Non-combinatorial library screening reveals subsite cooperativity and identifies new high-efficiency substrates for kallikrein-related peptidase 14

An array of substrates link the tryptic serine protease, kallikrein-related peptidase 14 (KLK14), to physiological functions including desquamation and activation of signaling molecules associated with inflammation and cancer. Recognition of protease cleavage sequences is driven by complementarity between exposed substrate motifs and the physicochemical signature of an enzyme's active site cleft. However, conventional substrate screening methods have generated conflicting subsite profiles for KLK14. This study utilizes a recently developed screening technique, the sparse matrix library, to identify five novel high-efficiency sequences for KLK14. The optimal sequence, YASR, was cleaved with higher efficiency (k(cat)/K(m)=3.81 ± 0.4 × 10(6) M(-1) s(-1)) than favored substrates from positional scanning and phage display by 2- and 10-fold, respectively. Binding site cooperativity was prominent among preferred sequences, which enabled optimal interaction at all subsites as indicated by predictive modeling of KLK14/substrate complexes. These simulations constitute the first molecular dynamics analysis of KLK14 and offer a structural rationale for the divergent subsite preferences evident between KLK14 and closely related KLKs, KLK4 and KLK5. Collectively, these findings highlight the importance of binding site cooperativity in protease substrate recognition, which has implications for discovery of optimal substrates and engineering highly effective protease inhibitors.

Effects of enhanced somatosensory information on postural stability in older people and people with Parkinson’s disease

The somatosensory system plays an important role in balance control and age-related changes to this system have been implicated in falls. Parkinson’s disease (PD) is a chronic and progressive disease of the brain, characterized by postural instability and gait disturbance. Previous research has shown that deficiencies in somatosensory feedback may contribute to the poorer postural control demonstrated by PD individuals. However, few studies have comprehensively explored differences in somatosensory function and postural control between PD participants and healthy older individuals. The soles of the feet contain many cutaneous mechanoreceptors that provide important somatosensory information sources for postural control. Different types of insole devices have been developed to enhance this somatosensory information and improve postural stability, but these devices are often too complex and expensive to integrate into daily life. Textured insoles provide a more passive intervention that may be an inexpensive and accessible means to enhance the somatosensory input from the plantar surface of the feet. However, to date, there has been little work conducted to test the efficacy of enhanced somatosensory input induced by textured insoles in both healthy and PD populations during standing and walking. Therefore, the aims of this thesis were to determine: 1) whether textured insole surfaces can improve postural stability by enhancing somatosensory information in younger and older adults, 2) the differences between healthy older participants and PD participants for measures of physiological function and postural stability during standing and walking, 3) how changes in somatosensory information affect postural stability in both groups during standing and walking; and 4), whether textured insoles can improve postural stability in both groups during standing and walking. To address these aims, Study 1 recruited seven older individuals and ten healthy young controls to investigate the effects of two textured insole surfaces on postural stability while performing standing balance tests on a force plate. Participants were tested under three insole surface conditions: 1) barefoot; 2) standing on a hard textured insole surface; and 3), standing on a soft textured insole surface. Measurements derived from the centre of pressure displacement included the range of anterior-posterior and medial-lateral displacement, path length and the 90% confidence elliptical area (C90 area). Results of study 1 revealed a significant Group*Surface*Insole interaction for the four measures. Both textured insole surfaces reduced postural sway for the older group, especially in the eyes closed condition on the foam surface. However, participants reported that the soft textured insole surface was more comfortable and, hence, the soft textured insoles were adopted for Studies 2 and 3. For Study 2, 20 healthy older adults (controls) and 20 participants with Parkinson’s disease were recruited. Participants were evaluated using a series of physiological assessments that included touch sensitivity, vibratory perception, and pain and temperature threshold detection. Furthermore, nerve function and somatosensory evoked potentials tests were utilized to provide detailed information regarding peripheral nerve function for these participants. Standing balance and walking were assessed on different surfaces using a force plate and the 3D Vicon motion analysis system, respectively. Data derived from the force plate included the range of anterior-posterior and medial-lateral sway, while measures of stride length, stride period, cadence, double support time, stance phase, velocity and stride timing variability were reported for the walking assessment. The results of this study demonstrated that the PD group had decrements in somatosensory function compared to the healthy older control group. For electrodiagnosis, PD participants had poorer nerve function than controls, as evidenced by slower nerve conduction velocities and longer latencies in sural nerve and prolonged latency in the P37 somatosensory evoked potential. Furthermore, the PD group displayed more postural sway in both the anterior-posterior and medial-lateral directions relative to controls and these differences were increased when standing on a foam surface. With respect to the gait assessment, the PD group took shorter strides and had a reduced stride period compared with the control group. Furthermore, the PD group spent more time in the stance phase and had increased cadence and stride timing variability than the controls. Compared with walking on the firm surface, the two groups demonstrated different gait adaptations while walking on the uneven surface. Controls increased their stride length and stride period and decreased their cadence, which resulted in a consistent walking velocity on both surfaces. Conversely, while the PD patients also increased their stride period and decreased their cadence and stance period on the uneven surface, they did not increase their stride length and, hence walked slower on the uneven surface. In the PD group, there was a strong positive association between decreased somatosensory function and decreased clinical balance, as assessed by the Tinetti test. Poorer somatosensory function was also strongly positively correlated with the temporospatial gait parameters, especially shorter stride length. Study 3 evaluated the effects of manipulating the somatosensory information from the plantar surface of the feet using textured insoles in the same populations assessed in Study 2. For this study, participants performed the standing and walking balance tests under three footwear conditions: 1) barefoot; 2) with smooth insoles; and 3), with textured insoles. Standing balance and walking were evaluated using a force plate and a Vicon motion analysis system and the data were analysed in the same way outlined for Study 2. The findings showed that the smooth and textured insoles caused different effects on postural control during both the standing and walking trials. Both insoles decreased medial-lateral sway to the same level on the firm surface. The greatest benefits were observed in the PD group while wearing the textured insole. When standing under a more challenging condition on the foam surface with eyes closed, only the textured insole decreased medial-lateral sway in the PD group. With respect to the gait trials, both insoles increased walking velocity, stride length and stride time and decreased cadence, but these changes were more pronounced for the textured insoles. The effects of the textured insoles were evident under challenging conditions in the PD group and increased walking velocity and stride length, while decreasing cadence. Textured insoles were also effective in reducing the time spent in the double support and stance phases of the gait cycle and did not increase stride timing variability, as was the case for the smooth insoles for the PD group. The results of this study suggest that textured insoles, such as those evaluated in this research, may provide a low-cost means of improving postural stability in high-risk groups, such as people with PD, which may act as an important intervention to prevent falls.

