Cholesterol enhances phospholipid-dependent activated protein C anticoagulant activity

The influence of cholesterol on activated protein C (APC) anticoagulant activity in plasma and on factor Va inactivation was investigated. Anticoagulant and procoagulant activities of phosphatidylcholine/phosphatidylserine (PC/PS) vesicles containing cholesterol were assessed in the presence and absence of APC using factor Xa-1-stage clotting and factor Va inactivation assays. Cholesterol at approximate physiological membrane levels (30%) in PC/PS (60%/10% w/w) vesicles prolonged the factor Xa-1-stage clotting time dose-dependently in the presence of APC but not in the absence of APC. APC-mediated cleavage of purified recombinant factor Va variants that were modified at specific APC cleavage sites (Q306/Q679-factor Va; Q506/Q679-factor Va) was studied to define the effects of cholesterol on APC cleavage at R506 and R306. When compared to control PC/PS vesicles, cholesterol in PC/PS vesicles enhanced factor Va inactivation and the rate of APC cleavage at both R506 and R306. Cholesterol also enhanced APC cleavage rates at R306 in the presence of the APC cofactor, protein S. In summary, APC anticoagulant activity in plasma and factor Va inactivation as a result of cleavages at R506 and R306 by APC is markedly enhanced by cholesterol in phospholipid vesicles. These results suggest that cholesterol in a membrane surface may selectively enhance APC activities. © 2005 International Society on Thrombosis and Haemostasis.

Path planning, guidance and control for a UAV forced landing

A forced landing is an unscheduled event in flight requiring an emergency landing, and is most commonly attributed to engine failure, failure of avionics or adverse weather. Since the ability to conduct a successful forced landing is the primary indicator for safety in the aviation industry, automating this capability for unmanned aerial vehicles (UAVs) will help facilitate their integration into, and subsequent routine operations over civilian airspace. Currently, there is no commercial system available to perform this task; however, a team at the Australian Research Centre for Aerospace Automation (ARCAA) is working towards developing such an automated forced landing system. This system, codenamed Flight Guardian, will operate onboard the aircraft and use machine vision for site identification, artificial intelligence for data assessment and evaluation, and path planning, guidance and control techniques to actualize the landing. This thesis focuses on research specific to the third category, and presents the design, testing and evaluation of a Trajectory Generation and Guidance System (TGGS) that navigates the aircraft to land at a chosen site, following an engine failure. Firstly, two algorithms are developed that adapts manned aircraft forced landing techniques to suit the UAV planning problem. Algorithm 1 allows the UAV to select a route (from a library) based on a fixed glide range and the ambient wind conditions, while Algorithm 2 uses a series of adjustable waypoints to cater for changing winds. A comparison of both algorithms in over 200 simulated forced landings found that using Algorithm 2, twice as many landings were within the designated area, with an average lateral miss distance of 200 m at the aimpoint. These results present a baseline for further refinements to the planning algorithms. A significant contribution is seen in the design of the 3-D Dubins Curves planning algorithm, which extends the elementary concepts underlying 2-D Dubins paths to account for powerless flight in three dimensions. This has also resulted in the development of new methods in testing for path traversability, in losing excess altitude, and in the actual path formation to ensure aircraft stability. Simulations using this algorithm have demonstrated lateral and vertical miss distances of under 20 m at the approach point, in wind speeds of up to 9 m/s. This is greater than a tenfold improvement on Algorithm 2 and emulates the performance of manned, powered aircraft. The lateral guidance algorithm originally developed by Park, Deyst, and How (2007) is enhanced to include wind information in the guidance logic. A simple assumption is also made that reduces the complexity of the algorithm in following a circular path, yet without sacrificing performance. Finally, a specific method of supplying the correct turning direction is also used. Simulations have shown that this new algorithm, named the Enhanced Nonlinear Guidance (ENG) algorithm, performs much better in changing winds, with cross-track errors at the approach point within 2 m, compared to over 10 m using Park's algorithm. A fourth contribution is made in designing the Flight Path Following Guidance (FPFG) algorithm, which uses path angle calculations and the MacCready theory to determine the optimal speed to fly in winds. This algorithm also uses proportional integral- derivative (PID) gain schedules to finely tune the tracking accuracies, and has demonstrated in simulation vertical miss distances of under 2 m in changing winds. A fifth contribution is made in designing the Modified Proportional Navigation (MPN) algorithm, which uses principles from proportional navigation and the ENG algorithm, as well as methods specifically its own, to calculate the required pitch to fly. This algorithm is robust to wind changes, and is easily adaptable to any aircraft type. Tracking accuracies obtained with this algorithm are also comparable to those obtained using the FPFG algorithm. For all three preceding guidance algorithms, a novel method utilising the geometric and time relationship between aircraft and path is also employed to ensure that the aircraft is still able to track the desired path to completion in strong winds, while remaining stabilised. Finally, a derived contribution is made in modifying the 3-D Dubins Curves algorithm to suit helicopter flight dynamics. This modification allows a helicopter to autonomously track both stationary and moving targets in flight, and is highly advantageous for applications such as traffic surveillance, police pursuit, security or payload delivery. Each of these achievements serves to enhance the on-board autonomy and safety of a UAV, which in turn will help facilitate the integration of UAVs into civilian airspace for a wider appreciation of the good that they can provide. The automated UAV forced landing planning and guidance strategies presented in this thesis will allow the progression of this technology from the design and developmental stages, through to a prototype system that can demonstrate its effectiveness to the UAV research and operations community.

