Specificity and affinity motifs for Grb2 SH2-ligand interactions

Protein–protein interactions are often mediated by the recognition of short continuous amino acid stretches on target proteins by specific binding domains. Affinity-based selection strategies have successfully been used to define recognition motifs for a large series of such protein domains. However, in many biological systems specificity of interaction may be of equal or greater importance than affinity. To address this issue we have developed a peptide library screening technology that can be used to directly define ligands for protein domains based on both affinity and specificity of interaction. We demonstrate the value of this approach by the selection of peptide ligands that are either highly specific for the Grb2 Src homology 2 (SH2) domain or that are cross-reactive between a group of related SH2 domains. Examination of previously identified physiological ligands for the Grb2 SH2 domain suggests that for these ligands regulation of the specificity of interaction may be an important factor for in vivo ligand selection.

Time-resolved fluorescence microscopy of gunshot residue: an application to forensic science

Time-resolved fluorescence microscopy has rapidly emerged as the technique of choice for many researchers aiming to gain specific insights into the dynamics of intricate biological systems. Although the unique advantages the technique provides over other methods have proven to be particularly useful in the biosciences, to date they have been largely unexploited by other research disciplines. In this paper, we demonstrate the capacity of time-resolved fluorescence microscopy as a practical analytical tool in the forensic sciences via the imaging of gunshot residues that are expelled when a firearm is discharged. This information may prove to be useful for determination of the true sequence of events that took place in a firearm related crime.

Enabling industrial scale simulation / emulation models

OLE Process Control (OPC) is an industry standard that facilitates the communication between PCs and Programmable Logic Controllers (PLC). This communication allows for the testing of control systems with an emulation model. When models require faster and higher volume communications, limitations within OPC prevent this. In this paper an interface is developed to allow high speed and high volume communications between a PC and PLC enabling the emulation of larger and more complex control systems and their models. By switching control of elements within the model between the model engine and the control system it is possible to use the model to validate the system design, test the real world control systems and visualise real world operation.

The influence of magnetic fields exposure on neurite outgrowth in PC12 rat pheochromocytoma cells

The aim of present work was to investigate the influence of magnetic fields exposure on neurite outgrowth in PC12 cells. The neurite number per cell, length of neurites and directions of neurite growth with respect to the direction of the magnetic field were analyzed after exposure to 50 Hz electromagnetic field for 96 h. A promotion was observed under a weak field (0.23 mT), as the average number of neurites per cell increased to 2.38±0.06 compared to 1.91±0.07 neurites/cell of the control dishes, while inhibition and directional outgrowth was evident under a relatively stronger field (1.32 mT). Our work shows that biological systems can be very sensitive to the strength of electromagnetic field.

Using multi-criteria decision analysis in natural resource management

The proposed volume aims to provide useful insights on the use of Multi-criteria Decision Analysis (MCDA) in natural resource management by examining a number of empirical applications for several countries and natural resources. There is increasing interest among researchers and policy makers in using MCDA to evaluate complex management issues and problems. While several books with empirical applications have been published, these applications are very recent. Evidence from major studies suggests that MCDA approaches to the management of water, forestry, wetland and other natural resources have substantially improved the design and implementation of natural resource and environmental policies. Using innovative approaches, such as MCDA, to manage complex natural systems will enhance our understanding and management of those systems. Stakeholder involvement is an important determinant of successful resource management, and MCDA provides a useful and effective framework for getting stakeholders involved in resource management decisions. Despite the general acceptance of the role of MCDA in natural resource management, problems remain in applying these techniques. Problems include difficulties in applying the techniques, eliciting required information, lack of suitable measures for environmental variables, and development of innovative methods to simplify the use of MCDA. The proposed book examines several applications of MCDA for several countries (Australia, USA and Europe) and natural resources, including forestry, water resources and vegetation.

The Code Red epidemic : a case study

An analysis of log files from an immune World Wide Web server was used to discover the patterns of infection from the Code Red worm variants.  Analogies are drawn to biological systems.  The need for protection is commented on.

Decision making to support an integrated infrastructure supply chain industrial ecological approach within public private partnerships

