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.

Does legal heritage affect obesity? The channel of motor vehicle dependence

We find a robust relationship between motor vehicle ownership, its interaction with legal heritage and obesity in OECD countries. Our estimates indicate that an increase of 100 motor vehicles per thousand residents is associated with about a 6% point increase in obesity in common law countries, whereas it has a much smaller or insignificant impact in civil law countries. These relations hold whether we examine trend data and simple correlations, or conduct cross-section or panel data regression analysis. Our results suggest that obesity rises with motor vehicle ownership in countries following a common law tradition where individual liberty is encouraged, whereas the link is small or statistically non-existent in countries with a civil law background where the rights of the individual tend to be circumscribed by the power of the state.

Legal issues in the design and implementation of environmental offset and environmental trading frameworks

The Queensland Government released its new Environmental Offset Policy in July 2008. This policy creates a set of overarching principles which are to be incorporated into existing environmental offset policy. This article is the final article in a set of three interrelated articles discussing the operation and implementation of environmental offsets in Queensland. The first article discusses the Environmental Offsets Discussion Paper and the existing environmental offset requirements. No significant changes have been made to these existing offset requirements under the new Environmental Offset Policy. This article also touches briefly on the legal issues associated with design and implementation of environmental offset and trading frameworks. The second article considered the compatibility of different land tenure arrangements in Queensland against the requirements for the creation and trade of environmental offsets. The third article being the present article, discusses the application of the new Environmental Offset Policy while also analysing the legal issues associated with environmental offsets in further detail.

The legal nature of justice in REDD+

Formation of Reduced Emissions from Deforestation and Degradation (REDD+) policy within the international climate regime has raised a number of discussions about ‘justice’. REDD+ aims to provide an incentive for developing countries to preserve or increase the amount of carbon stored in their forested areas. Governance of REDD+ is multi-layered: at the international level, a guiding framework must be determined; at the national level, strong legal frameworks are a pre-requisite to ensure both public and private investor confidence and at the sub-national level, forest-dependent peoples need to agree to participate as stewards of forest carbon project areas. At the international level the overall objective of REDD+ is yet to be determined, with competing mitigation, biological and justice agendas. Existing international law pertaining to the environment (international environmental principles and law, IEL) and human rights (international human rights law, IHRL) should inform the development of international and national REDD+ policy especially in relation to ensuring the environmental integrity of projects and participation and benefit-sharing rights for forest dependent communities. National laws applicable to REDD+ must accommodate the needs of all stakeholders and articulate boundaries which define their interactions, paying particular attention to ensuring that vulnerable groups are protected. This paper i) examines justice theories and IEL and IHRL to inform our understanding of what ‘justice’ means in the context of REDD+, and ii) applies international law to create a reference tool for policy-makers dealing with the complex sub-debates within this emerging climate policy. We achieve this by: 1) Briefly outlining theories of justice (for example – perspectives offered by anthropogenic and ecocentric approaches, and views from ‘green economics’). 2) Commenting on what ‘climate justice’ means in the context of REDD+. 3) Outlining a selection of IEL and IHRL principles and laws to inform our understanding of ‘justice’ in this policy realm (for example – common but differentiated responsibilities, the precautionary principle, sovereignty and prevention drawn from the principles of IEL, the UNFCCC and CBD as relevant conventions of international environmental law; and UNDRIP and the Declaration on the Right to Development as applicable international human rights instruments) 4) Noting how this informs what ‘justice’ is for different REDD+ stakeholders 5) Considering how current law-making (at both the international and national levels) reflects these principles and rules drawn from international law 6) Presenting how international law can inform policy-making by providing a reference tool of applicable international law and how it could be applied to different issues linked to REDD+. As such, this paper will help scholars and policy-makers to understand how international law can assist us to both conceptualise and embody ‘justice’ within frameworks for REDD+ at both the international and national levels.

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.

Legal practitioners’ negligence liability for claim investigation and advice

Nigam v Harm (No 2) [2011] WASCA 221, Western Australia Court of Appeal, 18 October 2011

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.

The doctrine of command responsibility in the midst of war : legal fallacy or reflection of reality

The history of war is blighted with astonishing reminders of man’s ability to cast his sense of humanity aside and inflict unspeakable harm upon one another. The ruthless bombing of Dresden, the callousness of the Nazi concentration camps and the massacre of the Tutsis are but a few of the atrocities that have haunted our past. In response to these atrocities, society has imposed an ever-increasing number of laws and rules to regulate warfare. Amongst these is the doctrine of command responsibility. The doctrine of command responsibility states that a commander is criminally liable for the crimes of his subordinates if he knew or should have known of their crimes. This paper will examine whether the doctrine is an appropriate and realistic legal standard to hold commanders accountable to or whether the doctrine is more a reflection of social sentiment and legal rhetoric. If the doctrine, and indeed the law of war in general, is unrealistic then the law cannot fulfil its purpose - that is, the prevention of atrocities. Instead of being solely a reflection of moral authority and social sentiments the law must also be a tool that guides and shapes the decisions and actions of the military through the chaotic and brutal nature of war...

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.