Fatty acid synthesis and pyruvate metabolism pathways remain active in dihydroartemisinin induced dormant ring stages of Plasmodium falciparum

Artemisinin (ART) based combination therapy (ACT) is used as the first line treatment of uncomplicated falciparum malaria worldwide. However, despite high potency and rapid action there is a high rate of recrudescence associated with ART monotherapy or ACT long before the recent emergence of ART resistance. ART induced ring stage dormancy and recovery has been implicated as possible cause of recrudescence; however, little is known about the characteristics of dormant parasites including whether dormant parasites are metabolically active. We investigated the transcription of 12 genes encoding key enzymes in various metabolic pathways in P. falciparum during dihydroartemisinin (DHA) induced dormancy and recovery. Transcription analysis showed an immediate down regulation for 10 genes following exposure to DHA, but continued transcription of 2 genes encoding apicoplast and mitochondrial proteins. Transcription of several additional genes encoding apicoplast and mitochondrial proteins, particularly genes encoding enzymes in pyruvate metabolism and fatty acid synthesis pathways, were also maintained. Additions of inhibitors for biotin acetyl CoA carbozylase and enoyl-acyl carrier reductase of the fatty acid synthesis pathways delayed the recovery of dormant parasites by 6 and 4 days, respectively following DHA treatment. Our results demonstrate most metabolic pathways are down regulated in DHA induced dormant parasites. In contrast fatty acid and pyruvate metabolic pathways remain active. These findings highlight new targets to interrupt recovery of parasites from ART-induced dormancy and to reduce the rate of recrudescence following ART treatment.

Progression of human breast cancer cells from hormone-dependent to hormone-independent growth both in vitro and in vivo

We have isolated a series of sublines of the hormone-dependent MCF-7 human breast cancer cell line after selection both in vivo and in vitro for growth in the presence of subphysiological concentrations of estrogens. These sublines represent a model system for study of the processes leading to hormonal autonomy. The cells form growing tumors in ovariectomized athymic nude mice in the absence of estrogen supplementation but retain some responsivity to estrogen as determined by stimulation of the rate of tumor growth in vivo and by induction of progesterone receptor. An ovarian-independent but hormone-responsive phenotype may occur early in the natural progression to hormone-independent and unresponsive growth in breast cancer. We observed no change in the affinity or decrease in the level of expression of estrogen receptors and progesterone receptors among the sublines and the parental cells. Epidermal growth factor receptors are not overexpressed in ovarian-independent cells. Thus, altered hormone receptor expression may be a late event in the acquisition of a hormone-independent and unresponsive phenotype. Sublines isolated by in vivo but not in vitro selection are more invasive than the parental cells both in vivo and across an artificial basement membrane in vitro. Thus, as yet unknown tumor-host interactions may be important in the development of an invasive phenotype. Furthermore, acquisition of the ovarian-independent and invasive phenotypes can occur independently.

A review of Deeds of Company Arrangement

Deeds of company arrangement ('DOCAs') under Part 5.3A of the Corporations Act appear be something of a limited success. However, the use and outcomes of DOCAs raise legitimate questions as to whether the level of returns currently being achieved for creditors might be improved by legislative reform. The 2013 ARITA Terry Taylor Scholarship project entailed a review of a random sample of executed DOCAs effectuated between 1 August 2012 and 31 July 2013. This review was undertaken with the intention of producing a ‘snapshot’ of current trends and outcomes of the use of DOCAs in practice – ie, average (or typical) rates of dividends paid, what DOCAs customarily achieve, the profile of the companies executing DOCAs and the average duration of DOCAs. The purpose of this review was to empirically assess the use and effectiveness of DOCAs in order to inform the ongoing debate about the success or otherwise of Australia’s Part 5.3A voluntary administration regime (which recently marked its 20 year anniversary).

A sample review of Deeds of Company Arrangement under Part 5.3A of the Corporations Act

An empirical review of the operation of Part 5.3A of the Corporations Act 2001 (Cth) is timely given that Australia’s corporate rescue regime marked its 20 year anniversary in 2013. The research project culminating in this report was funded by the 2013 ARITA Terry Taylor Scholarship and entailed a review of a random sample of 72 executed DOCAs (and associated reports and returns) which were effectuated between 1 August 2012 and 31 July 2013. This sample review of DOCAs was undertaken with the intention of producing a ‘snapshot’ of current practices and trends pertaining to DOCAs – ie, average (or typical) rate of dividends paid, the outcomes or goals which DOCAs customarily achieve (eg, genuine company rescues, workouts, enhanced asset realisations or ‘quasi-liquidations’), the profile of the companies executing DOCAs and the average term/duration of DOCAs. The purpose and value of this sample review was to empirically assess the use and effectiveness of one important aspect of Part 5.3A and to further inform consideration and debate as to whether changes are warranted to Australia’s voluntary administration regime.

