Quantification of gammaH2AX foci in response to ionising radiation

DNA double-strand breaks (DSBs), which are induced by either endogenous metabolic processes or by exogenous sources, are one of the most critical DNA lesions with respect to survival and preservation of genomic integrity. An early response to the induction of DSBs is phosphorylation of the H2A histone variant, H2AX, at the serine-139 residue, in the highly conserved C-terminal SQEY motif, forming gammaH2AX(1). Following induction of DSBs, H2AX is rapidly phosphorylated by the phosphatidyl-inosito 3-kinase (PIKK) family of proteins, ataxia telangiectasia mutated (ATM), DNA-protein kinase catalytic subunit and ATM and RAD3-related (ATR)(2). Typically, only a few base-pairs (bp) are implicated in a DSB, however, there is significant signal amplification, given the importance of chromatin modifications in DNA damage signalling and repair. Phosphorylation of H2AX mediated predominantly by ATM spreads to adjacent areas of chromatin, affecting approximately 0.03% of total cellular H2AX per DSB(2,3). This corresponds to phosphorylation of approximately 2000 H2AX molecules spanning approximately 2 Mbp regions of chromatin surrounding the site of the DSB and results in the formation of discrete gammaH2AX foci which can be easily visualized and quantitated by immunofluorescence microscopy(2). The loss of gammaH2AX at DSB reflects repair, however, there is some controversy as to what defines complete repair of DSBs; it has been proposed that rejoining of both strands of DNA is adequate however, it has also been suggested that re-instatement of the original chromatin state of compaction is necessary(4-8). The disappearence of gammaH2AX involves at least in part, dephosphorylation by phosphatases, phosphatase 2A and phosphatase 4C(5,6). Further, removal of gammaH2AX by redistribution involving histone exchange with H2A.Z has been implicated(7,8). Importantly, the quantitative analysis of gammaH2AX foci has led to a wide range of applications in medical and nuclear research. Here, we demonstrate the most commonly used immunofluorescence method for evaluation of initial DNA damage by detection and quantitation of gammaH2AX foci in gamma-irradiated adherent human keratinocytes(9)

Out of the Box Festival for 3 to 8 year olds (Artistic Director)

The Out of the Box Festival was founded in 1994 by the Queensland Performing Arts Centre and has been held biannually ever since both within and around the centre in what is now known as the Cultural Precinct at Southbank. It is unique in Australia in that it caters entirely to children aged 8 years and under, with a highly curated program of ticketed performance events, workshops and free arts-based events. It is attended by school and kindergarten groups and by families, and besides engaging children in high quality arts experiences, the festival is also a platform for advocating the developmental and educational benefits of the arts for children. Dr Mark Radvan was the artistic director of the 2008 festival, with responsibility for developing the curatorial direction of each festival, for creating and programming its events, and for working with festival partners The Queensland Art Gallery, The Queensland Museum, The State Library of Queensland and The Queensland Theatre Company. Radvan designed selected and commissioned works to demonstrate how the arts create memorable, celebratory and immersive experiences that stimulate children’s imagination, their curiosity and confidence about the material world and the cultures of its people. A core event was an outdoor music and dance performance space featuring entirely Indigenous performers that was not only the beating heart of the festival, but served to underlie the importance of mainstreaming awareness of our first peoples in the increasingly culturally diverse communities of children attending.

Destined to design? How and why Australian women choose to study industrial design

Despite over three decades of legislation and initiatives designed to tackle the traditional gender divide in the science, technology and design fields, only a quarter of the registered architects in Australia are women. There are no statistics available for other design disciplines, with little known about why women choose design as a career path and who or what influences this decision. This qualitative research addresses this knowledge gap, through semi-structured in-depth interviews conducted with 19 Australian women who completed an industrial (product) design degree. Thematic analysis revealed three key themes: childhood aptitude and exposure; significant experiences and people; and design as a serendipitous choice. The findings emphasise the importance of early exposure to design as a potential career choice, highlighting the critical role played by parents, teachers, professionals and social networks.

