Involvement of Exo1b in DNA damage-induced apoptosis

Apoptosis is essential for the maintenance of inherited genomic integrity. During DNA damage-induced apoptosis, mechanisms of cell survival, such as DNA repair are inactivated to allow cell death to proceed. Here, we describe a role for the mammalian DNA repair enzyme Exonuclease 1 (Exo1) in DNA damage-induced apoptosis. Depletion of Exo1 in human fibroblasts, or mouse embryonic fibroblasts led to a delay in DNA damage-induced apoptosis. Furthermore, we show that Exo1 acts upstream of caspase-3, DNA fragmentation and cytochrome c release. In addition, induction of apoptosis with DNA-damaging agents led to cleavage of both isoforms of Exo1. The cleavage of Exo1 was mapped to Asp514, and shown to be mediated by caspase-3. Expression of a caspase-3 cleavage site mutant form of Exo1, Asp514Ala, prevented formation of the previously observed fragment without any affect on the onset of apoptosis. We conclude that Exo1 has a role in the timely induction of apoptosis and that it is subsequently cleaved and degraded during apoptosis, potentially inhibiting DNA damage repair.

Modulation of depth-dependent properties in tissue-engineered cartilage with a semi-permeable membrane and perfusion : a continuum model of matrix metabolism and transport

The functional properties of cartilaginous tissues are determined predominantly by the content, distribution, and organization of proteoglycan and collagen in the extracellular matrix. Extracellular matrix accumulates in tissue-engineered cartilage constructs by metabolism and transport of matrix molecules, processes that are modulated by physical and chemical factors. Constructs incubated under free-swelling conditions with freely permeable or highly permeable membranes exhibit symmetric surface regions of soft tissue. The variation in tissue properties with depth from the surfaces suggests the hypothesis that the transport processes mediated by the boundary conditions govern the distribution of proteoglycan in such constructs. A continuum model (DiMicco and Sah in Transport Porus Med 50:57-73, 2003) was extended to test the effects of membrane permeability and perfusion on proteoglycan accumulation in tissue-engineered cartilage. The concentrations of soluble, bound, and degraded proteoglycan were analyzed as functions of time, space, and non-dimensional parameters for several experimental configurations. The results of the model suggest that the boundary condition at the membrane surface and the rate of perfusion, described by non-dimensional parameters, are important determinants of the pattern of proteoglycan accumulation. With perfusion, the proteoglycan profile is skewed, and decreases or increases in magnitude depending on the level of flow-based stimulation. Utilization of a semi-permeable membrane with or without unidirectional flow may lead to tissues with depth-increasing proteoglycan content, resembling native articular cartilage.

