Polymer nanocarrier system for endosome escape and timed release of siRNA with complete gene silencing and cell death in cancer cells

An influenza virus-inspired polymer mimic nanocarrier was used to deliver siRNA for specific and near complete gene knockdown of an osteoscarcom cell line (U-2SO). The polymer was synthesized by single-electron transfer living radical polymerization (SET-LRP) at room temperature to avoid complexities of transfer to monomer or polymer. It was the only LRP method that allowed good block copolymer formation with a narrow molecular weight distribution. At nitrogen to phosphorus (N/P) ratios of equal to or greater than 20 (greater than a polymer concentration of 13.8 μg/mL) with polo-like kinase 1 (PLK1) siRNA gave specific and near complete (>98%) cell death. The polymer further degrades to a benign polymer that showed no toxicity even at polymer concentrations of 200 μg/mL (or N/P ratio of 300), suggesting that our polymer nanocarrier can be used as a very effective siRNA delivery system and in a multiple dose administration. This work demonstrates that with a well-designed delivery device, siRNA can specifically kill cells without the inclusion of an additional clinically used highly toxic cochemotherapeutic agent. Our work also showed that this excellent delivery is sensitive for the study of off-target knockdown of siRNA.

The impact of interface modality on police officers' visual behaviour when using an in-vehicle system

Background Standard operating procedures state that police officers should not drive while interacting with their mobile data terminal (MDT) which provides in-vehicle information essential to police work. Such interactions do however occur in practice and represent a potential source of driver distraction. The MDT comprises visual output with manual input via touch screen and keyboard. This study investigated the potential for alternative input and output methods to mitigate driver distraction with specific focus on eye movements. Method Nineteen experienced drivers of police vehicles (one female) from the NSW Police Force completed four simulated urban drives. Three drives included a concurrent secondary task: imitation licence plate search using an emulated MDT. Three different interface methods were examined: Visual-Manual, Visual-Voice, and Audio-Voice (“Visual” and “Audio” = output modality; “Manual” and “Voice” = input modality). During each drive, eye movements were recorded using FaceLAB™ (Seeing Machines Ltd, Canberra, ACT). Gaze direction and glances on the MDT were assessed. Results The Visual-Voice and Visual-Manual interfaces resulted in a significantly greater number of glances towards the MDT than Audio-Voice or Baseline. The Visual-Manual and Visual-Voice interfaces resulted in significantly more glances to the display than Audio-Voice or Baseline. For longer duration glances (>2s and 1-2s) the Visual-Manual interface resulted in significantly more fixations than Baseline or Audio-Voice. The short duration glances (<1s) were significantly greater for both Visual-Voice and Visual-Manual compared with Baseline and Audio-Voice. There were no significant differences between Baseline and Audio-Voice. Conclusion An Audio-Voice interface has the greatest potential to decrease visual distraction to police drivers. However, it is acknowledged that an audio output may have limitations for information presentation compared with visual output. The Visual-Voice interface offers an environment where the capacity to present information is sustained, whilst distraction to the driver is reduced (compared to Visual-Manual) by enabling adaptation of fixation behaviour.

Intelligent tutoring system for learning PHP

This thesis investigates the possibility of using an adaptive tutoring system for beginning programming students. The work involved, designing, developing and evaluating such a system and showing that it was effective in increasing the students’ test scores. In doing so, Artificial Intelligence techniques were used to analyse PHP programs written by students and to provide feedback based on any specific errors made by them. Methods were also included to provide students with the next best exercise to suit their particular level of knowledge.

