA SBOs on the phenotypical changes in normal ACCs and to unveil the potential involvement of MAPK signaling pathways during this process. Methods. Normal and arthritic cartilage and bone samples were collected for isolation of ACCs and SBOs. Direct and indirect coculture models were applied to study chondrocyte hypertrophy under the influence of OA SBOs. MAPKs in the regulation of the cell–cell interactions were monitored by phosphorylated antibodies and relevant inhibitors. Results. OA SBOs led to increased hypertrophic gene expression and matrix calcification in ACCs by means of both direct and indirect cell–cell interactions. In this study, we demonstrated for the first time that OA SBOs suppressed p38 phosphorylation and induced ERK-1/2 signal phosphorylation in cocultured ACCs. The ERK-1/2 pathway inhibitor PD98059 significantly attenuated the hypertrophic changes induced by conditioned medium from OA SBOs, and the p38 inhibitor SB203580 resulted in the up-regulation of hypertrophic genes in ACCs. Conclusion. The findings of this study suggest that the pathologic interaction of OA SBOs and ACCs is mediated via the activation of ERK-1/2 phosphorylation and deactivation of p38 phosphorylation, resulting in hypertrophic differentiation of ACCs.

Interactions between energy intake and expenditure in the development and treatment of obesity.

Summary There are four interactions to consider between energy intake (EI) and energy expenditure (EE) in the development and treatment of obesity. (1) Does sedentariness alter levels of EI or subsequent EE? and (2) Do high levels of EI alter physical activity or exercise? (3) Do exercise-induced increases in EE drive EI upwards and undermine dietary approaches to weight management and (4) Do low levels of EI elevate or decrease EE? There is little evidence that sedentariness alters levels of EI. This lack of cross-talk between altered EE and EI appears to promote a positive EB. Lifestyle studies also suggest that a sedentary routine actually offers the opportunity for over-consumption. Substantive changes in non exercise activity thermogenesis are feasible, but not clearly demonstrated. Cross talk between elevated EE and EI is initially too weak and takes too long to activate, to seriously threaten dietary approaches to weight management. It appears that substantial fat loss is possible before intake begins to track a sustained elevation of EE. There is more evidence that low levels of EI does lower physical activity levels, in relatively lean men under conditions of acute or prolonged semi-starvation and in dieting obese subjects. During altered EB there are a number of small but significant changes in the components of EE, including (i) sleeping and basal metabolic rate, (ii) energy cost of weight change alters as weight is gained or lost, (iii) exercise efficiency, (iv) energy cost of weight bearing activities, (v) during substantive overfeeding diet composition (fat versus carbohydrate) will influence the energy cost of nutrient storage by ~ 15%. The responses (i-v) above are all “obligatory” responses. Altered EB can also stimulate facultative behavioural responses, as a consequence of cross-talk between EI and EE. Altered EB will lead to changes in the mode duration and intensity of physical activities. Feeding behaviour can also change. The degree of inter-individual variability in these responses will define the scope within which various mechanisms of EB compensation can operate. The relative importance of “obligatory” versus facultative, behavioural responses -as components of EB control- need to be defined.

Complex Urban Systems

Presentation about research projects that build understanding of urban design and interactions and plan for future opportunities. What do we need to model?