Review of the under the limit drink driving rehabilitation program

The combination of alcohol and driving is a major health and economic burden to most communities in industrialised countries. The total cost of crashes for Australia in 1996 was estimated at approximately 15 billion dollars and the costs for fatal crashes were about 3 billion dollars (BTE, 2000). According to the Bureau of Infrastructure, Transport and Regional Development and Local Government (2009; BITRDLG) the overall cost of road fatality crashes for 2006 $3.87 billion, with a single fatal crash costing an estimated $2.67 million. A major contributing factor to crashes involving serious injury is alcohol intoxication while driving. It is a well documented fact that consumption of liquor impairs judgment of speed, distance and increases involvement in higher risk behaviours (Waller, Hansen, Stutts, & Popkin, 1986a; Waller et al., 1986b). Waller et al. (1986a; b) asserts that liquor impairs psychomotor function and therefore renders the driver impaired in a crisis situation. This impairment includes; vision (degraded), information processing (slowed), steering, and performing two tasks at once in congested traffic (Moskowitz & Burns, 1990). As BAC levels increase the risk of crashing and fatality increase exponentially (Department of Transport and Main Roads, 2009; DTMR). According to Compton et al. (2002) as cited in the Department of Transport and Main Roads (2009), crash risk based on probability, is five times higher when the BAC is 0.10 compared to a BAC of 0.00. The type of injury patterns sustained also tends to be more severe when liquor is involved, especially with injuries to the brain (Waller et al., 1986b). Single and Rohl (1997) reported that 30% of all fatal crashes in Australia where alcohol involvement was known were associated with Breadth Analysis Content (BAC) above the legal limit of 0.05gms/100ml. Alcohol related crashes therefore contributes to a third of the total cost of fatal crashes (i.e. $1 billion annually) and crashes where alcohol is involved are more likely to result in death or serious injury (ARRB Transport Research, 1999). It is a major concern that a drug capable of impairment such as is the most available and popular drug in Australia (Australian Institute of Health and Welfare, 2007; AIHW). According to the AIHW (2007) 89.9% of the approximately 25,000 Australians over the age of 14 surveyed had consumed at some point in time, and 82.9% had consumed liquor in the previous year. This study found that 12.1% of individuals admitted to driving a motor vehicle whilst intoxicated. In general males consumed more liquor in all age groups. In Queensland there were 21503 road crashes in 2001, involving 324 fatalities and the largest contributing factor was alcohol and or drugs (Road Traffic Report, 2001). 23438 road crashes in 2004, involving 289 fatalities and the largest contributing factor was alcohol and or drugs (DTMR, 2009). Although a number of measures such as random breath testing have been effective in reducing the road toll (Watson, Fraine & Mitchell, 1995) the recidivist drink driver remains a serious problem. These findings were later supported with research by Leal, King, and Lewis (2006). This Queensland study found that of the 24661 drink drivers intercepted in 2004, 3679 (14.9%) were recidivists with multiple drink driving convictions in the previous three years covered (Leal et al., 2006). The legal definition of the term “recidivist” is consistent with the Transport Operations (Road Use Management) Act (1995) and is assigned to individuals who have been charged with multiple drink driving offences in the previous five years. In Australia relatively little attention has been given to prevention programs that target high-risk repeat drink drivers. However, over the last ten years a rehabilitation program specifically designed to reduce recidivism among repeat drink drivers has been operating in Queensland. The program, formally known as the “Under the Limit” drink driving rehabilitation program (UTL) was designed and implemented by the research team at the Centre for Accident Research and Road Safety in Queensland with funding from the Federal Office of Road Safety and the Institute of Criminology (see Sheehan, Schonfeld & Davey, 1995). By 2009 over 8500 drink-drivering offenders had been referred to the program (Australian Institute of Crime, 2009).

Machine prognostics based on health state probability estimation

The ability to accurately predict the remaining useful life of machine components is critical for machine continuous operation and can also improve productivity and enhance system’s safety. In condition-based maintenance (CBM), maintenance is performed based on information collected through condition monitoring and assessment of the machine health. Effective diagnostics and prognostics are important aspects of CBM for maintenance engineers to schedule a repair and to acquire replacement components before the components actually fail. Although a variety of prognostic methodologies have been reported recently, their application in industry is still relatively new and mostly focused on the prediction of specific component degradations. Furthermore, they required significant and sufficient number of fault indicators to accurately prognose the component faults. Hence, sufficient usage of health indicators in prognostics for the effective interpretation of machine degradation process is still required. Major challenges for accurate longterm prediction of remaining useful life (RUL) still remain to be addressed. Therefore, continuous development and improvement of a machine health management system and accurate long-term prediction of machine remnant life is required in real industry application. This thesis presents an integrated diagnostics and prognostics framework based on health state probability estimation for accurate and long-term prediction of machine remnant life. In the proposed model, prior empirical (historical) knowledge is embedded in the integrated diagnostics and prognostics system for classification of impending faults in machine system and accurate probability estimation of discrete degradation stages (health states). The methodology assumes that machine degradation consists of a series of degraded states (health states) which effectively represent the dynamic and stochastic process of machine failure. The estimation of discrete health state probability for the prediction of machine remnant life is performed using the ability of classification algorithms. To employ the appropriate classifier for health state probability estimation in the proposed model, comparative intelligent diagnostic tests were conducted using five different classifiers applied to the progressive fault data of three different faults in a high pressure liquefied natural gas (HP-LNG) pump. As a result of this comparison study, SVMs were employed in heath state probability estimation for the prediction of machine failure in this research. The proposed prognostic methodology has been successfully tested and validated using a number of case studies from simulation tests to real industry applications. The results from two actual failure case studies using simulations and experiments indicate that accurate estimation of health states is achievable and the proposed method provides accurate long-term prediction of machine remnant life. In addition, the results of experimental tests show that the proposed model has the capability of providing early warning of abnormal machine operating conditions by identifying the transitional states of machine fault conditions. Finally, the proposed prognostic model is validated through two industrial case studies. The optimal number of health states which can minimise the model training error without significant decrease of prediction accuracy was also examined through several health states of bearing failure. The results were very encouraging and show that the proposed prognostic model based on health state probability estimation has the potential to be used as a generic and scalable asset health estimation tool in industrial machinery.

