Ex vivo investigation of novel wound healing therapies and development of a 3-D human skin equivalent wound model

It has previously been found that complexes comprised of vitronectin and growth factors (VN:GF) enhance keratinocyte protein synthesis and migration. More specifically, these complexes have been shown to significantly enhance the migration of dermal keratinocytes derived from human skin. In view of this, it was thought that these complexes may hold potential as a novel therapy for healing chronic wounds. However, there was no evidence indicating that the VN:GF complexes would retain their effect on keratinocytes in the presence of chronic wound fluid. The studies in this thesis demonstrate for the first time that the VN:GF complexes not only stimulate proliferation and migration of keratinocytes, but also these effects are maintained in the presence of chronic wound fluid in a 2-dimensional (2-D) cell culture model. Whilst the 2-D culture system provided insights into how the cells might respond to the VN:GF complexes, this investigative approach is not ideal as skin is a 3-dimensional (3-D) tissue. In view of this, a 3-D human skin equivalent (HSE) model, which reflects more closely the in vivo environment, was used to test the VN:GF complexes on epidermopoiesis. These studies revealed that the VN:GF complexes enable keratinocytes to migrate, proliferate and differentiate on a de-epidermalised dermis (DED), ultimately forming a fully stratified epidermis. In addition, fibroblasts were seeded on DED and shown to migrate into the DED in the presence of the VN:GF complexes and hyaluronic acid, another important biological factor in the wound healing cascade. This HSE model was then further developed to enable studies examining the potential of the VN:GF complexes in epidermal wound healing. Specifically, a reproducible partial-thickness HSE wound model was created in fully-defined media and monitored as it healed. In this situation, the VN:GF complexes were shown to significantly enhance keratinocyte migration and proliferation, as well as differentiation. This model was also subsequently utilized to assess the wound healing potential of a synthetic fibrin-like gel that had previously been demonstrated to bind growth factors. Of note, keratinocyte re-epitheliasation was shown to be markedly improved in the presence of this 3-D matrix, highlighting its future potential for use as a delivery vehicle for the VN:GF complexes. Furthermore, this synthetic fibrin-like gel was injected into a 4 mm diameter full-thickness wound created in the HSE, both keratinocytes and fibroblasts were shown to migrate into this gel, as revealed by immunofluorescence. Interestingly, keratinocyte migration into this matrix was found to be dependent upon the presence of the fibroblasts. Taken together, these data indicate that reproducible wounds, as created in the HSEs, provide a relevant ex vivo tool to assess potential wound healing therapies. Moreover, the models will decrease our reliance on animals for scientific experimentation. Additionally, it is clear that these models will significantly assist in the development of novel treatments, such as the VN:GF complexes and the synthetic fibrin-like gel described herein, ultimately facilitating their clinical trial in the treatment of chronic wounds.

Abstracting and correlating heterogeneous events to detect complex scenarios

The research presented in this thesis addresses inherent problems in signaturebased intrusion detection systems (IDSs) operating in heterogeneous environments. The research proposes a solution to address the difficulties associated with multistep attack scenario specification and detection for such environments. The research has focused on two distinct problems: the representation of events derived from heterogeneous sources and multi-step attack specification and detection. The first part of the research investigates the application of an event abstraction model to event logs collected from a heterogeneous environment. The event abstraction model comprises a hierarchy of events derived from different log sources such as system audit data, application logs, captured network traffic, and intrusion detection system alerts. Unlike existing event abstraction models where low-level information may be discarded during the abstraction process, the event abstraction model presented in this work preserves all low-level information as well as providing high-level information in the form of abstract events. The event abstraction model presented in this work was designed independently of any particular IDS and thus may be used by any IDS, intrusion forensic tools, or monitoring tools. The second part of the research investigates the use of unification for multi-step attack scenario specification and detection. Multi-step attack scenarios are hard to specify and detect as they often involve the correlation of events from multiple sources which may be affected by time uncertainty. The unification algorithm provides a simple and straightforward scenario matching mechanism by using variable instantiation where variables represent events as defined in the event abstraction model. The third part of the research looks into the solution to address time uncertainty. Clock synchronisation is crucial for detecting multi-step attack scenarios which involve logs from multiple hosts. Issues involving time uncertainty have been largely neglected by intrusion detection research. The system presented in this research introduces two techniques for addressing time uncertainty issues: clock skew compensation and clock drift modelling using linear regression. An off-line IDS prototype for detecting multi-step attacks has been implemented. The prototype comprises two modules: implementation of the abstract event system architecture (AESA) and of the scenario detection module. The scenario detection module implements our signature language developed based on the Python programming language syntax and the unification-based scenario detection engine. The prototype has been evaluated using a publicly available dataset of real attack traffic and event logs and a synthetic dataset. The distinct features of the public dataset are the fact that it contains multi-step attacks which involve multiple hosts with clock skew and clock drift. These features allow us to demonstrate the application and the advantages of the contributions of this research. All instances of multi-step attacks in the dataset have been correctly identified even though there exists a significant clock skew and drift in the dataset. Future work identified by this research would be to develop a refined unification algorithm suitable for processing streams of events to enable an on-line detection. In terms of time uncertainty, identified future work would be to develop mechanisms which allows automatic clock skew and clock drift identification and correction. The immediate application of the research presented in this thesis is the framework of an off-line IDS which processes events from heterogeneous sources using abstraction and which can detect multi-step attack scenarios which may involve time uncertainty.