Supply chains are complex adaptive systems for which final performance depends upon numerous interdependent decisions made by numerous firms which synthesise inputs from various resources systems.  The dynamic interdependent behaviour of social, economic, material and informational resource systems within eco-industrial settings that support the built environment life cycle supply chains can be studied at the supply chain level.  The impact of megaprojects is significant and holds promise to explore the impact of decisions on various systems as it combines project and system boundaries.  Megaoprojects considered as major events within systems can produce critical revolutionary impacts on the systems within which they are embedded.  The decisions that are made on megaprojects are central to risk management.  typically major infrastructure projects are procured through a form of public private partnership (PPP).  The core principle of PPP is value for money which refers to the best available outcome attempting to take account of all benefits, costs and risks over the whole life of the procurement.  In this paper the focus is on Australia where there has been considerable acitivity in the use of PPPs.  With recent national infrastucture packages proposed to stimulate the economy due to the global financial crisis, decision modelling on risks is a revelant and critical matter not only in practice but also in the research community.  PPPs encourage the whole-of-lifecycle approach in the procurement and management of public sector assets by transparently recognising the costs and risks associated with the whole life of the required service or facility, thus integrated whole of life supply chains can be considered.  By creating a single point of responsibility for an entire project from inception through operation, a strong incentive is created for thinking about the effects that a design or construction decision will have on the effectiveness and efficiency of managing and maintaining a facility during its operational life.  The decision to procure holistic supply chains becomes a much more viable commercial reality in the PPP environment than previously considered in the usual commercial construction spot transactional approach.  These types of decisions tend to be imprecise, approximate and complex requireing justification and reasoning logic rather than the classical 'truth' logic.  The purpose of this paper is to develop a theoretical decision framework which combines interdependency and multi-values logic for supply chain procurement modelling.

Computational aspects of the numerical solution of SDEs

In the last 30 to 40 years, many researchers have combined to build the knowledge base of theory and solution techniques that can be applied to the case of differential equations which include the effects of noise. This class of ``noisy'' differential equations is now known as stochastic differential equations (SDEs). Markov diffusion processes are included within the field of SDEs through the drift and diffusion components of the Itô form of an SDE. When these drift and diffusion components are moderately smooth functions, then the processes' transition probability densities satisfy the Fokker-Planck-Kolmogorov (FPK) equation -- an ordinary partial differential equation (PDE). Thus there is a mathematical inter-relationship that allows solutions of SDEs to be determined from the solution of a noise free differential equation which has been extensively studied since the 1920s. The main numerical solution technique employed to solve the FPK equation is the classical Finite Element Method (FEM). The FEM is of particular importance to engineers when used to solve FPK systems that describe noisy oscillators. The FEM is a powerful tool but is limited in that it is cumbersome when applied to multidimensional systems and can lead to large and complex matrix systems with their inherent solution and storage problems. I show in this thesis that the stochastic Taylor series (TS) based time discretisation approach to the solution of SDEs is an efficient and accurate technique that provides transition and steady state solutions to the associated FPK equation. The TS approach to the solution of SDEs has certain advantages over the classical techniques. These advantages include their ability to effectively tackle stiff systems, their simplicity of derivation and their ease of implementation and re-use. Unlike the FEM approach, which is difficult to apply in even only two dimensions, the simplicity of the TS approach is independant of the dimension of the system under investigation. Their main disadvantage, that of requiring a large number of simulations and the associated CPU requirements, is countered by their underlying structure which makes them perfectly suited for use on the now prevalent parallel or distributed processing systems. In summary, l will compare the TS solution of SDEs to the solution of the associated FPK equations using the classical FEM technique. One, two and three dimensional FPK systems that describe noisy oscillators have been chosen for the analysis. As higher dimensional FPK systems are rarely mentioned in the literature, the TS approach will be extended to essentially infinite dimensional systems through the solution of stochastic PDEs. In making these comparisons, the advantages of modern computing tools such as computer algebra systems and simulation software, when used as an adjunct to the solution of SDEs or their associated FPK equations, are demonstrated.

Oxidative stress : emerging mitochondrial and cellular themes and variations in neuronal injury

Oxidative stress plays a central role in neuronal injury and cell death in acute and chronic pathological conditions. The cellular responses to oxidative stress embrace changes in mitochondria and other organelles, notably endoplasmic reticulum, and can lead to a number of cell death paradigms, which cover a spectrum from apoptosis to necrosis and include autophagy. In Alzheimer's disease, and other pathologies including Parkinson's disease, protein aggregation provides further cellular stresses that can initiate or feed into the pathways to cell death engendered by oxidative stress. Specific attention is paid here to mitochondrial dysfunction and programmed cell death, and the diverse modes of cell death mediated by mitochondria under oxidative stress. Novel insights into cellular responses to neuronal oxidative stress from a range of different stressors can be gained by detailed transcriptomics analyses. Such studies at the cellular level provide the key for understanding the molecular and cellular pathways whereby neurons respond to oxidative stress and undergo injury and death. These considerations underpin the development of detailed knowledge in more complex integrated systems, up to the intact human bearing the neuropathology, facilitating therapeutic advances.

Charismatic cops, patriarchs and a few good women : leadership, club culture and young peoples' drinking

The paper reports on key findings of a research project that examined the roles that communitybased
sporting clubs in the Australian state of Victoria play in shaping young people’s understandings and uses of alcohol. Our research imagined clubs as community hubs that are located in complex networks that impact on the ways that clubs understand their locations in communities, and which have unpredictable influences and consequences on club histories, culture and orientations to issues such as young people and alcohol use. The paper focuses on understanding the key roles played by club leaders in facilitating change and transformation in these contexts, particularly in terms of alcohol-related practices and the potential impact of these on young people’s uses and understanding of alcohol. We situate these findings in a framework that draws on the literature of complexity science and complex adaptive systems (CAS) to suggest that these practices and changes need to be understood in ways that allow for complexity, uncertainty, emergent behaviours and adaptive change.