Preliminary characterisation of the surface of cartilage following exposure to saturated and unsaturated synthetic lipids

Articular cartilage is covered by a microscopic structure known as surface amorphous layer. This surface structure is often the first victim of attack during cartilage degeneration, thereby resulting in a gross impairment in cartilage function such as lubrication and load bearing. We hypothesize that incubation of degraded cartilage in solutions of different species of synthetic surface active phospholipids (saturated and unsaturated species) can remodel this lost surface structure. To test this hypothesis, the structural configuration of the surface of articular cartilage was studied and characterised with the lipid filled surface amorphous layer intact using the AFM. The results were then compared with those obtained following a systematic removal (delipidization) and replacement (relipidization) of this layer. Our results show that the unsaturated surfactant partially restored the lost surface amorphous layer while the saturated surfactant specie settled on the surface due to its poor solubility in aqueous solution.

Measuring and monitoring soil organic carbon stocks in agricultural lands for climate mitigation

Policies that encourage greenhouse-gas emitters to mitigate emissions through terrestrial carbon (C) offsets – C sequestration in soils or biomass – will promote practices that reduce erosion and build soil fertility, while fostering adaptation to climate change, agricultural development, and rehabilitation of degraded soils. However none of these benefits will be possible until changes in C stocks can be documented accurately and cost-effectively. This is particularly challenging when dealing with changes in soil organic C (SOC) stocks. Precise methods for measuring C in soil samples are well established, but spatial variability in the factors that determine SOC stocks makes it difficult to document change. Widespread interest in the benefits of SOC sequestration has brought this issue to the fore in the development of US and international climate policy. Here, we review the challenges to documenting changes in SOC stocks, how policy decisions influence offset documentation requirements, and the benefits and drawbacks of different sampling strategies and extrapolation methods.

Use of precision time protocol to synchronize sampled value process buses

Transmission smart grids will use a digital platform for the automation of high voltage substations. The IEC 61850 series of standards, released in parts over the last ten years, provide a specification for substation communications networks and systems. These standards, along with IEEE Std 1588-2008 Precision Time Protocol version 2 (PTPv2) for precision timing, are recommended by the both IEC Smart Grid Strategy Group and the NIST Framework and Roadmap for Smart Grid Interoperability Standards for substation automation. IEC 61850, PTPv2 and Ethernet are three complementary protocol families that together define the future of sampled value digital process connections for smart substation automation. A time synchronisation system is required for a sampled value process bus, however the details are not defined in IEC 61850-9-2. PTPv2 provides the greatest accuracy of network based time transfer systems, with timing errors of less than 100 ns achievable. The suitability of PTPv2 to synchronise sampling in a digital process bus is evaluated, with preliminary results indicating that steady state performance of low cost clocks is an acceptable ±300 ns, but that corrections issued by grandmaster clocks can introduce significant transients. Extremely stable grandmaster oscillators are required to ensure any corrections are sufficiently small that time synchronising performance is not degraded.

Music selection using a touch screen interface : effect of auditory and visual feedback on driving and usability

This study aimed to examine the effects on driving, usability and subjective workload of performing music selection tasks using a touch screen interface. Additionally, to explore whether the provision of visual and/or auditory feedback offers any performance and usability benefits. Thirty participants performed music selection tasks with a touch screen interface while driving. The interface provided four forms of feedback: no feedback, auditory feedback, visual feedback, and a combination of auditory and visual feedback. Performance on the music selection tasks significantly increased subjective workload and degraded performance on a range of driving measures including lane keeping variation and number of lane excursions. The provision of any form of feedback on the touch screen interface did not significantly affect driving performance, usability or subjective workload, but was preferred by users over no feedback. Overall, the results suggest that touch screens may not be a suitable input device for navigating scrollable lists.