Identification and analysis of business and software services : A consolidated approach

Although the benefits of service orientation are prevalent in literature, a review, analysis, and evaluation of the 30 existing service analysis approaches presented in this paper have shown that a comprehensive approach to the identification and analysis of both business and supporting software services is missing. Based on this evaluation of existing approaches and additional sources, we close this gap by proposing an integrated, consolidated approach to business and software service analysis that combines and extends the strengths of the examined methodologies.

Indoor environments : design, productivity and health

In a typical large office block, by far the largest lifetime expense is the salaries of the workers - 84% for salaries compared with : office rent (14%), total energy (1%), and maintenance (1%). The key drive for business is therefore the maximisation of the productivity of the employees as this is the largest cost. Reducing total energy use by 50% will not produce the same financial return as 1% productivity improvement? The aim of the project which led to this review of the literature was to understand as far as possible the state of knowledge internationally about how the indoor environment of buildings does influence occupants and the impact this influence may have on the total cost of ownership of buildings. Therefore one of the main focus areas for the literature has been identifying whether there is a link between productivity and health of building occupants and the indoor environment. Productivity is both easy to define - the ratio of output to input - but at the same time very hard to measure in a relatively small environment where individual contributions can influence the results, in particular social interactions. Health impacts from a building environment are also difficult to measure well, as establishing casual links between the indoor environment and a particular health issue can be very difficult. All of those issues are canvassed in the literature reported here. Humans are surprisingly adaptive to different physical environments, but the workplace should not test the limits of human adaptability. Physiological models of stress, for example, accept that the body has a finite amount of adaptive energy available to cope with stress. The importance of, and this projects' focus on, the physical setting within the integrated system of high performance workplaces, means this literature survey explores research which has been undertaken on both physical and social aspects of the built environment. The literature has been largely classified in several different ways, according to the classification scheme shown below. There is still some inconsistency in the use of keywords, which is being addressed and greater uniformity will be developed for a CD version of this literature, enabling searching using this classification scheme.

Security and legal issues in E-tendering

The Queensland Department of Public Works (QDPW) and the Queensland Department of Main Roads (QDMR) have identified a need for industry e-contracting guidelines in the short to medium term. Each of these organisations conducts tenders and contracts for over $600 million annually. This report considers the security and legal issues relating to the shift from a paper-based tendering system to an electronic tendering system. The research objectives derived from the industry partners include: • a review of current standards and e-tendering systems; • a summary of legal requirements impacting upon e-tendering; • an analysis of the threats and requirements for any e-tendering system; • the identification of outstanding issues; • an evaluation of possible e-tendering architectures; • recommendations for e-tendering systems.

