Commentary on papers by Professor Fletcher and Mr Martin

In light of the time available today, I will limit my comments to addressing that aspect of Professor Fletcher’s paper in which he refers to the 2012 report he co-authored with Professor Wessels of the Netherlands for the American Law Institute (ALI) and the International Insolvency Institute (III) on Transnational Insolvency: Global Principles for Cooperation in International Insolvency Cases. I will comment on the potential benefits for Australian courts as well as insolvency administrators and their advisers in referring to the ALI-III Report - in light of Australia’s adoption of the UNCITRAL Model Law. In so doing, I would like to acknowledge the support of the Australian Academy of Law, under the leadership of The Hon Dr Kevin Lindgren for the research project underpinning these comments, as well as to acknowledge the contributions of my colleagues Associate Professor Sheryl Jackson and Mark Wellard.

A concise approach to the polycyclic scaffold of frondosin D

Frondosins A−E, 1−5 (Figure 1), are a family of related marine sesquiterpenoids first isolated in their dextro-rotatory form from the sponge Dysidea frondosa.(1a) Additionally, levo-rotatory frondosins A and D were isolated from an unidentified Eurospongia species.(1b) Frondosins A−E are compounds of interest due to their promising interleukin-8 (IL-8) affinity and protein kinase C inhibition.(1a) IL-8 antagonists are of particular interest in view of their antiinflammatory,(2a) anti-HIV,(1b, 2b) and antitumor(2c-2f) properties. To date, frondosins A, B, and C have been synthesized.(3) Notwithstanding these successes, the frondosins have proved quite a formidable synthetic challenge, and as of yet, there has been no synthesis of frondosin D or E. In this report, we describe our approaches to the molecular scaffold of frondosins D. This work has culminated in a very effective means of producing the trimethylbicyclo[5.4.0]undecane ring system common to all frondosins (shown in bold, Figure 1).

Eutrophication weakens stabilizing effects of diversity in natural grasslands

Studies of experimental grassland communities have demonstrated that plant diversity can stabilize productivity through species asynchrony, in which decreases in the biomass of some species are compensated for by increases in others. However, it remains unknown whether these findings are relevant to natural ecosystems, especially those for which species diversity is threatened by anthropogenic global change. Here we analyse diversity-stability relationships from 41 grasslands on five continents and examine how these relationships are affected by chronic fertilization, one of the strongest drivers of species loss globally. Unmanipulated communities with more species had greater species asynchrony, resulting in more stable biomass production, generalizing a result from biodiversity experiments to real-world grasslands. However, fertilization weakened the positive effect of diversity on stability. Contrary to expectations, this was not due to species loss after eutrophication but rather to an increase in the temporal variation of productivity in combination with a decrease in species asynchrony in diverse communities. Our results demonstrate separate and synergistic effects of diversity and eutrophication on stability, emphasizing the need to understand how drivers of global change interactively affect the reliable provisioning of ecosystem services in real-world systems.

Sports dietitians Australia position statement : sports nutrition for the adolescent athlete

It is the position of Sports Dietitians Australia (SDA) that adolescent athletes have unique nutritional requirements as a consequence of undertaking daily training and competition in addition to the demands of growth and development. As such, SDA established an expert multidisciplinary panel to undertake an independent review of the relevant scientific evidence and consulted with its professional members to develop sports nutrition recommendations for active and competitive adolescent athletes. The position of SDA is that dietary education and recommendations for these adolescent athletes should reinforce eating for long term health. More specifically, the adolescent athlete should be encouraged to moderate eating patterns to reflect daily exercise demands and provide a regular spread of high quality carbohydrate and protein sources over the day, especially in the period immediately after training. SDA recommends that consideration also be given to the dietary calcium, Vitamin D and iron intake of adolescent athletes due to the elevated risk of deficiency of these nutrients. In order to maintain optimal hydration, adolescent athletes should have access to fluids that are clean, cool and supplied in sufficient quantities before, during and after participation in sport. Finally, it is the position of SDA that use of nutrient needs should be met by core foods rather than supplements, as the recommendation of dietary supplements to developing athletes over-emphasises their ability to manipulate performance in comparison to other training and dietary strategies.

