Identification of eusynstyelamide B as a potent cell cycle inhibitor following the generation and screening of an ascidian-derived extract library using a real time cell analyzer

Ascidians are marine invertebrates that have been a source of numerous cytotoxic compounds. Of the first six marine-derived drugs that made anticancer clinical trials, three originated from ascidian specimens. In order to identify new anti-neoplastic compounds, an ascidian extract library (143 samples) was generated and screened in MDA-MB-231 breast cancer cells using a real-time cell analyzer (RTCA). This resulted in 143 time-dependent cell response profiles (TCRP), which are read-outs of changes to the growth rate, morphology, and adhesive characteristics of the cell culture. Twenty-one extracts affected the TCRP of MDA-MB-231 cells and were further investigated regarding toxicity and specificity, as well as their effects on cell morphology and cell cycle. The results of these studies were used to prioritize extracts for bioassay-guided fractionation, which led to the isolation of the previously identified marine natural product, eusynstyelamide B (1). This bis-indole alkaloid was shown to display an IC50 of 5 μM in MDA-MB-231 cells. Moreover, 1 caused a strong cell cycle arrest in G2/M and induced apoptosis after 72 h treatment, making this molecule an attractive candidate for further mechanism of action studies.

Resistance to amoebic gill disease (AGD) is characterised by the transcriptional dysregulation of immune and cell cycle pathways

Amoebic gill disease (AGD) is a parasite-mediated proliferative gill disease capable of affecting a range of teleost hosts. While a moderate heritability for AGD resistance in Atlantic salmon has been reported previously, the mechanisms by which individuals resist the proliferative effects remain poorly understood. To gain more knowledge of this commercially important trait, we compared gill transcriptomes of two groups of Atlantic salmon, one designated putatively resistant, and one designated putatively susceptible to AGD. Utilising a 17k Atlantic salmon cDNA microarray we identified 196 transcripts that were differentially expressed between the two groups. Expression of 11 transcripts were further examined with real-time quantitative RT-PCR (qPCR) in the AGD-resistant and AGD-susceptible animals, as well as non-infected naïve fish. Gene expression determined by qPCR was in strong agreement with the microarray analysis. A large number of differentially expressed genes were involved in immune and cell cycle responses. Resistant individuals displayed significantly higher expression of genes involved in adaptive immunity and negative regulation of the cell cycle. In contrast, AGD-susceptible individuals showed higher expression of acute phase proteins and positive regulators of the cell cycle. Combined with the gill histopathology, our results suggest AGD resistance is acquired rather than innately present, and that this resistance is for the most part associated with the dysregulation of immune and cell cycle pathways. © 2008 Elsevier Ltd. All rights reserved.

Inter-cycle variability of ignition delay in an ethanol fumigated common rail diesel engine

An experimental study has been performed to investigate the ignition delay of a modern heavy-duty common-rail diesel engine run with fumigated ethanol substitutions up to 40% on an energy basis. The ignition delay was determined through the use of statistical modelling in a Bayesian framework this framework allows for the accurate determination of the start of combustion from single consecutive cycles and does not require any differentiation of the in-cylinder pressure signal. At full load the ignition delay has been shown to decrease with increasing ethanol substitutions and evidence of combustion with high ethanol substitutions prior to diesel injection have also been shown experimentally and by modelling. Whereas, at half load increasing ethanol substitutions have increased the ignition delay. A threshold absolute air to fuel ratio (mole basis) of above ~110 for consistent operation has been determined from the inter-cycle variability of the ignition delay, a result that agrees well with previous research of other in-cylinder parameters and further highlights the correlation between the air to fuel ratio and inter-cycle variability. Numerical modelling to investigate the sensitivity of ethanol combustion has also been performed. It has been shown that ethanol combustion is sensitive to the initial air temperature around the feasible operating conditions of the engine. Moreover, a negative temperature coefficient region of approximately 900{1050 K (the approximate temperature at fuel injection) has been shown with for n-heptane and n-heptane/ethanol blends in the numerical modelling. A consequence of this is that the dominate effect influencing the ignition delay under increasing ethanol substitutions may rather be from an increase in chemical reactions and not from in-cylinder temperature. Further investigation revealed that the chemical reactions at low ethanol substitutions are different compared to the high (> 20%) ethanol substitutions.

The Reef Cycle: Engaging in creativity and global awareness

This is a report of a musical theatre production performed at QUT Gardens Point Campus in November 2014 for the occasion of the end of year Annual Art Exhibition and concert of the Post graduate research students. Both the performance and the exhibition focused on environmental issues especially in relation to coal and coral in Queensland. The poster was prepared by Stephen Bennett former student in Creative Industries.

The Reef Cycle: Paradise; Paradise Plundered; Paradise Preserved by people Power

This is a musical theatre production with an environmental message addressing a Queensland, Australia tussle between the development of the Galilee Coal Basin and the potential threat to the health of the Great Barrier Reef along the Queensland coast. The drama is enacted by characters representing "goodies" and "baddies" and includes epic poetry, dance, orchestra and drama. The whole performance is enacted in the midst of a post graduate student art exhibition with a coral and coal theme.