A comparison of the effects of a chlamydial vaccine administered during or after a C. muridarum urogenital infection of female mice

There are approximately 92 million new chlamydial infections of the genital tract in humans diagnosed each year, costing health care systems billions of dollars in treatment not only of acute infections, but also of associated inflammatory sequelae, such as pelvic inflammatory disease (PID) and ectopic pregnancy. These numbers are increasing at a steady rate and, due to the asymptomatic nature of infections, the incidence may be underestimated and the costs of treatment therefore higher. Over the previous few decades there has been a large amount of research into the development of an efficacious vaccine against genital tract chlamydial infections. The majority of this research has focused on females, due to the high rate of development of associated diseases, including PID, which can lead to ectopic pregnancy and infertility. In light of the increasing infection rates that have occurred despite the availability of antibiotics, and the asymptomatic nature of chlamydial infections, it is imperative that an efficacious vaccine that protects against infection and associated pathology be developed.

Explanations of police racism

This paper describes the development of a substantive theory about police racism as the most significant factor, from among a number of competing societal based explanations, in accounting for Aboriginal over-representation in police arrest rates.

Gonadotropin-induced ovarian cancer cell migration and proliferation require extracellular signal-regulated kinase 1/2 activation regulated by calcium and protein kinase Cδ

The gonadotropin hypothesis proposes that elevated serum gonadotropin levels may increase the risk of epithelial ovarian cancer (EOC). We have studied the effect of treating EOC cell lines (OV207 and OVCAR-3) with FSH or LH. Both gonadotropins activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and increased cell migration that was inhibited by the MAPK 1 inhibitor PD98059. Both extra- and intracellular calcium ion signalling were implicated in gonadotropin-induced ERK1/2 activation as treatment with either the calcium chelator EGTA or an inhibitor of intracellular calcium release, dantrolene, inhibited gonadotropin-induced ERK1/2 activation. Verapamil was also inhibitory, indicating that gonadotropins activate calcium influx via L-type voltage-dependent calcium channels. The cAMP/protein kinase A (PKA) pathway was not involved in the mediation of gonadotropin action in these cells as gonadotropins did not increase intracellular cAMP formation and inhibition of PKA did not affect gonadotropin-induced phosphorylation of ERK1/2. Activation of ERK1/2 was inhibited by the protein kinase C (PKC) inhibitor GF 109203X as well as by the PKCδ inhibitor rottlerin, and downregulation of PKCδ was inhibited by small interfering RNA (siRNA), highlighting the importance of PKCδ in the gonadotropin signalling cascade. Furthermore, in addition to inhibition by PD98059, gonadotropin-induced ovarian cancer cell migration was also inhibited by verapamil, GF 109203X and rottlerin. Similarly, gonadotropin-induced proliferation was inhibited by PD98059, verapamil, GF 109203X and PKCδ siRNA. Taken together, these results demonstrate that gonadotropins induce both ovarian cancer cell migration and proliferation by activation of ERK1/2 signalling in a calcium- and PKCδ-dependent manner.