Optical and biomechanical factors, associated with near work and myopia

Near work may play an important role in the development of myopia in the younger population. The prevalence of myopia has also been found to be higher in occupations that involve substantial near work tasks, for example in microscopists and textile workers. When nearwork is performed, it typically involves accommodation, convergence and downward gaze. A number of previous studies have examined the effects of accommodation and convergence on changes in the optics and biometrics of the eye in primary gaze. However, little is known about the influence of accommodation on the eye in downward gaze. This thesis is primarily concerned with investigating the changes in the eye during near work in downward gaze under natural viewing conditions. To measure wavefront aberrations in downward gaze under natural viewing conditions, we modified a commercial Shack-Hartmann wavefront sensor by adding a relay lens system to allow on-axis ocular aberration measurements in primary gaze and downward gaze, with binocular fixation. Measurements with the modified wavefront sensor in primary and downward gaze were validated against a conventional aberrometer using both a model eye and in 9 human subjects. We then conducted an experiment to investigate changes in ocular aberrations associated with accommodation in downward gaze over 10 mins in groups of both myopes (n = 14) and emmetropes (n =12) using the modified Shack-Hartmann wavefront sensor. During the distance accommodation task, small but significant changes in refractive power (myopic shift) and higher order aberrations were observed in downward gaze compared to primary gaze. Accommodation caused greater changes in higher order aberrations (in particular coma and spherical aberration) in downward gaze than primary gaze, and there was evidence that the changes in certain aberrations with accommodation over time were different in downward gaze compared to primary gaze. There were no obvious systematic differences in higher order aberrations between refractive error groups during accommodation or downward gaze for fixed pupils. However, myopes exhibited a significantly greater change in higher order aberrations (in particular spherical aberration) than emmetropes for natural pupils after 10 mins of a near task (5 D accommodation) in downward gaze. These findings indicated that ocular aberrations change from primary to downward gaze, particularly with accommodation. To understand the mechanism underlying these changes in greater detail, we then extended this work to examine the characteristics of the corneal optics, internal optics, anterior biometrics and axial length of the eye during a near task, in downward gaze, over 10 mins. Twenty young adult subjects (10 emmetropes and 10 myopes) participated in this study. To measure corneal topography and ocular biometrics in downward gaze, a rotating Scheimpflug camera and an optical biometer were inclined on a custom built, height and tilt adjustable table. We found that both corneal optics and internal optics change with downward gaze, resulting in a myopic shift (~0.10 D) in the spherical power of the eye. The changes in corneal optics appear to be due to eyelid pressure on the anterior surface of the cornea, whereas the changes in the internal optics (an increase in axial length and a decrease in anterior chamber depth) may be associated with movement of the crystalline lens, under the action of gravity, and the influence of altered biomechanical forces from the extraocular muscles on the globe with downward gaze. Changes in axial length with accommodation were significantly greater in downward gaze than primary gaze (p < 0.05), indicating an increased effect of the mechanical forces from the ciliary muscle and extraocular muscles. A subsequent study was conducted to investigate the changes in anterior biometrics, axial length and choroidal thickness in nine cardinal gaze directions under the actions of the extraocular muscles. Ocular biometry measurements were obtained from 30 young adults (10 emmetropes, 10 low myopes and 10 moderate myopes) through a rotating prism with 15° deviation, along the foveal axis, using a non-contact optical biometer in each of nine different cardinal directions of gaze, over 5 mins. There was a significant influence of gaze angle and time on axial length (both p < 0.001), with the greatest axial elongation (+18 ± 8 μm) occurring with infero-nasal gaze (p < 0.001) and a slight decrease in axial length in superior gaze (−12 ± 17 μm) compared with primary gaze (p < 0.001). There was a significant correlation between refractive error (spherical equivalent refraction) and the mean change in axial length in the infero-nasal gaze direction (Pearson's R2 = 0.71, p < 0.001). To further investigate the relative effect of gravity and extraocular muscle force on the axial length, we measured axial length in 15° and 25° downward gaze with the biometer inclined on a tilting table that allowed gaze shifts to occur with either full head turn but no eye turn (reflects the effect of gravity), or full eye turn with no head turn (reflects the effect of extraocular muscle forces). We observed a significant axial elongation in 15° and 25° downward gaze in the full eye turn condition. However, axial length did not change significantly in downward gaze over 5 mins (p > 0.05) in the full head turn condition. The elongation of the axial length in downward gaze appears to be due to the influence of the extraocular muscles, since the effect was not present when head turn was used instead of eye turn. The findings of these experiments collectively show the dynamic characteristics of the optics and biometrics of the eye in downward gaze during a near task, over time. These were small but significant differences between myopic and emmetropic eyes in both the optical and biomechanical changes associated with shifts of gaze direction. These differences between myopes and emmetropes could arise as a consequence of excessive eye growth associated with myopia. However the potentially additive effects of repeated or long lasting near work activities employing infero-nasal gaze could also act to promote elongation of the eye due to optical and/or biomechanical stimuli.

Professional development and technology in second language learning : do best practices work?