Implementing an enhanced repository statistics system for QUT ePrints

Queensland University of Technology (QUT) was one of the first universities in Australia to establish an institutional repository. Launched in November 2003, the repository (QUT ePrints) uses the EPrints open source repository software (from Southampton) and has enjoyed the benefit of an institutional deposit mandate since January 2004. Currently (April 2012), the repository holds over 36,000 records, including 17,909 open access publications with another 2,434 publications embargoed but with mediated access enabled via the ‘Request a copy’ button which is a feature of the EPrints software. At QUT, the repository is managed by the library.QUT ePrints (http://eprints.qut.edu.au) The repository is embedded into a number of other systems at QUT including the staff profile system and the University’s research information system. It has also been integrated into a number of critical processes related to Government reporting and research assessment. Internally, senior research administrators often look to the repository for information to assist with decision-making and planning. While some statistics could be drawn from the advanced search feature and the existing download statistics feature, they were rarely at the level of granularity or aggregation required. Getting the information from the ‘back end’ of the repository was very time-consuming for the Library staff. In 2011, the Library funded a project to enhance the range of statistics which would be available from the public interface of QUT ePrints. The repository team conducted a series of focus groups and individual interviews to identify and prioritise functionality requirements for a new statistics ‘dashboard’. The participants included a mix research administrators, early career researchers and senior researchers. The repository team identified a number of business criteria (eg extensible, support available, skills required etc) and then gave each a weighting. After considering all the known options available, five software packages (IRStats, ePrintsStats, AWStats, BIRT and Google Urchin/Analytics) were thoroughly evaluated against a list of 69 criteria to determine which would be most suitable. The evaluation revealed that IRStats was the best fit for our requirements. It was deemed capable of meeting 21 out of the 31 high priority criteria. Consequently, IRStats was implemented as the basis for QUT ePrints’ new statistics dashboards which were launched in Open Access Week, October 2011. Statistics dashboards are now available at four levels; whole-of-repository level, organisational unit level, individual author level and individual item level. The data available includes, cumulative total deposits, time series deposits, deposits by item type, % fulltexts, % open access, cumulative downloads, time series downloads, downloads by item type, author ranking, paper ranking (by downloads), downloader geographic location, domains, internal v external downloads, citation data (from Scopus and Web of Science), most popular search terms, non-search referring websites. The data is displayed in charts, maps and table format. The new statistics dashboards are a great success. Feedback received from staff and students has been very positive. Individual researchers have said that they have found the information to be very useful when compiling a track record. It is now very easy for senior administrators (including the Deputy Vice Chancellor-Research) to compare the full-text deposit rates (i.e. mandate compliance rates) across organisational units. This has led to increased ‘encouragement’ from Heads of School and Deans in relation to the provision of full-text versions.

