Dynamical systems for discovering protein complexes and functional modules from biological networks

Recent advances in high throughput experiments and annotations via published literature have provided a wealth of interaction maps of several biomolecular networks, including metabolic, protein-protein, and protein-DNA interaction networks. The architecture of these molecular networks reveals important principles of cellular organization and molecular functions. Analyzing such networks, i.e., discovering dense regions in the network, is an important way to identify protein complexes and functional modules. This task has been formulated as the problem of finding heavy subgraphs, the Heaviest k-Subgraph Problem (k-HSP), which itself is NPhard. However, any method based on the k-HSP requires the parameter k and an exact solution of k-HSP may still end up as a “spurious” heavy subgraph, thus reducing its practicability in analyzing large scale biological networks. We proposed a new formulation, called the rank-HSP, and two dynamical systems to approximate its results. In addition, a novel metric, called the Standard deviation and Mean Ratio (SMR), is proposed for use in “spurious” heavy subgraphs to automate the discovery by setting a fixed threshold. Empirical results on both the simulated graphs and biological networks have demonstrated the efficiency and effectiveness of our proposal.

Characterization of the MEK5-ERK5 module in human neutrophils and its relationship to ERK1/ERK2 in the chemotactic response

The role of the extracellular signal-regulated kinase (ERK) 1 and ERK2 in the neutrophil chemotactic response remains to be identified since a previously used specific inhibitor of MEK1 and MEK2, PD98059, that was used to provide evidence for a role of ERK1 and ERK2 in regulating chemotaxis, has recently been reported to also inhibit MEK5. This issue is made more critical by our present finding that human neutrophils express mitogen-activated protein (MAP) kinase/ERK kinase (MEK)5 and ERK5 (Big MAP kinase), and that their activities were stimulated by the bacterial tripeptide, formyl methionyl-leucyl-phenylalanine (fMLP). Dose response studies demonstrated a bell-shaped profile of fMLP-stimulated MEK5 and ERK5 activation, but this was left-shifted when compared with the profile of fMLP-stimulated chemotaxis. Kinetics studies demonstrated increases in kinase activity within 2 min, peaking at 3–5 min, and MEK5 activation was more persistent than that of ERK5. There were some similarities as well as differences in the pattern of activation between fMLP-stimulated ERK1 and ERK2, and MEK5-ERK5 activation. The up-regulation of MEK5-ERK5 activities was dependent on phosphatidylinositol 3-kinase. Studies with the recently described specific MEK inhibitor, PD184352, at concentrations that inhibited ERK1 and ERK2 but not ERK5 activity demonstrate that the ERK1 and ERK2 modules were involved in regulating fMLP-stimulated chemotaxis and chemokinesis. Our data suggest that the MEK5-ERK5 module is likely to regulate neutrophil responses at very low chemoattractant concentrations whereas at higher concentrations, a shift to the ERK1/ERK2 and p38 modules is apparent.

International network for food and obesity/NCD research, monitoring and action support: benchmarking food environments towards healthier diets

Background and objectives: 

Tomorrow’s car – for today’s people : can tilting three wheeled vehicles be a solution for the problems of today and the future?

The current automotive industry and todays car drivers are faced with every increasing challenges, not previously experienced. Climate Change, financial issues, rising fuel prices, increased traffic congestion and reduced parking space in cities are all leading to changes in consumer preferences and the requirements of modern passenger vehicles. However, despite the shift in the industry dynamics, the principal layout of a car hasn’t changed since its invention. The design of a ’conventional’ vehicle is still principally a matchbox with four wheels, one at each corner. The concept has served its purpose well for over 100 years, but such a layout is not suited to solving today’s problems. To address the range of problems faced by the industry, a number of alternative commuting vehicles have been developed. Yet the commercialization of these ‘alternative’ vehicles has yet to be successful. This is largely due failure of these vehicles to meet the changing demands of the industry and the limited understanding of consumer behaviour, motivation and attitudes. Deakin University’s Tomorrow’s Car concept tackles all of these problems. The vehicle is a novel three-wheeler cross over concept between a car and a motorbike that combines the best of both worlds. The vehicle combines the low cost, small size and ‘fun’ factor of a motorbike together with the safety, comfort and easy to drive features of a car produce a vehicle with a fuel efficiency better than either car or scooter. Intensive market research has been conducted for various major potential markets of alternative vehicles including India, China and Australia. The research analysed consumer attitudes in relation to narrow tilting vehicles, and in particular towards Deakin’s Tomorrow’s Car (TC). The study revealed that a relatively large percentage of consumers find such a concept very appealing. For the other consumers, the overall appearance and perception of safety and not the actual safety performance were found to be the most impeding factors of such vehicles. By addressing these issues and marketing the vehicle accordingly the successful commercialization of Tomorrow’s Car can be ensured.

