Selective cleavage of human sex hormone-binding globulin by kallikrein-related peptidases and effects on androgen action in LNCaP prostate cancer cells

Stimulation of the androgen receptor via bioavailable androgens, including testosterone and testosterone metabolites, is a key driver of prostate development and the early stages of prostate cancer. Androgens are hydrophobic and as such require carrier proteins, including sex hormone-binding globulin (SHBG), to enable efficient distribution from sites of biosynthesis to target tissues. The similarly hydrophobic corticosteroids also require a carrier protein whose affinity for steroid is modulated by proteolysis. However, proteolytic mechanisms regulating the SHBG/androgen complex have not been reported. Here, we show that the cancer-associated serine proteases, kallikrein-related peptidase (KLK)4 and KLK14, bind strongly to SHBG in glutathione S-transferase interaction analyses. Further, we demonstrate that active KLK4 and KLK14 cleave human SHBG at unique sites and in an androgen-dependent manner. KLK4 separated androgen-free SHBG into its two laminin G-like (LG) domains that were subsequently proteolytically stable even after prolonged digestion, whereas a catalytically equivalent amount of KLK14 reduced SHBG to small peptide fragments over the same period. Conversely, proteolysis of 5α-dihydrotestosterone (DHT)-bound SHBG was similar for both KLKs and left the steroid binding LG4 domain intact. Characterization of this proteolysis fragment by [(3)H]-labeled DHT binding assays revealed that it retained identical affinity for androgen compared with full-length SHBG (dissociation constant = 1.92 nM). Consistent with this, both full-length SHBG and SHBG-LG4 significantly increased DHT-mediated transcriptional activity of the androgen receptor compared with DHT delivered without carrier protein. Collectively, these data provide the first evidence that SHBG is a target for proteolysis and demonstrate that a stable fragment derived from proteolysis of steroid-bound SHBG retains binding function in vitro.

Information practices of teen content creators : the intersection of action and experiences a grounded theory study

What are the information practices of teen content creators? In the United States over two thirds of teens have participated in creating and sharing content in online communities that are developed for the purpose of allowing users to be producers of content. This study investigates how teens participating in digital participatory communities find and use information as well as how they experience the information. From this investigation emerged a model of their information practices while creating and sharing content such as film-making, visual art work, story telling, music, programming, and web site design in digital participatory communities. The research uses grounded theory methodology in a social constructionist framework to investigate the research problem: what are the information practices of teen content creators? Data was gathered through semi-structured interviews and observation of teen’s digital communities. Analysis occurred concurrently with data collection, and the principle of constant comparison was applied in analysis. As findings were constructed from the data, additional data was collected until a substantive theory was constructed and no new information emerged from data collection. The theory that was constructed from the data describes five information practices of teen content creators. The five information practices are learning community, negotiating aesthetic, negotiating control, negotiating capacity, and representing knowledge. In describing the five information practices there are three necessary descriptive components, the community of practice, the experiences of information and the information actions. The experiences of information include information as participation, inspiration, collaboration, process, and artifact. Information actions include activities that occur in the categories of gathering, thinking and creating. The experiences of information and information actions intersect in the information practices, which are situated within the specific community of practice, such as a digital participatory community. Finally, the information practices interact and build upon one another and this is represented in a graphic model and explanation.

Kernel analysis on Grassmann manifolds for action recognition

Modelling video sequences by subspaces has recently shown promise for recognising human actions. Subspaces are able to accommodate the effects of various image variations and can capture the dynamic properties of actions. Subspaces form a non-Euclidean and curved Riemannian manifold known as a Grassmann manifold. Inference on manifold spaces usually is achieved by embedding the manifolds in higher dimensional Euclidean spaces. In this paper, we instead propose to embed the Grassmann manifolds into reproducing kernel Hilbert spaces and then tackle the problem of discriminant analysis on such manifolds. To achieve efficient machinery, we propose graph-based local discriminant analysis that utilises within-class and between-class similarity graphs to characterise intra-class compactness and inter-class separability, respectively. Experiments on KTH, UCF Sports, and Ballet datasets show that the proposed approach obtains marked improvements in discrimination accuracy in comparison to several state-of-the-art methods, such as the kernel version of affine hull image-set distance, tensor canonical correlation analysis, spatial-temporal words and hierarchy of discriminative space-time neighbourhood features.