A microanalytical study of the surfaces of normal, delipidized, and artificially “resurfaced” articular cartilage

The surface amorphous layer of articular cartilage is of primary importance to its load-bearing and lubrication function. This lipid-filled layer is degraded/disrupted or eliminated when cartilage degenerates due to diseases. This article examines further the characteristic of this surface overlay using a combination of microscopy and imaging methods to evaluate the hypothesis that the surface of articular cartilage can be repaired by exposing degraded cartilage to aqueous synthetic lipid mixtures. The preliminary results demonstrate that it is possible to create a new surface layer of phospholipids on the surface of cartilage following artificial lipid removal, but such a layer does not possess enough mechanical strength for physiological function when created with either unsaturated palmitoyloleoyl- phosphatidylcholine or saturated dipalmitoyl-phosphatidylcholine component of joint lipid composition alone. We conclude that this may be due to low structural cohesivity, inadequate time of exposure, and the mix/content of lipid in the incubation environment.

Even moderate visual impairments degrade drivers’ ability to see pedestrians at night

Purpose: To determine the effect of moderate levels of refractive blur and simulated cataracts on nighttime pedestrian conspicuity in the presence and absence of headlamp glare. Methods: The ability to recognize pedestrians at night was measured in 28 young adults (M=27.6 years) under three visual conditions: normal vision, refractive blur and simulated cataracts; mean acuity was 20/40 or better in all conditions. Pedestrian recognition distances were recorded while participants drove an instrumented vehicle along a closed road course at night. Pedestrians wore one of three clothing conditions and oncoming headlamps were present for 16 participants and absent for 12 participants. Results: Simulated visual impairment and glare significantly reduced the frequency with which drivers recognized pedestrians and the distance at which the drivers first recognized them. Simulated cataracts were significantly more disruptive than blur even though photopic visual acuity levels were matched. With normal vision, drivers responded to pedestrians at 3.6x and 5.5x longer distances on average than for the blur or cataract conditions, respectively. Even in the presence of visual impairment and glare, pedestrians were recognized more often and at longer distances when they wore a “biological motion” reflective clothing configuration than when they wore a reflective vest or black clothing. Conclusions: Drivers’ ability to recognize pedestrians at night is degraded by common visual impairments even when the drivers’ mean visual acuity meets licensing requirements. To maximize drivers’ ability to see pedestrians, drivers should wear their optimum optical correction, and cataract surgery should be performed early enough to avoid potentially dangerous reductions in visual performance.

Phenolics in sugar cane juice : potential degradation by hydrogen peroxide and Fenton's reagent

The presence of colour in raw sugar plays a key role in the marketing strategy of the Australian raw sugar industry. Some sugars are relatively difficult to decolourise during refining and develop colour during storage. A new approach that might result in efficient and cost-effective colour removal during the sugar manufacturing process is the use of an advanced oxidation process (AOP), known as Fenton oxidation, that is, catalytic production of hydroxyl radicals from the decomposition of hydrogen peroxide using ferrous iron. As a first step towards developing this technology, this study determined the composition of colour precursors present in the juice of cane harvested by three different methods. The methods were harvesting cane after burning, harvesting the whole crop with half of the trash extracted and harvesting the whole crop with no trash extracted. The study also investigated the degradation at pH 3, 4 and 5 of a phenolic compound, caffeic acid (3,4–dihydroxycinnamic acid), which is present in sugar cane juice, using both hydrogen peroxide and Fenton’s reagent. The results show that juice expressed from whole crop cane has significantly higher colour than juices expressed from burnt cane. However, the concentrations of phenolic acids were lower in the juices expressed from whole crop cane. The main phenolic acids present in these juices were p-coumaric, vanillic, 2,3–dihydroxybenzoic, gallic and 3,4–dihydroxybenzoic acids. The degradation of caffeic acid significantly improved using Fenton’s reagent in comparison to hydrogen peroxide alone. The Fenton oxidation was optimum at pH 5 when up to ~86 % of caffeic acid degraded within 5 min.