A randomised controlled trial of an enhanced interdisciplinary community based group program for people with Parkinson’s disease: study rationale and protocol

Parkinson’s disease (PD) is a progressive, chronic neurodegenerative disorder for which there is no known cure. Physical exercise programs may be used to assist with the physical management of PD. Several studies have demonstrated that community based physical therapy programs are effective in reducing physical aspects of disability among people with PD. While multidisciplinary therapy interventions may have the potential to reduce disability and improve the quality of life of people with PD, there is very limited clinical trial evidence to support or refute the use of a community based multidisciplinary or interdisciplinary programs for people with PD. A two group randomized trial is being undertaken within a community rehabilitation service in Brisbane, Australia. Community dwelling adults with a diagnosis of Idiopathic Parkinson’s disease are being recruited. Eligible participants are randomly allocated to a standard exercise rehabilitation group program or an intervention group which incorporates physical, cognitive and speech activities in a multi-tasking framework. Outcomes will be measured at 6-week intervals for a period of six months. Primary outcome measures are the Montreal Cognitive Assessment (MoCA) and the Timed Up and Go (TUG) cognitive test. Secondary outcomes include changes in health related quality of life, communication, social participation, mobility, strength and balance, and carer burden measures. This study will determine the immediate and long-term effectiveness of a unique multifocal, interdisciplinary, dual-tasking approach to the management of PD as compared to an exercise only program. We anticipate that the results of this study will have implications for the development of cost effective evidence based best practice for the treatment of people with PD living in the community.

Assessing efficiency of a transit oriented development (TOD) by comparative analysis

Transit oriented developments (TODs) are master planned communities constructed to reduce the dependence on the private car and promote the modes of transport such as public transport, walking and cycling, which are presumed by many transport professionals to be more sustainable. This paper tests this assumption that TOD is a more sustainable form of development than traditional development, with respect to travel demand, by conducting travel surveys for a case study TOD and comparing the travel characteristics of TOD residents with the travel characteristics of residents of Brisbane, Australia who live in non TOD suburbs. The results of a household comparison showed that the Kelvin Grove Urban Village (KGUV) households had slightly smaller household size, lower vehicle and bicycle ownership compared to Brisbane Statistical Division (BSD), Brisbane’s inner north and inner south suburbs. The comparison of average trip characteristics showed that on an average KGUV residents undertook fewer trips on the given travel day (2.6 trips/person) compared to BSD (3.1 trips/person), Brisbane Inner North Suburbs (BINS) (3.6 trips/person) and Brisbane Inner South Suburbs (BISS) (3.5 trips/person) residents. The mode share comparison indicated that KGUV residents used more public transport and made more walk-only trips in comparison to BSD, BINS and BISS residents. Overall, 72.4 percent of KGUV residents used a sustainable mode of transport for their travel on a typical weekday. On the other hand, only 17.4 percent, 22.2 percent and 24.4 percent residents of BSD, BINS and BISS used sustainable modes of transport for this travel. The results of trip length comparison showed that overall KGUV residents have smaller average trip lengths as compared to its counterparts. KGUV & BINS residents used car for travelling farther and used public transport for accessing destinations located closer to their homes. On the contrary, BSD and BISS residents exhibited an opposite trend. These results support the transportation claims of many transport professionals that TODs are more transport efficient and therefore more sustainable in this respect.