This study was undertaken to examine the influence that a set of Professional Development (PD) initiatives had on faculty use of Moodle, a well known Course Management System. The context of the study was a private language university just outside Tokyo, Japan. Specifically, it aimed to identify the way in which the PD initiatives adhered to professional development best practice criteria; how faculty members perceived the PD initiatives; what impact the PD initiatives had on faculty use of Moodle; and other variables that may have influenced faculty in their use of Moodle. The study utilised a mixed methods approach. Participants in the study were 42 teachers who worked at the university in the academic year 2008/9. The online survey consisted of 115 items, factored into 10 constructs. Data was collected through an online survey, semi-structured face-to-face interviews, post-workshop surveys, and a collection of textual artefacts. The quantitative data were analysed in SPSS, using descriptive statistics, Spearman's Rank Order correlation tests and a Kruskal-Wallis means test. The qualitative data was used to develop and expand findings and ideas. The results indicated that the PD initiatives adhered closely to criteria posited in technology-related professional development best practice criteria. Further, results from the online survey, post workshop surveys, and follow up face-to-face interviews indicated that while the PD initiatives that were implemented were positively perceived by faculty, they did not have the anticipated impact on Moodle use among faculty. Further results indicated that other variables, such as perceptions of Moodle, and institutional issues, had a considerable influence on Moodle use. The findings of the study further strengthened the idea that the five variables Everett Rogers lists in his Diffusion of Innovations model, including perceived attributes of an innovation; type of innovation decision; communication channels; nature of the social system; extent of change agents' promotion efforts, most influence the adoption of an innovation. However, the results also indicated that some of the variables in Rogers' DOI seem to have more of an influence than others, particularly the perceived attributes of an innovation variable. In addition, the findings of the study could serve to inform universities that have Course Management Systems (CMS), such as Moodle, about how to utilise them most efficiently and effectively. The findings could also help to inform universities about how to help faculty members acquire the skills necessary to incorporate CMSs into curricula and teaching practice. A limitation of this study was the use of a non-randomised sample, which could appear to have limited the generalisations of the findings to this particular Japanese context.

System level tests of transformer differential protection using an IEC 61850 process bus

The IEC 61850 family of standards for substation communication systems were released in the early 2000s, and include IEC 61850-8-1 and IEC 61850-9-2 that enable Ethernet to be used for process-level connections between transmission substation switchyards and control rooms. This paper presents an investigation of process bus protection performance, as the in-service behavior of multi-function process buses is largely unknown. An experimental approach was adopted that used a Real Time Digital Simulator and 'live' substation automation devices. The effect of sampling synchronization error and network traffic on transformer differential protection performance was assessed and compared to conventional hard-wired connections. Ethernet was used for all sampled value measurements, circuit breaker tripping, transformer tap-changer position reports and Precision Time Protocol synchronization of sampled value merging unit sampling. Test results showed that the protection relay under investigation operated correctly with process bus network traffic approaching 100% capacity. The protection system was not adversely affected by synchronizing errors significantly larger than the standards permit, suggesting these requirements may be overly conservative. This 'closed loop' approach, using substation automation hardware, validated the operation of protection relays under extreme conditions. Digital connections using a single shared Ethernet network outperformed conventional hard-wired solutions.

Fashion system Shanghai : the advent of a new gatekeeper

The term fashion system describes inter-relationships between production and consumption illustrating how the production of fashion is a collective activity. For instance, Yuniya Kawamura notes systems for the production of fashion differ around the globe and are subject to constant change, and Jennifer Craik draws attention to an ‘array of competing and intermeshing systems cutting across western and non-western cultures. In China, Shanghai’s nascent fashion system seeks to emulate the Eurocentric system of Fashion Weeks and industry support groups. It promises emergent designers a platform for global competition, yet there are tensions from within. Interaction with a fashion system inevitably means becoming validated or legitimised. Legitimisation in turn depends upon gatekeepers who make aesthetic judgments about the status, quality and cultural value of a designers work. Notwithstanding the proliferation of fashion media, in Shanghai a new gatekeeper has arrived, seeking to filter authenticity from artifice, offering truth in a fashion market saturated with fakery and the hollowness of foreign consumptive practice, and providing a place of sanctuary for Chinese fashion design. Thus this paper discusses how new agencies are allowing designers in Shanghai greater control over their brand image while creating novel opportunities for promotion and sales. It explores why designers choose this new model and provides new knowledge of the curation of fashion by these gatekeepers.