A new fuzzy ratio and its application to the single input rule modules connected fuzzy inference system

The principle of ratios has been applied to many real world problems, e.g. the part-to-part and part-to-whole ratio formulations. As it is difficult for humans to provide an exact ratio in many real situations, we introduce a fuzzy ratio in this paper. We use some notions from fuzzy arithmetic to analyze fuzzy ratios captured from humans. An application of the formulated fuzzy ratio to a Single Input Rule Modules connected Fuzzy Inference System (SIRMs-FIS) is demonstrated. Instead of using a precise weight, fuzzy sets are employed to represent the relative importance of each rule module. The resulting fuzzy weights are explained as a fuzzy ratio on a weight domain. In addition, a new SIRMs-FIS model with fuzzy weights and part-to-whole fuzzy ratio is devised. A simulated example is presented to clarify the proposed SIRM-FIS model.

Engineering flexible teaching and learning in engineering education

The key challenges for achieving flexibility in flexible mode programmes in engineering and technology include: the integration of the explicit and implicit content in potentially disparate and isolated study modules across the whole programme curriculum; ensuring the validity and consistency of policies for granting students advanced standing based on recognition for prior learning and workplace experience; developing learning materials and experiences that cater for a wide and diverse audience, while at the same time offering relevance to the individual student in their own context; creating innovative communication environments that bring remote students into both the directed and the discursive discussion that are an important part of the learning process; and the financial and resourcing sustainability of the development, maintenance and delivery of high quality flexible mode  engineering and technology study programmes.

Development and application of model of resource utilization, costs, and outcomes for stroke (MORUCOS): an Australian economic model for stroke.

Objectives: To outline the development, structure, data assumptions, and application of an Australian economic model for stroke (Model of Resource Utilization, Costs, and Outcomes for Stroke [MORUCOS]). Methods: The model has a linked spreadsheet format with four modules to describe the disease burden and treatment pathways, estimate prevalence-based and incidence-based costs, and derive life expectancy and quality of life consequences. The model uses patient-level, community-based, stroke cohort data and macro-level simulations. An interventions module allows options for change to be consistently evaluated by modifying aspects of the other modules. To date, model validation has included sensitivity testing, face validity, and peer review. Further validation of technical and predictive accuracy is needed. The generic pathway model was assessed by comparison with a stroke subtypes (ischemic, hemorrhagic, or undetermined) approach and used to determine the relative cost-effectiveness of four interventions. Results: The generic pathway model produced lower costs compared with a subtypes version (total average first-year costs/case AUD$15,117 versus AUD$17,786, respectively). Optimal evidence-based uptake of anticoagulation therapy for primary and secondary stroke prevention and intravenous thrombolytic therapy within 3 hours of stroke were more cost-effective than current practice (base year, 1997). Conclusions: MORUCOS is transparent and flexible in describing Australian stroke care and can effectively be used to systematically evaluate a range of different interventions. Adjusting results to account for stroke subtypes, as they influence cost estimates, could enhance the generic model.

Passion in Jamie's kitchen : the vital ingredient in education and training for young workers?

In this paper we will sketch out and briefly analyse a recurring and central theme throughout the reality TV series Jamie’s Kitchen – that of passion:

• Passion for food;
• Being passionate as you construct and present yourself;
• Being passionate about your work;
• Having a go, getting passionate in a training environment which compresses years of training into months of training.

In this series the high profile celebrity chef Jamie Oliver set out to transform a group of unemployed young Londoners into the enterprising, entrepreneurial, ideal worker of 21st century flexible capitalism. This series, and its figure of the entrepreneurial, risk taking, small businessman (who in this instance is also a global celebrity brand) seeking to develop similar dispositions and behaviours in a workforce that initially does not display such character features, illuminates, and provides a means to explore, key features of new work regimes. The emphasis on passion in the analysis – which draws on Foucault’s later work on the care of the self - allows us to connect to discussions about education and training that highlight the passionate/pleasure dimensions of pedagogy. These elements of education and training very rarely get discussed in a vocational education and training environment which is largely driven by modules/competencies/outcomes.

Using multimedia and interactive games to enhance students' understanding of SCM

It is challenging to teach supply chain management (SCM) practices and technologies to tertiary students. This is because the back-end and highly dynamic processes can be difficult to visualise and because many students only have experience as a consumer. This paper reports the authors' experiences using a variety of multimedia and interactive enhancements we have used with our SCM learning materials: SCM business simulations; online learning modules with interactive games; and multimedia resources such as videos and animations. The paper also provides an overview of the challenges faced using these approaches, which gives rise to a number of future research opportunities. It also argues that these approaches can support educators with any epistemological view of learning. The paper makes a significant contribution because there has been little if any research into the use of these approaches in SCM education.