Pituitary volume and early treatment response in drug-naïve first-episode psychosis patients

BACKGROUND: An early response to antipsychotic treatment in patients with psychosis has been associated with a better course and outcome. However, factors that predict treatment response are not well understood. The onset of schizophrenia and related disorders has been associated with increased levels of stress and hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis. This study examined whether pituitary volume at the onset of psychosis may be a potential predictor of early treatment response in first-episode psychosis (FEP) patients. METHODS: We investigated the relationship between baseline pituitary volume and symptomatic treatment response over 12 weeks using mixed model analysis in a sample of 42 drug-naïve or early treated FEP patients who participated in a controlled dose-finding study of quetiapine fumarate. Logistic regression was used to examine predictors of treatment response. Pituitary volume was measured from magnetic resonance imaging scans that were obtained upon entry into the trial. RESULTS: Larger pituitary volume was associated with less improvement in overall psychotic symptoms (Brief Psychiatric Rating Scale (BPRS) P=0.031) and positive symptoms (BPRS positive symptom subscale P=0.010). Regardless of gender, patients with a pituitary volume at the 25th percentile (413 mm(3)) were approximately three times more likely to respond to treatment by week 12 than those at the 75th percentile (635 mm(3)) (odds ratio=3.07, CI: 0.90-10.48). CONCLUSION: The association of baseline pituitary volumes with early treatment response highlights the importance of the HPA axis in emerging psychosis. Potential implications for treatment strategies in early psychosis are discussed.

Optimum position of steel outrigger system for high rise composite buildings subjected to wind loads

The responses of composite buildings under wind loads clearly become more critical as the building becomes taller, less stiff and more lightweight. When the composite building increases in height, the stiffness of the structure becomes more important factor and introduction to belt truss and outrigger system is often used to provide sufficient lateral stiffness to the structure. Most of the research works to date is limited to reinforced concrete building with outrigger system of concrete structure, simple building plan layout, single height of a building, one direction wind and single level of outrigger arrangement. There is a scarcity in research works about the effective position of outrigger level on composite buildings under lateral wind loadings when the building plan layout, height and outrigger arrangement are varied. The aim of this paper is to determine the optimum location of steel belt and outrigger systems by using different arrangement of single and double level outrigger for different size, shape and height of composite building. In this study a comprehensive finite element modelling of composite building prototypes is carried out, with three different layouts (Rectangular, Octagonal and L shaped) and for three different storey (28, 42 and 57-storey). Models are analysed for dynamic cyclonic wind loads with various combination of steel belt and outrigger bracings. It is concluded that the effectiveness of the single and double level steel belt and outrigger bracing are varied based on their positions for different size, shape and height of composite building.

Spatiotemporal pattern of bacillary dysentery in China from 1990 to 2009: What is the driver behind?

BACKGROUND Little is known about the spatiotemporal pattern of bacillary dysentery (BD) in China. This study assessed the geographic distribution and seasonality of BD in China over the past two decades. METHODS Data on monthly BD cases in 31 provinces of China from January 1990 to December 2009 obtained from Chinese Center for Disease Control and Prevention, and data on demographic and geographic factors, as well as climatic factors, were compiled. The spatial distributions of BD in the four periods across different provinces were mapped, and heat maps were created to present the seasonality of BD by geography. A cosinor function combined with Poisson regression was used to quantify the seasonal parameters of BD, and a regression analysis was conducted to identify the potential drivers of morbidity and seasonality of BD. RESULTS Although most regions of China have experienced considerable declines in BD morbidity over the past two decades, Beijing and Ningxia still had high BD morbidity in 2009. BD morbidity decreased more slowly in North-west China than other regions. BD in China mainly peaked from July to September, with heterogeneity in peak time between regions. Relative humidity was associated with BD morbidity and peak time, and latitude was the major predictor of BD amplitude. CONCLUSIONS The transmission of BD was heterogeneous in China. Improved sanitation and hygiene in North-west China, and better access to clean water and food in the big floating population in some metropolises could be the focus of future preventive interventions against BD. BD control efforts should put more emphasis on those dry areas in summer.