Fusion of in-vehicle sensor data to develop Intelligent Driver Training System (IDTS)

The over represented number of novice drivers involved in crashes is alarming. Driver training is one of the interventions aimed at mitigating the number of crashes that involve young drivers. To our knowledge, Advanced Driver Assistance Systems (ADAS) have never been comprehensively used in designing an intelligent driver training system. Currently, there is a need to develop and evaluate ADAS that could assess driving competencies. The aim is to develop an unsupervised system called Intelligent Driver Training System (IDTS) that analyzes crash risks in a given driving situation. In order to design a comprehensive IDTS, data is collected from the Driver, Vehicle and Environment (DVE), synchronized and analyzed. The first implementation phase of this intelligent driver training system deals with synchronizing multiple variables acquired from DVE. RTMaps is used to collect and synchronize data like GPS, vehicle dynamics and driver head movement. After the data synchronization, maneuvers are segmented out as right turn, left turn and overtake. Each maneuver is composed of several individual tasks that are necessary to be performed in a sequential manner. This paper focuses on turn maneuvers. Some of the tasks required in the analysis of ‘turn’ maneuver are: detect the start and end of the turn, detect the indicator status change, check if the indicator was turned on within a safe distance and check the lane keeping during the turn maneuver. This paper proposes a fusion and analysis of heterogeneous data, mainly involved in driving, to determine the risk factor of particular maneuvers within the drive. It also explains the segmentation and risk analysis of the turn maneuver in a drive.

Extending the advanced forensic format to accommodate multiple data sources, logical evidence, arbitrary information and forensic workflow

Forensic analysis requires the acquisition and management of many different types of evidence, including individual disk drives, RAID sets, network packets, memory images, and extracted files. Often the same evidence is reviewed by several different tools or examiners in different locations. We propose a backwards-compatible redesign of the Advanced Forensic Formatdan open, extensible file format for storing and sharing of evidence, arbitrary case related information and analysis results among different tools. The new specification, termed AFF4, is designed to be simple to implement, built upon the well supported ZIP file format specification. Furthermore, the AFF4 implementation has downward comparability with existing AFF files.

Integrating hardware and software information flow analyses

Security-critical communications devices must be evaluated to the highest possible standards before they can be deployed. This process includes tracing potential information flow through the device's electronic circuitry, for each of the device's operating modes. Increasingly, however, security functionality is being entrusted to embedded software running on microprocessors within such devices, so new strategies are needed for integrating information flow analyses of embedded program code with hardware analyses. Here we show how standard compiler principles can augment high-integrity security evaluations to allow seamless tracing of information flow through both the hardware and software of embedded systems. This is done by unifying input/output statements in embedded program execution paths with the hardware pins they access, and by associating significant software states with corresponding operating modes of the surrounding electronic circuitry.

Hybrid system simulation of computer control applications over communication networks

Discrete event-driven simulations of digital communication networks have been used widely. However, it is difficult to use a network simulator to simulate a hybrid system in which some objects are not discrete event-driven but are continuous time-driven. A networked control system (NCS) is such an application, in which physical process dynamics are continuous by nature. We have designed and implemented a hybrid simulation environment which effectively integrates models of continuous-time plant processes and discrete-event communication networks by extending the open source network simulator NS-2. To do this a synchronisation mechanism was developed to connect a continuous plant simulation with a discrete network simulation. Furthermore, for evaluating co-design approaches in an NCS environment, a piggybacking method was adopted to allow the control period to be adjusted during simulations. The effectiveness of the technique is demonstrated through case studies which simulate a networked control scenario in which the communication and control system properties are defined explicitly.

Towards continuous surveillance of fruit flies using sensor networks and machine vision

In Australia, the Queensland fruit fly (B. tryoni), is the most destructive insect pest of horticulture, attacking nearly all fruit and vegetable crops. This project has researched and prototyped a system for monitoring fruit flies so that authorities can be alerted when a fly enters a crop in a more efficient manner than is currently used. This paper presents the idea of our sensor platform design as well as the fruit fly detection and recognition algorithm by using machine vision techniques. Our experiments showed that the designed trap and sensor platform is capable to capture quality fly images, the invasive flies can be successfully detected and the average precision of the Queensland fruit fly recognition is 80% from our experiment.