A detailed investigation of nominally 2-D radical-farming scramjet combustion

This paper reports on an investigation of the flow/chemistry coupling inside a nominally two-dimensional inlet-fuelled scramjet configuration. The experiments were conducted at a freestream Mach number of 7.3 and a total flow enthalpy of 4.3MJ/kg corresponding to a Mach 9.7 flight condition. The phenomenon of radical-farming has been studied in detail using two-dimensional OH* chemiluminescence imaging and emission spectroscopy. High signal levels of excited OH (OH*) were detected behind the first shock reflections inside the combustion chamber upstream of any measurable pressure rise from combustion, which occurred towards the rear of the combustor. The production of OH in the first hot pocket initiates the ignition process and then accelerates the combustion process in the next downstream hot pocket. This was confirmed by numerical simulations of premixed hydrogen/air flow through the scramjet. Chemical kinetics analyses reveal that the ignition process is governed by the interaction between various reaction groups leading to a chainbranching explosion for low mean temperature and pressure combustion flowfields.

High-level expression of Rhodotorula gracilis d-amino acid oxidase in Pichia pastoris

By combining gene design and heterologous over-expression of Rhodotorula gracilis D-amino acid oxidase (RgDAO) in Pichia pastoris, enzyme production was enhanced by one order of magnitude compared to literature benchmarks, giving 350 kUnits/l of fed-batch bioreactor culture with a productivity of 3.1 kUnits/l h. P. pastoris cells permeabilized by freeze-drying and incubation in 2-propanol (10% v/v) produce a highly active (1.6 kUnits/g dry matter) and stable oxidase preparation. Critical bottlenecks in the development of an RgDAO catalyst for industrial applications have been eliminated.

Stepwise engineering of a Pichia pastoris D-amino acid oxidase whole cell catalyst

Trigonopsis variabilis D-amino acid oxidase (TvDAO) is a well characterized enzyme used for cephalosporin C conversion on industrial scale. However, the demands on the enzyme with respect to activity, operational stability and costs also vary with the field of application. Processes that use the soluble enzyme suffer from fast inactivation of TvDAO while immobilized oxidase preparations raise issues related to expensive carriers and catalyst efficiency. Therefore, oxidase preparations that are more robust and active than those currently available would enable a much broader range of economically viable applications of this enzyme in fine chemical syntheses. A multi-step engineering approach was chosen here to develop a robust and highly active Pichia pastoris TvDAO whole-cell biocatalyst. As compared to the native T. variabilis host, a more than seven-fold enhancement of the intracellular level of oxidase activity was achieved in P. pastoris through expression optimization by codon redesign as well as efficient subcellular targeting of the enzyme to peroxisomes. Multi copy integration further doubled expression and the specific activity of the whole cell catalyst. From a multicopy production strain, about 1.3 x 103 U/g wet cell weight (wcw) were derived by standard induction conditions feeding pure methanol. A fed-batch cultivation protocol using a mixture of methanol and glycerol in the induction phase attenuated the apparent toxicity of the recombinant oxidase to yield final biomass concentrations in the bioreactor of >or= 200 g/L compared to only 117 g/L using the standard methanol feed. Permeabilization of P. pastoris using 10% isopropanol yielded a whole-cell enzyme preparation that showed 49% of the total available intracellular oxidase activity and was notably stabilized (by three times compared to a widely used TvDAO expressing Escherichia coli strain) under conditions of D-methionine conversion using vigorous aeration. Stepwise optimization using a multi-level engineering approach has delivered a new P. pastoris whole cell TvDAO biocatalyst showing substantially enhanced specific activity and stability under operational conditions as compared to previously reported preparations of the enzyme. The production of the oxidase through fed-batch bioreactor culture and subsequent cell permeabilization is high-yielding and efficient. Therefore this P. pastoris catalyst has been evaluated for industrial purposes.

