Process considerations related to the microencapsulation of plasmid DNA via ultrasonic atomization

An effective means of facilitating DNA vaccine delivery to antigen presenting cells is through biodegradable microspheres. Microspheres offer distinct advantages over other delivery technologies by providing release of DNA vaccine in its bioactive form in a controlled fashion. In this study, biodegradable poly(D,L-lactide-coglycolide) (PLGA) microspheres containing polyethylenimine (PEI) condensed plasmid DNA (pDNA) were prepared using a 40 kHz ultrasonic atomization system. Process synthesis parameters, which are important to the scale-up of microspheres that are suitable for nasal delivery (i.e., less than 20 μm), were studied. These parameters include polymer concentration; feed flowrate; volumetric ratio of polymer and pDNA-PEI (plasmid DNA-polyethylenimine) complexes; and nitrogen to phosphorous (N/P) ratio. PDNA encapsulation efficiencies were predominantly in the range 82-96%, and the mean sizes of the particle were between 6 and 15 μm. The ultrasonic synthesis method was shown to have excellent reproducibility. PEI affected morphology of the microspheres, as it induced the formation of porous particles that accelerate the release rate of pDNA. The PLGA microspheres displayed an in vitro release of pDNA of 95-99% within 30 days and demonstrated zero order release kinetics without an initial spike of pDNA. Agarose electrophoresis confirmed conservation of the supercoiled form of pDNA throughout the synthesis and in vitro release stages. It was concluded that ultrasonic atomization is an efficient technique to overcome the key obstacles in scaling-up the manufacture of encapsulated vaccine for clinical trials and ultimately, commercial applications.

From the bush to the burbs : a comparison of driver situation awareness at rural and urban railway level crossings

The problem of collisions between road users and trains at rail level crossings (RLXs) remains resistant to current countermeasures. One factor underpinning these collisions is poor Situation Awareness (SA) on behalf of the road user involved (i.e. not being aware of an approaching train). Although this is a potential threat at any RLX, the factors influencing SA may differ depending on whether the RLX is located in a rural or urban road environment. Despite this, there has been no empirical investigation regarding how road user SA might differ across distinct RLX environments. This knowledge is needed to establish the extent to which a uniform approach to RLX design and safety is acceptable. The aim of this paper is to investigate the differences in driver SA at rural versus urban RLXs. We present analyses of driver SA in both rural and urban RLX environments based on two recent on-road studies undertaken in Victoria, Melbourne. The findings demonstrate that driver SA is markedly different at rural and urban RLXs, and also that poor SA regarding approaching trains may be caused by different factors. The implications for RLX design and safety are discussed.

Protecting World Heritage sites from the adverse impacts of climate change : obligations for States Parties to the World Heritage Convention

Through its mandate to protect and preserve places of ‘outstanding universal value’, the World Heritage Convention provides an unlikely yet effective tool in global efforts to mitigate climate change. The practical efficacy of the Strategy to Assist States Parties to Implement Appropriate Management Responses (‘the Strategy’), which represents the World Heritage Committee’s primary response to the threats posed by climate change to World Heritage sites, is undermined by its weak stance on mitigation. This paper argues that the World Heritage Convention imposes stronger obligations on States Parties than those contained in the Strategy, including a duty on States Parties to commit to ‘deep cuts’ in greenhouse gas emissions. In order to ensure the continuing success of the World Heritage Convention States Parties must engage in extensive mitigation strategies without delay.

Flying robots to the rescue

UAVs could one day save the lives of lost civilians and those sent to find them, and a competition in outback Australia is proving how soon that day might come. We have all seen news stories of people who ventured beyond the day-to-day reach of the community and got lost: search parties are formed, aircraft drafted in, and often large sums of money expended in the quest to find them.

Comprehensive contribution of filament thickness and crosslinker failure to the rheological property of F-actin cytoskeleton

Rheological property of F-actin cytoskeleton is significant to the restructuring of cytoskeleton under a variety of cell activities. This study numerically validates the rheological property of F-actin cytoskeleton is not only a result of kinetic energy dissipation of F-actin, but also greatly depends on the configuration remodeling of networks structure. Both filament geometry and crosslinker properties can affect the remodeling of F-actin cytoskeleton. The crosslinker unbinding is found to dissipate energy and induce prominent stress relaxation in the F-actin adjacent to cross-linkages. Coupled with F-actin elasticity, the energy dissipation and stress relaxation are more significant in bundled F-actin networks than in single F-actin networks.