Restraint in the age of speed: Protecting vulnerable news sources in the 24/7 global news cycle

As news communication speeds up, investigative journalists have an increasing responsibility to minimise the risk of harm to vulnerable news sources. In addition, the increased longevity and instant global search-ability of news coverage and investigative journalism outputs such as documentaries, places upon journalists an increased responsibility for accuracy since online coverage cannot be easily corrected or retracted. This paper will examine how the risks to a news source and her family were considered and mitigated during the production of a radio documentary and newspaper story about an intended victim of child sacrifice. Pre-publication considerations included the possible risks to the mental health of the news source, the potential physical risk to her children and the risk to future family relationships. To hear the ABC Radio National documentary, A living sacrifice, on 360 Documentaries prior to the conference, see http://www.abc.net.au/radionational/programs/360/a-living-sacrifice/5359744. To read the Sunday Mail newspaper coverage of the story see http://www.couriermail.com.au/news/queensland/susannah-birch-talks-about-her-throat-being-slit-by-her-mother-when-she-was-a-baby/story-fnihsrf2-1226881911465.

Robust design and optimisation of a radial turbine within a supercritical CO2 solar Brayton Cycle

The generation of solar thermal power is dependent upon the amount of sunlight exposure,as influenced by the day-night cycle and seasonal variations. In this paper, robust optimisation is applied to the design of a power block and turbine, which is generating 30 MWe from a concentrated solar resource of 560oC. The robust approach is important to attain a high average performance (minimum efficiency change) over the expected operating ranges of temperature, speed and mass flow. The final objective function combines the turbine performance and efficiency weighted by the off-design performance. The resulting robust optimisation methodology as presented in the paper gives further information that greatly aids in the design of non-classical power blocks through considering off-design conditions and resultant performance.

A life cycle assessment approach to quantifying greenhouse gas emissions from land-use change for beef production in eastern Australia

In life cycle assessment studies, greenhouse gas (GHG) emissions from direct land-use change have been estimated to make a significant contribution to the global warming potential of agricultural products. However, these estimates have a high uncertainty due to the complexity of data requirements and difficulty in attribution of land-use change. This paper presents estimates of GHG emissions from direct land-use change from native woodland to grazing land for two beef production regions in eastern Australia, which were the subject of a multi-impact life cycle assessment study for premium beef production. Spatially- and temporally consistent datasets were derived for areas of forest cover and biomass carbon stocks using published remotely sensed tree-cover data and regionally applicable allometric equations consistent with Australia's national GHG inventory report. Standard life cycle assessment methodology was used to estimate GHG emissions and removals from direct land-use change attributed to beef production. For the northern-central New South Wales region of Australia estimates ranged from a net emission of 0.03 t CO2-e ha-1 year-1 to net removal of 0.12 t CO2-e ha-1 year-1 using low and high scenarios, respectively, for sequestration in regrowing forests. For the same period (1990-2010), the study region in southern-central Queensland was estimated to have net emissions from land-use change in the range of 0.45-0.25 t CO2-e ha-1 year-1. The difference between regions reflects continuation of higher rates of deforestation in Queensland until strict regulation in 2006 whereas native vegetation protection laws were introduced earlier in New South Wales. On the basis of liveweight produced at the farm-gate, emissions from direct land-use change for 1990-2010 were comparable in magnitude to those from other on-farm sources, which were dominated by enteric methane. However, calculation of land-use change impacts for the Queensland region for a period starting 2006, gave a range from net emissions of 0.11 t CO2-e ha-1 year-1 to net removals of 0.07 t CO2-e ha-1 year-1. This study demonstrated a method for deriving spatially- and temporally consistent datasets to improve estimates for direct land-use change impacts in life cycle assessment. It identified areas of uncertainty, including rates of sequestration in woody regrowth and impacts of land-use change on soil carbon stocks in grazed woodlands, but also showed the potential for direct land-use change to represent a net sink for GHG.

Life cycle energy analysis of eight residential houses in Brisbane, Australia

Life cycle energy analysis (LCEA) of eight residential buildings in and around Brisbane, Queensland, Australia, is undertaken in this study. Energy used in all three phases of construction, operation and demolition are considered. It is found that the main contribution to the operational energy in residential buildings is from use of general appliance. The choice of building materials is shown to have significant effects on the embodied energy for the production, construction, maintenance and demolition phases. From this study, it is shown that the embodied energy may vary from 10% to 30%, while the operational energy may vary from 65% to 90%. The demolition energy generally accounts for less than 4% of life cycle energy.