Environmental regulation of leaf colour in red 35S : PAP1 Arabidopsis thaliana

High-temperature, low-light (HTLL) treatment of 35S:PAP1 Arabidopsis thaliana over-expressing the PAP1 (Production of Anthocyanin Pigment 1) gene results in reversible reduction of red colouration, suggesting the action of additional anthocyanin regulators. High-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LCMS) and Affimetrix®-based microarrays were used to measure changes in anthocyanin, flavonoids, and gene expression in response to HTLL. HTLL treatment of control and 35S:PAP1 A. thaliana resulted in a reversible reduction in the concentrations of major anthocyanins despite ongoing over-expression of the PAP1 MYB transcription factor. Twenty-one anthocyanins including eight cis-coumaryl esters were identified by LCMS. The concentrations of nine anthocyanins were reduced and those of three were increased, consistent with a sequential process of anthocyanin degradation. Analysis of gene expression showed down-regulation of flavonol and anthocyanin biosynthesis and of transport-related genes within 24 h of HTLL treatment. No catabolic genes up-regulated by HTLL were found. Reductions in the concentrations of anthocyanins and down-regulation of the genes of anthocyanin biosynthesis were achieved by environmental manipulation, despite ongoing over-expression of PAP1. Quantitative PCR showed reduced expression of three genes (TT8, TTG1 and EGL3) of the PAP1 transcriptional complex, and increased expression of the potential transcriptional repressors AtMYB3, AtMYB6 and AtMYBL2 coincided with HTLL-induced down-regulation of anthocyanin biosynthesis. HTLL treatment offers a model system with which to explore anthocyanin catabolism and to discover novel genes involved in the environmental control of anthocyanins.

Loss of epithelial markers and acquisition of vimentin expression in adriamycin- and vinblastine-resistant human breast cancer cell lines

We have previously observed that breast cancer cell lines could exhibit either epithelial or fibroblastic phenotypes as reflected by their morphologies and intermediate filament protein expression (C. L. Sommers, D. Walker-Jones, S. E. Heckford, P. Worland, E. Valverius, R. Clark, M. Stampfer, and E. P. Gelmann, Cancer Res., 49: 4258-4263, 1989). Fibroblastoid, vimentin-expressing breast cancer cell lines are more invasive in vitro and in vivo (E. W. Thompson, S. Paik, N. Brunner, C. L. Sommers, G. Zugmaier, R. Clarke, T. B. Shima, J. Torri, S. Donahue, M. E. Lippman, G. R. Martin, and R. B. Dickson, J. Cell. Physiol., 150: 534-544, 1992). We hypothesized that a breast cancer cell with an epithelial phenotype could undergo a transition to a fibroblastic phenotype, possibly resulting in more invasive capacity. We now show that two Adriamycin-resistant MCF-7 cell lines and a vinblastine-resistant ZR-75-B cell line have undergone such a transition. Adriamycin-resistant MCF-7 cells express vimentin, have diminished keratin 19 expression, have lost cell adhesion molecule uvomorulin expression, and have reduced formation of desmosomes and tight junctions as determined by reduced immunodetection of their components desmoplakins I and II and zonula occludens (ZO)-1. Other MCF-7 cell lines selected for resistance to vinblastine and to Adriamycin and verapamil did not have these characteristics, indicating that drug selection does not invariably cause these phenotypic changes. In addition, to determine if vimentin expression in MCF-7 cells alone could manifest a fibroblastic phenotype, we transfected the full-length human vimentin complementary DNA into MCF-7 cells. Although vimentin expression was achieved in MCF-7 cells, it did not affect the phenotype of the cells in terms of the distribution of keratins, desmoplakins I and II, ZO-1, or uvomorulin or in terms of in vitro invasiveness. We conclude that vimentin expression is a marker for a fibroblastic and invasive phenotype in breast cancer cells but does not by itself give rise to this phenotype.

Calibration of the biotrainer pro activity monitor in children

The unique physical and movement characteristics of children necessitate the development of accelerometer equations and cut points that are population specific. The purpose of this study is to develop an ecologically valid cut point for the Biotrainer Pro monitor that reflects a threshold for moderate-intensity physical activity in elementary school children. A sample of 30 children (ages 8-12) wore a Biotrainer monitor while completing a series of 7 movement tasks (calibration phase) and while participating in an organized group activity (cross-validation phase). Videotapes from each session were processed using a computerized direct-observation technique to provide a criterion measure of physical activity. Analyses involved the use of mixed-model regression and receiver operator characteristic (ROC) curves. The results indicated that a cut point of 4 counts/min provides the optimal balance between the related needs for sensitivity (accurately detecting activity) and specificity (limiting misclassification of activity as inactivity). Results with the cross-validation data demonstrated that this value yielded the best overall kappa (.58) and a high classification agreement (84%) for activity determination. The specificity of 93% demonstrates that the proposed cut point can accurately detect activity; however, the lower sensitivity value of 61% suggests that some minutes of activity might be incorrectly classified as inactivity. The cut point of 4 counts/min provides an ecologically valid cut point to capture physical activity in children using the Biotrainer Pro activity monitor.