Suppression of cluster ions during particle formation events in the atmosphere

Cluster ions and charged and neutral nanoparticle concentrations were monitored using a neutral cluster and air ion spectrometer (NAIS) over a period of one year in Brisbane, Australia. The study yielded 242 complete days of usable data, of which particle formation events were observed on 101 days. Small, intermediate and large ion concentrations were evaluated in real time. In the diurnal cycle, small ion concentration was highest during the second half of the night while large ion concentrations were a maximum during the day. The small ion concentration showed a decrease when the large ion concentration increased. Particle formation was generally followed by a peak in the intermediate ion concentration. The rate of increase of intermediate ions was used as the criteria for identifying particle formation events. Such events were followed by a period of growth to larger sizes and usually occurred between 8 am and 2 pm. Particle formation events were found to be related to the wind direction. The gaseous precursors for the production of secondary particles in the urban environment of Brisbane have been shown to be ammonia and sulfuric acid. During these events, the nanoparticle number concentrations in the size range 1.6 to 42 nm, which were normally lower than 1x104 cm-3, often exceeded 5x104 cm-3 with occasional values over 1x105 cm-3. Cluster ions generally occurred in number concentrations between 300 and 600 cm-3 but decreased significantly to about 200 cm-3 during particle formation events. This was accompanied by an increase in the large ion concentration. We calculated the fraction of nanoparticles that were charged and investigated the occurrence of possible overcharging during particle formation events. Overcharging is defined as the condition where the charged fraction of particles is higher than in charge equilibrium. This can occur when cluster ions attach to neutral particles in the atmosphere, giving rise to larger concentrations of charged particles in the short term. Ion-induced nucleation is one of the mechanisms of particle formation in the atmosphere, and overcharging has previously been considered as an indicator of this process. The possible role of ions in particle formation was investigated.

Wet hail and thunderstorm electrification

Hailstones in wet growth are commonly found in thunderclouds. While the ice-ice relative growth rate mechanism is generally accepted as the most likely cause of thunderstorm electrification, it is uncertain if this mechanism will operate under wet growth conditions because ice crystals are more likely to stick to the wet surface of a hailstone rather than bounce off it. Experiments were carried out in the laboratory to investigate if there was any charge separated when vapor-grown ice crystals bounced off a wet hailstone. A cloud of supercooled droplets, with and without ice crystals, was drawn past a simulated hailstone. In the dry growth regime, the hailstone charged strongly positive when droplets and crystals co-existed in the cloud. With only droplets in the cloud, there was no charging in the dry growth regime. However, as the hailstone attained wet growth, positive charging currents of about 0.5 and 3.5 pA were observed at 12 and 20 m s-1, respectively. We hypothesize that this observed charging was due to the evaporation of melt water. This so called Dinger-Gunn Effect is due to the ejection of negatively charged minute droplets produced by air bubbles bursting at the surface of the melt water. However the charge separated in wet growth was an order of magnitude smaller than that in dry growth and, therefore, we conclude that it is unlikely to play an important role in the electrification of thunderstorms.

Kirsten ras mutations in patients with colorectal cancer : the ‘RASCAL II’ study

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes’ C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes’ B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.

Marx as a Critical Discourse Analyst : The Genesis of a Critical Method and its Relevance to the Critique of Global Capital (with Phil Graham)

In this paper we identify elements in Marx’s economic and political writings that are relevant to contemporary critical discourse analysis (CDA). We argue that Marx can be seen to be engaging in a form of discourse analysis. We identify the elements in Marx’s historical materialist method that support such a perspective, and exemplify these in longitudinal comparison of Marx’s texts.

Health consequences of exposure to brominated flame retardants : a systematic review

Background Brominated flame retardants (BFRs), are chemicals widely used in consumer products including electronics, vehicles, plastics and textiles to reduce flammability. Experimental animal studies have confirmed that these compounds may interfere with thyroid hormone homeostasis and neurodevelopment but to date health effects in humans have not been systematically examined. Objectives To conduct a systematic review of studies on the health impacts of exposure to BFRs in humans, with a particular focus on children. Methods A systematic review was conducted using the Medline and EMBASE electronic databases up to 1 February 2012. Published cohort, cross-sectional, and case-control studies exploring the relationship between BFR exposure and various health outcomes were included. Results In total, 36 epidemiological studies meeting the pre-determined inclusion criteria were included. Plausible outcomes associated with BFR exposure include diabetes, neurobehavioral and developmental disorders, cancer, reproductive health effects and alteration in thyroid function. Evidence for a causal relationship between exposure to BFRs and health outcomes was evaluated within the Bradford Hill framework. Conclusion Although there is suggestive evidence that exposure to BFRs is harmful to health, further epidemiological investigations particularly among children, and long-term monitoring and surveillance of chemical impacts on humans are required to confirm these relationships.