A framing analysis on Nepalese media portrayal of disaster events using news frames and PPRR cycle

This study seeks to understand the prevailing status of Nepalese media portrayal of natural disasters and develop a disaster management framework to improve the effectiveness and efficiency of news production through the continuum of prevention, preparedness, response and recovery (PPRR) phases of disaster management. The study is currently under progress. It is being undertaken in three phases. In phase-1, a qualitative content analysis is conducted. The news contents are categorized in frames as proposed in the 'Framing theory' and pre-defined frames. However, researcher has looked at the theories of the Press, linking to social responsibility theory as it is regarded as the major obligation of the media towards the society. Thereafter, the contents are categorized as per PPRR cycle. In Phase-2, based on the findings of content analysis, 12 in-depth interviews with journalists, disaster managers and community leaders are conducted. In phase-3, based on the findings of content analysis and in-depth interviews, a framework for effective media management of disaster are developed using thematic analysis. As the study is currently under progress hence, findings from the pilot study are elucidated. The response phase of disasters is most commonly reported in Nepal. There is relatively low coverage of preparedness and prevention. Furthermore, the responsibility frame in the news is most prevalent following human interest. Economic consequences and conflict frames are also used while reporting and vulnerability assessment has been used as an additional frame. The outcomes of this study are multifaceted: At the micro-level people will be benefited as it will enable a reduction in the loss of human lives and property through effective dissemination of information in news and other mode of media. They will be ‘well prepared for', 'able to prevent', 'respond to' and 'recover from' any natural disasters. At the meso level the media industry will be benefited and have their own 'disaster management model of news production' as an effective disaster reporting tool which will improve in media's editorial judgment and priority. At the macro-level it will assist government and other agencies to develop appropriate policies and strategies for better management of natural disasters.

Determination of the effect of JO146, a CtHtrA inhibitor, on the chlamydial developmental cycle and persistence

The role of Chlamydia trachomatis HtrA (CtHtrA) for the growth and pathogenesis of this organism is presented. Inhibition of CtHtrA led to loss of infectious progeny in Chlamydia, particularly during heat stress or recovery from penicillin persistence. Isolation of CtHtrA inhibitor resistant mutants identified positive selection for mutants in fatty acid related pathways. Importantly, HtrA inhibition was effective against clinical isolates of C. trachomatis. Thus the findings combined indicate that CtHtrA is an important chlamydial growth factor that has the potential to be targeted for the development of anti-chlamydial drugs in the future.

An effective, economic way of monitoring menstrual cycle hormones in at risk female athletes

PURPOSE: Female athletes, in response to intensive training, competition stress and a lean, athletic physique, are at increased risk of altered hypothalamic-pituitary ovarian (HPO) axis function associated with menstrual cycle disturbance and reduced secretion of the ovarian hormones estrogen and progesterone. Because there is evidence suggesting possible detrimental effects on skeletal health associated with deficiencies in these hormones, a suitable means to asses ovarian hormone concentrations in at risk athletes is needed. The aim of this study was to evaluate a simple, economical means to monitor the ovarian hormone production in athletes, in the setting of intensive training. METHODS: Subjects comprised 14 adolescent rowers, 12 lightweight rowers, and two groups of 10 matched control subjects. Ovarian function was monitored during the competition season by estimation of urinary excretion of estrone glucuronide (E1G) and pregnanediol glucuronide (PdG), enabling the menstrual cycles to be classified as ovulatory or anovulatory. RESULTS: Results indicated 35% and 75% of schoolgirl and lightweight rowers had anovulatory menstrual cycles, respectively. These findings were highlighted by significantly lower excretion of E1G and PdG during phases of intensive training in both the lightweight and schoolgirl rowers, compared with the control subjects. CONCLUSION: It was concluded that the urinary E1G and PdG assays were an effective means to assess the influence of intense training on ovarian hormone concentrations in at risk athletes. It is recommended that this technique be applied more widely as a means of early detection of athletes with low estrogen and progesterone levels, in an attempt to avoid detrimental influences on skeletal health.

Changes in CO2 emissions over business cycle recessions and expansions in the United States: A decomposition analysis

This paper examines the asymmetry of changes in CO2 emissions over business cycle recessions and expansions using yearly data from 1949 and monthly data from 1973 for the United States (US). In addition, decomposition analysis is applied to investigate the relative roles of various proximate contributing factors to observed changes in total and per capita CO2 emissions and emissions intensity, over business cycle phases. The results suggest, inter alia, that aggregate emissions and emissions intensity reduce much faster in contractions than they increase in expansions. In addition, unlike the three previous expansions, in the most recent post-GFC US expansion, emissions per capita have continued to decline, and at a rate very similar to the rate of reduction in preceding contractions. This suggests the real possibility that the most recent contraction may have had an ongoing impact on the path of per capita emissions well beyond the immediate impact experienced during the contraction itself.

Time-driven life cycle cost estimation system for product family design

This research develops a design support system, which is able to estimate the life cycle cost of different product families at the early stage of product development. By implementing the system, a designer is able to develop various cost effective product families in a shorter lead-time and minimise the destructive impact of the product family on the environment.