Strategic review of enhancements and culture-based fisheries

Enhancements are interventions in the life cycle of common-pool aquatic resources. Enhancement technologies include culture-based fisheries, habitat modifications, fertilization, feeding and elimination of predators/competitors. Enhancements are estimated to yield about two million mt per year, mostly from culture-based fisheries in fresh waters where they account for some 20 percent of capture, or 10 percent of combined capture and culture production. Marine enhancements are still at an experimental stage, but some have reached commercial production. Enhancements use limited external feed and energy inputs, and can provide very high returns for labour and capital input. Moreover, enhancement initiatives can facilitate institutional change and a more active management of aquatic resources, leading to increased productivity, conservation and wider social benefits. Enhancements may help to maintain population abundance, community structure and ecosystem functioning in the face of heavy exploitation and/or environmental degradation. Negative environmental impacts may arise from ecological and genetic interactions between enhanced and wild stocks. Many enhancements have not realised their full potential because of a failure to address specific institutional, technological, management and research requirements emanating from two key characteristics. Firstly, enhancement involves investment in common-pool resources and can only be sustained under institutional arrangements that allow regulation of use and a flow of benefits to those who bear the costs of enhancement. Secondly, interventions are limited to certain aspects of the life cycle of stocks, and outcomes are strongly dependent on natural conditions beyond management control. Hence, management must be adapted to local conditions to be effective, and certain conditions may preclude successful enhancement altogether. Governments have a major role to play in facilitating enhancement initiatives through the establishment of conducive institutional arrangements, appropriate research support, and the management of environmental and other impacts on and from enhancements.

Detection and classification of road signs in natural environments

An automatic road sign recognition system first locates road signs within images captured by an imaging sensor on-board of a vehicle, and then identifies the detected road signs. This paper presents an automatic neural-network-based road sign recognition system. First, a study of the existing road sign recognition research is presented. In this study, the issues associated with automatic road sign recognition are described, the existing methods developed to tackle the road sign recognition problem are reviewed, and a comparison of the features of these methods is given. Second, the developed road sign recognition system is described. The system is capable of analysing live colour road scene images, detecting multiple road signs within each image, and classifying the type of road signs detected. The system consists of two modules: detection and classification. The detection module segments the input image in the hue-saturation-intensity colour space, and then detects road signs using a Multi-layer Perceptron neural-network. The classification module determines the type of detected road signs using a series of one to one architectural Multi-layer Perceptron neural networks. Two sets of classifiers are trained using the Resillient-Backpropagation and Scaled-Conjugate-Gradient algorithms. The two modules of the system are evaluated individually first. Then the system is tested as a whole. The experimental results demonstrate that the system is capable of achieving an average recognition hit-rate of 95.96% using the scaled-conjugate-gradient trained classifiers.

Visual tracking of vehicles using multiresolution analysis and neural network

This paper describes the procedure for detection and tracking of a vehicle from an on-road image sequence taken by a monocular video capturing device in real time. The main objective of such a visual tracking system is to closely follow objects in each frame of a video stream, such that the object position as well as other geometric information are always known. In the tracking system described, the video capturing device is also moving. It is a challenge to detect and track a moving vehicle under a constantly changing environment coupled to real time video processing. The system suggested is robust to implement under different illuminating conditions by using the monocular video capturing device. The vehicle tracking algorithm is one of the most important modules in an autonomous vehicle system, not only it should be very accurate but also must have the safety of other vehicles, pedestrians, and the moving vehicle itself. In order to achieve this an algorithm of multi resolution technique based on Haar basis functions were used for the wavelet transform, where a combination of classification was carried out with the multilayer feed forward neural network. The classification is done in a reduced dimensional space, where principle component analysis (PCA) dimensional reduction technique has been applied to make the classification process much more efficient. The results show the effectiveness of the proposed methodology.

