Signal transduction mechanisms underlying growth hormone receptor action

Our understanding of the mechanisms of action of GH and its receptor, the GHR, has advanced significantly in the last decade and has provided some important surprises. It is now clear that the GH-GHR axis activates a number of inter-related signalling pathways, not all of which are dependent on the intracellular tyrosine kinase, JAK2 as originally postulated. JAK2-independent pathways, mediated via the Src family kinases, together with a number of negative regulators of GH signalling and emerging cross-talk mechanisms with other growth factor receptors, provide a complex array of mechanisms that are capable of fine-tuning responses to GH in a cell context dependent manner. Additionally, it is also now clear that GH and the GHR can translocate to the nucleus of target cells and initiate, as yet not well defined, nuclear responses. Continued emphasis on elucidation of these complex mechanisms is critical to provide further insights into the diverse physiological and pathophysiological effects of GH.

Compensation for lost services of an employee : pure economic loss and per quod action

Under the common law an employer may take action against a defendant for the loss of an employee’s services due to the act of the defendant (per quod servitium amisit - by reason of which the services were lost). The High Court has recently affirmed the existence of this ancient tort in Barclay v Penberthy [2012] HCA 40.

Participatory photography and self-empowerment in different nations

Volunteering Qld’s Project Creatives continues to explore the critical role creative disciplines and creative people play in providing new models of engagement and action in social change and community work. This article explores three different non-profit organisations that have used collaborative photography to enable locals to empower themselves. Written by Alice Baroni a volunteer with the Education, Research and Policy Unit of Volunteering Qld. Alice is undertaking a PhD at the Queensland University of Technology, exploring (photo) journalism, participatory content creation and community photography in Brazil’s low income suburbs. She is part of the ARC Centre of Excellence for Creative Industries and Innovation, and a Brazilian research group ‘Storytellers and Narratives: Contemporary Journalism’. Two of the initiatives explored in this publication are Viva Favela and Imagens do Povo that are ideologically and physically supported by, respectively, Viva Rio and Observatório de Favelas, based in Rio de Janeiro, Brazil. ‘Favela’ is often translated simply as ‘slum’ or ‘shantytown’, but these terms connote negative characteristics such as shortage, poverty, and deprivation, which end up stigmatising these low-income suburbs. Fotografi Senza Frontiere (FSF) (Photographers Without Borders) is an Italian non-governmental organisation that gathers together a group of photographers who aim to provide youth from extreme regions in Nicaragua, Algeria, Argentina, Panama, Uganda, and Palestine with skills to photograph and document their own reality by establishing permanent photo laboratories. This idea, which is similar to that of Viva Favela and Imagens do Povo, is to enable youth to become professional photographers as a means of self-representation and self-empowerment. Afterwards, students become educators in established photographic labs so as to pass on what they have learnt through FSF’s photographic courses.

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.

Disproportionate over-representation of Indigenous students in New South Wales government special schools

A significant gap exists in the Australian research literature on the disproportionate over-representation of minority groups in special education. The aim of this paper is to make a contribution to the research evidence-base by sketching an outline of the issue as it presents in Australia’s largest education system in the state of New South Wales. Findings from this research show that Indigenous students are equally represented in special schools enrolling students with autism, physical, sensory, and intellectual disabilities, but significantly over-represented in special schools enrolling students under the categories of emotional disturbance, behaviour disorder and juvenile detention. Factors that might influence the disproportionate over-representation of Indigenous children and young people are discussed, and based on these observations, some practical implications for policy and practice are provided.

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.

Feasibility of agent-based modelling of articular cartilage including a conceptual representation of its structure

Articular cartilage is a complex structure with an architecture in which fluid-swollen proteoglycans constrained within a 3D network of collagen fibrils. Because of the complexity of the cartilage structure, the relationship between its mechanical behaviours at the macroscale level and its components at the micro-scale level are not completely understood. The research objective in this thesis is to create a new model of articular cartilage that can be used to simulate and obtain insight into the micro-macro-interaction and mechanisms underlying its mechanical responses during physiological function. The new model of articular cartilage has two characteristics, namely: i) not use fibre-reinforced composite material idealization ii) Provide a framework for that it does probing the micro mechanism of the fluid-solid interaction underlying the deformation of articular cartilage using simple rules of repartition instead of constitutive / physical laws and intuitive curve-fitting. Even though there are various microstructural and mechanical behaviours that can be studied, the scope of this thesis is limited to osmotic pressure formation and distribution and their influence on cartilage fluid diffusion and percolation, which in turn governs the deformation of the compression-loaded tissue. The study can be divided into two stages. In the first stage, the distributions and concentrations of proteoglycans, collagen and water were investigated using histological protocols. Based on this, the structure of cartilage was conceptualised as microscopic osmotic units that consist of these constituents that were distributed according to histological results. These units were repeated three-dimensionally to form the structural model of articular cartilage. In the second stage, cellular automata were incorporated into the resulting matrix (lattice) to simulate the osmotic pressure of the fluid and the movement of water within and out of the matrix; following the osmotic pressure gradient in accordance with the chosen rule of repartition of the pressure. The outcome of this study is the new model of articular cartilage that can be used to simulate and study the micromechanical behaviours of cartilage under different conditions of health and loading. These behaviours are illuminated at the microscale level using the socalled neighbourhood rules developed in the thesis in accordance with the typical requirements of cellular automata modelling. Using these rules and relevant Boundary Conditions to simulate pressure distribution and related fluid motion produced significant results that provided the following insight into the relationships between osmotic pressure gradient and associated fluid micromovement, and the deformation of the matrix. For example, it could be concluded that: 1. It is possible to model articular cartilage with the agent-based model of cellular automata and the Margolus neighbourhood rule. 2. The concept of 3D inter connected osmotic units is a viable structural model for the extracellular matrix of articular cartilage. 3. Different rules of osmotic pressure advection lead to different patterns of deformation in the cartilage matrix, enabling an insight into how this micromechanism influences macromechanical deformation. 4. When features such as transition coefficient were changed, permeability (representing change) is altered due to the change in concentrations of collagen, proteoglycans (i.e. degenerative conditions), the deformation process is impacted. 5. The boundary conditions also influence the relationship between osmotic pressure gradient and fluid movement at the micro-scale level. The outcomes are important to cartilage research since we can use these to study the microscale damage in the cartilage matrix. From this, we are able to monitor related diseases and their progression leading to potential insight into drug-cartilage interaction for treatment. This innovative model is an incremental progress on attempts at creating further computational modelling approaches to cartilage research and other fluid-saturated tissues and material systems.

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.

Representation of assertions in clinical free-­text using SNOMED CT

Information retrieval (IR) by clinicians in the healthcare setting is critical for informing clinical decision-making. However, a large part of this information is in the form of free-text and inhibits clinical decision support and effective healthcare services. This makes meaningful use of clinical free-­text in electronic health records (EHRs) for patient care a difficult task. Within the context of IR, given a repository of free-­text clinical reports, one might want to retrieve and analyse data for patients who have a known clinical finding.