Designing university, government and industry community engagement to build informed and effective interventions in the area of road safety

Individuals, community organisations and industry have always been involved to varying degrees in efforts to address the Queensland road toll. Traditionally, road crash prevention efforts have been led by state and local government organisations. While community and industry groups have sometimes become involved (e.g. Driver Reviver campaign), their efforts have largely been uncoordinated and under-resourced. A common strength of these initiatives lies in the energy, enthusiasm and persistence of community-based efforts. Conversely, a weakness has sometimes been the lack of knowledge, awareness or prioritisation of evidence-based interventions or their capacity to build on collaborative efforts. In 2000, the Queensland University of Technology’s Centre for Accident Research and Road Safety – Queensland (CARRS-Q) identified this issue as an opportunity to bridge practice and research and began acknowledging a selection of these initiatives, in partnership with the RACQ, through the Queensland Road Safety Awards program. After nine years it became apparent there was need to strengthen this connection, with the Centre establishing a Community Engagement Workshop in 2009 as part of the overall Awards program. With an aim of providing community participants opportunities to see, hear and discuss the experiences of others, this event was further developed in 2010, and with the collaboration of the Queensland Department of Transport and Main Roads, the RACQ, Queensland Police Service and Leighton Contractors Pty Ltd, a stand-alone Queensland Road Safety Awards Community Engagement Workshop was held in 2010. Each collaborating organisation recognised a need to mobilise the community through effective information and knowledge sharing, and recognised that learning and discussion can influence lasting behaviour change and action in this often emotive, yet not always evidence-based, area. This free event featured a number of speakers representing successful projects from around Australia and overseas. Attendees were encouraged to interact with the speakers, to ask questions, and most importantly, build connections with other attendees to build a ‘community road safety army’ all working throughout Australia on projects underpinned by evaluated research. The workshop facilitated the integration of research, policy and grass-roots action enhancing the success of community road safety initiatives. For collaboration partners, the event enabled them to transfer their knowledge in an engaged approach, working within a more personal communication process. An analysis of the success factors for this event identified openness to community groups and individuals, relevance of content to local initiatives, generous support with the provision of online materials and ongoing communication with key staff members as critical and supports the view that the university can directly provide both the leadership and the research needed for effective and credible community-based initiatives to address injury and death on the roads.

Car ownership, mileage, and risky driving among young intermediate drivers

Introduction: Young drivers are at greatest risk of injury or death from a car crash in the first six months of independent driving. In Queensland, the graduated driver licensing (GDL) program was extensively modified in July 2007 and aims to minimise this risk. Increased mileage and car ownership have been found to play a role in risky driving, offences and crashes; however GDL programs typically do not consider these variables. The paper explores the mileage and car ownership characteristics of young newly-licensed intermediate (Provisional) drivers and their relation to risky driving, crashes and offences. Methods: Drivers (n = 1032) aged 17-19 years recruited from across Queensland for longitudinal research completed Survey 1 exploring pre-licence and Learner experiences and sociodemographic characteristics. Survey 2 explored the same variables with a subset of these drivers (n = 341) after they had completed their first six months of independent driving. Results: At Survey 2, most young drivers owned their vehicle. Novices who drove more kilometres and who spent more hours each week driving were more likely to report risky driving. These drivers were also more likely to report being detected by Police for a driving-related offence. Conclusions: GDL programs should incorporate education for the parent and novice driver regarding the increased risks associated with increased driving exposure, particularly where the novices own their vehicle. Parents should be encouraged to delay exclusive access to a vehicle for the novice driver.