Determination of strain-rate-dependent mechanical behavior of living and fixed osteocytes and chondrocytes using atomic force microscopy and inverse finite element analysis

The aim of this paper is to determine the strain-rate-dependent mechanical behavior of living and fixed osteocytes and chondrocytes, in vitro. Firstly, Atomic Force Microscopy (AFM) was used to obtain the force-indentation curves of these single cells at four different strain-rates. These results were then employed in inverse finite element analysis (FEA) using Modified Standard neo-Hookean Solid (MSnHS) idealization of these cells to determine their mechanical properties. In addition, a FEA model with a newly developed spring element was employed to accurately simulate AFM evaluation in this study. We report that both cytoskeleton (CSK) and intracellular fluid govern the strain-rate-dependent mechanical property of living cells whereas intracellular fluid plays a predominant role on fixed cells’ behavior. In addition, through the comparisons, it can be concluded that osteocytes are stiffer than chondrocytes at all strain-rates tested indicating that the cells could be the biomarker of their tissue origin. Finally, we report that MSnHS is able to capture the strain-rate-dependent mechanical behavior of osteocyte and chondrocyte for both living and fixed cells. Therefore, we concluded that the MSnHS is a good model for exploration of mechanical deformation responses of single osteocytes and chondrocytes. This study could open a new avenue for analysis of mechanical behavior of osteocytes and chondrocytes as well as other similar types of cells.

Modelling total duration of traffic incidents including incident detection and recovery time

Traffic incidents are key contributors to non-recurrent congestion, potentially generating significant delay. Factors that influence the duration of incidents are important to understand so that effective mitigation strategies can be implemented. To identify and quantify the effects of influential factors, a methodology for studying total incident duration based on historical data from an ‘integrated database’ is proposed. Incident duration models are developed using a selected freeway segment in the Southeast Queensland, Australia network. The models include incident detection and recovery time as components of incident duration. A hazard-based duration modelling approach is applied to model incident duration as a function of a variety of factors that influence traffic incident duration. Parametric accelerated failure time survival models are developed to capture heterogeneity as a function of explanatory variables, with both fixed and random parameters specifications. The analysis reveals that factors affecting incident duration include incident characteristics (severity, type, injury, medical requirements, etc.), infrastructure characteristics (roadway shoulder availability), time of day, and traffic characteristics. The results indicate that event type durations are uniquely different, thus requiring different responses to effectively clear them. Furthermore, the results highlight the presence of unobserved incident duration heterogeneity as captured by the random parameter models, suggesting that additional factors need to be considered in future modelling efforts.

The child pose : the role of the nonhuman natural world in recovery from psychological trauma

This thesis by creative work explores relationships among human beings, the nonhuman natural world and language. It addresses the central research question: 'How can a novel embody a narrative of recovery from psychological trauma in which recovery is primarily a function of the character's subjective interaction with nature?' The novel, 'The Child Pose', tells the story of a woman's recovery from psychological trauma. The thesis draws on the psychoanalytic theory of Jacques Lacan, who saw the human subject as fundamentally split and alienated, and therefore inherently vulnerable to being destabilised by trauma. Situating the narrative of recovery within the emerging fields of ecocriticism and ecopsychology, the research constructs psychological recovery through interaction with nature as a transformation of subjectivity: the creation of a new, more stable and connected kind of subject, which Jordan (2012) has called 'the ecological subject'.

Artemisinin-induced parasite dormancy : a plausible mechanism for treatment failure

Background Artemisinin-combination therapy is a highly effective treatment for uncomplicated falciparum malaria but parasite recrudescence has been commonly reported following artemisinin (ART) monotherapy. The dormancy recovery hypothesis has been proposed to explain this phenomenon, which is different from the slower parasite clearance times reported as the first evidence of the development of ART resistance. Methods In this study, an existing P. falciparum infection model is modified to incorporate the hypothesis of dormancy. Published in vitro data describing the characteristics of dormant parasites is used to explore whether dormancy alone could be responsible for the high recrudescence rates observed in field studies using monotherapy. Several treatment regimens and dormancy rates were simulated to investigate the rate of clinical and parasitological failure following treatment. Results The model output indicates that following a single treatment with ART parasitological and clinical failures occur in up to 77% and 67% of simulations, respectively. These rates rapidly decline with repeated treatment and are sensitive to the assumed dormancy rate. The simulated parasitological and clinical treatment failure rates after 3 and 7 days of treatment are comparable to those reported from several field trials. Conclusions Although further studies are required to confirm dormancy in vivo, this theoretical study adds support for the hypothesis, highlighting the potential role of this parasite sub-population in treatment failure following monotherapy and reinforcing the importance of using ART in combination with other anti-malarials.