Cutting on action : interference strategies in contemporary art practice

The domestication of creative software and hardware has been a significant factor in the recent proliferation of still and moving image creation. Booming numbers of amateur image-makers have the resources, skills and ambitions to create and distribute their work on a mass scale. At the same time, contemporary art seems increasingly dominated by ‘post-medium’ practices that adopt and adapt the representational techniques of mass culture, rather than overtly reject or oppose them. As a consequence of this network of forces, the field of image and video production is no longer the exclusive specialty of art and the mass media, and art may no longer be the most prominent watchdog of mass image culture. Intuitively and intentionally, contemporary artists are responding to these shifting conditions. From the position of a creative practitioner and researcher, this paper examines the strategies that contemporary artists use to engage with the changing relationships between image culture, lived experience and artistic practice. By examining the intersections between W.J.T. Mitchell’s detailed understanding of visual literacy and Jacques Derrida’s philosophical models of reading and writing, I identify ‘editing’ as a broad methodology that describes how practitioners creatively and critically engage with the field of still and moving images. My contention is that by emphasising the intersections of looking and making, ‘reading’ and ‘writing’, artists provide crucial jump cuts, pauses and distortions in the medley of our mediated experiences.

Action research and unit improvement in higher education : a case study approach

Student satisfaction data has been collected on a national basis in Australia since 1972. In recent years this data has been used by federal government agencies to allocate funding, and by students in selecting their universities of choice. The purpose of this paper is to present the findings of an action research project designed to identify and implement unit improvement initiatives over a three year period for an underperforming unit. This research utilises student survey data and teacher reflections to identify areas of unit improvement, with a view to aligning learning experiences, teaching and assessment to learning outcomes and improved student satisfaction. This research concludes that whilst a voluntary student survey system may be imperfect, it nevertheless provides important data that can be utilised to the benefit of the unit, learning outcomes and student satisfaction ratings, as well as wider course related outcomes. Extrapolation of these findings is recommended to other underperforming units.

Dimensions of the venture creation process : amount, dynamics, and sequences of action in nascent entrepreneurship

This research examines the entrepreneurship phenomenon, and the question: Why are some venture attempts more successful than others? This question is not a new one. Prior research has answered this by describing those that engage in nascent entrepreneurship. Yet, this approach yielded little consensus and offers little comfort for those newly considering venture creation (Gartner, 1988). Rather, this research considers the process of venture creation, by focusing on the actions of nascent entrepreneurs. However, the venture creation process is complex (Liao, Welsch, & Tan, 2005), and multi-dimensional (Davidsson, 2004). The process can vary in the amount of action engaged by the entrepreneur; the temporal dynamics of how action is enacted (Lichtenstein, Carter, Dooley, and Gartner 2007); or the sequence in which actions are undertaken. And little is known about whether any, or all three, of these dimensions matter. Further, there exists scant general knowledge about how the venture creation process influences venture creation outcomes (Gartner & Shaver, 2011). Therefore, this research conducts a systematic study of what entrepreneurs do as they create a new venture. The primary goal is to develop general principles so that advice may be offered on how to ‘proceed’, rather than how to ‘be’. Three integrated empirical studies were conducted that separately focus on each of the interrelated dimensions. The basis for this was a randomly sampled, longitudinal panel, of nascent ventures. Upon recruitment these ventures were in the process of being created, but yet to be established as new businesses. The ventures were tracked one year latter to follow up on outcomes. Accordingly, this research makes the following original contributions to knowledge. First, the findings suggest that all three of the dimensions play an important role: action, dynamics, and sequence. This implies that future research should take a multi-dimensional view of the venture creation process. Failing to do so can only result in a limited understanding of a complex phenomenon. Second, action is the fundamental means through which venture creation is achieved. Simply put, more active venture creation efforts are more likely more successful. Further, action is the medium which allows resource endowments their effect upon venture outcomes. Third, the dynamics of how venture creation plays out over time is also influential. Here, a process with a high rate of action which increases in intensity will more likely achieve positive outcomes. Forth, sequence analysis, suggests that the order in which actions are taken will also drive outcomes. Although venture creation generally flows in sequence from discovery toward exploitation (Shane & Venkataraman, 2000; Eckhardt & Shane, 2003; Shane, 2003), processes that actually proceed in this way are less likely to be realized. Instead, processes which specifically intertwine discovery and exploitation action together in symbiosis more likely achieve better outcomes (Sarasvathy, 2001; Baker, Miner, & Eesley, 2003). Further, an optimal venture creation order exists somewhere between these sequential and symbiotic process archetypes. A process which starts out as symbiotic discovery and exploitation, but switches to focus exclusively on exploitation later on is most likely to achieve venture creation. These sequence findings are unique, and suggest future integration between opposing theories for order in venture creation.