Phenolics in sugar cane juice : potential degradation by hydrogen peroxide and Fenton’s reagent

The presence of colour in raw sugar plays a key role in the marketing strategy of the Australian raw sugar industry. Some sugars are relatively difficult to decolourise during refining and develop colour during storage. A new approach that might result in efficient and cost-effective colour removal during the sugar manufacturing process is the use of an advanced oxidation process (AOP), known as Fenton oxidation, that is, catalytic production of hydroxyl radicals from the decomposition of hydrogen peroxide using ferrous iron. As a first step towards developing this technology, this study determined the composition of colour precursors present in the juice of cane harvested by three different methods. The methods were harvesting cane after burning, harvesting the whole crop with half of the trash extracted and harvesting the whole crop with no trash extracted. The study also investigated the degradation at pH 3, 4 and 5 of a phenolic compound, caffeic acid (3,4–dihydroxycinnamic acid), which is present in sugar cane juice, using both hydrogen peroxide and Fenton’s reagent. The results show that juice expressed from whole crop cane has significantly higher colour than juices expressed from burnt cane. However, the concentrations of phenolic acids were lower in the juices expressed from whole crop cane. The main phenolic acids present in these juices were p-coumaric, vanillic, 2,3–dihydroxybenzoic, gallic and 3,4–dihydroxybenzoic acids. The degradation of caffeic acid significantly improved using Fenton’s reagent in comparison to hydrogen peroxide alone. The Fenton oxidation was optimum at pH 5 when up to ~86% of caffeic acid degraded within 5 min.

Proteasome inhibitors as anti-cancer agents

The ubiquitin (Ub)-proteasome pathway is the major nonlysosomal pathway of proteolysis in human cells and accounts for the degradation of most short-lived, misfolded or damaged proteins. This pathway is important in the regulation of a number of key biological regulatory mechanisms. Proteins are usually targeted for proteasome-mediated degradation by polyubiquitinylation, the covalent addition of multiple units of the 76 amino acid protein Ub, which are ligated to 1-amino groups of lysine residues in the substrate. Polyubiquitinylated proteins are degraded by the 26S proteasome, a large, ATP-dependent multicatalytic protease complex, which also regenerates monomeric Ub. The targets of this pathway include key regulators of cell proliferation and cell death. An alternative form of the proteasome, termed the immunoproteasome, also has important functions in the generation of peptides for presentation by MHC class I molecules. In recent years there has been a great deal of interest in the possibility that proteasome inhibitors, through elevation of the levels of proteasome targets, might prove useful as a novel class of anti-cancer drugs. Here we review the progress made to date in this area and highlight the potential advantages and weaknesses of this approach.

Unsupervised multi-label text classification using a world knowledge ontology

The development of text classification techniques has been largely promoted in the past decade due to the increasing availability and widespread use of digital documents. Usually, the performance of text classification relies on the quality of categories and the accuracy of classifiers learned from samples. When training samples are unavailable or categories are unqualified, text classification performance would be degraded. In this paper, we propose an unsupervised multi-label text classification method to classify documents using a large set of categories stored in a world ontology. The approach has been promisingly evaluated by compared with typical text classification methods, using a real-world document collection and based on the ground truth encoded by human experts.

Design of flight avoidance manoeuvre alphabets for mixed centralised-decentralised separation management

This paper investigates a mixed centralised-decentralised air traffic separation management system, which combines the best features of the centralised and decentralised systems whilst ensuring the reliability of the air traffic management system during degraded conditions. To overcome communication band limits, we propose a mixed separation manager on the basis of a robust decision (or min-max) problem that is posed on a reduced set of admissible flight avoidance manoeuvres (or a FAM alphabet). We also present a design method for selecting an appropriate FAM alphabet for use in the mixed separation management system. Simulation studies are presented to illustrate the benefits of our proposed FAM alphabet based mixed separation manager.