Artemisinin induced dormancy in Plasmodium falciparum : duration, recovery rates and implications in treatment failure

Background Despite the remarkable activity of artemisinin and its derivatives, monotherapy with these agents has been associated with high rates of recrudescence. The temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to artemisinin drugs provides a plausible explanation for this phenomenon. Methods Ring-stage parasites of several Plasmodium falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine. For each regime, the proportion of recovering parasites was determined daily for 20 days. Results Parasite development was abruptly arrested after a single exposure to DHA, with some parasites being dormant for up to 20 days. Approximately 50% of dormant parasites recovered to resume growth within the first 9 days. The overall proportion of parasites recovering was dose dependent, with recovery rates ranging from 0.044% to 1.313%. Repeated treatment with DHA or with DHA in combination with mefloquine led to a delay in recovery and an ∼10-fold reduction in total recovery. Strains with different genetic backgrounds appeared to vary in their capacity to recover. Conclusions These results imply that artemisinin-induced arrest of growth occurs readily in laboratory-treated parasites and may be a key factor in P. falciparum malaria treatment failure.

Pasture Degradation and Recovery in Australia's Rangelands : Learning from History

"The extended drought periods in each degradation episode have provided a test of the capacity of grazing systems (i.e. land, plants, animals, humans and social structure) to handle stress. Evidence that degradation was already occurring was identified prior to the extended drought sequences. The sequence of dry years, ranging from two to eight years, exposed and/or amplified the degradation processes. The unequivocal evidence was provided by: (a) the physical 'horror' of bare landscapes, erosion scalds and gullies and dust storms; (b) the biological devastation of woody weeds and animal suffering/deaths or forced sales, and; (c) the financial and emotional plight of graziers and their families due to reduced production in some cases leading to abandonment of properties or, sadly, deaths (e.g. McDonald 1991, Ker Conway 1989)."--Publisher website

A Tradable Permit System in an Intertemporal Economy

It is known that in an intertemporal competitive economy, a tradable permit system may not achieve efficiency without setting appropriate permit interest rates (i.e., rewards for holding permits). To find the rates, however, we need to know in advance the path of efficient permit prices, which is difficult to obtain. This study intends to solve this problem in two ways. First, we analyze a special case in which the permit interest rates are given by a simple rule. For example, if the marginal abatement cost of pollution emission is constant, then the appropriate rate is to equal the monetary interest rate. As is the case for global warming, if the damage is caused in the future far beyond the planning period of the environmental program, the appropriate rate coincides with the marginal self-recovery of environmental stock under certain conditions. As a second approach, we propose a tradable permit system with a permit bank, as a mechanism by which the permit interest rates are generated endogenously without governmental intervention other than the issuance of permits. However, we also show that this approach raises the problem of indeterminacy of the equilibrium. © 2013 Springer Science+Business Media Dordrecht.

The impacts of exchange rate volatility on vegetable trade flows

Trade flows of commodities are generally affected by the principles of comparative advantage in a free trade. However, trade flows might be enhanced or distorted not only by various government interventions, but also by exchange rate fluctuations among others. This study applies a commodity-specific gravity model to selected vegetable trade flows among Organization for Economic Co-operation and Development (OECD) countries to determine the effects of exchange rate uncertainty on the trade flows. Using the data from 1996 to 2002, the results show that, while the exchange rate uncertainty significantly reduces trade in the majority of commodity flows, there is evidence that both short- and long-term volatility have positive effect on trade flows of specific commodities. This study also tests the regional preferential trade agreements such as the North American Free Trade Agreement (NAFTA), the Asia-Pacific Economic Cooperation (APEC) and the EU, and their different effects on commodities.

Non-invasive techniques for imaging in-vivo human corneal sub basal nerve mapping and migration rate in diabetic neuropathy

Purpose Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic technique, which has been shown to diagnose and stratify the severity of diabetic neuropathy. Current morphometric techniques assess individual static images of the subbasal nerve plexus; this work explores the potential for non-invasive assessment of the wide-field morphology and dynamic changes of this plexus in vivo. Methods In this pilot study, laser scanning CCM was used to acquire maps (using a dynamic fixation target and semi-automated tiling software) of the central corneal sub-basal nerve plexus in 4 diabetic patients with and 6 without neuropathy and in 2 control subjects. Nerve migration was measured in an additional 7 diabetic patients with neuropathy, 4 without neuropathy and in 2 control subjects by repeating a modified version of the mapping procedure within 2-8 weeks, thus facilitating re-identification of distinctive nerve landmarks in the 2 montages. The rate of nerve movement was determined from these data and normalised to a weekly rate (µm/week), using customised software. Results Wide-field corneal nerve fibre length correlated significantly with the Neuropathy Disability Score (r = -0.58, p < 0.05), vibration perception (r = -0.66, p < 0.05) and peroneal conduction velocity (r = 0.67, p < 0.05). Central corneal nerve fibre length did not correlate with any of these measures of neuropathy (p > 0.05 for all). The rate of corneal nerve migration was 14.3 ± 1.1 µm/week in diabetic patients with neuropathy, 19.7 ± 13.3µm/week in diabetic patients without neuropathy, and 24.4 ± 9.8µm/week in control subjects; however, these differences were not significantly different (p = 0.543). Conclusions Our data demonstrate that it is possible to capture wide-field images of the corneal nerve plexus, and to quantify the rate of corneal nerve migration by repeating this procedure over a number of weeks. Further studies on larger sample sizes are required to determine the utility of this approach for the diagnosis and monitoring of diabetic neuropathy.