Development of DAL and DAPL languages for building distributed applications

A common characteristic among parallel/distributed programming languages is that the one language is used to specify not only the overall organisation of the distributed application, but also the functionality of the application. That is, the connectivity and functionality of processes are specified within a single program. Connectivity and functionality are independent aspects of a distributed application. This thesis shows that these two aspects can be specified separately, therefore allowing application designers to freely concentrate on either aspect in a modular fashion. Two new programming languages have been developed for specifying each aspect. These languages are for loosely coupled distributed applications based on message passing, and have been designed to simplify distributed programming by completely removing all low level interprocess communication. A suite of languages and tools has been designed and developed. It includes the two new languages, parsers, a compilation system to generate intermediate C code that is compiled to binary object modules, a run-time system to create, manage and terminate several distributed applications, and a shell to communicate with the run-tune system. DAL (Distributed Application Language) and DAPL (Distributed Application Process Language) are the new programming languages for the specification and development of process oriented, asynchronous message passing, distributed applications. These two languages have been designed and developed as part of this doctorate in order to specify such distributed applications that execute on a cluster of computers. Both languages are used to specify orthogonal components of an application, on the one hand the organisation of processes that constitute an application, and on the other the interface and functionality of each process. Consequently, these components can be created in a modular fashion, individually and concurrently. The DAL language is used to specify not only the connectivity of all processes within an application, but also a cluster of computers for which the application executes. Furthermore, sub-clusters can be specified for individual processes of an application to constrain a process to a particular group of computers. The second language, DAPL, is used to specify the interface, functionality and data structures of application processes. In addition to these languages, a DAL parser, a DAPL parser, and a compilation system have been designed and developed (in this project). This compilation system takes DAL and DAPL programs to generate object modules based on machine code, one module for each application process. These object modules are used by the Distributed Application System (DAS) to instantiate and manage distributed applications. The DAS system is another new component of this project. The purpose of the DAS system is to create, manage, and terminate many distributed applications of similar and different configurations. The creation procedure incorporates the automatic allocation of processes to remote machines. Application management includes several operations such as deletion, addition, replacement, and movement of processes, and also detection and reaction to faults such as a processor crash. A DAS operator communicates with the DAS system via a textual shell called DASH (Distributed Application SHell). This suite of languages and tools allowed distributed applications of varying connectivity and functionality to be specified quickly and simply at a high level of abstraction. DAL and DAPL programs of several processes may require a few dozen lines to specify as compared to several hundred lines of equivalent C code that is generated by the compilation system. Furthermore, the DAL and DAPL compilation system is successful at generating binary object modules, and the DAS system succeeds in instantiating and managing several distributed applications on a cluster.

Programmer friendly and efficient distributed shared memory integrated into a distributed operating system

Distributed Shared Memory (DSM) provides programmers with a shared memory environment in systems where memory is not physically shared. Clusters of Workstations (COWs), an often untapped source of computing power, are characterised by a very low cost/performance ratio. The combination of Clusters of Workstations (COWs) with DSM provides an environment in which the programmer can use the well known approaches and methods of programming for physically shared memory systems and parallel processing can be carried out to make full use of the computing power and cost advantages of the COW. The aim of this research is to synthesise and develop a distributed shared memory system as an integral part of an operating system in order to provide application programmers with a convenient environment in which the development and execution of parallel applications can be done easily and efficiently, and which does this in a transparent manner. Furthermore, in order to satisfy our challenging design requirements we want to demonstrate that the operating system into which the DSM system is integrated should be a distributed operating system. In this thesis a study into the synthesis of a DSM system within a microkernel and client-server based distributed operating system which uses both strict and weak consistency models, with a write-invalidate and write-update based approach for consistency maintenance is reported. Furthermore a unique automatic initialisation system which allows the programmer to start the parallel execution of a group of processes with a single library call is reported. The number and location of these processes are determined by the operating system based on system load information. The DSM system proposed has a novel approach in that it provides programmers with a complete programming environment in which they are easily able to develop and run their code or indeed run existing shared memory code. A set of demanding DSM system design requirements are presented and the incentives for the placement of the DSM system with a distributed operating system and in particular in the memory management server have been reported. The new DSM system concentrated on an event-driven set of cooperating and distributed entities, and a detailed description of the events and reactions to these events that make up the operation of the DSM system is then presented. This is followed by a pseudocode form of the detailed design of the main modules and activities of the primitives used in the proposed DSM system. Quantitative results of performance tests and qualitative results showing the ease of programming and use of the RHODOS DSM system are reported. A study of five different application is given and the results of tests carried out on these applications together with a discussion of the results are given. A discussion of how RHODOS’ DSM allows programmers to write shared memory code in an easy to use and familiar environment and a comparative evaluation of RHODOS DSM with other DSM systems is presented. In particular, the ease of use and transparency of the DSM system have been demonstrated through the description of the ease with which a moderately inexperienced undergraduate programmer was able to convert, write and run applications for the testing of the DSM system. Furthermore, the description of the tests performed using physically shared memory shows that the latter is indistinguishable from distributed shared memory; this is further evidence that the DSM system is fully transparent. This study clearly demonstrates that the aim of the research has been achieved; it is possible to develop a programmer friendly and efficient DSM system fully integrated within a distributed operating system. It is clear from this research that client-server and microkernel based distributed operating system integrated DSM makes shared memory operations transparent and almost completely removes the involvement of the programmer beyond classical activities needed to deal with shared memory. The conclusion can be drawn that DSM, when implemented within a client-server and microkernel based distributed operating system, is one of the most encouraging approaches to parallel processing since it guarantees performance improvements with minimal programmer involvement.