Parameter estimation for a phenomenological model of the cardiac action potential

The action potential (ap) of a cardiac cell is made up of a complex balance of ionic currents which flow across the cell membrane in response to electrical excitation of the cell. Biophysically detailed mathematical models of the ap have grown larger in terms of the variables and parameters required to model new findings in subcellular ionic mechanisms. The fitting of parameters to such models has seen a large degree of parameter and module re-use from earlier models. An alternative method for modelling electrically exciteable cardiac tissue is a phenomenological model, which reconstructs tissue level ap wave behaviour without subcellular details. A new parameter estimation technique to fit the morphology of the ap in a four variable phenomenological model is presented. An approximation of a nonlinear ordinary differential equation model is established that corresponds to the given phenomenological model of the cardiac ap. The parameter estimation problem is converted into a minimisation problem for the unknown parameters. A modified hybrid Nelder–Mead simplex search and particle swarm optimization is then used to solve the minimisation problem for the unknown parameters. The successful fitting of data generated from a well known biophysically detailed model is demonstrated. A successful fit to an experimental ap recording that contains both noise and experimental artefacts is also produced. The parameter estimation method’s ability to fit a complex morphology to a model with substantially more parameters than previously used is established.

Cerclage, evolution and potential of a Cinderella Technology : an overview with reference to periprosthetic fractures

Periprosthetic fractures are increasingly frequent. The fracture may be located over the shaft of the prosthesis, at its tip or below (21). The treatment of explosion fractures is difficult because the shaft blocks the application of implants, like screws, which need to penetrate the medullary cavity. The cerclage, as a simple periosteal loop, made of wire or more recently cable, does not only avoid the medullary cavity. Its centripetal mode of action is well suited for reducing and maintaining radially displaced fractures. Furthermore, the cerclage lends itself well for minimally invasive internal fixation. New insight challenges the disrepute of which the cerclage technology suffered for decades. The outcome of cerclage fixation benefits from an improved understanding of its technology, mechano-biology and periosteal blood supply. Preconceived and generally accepted opinions like "strangulation of blood supply" need to be re-examined. Recent mechanical evaluations (22) demonstrate that the wire application may be improved but cable is superior in hand- ling, maintenance of tension and strength. Beside the classical concepts of absolute and relative stability a defined stability condition needs consideration. It is typical for cerclage. Called "loose-lock stability" it specifies the situation where a loosened implant allows first unimpeded displacement changing abruptly into a locked fixation preventing further dislocation.

Hyaluronic acid : evaluation as a potential delivery vehicle for vitronectin:growth factor complexes in wound healing applications

We have previously reported that novel vitronectin:growth factor (VN:GF) complexes significantly increase re-epithelialization in a porcine deep dermal partial-thickness burn model. However, the potential exists to further enhance the healing response through combination with an appropriate delivery vehicle which facilitates sustained local release and reduced doses of VN:GF complexes. Hyaluronic acid (HA), an abundant constituent of the interstitium, is known to function as a reservoir for growth factors and other bioactive species. The physicochemical properties of HA confer it with an ability to sustain elevated pericellular concentrations of these species. This has been proposed to arise via HA prolonging interactions of the bioactive species with cell surface receptors and/or protecting them from degradation. In view of this, the potential of HA to facilitate the topical delivery of VN:GF complexes was evaluated. Two-dimensional (2D) monolayer cell cultures and 3D de-epidermised dermis (DED) human skin equivalent (HSE) models were used to test skin cell responses to HA and VN:GF complexes. Our 2D studies revealed that VN:GF complexes and HA stimulate the proliferation of human fibroblasts but not keratinocytes. Experiments in our 3D DED-HSE models showed that VN:GF complexes, both alone and in conjunction with HA, led to enhanced development of both the proliferative and differentiating layers in the DED-HSE models. However, there was no significant difference between the thicknesses of the epidermis treated with VN:GF complexes alone and VN:GF complexes together with HA. While the addition of HA did not enhance all the cellular responses to VN:GF complexes examined, it was not inhibitory, and may confer other advantages related to enhanced absorption and transport that could be beneficial in delivery of the VN:GF complexes to wounds.

