Australia, Asia and cultural anxiety : inaugural AHA Anniversary Public Lecture, given at the Grand Hotel, Mildura on 29 September (2003).

My theme tonight is the recurrent idea that Australia could be expected to have an Asian future. From the 1880s there developed a speculative literature around the notion that Asia ('generic Asia' as I prefer to call it) would exert an increasing influence, possibly a determining influence, on the development and settlement of the Australian continent. There is a certain pathos about this story of a young, newly formed community on the threshold of nationhood finding Asia blocking its path. Would the ensuing contest be the making of white Australia; would the young nation define its national purpose and assert its right to exist or would it succumb to a force more powerful? Would white Australia become nothing more than a faint historical memory, a failed experiment in the complex and uncertain business of nation building? In short, would white Australia fail?

Targeting Hsp90 with small molecule inhibitors induces the over-expression of the anti-apoptotic molecule, survivin, in human A549, HONE-1 and HT-29 cancer cells

Survivin is a dual functioning protein. It inhibits the apoptosis of cancer cells by inhibiting caspases, and also promotes cancer cell growth by stabilizing microtubules during mitosis. Since the molecular chaperone Hsp90 binds and stabilizes survivin, it is widely believed that down-regulation of survivin is one of the important therapeutic functions of Hsp90 inhibitors such as the phase III clinically trialed compound 17-AAG. However, Hsp90 interferes with a number of molecules that up-regulate the intracellular level of survivin, raising the question that clinical use of Hsp90 inhibitors may indirectly induce survivin expression and subsequently enhance cancer anti-drug responses. The purpose of this study is to determine whether targeting Hsp90 can alter survivin expression differently in different cancer cell lines and to explore possible mechanisms that cause the alteration in survivin expression.

Effects of bone-specific physical activity, gender and maturity on tibial cross-sectional bone material distribution; a cross-sectional pQCT comparison of children and young adults aged 5-29 years

Growth is the opportune time to modify bone accrual. While bone adaptation is known to be dependent on local loading and consequent deformations (strain) of bone, little is known about the effects of sex, and bone-specific physical activity on location-specific cross-sectional bone geometry during growth. To provide more insight we examined bone traits at different locations around tibial cross sections, and along the tibia between individuals who vary in terms of physical activity exposure, sex, and pubertal status. Data from 304 individuals aged 5-29 years (172 male, 132 female) were examined. Peripheral quantitative computed tomography (pQCT) was applied at 4%, 14%, 38%, and 66% of tibial length. Maturity was established by estimating age at peak height velocity (APHV). Loading history was quantified with the bone-specific physical activity questionnaire (BPAQ). Comparisons, adjusted for height, weight and age were made between sex, maturity, and BPAQ tertile groups. Few to no differences were observed between sexes or BPAQ tertiles prior to APHV, whereas marked sexual dimorphism and differences between BPAQ tertiles were observed after APHV. Cross-sectional location-specific differences between BPAQ tertiles were not evident prior to APHV, whereas clear location-specificity was observed after APHV. In conclusion, the skeletal benefits of physical activity are location-specific in the tibia. The present results indicate that the peri- or post-pubertal period is likely a more favourable window of opportunity for enhancing cross-sectional bone geometry than pre puberty. Increased loading during the peri-pubertal period may enhance the bone of both sexes.

Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles.

Abstract The incorporation of a high percentage of targeting molecules into drug delivery system is one of the important methods for improving efficacy of targeting therapeutic drugs to cancer cells. PLGA-based drug delivery carriers with folic acid (FA) as targeting molecule have a low targeting efficiency due to a low FA conjugation ratio. In this work, we fabricated a FA-conjugated PLGA system using a crosslinker 1, 3-diaminopropane and have achieved a high conjugation ratio of 46.7% (mol/mol). The as-prepared PLGA-based biomaterial was used to encapsulate therapeutic drug 5-fluorouracil (5-FU) into nanoparticles. In the in vitro experiments, an IC50 of 5.69 µg/mL has been achieved for 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles on HT-29 cancer cells and is significantly lower than that of 5-FU and 5-FU loaded PLGA nanoparticles which only have an IC50 of 22.9 and 14.17 µg/mL, respectively. The fluorescent microscopy images showed that nanoparticles with FA are largely taken up by HT-29 cancer cells and the targeting nanoparticles have more affinity to cancer cells than the pure drugs and untreated nanoparticles. Therefore, the 1, 3-diaminopropane can facilitate the conjugation of FA to PLGA to form a novel polymer and 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles can be a highly efficient system for specific delivery of drugs to cancer cells.