Formative and reflective measurement and validation mismatch in survey research : an archival analysis of information systems success constructs 1985-2007

The generic IS-success constructs first identified by DeLone and McLean (1992) continue to be widely employed in research. Yet, recent work by Petter et al (2007) has cast doubt on the validity of many mainstream constructs employed in IS research over the past 3 decades; critiquing the almost universal conceptualization and validation of these constructs as reflective when in many studies the measures appear to have been implicitly operationalized as formative. Cited examples of proper specification of the Delone and McLean constructs are few, particularly in light of their extensive employment in IS research. This paper introduces a four-stage formative construct development framework: Conceive > Operationalize > Respond > Validate (CORV). Employing the CORV framework in an archival analysis of research published in top outlets 1985-2007, the paper explores the extent of possible problems with past IS research due to potential misspecification of the four application-related success dimensions: Individual-Impact, Organizational-Impact, System-Quality and Information-Quality. Results suggest major concerns where there is a mismatch of the Respond and Validate stages. A general dearth of attention to the Operationalize and Respond stages in methodological writings is also observed.

Reconceptualising the information system as a service

The study will cross-fertilise Information Systems (IS) and Services Marketing ideas through reconceptualising the information system as a service (ISaaS). The study addresses known limitations of arguably the two most significant dependent variables in these disciplines - Information System Success or IS-Impact, and Service Quality. Planned efforts to synthesise analogous conceptions across these disciplines, are expected to force a deeper theoretical understanding of the broad notions of success, quality, value and satisfaction and their interrelations. The aims of this research are to: (1) yield a conceptually superior and more extensively validated IS success measurement model, and (2) develop and operationalise a more rigorously validated Service Quality measurement model, while extending the ‘service’ notion to ‘operational computer-based information systems in organisations’. In the development of the new models the study will address contemporary validation issues.

Open and trusted information systems/health informatics access control (OTHIS/HIAC)

Information and Communications Technologies globally are moving towards Service Oriented Architectures and Web Services. The healthcare environment is rapidly moving to the use of Service Oriented Architecture/Web Services systems interconnected via this global open Internet. Such moves present major challenges where these structures are not based on highly trusted operating systems. This paper argues the need of a radical re-think of access control in the contemporary healthcare environment in light of modern information system structures, legislative and regulatory requirements, and security operation demands in Health Information Systems. This paper proposes the Open and Trusted Health Information Systems (OTHIS), a viable solution including override capability to the provision of appropriate levels of secure access control for the protection of sensitive health data.

Detecting and resolving redundancies in EP3P policies

Current regulatory requirements on data privacy make it increasingly important for enterprises to be able to verify and audit their compliance with their privacy policies. Traditionally, a privacy policy is written in a natural language. Such policies inherit the potential ambiguity, inconsistency and mis-interpretation of natural text. Hence, formal languages are emerging to allow a precise specification of enforceable privacy policies that can be verified. The EP3P language is one such formal language. An EP3P privacy policy of an enterprise consists of many rules. Given the semantics of the language, there may exist some rules in the ruleset which can never be used, these rules are referred to as redundant rules. Redundancies adversely affect privacy policies in several ways. Firstly, redundant rules reduce the efficiency of operations on privacy policies. Secondly, they may misdirect the policy auditor when determining the outcome of a policy. Therefore, in order to address these deficiencies it is important to identify and resolve redundancies. This thesis introduces the concept of minimal privacy policy - a policy that is free of redundancy. The essential component for maintaining the minimality of privacy policies is to determine the effects of the rules on each other. Hence, redundancy detection and resolution frameworks are proposed. Pair-wise redundancy detection is the central concept in these frameworks and it suggests a pair-wise comparison of the rules in order to detect redundancies. In addition, the thesis introduces a policy management tool that assists policy auditors in performing several operations on an EP3P privacy policy while maintaining its minimality. Formal results comparing alternative notions of redundancy, and how this would affect the tool, are also presented.

Enforcing P3P policies using a digital rights management system

The protection of privacy has gained considerable attention recently. In response to this, new privacy protection systems are being introduced. SITDRM is one such system that protects private data through the enforcement of licenses provided by consumers. Prior to supplying data, data owners are expected to construct a detailed license for the potential data users. A license specifies whom, under what conditions, may have what type of access to the protected data. The specification of a license by a data owner binds the enterprise data handling to the consumer’s privacy preferences. However, licenses are very detailed, may reveal the internal structure of the enterprise and need to be kept synchronous with the enterprise privacy policy. To deal with this, we employ the Platform for Privacy Preferences Language (P3P) to communicate enterprise privacy policies to consumers and enable them to easily construct data licenses. A P3P policy is more abstract than a license, allows data owners to specify the purposes for which data are being collected and directly reflects the privacy policy of an enterprise.