Modelling and execution of asset management process via workflow automation

An Asset Management (AM) life-cycle constitutes a set of processes that align with the development, operation and maintenance of assets, in order to meet the desired requirements and objectives of the stake holders of the business. The scope of AM is often broad within an organization due to the interactions between its internal elements such as human resources, finance, technology, engineering operation, information technology and management, as well as external elements such as governance and environment. Due to the complexity of the AM processes, it has been proposed that in order to optimize asset management activities, process modelling initiatives should be adopted. Although organisations adopt AM principles and carry out AM initiatives, most do not document or model their AM processes, let alone enacting their processes (semi-) automatically using a computer-supported system. There is currently a lack of knowledge describing how to model AM processes through a methodical and suitable manner so that the processes are streamlines and optimized and are ready for deployment in a computerised way. This research aims to overcome this deficiency by developing an approach that will aid organisations in constructing AM process models quickly and systematically whilst using the most appropriate techniques, such as workflow technology. Currently, there is a wealth of information within the individual domains of AM and workflow. Both fields are gaining significant popularity in many industries thus fuelling the need for research in exploring the possible benefits of their cross-disciplinary applications. This research is thus inspired to investigate these two domains to exploit the application of workflow to modelling and execution of AM processes. Specifically, it will investigate appropriate methodologies in applying workflow techniques to AM frameworks. One of the benefits of applying workflow models to AM processes is to adapt and enable both ad-hoc and evolutionary changes over time. In addition, this can automate an AM process as well as to support the coordination and collaboration of people that are involved in carrying out the process. A workflow management system (WFMS) can be used to support the design and enactment (i.e. execution) of processes and cope with changes that occur to the process during the enactment. So far few literatures can be found in documenting a systematic approach to modelling the characteristics of AM processes. In order to obtain a workflow model for AM processes commonalities and differences between different AM processes need to be identified. This is the fundamental step in developing a conscientious workflow model for AM processes. Therefore, the first stage of this research focuses on identifying the characteristics of AM processes, especially AM decision making processes. The second stage is to review a number of contemporary workflow techniques and choose a suitable technique for application to AM decision making processes. The third stage is to develop an intermediate ameliorated AM decision process definition that improves the current process description and is ready for modelling using the workflow language selected in the previous stage. All these lead to the fourth stage where a workflow model for an AM decision making process is developed. The process model is then deployed (semi-) automatically in a state-of-the-art WFMS demonstrating the benefits of applying workflow technology to the domain of AM. Given that the information in the AM decision making process is captured at an abstract level within the scope of this work, the deployed process model can be used as an executable guideline for carrying out an AM decision process in practice. Moreover, it can be used as a vanilla system that, once being incorporated with rich information from a specific AM decision making process (e.g. in the case of a building construction or a power plant maintenance), is able to support the automation of such a process in a more elaborated way.

Workplace design in the knowledge economy : a case of the NetWorkPlace™©

This thesis explores a way to inform the architectural design process for contemporary workplace environments. It reports on both theoretical and practical outcomes through an exclusively Australian case study of a network enterprise comprised of collaborative, yet independent business entities. The internet revolution, substantial economic and cultural shifts, and an increased emphasis on lifestyle considerations have prompted a radical re-ordering of organisational relationships and the associated structures, processes, and places of doing business. The social milieu of the information age and the knowledge economy is characterised by an almost instantaneous flow of information and capital. This has culminated in a phenomenon termed by Manuel Castells as the network society, where physical locations are joined together by continuous communication and virtual connectivity. A new spatial logic encompassing redefined concepts of space and distance, and requiring a comprehensive shift in the approach to designing workplace environments for today’s adaptive, collaborative organisations in a dynamic business world, provides the backdrop for this research. Within the duality of space and an augmentation of the traditional notions of place, organisational and institutional structures pose new challenges for the design professions. The literature revealed that there has always been a mono-organisational focus in relation to workplace design strategies. The phenomenon of inter-organisational collaboration has enabled the identification of a gap in the knowledge relative to workplace design. This new context generated the formulation of a unique research construct, the NetWorkPlace™©, which captures the complexity of contemporary employment structures embracing both physical and virtual work environments and practices, and provided the basis for investigating the factors that are shaping and defining interactions within and across networked organisational settings. The methodological orientation and the methods employed follow a qualitative approach and an abductively driven strategy comprising two distinct components, a cross-sectional study of the whole of the network and a longitudinal study, focusing on a single discrete workplace site. The complexity of the context encountered dictated that a multi-dimensional investigative framework was required to be devised. The adoption of a pluralist ontology and the reconfiguration of approaches from traditional paradigms into a collaborative, trans-disciplinary, multi-method epistemology provided an explicit and replicatable method of investigation. The identification and introduction of the NetWorkPlace™© phenomenon, by necessity, spans a number of traditional disciplinary boundaries. Results confirm that in this context, architectural research, and by extension architectural practice, must engage with what other disciplines have to offer. The research concludes that no single disciplinary approach to either research or practice in this area of design can suffice. Pierre Bourdieau’s philosophy of ‘practice’ provides a framework within which the governance and technology structures, together with the mechanisms enabling the production of social order in this context, can be understood. This is achieved by applying the concepts of position and positioning to the corporate power dynamics, and integrating the conflict found to exist between enterprise standard and ferally conceived technology systems. By extending existing theory and conceptions of ‘place’ and the ‘person-environment relationship’, relevant understandings of the tensions created between Castells’ notions of the space of place and the space of flows are established. The trans-disciplinary approach adopted, and underpinned by a robust academic and practical framework, illustrates the potential for expanding the range and richness of understanding applicable to design in this context. The outcome informs workplace design by extending theoretical horizons, and by the development of a comprehensive investigative process comprising a suite of models and techniques for both architectural and interior design research and practice, collectively entitled the NetWorkPlace™© Application Framework. This work contributes to the body of knowledge within the design disciplines in substantive, theoretical, and methodological terms, whilst potentially also influencing future organisational network theories, management practices, and information and communication technology applications. The NetWorkPlace™© as reported in this thesis, constitutes a multi-dimensional concept having the capacity to deal with the fluidity and ambiguity characteristic of the network context, as both a topic of research and the way of going about it.