Consumer product-related injuries in Queensland children : A snapshot of current problem areas for potential action

This report presents a snapshot from work which was funded by the Queensland Injury Prevention Council in 2010-11 titled “Feasibility of Using Health Data Sources to Inform Product Safety Surveillance in Queensland children”. The project provided an evaluation of the current available evidence-base for identification and surveillance of product-related injuries in children in Queensland and Australia. A comprehensive 300 page report was produced (available at: http://eprints.qut.edu.au/46518/) and a series of recommendations were made which proposed: improvements in the product safety data system, increased utilisation of health data for proactive and reactive surveillance, enhanced collaboration between the health sector and the product safety sector, and improved ability of health data to meet the needs of product safety surveillance. At the conclusion of the project, a Consumer Product Injury Research Advisory group (CPIRAG) was established as a working party to the Queensland Injury Prevention Council (QIPC), to prioritise and advance these recommendations and to work collaboratively with key stakeholders to promote the role of injury data to support product safety policy decisions at the Queensland and national level. This group continues to meet monthly and is comprised of the organisations represented on the second page of this report. One of the key priorities of the CPIRAG group for 2012 was to produce a snapshot report to highlight problem areas for potential action arising out of the larger report. Subsequent funding to write this snapshot report was provided by the Institute for Health and Biomedical Innovation, Injury Prevention and Rehabilitation Domain at QUT in 2012. This work was undertaken by Dr Kirsten McKenzie and researchers from QUT's Centre for Accident Research and Road Safety - Queensland. This snapshot report provides an evidence base for potential further action on a range of children’s products that are significantly represented in injury data. Further information regarding injury hazards, safety advice and regulatory responses are available on the Office of Fair Trading (OFT) Queensland website and the Product Safety Australia websites. Links to these resources are provided for each product reviewed.

Linking the fifth pillar to the first in the UN Decade of Action

The UN Decade of Action outlines five pillars of activity within a safe system framework to achieve the goal of slowing and then reversing the global growth in road traffic fatalities, especially in low-income and middle-income countries. The first four pillars - road safety management, safer roads and mobility, safer vehicles, and safer road users – have a strong focus on prevention of road traffic crashes and mitigation of energy exchange when a crash occurs. The fifth pillar – post-crash response – is far more specific, focusing only on crash victims in the event of a safe system failure. The victims appear to be relevant to the first four pillars only insofar as their numbers can be used to evaluate the success of road safety programs and identify the target groups and contributing factors. This paper argues that a better understanding of the lived experience of long term disability from traffic crashes has the potential to provide a feedback loop from the fifth pillar to the first. Research conducted in Thailand with male crash victims with spinal injury demonstrates that patterns of attribution and social and cultural factors have important implications for road safety management and for interventions aimed at influencing behaviour. In addition, the mobility constraints experienced by people with long term disability can point to systemic issues that might otherwise go unnoticed. The UN Decade of Action can benefit from a more thorough exploration of the experiences and circumstances of people with long term disability as the result of a road traffic crash. Rather than being evidence of the failure of the safe system, they can inform the development of more effective road safety management on low-income and middle-income countries.