Marking machinima : a case study in assessing student use of a Web 2.0 technology

The model of learning best suited to the future may be one which sees learning as the process of managing the different kinds of participation an individual might have in complex social systems. Learning capability and engagement is thus dependent on the relationship between an individual identity and social systems. We report on the incorporation of machinima, a Web 2.0 technology, as part of an interdisciplinary and collaborative project where the focus is not on the mastery of the tools or the acquisition of predetermined knowledge, but on the development of learning engagement. We provide the case study of a pilot project involving students across two Arts disciplines collaborating via the game, World of Warcraft, to produce an animated adaptation of one of Geoffrey Chaucer's Canterbury Tales. Their contributions were differently assessed according to the pre-existing requirements of their home disciplines. We argue that the assessment in such projects, in conjunction with innovations and experimentation with Web 2.0 technologies, should shift from an emphasis on product to process. We believe that this has a sound pedagogical and theoretical foundation, and also fits better with the increasingly digitalised, unfixed and interdisciplinary world that students will face on graduation.

Evolution of JAK-STAT pathway components : mechanisms and role in immune system development

Background
Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK) – Signal transducer and activator of transcription (STAT) pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP), Protein inhibitors against Stats (PIAS), and Suppressor of cytokine signaling (SOCS) proteins across a diverse range of organisms.

Results
Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components.

Conclusion
Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity.

Biofunctionalization of 3D nylon 6,6 scaffolds using a two-step surface modification

Nylon is a relatively inert polymer. The ability to easily functionalize nylon with biomolecules will improve the utilization of nylon in biological systems. A potential use of the biofunctionalized nylon scaffolds is in devices for cell therapeutics that can specifically select cells present in small numbers, such as hematopoietic stem cells. This study developed a versatile and simple two-step technique combining oxygen plasma treatment with wet silanization to graft biomolecules onto nylon 6,6 3D porous scaffolds. Scaffolds that were exposed to oxygen plasma exhibited up to 13-fold increase in silane attachment ((3-mercaptopropyl)trimethoxysilane/(3-aminopropyl)trimethoxysilane) compared to untreated scaffolds. To address the limitation of nondestructive characterization of the surface chemistry of 3D scaffolds, fluorescent CdSe/ZnS nanoparticles were used as a reporting tool for -NH(2) functionalized surfaces. Scaffolds that were covalently bound with neutravidin protein remained stable in phosphate buffered saline up to four months. Functionality of the neutravidin-grafted scaffolds was demonstrated by the specific binding of CD4 cells to the scaffold via CD4-specific antibody. Ultimately, these neutravidin-functionalized 3D nylon scaffolds could be easily customized on demand utilizing a plethora of biotinylated biomolecules (antibodies, enzymes and proteins) to select for specific cell of interest. This technique can be extended to other applications, including the enhancement of cell-scaffold interactions.

Developing a facility for glass façade performance testing

This research aims to investigate whether real spaces can support legitimate measurements on glazing energy and thermal comfort analysis. This paper presents the development of a research facility for doing this. It will test simple to complex glazing and shading systems in a real (occupied) interior office environment. The purpose of this research project is to compare measured results with those being simulated with existing software and to discover discrepancies between simulation and real measured results. What parameters characterize a glazing system, whether simple or complex? Can these parameters be used to predict the energy transfer and comfort in the space? One must begin with simple glazing systems and verify measured with readily known simulated results. It is, at present, very difficult to use geometric based software with thermal based software to predict the performance of complex glazing systems. However, if we can characterize glazing systems with a set of reliable measurements, we can provide the data necessary for predicting performance in a live space. Specifically, the Solar Heat Gain Coefficient (SHGC) is a variable parameter based upon solar incident angle to a glazing system and is intended to be measured in its integral components: solar transmittance and inward-flowing fraction (radiative/convective) heat gain. A new instrumental approach through variable surface coated heat flux meters is being investigated to provide the measurement of interior glazing surface radiative and convective heat gain. The results suggest that this instrumentation may support be a viable method of testing inward-flowing heat gains from the interior glass surface. The test set-up also considers the application of a well-known B&K 1221 Comfort Meter for determining thermal comfort responses in the ‘perimeter zone’ on the interior side of a façade. This work requires further investigation, but is intended to be used in conjunction with solar pyranometers measuring transmittance as well as the heat flux meter and surface temperature instrumentation.

Simulation-based knowledge management in airport operations

Capturing and retaining knowledge in any organization is a major challenge. This talk describes how these challenges have been addressed through simulation and modeling techniques for complex engineered systems. A series of case studies that focus on airport processes are used to demonstrate the concepts. Furthermore, the additional benefits that a simulation model can bring, through online control and decision-making support, are discussed.