Can playing Monopoly™ enhance learning for property students

This paper outlines the initial results from a pilot study into the educational use of the board game Monopoly City™ in a first year property economics unit. This game play was introduced as a fun and interactive way of achieving a number of desired outcomes including: enhanced engagement of first year students; introduction of foundational threshold concepts in property education; introduction of problem solving and critical analysis skills; early acculturation of property students to enhance student retention; and early team building within the Property Economics cohort, all in an engaging and entertaining way. Preliminary results in this research project are encouraging. The students participating in this initial cycle have demonstrated explicit linkages between their Monopoly City™ experiences and foundation urban economic and valuation theories. Students are also recognising the role strategy and chance play in the property sector. However, linking Monopoly City™ activities to assessment has proved important in student attendance and hence engagement.

Synonymization of key pest species within the Bactrocera dorsalis species complex (Diptera: Tephritidae): Taxonomic changes based on a review of 20 years of integrative morphological, molecular, cytogenetic, behavioural and chemoecological data

Bactrocera papayae Drew & Hancock, Bactrocera philippinensis Drew & Hancock, Bactrocera carambolae Drew & Hancock, and Bactrocera invadens Drew, Tsuruta & White are four horticultural pest tephritid fruit fly species that are highly similar, morphologically and genetically, to the destructive pest, the Oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). This similarity has rendered the discovery of reliable diagnostic characters problematic, which, in view of the economic importance of these taxa and the international trade implications, has resulted in ongoing difficulties for many areas of plant protection and food security. Consequently, a major international collaborative and integrated multidisciplinary research effort was initiated in 2009 to build upon existing literature with the specific aim of resolving biological species limits among B. papayae, B. philippinensis, B. carambolae, B. invadens and B. dorsalis to overcome constraints to pest management and international trade. Bactrocera philippinensis has recently been synonymized with B. papayae as a result of this initiative and this review corroborates that finding; however, the other names remain in use. While consistent characters have been found to reliably distinguish B. carambolae from B. dorsalis, B. invadens and B. papayae, no such characters have been found to differentiate the latter three putative species. We conclude that B. carambolae is a valid species and that the remaining taxa, B. dorsalis, B. invadens and B. papayae, represent the same species. Thus, we consider B. dorsalis (Hendel) as the senior synonym of B. papayae Drew and Hancock syn.n. and B. invadens Drew, Tsuruta & White syn.n. A redescription of B. dorsalis is provided. Given the agricultural importance of B. dorsalis, this taxonomic decision will have significant global plant biosecurity implications, affecting pest management, quarantine, international trade, postharvest treatment and basic research. Throughout the paper, we emphasize the value of independent and multidisciplinary tools in delimiting species, particularly in complicated cases involving morphologically cryptic taxa.

Electrocatalytic and SERS activity of Pt rich Pt-Pb nanostructures formed via the utilisation of in-situ underpotential deposition of lead

The controlled synthesis of nanostructured materials remains an ongoing area of research, especially as the size, shape and composition of nanomaterials can greatly influence their properties and applications. In this work we present the electrodeposition of highly dendritic platinum rich platinum-lead nanostructures, where lead acetate acts as an inorganic shape directing agent via underpotential deposition on the growing electrodeposit. It was found that these nanomaterials readily oxidise at potentials below monolayer oxide formation, which significantly impacts on the methanol electrooxidation reaction and correlates with the incipient hydrous oxide adatom mediator (IHOAM) model of electrocatalysis. Additionally these materials were tested for their surface enhanced Raman scattering (SERS) activity, where the high density of sharp tips provides promise for their application as SERS substrates.

Hardware design and implementation of a MAVLink interface for an FPGA-based autonomous UAV flight control system

This paper details the initial design and planning of a Field Programmable Gate Array (FPGA) implemented control system that will enable a path planner to interact with a MAVLink based flight computer. The design is aimed at small Unmanned Aircraft Vehicles (UAV) under autonomous operation which are typically subject to constraints arising from limited on-board processing capabilities, power and size. An FPGA implementation for the de- sign is chosen for its potential to address such limitations through low power and high speed in-hardware computation. The MAVLink protocol offers a low bandwidth interface for the FPGA implemented path planner to communicate with an on-board flight computer. A control system plan is presented that is capable of accepting a string of GPS waypoints generated on-board from a previously developed in- hardware Genetic Algorithm (GA) path planner and feeding them to the open source PX4 autopilot, while simultaneously respond- ing with flight status information.