UCPR 229 - defamation proceedings – damages to be assessed – application to interrogate as to defendant’s motive - implications of Defamation ACT 2005 - application to interrogate before action - when in the interests of justice

In Hogan v Ellery [2009] QDC 154 McGill DCJ considered two applications for leave to deliver interrogatories under r 229 of the Uniform Civil Procedure Rules 1999 (Qld) (UCPR). The judgment provides useful analysis of the circumstances in which a plaintiff may obtain leave to deliver interrogatories to a defendant in defamation proceedings, and also to a non-party before action.

Review of 'Responding to CALD learners: cultural diversity in action'

This review evaluates a report prepared by Lynda Achren, Jude Newcombe and Drew Roberts of Adult Migrant Education Services (AMES) for the ACFE (Adult, Community and Further Education Board), Victoria, Australia.

Exercise-induced alterations in neutrophil degranulation and respiratory burst activity : possible mechanisms of action

Neutrophils constitute 50-60% of all circulating leukocytes; they present the first line of microbicidal defense and are involved in inflammatory responses. To examine immunocompetence in athletes, numerous studies have investigated the effects of exercise on the number of circulating neutrophils and their response to stimulation by chemotactic stimuli and activating factors. Exercise causes a biphasic increase in the number of neutrophils in the blood, arising from increases in catecholamine and cortisol concentrations. Moderate intensity exercise may enhance neutrophil respiratory burst activity, possibly through increases in the concentrations of growth hormone and the inflammatory cytokine IL-6. In contrast, intense or long duration exercise may suppress neutrophil degranulation and the production of reactive oxidants via elevated circulating concentrations of epinephrine (adrenaline) and cortisol. There is evidence of neutrophil degranulation and activation of the respiratory burst following exercise-induced muscle damage. In principle, improved responsiveness of neutrophils to stimulation following exercise of moderate intensity could mean that individuals participating in moderate exercise may have improved resistance to infection. Conversely, competitive athletes undertaking regular intense exercise may be at greater risk of contracting illness. However, there are limited data to support this concept. To elucidate the cellular mechanisms involved in the neutrophil responses to exercise, researchers have examined changes in the expression of cell membrane receptors, the production and release of reactive oxidants and more recently, calcium signaling. The investigation of possible modifications of other signal transduction events following exercise has not been possible because of current methodological limitations. At present, variation in exercise-induced alterations in neutrophil function appears to be due to differences in exercise protocols, training status, sampling points and laboratory assay techniques.

iRAP Malaysia training course: Decade of Action for Road Safety. Report to Department of Foreign Affairs and Trade, Australia-Malaysia Institute

The International Road Assessment Program (iRAP) is a not-for-profit organisation that works in partnership with governments and non-government organisations in all parts of the world to make roads safe. The iRAP Malaysia pilot study on 3,700km of road identified the potential to save 31,800 deaths and serious injuries over the next 20 years from proven engineering improvements. To help ensure the iRAP data and results are available to planners and engineers, iRAP, together with staff from the Centre for Accident Research and Road Safety – Queensland (CARRS-Q) and the Malaysian Institute of Road Safety Research (MIROS) developed a 5-day iRAP training course that covers the background, theory and practical application of iRAP protocols, with a special focus on Malaysian case studies. Funding was provided by a competitive grant from the Australian-Malaysia Institute.

Strengthening critical health psychology : a critical action orientation

The commentaries on my original article ‘The Emergence of Critical Health Psychology: Can it Contribute to Promoting Public Health?’ provided engaging views on what critical health psychology (CHP) actually is and does. Consideration of each commentary gave rise to numerous themes and generated my own further thoughts on CHP which I frame as five key areas of a continuing dialogue: (1) reflexivity and CHP; (2) health psychology: pluralist or not? (3) CHP as a moral project; (4) social action and change; and (5) strengthening critical approaches to health. Throughout I highlight concepts and issues that are integral to the capacity of CHP to create a shift towards a reinvigorated action-orientated agenda.