Assessing efficiency of a transit oriented development by comparative analysis

TOD: - A fully planned, mixed use development equipped with good quality transit service and infrastructure for walking and cycling Hypothesis: -TOD will help to reduce urban transport congestion Method: -Comparison of a TOD with non TOD urban environments -Residents’ trip characteristics

The impact of an enhanced graduated driver licensing program in Queensland

The Queensland graduated driver licensing (GDL) context (post-July 2007) - The experiences of young Learner drivers - Comparison of pre- (‘Original-GDL’) and post-July 2007 (‘Enhanced-GDL’) experiences - Post-July 2007 experiences - GDL-related issues - Other factors in young novice driver safety - Person-related factors - Social factors

The experiences of novices in an enhanced graduated driver licensing program in Queensland, Australia

- Young novice drivers - The Queensland graduated driver licensing (GDL) context - Pre-July 2007 (‘Original-GDL’) - Post-July 2007 (‘Enhanced-GDL’) - Experiences of Learners in Queensland’s enhanced-GDL program - Pre-/post-July 2007 comparison - Post-July 2007 only - Implications - Strengths and limitations

Factors affecting technical efficiency of rice farmers in village reservoir irrigation systems of Sri Lanka

Given the importance of water for rice production, this study examines the factors affecting the technical efficiency (TE) of irrigated rice farmers in village irrigation systems (VIS) in Sri Lanka. Primary data were collected from 460 rice farmers in the Kurunagala District, Sri Lanka, to estimate a stochastic translog production frontier for rice production. The mean TE of rice farming in village irrigation was found to be 0.72, although 63% of rice farmers exceeded this average. The most influential factors of TE are membership of Farmer Organisations (FOs) and the participatory rate in collective actions organised by FOs. The results suggest that enhancement of co-operative arrangements of farmers by strengthening the membership of FOs is considered important for increasing TE in rice farming in VIS.

The impact of anxiety on processing efficiency : implications for the attentional control theory

The Attentional Control Theory (ACT) proposes that high-anxious individuals maintain performance effectiveness (accuracy) at the expense of processing efficiency (response time), in particular, the two central executive functions of inhibition and shifting. In contrast, research has generally failed to consider the third executive function which relates to the function of updating. In the current study, seventy-five participants completed the Parametric Go/No-Go and n-back tasks, as well as the State-Trait Anxiety Inventory in order to explore the effects of anxiety on attention. Results indicated that anxiety lead to decay in processing efficiency, but not in performance effectiveness, across all three Central Executive functions (inhibition, set-shifting and updating). Interestingly, participants with high levels of trait anxiety also exhibited impaired performance effectiveness on the n-back task designed to measure the updating function. Findings are discussed in relation to developing a new model of ACT that also includes the role of preattentive processes and dual-task coordination when exploring the effects of anxiety on task performance.

Input-orientated data envelopment analysis framework for measuring and decomposing economic, environmental and ecological efficiency : an application to OECD agriculture

This paper presents an input-orientated data envelopment analysis (DEA) framework which allows the measurement and decomposition of economic, environmental and ecological efficiency levels in agricultural production across different countries. Economic, environmental and ecological optimisations search for optimal input combinations that minimise total costs, total amount of nutrients, and total amount of cumulative exergy contained in inputs respectively. The application of the framework to an agricultural dataset of 30 OECD countries revealed that (i) there was significant scope to make their agricultural production systemsmore environmentally and ecologically sustainable; (ii) the improvement in the environmental and ecological sustainability could be achieved by being more technically efficient and, even more significantly, by changing the input combinations; (iii) the rankings of sustainability varied significantly across OECD countries within frontier-based environmental and ecological efficiency measures and between frontier-based measures and indicators.

Improving the efficiency of RFID authentication with pre-computation

Security of RFID authentication protocols has received considerable interest recently. However, an important aspect of such protocols that has not received as much attention is the efficiency of their communication. In this paper we investigate the efficiency benefits of pre-computation for time-constrained applications in small to medium RFID networks. We also outline a protocol utilizing this mechanism in order to demonstrate the benefits and drawbacks of using thisapproach. The proposed protocol shows promising results as it is able to offer the security of untraceableprotocols whilst only requiring the time comparable to that of more efficient but traceable protocols.