Temporal characteristics of melanopsin inputs to the human pupil light reflex

Rods, cones and melanopsin containing intrinsically photosensitive retinal ganglion cells (ipRGCs) operate in concert to regulate pupil diameter. The temporal properties of intrinsic ipRGC signalling are distinct to those of rods and cones, including longer latencies and sustained signalling after light offset. We examined whether the melanopsin mediated post-illumination pupil response (PIPR) and pupil constriction were dependent upon the inter-stimulus interval (ISI) between successive light pulses and the temporal frequency of sinusoidal light stimuli. Melanopsin excitation was altered by variation of stimulus wavelength (464 nm and 638 nm lights) and irradiance (11.4 and 15.2 log photons cm(-2) s(-1)). We found that 6s PIPR amplitude was independent of ISI and temporal frequency for all melanopsin excitation levels, indicating complete summation. In contrast to the PIPR, the maximum pupil constriction increased with increasing ISI with high and low melanopsin excitation, but time to minimum diameter was slower with high melanopsin excitation only. This melanopsin response to briefly presented pulses (16 and 100 ms) slows the temporal response of the maximum pupil constriction. We also demonstrate that high melanopsin excitation attenuates the phasic peak-trough pupil amplitude compared to conditions with low melanopsin excitation, indicating an interaction between inner and outer retinal inputs to the pupil light reflex. We infer that outer retina summation is important for rapidly controlling pupil diameter in response to short timescale fluctuations in illumination and may occur at two potential sites, one that is presynaptic to extrinsic photoreceptor input to ipRGCs, or another within the pupil control pathway if ipRGCs have differential temporal tuning to extrinsic and intrinsic signalling.

The contribution of ISO 14067 to the evolution of global greenhouse gas standards—A review

Due to the increasing recognition of global climate change, the building and construction industry is under pressure to reduce carbon emissions. A central issue in striving towards reduced carbon emissions is the need for a practicable and meaningful yardstick for assessing and communicating greenhouse gas (GHG) results. ISO 14067 was published by the International Organization for Standardization in May 2013. By providing specific requirements in the life cycle assessment (LCA) approach, the standard clarifies the GHG assessment in the aspects of choosing system boundaries and simulating use and end-of-life phases when quantifying carbon footprint of products (CFPs). More importantly, the standard, for the first time, provides step-to-step guidance and standardized template for communicating CFPs in the form of CFP external communication report, CFP performance tracking report, CFP declaration and CFP label. ISO 14067 therefore makes a valuable contribution to GHG quantification and transparent communication and comparison of CFPs. In addition, as cradle-to-grave should be used as the system boundary if use and end-of-life phases can be simulated, ISO 14067 will hopefully promote the development and implementation of simulation technologies, with Building Information Modelling (BIM) in particular, in the building and construction industry.

Focus group discussions exploring major social influences on young driver safety in Oman. Report to the Research Council of Oman, Muscat.

This report documents the findings of in-depth focus groups conducted with 17 young drivers. The main aim of these focus groups was to explore key themes related to the risky behaviour of young drivers (17-25 years) in Oman. Specifically the interviews explored the influence of parents and peers, who may serve as a source of imitation, reward and punishment. Additionally, the interviews explored the influence of policing and licensing on young driver behaviour.

A review and comparative analysis of international drug driving policies. Report to the New South Wales (NSW) Centre for Road Safety

The New South Wales (NSW) Centre for Road Safety (CRS) called for research services to conduct a review of international policy and practice to address drug-driving. The project sought to provide Transport for NSW (TfNSW) with a comprehensive review of current and emerging international practices in this area1. This report is submitted by the Centre for Accident Research and Road Safety – Queensland (CARRS-Q)...

Access to the Internet Submission to ALRC IP 46

This submission is directed to issues arising in respect of the need to recognise and support access to the internet for all Australian residents and citizens. As such it addresses the following questions only: Questions 2-1: What general principles or criteria should be applied to help determine whether a law that interferes with freedom of speech is justified? Question 2-2: Which Commonwealth laws unjustifiably interfere with freedom of speech, and why are these laws unjustified?