Development of an autonomous unmanned aerial system to collect time-stamped samples from the atmosphere and localize potential pathogen sources

This paper presents the hardware development and testing of a new concept for air sampling via the integration of a prototype spore trap onboard an unmanned aerial system (UAS).We propose the integration of a prototype spore trap onboard a UAS to allow multiple capture of spores of pathogens in single remote locations at high or low altitude, otherwise not possible with stationary sampling devices.We also demonstrate the capability of this system for the capture of multiple time-stamped samples during a single mission.Wind tunnel testing was followed by simulation, and flight testing was conducted to measure and quantify the spread during simulated airborne air sampling operations. During autonomous operations, the onboard autopilot commands the servo to rotate the sampling device to a new indexed location once the UAS vehicle reaches the predefined waypoint or set of waypoints (which represents the region of interest). Time-stamped UAS data are continuously logged during the flight to assist with analysis of the particles collected. Testing and validation of the autopilot and spore trap integration, functionality, and performance is described. These tools may enhance the ability to detect new incursions of spores

Iron biogeochemistry and associated greenhouse gas evolution in a forested subtropical Australian coastal catchment : Poona Creek, Southeast Queensland

Iron (Fe) is the fourth most abundant element in the Earth’s crust. Excess Fe mobilization from terrestrial into aquatic systems is of concern for deterioration of water quality via biofouling and nuisance algal blooms in coastal and marine systems. Substantial Fe dissolution and transport involve alternate Fe(II) oxidation followed by Fe(III) reduction, with a diversity of Bacteria and Archaea acting as the key catalyst. Microbially-mediated Fe cycling is of global significance with regard to cycles of carbon (C), sulfur (S) and manganese (Mn). However, knowledge regarding microbial Fe cycling in circumneutral-pH habitats that prevail on Earth has been lacking until recently. In particular, little is known regarding microbial function in Fe cycling and associated Fe mobilization and greenhouse (CO2 and CH4, GHG) evolution in subtropical Australian coastal systems where microbial response to ambient variations such as seasonal flooding and land use changes is of concern. Using the plantation-forested Poona Creek catchment on the Fraser Coast of Southeast Queensland (SEQ), this research aimed to 1) study Fe cycling-associated bacterial populations in diverse terrestrial and aquatic habitats of a representative subtropical coastal circumneutral-pH (4–7) ecosystem; and 2) assess potential impacts of Pinus plantation forestry practices on microbially-mediated Fe mobilization, organic C mineralization and associated GHG evolution in coastal SEQ. A combination of wet-chemical extraction, undisturbed core microcosm, laboratory bacterial cultivation, microscopy and 16S rRNA-based molecular phylogenetic techniques were employed. The study area consisted primarily of loamy sands, with low organic C and dissolved nutrients. Total reactive Fe was abundant and evenly distributed within soil 0–30 cm profiles. Organic complexation primarily controlled Fe bioavailability and forms in well-drained plantation soils and water-logged, native riparian soils, whereas tidal flushing exerted a strong “seawater effect” in estuarine locations and formed a large proportion of inorganic Fe(III) complexes. There was a lack of Fe(II) sources across the catchment terrestrial system. Mature, first-rotation plantation clear-felling and second-rotation replanting significantly decreased organic matter and poorly crystalline Fe in well-drained soils, although variations in labile soil organic C fractions (dissolved organic C, DOC; and microbial biomass C, MBC) were minor. Both well-drained plantation soils and water-logged, native-vegetation soils were inhabited by a variety of cultivable, chemotrophic bacterial populations capable of C, Fe, S and Mn metabolism via lithotrophic or heterotrophic, (micro)aerobic or anaerobic pathways. Neutrophilic Fe(III)-reducing bacteria (FeRB) were most abundant, followed by aerobic, heterotrophic bacteria (heterotrophic plate count, HPC). Despite an abundance of FeRB, cultivable Fe(II)-oxidizing bacteria (FeOB) were absent in associated soils. A lack of links between cultivable Fe, S or Mn bacterial densities and relevant chemical measurements (except for HPC correlated with DOC) was likely due to complex biogeochemical interactions. Neither did variations in cultivable bacterial densities correlate with plantation forestry practices, despite total cultivable bacterial densities being significantly lower in estuarine soils when compared with well-drained plantation soils and water-logged, riparian native-vegetation soils. Given that bacterial Fe(III) reduction is the primary mechanism of Fe oxide dissolution in soils upon saturation, associated Fe mobilization involved several abiotic and biological processes. Abiotic oxidation of dissolved Fe(II) by Mn appeared to control Fe transport and inhibit Fe dissolution from mature, first-rotation plantation soils post-saturation. Such an effect was not observed in clear-felled and replanted soils associated with low SOM and potentially low Mn reactivity. Associated GHG evolution post-saturation mainly involved variable CO2 emissions, with low, but consistently increasing CH4 effluxes in mature, first-rotation plantation soil only. In comparison, water-logged soils in the riparian native-vegetation buffer zone functioned as an important GHG source, with high potentials for Fe mobilization and GHG, particularly CH4 emissions in riparian loam soils associated with high clay and crystalline Fe fractions. Active Fe–C cycling was unlikely to occur in lower-catchment estuarine soils associated with low cultivable bacterial densities and GHG effluxes. As a key component of bacterial Fe cycling, neutrophilic FeOB widely occurred in diverse aquatic, but not terrestrial, habitats of the catchment study area. Stalked and sheathed FeOB resembling Gallionella and Leptothrix were limited to microbial mat material deposited in surface fresh waters associated with a circumneutral-pH seep, and clay-rich soil within riparian buffer zones. Unicellular, Sideroxydans-related FeOB (96% sequence identity) were ubiquitous in surface and subsurface freshwater environments, with highest abundance in estuary-adjacent shallow coastal groundwater water associated with redox transition. The abundance of dissolved C and Fe in the groundwater-dependent system was associated with high numbers of cultivable anaerobic, heterotrophic FeRB, microaerophilic, putatively lithotrophic FeOB and aerobic, heterotrophic bacteria. This research represents the first study of microbial Fe cycling in diverse circumneutral-pH environments (terrestrial–aquatic, freshwater–estuarine, surface–subsurface) of a subtropical coastal ecosystem. It also represents the first study of its kind in the southern hemisphere. This work highlights the significance of bacterial Fe(III) reduction in terrestrial, and bacterial Fe(II) oxidation in aquatic catchment Fe cycling. Results indicate the risk of promotion of Fe mobilization due to plantation clear-felling and replanting, and GHG emissions associated with seasonal water-logging. Additional significant outcomes were also achieved. The first direct evidence for multiple biomineralization patterns of neutrophilic, microaerophilic, unicellular FeOB was presented. A putatively pure culture, which represents the first cultivable neutrophilic FeOB from the southern hemisphere, was obtained as representative FeOB ubiquitous in diverse catchment aquatic habitats.

Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs) are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b) are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP) could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as well as contributing to the ongoing controversy about differentiation capacities of MSCs. Therefore, further studies need to consider the differences between donor samples prior to any treatment as well as the possibility of harvesting donor cells that may be inappropriate for transplantation strategies.

Formation mechanisms of secondary organic aerosols in relation to laser printer emissions

Due to their large surface area, complex chemical composition and high alveolar deposition rate, ultrafine particles (UFPs) (< 0.1 ìm) pose a significant risk to human health and their toxicological effects have been acknowledged by the World Health Organisation. Since people spend most of their time indoors, there is a growing concern about the UFPs present in some indoor environments. Recent studies have shown that office machines, in particular laser printers, are a significant indoor source of UFPs. The majority of printer-generated UFPs are organic carbon and it is unlikely that these particles are emitted directly from the printer or its supplies (such as paper and toner powder). Thus, it was hypothesised that these UFPs are secondary organic aerosols (SOA). Considering the widespread use of printers and human exposure to these particles, understanding the processes involved in particle formation is of critical importance. However, few studies have investigated the nature (e.g. volatility, hygroscopicity, composition, size distribution and mixing state) and formation mechanisms of these particles. In order to address this gap in scientific knowledge, a comprehensive study including state-of-art instrumental methods was conducted to characterise the real-time emissions from modern commercial laser printers, including particles, volatile organic compounds (VOCs) and ozone (O3). The morphology, elemental composition, volatility and hygroscopicity of generated particles were also examined. The large set of experimental results was analysed and interpreted to provide insight into: (1) Emissions profiles of laser printers: The results showed that UFPs dominated the number concentrations of generated particles, with a quasi unimodal size distribution observed for all tests. These particles were volatile, non-hygroscopic and mixed both externally and internally. Particle microanalysis indicated that semi-volatile organic compounds occupied the dominant fraction of these particles, with only trace quantities of particles containing Ca and Fe. Furthermore, almost all laser printers tested in this study emitted measurable concentrations of VOCs and O3. A positive correlation between submicron particles and O3 concentrations, as well as a contrasting negative correlation between submicron particles and total VOC concentrations were observed during printing for all tests. These results proved that UFPs generated from laser printers are mainly SOAs. (2) Sources and precursors of generated particles: In order to identify the possible particle sources, particle formation potentials of both the printer components (e.g. fuser roller and lubricant oil) and supplies (e.g. paper and toner powder) were investigated using furnace tests. The VOCs emitted during the experiments were sampled and identified to provide information about particle precursors. The results suggested that all of the tested materials had the potential to generate particles upon heating. Nine unsaturated VOCs were identified from the emissions produced by paper and toner, which may contribute to the formation of UFPs through oxidation reactions with ozone. (3) Factors influencing the particle emission: The factors influencing particle emissions were also investigated by comparing two popular laser printers, one showing particle emissions three orders of magnitude higher than the other. The effects of toner coverage, printing history, type of paper and toner, and working temperature of the fuser roller on particle number emissions were examined. The results showed that the temperature of the fuser roller was a key factor driving the emission of particles. Based on the results for 30 different types of laser printers, a systematic positive correlation was observed between temperature and particle number emissions for printers that used the same heating technology and had a similar structure and fuser material. It was also found that temperature fluctuations were associated with intense bursts of particles and therefore, they may have impact on the particle emissions. Furthermore, the results indicated that the type of paper and toner powder contributed to particle emissions, while no apparent relationship was observed between toner coverage and levels of submicron particles. (4) Mechanisms of SOA formation, growth and ageing: The overall hypothesis that UFPs are formed by reactions with the VOCs and O3 emitted from laser printers was examined. The results proved this hypothesis and suggested that O3 may also play a role in particle ageing. In addition, knowledge about the mixing state of generated particles was utilised to explore the detailed processes of particle formation for different printing scenarios, including warm-up, normal printing, and printing without toner. The results indicated that polymerisation may have occurred on the surface of the generated particles to produce thermoplastic polymers, which may account for the expandable characteristics of some particles. Furthermore, toner and other particle residues on the idling belt from previous print jobs were a very clear contributing factor in the formation of laser printer-emitted particles. In summary, this study not only improves scientific understanding of the nature of printer-generated particles, but also provides significant insight into the formation and ageing mechanisms of SOAs in the indoor environment. The outcomes will also be beneficial to governments, industry and individuals.