A process for the management of physical infrastructure

Physical infrastructure assets are important components of our society and our economy. They are usually designed to last for many years, are expected to be heavily used during their lifetime, carry considerable load, and are exposed to the natural environment. They are also normally major structures, and therefore present a heavy investment, requiring constant management over their life cycle to ensure that they perform as required by their owners and users. Given a complex and varied infrastructure life cycle, constraints on available resources, and continuing requirements for effectiveness and efficiency, good management of infrastructure is important. While there is often no one best management approach, the choice of options is improved by better identification and analysis of the issues, by the ability to prioritise objectives, and by a scientific approach to the analysis process. The abilities to better understand the effect of inputs in the infrastructure life cycle on results, to minimise uncertainty, and to better evaluate the effect of decisions in a complex environment, are important in allocating scarce resources and making sound decisions. Through the development of an infrastructure management modelling and analysis methodology, this thesis provides a process that assists the infrastructure manager in the analysis, prioritisation and decision making process. This is achieved through the use of practical, relatively simple tools, integrated in a modular flexible framework that aims to provide an understanding of the interactions and issues in the infrastructure management process. The methodology uses a combination of flowcharting and analysis techniques. It first charts the infrastructure management process and its underlying infrastructure life cycle through the time interaction diagram, a graphical flowcharting methodology that is an extension of methodologies for modelling data flows in information systems. This process divides the infrastructure management process over time into self contained modules that are based on a particular set of activities, the information flows between which are defined by the interfaces and relationships between them. The modular approach also permits more detailed analysis, or aggregation, as the case may be. It also forms the basis of ext~nding the infrastructure modelling and analysis process to infrastructure networks, through using individual infrastructure assets and their related projects as the basis of the network analysis process. It is recognised that the infrastructure manager is required to meet, and balance, a number of different objectives, and therefore a number of high level outcome goals for the infrastructure management process have been developed, based on common purpose or measurement scales. These goals form the basis of classifYing the larger set of multiple objectives for analysis purposes. A two stage approach that rationalises then weights objectives, using a paired comparison process, ensures that the objectives required to be met are both kept to the minimum number required and are fairly weighted. Qualitative variables are incorporated into the weighting and scoring process, utility functions being proposed where there is risk, or a trade-off situation applies. Variability is considered important in the infrastructure life cycle, the approach used being based on analytical principles but incorporating randomness in variables where required. The modular design of the process permits alternative processes to be used within particular modules, if this is considered a more appropriate way of analysis, provided boundary conditions and requirements for linkages to other modules, are met. Development and use of the methodology has highlighted a number of infrastructure life cycle issues, including data and information aspects, and consequences of change over the life cycle, as well as variability and the other matters discussed above. It has also highlighted the requirement to use judgment where required, and for organisations that own and manage infrastructure to retain intellectual knowledge regarding that infrastructure. It is considered that the methodology discussed in this thesis, which to the author's knowledge has not been developed elsewhere, may be used for the analysis of alternatives, planning, prioritisation of a number of projects, and identification of the principal issues in the infrastructure life cycle.