How do Chinese fashion designers become global fashion leaders? A new perspective on legitimisation in China’s fashion system

The term fashion system describes inter-relationships between production and consumption, illustrating how the production of fashion is a collective activity. For instance, Yuniya Kawamura (2011) notes systems for the production of fashion differ around the globe and are subject to constant change, and Jennifer Craik (1994, 6) draws attention to an ‘array of competing and intermeshing systems cutting across western and non-western cultures. In China, Shanghai’s nascent fashion system seeks to emulate the Eurocentric system of Fashion Weeks and industry support groups. It promises designers a platform for global competition, yet there are tensions from within. Interaction with a fashion system inevitably means becoming validated or legitimised. Legitimisation in turn depends upon gatekeepers who make aesthetic judgments about the status, quality, and cultural value of a designers work (Becker 2008). My paper offers a new perspective on legitimisation that is drawn mainly from my PhD research. I argue that some Chinese fashion designers are on the path to becoming global fashion designers because they have embraced a global aesthetic that resonates with the human condition, rather than the manufactured authenticity of a Eurocentric fashion system that perpetuates endless consumption. In this way, they are able to ‘self-legitimise’. I contend these designers are ‘designers for humans’, because they are able to look beyond the mythology of fashion brands, and the Eurocentric fashion system, where they explore the tensions of man and culture in their practice. Furthermore, their design ethos pursues beauty, truth and harmony in the Chinese philosophical sense, as well as incorporating financial return in a process that is still enacted through a fashion system. Accordingly, cultural tradition, heritage and modernity, while still valuable, have less impact on their practice.

On parallel hybrid-electric propulsion system for unmanned aerial vehicles

This paper presents a review of existing and current developments and the analysis of Hybrid-Electric Propulsion Systems (HEPS) for small fixed-wing Unmanned Aerial Vehicles (UAVs). Efficient energy utilisation on an UAV is essential to its functioning, often to achieve the operational goals of range, endurance and other specific mission requirements. Due to the limitations of the space available and the mass budget on the UAV, it is often a delicate balance between the onboard energy available (i.e. fuel) and achieving the operational goals. One technology with potential in this area is with the use of HEPS. In this paper, information on the state-of-art technology in this field of research is provided. A description and simulation of a parallel HEPS for a small fixed-wing UAV by incorporating an Ideal Operating Line (IOL) control strategy is described. Simulation models of the components in a HEPS were designed in the MATLAB Simulink environment. An IOL analysis of an UAV piston engine was used to determine the most efficient points of operation for this engine. The results show that an UAV equipped with this HEPS configuration is capable of achieving a fuel saving of 6.5%, compared to the engine-only configuration.

Agreement between temporal and spatial gait parameters from an instrumented walkway and treadmill system at matched walking speed

Background Commercially available instrumented treadmill systems that provide continuous measures of temporospatial gait parameters have recently become available for clinical gait analysis. This study evaluated the level of agreement between temporospatial gait parameters derived from a new instrumented treadmill, which incorporated a capacitance-based pressure array, with those measured by a conventional instrumented walkway (criterion standard). Methods Temporospatial gait parameters were estimated from 39 healthy adults while walking over an instrumented walkway (GAITRite®) and instrumented treadmill system (Zebris) at matched speed. Differences in temporospatial parameters derived from the two systems were evaluated using repeated measures ANOVA models. Pearson-product-moment correlations were used to investigate relationships between variables measured by each system. Agreement was assessed by calculating the bias and 95% limits of agreement. Results All temporospatial parameters measured via the instrumented walkway were significantly different from those obtained from the instrumented treadmill (P < .01). Temporospatial parameters derived from the two systems were highly correlated (r, 0.79–0.95). The 95% limits of agreement for temporal parameters were typically less than ±2% of gait cycle duration. However, 95% limits of agreement for spatial measures were as much as ±5 cm. Conclusions Differences in temporospatial parameters between systems were small but statistically significant and of similar magnitude to changes reported between shod and unshod gait in healthy young adults. Temporospatial parameters derived from an instrumented treadmill, therefore, are not representative of those obtained from an instrumented walkway and should not be interpreted with reference to literature on overground walking.