Raising awareness of traffic pollution: the potential benefits and problems of using a warning smell

Exposure to traffic pollution is increasing worldwide as people move to cities, and as more vehicles join the roads, creating longer journeys and more traffic jams. Most traffic pollutants are odourless and invisible, which hides exposure from the public. If traffic pollution had a distinctive smell it would enable people to avoid exposure, and increase the political will for difficult policy changes. A smell may also instigate longer-term changes, such as switching to active transport for school pick-ups. A smell could be added using a fuel additive or a temporary device attached to vehicle exhausts.

A fragment of the LG3 peptide of endorepellin is present in the urine of physically active mining workers : a potential marker of physical activity

Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic / anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3 / endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk / survival.

Screening to identify large truck potential blackspots : methodological issues and concerns

1. Overview of hotspot identification (HSID)methods 2. Challenges with HSID 3. Bringing crash severity into the ‘mix’ 4. Case Study: Truck Involved Crashes in Arizona 5. Conclusions • Heavy duty trucks have different performance envelopes than passenger cars and have more difficulty weaving, accelerating, and braking • Passenger vehicles have extremely limited sight distance around trucks • Lane and shoulder widths affect truck crash risk more than passenger cars • Using PDOEs to model truck crashes results in a different set of locations to examine for possible engineering and behavioral problems • PDOE models point to higher societal cost locations, whereas frequency models point to higher crash frequency locations • PDOE models are less sensitive to unreported crashes • PDOE models are a great complement to existing practice

ACE research briefing paper 004 : emerging and young high potential start-ups

In this report we take a look at what separates high potential emerging and young start-ups from others. We compare the characteristics, intentions and behaviours of start-ups that we judge to be 'high potential' with other start-ups. We utilise the first two years of data from the CAUSEE study. We also compare Australian start-ups with a similar study conduced in the US.

Submission to House Standing Committee on Infrastructure and Communications : inquiry into the role and potential of the National Broadband Network

Just as telecommunications has played a key role in the global economy,1 high-speed broadband will have a significant role to play in the future of the digital economy. In particular high-speed broadband will have a role to play in the delivery of applications and services necessary for acquiring, and maintaining into the future Australia and Australians’ appropriate education level; community; health services, information provision and support; government services and engagement and participation by the public in the political process.

Hydrothermal technologies for the production of fuels and chemicals from biomass

Biomass and non-food crop residues are seen as relatively low cost and abundant renewable sources capable of making a large contribution to the world’s future energy and chemicals supply. Signifi cant quantities of ethanol are currently produced from biomass via biochemical processes, but thermochemical conversion processes offer greater potential to utilize the entire biomass source to produce a range of products. This chapter will review thermochemical gasifi cation and pyrolysis methods with a focus on hydrothermal liquefaction processes. Hydrothermal liquefaction is the most energetically advantageous thermochemical biomass conversion process. If the target is to produce sustainable liquid fuels and chemicals and reduce the impact of global warming as a result of carbon dioxide, nitrous oxide, and methane emissions (i.e., protect the natural environment), the use of “green” solvents, biocatalysts and heterogeneous catalysts must be the main R&D initiatives. As the biocrude produced from hydrothermal liquefaction is a complex mixture which is relatively viscous, corrosive, and unstable to oxidation (due to the presence of water and oxygenated compounds), additional upgrading processes are required to produce suitable biofuels and chemicals.