Invasive activity and chemotactic response to growth factors by Kaposi's sarcoma cells

Kaposi's sarcoma (KS) is a relatively low grade neoplasm, classically occurring in the skin of elderly men. A more virulent and invasive form of Kaposi's sarcoma has been described in patients with acquired immune deficiency syndrome (AIDS). The origin and identification of the tumor cells in these lesions is controversial. Here we have studied the behavior of cells derived from KS lesions in an in vitro assay which measures the ability of cells to invade through a reconstituted basement membrane. In agreement with previous work, KS cells obtained under selective culture conditions were invasive showing activity comparable to that of malignant tumor cells. Normal fibroblasts, smooth muscle cells, and endothelial cells did not demonstrate invasive behavior under the same experimental conditions. To characterize further the nature of the KS cells we tested the chemotactic response of cells from the most invasive line to a variety of growth factors and compared their response to those of fibroblasts, smooth muscle, and endothelial cells. These studies suggest that normal cells respond to a unique repertoire of chemotactic factors. The chemotactic response of the KS cells most closely resembled that of smooth muscle cells and was quite distinct from endothelial cells. These results indicate that the KS-derived cultures contain invasive cells with a smooth muscle cell-like phenotype.

Herbivores and nutrients control grassland plant diversity via light limitation

Human alterations to nutrient cycles1, 2 and herbivore communities3, 4, 5, 6, 7 are affecting global biodiversity dramatically2. Ecological theory predicts these changes should be strongly counteractive: nutrient addition drives plant species loss through intensified competition for light, whereas herbivores prevent competitive exclusion by increasing ground-level light, particularly in productive systems8, 9. Here we use experimental data spanning a globally relevant range of conditions to test the hypothesis that herbaceous plant species losses caused by eutrophication may be offset by increased light availability due to herbivory. This experiment, replicated in 40 grasslands on 6 continents, demonstrates that nutrients and herbivores can serve as counteracting forces to control local plant diversity through light limitation, independent of site productivity, soil nitrogen, herbivore type and climate. Nutrient addition consistently reduced local diversity through light limitation, and herbivory rescued diversity at sites where it alleviated light limitation. Thus, species loss from anthropogenic eutrophication can be ameliorated in grasslands where herbivory increases ground-level light.

Embedded creatives in Australian healthcare: An update

The contribution of creative occupations to Australian healthcare was examined using a mix of statistics and case studies. Creative occupations were found to be making widespread contributions in healthcare, in particular, to the development and delivery of healthcare goods and services, the initial training and ongoing professionalism of doctors and nurses and the effective functioning of healthcare buildings. Within most facets of healthcare, increasing employment over the period examined indicated that these contributions were growing. Key functions that creative activities addressed were information management and analysis and making complex information comprehensible, assisting communication and reducing psycho-social and distance-mediated barriers, and improving the efficiency and effectiveness of services.

Embedded creatives in the Australian manufacturing industry

According to 2011 Australian Census figures, embedded creative employees (creative employees not working in the core Creative Industries) make up 2 per cent (or a total of 17 635) of manufacturing industry employees. The average for all industries is 1.6 per cent. In the 2011–2012 financial year the manufacturing industry formed 7.3 per cent of Australia’s gross domestic product (GDP), contributing approximately AU$106.5 billion to the economy (Department of Industry, Innovation, Science, Research and Tertiary Education 2013). Manufacturing is central to innovation, accounting for over one-quarter of all business expenditure in R&D in 2010–2011, representing around AU$4.8 billion invested in R&D (ibid.). Facing challenges such as sustainability concerns, ever-increasing offshore production and the global financial crisis, the Australian manufacturing industry needs to remain relevant and competitive to succeed. Innovation is one way to do this. Given the contribution of the manufacturing industry to the Australian economy, and the above-average portion of embedded creatives in manufacturing, it is important to consider what exactly embedded creatives add to the industry. This chapter, inspired by the Getting Creative in Healthcare report (Pagan, Higgs and Cunningham 2008), examines the contribution of embedded creatives to innovation in the manufacturing industry via case studies and supplemental data.