Reliability of spatiotemporal and kinetic gait parameters determined by a new instrumented treadmill system

Background Despite the emerging use of treadmills integrated with pressure platforms as outcome tools in both clinical and research settings, published evidence regarding the measurement properties of these new systems is limited. This study evaluated the within– and between–day repeatability of spatial, temporal and vertical ground reaction forces measured by a treadmill system instrumented with a capacitance–based pressure platform. Methods Thirty three healthy adults (mean age, 21.5 ± 2.8 years; height, 168.4 ± 9.9 cm; and mass, 67.8 ± 18.6 kg), walked barefoot on a treadmill system (FDM–THM–S, Zebris Medical GmbH) on three separate occasions. For each testing session, participants set their preferred pace but were blinded to treadmill speed. Spatial (foot rotation, step width, stride and step length), temporal (stride and step times, duration of stance, swing and single and double support) and peak vertical ground reaction force variables were collected over a 30–second capture period, equating to an average of 52 ± 5 steps of steady–state walking. Testing was repeated one week following the initial trial and again, for a third time, 20 minutes later. Repeated measures ANOVAs within a generalized linear modelling framework were used to assess between–session differences in gait parameters. Agreement between gait parameters measured within the same day (session 2 and 3) and between days (session 1 and 2; 1 and 3) were evaluated using the 95% repeatability coefficient. Results There were statistically significant differences in the majority (14/16) of temporal, spatial and kinetic gait parameters over the three test sessions (P < .01). The minimum change that could be detected with 95% confidence ranged between 3% and 17% for temporal parameters, 14% and 33% for spatial parameters, and 4% and 20% for kinetic parameters between days. Within–day repeatability was similar to that observed between days. Temporal and kinetic gait parameters were typically more consistent than spatial parameters. The 95% repeatability coefficient for vertical force peaks ranged between ± 53 and ± 63 N. Conclusions The limits of agreement in spatial parameters and ground reaction forces for the treadmill system encompass previously reported changes with neuromuscular pathology and footwear interventions. These findings provide clinicians and researchers with an indication of the repeatability and sensitivity of the Zebris treadmill system to detect changes in common spatiotemporal gait parameters and vertical ground reaction forces.

Autonomous forced landing system for light general aviation aircraft in unknown environments

This paper presents a system which enhances the capabilities of a light general aviation aircraft to land autonomously in case of an unscheduled event such as engine failure. The proposed system will not only increase the level of autonomy for the general aviation aircraft industry but also increase the level of dependability. Safe autonomous landing in case of an engine failure with a certain level of reliability is the primary focus of our work as both safety and reliability are attributes of dependability. The system is designed for a light general aviation aircraft but can be extended for dependable unmanned aircraft systems. The underlying system components are computationally efficient and provides continuous situation assessment in case of an emergency landing. The proposed system is undergoing an evaluation phase using an experimental platform (Cessna 172R) in real world scenarios.

The research lottery : the pressures on the Australian grant system

NHMRC Project Grants and ARC Discovery Grants are two of the major sources of funding for new ideas in Australian science. Many scientists rely on them for their job or the jobs of their staff. They are highly competitive with only around 1 in 5 applications winning funding. To increase the chances of winning funding, scientists spend a long time writing carefully crafted applications, generally at the sacrifice of their research output. And the pressures on the system and our scientists are only going to get worse.

A demand-responsive decision support system for coal transportation

In this paper, a demand-responsive decision support system is proposed by integrating the operations of coal shipment, coal stockpiles and coal railing within a whole system. A generic and flexible scheduling optimisation methodology is developed to identify, represent, model, solve and analyse the coal transport problem in a standard and convenient way. As a result, the integrated train-stockpile-ship timetable is created and optimised for improving overall efficiency of coal transport system. A comprehensive sensitivity analysis based on extensive computational experiments is conducted to validate the proposed methodology. The mathematical proposition and proof are concluded as technical and insightful advices for industry practice. The proposed methodology provides better decision making on how to assign rail rolling-stocks and upgrade infrastructure in order to significantly improve capacity utilisation with the best resource-effectiveness ratio. The proposed decision support system with train-stockpile-ship scheduling optimisation techniques is promising to be applied in railway or mining industry, especially as a useful quantitative decision making tool on how to use more current rolling-stocks or whether to buy additional rolling-stocks for mining transportation.